Record 1 from database: MEDLINE
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- Title
- Familial amyloid polyneuropathy associated with the transthyretin Cys114
gene in a Japanese kindred.
- Author
- Ueno S; Fujimura H; Yorifuji S; Nakamura Y; Takahashi M; Tarui S;
Yanagihara T
- Address
- Department of Neurology, Osaka University Medical School, Japan.
- Source
- Brain, 1992 Oct, 115 ( Pt 5):, 1275-89
- Abstract
- A Japanese kindred with dominantly inherited amyloid polyneuropathy,
commonly called familial amyloid polyneuropathy (FAP), has been
identified. Amyloid protein was transthyretin (TTR) related and the
patients were heterozygous for the mutant gene encoding TTR with a single
amino acid substitution of cysteine for tyrosine at position 114. This
family originated in Nagasaki Prefecture, Japan, and 12 of the 36 known
members of six generations have been affected. The initial symptoms
occurred in their thirties with the cardinal features of polyneuropathy,
vitreous opacities and cardiac disease. Sensory neuropathy was severe in
the lower limbs. Autonomic disturbances, especially postural hypotension,
were the most debilitating to the patients. Amyloid deposits were detected
widely in most organs except for the central nervous system. The duration
from the onset of the disease to death was within 10 yrs. Heart failure
caused by heavy amyloid deposits was the most common cause of sudden
death.
- Language of Publication
- English
- Unique Identifier
- 93045439
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- MeSH Heading (Major)
- Amyloidosis|*GE/ME/PA; Nervous System Diseases|*GE/ME/PA; Prealbumin|AN/*GE
- MeSH Heading
- Adult; Amino Acid Sequence; Amyloid|AN; Autonomic Nervous System
Diseases|GE/ME/PA; Blood Pressure; Case Report; Cysteine|GE; Heart Rate;
Human; Japan; Male; Molecular Sequence Data; Mutation; Pedigree;
Peripheral Nervous System Diseases|GE/ME/PA; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-8950
- Country of Publication
- ENGLAND
Record 2 from database: MEDLINE
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- Title
- Unique efficiency of methionine metabolism in premenopausal women may
protect against vascular disease in the reproductive years.
- Author
- Boers GH; Smals AG; Trijbels FJ; Leermakers AI; Kloppenborg PW
- Address
-
- Source
- J Clin Invest, 1983 Dec, 72:6, 1971-6
- Abstract
- Premenopausal women develop occlusive artery disease less frequently
than postmenopausal women. In coronary heart disease, higher blood levels
of homocysteine-cysteine mixed disulphide have been reported. Therefore,
in healthy subjects, we studied the role of menopausal status in the
transsulphuration of methionine in 10 premenopausal and 10 postmenopausal
women. To exclude the role of aging, we compared these results with those
in 10 younger and 10 older men of comparable age groups. An oral
methionine load (0.1 g/kg of body weight) was administered after overnight
fasting. Before and during 8 h, thereafter, serum levels of methionine,
homocystine, and homocysteine-cysteine mixed disulphide were measured. In
the fasting state, serum methionine levels were similar in the
premenopausal women and both groups of men. Postmenopausal women had
significantly lower fasting levels. Peak levels and clearances of
methionine after loading did not differ between the groups. In the fasting
state, homocystine was never detectable; yet, after methionine loading,
slight homocystinemia was present in 12 out of 20 men, and was more
pronounced in all postmenopausal women. However, homocystinemia did not
occur in any of the premenopausal women after loading. Fasting serum
homocysteine-cysteine mixed disulphide levels did not differ between both
groups of men and postmenopausal women. In premenopausal women, both
fasting and postloading disulphide levels were significantly lower than in
any other group. We conclude that premenopausal women have a unique
efficiency of methionine handling, and thereby are preserved against the
accumulation of homocysteine after methionine loading. We speculate that
this phenomenon might account for the lower incidence of vascular disease
in women in the reproductive life cycle.
- Language of Publication
- English
- Unique Identifier
- 84062261
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- MeSH Heading (Major)
- Arterial Occlusive Diseases|*BL/PP; Cysteine|*BL; Homocysteine|*BL;
Menstruation|*; Methionine|BL/*ME
- MeSH Heading
- Adult; Age Factors; Comparative Study; Female; Human; Male; Sex Factors;
Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-9738
- Country of Publication
- UNITED STATES
Record 3 from database: MEDLINE
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- Title
- Evidence of apoptosis in arrhythmogenic right ventricular dysplasia [see
comments]
- Author
- Mallat Z; Tedgui A; Fontaliran F; Frank R; Durigon M; Fontaine G
- Address
- Centre de Rythmologie et de Stimulation Cardiaque, HÈopital Jean
Rostand, Ivry-sur-Seine, France.
- Source
- N Engl J Med, 1996 Oct, 335:16, 1190-6
- Abstract
- BACKGROUND: Arrhythmogenic right ventricular dysplasia, a disorder that
may lead to severe ventricular arrhythmias and sudden death, is
characterized by the progressive replacement of myocardial cells by fat
and fibrous tissue. We examined whether the loss of myocardial cells in
this disease could result from cell death by apoptosis (programmed cell
death). METHODS: Specimens obtained at autopsy from the right ventricular
myocardium of eight patients with arrhythmogenic right ventricular
dysplasia and four age-matched normal subjects were analyzed. To identify
individual cells undergoing apoptosis, we performed in situ end-labeling
of fragmented DNA on paraffin sections using biotinylated deoxyuridine
triphosphate and the enzyme terminal deoxynucleotidyl transferase. We also
examined the level of expression of CPP-32, a cysteine protease required
for apoptotic cell death in mammalian cells, using immunohistochemical
techniques. RESULTS: Apoptosis was detected in the right ventricular
myocardium of six of the eight patients with arrhythmogenic right
ventricular dysplasia and was absent in the controls. High levels of
expression of CPP-32 were associated with positive in situ end-labeling of
fragmented DNA. CONCLUSIONS: These results indicate that apoptotic
myocardial cell death occurs in arrhythmogenic right ventricular dysplasia
and may contribute to the loss of myocardial cells in this disorder.
- Language of Publication
- English
- Unique Identifier
- 96399026
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- MeSH Heading (Major)
- Apoptosis|*; Myocardial Diseases|CO/*PA/PP; Myocardium|CH/EN/*PA
- MeSH Heading
- Adult; Arrhythmia|ET; Cysteine Proteinases|AN; Deoxyuracil
Nucleotides|ME; DNA Damage; DNA Nucleotidylexotransferase|ME; Female;
Heart Ventricle|CH/PA; Human; Male; Middle Age; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0028-4793
- Country of Publication
- UNITED STATES
Record 4 from database: MEDLINE
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- Title
- To die or not to die: an overview of apoptosis and its role in disease
[see comments]
- Author
- Hetts SW
- Address
- Oliver Wendell Holmes Society, Harvard Medical School, Boston, Mass
02115, USA. shetts@student.med.harvard.edu
- Source
- JAMA, 1998 Jan, 279:4, 300-7
- Abstract
- The death of cells in tissues of humans and other multicellular
organisms is neither always abnormal nor always detrimental. Although
necrosis ensues at the sites of massive cellular injury, most cells in the
body die through a more subtle, noninflammatory, energy-dependent form of
cell death called apoptosis. The number of cells in tissues is determined
by the homeostatic balance between proliferation of new cells and death of
senescent cells; the rates of proliferation and apoptosis vary widely from
tissue to tissue. Recent research into the molecular mechanisms of
apoptosis has revealed that apoptosis is a genetically programmed process
that can become deranged when the components of the cellular apoptotic
machinery are mutated or present in inappropriate quantities.
Dysregulation of apoptosis is associated with the pathogenesis of a wide
array of diseases: cancer, neurodegeneration, autoimmunity, heart disease,
and other disorders. Products of genes involved in the regulation and
execution of apoptosis are potentially excellent targets for diagnosis and
therapeutic intervention in disease processes, and they offer renewed hope
for cures and treatments for a wide array of maladies.
- Language of Publication
- English
- Unique Identifier
- 98111176
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- MeSH Heading (Major)
- Apoptosis|*/GE/PH
- MeSH Heading
- Animal; Autoimmune Diseases; Autoimmunity; Caenorhabditis elegans;
Cysteine Proteinases|PH; Genes, bcl-2|PH; Graft Rejection; Heart Diseases;
Human; Ligands; Lymphoproliferative Disorders; Mitochondria|PH;
Neurodegenerative Diseases; Proteins|PH; Receptors, Cell Surface|PH; T-Lymphocytes|PH
- Publication Type
- JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
- ISSN
- 0098-7484
- Country of Publication
- UNITED STATES
Record 5 from database: MEDLINE
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- Title
- Chlamydia infections and heart disease linked through antigenic mimicry
[see comments]
- Author
- Bachmaier K; Neu N; de la Maza LM; Pal S; Hessel A; Penninger JM
- Address
- Amgen Institute, Ontario Cancer Institute, Departments of Medical
Biophysics and Immunology, University of Toronto, Toronto, Ontario M5G
2C1, Canada.
- Source
- Science, 1999 Feb, 283:5406, 1335-9
- Abstract
- Chlamydia infections are epidemiologically linked to human heart
disease. A peptide from the murine heart muscle-specific alpha myosin
heavy chain that has sequence homology to the 60-kilodalton cysteine-rich
outer membrane proteins of Chlamydia pneumoniae, C. psittaci, and C.
trachomatis was shown to induce autoimmune inflammatory heart disease in
mice. Injection of the homologous Chlamydia peptides into mice also
induced perivascular inflammation, fibrotic changes, and blood vessel
occlusion in the heart, as well as triggering T and B cell reactivity to
the homologous endogenous heart muscle-specific peptide. Chlamydia DNA
functioned as an adjuvant in the triggering of peptide-induced
inflammatory heart disease. Infection with C. trachomatis led to the
production of autoantibodies to heart muscle-specific epitopes. Thus,
Chlamydia-mediated heart disease is induced by antigenic mimicry of a
heart muscle-specific protein.
- Language of Publication
- English
- Unique Identifier
- 99157122
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- MeSH Heading (Major)
- Autoimmune Diseases|IM/*MI/PA; Bacterial Outer Membrane Proteins|CH/*IM;
Chlamydia|*IM; Chlamydia Infections|CO/*IM; Molecular Mimicry|*;
Myocarditis|IM/*MI/PA; Myosin Heavy Chains|CH/*IM
- MeSH Heading
- Adoptive Transfer; Amino Acid Sequence; Animal; Antigens, Bacterial|CH/IM;
Autoantibodies|BI; B-Lymphocytes|IM; Chlamydia trachomatis|IM; CpG
Islands; CD4-Positive T-Lymphocytes|IM; Human; Immunization; Lymphocyte
Transformation; Mice; Mice, Inbred BALB C; Molecular Sequence Data;
Myocardium|IM/PA; Oligodeoxyribonucleotides|IM; Sequence Homology, Amino
Acid; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0036-8075
- Country of Publication
- UNITED STATES
Record 6 from database: MEDLINE
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- Title
- Immunoreactive alpha-human atrial natriuretic polypeptide in human
plasma.
- Author
- Naruse M; Naruse K; Obana K; Kurimoto F; Sakurai H; Honda T; Higashida
T; Demura H; Inagami T; Shizume K
- Address
-
- Source
- Peptides, 1986 Jan, 7:1, 141-5
- Abstract
- A radioimmunoassay (RIA) has been developed for the determination of
alpha-human atrial natriuretic polypeptide (alpha-hANP) in human plasma.
Antibodies generated in rabbits recognized alpha-hANP-related peptides
containing the subsequence flanked by two cysteine residues at position 7
and 23 equally. Radiolabelled tracer prepared by iodination with
chloramine-T method was purified by high performance liquid
chromatography. Immunoreactive (ir-) alpha-hANP was extracted from human
plasma by Sep-Pak C18 column. The plasma ir-alpha-hANP concentrations in
normal, healthy adults were 178 +/- 16 pg/ml in male and 182 +/- 18 pg/ml
in female, respectively. Plasma ir-alpha-hANP increased significantly
after acute intravenous administration of isotonic saline. Plasma levels
were elevated in patients with various disease states accompanying
increased body fluid volume, whereas those in patients with idiopathic
edema were decreased despite excessive salt and water retention. These
results suggest that alpha-hANP plays an important role in the regulation
of body fluids and may have primary or secondary pathophysiological
significance in various disease states.
- Language of Publication
- English
- Unique Identifier
- 86232776
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- MeSH Heading (Major)
- Atrial Natriuretic Factor|*BL
- MeSH Heading
- Adolescence; Adult; Endocrine Diseases|BL; Female; Heart
Catheterization; Heart Failure, Congestive|BL; Human; Hypertension|BL;
Male; Middle Age; Myocardial Infarction|BL; Radioimmunoassay|MT; Reference
Values; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0196-9781
- Country of Publication
- UNITED STATES
Record 7 from database: MEDLINE
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- Title
- Homocysteinemia, ischemic heart disease, and the carrier state for
homocystinuria.
- Author
- Wilcken DE; Reddy SG; Gupta VJ
- Address
-
- Source
- Metabolism, 1983 Apr, 32:4, 363-70
- Abstract
- Precocious atherosclerosis occurs in homocystinuria due to cystathionine
beta-synthase deficiency and there is evidence that homocysteine may
produce endothelial damage. Mild homocysteinemia has been reported in
heterozygotes after methionine loads and it has been suggested that they
could have an increased risk of atherogenesis. We measured plasma amino
acids before and after a methionine load (100 mg per kg) in 17 obligatory
heterozygotes, in 20 men under 50 yr with established ischemic heart
disease, and in matched controls, to determine whether methionine loading
allows identification of heterozygotes, and whether there is an altered
rate of methionine metabolism in patients with premature coronary artery
disease. The obligate heterozygotes had higher mean plasma concentrations
of methionine and total homocysteine at 4, 8 and 12 hours after the load
than their controls, and lower concentrations of total cysteine and
taurine in fasting and all post load samples; however, there was
considerable overlap of measurements in heterozygotes and their controls
even when differential weightings were applied. There were no differences
in mean plasma concentrations of methionine, total homocysteine or total
cysteine between the patients with ischemic heart disease and their
controls at any measurement point. However, two patients with premature
coronary artery disease, identical twins, had persistent elevation of
total plasma homocysteine and an exaggerated homocysteine response to
methionine. Oral folate restored homocysteine concentrations before and
after methionine to normal.(ABSTRACT TRUNCATED AT 250 WORDS)
- Language of Publication
- English
- Unique Identifier
- 84013393
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- MeSH Heading (Major)
- Coronary Disease|BL/*GE; Homocysteine|*BL; Homocystinuria|BL/*GE
- MeSH Heading
- Adult; Amino Acids, Sulfur|BL; Aminobutyric Acids|BL; Diseases in Twins;
Female; Heterozygote; Human; Male; Methionine|ME; Middle Age; Myocardial
Infarction|GE; Pregnancy; Support, Non-U.S. Gov't; Twins, Monozygotic
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0026-0495
- Country of Publication
- UNITED STATES
Record 8 from database: MEDLINE
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- Title
- Prospective randomized study of the role of N-acetyl cysteine in
reversing doxorubicin-induced cardiomyopathy.
- Author
- Dresdale AR; Barr LH; Bonow RO; Mathisen DJ; Myers CE; Schwartz DE;
dAngelo T; Rosenberg SA
- Address
-
- Source
- Am J Clin Oncol, 1982 Dec, 5:6, 657-63
- Abstract
- We conducted a randomized prospective trial in 19 disease-free soft
tissue sarcoma patients with doxorubicin-induced cardiomyopathy identified
by ECG radionuclide angiography at rest and during exercise to determine
the efficacy of the free radical scavenger, N-Acetyl Cysteine (NAC), in
reversing the drug's cardiotoxic effect. Of the 19 patients, 11 received
oral NAC (5.5 gm/m2 daily for 30 days) and eight patients served as
controls. Patients were stratified for age less than greater than 45
years, time from final dose of doxorubicin to randomization less than
greater than 8 months, and history of treatment with mediastinal
irradiation. The two groups were well-matched for all parameters.
Cumulative mean doxorubicin dose (523 mg/m2 and 532 mg/m2) and range
500-600 mg/m2 was comparable. Left ventricular (LV) ejection fraction
before randomization was not significantly different between the two
groups either at rest (39 +/- 10% control, 38 +/- 13% NAC) or during
exercise (38 +/- 12% control, 35 +/- 11% NAC). Neither rest nor exercise
ejection fraction values changed significantly in either group between
prerandomization and 1-month postrandomization studies. Late studies
performed in seven NAC patients 3-5 months after randomization revealed no
difference in LV ejection fraction compared to 1-month postrandomization
values. Clinical course in patients with overt congestive heart failure
was similar in both groups. LV function did not return to normal in any
patient in either group. We conclude that N-Acetyl Cysteine has no effect
in reversing long standing doxorubicin-induced cardiomyopathy.
- Language of Publication
- English
- Unique Identifier
- 83149732
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- MeSH Heading (Major)
- Acetylcysteine|*TU; Doxorubicin|*AE; Myocardial Diseases|CI/*DT;
Sarcoma|*DT; Soft Tissue Neoplasms|*DT
- MeSH Heading
- Adolescence; Adult; Child; Female; Heart Function Tests; Human; Male;
Middle Age; Prospective Studies; Random Allocation
- Publication Type
- CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
- ISSN
- 0277-3732
- Country of Publication
- UNITED STATES
Record 9 from database: MEDLINE
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- Title
- Early changes in human myocardial nuclei after doxorubicin.
- Author
- Unverferth BJ; Magorien RD; Balcerzak SP; Leier CV; Unverferth DV
- Address
-
- Source
- Cancer, 1983 Jul, 52:2, 215-21
- Abstract
- Ten nuclei from the endomyocardial biopsies for each of the following 32
patients were examined by electron microscopy: seven patients before and
then four and 24 hours after treatment with first-dose doxorubicin; seven
patients before and four and 24 hours after treatment with first-dose
doxorubicin plus N-acetyl cysteine; nine patients with doxorubicin induced
cardiomyopathy; and nine patients with idiopathic congestive
cardiomyopathy. Five criteria were used to semiquantitatively compare
nuclei and nucleoli from each group. The most dramatic changes in nuclear
and nucleolar morphology were seen four hours after doxorubicin
administration. Nucleoli were smaller, contracted or segregated and
contained fewer fibrillar centers and a collapsed or fragmented
nucleolonema. The addition of N-acetylcysteine to treatment did not alter
these results. By 24 hours, nuclei had returned to the pre-treatment
status. Long-term doxorubicin therapy produced increased chromatin
clumping and slightly contracted nucleoli. The idiopathic congestive
cardiomyopathic nuclei differed significantly from these doxorubicin
cardiomyopathic nuclei in the decreased amount of chromatin clumping and
the increase in fibrillar centers and nucleonema pattern. It is concluded
from this study that: (1) doxorubicin markedly alters the morphology of
the human myocardial nucleus and nucleolus four hours after treatment, but
these changes diminish by 24 hours; (2) N-acetylcysteine treatment fails
to prevent these changes; and (3) the nuclei and nucleoli of chronic
doxorubicin-induced cardiomyopathy differ significantly from other
congestive cardiomyopathies, but do resemble changes seen four hours after
the first dose of doxorubicin.
- Language of Publication
- English
- Unique Identifier
- 83232573
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- MeSH Heading (Major)
- Cell Nucleus|*DE/UL; Doxorubicin|AE/*PD; Heart|*DE
- MeSH Heading
- Acetylcysteine|PD; Cell Nucleolus|DE/UL; Chronic Disease; Dose-Response
Relationship, Drug; Human; Myocardial Diseases|CI/PA; Myocardium|UL;
Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0008-543X
- Country of Publication
- UNITED STATES
Record 10 from database: MEDLINE
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- Title
- Association between hyperhomocysteinemia and ischemic heart disease in
Sri Lankans [see comments]
- Author
- Mendis S; Athauda SB; Takashi K
- Address
- Department of Medicine, Faculty of Medicine, Peradeniya, Sri Lanka.
- Source
- Int J Cardiol, 1997 Dec, 62:3, 221-5
- Abstract
- OBJECTIVE: The objective of this study was to examine the relation
between hyperhomocysteinaemia and ischemic heart disease in a cohort of
Sri Lankan patients with ischemic heart disease. METHOD: Serum
homocysteine, cysteine and cysteinylglyceine were measured in 54 patients
with a definite diagnosis of ischemic heart disease and compared with
those of an age and sex matched control group. RESULTS: Patients with
coronary ischaemia had significantly higher mean concentrations of
homocysteine and its metabolite cysteine (P<0.01). Of the 54 patients
with ischemic heart disease 14 (35%) had fasting homocysteine
concentrations above the 90th percentile of the controls (odds ratio 3.2,
95% CL 1.0-11.3). CONCLUSION: Hyperhomocysteinaemia is associated with a
three fold increase in coronary risk.
- Language of Publication
- English
- Unique Identifier
- 98135549
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- MeSH Heading (Major)
- Homocysteine|*BL; Myocardial Ischemia|*EP
- MeSH Heading
- Adult; Aged; Causality; Cohort Studies; Comparative Study; Cysteine|BL;
Dipeptides|BL; Female; Human; Male; Middle Age; Odds Ratio; Reference
Values; Risk Factors; Sri Lanka|EP; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0167-5273
- Country of Publication
- IRELAND
Record 11 from database: MEDLINE
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- Title
- Plasma total homocysteine levels in patients with early-onset coronary
heart disease and a low cardiovascular risk profile.
- Author
- Donner MG; Klein GK; Mathes PB; Schwandt P; Richter WO
- Address
- Medical Department II, University of Munich, Klinikum Grosshadern,
Germany.
- Source
- Metabolism, 1998 Mar, 47:3, 273-9
- Abstract
- Mild hyperhomocysteinemia has been associated with an increased risk to
develop premature coronary heart disease. Recently, the homocysteine
concentration has been positively correlated with several main
cardiovascular risk factors. We addressed the issue as to whether patients
with coronary heart disease and a low cardiovascular risk profile also
have a higher prevalence of hyperhomocysteinemia than matched controls.
Ninety-five patients (aged 50.5 +/- 6.6 years) and 34 controls (50.0 +/-
6.7 years) less than 60 years of age were selected from a sample of
patients after coronary angiography. Subjects with hypertension, diabetes,
and moderate or severe hyperlipidemia were excluded. We determined plasma
aminothiols (total homocysteine, cysteine, and glutathione), lipoprotein
fractions, fibrinogen, and uric acid, the body mass index (weight in
kilograms divided by height in meters squared), and the waist to hip
ratio. Furthermore, 37 healthy subjects aged 30.8 +/- 7.5 years underwent
aminothiol determinations. Patients and controls were similar with regard
to age and primary cardiovascular risk factors. Total homocysteine
concentrations in the patient group (9.2 +/- 2.4 micromol/L) were
significantly higher than in the healthy subjects (8.0 +/- 2.0 micromol/L).
However, they did not differ from the levels in the age-matched controls
(9.3 +/- 3.0 micromol/L). Neither total cysteine nor glutathione
concentrations were significantly different between patients and controls.
Male patients (n = 85) had higher mean very-low-density lipoprotein (VLDL)
triglycerides (1.36 +/- 0.90 mmol/L) and lower high-density lipoprotein 3
(HDL3) cholesterol (0.75 +/- 0.21 mmol/L) than male controls (n = 28; 1.01
+/- 0.62 and 0.88 +/- 0.26 mmol/L, respectively). Female patients did not
have any significant differences in lipoprotein concentrations versus the
controls. Among further cardiovascular risk factors, we found a higher
prevalence of central obesity in male patients. In conclusion, there was
not a higher incidence of hyperhomocysteinemia among patients with
premature coronary heart disease and a low cardiovascular risk profile.
The higher prevalence of hyperhomocysteinemia found in other studies may
be related to the primary risk factors seen in these populations, and may
therefore be an indicator of the global cardiovascular risk.
- Language of Publication
- English
- Unique Identifier
- 98160198
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- MeSH Heading (Major)
- Coronary Disease|*BL; Homocysteine|*BL
- MeSH Heading
- Adult; Body Constitution; Body Mass Index; Cysteine|BL; Female;
Fibrinogen|ME; Glutathione|BL; Human; Lipoproteins|BL; Lipoproteins, HDL
Cholesterol|BL; Lipoproteins, VLDL|BL; Male; Middle Age; Risk Factors; Sex
Characteristics; Triglycerides|BL; Uric Acid|BL
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0026-0495
- Country of Publication
- UNITED STATES
Record 12 from database: MEDLINE
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- Title
- Heterozygosity for apolipoprotein E-4Philadelphia(Glu13----Lys,
Arg145----Cys) is associated with incomplete dominance of type III
hyperlipoproteinemia.
- Author
- Lohse P; Rader DJ; Brewer HB Jr
- Address
- Molecular Disease Branch, National Heart, Lung, and Blood Institute,
National Institutes of Health, Bethesda, Maryland 20892.
- Source
- J Biol Chem, 1992 Jul, 267:19, 13642-6
- Abstract
- Apolipoprotein (apo) E-4Philadelphia is a double mutant of apoE in which
residue 13 of the mature protein, glutamic acid (GAG), is replaced by
lysine (AAG) and amino acid 145, arginine (CGT), is converted to cysteine
(TGT). These mutations result in two restriction fragment length
polymorphisms for the enzymes AvaI and BbvI, a smaller apparent molecular
weight of apoE-4Philadelphia on sodium dodecyl polyacrylamide gels, and
severe type III hyperlipoproteinemia (HLP) in a 24-year-old homozygous
female (Lohse, P., Mann, W. A., Stein, E. A., and Brewer, H. B., Jr.
(1991) J. Biol. Chem. 266, 10479-10484). In the current study, we have
extended our analysis to include nine additional family members of the
Philadelphia kindred spanning four generations. DNA and protein analysis
demonstrated that the originally described propositus is a true homozygote
for the epsilon-4Philadelphia allele and that six of the nine family
members are heterozygous for the mutated allele and the normal epsilon-3
allele or, in one case, the epsilon-4 allele. Heterozygosity for
apoE-4Philadelphia leads to the expression of a moderate form of type III
HLP without clinical manifestations. These results are consistent with a
dominant mode of inheritance of this dyslipoproteinemia. The simultaneous
presence of unaffected individuals, heterozygotes, and a homozygote in the
Philadelphia kindred makes it possible for the first time to demonstrate
that the mutant apoE exhibits an incomplete or partial dominance of type
III HLP. Heterozygosity for the normal epsilon-3 allele appears to have an
influence on the expression of type III HLP, resulting in a phenotype
intermediate between that of the two homozygous states.
- Language of Publication
- English
- Unique Identifier
- 92317096
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- MeSH Heading (Major)
- Apolipoproteins E|*GE/ME; Genes, Dominant|*; Heterozygote|*;
Hyperlipoproteinemia Type III|*GE
- MeSH Heading
- Adolescence; Adult; Aged; Arginine|GE; Child; Cysteine|GE; DNA;
Electrophoresis, Polyacrylamide Gel; Female; Glutamates|GE; Homozygote;
Human; Lysine|GE; Male; Middle Age; Pedigree; Phenotype; Polymerase Chain
Reaction; Polymorphism, Restriction Fragment Length; Support, Non-U.S.
Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-9258
- Country of Publication
- UNITED STATES
Record 13 from database: MEDLINE
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- Title
- L-2-Oxothiazolidine-4-carboxylic acid reverses endothelial dysfunction
in patients with coronary artery disease.
- Author
- Vita JA; Frei B; Holbrook M; Gokce N; Leaf C; Keaney JF Jr
- Address
- Evans Memorial Department of Medicine, Cardiology Section and Whitaker
Cardiovascular Institute, Boston University School of Medicine, Boston,
Massachusetts 02118, USA. jvita@acs.bu.edu
- Source
- J Clin Invest, 1998 Mar, 101:6, 1408-14
- Abstract
- The effective action of endothelium-derived nitric oxide (EDNO) is
impaired in patients with atherosclerosis. This impairment has been
attributed in part to increased vascular oxidative stress. EDNO action is
improved by administration of ascorbic acid, a water-soluble antioxidant.
Ascorbic acid is a potent free-radical scavenger in plasma, and also
regulates intracellular redox state in part by sparing cellular
glutathione. We specifically investigated the role of intracellular redox
state in EDNO action by examining the effect of L-2-oxo-4-thiazolidine
carboxylate (OTC) on EDNO-dependent, flow-mediated dilation in a
randomized double-blind placebo-controlled study of patients with
angiographically proven coronary artery disease. OTC augments
intracellular glutathione by providing substrate cysteine for glutathione
synthesis. Brachial artery flow-mediated dilation was examined with
high-resolution ultrasound before and after oral administration of 4.5 g
of OTC or placebo in 48 subjects with angiographically documented coronary
artery disease. Placebo treatment produced no change in flow-mediated
dilation (7.0+/-3.9% vs. 7.2+/-3.7%), whereas OTC treatment was associated
with a significant improvement in flow-mediated dilation (6.6+/-4.4% vs.
11.0+/-6.3%; P = 0.005). OTC had no effect on arterial dilation to
nitroglycerin, systemic blood pressure, heart rate, or reactive hyperemia.
These data suggest that augmenting cellular glutathione levels improves
EDNO action in human atherosclerosis. Cellular redox state may be an
important regulator of EDNO action, and is a potential target for therapy
in patients with coronary artery disease.
- Language of Publication
- English
- Unique Identifier
- 98171529
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- MeSH Heading (Major)
- Coronary Disease|*DT/ME/US; Endothelium, Vascular|*DE/ME/PH;
Thiazoles|AD/PK/*TU
- MeSH Heading
- Administration, Oral; Aged; Atherosclerosis|DT/ME; Blood Flow Velocity;
Blood Glucose; Blood Pressure; Cholesterol|BL; Cysteine|ME; Double-Blind
Method; Female; Glutathione|BI/ME; Heart Rate; Human; Hyperemia; Male;
Middle Age; Nitric Oxide|ME; Nitroglycerin|TU; Oxidation-Reduction;
Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Triglycerides|BL
- Publication Type
- CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
- ISSN
- 0021-9738
- Country of Publication
- UNITED STATES
Record 14 from database: MEDLINE
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- Title
- The crystal structure of cruzain: a therapeutic target for Chagas'
disease.
- Author
- McGrath ME; Eakin AE; Engel JC; McKerrow JH; Craik CS; Fletterick RJ
- Address
- Department of Biochemistry & Biophysics, University of California,
San Francisco 94143, USA.
- Source
- J Mol Biol, 1995 Mar, 247:2, 251-9
- Abstract
- Trypanosoma cruzi, a protozoan parasite, is the etiologic agent of
American trypanosomiasis or Chagas' disease. Chagas' disease afflicts more
than 24 million individuals in South and Central America producing a
debilitating life-long disease. It is the leading cause of heart failure
in many Latin American countries. Currently, there is no satisfactory
treatment for this parasitic infection. Cruzain (also known as cruzipain,
gp 57/51), the major cysteine protease present in T. cruzi, is critical
for the development and survival of the parasite within the host cells,
making this enzyme a target for potential trypanocidal drugs. Here we
report the X-ray crystal structure of cruzain complexed with the potent
inhibitor Z-Phe-Ala-fluoromethyl ketone. The structure was determined at
2.35 A (Rcryst = 0.15) by molecular replacement using a modified papain as
the search model. The refined structure is compared to papain. Features
which distinguish cruzain from papain are discussed since they may aid in
the design of specificity inhibitors. Fluorescence microscopy shows that a
biotinylated form of the bound inhibitor does not effectively reach host
proteases in their lysosomal compartment, but is selectively taken up by
the parasite. The inhibitor greatly reduces parasitemia in a cell culture
system, without adverse effects to mammalian cells. This biological
selectivity can be exploited, in conjunction with unique active site
features revealed by the crystal structure, to develop chemotherapy for
Chagas' disease.
- Language of Publication
- English
- Unique Identifier
- 95222588
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- MeSH Heading (Major)
- Cysteine Proteinases|*CH/GE; Dipeptides|*CH/PD; Ketones|*CH/PD;
Protozoan Proteins|*CH/GE; Trypanosoma cruzi|*CH/DE/GE
- MeSH Heading
- Animal; Comparative Study; Crystallography, X-Ray; Cysteine Proteinase
Inhibitors|PD; Drug Design; Escherichia coli|GE; Human; Macrophages|DE/PS;
Models, Molecular; Molecular Sequence Data; Papain|CH; Recombinant
Proteins|CH; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.;
Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0022-2836
- Country of Publication
- ENGLAND
Record 15 from database: MEDLINE
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- Title
- The replacement of arginine by cysteine at residue 151 in apolipoprotein
A-I produces a phenotype similar to that of apolipoprotein A-IMilano.
- Author
- Bruckert E; von Eckardstein A; Funke H; Beucler I; Wiebusch H; Turpin G;
Assmann G
- Address
- Service d'Endocrinologie-MÆetabolisme, HÈopital PitiÆe
SalpÆetriÄere, Paris, France.
- Source
- Atherosclerosis, 1997 Jan, 128:1, 121-8
- Abstract
- Rare nonsynonymous mutations in the apolipoprotein A-I (apo A-I) gene
are associated with low HDL-cholesterol levels. Despite the inverse
correlation of high density lipoprotein (HDL)-cholesterol levels with the
risk of coronary heart disease (CHD) in the population, reduced
circulating concentrations of HDL do not necessarily predispose to
premature CHD. One apo A-I defect was even reported to cause longevity. We
describe a French patient who presented with very low serum
HDL-cholesterol levels (10 mg/dl). Sequence analysis of the apo A-I gene
identified a heterozygous mutation in the apo A-I gene which causes a
cysteine for arginine replacement at residue 151. Family members with the
mutation displayed 50% lower levels of plasma HDL-cholesterol and of apo
A-I than unaffected members. Plasma activity of lecithin:cholesterol acyl
transferase (LCAT) was significantly lower in apo A-I(R151C) heterozygotes
than in controls. Furthermore, we found that as for apo A-IMilano (R173C),
apo A-I(R151C) forms heterodimers with apo A-II. Moreover, HDL particles
were abnormal in both lipid composition and size distribution. Despite
these quantitative and qualitative differences in HDL, neither the history
of the family over three generations nor the examination of the patient,
gave any indication of premature occurrence of atherosclerosis or CHD. We
conclude that apo A-I(R151C) causes a phenocopy of apo A-IMilano (R173C),
an apo A-I variant which is assumed to cause longevity and which is
considered as a potentially anti-atherogenic agent.
- Language of Publication
- English
- Unique Identifier
- 97203633
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- MeSH Heading (Major)
- Apolipoprotein A-I|BL/*GE; Point Mutation|*
- MeSH Heading
- Adult; Aged; Arginine|GE; Case Report; Child; Coronary Disease|BL/GE;
Cysteine|GE; Electrophoresis; Female; Heterozygote; Human; Lipoproteins|BL;
Lipoproteins, HDL Cholesterol|BL/GE; Male; Middle Age; Pedigree;
Phenotype; Phosphatidylcholine-Sterol O-Acyltransferase|BL; Risk Factors;
Sequence Analysis, DNA; Support, Non-U.S. Gov't; Tangier Disease|BL/GE
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-9150
- Country of Publication
- IRELAND
Record 16 from database: MEDLINE
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- Title
- Metformin increases total serum homocysteine levels in non-diabetic male
patients with coronary heart disease.
- Author
- Carlsen SM; F‡lling I; Grill V; Bjerve KS; Schneede J; Refsum H
- Address
- Department of Medicine, University Hospital of Trondheim, Norway.
- Source
- Scand J Clin Lab Invest, 1997 Oct, 57:6, 521-7
- Abstract
- It is known that the metabolism of homocysteine (Hcy) depends on the
vitamins B6, B12 and folate, and furthermore that metformin reduces serum
vitamin B12 levels. In order to investigate whether metformin treatment
affects serum total Hcy (tHcy) levels we performed an open, prospective,
randomised study in 60 non-diabetic male patients with cardiovascular
disease. After a 4-week run-in period with lovastatin 40 mg day-1, and
diet and lifestyle advice, patients were randomised into two groups, both
continuing the run-in treatment. One group received metformin up to 2000
mg day-1, whereas the control group got no additional treatment. After 12
and 40 weeks of metformin treatment, tHcy levels increased moderately but
significantly by 7.2% (p < 0.05) and 13.8% (p < 0.05) in the
metformin group relative to the control group, whereas serum vitamin B12
levels decreased by 13.4% (p < 0.0005) and 17.7% (p < 0.0005),
respectively. Serum folate levels did not change after 12 weeks, but
decreased by 8.0% after 40 weeks (p = 0.061) relative to the control
group. Serum levels of total cysteine and methylmalonic acid (MMA) did not
change. In conclusion, metformin treatment increased tHcy levels and
decreased levels of vitamin B12 and folate. Since MMA levels were
unchanged, it remains an open question whether the increase in tHcy levels
is secondary to reduced vitamin B12 levels, folate levels or a combination
of both.
- Language of Publication
- English
- Unique Identifier
- 98011012
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- MeSH Heading (Major)
- Coronary Disease|*BL; Homocysteine|*BL; Hypoglycemic Agents|*AE;
Metformin|*AE
- MeSH Heading
- Adult; Cysteine|BL; Folic Acid|BL; Human; Male; Methylmalonic Acid|BL;
Middle Age; Vitamin B 12|BL
- Publication Type
- CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
- ISSN
- 0036-5513
- Country of Publication
- NORWAY
Record 17 from database: MEDLINE
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- Title
- Role of leukotrienes in coronary artery surgery.
- Author
- Allen SP; Yacoub MH
- Address
- Harefield Heart Science Center, Harefield Hospital, Middlesex, UK.
- Source
- Curr Opin Cardiol, 1995 Nov, 10:6, 605-13
- Abstract
- In recent years there has been a heightened awareness of the importance
of inflammatory processes in both coronary artery disease and
cardiopulmonary bypass. Leukotrienes are a group of proinflammatory
metabolites of arachidonic acid whose biologic effects have led to the
postulation that they have a role in a broad number of functions and
inflammatory disease processes. There is evidence to suggest a putative
role of leukotrienes in coronary artery disease. In particular, the
cysteinyl leukotrienes are potent vasoconstrictors of coronary arteries
and can be generated by cell types known to be found in atherosclerotic
arteries and that can participate in the process of atherosclerosis. In
addition, leukotrienes are elevated in patients with cardiac ischemia, and
following coronary artery bypass graft surgery, suggesting that the
leukotrienes as well as other inflammatory mediators participate in the
pathogenesis of cardiac ischemic syndromes. Understanding of the role of
mediators involved in coronary heart disease and cardiopulmonary bypass
could be of great value in managing these patients as well as developing
new strategies for treatment.
- Language of Publication
- English
- Unique Identifier
- 96163666
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- MeSH Heading (Major)
- Coronary Artery Bypass|*; Leukotrienes|ME/*PH
- MeSH Heading
- Cardiopulmonary Bypass; Coronary Arteriosclerosis|PP/TH; Coronary
Disease|PP/TH; Coronary Vessels|PH; Cysteine; Human; Inflammation;
Inflammation Mediators|PH; Myocardial Ischemia|PP/TH; Vasoconstrictor
Agents
- Publication Type
- JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
- ISSN
- 0268-4705
- Country of Publication
- UNITED STATES
Record 18 from database: MEDLINE
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- Title
- Human T cell responses against the major cysteine proteinase (cruzipain)
of Trypanosoma cruzi: role of the multifunctional alpha 2-macroglobulin
receptor in antigen presentation by monocytes.
- Author
- Morrot A; Strickland DK; Higuchi M de L; Reis M; Pedrosa R; Scharfstein
J
- Address
- Instituto de Biofisica Carlos Chagas Filho-UFRJ, LaboratÆorio de
Imunologia Molecular, Rio de Janeiro, Brazil.
- Source
- Int Immunol, 1997 Jun, 9:6, 825-34
- Abstract
- Chagas' disease patients (CDP) develop both humoral and cellular immune
responses against the major cysteine proteinase (cruzipain) from
Trypanosoma cruzi. Here we demonstrate that complexes formed by cruzipain
and alpha 2-macroglobulin (alpha 2M) are efficiently internalized by human
monocytes, and that this process results in enhanced presentation of
cruzipain peptides to CD4+ T cells from CDP. Purified or serum alpha 2M
binds to polymorphic cruzipains, but only a fraction of the proteinases
become covalently linked. Once bound to alpha 2M, fluorescein-labeled
cruzipain (FITC-cruzipain) or [125I]cruzipain were more efficiently
internalized by normal peripheral blood mononuclear cells (PBMC) or
monocytes; this effect was abolished by (I) pre-treating the cells with
receptor-associated protein (rRAP), a known antagonist the of alpha 2M
receptor (alpha 2MR/LRP), and (II) inactivating [125I]cruzipain's active
site prior to the reaction with alpha 2M, indicating that the exposure of
receptor binding sites on alpha 2M complexes required bait region
cleavage. We then sought to determine if the alpha 2MR/LRP-dependent
uptake of alpha 2M:cruzipain by monocytes resulted in increased CD4+ T
cell responses of PBMC-CDP (n = 13). These effects were only revealed
after depletion of CD19+ B lymphocytes from PBMC-CDP; the threshold of T
cell stimulation was far lower in cultures stimulated with alpha
2M:cruzipain, as compared to antigen alone. Myocardial specimens from CDP
with chronic myocardiopathy (three necropsies) were analyzed by
immunohistochemistry with mAb anti-cruzipain or anti-alpha 2MR/LRP
(CD81+). Extracellular depots of cruzipain were localized amidst
inflammatory mononuclear infiltrates, part of which contained CD91+
macrophage-like cells. Ongoing studies should clarify if T. cruzi
cysteinyl proteinases play a role in the pathogenesis of Chagas' heart
disease.
- Language of Publication
- English
- Unique Identifier
- 97343409
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- MeSH Heading (Major)
- Antigen Presentation|*; Antigens, Protozoan|*IM; Cysteine Proteinases|*IM/ME;
Monocytes|*EN/IM; Receptors, Immunologic|IM/*PH; T-Lymphocytes|*IM;
Trypanosoma cruzi|*EN/*IM
- MeSH Heading
- alpha-Macroglobulins|ME; Animal; Glycoproteins|IM; Human; Lymphocyte
Transformation; Myocarditis|EN/IM/PA; Support, Non-U.S. Gov't; Support,
U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0953-8178
- Country of Publication
- ENGLAND
Record 19 from database: MEDLINE
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- Title
- Myocardial protection by the leukotriene synthesis inhibitor BAY X1005:
importance of transcellular biosynthesis of cysteinyl-leukotrienes.
- Author
- Rossoni G; Sala A; Berti F; Testa T; Buccellati C; Molta C; Muller
Peddinghaus R; Maclouf J; Folco GC
- Address
- Center for Cardiopulmonary Pharmacology, School of Pharmacy, University
of Milan, Italy.
- Source
- J Pharmacol Exp Ther, 1996 Jan, 276:1, 335-41
- Abstract
- Perfusion of the isolated rabbit heart with 5 x 10(6) human
polymorphonuclear leukocytes, under recirculating conditions (50 ml), and
challenge with A-23187 (0.5 microM) caused an increase in coronary
perfusion pressure (from a prechallenge value of 46 +/- 1.1 to 176.2 +/-
29.7 mm Hg, 30 min after challenge, n = 6-4), which was linearly
correlated (P < .006) with formation of cysteinyl leukotrienes (29.7
+/- 7.3 pmol/ml, 30 min after challenge). Pretreatment with the
leukotriene synthesis inhibitor BAY X1005 (1 microM) (n = 6) resulted in
significant protection against the increase in coronary perfusion pressure
(76.7 +/- 12.8 mm Hg, 30 min after challenge) and in almost complete
inhibition of sulfidopeptide leukotriene synthesis (3.2 +/- 1.7 pmol/ml,
30 min after challenge). In in vivo experiments, ligation of the left
anterior descending coronary artery in the rabbit (n = 10) resulted in
acute myocardial infarction marked by a mortality rate of 60% compared
with sham-operated animals (n = 10). Intravenous treatment of the rabbits
with BAY X1005 (10 mg/kg/h, for 2 h) (n = 10) markedly reduced the
mortality rate (20%), protected the rabbits against the marked
electrocardiogram derangement and abolished the significant increase in
plasma creatine phosphokinase activity and cardiac tissue myeloperoxidase
activity induced by coronary artery ligation. BAY X1005 exerts a
significant cardioprotection and suggests that specific leukotriene
synthesis inhibitors may lead to innovative therapy in myocardial
ischemia.
- Language of Publication
- English
- Unique Identifier
- 96135085
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- MeSH Heading (Major)
- Cysteine|*BI; Heart|*DE; Heart Diseases|*PC; Leukotrienes|*BI;
Lipoxygenase Inhibitors|*TU; Myocardium|EN/*ME; Quinolines|*TU
- MeSH Heading
- Animal; Arachidonate 5-Lipoxygenase|DE/ME; Calcimycin|PD; Coronary
Vessels|CY/PH; Creatine Kinase|DE/ME; Electrocardiography; Endothelium,
Vascular|DE; Enzyme Activation|DE; Human; In Vitro; Lactate
Dehydrogenase|ME; Male; Myocardial Ischemia|DT; Neutrophils|CY/DE/PH;
Peroxidase|DE/ME; Rabbits; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0022-3565
- Country of Publication
- UNITED STATES
Record 20 from database: MEDLINE
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- Title
- Regulation of programmed cell death or apoptosis in atherosclerosis.
- Author
- Geng YJ
- Address
- Cardiovascular and Pulmonary Research Institute, Allegheny University of
the Health Sciences, Pittsburgh, PA 15212, USA.
- Source
- Heart Vessels, 1997, Suppl 12:, 76-80
- Abstract
- Intimal thickening caused by accumulation of cells, lipids, and
connective tissue characterizes atherosclerosis, an arterial disease that
leads to cardiac and cerebral infarction. Apoptosis, or genetically
programmed cell death, is important for the development and morphogenesis
of organs and tissues. As in other tissues, cells of cardiovascular
tissues can undergo apoptosis. Increased apoptosis has been found in both
human and animal atherosclerotic lesions, mediating tissue turnover and
lesion development. In addition to vascular cells, many activated immune
cells, mainly macrophages and T cells, are present in atherosclerotic
lesions, where these cells produce biologically active substances such as
the proinflammatory cytokines tumor necrosis factor, interleukin-1 (IL-1),
and interferon-gamma. Simultaneous exposure to these cytokines may trigger
apoptosis of vascular smooth muscle cells. The products of
death-regulating genes including Fas/Fas ligand, members of IL-1 beta
cysteinyl protease (caspase) family, the tumor suppressive gene p53, and
the protooncogene c-myc have been found in vascular cells and may
participate in the regulation of vascular apoptosis during the development
of atherosclerosis. Abnormal occurrence of apoptosis may take place in
atherosclerotic lesions, including attenuation or acceleration of the
apoptotic death process. The former may cause an increase in the
cellularity of the lesions, and the latter can reduce cellular components
important for maintaining the integrity and stability of the plaques.
Clarification of the molecular mechanism that regulates apoptosis may help
design a new strategy for treatment of patients with atherosclerosis and
its major complications, heart attack and stroke.
- Language of Publication
- English
- Unique Identifier
- 98137030
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- MeSH Heading (Major)
- Apoptosis|*PH; Atherosclerosis|PA/*PP
- MeSH Heading
- Animal; Antigens, CD95|PH; Cysteine Proteinases|ME; Genes, p53|PH;
Human; Macrophages|PH; Proto-Oncogene Proteins c-myc|PH; Signal
Transduction|PH; T-Lymphocytes|PH
- Publication Type
- JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
- ISSN
- 0910-8327
- Country of Publication
- JAPAN
Record 21 from database: MEDLINE
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- Title
- A cysteine-containing truncated apo A-I variant associated with HDL
deficiency.
- Author
- Moriyama K; Sasaki J; Takada Y; Matsunaga A; Fukui J; Albers JJ; Arakawa
K
- Address
- Department of Internal Medicine, Fukuoka University, School of Medicine,
Japan.
- Source
- Arterioscler Thromb Vasc Biol, 1996 Dec, 16:12, 1416-23
- Abstract
- We identified a 50-year-old Japanese woman with a novel mutation in the
apolipoprotein (apo) A-I gene causing high-density lipoprotein (HDL)
deficiency. The patient had extremely low HDL cholesterol and apo A-I
levels (0.14 mmol/L and 0.8 mg/dL, respectively) but no evidence of
coronary heart disease. However, she had bilateral xanthomas of the
Achilles tendon, elbow, and knee joint as well as corneal opacities.
Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of serum
followed by immunoblotting revealed that the patient's apo A-I had a lower
molecular weight (24,000) than normal apo A-I. A partial gene duplication
encompassing 23 nucleotides was found by DNA sequence analysis, resulting
in a tandem repeat of bases 333 to 355 from the 5' end of exon 4. This
tandem repeat caused a frameshift mutation with premature termination
after amino acid 207. The frameshift gives rise to a predicted protein
sequence that contains two cysteines. We designated this mutant as apo A-ISasebo.
Apo A-ISasebo formed heterodimers with apo A-II and apo E in the patient's
plasma and was associated with both the low-density lipoprotein and HDL
fractions. The patient's cholesterol esterification rate and
lecithin-cholesterol acyltransferase activity were reduced to about 30% of
normal, although specific enzyme activity was unaffected, suggesting that
it remained functionally normal. In addition, cholesteryl ester transfer
activity was reduced to about half of normal. Thus, apo A-ISasebo was
associated with complex derangements of lipoprotein metabolism.
- Language of Publication
- English
- Unique Identifier
- 97131987
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- MeSH Heading (Major)
- Apolipoprotein A-I|*GE/ME; Lipoproteins, HDL|*DF/GE
- MeSH Heading
- Amino Acid Sequence; Base Sequence; Case Report; Cysteine|GE; Female;
Human; Middle Age; Molecular Sequence Data; Mutation; Pedigree; Support,
Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 1079-5642
- Country of Publication
- UNITED STATES
Record 22 from database: MEDLINE
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- Title
- The apolipoprotein E2 (Arg145Cys) mutation causes autosomal dominant
type III hyperlipoproteinemia with incomplete penetrance.
- Author
- de Villiers WJ; van der Westhuyzen DR; Coetzee GA; Henderson HE; Marais
AD
- Address
- Department of Medical Biochemistry, University of Cape Town Medical
School, South Africa.
- Source
- Arterioscler Thromb Vasc Biol, 1997 May, 17:5, 865-72
- Abstract
- Type III hyperlipoproteinemia (type III HLP) is an atherogenic disorder
of lipoprotein metabolism characterized by the accumulation of
cholesterol-enriched VLDL and is usually associated with homozygosity for
a normal variant of apoE, apoE2. ApoE2(Arg145Cys) is a rare variant
arising from a C-->T transition at nucleotide 4031 and has been linked
to type III HLP. Ten subjects from a group of 42 unrelated individuals
with proven type III HLP were found to be either heterozygous or
homozygous for the apoE2(Arg145Cys) mutation by DNA sequencing. The
apoE4-Philadelphia (Glu13Lys, Arg145Cys) variant was subsequently
excluded. None of 4 homozygotes (3 blacks and 1 of mixed ancestry)
developed ischemic heart disease, but they did present with xanthomata. In
contrast, 6 heterozygous subjects presented mainly with ischemic heart
disease but generally lacked physical signs. Cholesterol concentrations
ranged from 6.2 mmol/L to 13.3 mmol/L and triglyceride levels from 3.2 to
13.2 mmol/L. The dyslipoproteinemia in homozygous and heterozygous
subjects was indistinguishable. Family investigation identified an
additional 10 heterozygous mutant-allele carriers, of whom 3 had type III
HLP. This unique cohort of patients indicates that the apoE2(Arg145Cys)
mutation is relatively common in several population groups in our region
and may be particularly prevalent in blacks. There was no clear allele
dosage effect present for the development of dyslipoproteinemia or
atherosclerosis. The mode of inheritance is for the first time clearly
established to be autosomal dominant with incomplete penetrance.
- Language of Publication
- English
- Unique Identifier
- 97301548
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- MeSH Heading (Major)
- Apolipoproteins E|*GE; Hyperlipoproteinemia|*GE; Point Mutation|*
- MeSH Heading
- Adolescence; Adult; Arginine; Cysteine; Female; Heterozygote; Homozygote;
Human; Lipoproteins, HDL Cholesterol|BL; Male; Middle Age; Pedigree;
Polymorphism, Restriction Fragment Length; Restriction Mapping; Sequence
Analysis, DNA; Triglycerides|BL
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 1079-5642
- Country of Publication
- UNITED STATES
Record 23 from database: MEDLINE
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- Title
- Role of Fas ligand and receptor in the mechanism of T-cell depletion in
acquired immunodeficiency syndrome: effect on CD4+ lymphocyte depletion
and human immunodeficiency virus replication.
- Author
- Sloand EM; Young NS; Kumar P; Weichold FF; Sato T; Maciejewski JP
- Address
- National Heart, Lung, and Blood Institute, Bethesda, MD, USA.
- Source
- Blood, 1997 Feb, 89:4, 1357-63
- Abstract
- Direct killing of CD4+ lymphocytes by human immunodeficiency virus-1
(HIV-1) probably cannot account for the magnitude of the loss of these
cells during the course of HIV-1 infection. Experimental evidence supports
a pathophysiologic role of the apoptotic process in depletion of CD4 cells
in acquired immunodeficiency syndrome (AIDS). The Fas-receptor/Fas-ligand
(Fas-R/Fas-L) system mediates signals for apoptosis of susceptible
lymphocytes and lympoblastoid cell lines. A number of investigators have
recently reported increased expression of the Fas receptor in individuals
with HIV infection, along with increased sensitivity of their lymphocytes
to anti-Fas antibody mimicking Fas ligand. We attempted to determine the
role of Fas-mediated apoptosis in disease progression and viral
replication. Increased Fas-receptor (CD95) expression on CD4+ and CD8+
lymphocytes was found in a large group of HIV-1-infected patients compared
with normal controls; individuals with a diagnosis of AIDS and a history
of opportunistic infection had significantly more Fas receptor expression
than did asymptomatic HIV-infected persons and normal blood donor controls
(P < .01). Triggering of the Fas-R by agonistic anti-Fas monoclonal
antibody, CH11, was preferentially associated with apoptosis in the CD4+
cells; this effect was more pronounced in lymphocytes derived from HIV+
individuals. Soluble and membrane-bound forms of Fas-L were produced in
greater amounts in peripheral blood mononuclear cells (PBMC) cultures and
in plasma obtained from HIV-1-infected persons than from normal controls.
Furthermore, triggering of lymphocytes from HIV-infected persons by CH11
increased levels of interleukin-1beta converting enzyme (ICE), a protein
associated with apoptosis. When PBMC were cultured in the presence of
CH11, p24 production per number of viable cells was decreased as compared
with the same PBMC without CH11 (P < .01). These findings suggest that
multiple mechanisms, including increased production of Fas-L by infected
PBMC, increased Fas-R expression, and induction of a protease of ICE
family, may play roles in the apoptotic depletion of CD4+ cells in HIV
infection.
- Language of Publication
- English
- Unique Identifier
- 97180741
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- MeSH Heading (Major)
- Acquired Immunodeficiency Syndrome|*IM; Antigens, CD95|*PH; Apoptosis|*;
CD4-Positive T-Lymphocytes|IM/*PA; HIV-1|*PH; Membrane Glycoproteins|*PH;
Virus Replication|*
- MeSH Heading
- Cell Cycle; Cohort Studies; Cysteine Proteinases|BI; Enzyme Induction;
Human; Lymphocyte Transformation|DE; Phytohemagglutinins|PD; Signal
Transduction
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-4971
- Country of Publication
- UNITED STATES
Record 24 from database: MEDLINE
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- Title
- Amino acid metabolism in the heart muscle in subjects with ischaemic
heart disease at rest and during pacing.
- Author
- Brodan V; Fabián J; Andel M; Tomková D
- Address
-
- Source
- Czech Med, 1978, 1:1, 53-61
- Abstract
- In nine patients with ischaemic heart disease at rest and during pacing
differences of free plasma amino acids, lactate, ammonia and uric acid
between arterial blood and blood in the coronary sinus (a-cs differences)
were investigated. At rest one single significant difference was found,
i.e. a positive a-cs difference in aspartate. During pacing significant
positive differences were recorded in aspartate, glutamate, leucine and
isoleucine and significant negative a-cs differences in cystine-cysteine,
glutamine and aspartic acid and in alanine. Among the correlations between
a-cs differences the negative relationship between lactate and alanine and
the negative correlation between cystine-cysteine and leucine, isoleucine
and glutamine is significant. There is a positive relationship between the
a-cs difference of alanine and glutamine and between the differences of
leucine, isoleucine and glutamate. The a-cs differences of ammonia and
uric acid correlate negatively.
- Language of Publication
- English
- Unique Identifier
- 79024263
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- MeSH Heading (Major)
- Amino Acids|*ME; Coronary Disease|*ME; Myocardium|*ME
- MeSH Heading
- Adult; Alanine|ME; Ammonia|ME; Cardiac Pacing, Artificial; Human;
Lactates|ME; Male; Middle Age; Rest; Uric Acid|ME
- Publication Type
- JOURNAL ARTICLE
- Country of Publication
- CZECHOSLOVAKIA
Record 25 from database: MEDLINE
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- Title
- Attempt to prevent doxorubicin-induced acute human myocardial
morphologic damage with acetylcysteine.
- Author
- Unverferth DV; Jagadeesh JM; Unverferth BJ; Magorien RD; Leier CV;
Balcerzak SP
- Address
-
- Source
- J Natl Cancer Inst, 1983 Nov, 71:5, 917-20
- Abstract
- Doxorubicin induced acute as well as chronic myocardial morphologic
alterations. Twenty patients with normal cardiovascular function were
randomized to 2 groups based on age and dose of doxorubicin. Group I
received placebo 1 hour before doxorubicin administration; group II
received acetylcysteine (N-acetyl-L-cysteine) (Nac) 1 hour before
doxorubicin. Endomyocardial biopsies were performed at base line at 4 and
24 hours after doxorubicin administration. Biopsy tissue was viewed by
electron microscopy, and stereoscopic techniques were used to determine
tubular and mitochondrial area. The change of the tubular area was similar
in the 2 groups, was maximum at 4 hours, and was proportionately spread
throughout the cell. The mitochondrial swelling was also similar in the 2
groups and proportionate throughout the cell but was maximum at 24 hours.
This study demonstrated that the acute doxorubicin-induced damage was
diffuse and not prevented by Nac.
- Language of Publication
- English
- Unique Identifier
- 84065555
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- MeSH Heading (Major)
- Acetylcysteine|*PD; Doxorubicin|*AE; Myocardium|*UL
- MeSH Heading
- Adult; Aged; Biopsy; Drug Evaluation; Endocardium|DE/UL; Human;
Microscopy, Electron; Middle Age; Mitochondria, Heart|DE/UL; Myocardial
Diseases|CI; Support, Non-U.S. Gov't
- Publication Type
- CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
- ISSN
- 0027-8874
- Country of Publication
- UNITED STATES
Record 26 from database: MEDLINE
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- Title
- Signalling by protein kinase C isoforms in the heart.
- Author
- Pucéat M; Vassort G
- Address
- Laboratoire de Physiopathologie Cardiovasculaire, INSERM U390,
Montpellier, France.
- Source
- Mol Cell Biochem, 1996 Apr, 157:1-2, 65-72
- Abstract
- Understanding transmembrane signalling process is one of the major
challenge of the decade. In most tissues, since Fisher and Krebs's
discovery in the 1950's, protein phosphorylation has been widely
recognized as a key event of this cellular function. Indeed, binding of
hormones or neurotransmitters to specific membrane receptors leads to the
generation of cytosoluble second messengers which in turn activate a
specific protein kinase. Numerous protein kinases have been so far
identified and roughly classified into two groups, namely serine/threonine
and tyrosine kinases on the basis of the target acid although some more
recently discovered kinases like MEK (or MAP kinase kinase) phosphorylate
both serine and tyrosine residues. Protein kinase C is a serine/threonine
kinase that was first described by Takai et al. [1] as a Ca- and
phospholipid-dependent protein kinase. Later on, Kuo et al. [2] found that
PKC was expressed in most tissues including the heart. The field of
investigation became more complicated when it was found that the kinase is
not a single molecular entity and that several isoforms exist. At present,
12 PKC isoforms and other PKC-related kinases [3] were identified in
mammalian tissues. These are classified into three groups. (1) the
Ca-activated alpha-, beta-, and gamma-PKCs which display a Ca-binding site
(C2); (2) the Ca-insensitive delta-, epsilon-, theta-, eta-, and mu-PKCs.
The kinases that belong to both of these groups display two cysteine-rich
domains (C1) which bind phorbol esters (for recent review on PKC
structure, see [4]). (3) The third group was named atypical PKCs and
include zeta, lambda, and tau-PKCs that lack both the C2 and one
cysteine-rich domain. Consequently, these isoforms are Ca-insensitive and
cannot be activated by phorbol esters [5]. In the heart, evidence that
multiple PKC isoforms exist was first provided by Kosaka et at. [6] who
identified by chromatography at least two PKC-related isoenzymes. Numerous
studies were thus devoted to the biochemical characterization of these
isoenzymes (see [7] for review on cardiac PKCs) as well as to the
identification of their substrates. This overview aims at updating the
present knowledge on the expression, activation and functions of PKC
isoforms in cardiac cells.
- Language of Publication
- English
- Unique Identifier
- 96323861
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- MeSH Heading (Major)
- Heart|*PH; Heart Diseases|*EN/PP; Isoenzymes|*ME; Myocardium|*EN;
Protein Kinase C|*ME; Signal Transduction|*
- MeSH Heading
- Animal; Binding Sites; Calcium|ME; Cell Membrane|PH; Contractile
Proteins|ME; Heart Hypertrophy|EN; Human; Protein Kinases|ME;
Protein-Serine-Threonine Kinases|ME; Protein-Tyrosine Kinase|ME
- Publication Type
- JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
- ISSN
- 0300-8177
- Country of Publication
- NETHERLANDS
Record 27 from database: MEDLINE
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- Title
- Reduction of oxidative stress does not affect recovery of myocardial
function: warm continuous versus cold intermittent blood cardioplegia.
- Author
- Biagioli B; Borrelli E; Maccherini M; Bellomo G; Lisi G; Giomarelli P;
Sani G; Toscano M
- Address
- Instituto di Chirurgia Toracica e Cardiovascolare e Tecnologie
Biomediche, UniversitÄa degli Studi di Siema, Italy.
- Source
- Heart, 1997 May, 77:5, 465-73
- Abstract
- OBJECTIVE: To compare oxidative stress after cardiac surgery in patients
treated with two different methods of myocardial protection: warm
continuous versus cold intermittent blood cardioplegia. To correlate
oxidative stress with postoperative myocardial dysfunction. DESIGN:
Prospective, randomised, double blind, trial. SETTING: Institutional
centre of cardiovascular surgery. PATIENTS: 20 patients were selected for
coronary artery bypass surgery (CABG) on the following basis: stable
angina, ejection fraction > 50%, double or triple vessel disease, no
previous CABG or associated disease. Patients were randomised to two
groups of 10 patients each. INTERVENTIONS: Patients underwent CABG with
one of two different methods of myocardial protection and cardiopulmonary
bypass. CBC group: intermittent cold blood antegrade-retrograde
cardioplegia with moderate hypothermic cardiopulmonary bypass; WBC group:
continuous warm blood antegrade-retrograde cardioplegia with mild
hypothermic cardiopulmonary bypass. MAIN OUTCOME MEASURE: The index of
oxidative stress used was the alteration of whole blood and plasma
glutathione redox status. Samples were collected from the coronary sinus
and peripheral vein before anaesthesia (T1), before aortic unclamping
(T2), 15 minutes (T3), and 30 minutes (T4) after unclamping. Haemodynamic
parameters were measured with thermodilution techniques. RESULTS: Oxidised
glutathione and glutathione-cysteine mixed disulphide significantly
increased in the coronary sinus plasma in the CBC group, and the overall
redox balance of glutathione was decreased (P < 0.01) at T2-T4 versus
T1, and compared with the WBC group. Comparable results were obtained for
coronary sinus blood. There was no correlation between postoperative
haemodynamic measurements and oxidative stress markers. CONCLUSIONS:
Oxidative stress was significant in patients undergoing CABG using cold
blood cardioplegia, while the warm technique minimised the effects of
ischaemia. However, oxidative stress was not correlated with myocardial
dysfunction following CABG.
- Language of Publication
- English
- Unique Identifier
- 97339865
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- MeSH Heading (Major)
- Coronary Artery Bypass|*; Heart Arrest, Induced|*MT; Heat|*;
Myocardium|*ME; Oxidative Stress|*
- MeSH Heading
- Analysis of Variance; Cardiopulmonary Bypass; Cold; Comparative Study;
Coronary Disease|BL/ME/SU; Double-Blind Method; Female; Glutathione|BL;
Hemodynamics; Human; Male; Middle Age; Prospective Studies; Support,
Non-U.S. Gov't
- Publication Type
- CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
- ISSN
- 1355-6037
- Country of Publication
- ENGLAND
Record 28 from database: MEDLINE
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- Title
- Legionella birminghamensis sp. nov. isolated from a cardiac transplant
recipient.
- Author
- Wilkinson HW; Thacker WL; Benson RF; Polt SS; Brookings E; Mayberry WR;
Brenner DJ; Gilley RG; Kirklin JK
- Address
- Division of Bacterial Diseases, Centers for Disease Control, Atlanta,
Georgia 30333.
- Source
- J Clin Microbiol, 1987 Nov, 25:11, 2120-2
- Abstract
- A Legionella-like organism, strain 1407-AL-H, was isolated from a
transbronchial lung biopsy specimen from a cardiac transplant recipient
undergoing immunosuppressive therapy. The strain grew on buffered
charcoal-yeast extract agar (BCYE) but not on BCYE in the absence of
cysteine, and it showed gas-liquid chromatographic fatty acid profiles
that were predominantly branch chained. Strain 1407-AL-H was antigenically
distinct in slide agglutination tests from the 23 Legionella species and
39 serogroups previously described. DNA hybridization studies placed it in
a new Legionella species, Legionella birminghamensis (ATCC 43702).
- Language of Publication
- English
- Unique Identifier
- 88087814
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- MeSH Heading (Major)
- Heart|*TR; Heart Transplantation|*; Legionella|AN/*CL/GD/IP;
Legionellosis|*MI; Lung|*MI
- MeSH Heading
- Agglutination Tests; Case Report; DNA, Bacterial|AN; Fatty Acids|AN;
Human; Immunosuppression; Male; Middle Age
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0095-1137
- Country of Publication
- UNITED STATES
Record 29 from database: MEDLINE
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- Title
- Complexity of molecular genetics of dyslipidemia in a family highly
susceptible to ischemic heart disease.
- Author
- Jensen HK; Hansen PS; Jensen LG; Kristensen MJ; Klausen IC; Kjeldsen M;
Lemming L; Bolund L; Gregersen N; Faergeman O
- Address
- Center for Medical Molecular Biology, Aarhus University Hospital, Skejby
Sygehus, Denmark.
- Source
- Clin Genet, 1995 Jul, 48:1, 23-8
- Abstract
- In a Danish family highly susceptible to ischemic heart disease,
hyperlipidemia did not simply cosegregate with a previously undescribed 10
bp deletion in the LDL receptor gene causing heterozygous familial
hypercholesterolemia (FH). This mutation, designated as FH DK-4, deletes
10 nucleotides from exon 4 coding for the third cysteine-rich repeat of
the ligand-binding domain. The resulting translational frameshift and stop
codon corresponding to amino acid position 181 in the LDL receptor cDNA is
predicted to result in a truncated LDL receptor protein. Several family
members had hyperlipidemia and early onset of ischemic heart disease not
due to the 10 bp deletion, and several family members had unexpectedly
high serum lipoprotein(a) contributing to high concentrations of serum LDL
cholesterol. The study illustrates important limitations and possibilities
of molecular genetic diagnosis.
- Language of Publication
- English
- Unique Identifier
- 96066156
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- MeSH Heading (Major)
- Hypercholesterolemia|BL/CO/*GE; Myocardial Ischemia|CO/*GE
- MeSH Heading
- Base Sequence; Disease Susceptibility|GE; DNA|AN; DNA Primers; Exons;
Female; Gene Deletion; Heterozygote; Human; Lipids|BL; Male; Molecular
Sequence Data; Pedigree; Receptors, LDL|GE; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0009-9163
- Country of Publication
- DENMARK
Record 30 from database: MEDLINE
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- Title
- Oxygen free radicals and myocardial damage: protective role of thiol-containing
agents.
- Author
- Ferrari R; Ceconi C; Curello S; Cargnoni A; Alfieri O; Pardini A;
Marzollo P; Visioli O
- Address
- Cattedra di Cardiologia, UniversitÄa degli Studi di Brescia, Italy.
- Source
- Am J Med, 1991 Sep, 91:3C, 95S-105S
- Abstract
- It has been suggested that the sudden presence of oxygen during
reperfusion after a period of ischemia may be toxic for the myocardial
cell. The oxygen molecule is capable of producing reactions in the cell,
forming highly reactive free radicals, and inducing lipid peroxidation of
membranes, altering their integrity and increasing their fluidity and
permeability. The ischemic and reperfused cardiac cell is the prime
candidate for this reaction sequence and may explain the molecular
mechanism underlying the pathologic events related to membrane dysfunction
and calcium homeostasis. However, the myocardium has a series of defense
mechanisms including the enzymes superoxide dismutase (SOD), catalase, and
glutathione peroxidase plus other endogenous antioxidants such as vitamin
E, ascorbic acid, and cysteine to protect the cell against the cytotoxic
oxygen metabolites. The prerequisite for oxygen free radical involvement
in ischemia and reperfusion damage is that ischemia alters the defense
mechanisms against oxygen toxicity. It is known that ischemia may impair
mitochondrial SOD and, with reperfusion, oxidative stress may occur as
shown by tissue accumulation and release of oxidized glutathione. This
tripeptide molecule in the cofactor of glutathione peroxidase, the enzyme
that removes hydrogen and lipid peroxides. Its formation and subsequent
release is a reliable index of oxidative damage. In our study, we
investigated the effects of N-acetylcysteine on oxidative damage in the
isolated rabbit heart. N-acetylcysteine increases, in a dose-dependent
manner (from 10(-7) to 10(-5) M), the myocardial glutathione content and
provides an important degree of protection against ischemia and
reperfusion. Oxidative stress does not occur, mitochondrial function is
maintained, enzyme release is reduced, and contractile recovery is
increased. Similarly, we administered N-acetylcysteine in the pulmonary
artery of coronary artery disease patients undergoing coronary bypass
grafting (150 mg/kg in 1 hour followed by 150 mg/kg in 4 hours). The
degree of oxidative stress on reperfusion was reduced and recovery of
cardiac function improved. In this article, we review the cardioprotective
role of thiol-containing agents.
- Language of Publication
- English
- Unique Identifier
- 92026237
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- MeSH Heading (Major)
- Antioxidants|ME/*TU; Myocardial Reperfusion Injury|*PC; Myocardium|*ME;
Oxidants|*ME; Sulfhydryl Compounds|*TU
- MeSH Heading
- Animal; Coronary Disease|ME; Free Radicals|ME; Human; Models,
Biological; Neutrophils|DE/ME; Oxygen|AI; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC
- ISSN
- 0002-9343
- Country of Publication
- UNITED STATES
Record 31 from database: MEDLINE
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- Title
- Cysteine endopeptidase activity levels in normal human tissues,
colorectal adenomas and carcinomas.
- Author
- Shuja S; Sheahan K; Murnane MJ
- Address
- Mallory Institute of Pathology, Boston, MA 02118.
- Source
- Int J Cancer, 1991 Sep, 49:3, 341-6
- Abstract
- We have assayed cysteine endopeptidase activities in 17 types of normal
human tissue and in matched sets of colorectal mucosa, adenoma and
carcinoma samples. Our data indicate that cathepsin B enzyme levels vary
70-fold and cathepsin L enzyme levels vary 20-fold from one normal tissue
to another. Cathepsin B specific activity in normal tissues fell into 3
categories. High activity, with a mean of 156.7 +/- 41.5 nmoles min-1 mg-1
protein, was measured in liver, thyroid, kidney and spleen; intermediate
activity, with a mean of 60.2 +/- 8.3 nmoles min-1 mg-1 protein, was
measured in heart, colon, adrenal and lung; and low activity, with a mean
of 18.4 +/- 9.7 nmoles min-1 mg-1 protein, was measured in prostate,
testis, nerve, stomach, pancreas, brain, skeletal muscle, skin and breast.
Cathepsin L specific activity fell into 2 categories. High activity, with
a mean of 51.1 +/- 4.9 nmoles min-1 mg-1 protein, was measured in thyroid,
liver and kidney; and low activity, with a mean of 11.4 +/- 5.5 nmoles
min-1 mg-1 protein, was measured in spleen, colon, heart, adrenal, lung,
testis, brain, nerve, skin, stomach, pancreas, skeletal muscle, prostate
and breast. Our characterization of these enzyme levels provides a
reference standard for normal cathepsin B and L activities in human
tissues that should enhance the detection of their deregulation in disease
states. For example, in studies of colorectal carcinoma and normal mucosa,
we observed a significant tumor-specific increase in cathepsin B and L
activities with particularly high activity levels in earlier (Dukes' A and
B) compared to later (Dukes' C and D) stages of colorectal cancer. In
contrast, adenomas from colorectal cancer patients expressed normal levels
of cathepsin B activity, providing evidence that the increase in
expression of cathepsin B may be a sensitive marker for progression from
the pre-malignant to the malignant state in the development of colorectal
cancer.
- Language of Publication
- English
- Unique Identifier
- 92010343
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- MeSH Heading (Major)
- Adenoma|*EN/PA; Carcinoma|*EN/PA; Cathepsin B|*ME; Cathepsins|*ME;
Colorectal Neoplasms|*EN/PA
- MeSH Heading
- Human; Intestinal Mucosa|EN; Neoplasm Staging; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0020-7136
- Country of Publication
- UNITED STATES
Record 32 from database: MEDLINE
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- Title
- Enantioselectivity in the metabolism of mexiletine by conjugation in
female patients with the arrhythmic form of chronic Chagas' heart disease.
- Author
- Lanchote VL; Cesarino EJ; Santos VJ; Mere Júnior Y; Santos SR
- Address
- Faculdade de CiÈencias FarmacÈeuticas de RibeirÃao Preto,
Universidade de SÃao Paulo, RibeirÃao Preto, Brazil.
- Source
- Chirality, 1999, 11:1, 29-32
- Abstract
- The phenomenon of enantioselectivity in the metabolism of mexiletine (MEX)
conjugation was investigated in eight female patients with the arrhythmic
form of chronic Chagas' heart disease treated with racemic mexiletine
hydrochloride (two 100 mg capsules every 8 hr). Blood samples were
collected up to 24 hr after the administration of the morning dose, with
discontinuation of the subsequent doses during the study period. Plasma
concentrations of N-hydroxymexiletine glucuronide were calculated as the
difference between the concentrations of unchanged and total (unchanged +
conjugated) MEX enantiomers. Total plasma MEX concentrations were analyzed
by HPLC after enzymatic hydrolysis with beta-glucuronidase, the formation
of diastereomeric derivatives with the chiral reagent
N-acetyl-L-cysteine/o-phthalaldehyde, and fluorescence detection. The
differences in the pharmacokinetic parameters of the enantiomers were
evaluated by the paired t-test. The plasma concentrations of the (+)-(S)-MEX
did not differ before and after enzymatic hydrolysis. The pharmacokinetic
parameters calculated for (-)-(R)-N-hydroxymexiletine glucuronide are
presented as means (95% confidence interval): maximum plasma concentration
Cmax = 194.0 ng.ml-1 (154.3-233.7), time to maximum plasma concentration
tmax = 1.4 hr (0.3-2.5), area under the plasma concentration versus time
curve AUC0-24 = 2099.2 ng.h.ml-1 (1585.6-2612.6), elimination half-life
t1/2 beta = 12.8 hr (9.9-15.6) and extent of conjugation of 31.6%
(24.3-38.9%). The present data indicate stereospecific conjugation of
(-)-(R)-N-hydroxymexiletine in the female patients with the arrhythmic
form of Chagas' heart disease.
- Language of Publication
- English
- Unique Identifier
- 99113079
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- MeSH Heading (Major)
- Anti-Arrhythmia Agents|CH/*PK; Chagas Cardiomyopathy|*ME/PP;
Mexiletine|CH/*PK
- MeSH Heading
- Adult; Aged; Area Under Curve; Arrhythmia|ME/PP; Biotransformation;
Chronic Disease; Female; Glucuronates|ME; Human; Hydroxylation; Middle
Age; Stereoisomerism
- Publication Type
- CLINICAL TRIAL; JOURNAL ARTICLE
- ISSN
- 0899-0042
- Country of Publication
- UNITED STATES
Record 33 from database: MEDLINE
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- Title
- Malignant familial hypertrophic cardiomyopathy in a family with a
453Arg-->Cys mutation in the beta-myosin heavy chain gene: coexistence
of sudden death and end-stage heart failure.
- Author
- Ko YL; Chen JJ; Tang TK; Cheng JJ; Lin SY; Liou YC; Kuan P; Wu CW; Lien
WP; Liew CC
- Address
- Department of Internal Medicine, National Taiwan University Hospital,
Taipei, Republic of China.
- Source
- Hum Genet, 1996 May, 97:5, 585-90
- Abstract
- Recent genotype-phenotype correlation studies in familial hypertrophic
cardiomyopathy (FHC) have revealed that some mutations in the beta- myosin
heavy chain (BMHC) gene may be associated with a high incidence of sudden
death and a poor prognosis. Coexistence of sudden death and end-stage
heart failure in several families with FHC has recently being reported;
however, the genetic basis of such families has not been clearly
demonstrated. A three-generation Chinese familial hypertrophic
cardiomyopathy (FHC) family (family HLI) with two cases of end-stage heart
failure and three cases of sudden death was analyzed. The average age of
death in the affected members in this family was 34 years old. Genetic
linkage analysis using polymorphisms in the (alpha- and beta-myosin heavy
chain genes revealed that FHC in this family is significantly linked to
the BMHC gene without recombinations. Single-strand conformation
polymorphism analysis of exons 8, 9 and 13 to 23 in the BMHC gene showed a
polymorphic band on exon 14 that is in complete linkage with the disease
status in this family. DNA sequencing analysis in the affected members
revealed an 453Arg-->Cys mutation in the BMHC gene. To our knowledge
this is the first reported mutation of FHC in Chinese. Our data suggest
that the 453Arg-->Cys mutation is associated with a malignant clinical
course in FHC due not only to sudden death but also to end-stage heart
failure.
- Language of Publication
- English
- Unique Identifier
- 96209901
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- MeSH Heading (Major)
- Arginine|*; Cardiomyopathy, Hypertrophic|*GE/MO/PP; Chromosomes, Human,
Pair 14|*; Cysteine|*; Death, Sudden|*; Heart Failure, Congestive|*GE/MO;
Myosin Heavy Chains|*GE; Point Mutation|*; Polymorphism, Restriction
Fragment Length|*
- MeSH Heading
- Adolescence; Adult; Amino Acid Sequence; Base Sequence; Case Report;
China; Chromosome Mapping; DNA Primers; Family; Female; Human; Linkage
(Genetics); Male; Molecular Sequence Data; Pedigree; Polymerase Chain
Reaction; Polymorphism, Single-Stranded Conformational; Prognosis;
Support, Non-U.S. Gov't; Survival Analysis
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0340-6717
- Country of Publication
- GERMANY
Record 34 from database: MEDLINE
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- Title
- Apolipoprotein E-1Harrisburg: a new variant of apolipoprotein E
dominantly associated with type III hyperlipoproteinemia.
- Author
- Mann WA; Gregg RE; Sprecher DL; Brewer HB Jr
- Address
- Molecular Disease Branch, National Heart, Lung and Blood Institute,
Bethesda, MD 20892.
- Source
- Biochim Biophys Acta, 1989 Oct, 1005:3, 239-44
- Abstract
- Apolipoprotein E (apoE) is important in the modulation of the catabolism
of chylomicron and very low density lipoprotein (VLDL) remnants. ApoE has
three major genetically determined isoproteins in plasma, designated
apoE-2, apoE-3 and apoE-4, with homozygosity for the allele coding for
apoE-2 being associated with dysbetalipoproteinemia or type III
hyperlipoproteinemia (HLP). We describe a new variant of apoE,
apoE-1Harrisburg, which is, in contrast to apoE-2, dominantly associated
with type III HLP. Five of twelve members of the affected kindred are
heterozygous for the mutant form of apoE, and four of the five have type
III HLP, while the fifth member has dysbetalipoproteinemia on diet
therapy. Neuraminidase digestion, which removes charged sialic acid
residues, did not alter the electrophoretic position of the
apoE-1Harrisburg isoprotein, indicating that the altered charge of
apoE-1Harrisburg was not due to sialic acid addition to the apolipoprotein.
Cysteamine modification, which adds a positively charged group to
cysteine, resulted in a shift of apoE-1Harrisburg from the E-1 to the E-2
isoform position, indicating that there is one cysteine in
apoE-1Harrisburg as is the case for apoE-3. These results are consistent
with apoE-1Harrisburg originating in the allele for apoE-3 with the
mutation leading to a negative two-unit charge shift. The definitive
identification of a kindred with an apoE variant, apoE-1Harrisburg,
dominantly associated with dysbetalipoproteinemia and type III HLP
provides a unique opportunity to gain important insights into the
structure-function requirements of the E apolipoprotein as well as the
mechanisms by which apoE modulates lipoprotein metabolism.
- Language of Publication
- English
- Unique Identifier
- 90028229
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- MeSH Heading (Major)
- Apolipoproteins E|*BL/GE/IP; Hyperlipoproteinemia Type III|*BL/GE;
Variation (Genetics)|*
- MeSH Heading
- Adolescence; Adult; Aged; Case Report; Electrophoresis, Gel,
Two-Dimensional; Electrophoresis, Polyacrylamide Gel; Female; Human;
Lipoproteins, VLDL|BL/IP; Male; Middle Age; Pedigree; Phenotype
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-3002
- Country of Publication
- NETHERLANDS
Record 35 from database: MEDLINE
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- Title
- Corin, a mosaic transmembrane serine protease encoded by a novel cDNA
from human heart.
- Author
- Yan W; Sheng N; Seto M; Morser J; Wu Q
- Address
- Departments of Cardiovascular Research and Biophysics, Berlex
Biosciences, Richmond, California 94804, USA.
- Source
- J Biol Chem, 1999 May, 274:21, 14926-35
- Abstract
- A novel cDNA has been identified from human heart that encodes an
unusual mosaic serine protease, designated corin. Corin has a predicted
structure of a type II transmembrane protein and contains two
frizzled-like cysteine-rich motifs, seven low density lipoprotein receptor
repeats, a macrophage scavenger receptor-like domain, and a trypsin-like
protease domain in the extracellular region. Northern analysis showed that
corin mRNA was highly expressed in the human heart. In mice, corin mRNA
was detected by in situ hybridization in the cardiac myocytes of the
embryonic heart as early as embryonic day (E) 9.5. By E11.5-13.5, corin
mRNA was most abundant in the primary atrial septum and the trabecular
ventricular compartment. Expression in the heart was maintained through
the adult. In addition, mouse corin mRNA was also detected in the
prehypertrophic chrondrocytes in developing bones. By fluorescent in situ
hybridization analysis, the human corin gene was mapped to 4p12-13 where a
congenital heart disease locus, total anomalous pulmonary venous return,
had been previously localized. The unique domain structure and specific
embryonic expression pattern suggest that corin may have a function in
cell differentiation during development. The chromosomal localization of
the human corin gene makes it an attractive candidate gene for total
anomalous pulmonary venous return.
- Language of Publication
- English
- Unique Identifier
- 99262646
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- MeSH Heading (Major)
- Myocardium|*EN; Serine Proteinases|*GE/IP
- MeSH Heading
- Amino Acid Sequence; Animal; Base Sequence; Chromosome Mapping; Cloning,
Molecular; DNA, Complementary|GE; Human; Mice; Molecular Sequence Data;
Protein Structure, Tertiary; RNA, Messenger|BI; Tumor Cells, Cultured
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-9258
- Country of Publication
- UNITED STATES
Record 36 from database: MEDLINE
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- Title
- Apolipoprotein E-4Philadelphia (Glu13----Lys,Arg145----Cys).
Homozygosity for two rare point mutations in the apolipoprotein E gene
combined with severe type III hyperlipoproteinemia.
- Author
- Lohse P; Mann WA; Stein EA; Brewer HB Jr
- Address
- Molecular Disease Branch, National Heart, Lung, and Blood Institute,
National Institutes of Health, Bethesda, Maryland 20892.
- Source
- J Biol Chem, 1991 Jun, 266:16, 10479-84
- Abstract
- The molecular defect in a 24-year-old white female with severe type III
hyperlipoproteinemia has been elucidated. The patient's apolipoprotein (apo)
E migrated in the apoE-4 position on isoelectric focusing gels. On sodium
dodecyl sulfate-polyacrylamide gel electrophoresis the apoE-4 variant had
a smaller apparent molecular weight than apoE-4(Cys112----Arg). Sequence
analysis of DNA amplified with the polymerase chain reaction revealed two
nucleotide substitutions in the proband's apoE gene. A C to T mutation
converted arginine (CGT) at position 145 of the mature protein to cysteine
(TGT) thus creating the apoE-2 variant. A second G to A substitution at
amino acid 13 led to the exchange of lysine (AAG) for glutamic acid (GAG),
thereby adding 2 positive charge units to the protein and producing the
apoE-5 variant. Computer analysis of the apoE-4Philadelphia gene revealed
that the G to A mutation in exon 3 resulted in the loss of an AvaI
restriction enzyme site. The second mutation, a C to T substitution in the
fourth exon of the apoE gene, eliminated a cleavage site for the enzyme
BbvI. Using these restriction fragment length polymorphisms as well as DNA
sequence analysis we have demonstrated that the patient is homozygous for
both point mutations in the apoE gene.
- Language of Publication
- English
- Unique Identifier
- 91244824
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- MeSH Heading (Major)
- Apolipoproteins E|*GE; Hyperlipoproteinemia Type III|*GE; Mutation|*
- MeSH Heading
- Adult; Amino Acid Sequence; Animal; Arginine|GE; Base Sequence; Case
Report; Cystine|GE; DNA|GE; Electrophoresis, Polyacrylamide Gel; Exons;
Female; Glutamine|GE; Human; Lysine|GE; Molecular Sequence Data;
Polymorphism, Restriction Fragment Length; Restriction Mapping; Support,
Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-9258
- Country of Publication
- UNITED STATES
Record 37 from database: MEDLINE
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- Title
- Mouse apolipoprotein J: characterization of a gene implicated in
atherosclerosis.
- Author
- Jordan Starck TC; Lund SD; Witte DP; Aronow BJ; Ley CA; Stuart WD;
Swertfeger DK; Clayton LR; Sells SF; Paigen B; et al
- Address
- Department of Pharmacology, College of Medicine, University of
Cincinnati, OH 45267.
- Source
- J Lipid Res, 1994 Feb, 35:2, 194-210
- Abstract
- Apolipoprotein J (apoJ), a glycoprotein associated with subclasses of
plasma high density lipoproteins (HDL), was found to accumulate in aortic
lesions in a human subject with transplantation-associated
arteriosclerosis and in mice fed a high-fat atherogenic diet. Foam cells
present in mouse aortic valve lesions expressed apoJ mRNA, suggesting
local synthesis contributes to apoJ's localization in atherosclerotic
plaque. As a prerequisite for elucidating the physiological function of
apoJ by using a mouse model, cDNA clones representing the mouse homolog of
apoJ were isolated, characterized, and sequenced. The nucleotide sequence
predicts a 448 amino acid, 50,260 dalton protein. There was 81% nucleotide
sequence similarity between mouse and human apoJ, and 75% similarity at
the amino acid level. Mouse apoJ contains six potential N-glycosylation
sites, a potential Arg-Ser cleavage site to generate alpha and beta
subunits, a cluster of five cysteine residues in each subunit, three
putative amphipathic helices, and four potential heparin-binding domains.
Southern blot analysis indicates that the gene encompasses approximately
23 kb of DNA. Recombinant inbred strains were used to map apoJ to mouse
chromosome 14, tightly linked to Mtv-11. All of the transcribed portions
of the gene were cloned and analyzed, and all intron-exon boundaries were
defined. The first of the 9 exons is untranslated. Single exons encode the
signal peptide, the cysteine-rich domain in the alpha subunit, two
potential amphipathic helices flanking a heparin-binding consensus
sequence, and a potential amphipathic helix overlapping a heparin-binding
domain, supporting their potential functional significance in apoJ. A
variety of mouse tissues constitutively express a 1.9 kb apoJ mRNA, with
apparently identical transcriptional start sites utilized in all tissues
tested. ApoJ mRNA was most abundant in stomach, liver, brain, and testis,
with intermediate levels in heart, ovary, and kidney. The high degree of
similarity between mouse and human apoJ, in structure and distribution of
the gene product, gene structure, and deposition in atherosclerotic
plaques, suggests that the mouse is an ideal model with which to elucidate
the role of apoJ in HDL metabolism and atherogenesis.
- Language of Publication
- English
- Unique Identifier
- 94223204
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- MeSH Heading (Major)
- Atherosclerosis|DI/*GE; Glycoproteins|AN/*GE
- MeSH Heading
- Amino Acid Sequence; Animal; Base Sequence; Blotting, Southern;
Chromosome Mapping; Coronary Vessels|PA; Disease Models, Animal; DNA,
Complementary|AN; Genetic Markers; Genome; Human; Immunoblotting;
Immunohistochemistry; In Situ Hybridization; Male; Mice; Mice, Inbred CBA;
Mice, Inbred C57BL; Molecular Sequence Data; RNA, Messenger|AN; Support,
Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0022-2275
- Country of Publication
- UNITED STATES
Record 38 from database: MEDLINE
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- Title
- Folic acid responsive postmenopausal homocysteinemia.
- Author
- Brattström LE; Hultberg BL; Hardebo JE
- Address
-
- Source
- Metabolism, 1985 Nov, 34:11, 1073-7
- Abstract
- Homocysteinemia is associated with juvenile arteriosclerosis, recurrent
thromboembolic complications and osteoporosis. Plasma homocysteine,
measured as homocysteine-cysteine mixed disulfide (MDS), has in other than
homocysteinemics been reported to be higher in patients with coronary
heart or cerebrovascular disease than in controls, and higher in men than
in premenopausal women. Here, in groups of normal men and normal
premenopausal and postmenopausal women, we measured plasma MDS in the
fasting state and four hours after a methionine load (100 mg/kg body
weight), before and after four weeks of folic acid therapy at 5 mg daily.
In their fasting plasma, postmenopausal women (n = 5) had significantly (P
less than 0.05) higher MDS concentrations than premenopausal women (n = 5)
and younger men (n = 5). After the methionine load MDS concentrations in
postmenopausal women rose markedly, reaching levels significantly higher
than those in younger men (P less than 0.05), and with no overlap with
values in premenopausal women (P less than 0.01), or in older men (n = 5,
P less than 0.01). Folic acid therapy resulted in substantial reductions
(n = 15, P less than 0.01) of MDS concentrations both before the
methionine load (-31%) and after (-28%), though subjects had initially had
normal concentrations of serum and erythrocyte folates. We speculate that
moderate homocysteinemia might contribute to postmenopausal
arteriosclerosis and osteoporosis. Should this prove to be the case, folic
acid might be a useful prophylactic.
- Language of Publication
- English
- Unique Identifier
- 86039781
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- MeSH Heading (Major)
- Folic Acid|BL/*PD; Homocysteine|*BL; Menopause|*
- MeSH Heading
- Adult; Aging; Cystine|BL; Dipeptides|BL; Fasting; Female; Glycine|BL;
Human; Male; Methionine|BL/DU; Middle Age; Serine|BL; Support, Non-U.S.
Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0026-0495
- Country of Publication
- UNITED STATES
Record 39 from database: MEDLINE
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- Title
- In vivo metabolism of a mutant form of apolipoprotein A-I, apo A-IMilano,
associated with familial hypoalphalipoproteinemia.
- Author
- Roma P; Gregg RE; Meng MS; Ronan R; Zech LA; Franceschini G; Sirtori CR;
Brewer HB Jr
- Address
- Molecular Disease Branch, National Heart, Lung and Blood Institute,
National Institutes of Health, Bethesda, Maryland 20892.
- Source
- J Clin Invest, 1993 Apr, 91:4, 1445-52
- Abstract
- Apo A-IMilano is a mutant form of apo A-I in which cysteine is
substituted for arginine at amino acid 173. Subjects with apo A-IMilano
are characterized by having low levels of plasma HDL cholesterol and apo
A-I. To determine the kinetic etiology of the decreased plasma levels of
the apo A-I in these individuals, normal and mutant apo A-I were isolated,
radiolabeled with either 125I or 131I, and both types of apo A-I were
simultaneously injected into two normal control subjects and two subjects
heterozygous for apo A-IMilano. In the normal subjects, apo A-IMilano was
catabolized more rapidly than the normal apo A-I (mean residence times of
5.11 d for normal apo A-I vs. 3.91 d for apo A-IMilano), clearly
establishing that apo A-IMilano is kinetically abnormal and that it has a
shortened residence time in plasma. In the two apo A-IMilano subjects,
both types of apo A-I were catabolized more rapidly than normal (residence
times ranging from 2.63 to 3.70 d) with normal total apo A-I production
rates (mean of 10.3 vs. 10.4 mg/kg per d in the normal subjects).
Therefore, in the subjects with apo A-IMilano, the decreased apo A-I
levels are caused by rapid catabolism of apo A-I and not to a decreased
production rate, and the abnormal apo A-IMilano leads to the rapid
catabolism of both the normal and mutant forms of apo A-I in the affected
subjects.
- Language of Publication
- English
- Unique Identifier
- 93232267
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- MeSH Heading (Major)
- Apolipoprotein A-I|*GE/*ME; Hypolipoproteinemia|*ME; Lipoproteins,
HDL|*BL
- MeSH Heading
- Adult; Cholesterol|BL; Female; Heterozygote; Human; Kinetics; Male;
Mutation; Support, Non-U.S. Gov't; Tangier Disease|ME; Triglycerides|BL
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-9738
- Country of Publication
- UNITED STATES
Record 40 from database: MEDLINE
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- Title
- Gamma-glutamyl transpeptidase-dependent iron reduction and LDL
oxidation--a potential mechanism in atherosclerosis.
- Author
- Paolicchi A; Minotti G; Tonarelli P; Tongiani R; De Cesare D; Mezzetti
A; Dominici S; Comporti M; Pompella A
- Address
- Department of Experimental Pathology, University of Pisa School of
Medicine, Italy.
- Source
- J Investig Med, 1999 Mar, 47:3, 151-60
- Abstract
- BACKGROUND: gamma-Glutamyl transpeptidase (gamma-GT) is found in serum
and in the plasma membranes of virtually all cell types. Its physiologic
role is to initiate the hydrolysis of extracellular glutathione (GSH), a
tripeptide in which cysteine lies between alpha-glycine and
gamma-glutamate residues. Cysteine and other thiol compounds are known to
promote LDL oxidation by reducing Fe(III) to redox active Fe(II);
therefore, we sought to determine whether similar reactions can be
sustained by GSH and influenced by gamma-GT. METHODS: Fe(III) reduction
and LDL oxidation were studied by monitoring the formation
bathophenanthroline-chelatable Fe(II) and the accumulation of
thiobarbituric acid-reactive substances, respectively. Human atheromatous
tissues were examined by histochemical techniques for the presence of
oxidized LDL and their colocalization with cells expressing gamma-GT
activity. RESULTS: A series of experiments showed that the gamma-glutamate
residue of GSH affected interactions of the juxtaposed cysteine thiol with
iron, precluding Fe(III) reduction and hence LDL oxidation. Both processes
increased remarkably after addition of purified gamma-GT, which acts by
removing the gamma-glutamate residue. GSH-dependent LDL oxidation was
similarly promoted by gamma-GT associated with the plasma membrane of
human monoblastoid cells, and this process required iron traces that can
be found in advanced or late stage atheromas. Collectively, these findings
suggested a possible role for gamma-GT in the cellular processes of LDL
oxidation and atherogenesis. Histochemical analyses confirmed that this
may be the case, showing that gamma-GT activity is expressed by
macrophage-derived foam cells within human atheromas, and that these cells
colocalize with oxidized LDL. CONCLUSIONS: Biochemical and histochemical
correlates indicate that gamma-GT can promote LDL oxidation by hydrolyzing
GSH into more potent iron reductants. These findings may provide
mechanistic clues to the epidemiologic evidence for a possible correlation
between persistent elevation of gamma-GT and the risk of fatal
reinfarction in patients with ischemic heart disease.
- Language of Publication
- English
- Unique Identifier
- 99214760
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- MeSH Heading (Major)
- gamma-Glutamyltransferase|*ME; Atherosclerosis|*ME; Iron|CH/*ME;
Lipoproteins, LDL|CH/*ME
- MeSH Heading
- Adult; Aged; Catalase|PD; Chelating Agents|ME; Foam Cells|EN/PA;
Glutathione|PD; Human; Immunoenzyme Techniques; Lipid Peroxidation|PH;
Male; Middle Age; Phenanthrolines|ME; Superoxide Dismutase|ME; Support,
Non-U.S. Gov't; Thiobarbituric Acid Reactive Substances|ME; U937 Cells
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 1081-5589
- Country of Publication
- UNITED STATES
Record 41 from database: MEDLINE
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- Title
- Guanylin regulatory peptides: structures, biological activities mediated
by cyclic GMP and pathobiology.
- Author
- Forte LR
- Address
- The Harry S. Truman Memorial V.A. Hospital, Columbia, MO 65212, USA. lrf@missouri.edu
- Source
- Regul Pept, 1999 May, 81:1-3, 25-39
- Abstract
- The guanylin family of bioactive peptides consists of three endogenous
peptides, including guanylin, uroguanylin and lymphoguanylin, and one
exogenous peptide toxin produced by enteric bacteria. These small
cysteine-rich peptides activate cell-surface receptors, which have
intrinsic guanylate cyclase activity, thus modulating cellular function
via the intracellular second messenger, cyclic GMP. Membrane guanylate
cyclase-C is an intestinal receptor for guanylin and uroguanylin that is
responsible for stimulation of Cl- and HCO3- secretion into the intestinal
lumen. Guanylin and uroguanylin are produced within the intestinal mucosa
to serve in a paracrine mechanism for regulation of intestinal fluid and
electrolyte secretion. Enteric bacteria secrete peptide toxin mimics of
uroguanylin and guanylin that activate the intestinal receptors in an
uncontrolled fashion to produce secretory diarrhea. Opossum kidney
guanylate cyclase is a key receptor in the kidney that may be responsible
for the diuretic and natriuretic actions of uroguanylin in vivo.
Uroguanylin serves in an endocrine axis linking the intestine and kidney
where its natriuretic and diuretic actions contribute to the maintenance
of Na+ balance following oral ingestion of NaCl. Lymphoguanylin is highly
expressed in the kidney and myocardium where this unique peptide may act
locally to regulate cyclic GMP levels in target cells. Lymphoguanylin is
also produced in cells of the lymphoid-immune system where other
physiological functions may be influenced by intracellular cyclic GMP.
Observations of nature are providing insights into cellular mechanisms
involving guanylin peptides in intestinal diseases such as colon cancer
and diarrhea and in chronic renal diseases or cardiac disorders such as
congestive heart failure where guanylin and/or uroguanylin levels in the
circulation and/or urine are pathologically elevated. Guanylin peptides
are clearly involved in the regulation of salt and water homeostasis, but
new findings indicate that these novel peptides have diverse physiological
roles in addition to those previously documented for control of intestinal
and renal function.
- Language of Publication
- English
- Unique Identifier
- 99321328
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- MeSH Heading (Major)
- Colonic Neoplasms|*ME; Cyclic GMP|*ME; Intestines|*ME; Kidney
Diseases|ME/*PP; Peptides|CH/GE/*ME/PD
- MeSH Heading
- Amino Acid Sequence; Animal; Diarrhea|ME; Guanylate Cyclase|ME; Human;
Molecular Sequence Data
- Publication Type
- JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
- ISSN
- 0167-0115
- Country of Publication
- NETHERLANDS
Record 42 from database: MEDLINE
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- Title
- Molecular cloning of the amino-terminal region of a rat MUC 2 mucin gene
homologue. Evidence for expression in both intestine and airway.
- Author
- Ohmori H; Dohrman AF; Gallup M; Tsuda T; Kai H; Gum JR Jr; Kim YS;
Basbaum CB
- Address
- Department of Anatomy, University of California, San Francisco 94143.
- Source
- J Biol Chem, 1994 Jul, 269:27, 17833-40
- Abstract
- To obtain cDNAs for analysis of mucin gene transcription in rat models
of human disease, we screened a rat intestinal cDNA library in lambda
ZAPII using an upstream non-tandem repeat cDNA fragment of the human MUC 2
gene (Gum, J., Hicks, J., Toribara, N., Rothe, E., Lagace, R., and Y., K.
(1992) J. Biol. Chem. 267, 21375-21383). Three cDNAs, 1-1, 8-1, and 21-1,
were isolated. A translation start site was found in cDNA 21-1. Combined
nucleotide sequence for the three cDNAs contained an open reading frame
spanning 4546 base pairs. This amino-terminal sequence contains a
non-tandem repeat domain enriched in cysteine (1391 residues) followed by
an irregular tandem repeat domain (122 residues). Identity with the human
gene is about 80% in the non-tandem repeat domain and about 38% in the
irregular tandem repeat domain. Primer extension and S1 nuclease
protection analysis indicate a transcription start site at 28 base pairs
upstream of translation initiation. Northern analysis showed expression of
cognate RNA in the intestine and airway but not heart and spleen. The
cDNAs have been used to isolate the gene promoter, the structure of which
should yield clues to the regulation of mucin expression in rat models of
human disease.
- Language of Publication
- English
- Unique Identifier
- 94299489
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- MeSH Heading (Major)
- Intestines|*ME; Mucins|BI/CH/*GE; Trachea|*ME
- MeSH Heading
- Amino Acid Sequence; Animal; Base Sequence; Blotting, Northern; Cloning,
Molecular; DNA; Human; In Situ Hybridization; Male; Molecular Sequence
Data; Rats; Rats, Sprague-Dawley; Sequence Homology, Amino Acid; Support,
Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't,
P.H.S.; Transcription, Genetic
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-9258
- Country of Publication
- UNITED STATES
Record 43 from database: MEDLINE
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- Title
- Human endocarditis due to nutritionally variant streptococci:
streptococcus adjacens and Streptococcus defectivus.
- Author
- Bouvet A
- Address
- UniversitÆe Paris VI, HÈopital HÈotel Dieu, Laboratoire de
Microbiologie, France.
- Source
- Eur Heart J, 1995 Apr, 16 Suppl B:, 24-7
- Abstract
- Streptococcus adjacens and S. defectivus are two recently individualized
species of viridans streptococci. Both species were previously designated
as nutritionally variant streptococci and characterized by their growth as
small satellite colonies supported by 'helper' bacteria, or requiring
complex media enriched with cysteine or with pyridoxal. Structural
abnormalities were observed under these conditions and balanced growth can
be obtained only with a semi-chemically defined medium, in which the cells
are morphologically normal and exhibit a parietal chromophore. The two
species are primarily isolated from the oral cavity, or from intestinal
and genito-urinary tracts. They are likely to be responsible for most
blood-culture-negative endocarditis and account for more than 4% of
streptococcal strains isolated from blood cultures during this disease.
Cases of endocarditis caused by these bacteria exhibit much higher rates
of failure, relapse and mortality than those due to other viridans
streptococci. The slow growth rate of the bacteria and the production of
large amounts of exopolysaccharide in vivo may account for the
difficulties encountered in treatment and suggest that a longer course of
antimicrobial therapy may be required for successful cures. Results
obtained from experimental models of endocarditis confirmed the efficacy
of vancomycin as an alternative therapy in patients when a combination of
penicillin and aminoglycoside is ineffective or contraindicated.
- Language of Publication
- English
- Unique Identifier
- 95401981
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- MeSH Heading (Major)
- Endocarditis, Bacterial|DI/DT/*MI; Streptococcal Infections|DI/DT/*MI;
Streptococcus|DE/*IP
- MeSH Heading
- Animal; Antibiotics|TU; Human; Microbial Sensitivity Tests
- Publication Type
- JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
- ISSN
- 0195-668X
- Country of Publication
- ENGLAND
Record 44 from database: MEDLINE
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- Title
- cDNA and genomic cloning of human palmitoyl-protein thioesterase (PPT),
the enzyme defective in infantile neuronal ceroid lipofuscinosis
[published erratum appears in Genomics 1996 Dec 15;38(3):458]
- Author
- Schriner JE; Yi W; Hofmann SL
- Address
- Department of Internal Medicine, University of Texas Southwestern
Medical Center, Dallas, Texas 75235, USA.
- Source
- Genomics, 1996 Jun, 34:3, 317-22
- Abstract
- Palmitoyl-protein thioesterase (PPT) is a small glycoprotein that
removes palmitate groups from cysteine residues in lipid-modified
proteins. We recently reported mutations in PPT in patients with infantile
neuronal ceroid lipofuscinosis (INCL), a severe neurodegenerative disorder
(J. Vesa et al., 1995, Nature 376: 584-587). INCL is characterized by the
accumulation of proteolipid storage material in brain and other tissues,
suggesting that the disease is a consequence of abnormal catabolism of
acylated proteins. In the current paper, we report the sequence of the
human PPT cDNA and the structure of the human PPT gene. The cDNA predicts
a protein of 306 amino acids that contains a 25-amino-acid signal peptide,
three N-linked glycosylation sites, and consensus motifs characteristic of
thioesterases. Northern analysis of a human tissue blot revealed
ubiquitous expression of a single 2.5-kb mRNA, with highest expression in
lung, brain, and heart. The human PPT gene spans 25 kb and is composed of
seven coding exons and a large eighth exon, containing the entire
3'-untranslated region of 1388 bp. An Alu repeat and promoter elements
corresponding to putative binding sites for several general transcription
factors were identified in the 1060 nucleotides upstream of the
transcription start site. The human PPT cDNA sequence and gene structure
will provide the means for the identification of further causative
mutations in INCL and facilitate genetic screening in selected high-risk
populations.
- Language of Publication
- English
- Unique Identifier
- 96374822
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- MeSH Heading (Major)
- Neuronal Ceroid-Lipofuscinosis|EN/*GE; Thiolester Hydrolases|*BI/DF/*GE
- MeSH Heading
- Amino Acid Sequence; Base Sequence; Brain|EN; Cloning, Molecular; DNA,
Complementary; Exons; Female; Human; Infant; Introns; Molecular Sequence
Data; Organ Specificity; Placenta|EN; Polymerase Chain Reaction;
Pregnancy; Restriction Mapping; RNA, Messenger|BI; Support, Non-U.S.
Gov't; Support, U.S. Gov't, P.H.S.; Temporal Lobe|EN; Transcription,
Genetic
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0888-7543
- Country of Publication
- UNITED STATES
Record 45 from database: MEDLINE
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- Title
- Development of nitrate tolerance in human arteries and veins: comparison
of nitroglycerin and SPM 5185.
- Author
- Arnet U; Yang Z; Siebenmann R; von Segesser LK; Turina M; Stulz P;
Lüscher TF
- Address
- Department of Research, University Hospitals, Basel, Switzerland.
- Source
- J Cardiovasc Pharmacol, 1995 Sep, 26:3, 401-6
- Abstract
- Nitrate tolerance is a clinical problem in patients with coronary artery
disease and heart failure. Human internal mammary arteries and saphenous
veins obtained intraoperatively were suspended in organ chambers, and
isometric tension was measured. In the artery, nitroglycerin elicited a
potent relaxation, which was significantly diminished after prolonged
incubation with nitroglycerin (10(-6) M, 1 h). In contrast, no tolerance
occurred in saphenous vein under the same conditions. However, incubation
with 10(-5) M nitroglycerin also developed tolerance. Compared to
nitroglycerin, the new cysteine-containing mononitrate SPM 5185 exhibited
a lower sensitivity but comparable maximal relaxation in arteries and
veins. In nitroglycerin-tolerant arteries and veins, SPM 5185 caused
relaxations similar to those under control conditions. Our results show
that in isolated blood vessels, vascular nitrate tolerance occurs more
readily in the mammary artery than in the saphenous vein. SPM 5185 seems
to be less prone to the development of tolerance, which may be
advantageous during chronic nitrate therapy.
- Language of Publication
- English
- Unique Identifier
- 96058636
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- MeSH Heading (Major)
- Dipeptides|ME/*PD/TU; Muscle, Smooth, Vascular|*DE; Nitroglycerin|ME/*PD/TU;
Vasodilator Agents|ME/*PD/TU
- MeSH Heading
- Acetylcysteine|PD/TU; Arginine|AA/PD/TU; Drug Tolerance; Free Radical
Scavengers|PD/TU; Human; In Vitro; Isometric Contraction|DE; Mammary
Arteries|DE/ME; Muscle Relaxation|DE; Myocardial Reperfusion Injury|DT;
Nitric-Oxide Synthase|AI; Saphenous Vein|DE/ME; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0160-2446
- Country of Publication
- UNITED STATES
Record 46 from database: MEDLINE
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- Title
- Mutations of the microsomal triglyceride-transfer-protein gene in
abetalipoproteinemia.
- Author
- Narcisi TM; Shoulders CC; Chester SA; Read J; Brett DJ; Harrison GB;
Grantham TT; Fox MF; Povey S; de Bruin TW; et al
- Address
- MRC Molecular Medicine Group, Royal Postgraduate Medical School,
Hammersmith Hospital, London, United Kingdom.
- Source
- Am J Hum Genet, 1995 Dec, 57:6, 1298-310
- Abstract
- Elevated plasma levels of apolipoprotein B (apoB)-containing
lipoproteins constitute a major risk factor for the development of
coronary heart disease. In the rare recessively inherited disorder
abetalipoproteinemia (ABL) the production of apoB-containing lipoproteins
is abolished, despite no abnormality of the apoB gene. In the current
study we have characterized the gene encoding a microsomal triglyceride-transfer
protein (MTP), localized to chromosome 4q22-24, and have identified a
mutation of the MTP gene in both alleles of all individuals in a cohort of
eight patients with classical ABL. Each mutant allele is predicted to
encode a truncated form of MTP with a variable number of aberrant amino
acids at its C-terminal end. Expression of genetically engineered forms of
MTP in Cos-1 cells indicates that the C-terminal portion of MTP is
necessary for triglyceride-transfer activity. Deletion of 20 amino acids
from the carboxyl terminus of the 894-amino-acid protein and a missense
mutation of cysteine 878 to serine both abolished activity. These results
establish that defects of the MTP gene are the predominant, if not sole,
cause of hereditary ABL and that an intact carboxyl terminus is necessary
for activity.
- Language of Publication
- English
- Unique Identifier
- 96065017
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- MeSH Heading (Major)
- Abetalipoproteinemia|*GE; Carrier Proteins|*GE; Mutation|*
- MeSH Heading
- Adult; Base Sequence; Chromosome Mapping; Female; Human; Infant; Male;
Microsomes|ME; Molecular Sequence Data; Polymerase Chain Reaction;
Polymorphism (Genetics)
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0002-9297
- Country of Publication
- UNITED STATES
Record 47 from database: MEDLINE
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- Title
- Identification of polymorphic sites of the human bradykinin B2 receptor
gene.
- Author
- Braun A; Kammerer S; Böhme E; Müller B; Roscher AA
- Address
- Children's Hospital, Department of Clinical Chemistry and Biochemistry,
University of Munich, Germany.
- Source
- Biochem Biophys Res Commun, 1995 Jun, 211:1, 234-40
- Abstract
- The characterization of the genomic organization of the B2 bradykinin
receptor gene enabled us to systematically search for polymorphic markers
in this gene in a South German cohort (N = 179). We identified at least
three polymorphic sites in each of the three exons existing: (i) in exon 1
next to the promoter region, a tandem repeat polymorphism consists of
three common alleles, (ii) in exon 2 at nucleotide position 181 of the
cDNA a C to T transition leads to an aminoacid substitution from arginine
to cysteine in the receptor protein at position 14 (R14C), and (iii) a
more complex repeat polymorphism, located in the 3' not-translated region
of exon 3, comprises at least two common alleles and two rare variants.
These new genetic markers provide valuable tools to elucidate a potential
role of a hereditary dysfunction of the B2 bradykinin receptor gene in
disorders such as hypertension or ischemic heart disease.
- Language of Publication
- English
- Unique Identifier
- 95298028
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- MeSH Heading (Major)
- Hominidae|*GE; Polymorphism (Genetics)|*; Receptors, Bradykinin|*GE
- MeSH Heading
- Alleles; Animal; Base Sequence; Cohort Studies; Comparative Study; DNA
Primers; Exons; Gene Frequency; Germany; Human; Molecular Sequence Data;
Polymerase Chain Reaction; Repetitive Sequences, Nucleic Acid; Support,
Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-291X
- Country of Publication
- UNITED STATES
Record 48 from database: MEDLINE
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- Title
- Enantioselective analysis of N-hydroxymexiletine glucuronide in human
plasma for pharmacokinetic studies.
- Author
- Lanchote VL; Santos VJ; Cesarino EJ; Dreossi SA; Mere Júnior Y; Santos
SR
- Address
- Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade
de São Paulo, Brazil.
- Source
- Chirality, 1999, 11:2, 85-90
- Abstract
- Enzymatic hydrolysis with beta-glucuronidase/sulfatase was used for the
enantioselective determination of N-hydroxymexiletine glucuronide in
plasma for pharmacokinetic studies. N-Hydroxymexiletine glucuronide was
determined as the quantity of mexiletine released by hydrolysis
(difference between the enantiomeric concentrations of mexiletine obtained
with and without hydrolysis). Plasma samples (100 microliters) were
treated at pH 5.0 with 10 mg of the enzyme (Limpet Acetone Powder type I)
for 16 hr at 37 degrees C and extracted at pH 10.4 with diisopropyl ether.
Chiral mexiletine discrimination was obtained by reaction with o-phthalaldehyde/N-acetyl-L-cysteine,
separation of the resulting diastereomers on a C-18 reversed-phase column
with a mobile phase of methanol-0.05 N acetate buffer, pH 5.5 (6.5:3.5,
v/v), and fluorescence detection (lambda ex 350 nm, lambda em 455 nm). The
performance characteristics for the enantioselective analysis of
mexiletine preceded by enzymatic hydrolysis were recovery approximately
90%, quantification limit 1 ng/ml, and linearity up to 1000 ng/ml plasma
for both enantiomers. The coefficients of variation obtained in the study
of intra- and inter-day precision were respectively 5% and 7% for both
enantiomers. The assay was shown to be suitable for a pharmacokinetic
study performed in a patient with the arrhythmic form of chronic Chagas'
heart disease treated with 200 mg t.i.d. of racemic mexiletine
hydrochloride. The high sensitivity of the method allows analysis of only
100 microliters plasma.
- Language of Publication
- English
- Unique Identifier
- 99136551
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- MeSH Heading (Major)
- Anti-Arrhythmia Agents|*BL; Mexiletine|*AA/BL
- MeSH Heading
- Calibration; Chromatography, High Pressure Liquid; Human; Hydrolysis;
Reproducibility of Results; Stereoisomerism; Substrate Specificity
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0899-0042
- Country of Publication
- UNITED STATES
- CAS Registry/EC Number
- 0 (Anti-Arrhythmia Agents); 151636-18-9 (N-hydroxymexiletine glucuronide);
31828-71-4 (Mexiletine)
Record 49 from database: MEDLINE
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- Title
- Clinical applications of N-acetylcysteine.
- Author
- Kelly GS
- Address
- Alternative Medicine Review, Greenwich, CT.
- Source
- Altern Med Rev, 1998 Apr, 3:2, 114-27
- Abstract
- N-acetylcysteine (NAC), the acetylated variant of the amino acid
L-cysteine, is an excellent source of sulfhydryl (SH) groups, and is
converted in the body into metabolites capable of stimulating glutathione
(GSH) synthesis, promoting detoxification, and acting directly as free
radical scavengers. Administration of NAC has historically been as a
mucolytic agent in a variety of respiratory illnesses; however, it appears
to also have beneficial effects in conditions characterized by decreased
GSH or oxidative stress, such as HIV infection, cancer, heart disease, and
cigarette smoking. An 18-dose oral course of NAC is currently the mainstay
of treatment for acetaminophen-induced hepatotoxicity. N-acetylcysteine
also appears to have some clinical usefulness as a chelating agent in the
treatment of acute heavy metal poisoning, both as an agent capable of
protecting the liver and kidney from damage and as an intervention to
enhance elimination of the metals.
- Language of Publication
- English
- Unique Identifier
- 98238108
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- MeSH Heading (Major)
- Acetylcysteine|AE/PD/*TU; Free Radical Scavengers|AE/PD/*TU
- MeSH Heading
- Antiviral Agents|TU; Expectorants|TU; Glutathione|BI; Human;
Poisoning|DT
- Publication Type
- JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
- ISSN
- 1089-5159
- Country of Publication
- UNITED STATES
Record 50 from database: MEDLINE
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- Title
- A major involvement of the cardiovascular system in patients affected by
Marfan syndrome: novel mutations in fibrillin 1 gene.
- Author
- Pepe G; Giusti B; Attanasio M; Comeglio P; Porciani MC; Giurlani L;
Montesi GF; Calamai GC; Vaccari M; Favilli S; Abbate R; Gensini GF
- Address
- Istituto di Clinica Medica Generale e Cardiologia, University of
Florence, Florence, Italy.
- Source
- J Mol Cell Cardiol, 1997 Jul, 29:7, 1877-84
- Abstract
- The aim of our study was to characterize the molecular defect in Italian
Marfan patients, thus contributing to the effort of correlating the
genotype with the phenotype. In particular, our ultimate goal was to
identify the region(s) of the fibrillin 1 (FBN1) gene mainly involved in
the health of the heart and of the aorta in terms of the cardiovascular
system. We searched for a molecular defect in three patients with classic
Marfan syndrome (MFS). The mutations were detected applying heteroduplex
analysis to each of the 65 exons of the FBN1 gene amplified by polymerase
chain reaction (PCR). Exons containing heteroduplex bands were sequenced
directly from PCR products. This study reports the detection of three
unique missense mutations in the FBN1 gene in three Italian patients: a
44-year-old adult male and 36-year-old female affected by classic MFS
(with all the cardinal manifestations in the cardiovascular, ocular and
skeletal systems), and an 11-year-old male affected by infantile (earlier
onset) classic MFS. The first two are sporadic cases and present a Cys-->Arg
amino acid substitution (T-->C substitution at nucleotide 7729) in exon
62 and a Cys-->Tyr amino acid substitution (G-->A substitution at
nucleotide 6695) in exon 54. The third is a familial case which presents a
Cys-->Trp aminoacidic substitution (C-->G substitution at nucleotide
3546) in exon 28. Our data confirm that cysteine substitutions in calcium
binding epidermal growth factor (cbEGF)-like domains cause severe Marfan
phenotype. Exon 24-32 cluster seems to produce an even more severe
phenotype. The early characterization may be of clinical relevance for
prevention and early surgical treatment of aortic aneurysm or dissection.
- Language of Publication
- English
- Unique Identifier
- 97383391
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- MeSH Heading (Major)
- Cardiovascular Diseases|*GE; Marfan Syndrome|*GE; Microfilament
Proteins|*GE
- MeSH Heading
- Adult; Base Sequence; Case Report; Child; Female; Human; Male; Mutation;
Protein Structure, Secondary; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0022-2828
- Country of Publication
- ENGLAND
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