Record 1 from database: MEDLINE
Return
To Top
- 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
Return
To Top
- 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
Return
To Top
- 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
Return
To Top
- 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
Return
To Top
- 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
Return
To Top
- 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
Return
To Top
- 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
Return
To Top
- 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
Return
To Top
- 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
Return
To Top
- 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
Return
To Top
- 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
Return
To Top
- 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
Return
To Top
- 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
Return
To Top
- 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
Return
To Top
- 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
Return
To Top
- 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
Return
To Top
Return
To Menu Position #10
- 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
Return
To Top
Return
To Menu Position #10
- 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
Return
To Top
Return
To Menu Position #10
- 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
Return
To Top
Return
To Menu Position #10
- 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
Return
To Top
Return
To Menu Position #10
- 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
Return
To Top
Return
To Menu Position #10
- 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
Return
To Top
Return
To Menu Position #10
- 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
Return
To Top
Return
To Menu Position #10
- 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
Return
To Top
Return
To Menu Position #10
- 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
Return
To Top
Return
To Menu Position #10
- 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
Return
To Top
Return
To Menu Position #10
- 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
Return
To Top
Return
To Menu Position #10
- 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
Return
To Top
Return
To Menu Position #10
- 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
Return
To Top
Return
To Menu Position #10
- 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
Return
To Top
Return
To Menu Position #10
- 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
Return
To Top
Return
To Menu Position #10
- 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
Return
To Top
Return
To Menu Position #10
- 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
Return
To Top
Return
To Menu Position #10
- 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
Return
To Top
Return
To Menu Position #10
Return
To Menu Position #20
- 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
Return
To Top
Return
To Menu Position #10
Return
To Menu Position #20
- 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
Return
To Top
Return
To Menu Position #10
Return
To Menu Position #20
- 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
Return
To Top
Return
To Menu Position #10
Return
To Menu Position #20
- 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
Return
To Top
Return
To Menu Position #10
Return
To Menu Position #20
- 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
Return
To Top
Return
To Menu Position #10
Return
To Menu Position #20
- 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
Return
To Top
Return
To Menu Position #10
Return
To Menu Position #20
- 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
Return
To Top
Return
To Menu Position #10
Return
To Menu Position #20
- 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
Return
To Top
Return
To Menu Position #20
- 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
Return
To Top
Return
To Menu Position #20
- 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
Return
To Top
Return
To Menu Position #20
- 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
Return
To Top
Return
To Menu Position #20
- 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
Return
To Top
Return
To Menu Position #20
- 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
Return
To Top
Return
To Menu Position #20
- 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
Return
To Top
Return
To Menu Position #20
- 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
Return
To Top
Return
To Menu Position #20
- 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
Return
To Top
Return
To Menu Position #20
- 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
Return
To Top
Return
To Menu Position #20
- 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
Return
To Top
Return
To Menu Position #20
- 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 w
Click on the image to go to
the page which links to all the other pages on this web site on the subject of "oral
chelation."
