Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Early in the course of studies of the Spanish toxic oil syndrome it was recognized that vascular lesions were a major problem, most logically attributable to endothelial damage by the toxic oil. However, most clinical attention has been directed to the pulmonary complications and the evolution into a scleroderma-like illness later. In this study of 11 victims of the toxic oil syndrome careful postmortem studies of the coronary arteries and conduction system and neural structures of the heart demonstrated major injury to all those components of the heart. Obliterative fibrosis of the sinus node in four cases resembled findings in fatal scleroderma heart disease, and in eight the cardiac lesions resembled those of lupus erythematosus. The more impressive pathologic features involved the coronary arteries and neural structures, which were abnormal in every heart. The arterial disease included widespread focal fibromuscular dysplasia, but there was also an unusual myointimal proliferative degeneration of both small and large coronary arteries in five patients, four of whom were young women. In two hearts, portions of the inner wall of the sinus node artery had actually detached and embolized downstream. Coronary arteritis was rarely found. Inflammatory and noninflammatory degeneration of cardiac nerves was widespread. Fatty infiltration, fibrosis and degeneration were present in the coronary chemoreceptor. In most respects these cardiac abnormalities resemble those described in the eosinophilia-myalgia syndrome caused by an altered form of L-tryptophan. In both diseases there is good reason to anticipate more clinical cardiac difficulties than have so far been reported, and even more basis for future concern, especially relative to coronary disease and cardiac electrical instability.
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PMID:Cardiac abnormalities in the toxic oil syndrome, with comparative observations on the eosinophilia-myalgia syndrome. 191 15

Kawasaki syndrome (KS), the main cause of acquired heart disease in children, is associated with the selective expansion of V beta 2+ T cells in peripheral blood. Our study suggests that KS may be caused by a superantigen--a staphylococcal or streptococcal toxin. Bacteria were cultured without knowledge of their origin, from the throat, rectum, axilla, and groin of 16 patients with untreated acute KS and 15 controls. Bacteria producing toxins were isolated from 13 of 16 KS patients but from only 1 of 15 controls (p < 0.0001). Toxic shock syndrome toxin (TSST) secreting Staphylococcus aureus was isolated from 11 of the 13 toxin-positive cultures, and streptococcal pyogenic exotoxin (SPE) B and C were found in the other 2. These toxins are known to stimulate V beta 2+ T cells. All TSST-producing KS isolates were tryptophan auxotrophs indicating they were clonally related. S aureus isolates from acute KS patients were unusual because they produced less lipase, haemolysin, and protease compared to other isolates (p < 0.01). S aureus colonies from KS patients were white, and could be easily mistaken for coagulase-negative staphylococci, whereas colonies of non-KS isolates were gold. These observations suggest that the expansion of V beta 2+ T cells in most patients with KS may be caused by a new clone of TSST-producing S aureus, and, in a minority of patients, SPEB-producing or SPEC-producing streptococci.
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PMID:Toxic shock syndrome toxin-secreting Staphylococcus aureus in Kawasaki syndrome. 790 29

I have discussed 10 "new" diseases. Some produce heart disease, some produce strokes, and some may produce both heart disease and stroke. It is of great interest to me that some of them are due not to nature's ravages but to the ingestion of agents such as toxic oil, L-tryptophan, ergot, adriamycin, and psychotropic drugs. I classify these man-made diseases as "environmental" diseases. Use of some of the offending agents cannot be justified; for example, toxic oil and L-tryptophan are not needed. On the other hand, drugs such as ergot preparations are extremely useful when used properly.
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PMID:"New" causes of heart disease and stroke. 814 82

The P0 protein is part of the ribosomal eukaryotic stalk, which is an elongated lateral protuberance of the large ribosomal subunit involved in the translocation step of protein synthesis. P0 is the minimal portion of the stalk that is able to support accurate protein synthesis. The P0 C-terminal peptide is highly antigenic and a major target of the antibody response in patients with systemic lupus erythematosus and patients suffering chronic heart disease produced by the Trypanosoma cruzi parasite. The T. cruzi P0 (TcP0) protein was cloned into the pRSET A vector and expressed in Escherichia coli fused to a His-tag. The identity of the protein was confirmed by immunoblotting. Due to the formation of inclusion bodies the protein was purified using the following steps: (i) differential centrifugation to separate the inclusion bodies from soluble proteins and (ii) affinity chromatography under denaturing conditions. TcP0 showed high tendency to aggregation during refolding assays. However, TcP0 could be efficiently folded in the presence of a low concentration of SDS. The folding of the protein was confirmed using urea gradient electrophoresis, limited proteolysis, circular dichroism, and tryptophan fluorescence. Native electrophoresis showed that the folded TcP0 (and not a folding intermediate) was the cause of aggregation in the absence of SDS. The protocol described here permitted us to obtain large amounts (up to 30 mg per culture liter) of pure and folded TcP0, a very hydrophobic protein with a high tendency to aggregation.
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PMID:Overexpression and refolding of the hydrophobic ribosomal P0 protein from Trypanosoma cruzi: a component of the P1/P2/P0 complex. 1143 98

Generation of new blood vessels from pre-existing vasculature (angiogenesis) is accompanied in almost all states by increased vascular permeability. This is true in physiological as well as pathological angiogenesis, but is more marked during disease states. Physiological angiogenesis occurs during tissue growth and repair in adult tissues, as well as during development. Pathological angiogenesis is seen in a wide variety of diseases, which include all the major causes of mortality in the west: heart disease, cancer, stroke, vascular disease and diabetes. Angiogenesis is regulated by vascular growth factors, particularly the vascular endothelial growth factor family of proteins (VEGF). These act on two specific receptors in the vascular system (VEGF-R1 and 2) to stimulate new vessel growth. VEGFs also directly stimulate increased vascular permeability to water and large-molecular-weight proteins. We have shown that VEGFs increase vascular permeability in mesenteric microvessels by stimulation of tyrosine auto-phosphorylation of VEGF-R2 on endothelial cells, and subsequent activation of phospholipase C (PLC). This in turn causes increased production of diacylglycerol (DAG) that results in influx of calcium across the plasma membrane through store-independent cation channels. We have proposed that this influx is through DAG-mediated TRP channels. It is not known how this results in increased vascular permeability in endothelial cells in vivo. It has been shown, however, that VEGF can stimulate formation of a variety of pathways through the endothelial cell, including transcellular gaps, vesiculovacuolar organelle formation, and fenestrations. A hypothesis is outlined that suggests that these all may be part of the same process.
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PMID:Regulation of microvascular permeability by vascular endothelial growth factors. 1216 26

The complications (thromboembolism and jaundice), averse effects (metabolic disorders, hypertension and bleeding) and the risks (cancer and teratologic effects) of oral contraceptives are summarized and compared to those of other methods. Venous thrombosis is more frequent than arterial thrombosis; both are rare but can be severe; risk is decreased with minidose pills. Cholostatic jaundice is likely only in those with history of such jaundice in pregnancy. Decreased oral glucose tolerance similar to diabetes of pregnancy, similarly, is more common with high dose pills. Triglycerides, pre-beta lipoproteins and t otal cholesterol levels are increased to the upper limit of normal, but stabilize after 3 months of pill intake in normal women. Mixed hyperlipidemia in some women can be detected by the cholesterol to triglycerides ratio after 8 and 12 hours of fasting. Other possible side effects are hypertension, elevated thyroid hormone, depression due to abnormal tryptophan metabolism, acne, cholasma, varices, spotting, amenorrhea. The risk of cancer is still unknown, but that of chromosomal defects in unfounded. To avoid these complications, the physician must observe the contraindications of history of thromboembolism, heart disease, jaundice, hypertension and cancer, and follow patients regularly by gynecologic exam, glucose tolerance and blood lipid tests and take blood pressure. In comparison, diaphragms give 15% failure rates, and copper IUDs less than 1%, but about 10% expulsions and 10% removals for bleeding.
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PMID:[Complications of contraception]. 1225 11

The carcinoid syndrome, associated with carcinoid tumors of the midgut, consists of symptoms such as diarrhea, flushing, wheezing and cardiovascular symptoms. This review focuses on these symptoms and discusses therapeutic options. The symptoms are caused by the secretion of biogenic amines, polypeptides and other factors of which serotonin is the most prominent. However, diarrhea is also due to factors such as malabsorption. Besides antitumor therapy, more specific interventions such as serotonin receptor blockers can be useful. The carcinoid heart disease involves the tricuspid and pulmonary valve. In the pathogenesis, serotonin plays a central role. The therapeutic approach is mostly symptomatic. Other cardiovascular complications include bowel ischemia and hypertension. Pellagra and psychiatric symptoms are due to a depletion of tryptophan, which is consumed by the carcinoid tumor for serotonin synthesis. Finally, follow-up and clinical practice of patients with carcinoid tumors are discussed.
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PMID:Complications of midgut carcinoid tumors and carcinoid syndrome. 1547 13

The Trypanosoma cruzi ribosomal P0 protein (TcP0) is part of the ribosomal stalk, which is an elongated lateral protuberance of the large ribosomal subunit involved in the translocation step of protein synthesis. The TcP0 C-terminal peptide is highly antigenic and a major target of the antibody response in patients with systemic lupus erythematosus and patients suffering chronic heart disease produced by Trypanosoma cruzi infection. The structural properties of TcP0 have been explored by circular dichroism, tryptophan fluorescence and limited proteolysis experiments. These studies were complemented by secondary structure consensus prediction analysis. The results suggest that the tertiary structure of TcP0 could be described as a compact, stable, trypsin-resistant, 200 residues long N-terminal domain belonging to the alpha/beta class and a more flexible, degradable, helical, 123 residues long C-terminal domain which could be involved in the formation of an unusual hydrophobic zipper with the ribosomal P1/P2 proteins to form the P0/P1/P2 complex.
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PMID:Preliminary structural studies of the hydrophobic ribosomal P0 protein from Trypanosoma cruzi, a part of the P0/P1/P2 complex. 1610 88

The congenital heart disease 5 (CHD5)/tryptophan rich basic protein (WRB) is a protein containing a tryptophan-rich carboxy-terminal region, which was discovered in the human fetal heart. In humans, this CHD5/WRB is located between the markers ACTL5-D21S268 within the Down syndrome (DS) Region-2 at chromosome 21. Congenital heart disease is commonly linked to DS patients. The functions of this gene product are unknown. To identify the functions of CHD5/WRB in heart formation during embryogenesis, the medaka CHD5 cDNA (mCHD5) was isolated and its gene expression pattern and the localization of its gene product were investigated. The obtained mCHD5 belongs to the CHD5 superfamily, whose members include coiled-coil proteins. The mCHD5 gene was found to be expressed in the developing heart after stage 28 at which the chamber (ventricle and atrium) differentiation in the heart tube is initiated in the embryo. Its gene product was also detected in the developing heart at embryonic stage 28 and 35. Knocking-down of mCHD5 function caused severe cardiac disorder, including abnormal chamber differentiation, abnormal looping and ocular abnormality such as Cyclops. Our results provide the mCHD5 gene expression pattern as well as its physiological role during heart formation in a vertebrate model system.
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PMID:Expression of the congenital heart disease 5/tryptophan rich basic protein homologue gene during heart development in medaka fish, Oryzias latipes. 1920 81

Arrhythmias are caused by the perturbation of physiological impulse formation, impaired conduction, or disturbed electrical recovery. Currently available antiarrhythmic drugs-perhaps with exception of amiodarone-are not sufficiently effective and are burdened by cardiac and extracardiac side effects that may offset their therapeutic benefits. Detailed knowledge about electrical and structural remodelling may provide a better understanding of the mechanisms leading to generation and maintenance of arrhythmias especially in the setting of underlying heart disease and accompanying autonomic dysfunction. Thus, targets for new pharmacological interventions could include atrial-selective ion channels (e.g. atrial I(Na), I(Kur) and I(K,ACh)), pathology-selective ion channels (constitutively active I(K,ACh), TRP channels), ischemia-uncoupled gap junctions, proteins related to malfunctioning intracellular Ca(2+) homeostasis (e.g. "leaky" ryanodine receptors, overactive Na(+),Ca(2+) exchanger) or risk factors for arrhythmias ("upstream" therapies). In ventricular arrhythmias implantable cardioverter-defibrillator devices rather than antiarrhythmic drugs are the safest treatment option. The domain for new approaches to drug treatment is atrial fibrillation.
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PMID:Novel pharmacological approaches for antiarrhythmic therapy. 2008 92


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