Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary hypothyroidism with marked hyperlipoproteinemia and modest to severe atherosclerosis was described in a family of Beagles. The disease was familial and probably hereditary, but the mode of inheritance was unknown. Signs of the disease occurred as early as 1.5 years of age and as late as 5 years of age. The onset of the disease was heralded by reduced concentrations of serum thyroxine, increased binding capacity of thyroxine-binding globulin, and reduced response to injected thyroxine-stimulating hormone. Thereafter, serum lipids, particularly serum cholesterol, increased markedly even though the dogs consumed a diet low in fats and cholesterol. Thyroxine administration resulted in a precipitous decline in serum cholesterol concentrations. Microscopic changes in the thyroid glands included neoplastic transformation, adenomatous hyperplasia, lymphocytic thyroiditis, and atrophy. Moderate to severe atherosclerosis occurred mainly in the coronary and renal arteries. Atherosclerotic arteries were stenotic but patent, and there was no evidence of prior occlusion or thrombosis.
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PMID:Thyroid gland and arterial lesions of Beagles with familial hypothyroidism and hyperlipoproteinemia. 47 33

We described here a seventy-one year-old male, who had repeated disseminated intravascular coagulation related to atherosclerosis and aneurysm of the aorta, and was successfully treated with self-subcutaneous injection of heparin sodium. He developed gingival bleeding and purpura in 1977. He was first treated with prednisolone (30 mg/day) and ACTH-Z under the diagnosis of idiopathic thrombocytopenic purpura associated with chronic thyroiditis, since platelet count (0.2 x 10(4)/microliters) was markedly decreased and megakaryocytes in the bone marrow were increased. By the treatment, platelet count recovered to 16.7 x 10(4)/microliters, while fibrin-degradation product levels were increased and hypofibrinogenemia developed, suggesting disseminated intravascular coagulopathy. Additional treatment with heparin was effective, and the coagulation studies became normal. In 1980, he again developed the episode with thrombocytopenia. At this time, prednisolone did not improve the episode, but heparin was effective. Since 1983, an enlargement of abdominal aorta had been recognized and gradually progressed. In 1983, he developed lumbago and abdominal pain, and received an emergency operation using artificial Y-graft vessel under the diagnosis of rupture of the aneurysm. There was no evidence of consumption coagulopathy at that time. He had been well until 1987, when he developed the third episode of thrombocytopenia with gingival bleeding. Thrombocytopenia was controlled with the treatment of heparin, but needed a continuous treatment with heparin. Thereafter, he has been well managed with self-injection of the anticoagulant, heparin sodium.
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PMID:[Disseminated intravascular coagulation related to atherosclerosis and aneurysm of aorta: successful management with subcutaneous self injection of heparin sodium]. 259 49

A total of 145 BB Wistar diabetic rats, 46 of their nondiabetic siblings, and 43 outbred Wistar rats were autopsied and the frequency of lesions in all organ systems were determined. Common strain-related lesions included pulmonary infections, granulomas, lymphoid hyperplasia, lymphomas, lymphocytopenia, eosinophilia, supradiaphragmatic accessory lobes of the liver, and prostatic atrophy. These suggest some basic strain-related abnormalities of the immune system that were selected by the process of inbreeding. Diabetes-related lesions were insulitis, testicular atrophy, cataracts, hepatic fatty change, pancreatitis, lymphocytic thyroiditis, hypoglycemic brain damage, central pontine myelinolysis, stomach erosions, and idiopathic megacolon. Many of these are sequelae of human juvenile-onset diabetes and support the validity of the BB Wistar rat as an animal model for human diabetes mellitus. The absence of several important sequelae of the human disease (i.e., diabetic nephropathy, atherosclerosis, and severe microangiopathy) suggests a degree of infidelity as a model for human diabetes mellitus. Nonspecific lesions occurring in all three groups of rats included myocardial degeneration and fibrosis, splenic extramedullary hematopoiesis, and chronic progressive glomerulonephropathy.
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PMID:Pathological lesions in the spontaneously diabetic BB Wistar rat: a comprehensive autopsy study. 634 94

Various forms of cellular injury, whether induced by immune effector cells, aberrant metabolic processes, chemotherapeutic drugs or temperature shifts, result in common morphological changes consisting of the formation and shedding of membrane vesicles from the injured cell surfaces, i.e., apoptosis. This dynamic cell surface membrane behavior appears to be dependent on the disruption of cytoplasmic microtubules. Concomitant with the altered cell surface morphology, certain physiological and biochemical events have been found to be associated with cell injury. These include changes in membrane permeability, elevated oxygen consumption rates and nuclear DNA fragmentation. However, it remains to be experimentally established which of these biological changes defines a state of irreparable cell injury and/or programmed cell death (PCD). Selective cell injury and death is the goal of many therapeutic modalities aimed at the destruction of malignant cells. On the other hand, prevention of cell injury is desirable in autoimmune diseases such as systemic lupus erythematosus, thyroiditis, insulin dependent diabetes and many others. Injury to the vascular endothelium may play a role not only in thrombosis, atherosclerosis and hypertension, but may also provide the avenues for the metastasis of malignant cells. The objective of the present review is to compare and evaluate the cell injury process induced by effector lymphocytes with that caused by low temperature. The latter mimics most, if not all, the currently known criteria of immune effector cell mediated PCD of target tumor cells.
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PMID:Cell injury and apoptosis. 774 62

Increasing amounts of evidence support the involvement of inflammation and immunity in atherogenesis, but mediators of communication between the major cell types in atherosclerotic plaques are poorly defined. Cells in human atherosclerotic lesions express the immune mediator CD40 and its ligand CD40L (also known as CD154 or gp39). The interaction of CD40 with CD40L figures prominently in both humoral and cell-mediated immune responses. CD40L-positive T cells accumulate in atheroma, and, by virtue of their early appearance, persistence and localization at sites of lesion growth and complication, activated T cells may coordinate important aspects of atherogenesis. Interruption of CD40L-CD40 signalling by administration of an anti-CD40L antibody limits experimental autoimmune diseases such as collagen-induced arthritis, lupus nephritis, acute or chronic graft-versus-host disease, multiple sclerosis and thyroiditis. Ligation of CD40 on atheroma-associated cells in vitro activates functions related to atherogenesis, including induction of proinflammatory cytokines, matrix metalloproteinases, adhesion molecules and tissue factor. However, the role of CD40 signalling in atherogenesis in vivo remains unknown. Here we determine whether interruption of CD40 signalling influences atherogenesis in vivo in hyperlipidaemic mice. Treatment with antibody against mouse CD40L limited atherosclerosis in mice lacking the receptor for low-density lipoprotein that had been fed a high-cholesterol diet for 12 weeks. This antibody reduces the size of aortic atherosclerotic lesions by 59% and their lipid content by 79%. Furthermore, atheroma of mice treated with anti-CD40L antibody contained significantly fewer macrophages (64%) and T lymphocytes (70%), and exhibited decreased expression of vascular cell adhesion molecule-1. These data support the involvement of inflammatory pathways in atherosclerosis and indicate a role for CD40 signalling during atherogenesis in hyperlipidaemic mice.
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PMID:Reduction of atherosclerosis in mice by inhibition of CD40 signalling. 967 6

Multiple mechanisms of tolerance are induced by oral antigen. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral antigen induces T-helper 2 [interleukin (IL)-4/IL-10] and Th3 [transforming growth factor (TGF)-beta] T cells plus CD4+CD25+ regulatory cells and latency-associated peptide+ T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-beta, cholera toxin B subunit, Flt-3 ligand, and anti-CD40 ligand. Oral (and nasal) antigen administration suppresses animal models of autoimmune diseases including experimental autoimmune encephalitis, uveitis, thyroiditis, myasthenia, arthritis, and diabetes in the non-obese diabetic (NOD) mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, graft rejection, allergy, colitis, stroke, and models of Alzheimer's disease. Oral tolerance has been tested in human autoimmune diseases including multiple sclerosis (MS), arthritis, uveitis, and diabetes and in allergy, contact sensitivity to dinitrochlorobenzene (DNCB), and nickel allergy. Although positive results have been observed in phase II trials, no effect was observed in phase III trials of CII in rheumatoid arthritis or oral myelin and glatiramer acetate (GA) in MS. Large placebo effects were observed, and new trials of oral GA are underway. Oral insulin has recently been shown to delay onset of diabetes in at-risk populations, and confirmatory trials of oral insulin are being planned. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time, and antigen-specific mechanisms of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral), formulation, mucosal adjuvants, combination therapy, and early therapy.
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PMID:Oral tolerance. 1604 53

Oral tolerance is classically defined as the suppression of immune responses to antigens (Ag) that have been administered previously by the oral route. Multiple mechanisms of tolerance are induced by oral Ag. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral Ag induces Th2 (IL-4/IL-10) and Th3 (TGF-beta) regulatory T cells (Tregs) plus CD4+CD25+ regulatory cells and LAP+T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-beta, cholera toxin B subunit (CTB), Flt-3 ligand, anti-CD40 ligand and continuous feeding of Ag. In addition to oral tolerance, nasal tolerance has also been shown to be effective in suppressing inflammatory conditions with the advantage of a lower dose requirement. Oral and nasal tolerance suppress several animal models of autoimmune diseases including experimental allergic encephalomyelitis (EAE), uveitis, thyroiditis, myasthenia, arthritis and diabetes in the nonobese diabetic (NOD) mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, colitis and stroke. Oral tolerance has been tested in human autoimmune diseases including MS, arthritis, uveitis and diabetes and in allergy, contact sensitivity to DNCB, nickel allergy. Positive results have been observed in phase II trials and new trials for arthritis, MS and diabetes are underway. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time and Ag-specific mechanism of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral), formulation, mucosal adjuvants, combination therapy and early therapy.
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PMID:Oral tolerance: therapeutic implications for autoimmune diseases. 1716 57

Subclinical thyroids disease (STD) is recently defined term in clinical thyroidology, which includes mainly functional disorders. Basic diagnostic signs are: normal values of thyroid hormones (fT4, fT3) and elevated TSH level (subclinical hypothyroidism) or suppresed TSH level (subclinical hyperthyroidism). In a category of STD may be included subclinical autoimunne thyroiditis (elevated level of thyroid antigens antibodies and/or hypoechogenity in sonographic screen, increased volume of the thyroid without clinical symptoms and/or autoimminity) and microscopic lesions of papillary thyroid carcinoma. Subclinical hypothyroidism may be dangerous for tendency to development of manifest hypothyroidism and for risk of disorders of lipid profile and development of atherosclerosis and its organ complication (esp. myocardial infarction). Subclinical hyperthyroidism is a risk factor of cardiac arythmias and probably can increase a risk of cardiovascular mortality) as well for osteoporosis (esp. in peri- and post-climacteric women), and last but not least for degenerative diseases of brain (?). Indication of treatment of STD is a matter of controversies. Recomendations of experts, varied from "no therapy, monitoring only" to "treat always". Treatment of risk groups (esp. pregnant women) is probably nowadays a most rationale recommendations since results of sofisticated prospective studies will be available.
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PMID:[Subclinical thyroid diseases]. 1791 20

Chlamydia trachomatis (CT) infection is one of the most common causes of reproductive tract diseases and infertility. CT-Hsp60 is synthesized during infection and is released in the bloodstream. As a consequence, immune cells will produce anti-CT-Hsp60 antibodies. Hsp60, a ubiquitous and evolutionarily conserved chaperonin, is normally sequestered inside the cell, particularly into mitochondria. However, upon cell stress, as well as during carcinogenesis, the chaperonin becomes exposed on the cell surface (sf-Hsp60) and/or is secreted from cells into the extracellular space and circulation. Reports in the literature on circulating Hsp and anti-Hsp antibodies are in many cases short on details about Hsp60 concentrations, and about the specificity spectra of the antibodies, their titers, and their true, direct, pathogenetic effects. Thus, more studies are still needed to obtain a definitive picture on these matters. Nevertheless, the information already available indicates that the concurrence of persistent CT infection and appearance of sf-Hsp60 can promote an autoimmune aggression towards stressed cells and the development of diseases such as autoimmune arthritis, multiple sclerosis, atherosclerosis, vasculitis, diabetes, and thyroiditis, among others. At the same time, immunocomplexes composed of anti-CT-Hsp60 antibodies and circulating Hsp60 (both CT and human) may form deposits in several anatomical locations, e.g., at the glomerular basal membrane. The opposite side of the coin is that pre-tumor and tumor cells with sf-Hsp60 can be destroyed with participation of the anti-Hsp60 antibody, thus stopping cancer progression before it is even noticed by the patient or physician.
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PMID:Chlamydia trachomatis infection and anti-Hsp60 immunity: the two sides of the coin. 1971 22

Mitochondrial disorders (MIDs) require biochemical or genetic investigations for being diagnosed. In some cases, however, the diagnosis can be suspected upon the syndromic phenotype or upon clinical presentation and family history, as in the following case. The patient was a 74-year-old male admitted for worsening of pre-existing left-sided ptosis and ophthalmoparesis after a birthday party. The history was positive for arterial hypertension, hypertrophic cardiomyopathy with systolic dysfunction, diabetes-type 2, mild renal insufficiency, thyroiditis, and polyneuropathy. Instrumental investigations additionally revealed hepatopathy, hyperlipidemia, hyperuricemia, bifascicular block, white matter lesions, and subacute stroke. Systolic dysfunction resolved upon adequate cardiac treatment. On hospital day 11 the patient suddenly developed asystole. He was successfully resuscitated but died a few hours later from acute myocardial infarction. Surprisingly, a more extensive family history was positive for myopathy (patient, brother, daughter), neuropathy (patient), hypoacusis (patient), Parkinson syndrome (mother), spasticity (son), diabetes (patient, son), renal failure (patient), and generalized atherosclerosis (patient). The individual and family history was strongly suggestive of an MID. In conclusion, individual and family history may strongly suggest MID. Phenotypic variability may be high between family members affected by an MID. MID may be associated with an increasing atherosclerotic risk lastly resulting in coronary heart disease and death.
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PMID:Diagnosing Mitochondrial Disorder without Sophisticated Means. 2661 82


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