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

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.
 ...
PMID:[Disseminated intravascular coagulation related to atherosclerosis and aneurysm of aorta: successful management with subcutaneous self injection of heparin sodium]. 259 49

In order to study the possible relation between blood viscosity and exercise ST segment depressions in hyperlipidemia the former was lowered by infusion of dextran and by treatment with clofibrate 1 g twice daily. Acute decrease of blood viscosity with dextran infusion in two cases increased the ST segment depressions during work. Nine subjects with asymptomatic hyperlipidemia, hyperfibrinogenemia and exercise ST segment depressions were treated with clofibrate in order to lower plasma fibrinogen and serum lipids. This did not influence the area of ST segment depression with either Frank leads or CH leads as determined by computer estimation. As the plasma fibrinogen level is of major importance for the blood viscosity it is concluded that the ischaemic ST segment depression seen in hyperlipidemia is not due to increased blood viscosity but more likely to a premature subclinical coronary atherosclerosis.
 ...
PMID:Effect of blood viscosity decrease on exercise ST segment depressions in hyperlipidemia. 616 35

Adenosine triphosphate (ATP), a co-transmitter in sympathetic nerves and released from platelets, has recently been shown to stimulate growth of vascular smooth muscle cells. It might therefore contribute to the development of vascular hypertrophy seen in hypertension and atherosclerosis. We aimed at characterising the receptor mediating this mitogenic effect in rat aorta smooth muscle cells. The potency of agonists indicates a P2 purinoceptor since ATP > or = ADP >> AMP, adenosine. The P2x-receptor subtype, which is responsible for ATP induced vasoconstriction in rat aorta, does not mediate the mitogenic effect since alpha, beta-methyleneATP had no effect and beta, gamma-methyleneATP had lower potency than ATP. The P2Y-receptor subtype was excluded since the selective agonist 2-methylthioATP had weak effect with lower potency than ATP. When we studied the involvement of other nucleotides similar effects were seen of the purines ATP, GTP and ITP; also the pyrimidine UTP had powerful mitogenic effects (Emax = 52% of ATP) with similar potency. Nucleotides with fewer phosphate groups showed a stepwise fall in mitogenic effect. This indicates involvement of a nucleotide-receptor (P2U). Ap4A were of equal potency and effect as ATP. There was strong correlation between the mitogenic effects of the nucleotides and analogues with both 45Ca(2+)-influx and inositol phosphate (IP) production, indicating that they may participate in mediating the mitogenic response. This is the first study describing the potencies for the mitogenic effects of the selective ATP-analogues and other nucleotides in vascular smooth muscle cells. The receptor characterisation indicates a nucleotide-receptor similar to the receptor which stimulates 45Ca(2+)-influx and inositol phosphate-formation in rat aorta smooth muscle cells. Substances related to ATP such as GTP, ITP, UTP and Ap4A which also can be released extracellularly in vivo stimulate mitogenesis of rat aorta smooth muscle cells through the same receptor.
 ...
PMID:Characterisation of an ATP receptor mediating mitogenesis in vascular smooth muscle cells. 778 5

An eighty-four-year-old man was admitted to the hospital because of pain at rest in the lower extremities. On physical examination, trophic changes of the skin and petechiae in the limbs were observed. Computed tomographic scan of the abdomen showed focal renal infarctions and calcification of the descending aorta. Moreover, radionuclide imaging of the arterial system revealed complete obstructions of the two right iliac arteries and the left external iliac artery, where collateral flows were observed. Laboratory examination showed a severe thrombocytopenia caused by immunoglobulin G (IgG)-type autoantibody against platelets. He was diagnosed as having arteriosclerosis obliterans complicated by idiopathic thrombocytopenic purpura, although no known risk factors promoting atherosclerosis other than age were evident. In such a case with hemorrhagic diathesis, a hemorheologic agent and the vasodilator prostaglandin could confer advantages in relieving and controlling the ischemic leg pain without hemorrhagic complications. Moreover, small doses of the initial prednisolone therapy for ITP might also be recommended to avoid thrombus formations in the atherosclerotic lesions.
 ...
PMID:A rare case of arteriosclerosis obliterans without prominent risk factors complicated by idiopathic thrombocytopenic purpura. A case report. 861 16

1. Extracellular adenosine triphosphate (ATP) is mitogenic for vascular smooth muscle cells (VSMC) and stimulates several events that are important for cell proliferation: DNA synthesis, protein synthesis, increase of cell number, immediate early genes, cell-cycle progression, and tyrosine phosphorylation. 2. Receptor characterization indicates mitogenic effects of both P2U and P2Y receptors. The P2X receptor is lost in cultured VSMC and is not involved. Several related biological substances such as UTP, ITP, GTP, AP4A, ADP, and UDP are also mitogenic. 3. Signal transduction is mediated via Gq-proteins, phospholipase C beta, phospholipase D, diacyl glycerol, protein kinase C alpha, delta, Raf-1, MEK, and MAPK. 4. ATP acts synergistically with polypeptide growth factors (PDGF, bFGF, IGF-1, EGF, insulin) and growth factors acting via G-protein-coupled receptors (noradrenaline, neuropeptide Y, 5-hydroxytryptamine, angiotensin II, endothelin-1). 5. The mitogenic effects have been demonstrated in rat, porcine, and bovine VSMC and cells from human coronary arteries, aorta, and subcutaneous arteries and veins. 6. The trophic effects on VSMC and the abundant sources for extracellular ATP in the vessel wall make a pathophysiological role probable in the development of atherosclerosis, neointima-formation after angioplasty, and possibly hypertension.
 ...
PMID:Extracellular ATP: a growth factor for vascular smooth muscle cells. 959 70

We report the case of a 65-year-old man affected by idiopathic thrombocytopenic purpura, who developed an acute myocardial infarction after 2 years of steroid therapy. Thrombocytopenia was initially recognized 11 years earlier, and became severe during the past 2 years [platelets (PLTS) 10000-30000/microl]. He was treated with steroids, initially to perform a surgical procedure (prednisone 75 mg/day), subsequently to maintain a platelet count of about 50000/microl (prednisone 12.5 mg/day). After 1 year of treatment, he began to complain about exertional angina and dyspnea. His blood pressure became elevated and cholesterol level raised. The exercise electrocardiogram, previously manifesting ischaemic changes, normalized after 1 month of steroid wash-out; however, steroid therapy was reinstituted (prednisone 5 mg per day). One year later, he suffered an infero-lateral non-Q-wave myocardial infarction. It seems likely that the severe coronary atherosclerosis present in our patient developed despite a low platelet count, under the spur of a heavier risk factor profile. Steroid therapy could have had a role as a precipitating agent of the acute event, and the opportunity of alternative treatments is considered.
 ...
PMID:Idiopathic thrombocytopenic purpura treated with steroid therapy does not prevent acute myocardial infarction: a case report. 1069 71

With donor and recipient matched at the major histocompatibility complex (MHC) locus, peripheral lymphoid tissue transplantation can be carried out without producing a graft-versus-host reaction or graft-versus-host disease (GVHD), thus correcting profound T cell immunodeficiencies of neonatally thymectomized mice. This analysis set the stage for clinical application of bone marrow transplantation (BMT) to provide for the first time cure of a human disease. With successful BMT, we cured immunologic deficiencies of a patient with XL severe combined immunodeficiency; thereafter we were the first to employ BMT to cure aplastic anemia. BMT regularly corrects immune and hematologic deficiencies caused by fatal irradiation without producing GVHD if the bone marrow (BM) used for the transplants has been purged of postthymic T cells. Over two decades in conjunction with Ikehara et al., we have shown that lethal total body irradiation (TBI) plus allogeneic BMT prevents or cures many organ-specific and systemic experimental autoimmune diseases. Animal models successfully treated by BMT include type I diabetes in nonobese diabetes (NOD) mice, type II diabetes in insulin-insensitive, glucose intolerant, diabetes mellitus (KK/Ay) mice, and autoimmune lupus erythematosus (LE) and glomerulonephritis in New Zealand Black x New Zealand White first generation hybrid (NZB x NZW)F1 females. El-Badri extended Ildstad's original research showing a high frequency of survival with a normal functioning immune system after stable mixed chimerism is produced by mixed BMT in C57BL/6 (normal long-lived black strain) mice transplanted with T cell-depleted marrow (TCDM) from BALB/c ("normal" long-lived strain) allogeneic donors and C57BL/6 syngeneic donors. We showed that osteoblasts act as facilitator cells for allogeneic BMT and promote engraftment of allogeneic hematopoietic stem cells. Wang et al. then showed that the autoimmunities and fulminating renal disease of BXSB (C57BL x SB cross and selective lupus-like systemic autoimmunity) male mice was prevented and could be cured by transplantation using TCDM from both BALB/c (resistant) and BXSB (susceptible) strains given to BXSB recipients after lethal TBI. This treatment produced mixed BMT and a stable mixed chimerism, increased longevity, corrected all manifestations of autoimmunity, and cured fulminant glomerulonephritis in these recipients. These studies generated a new perspective on the potential usefulness of BM and stem cell transplants to cure major diseases that can possibly be treated by BMT. Mixed BMT from TCD BALB/c and BXSB mice cured autoimmunities and fulminant glomerulonephritis in BXSB mice. LE disease plus coronary vascular disease that occurs in (NZW x BXSB)F1 mice, along with idiopathic thrombocytopenic purpura, is also cured in lethally irradiated (NZW x BXSB)F1 mice by BMT from C57BL/6 donors. Furthermore, hemolytic anemia, autoimmune phenomena, and hyalinizing glomerular renal disease of New Zealand Black (NZB) mice were prevented or cured by stem cell transplants using purified stem cells from MHC-matched DBA/2 donors or NZB donors. Consequently, we reasoned that autoimmunities reside in stem cells. More recently, we found that transplants of both BM cells and bones can completely and permanently prevent otherwise highly resistant autoimmune diseases of MRL/lpr lpr mice and an autoimmune polyarthritis of NZB/Kn mice. Ildstad concluded that lethal preparative measures would not be acceptable for preparations to treat autoimmune diseases, so we now employ a gentle method for producing stable mixed chimerism described by Sharabi and Sachs to achieve mixed marrow transplantation and mixed hematopoietic chimerism. Other diseases we are approaching using this gentle manipulation include two forms of diabetes: insulin-dependent diabetes mellitus (IDDM) type I in NOD mice and non-insulin-dependent diabetes mellitus (NIDDM) type II in KK/Ay mice, atherosclerosis of apolipoprotein-E + kno
 ...
PMID:Progress toward production of immunologic tolerance with no or minimal toxic immunosuppression for prevention of immunodeficiency and autoimmune diseases. 1083 46

Elderly individuals experience a disproportionate burden from cardiovascular disease. Global changes in aging will have a significant impact on the future of medical practice. However, most physicians have little formal training in geriatric medicine and sometimes fail to distinguish disease states from normal aging. Increasingly, it is recognised that a sedentary lifestyle may be responsible for a large fraction of the so-called 'age-related' changes in the cardiovascular system. Nonetheless, well characterised changes do occur in most individuals with aging. Loss of myocytes with subsequent hypertrophy of the remaining cells is usually observed. Calcification involving the conduction and valvular apparatus is seen in most elderly individuals and may predispose to the common arrhythmias of old age. Age-related loss of arterial compliance contributes to isolated systolic hypertension and left ventricular hypertrophy. Despite these changes, for the majority of healthy older adults, cardiac output is well maintained in the basal state through use of the Frank-Starling principle, in the setting of reduced early diastolic filling. Myocardial relaxation is slowed in part due to age-related changes in the sarcoplasmic reticulum Ca2+ ATPase pump. Elevated blood levels of catecholamines contribute to desensitisation to noradrenergic stimulation and this is associated with an age-related decline in maximum achievable heart rate. Changes in the baroreceptor reflex function and decreased sodium conservation may predispose some individuals to orthostatic and postprandial hypotension. The aetiology of cardiovascular aging is under intense study. The most likely mechanisms involve the result of cumulative damage mediated through a variety of insults. Oxidative stress, non-enzymatic glycation, inflammation and changes in cardiovascular gene expression all seem to influence cardiovascular aging. The benefits of exercise continue to be discovered. Endurance-type training has been shown to have a dramatic impact on parameters of cardiovascular aging. Favourable effects are seen in maximum oxygen consumption, diastolic filling, relaxation and arterial stiffness. Some changes such as the maximum heart rate response do not appear to change with conditioning. Pharmacotherapy may afford the opportunity to influence the aging process. Drugs that can reduce age-associated arterial stiffness, cardiac fibrosis and ventricular hypertrophy should prove useful. Antioxidants continue to be a topic of great interest and require more study. Despite some well described changes with aging, most elderly individuals maintain the opportunity for improved cardiovascular function through conditioning. Early recognition and treatment of diseases that are distinguishable from normal aging, including hypertension and atherosclerosis, together with preventive efforts, should reduce the predicted trends in cardiovascular morbidity and mortality among the aged.
 ...
PMID:Clinical implications of physiological changes in the aging heart. 1134 74

The CD40-CD40L system has pleiotropic effects in a variety of cells and biological processes including immune response, thrombosis and atherogenesis. Within the immune system, these molecules represent a critical link between its humoral and cellular arms. As a result of these attributes and based on preclinical data in animals, anti-CD40L antibodies were tested in a variety of immunologic diseases including idiopathic thrombocytopenic purpura, psoriasis, Crohn's disease, systemic lupus erythematosus and transplantation. Phase I/II studies in humans with lupus nephritis demonstrated reduction of anti-double-stranded DNA (anti-dsDNA) antibodies but not of protective antibodies. Reduction of anti-DNA was associated with increased serum complement levels and reduced glomerular inflammation. As a result of thrombotic effects, observed even in patients negative for anti-cardiolipin antibodies, there is a temporary halt on further human studies. The reasons for the prothrombotic effects are not clear at present but may represent effects on platelets and/or the endothelium. In view of the significant immunomodulatory effects of anti-CD40L treatment in patients with lupus nephritis, the increasing realization of the importance of premature atherosclerosis in lupus and an increasing amount of data supporting a role for the CD40-CD40L interactions in this process, inhibition of this pathway deserves further exploration in lupus.
 ...
PMID:Lessons learned from anti-CD40L treatment in systemic lupus erythematosus patients. 1523 Feb 98

Idiopathic thrombocytopenic purpura (ITP), an autoimmune disease caused by sensitization of platelets by autoantibodies leading to platelet destruction, has been associated with some infectious agents, including Helicobacter pylori. The study by Suzuki et al., published in this issue, provides further evidence of the role of H. pylori infection in the pathogenesis of ITP, as confirmed by the increase in the platelet count in patients with ITP, following H. pylori eradication. Interestingly, H. pylori infection has also been shown to play a role in other diseases in which autoimmune mechanisms may be predominant, such as acne rosacea, idiopathic chronic urticaria, and atherosclerosis. While H. pylori eradication is usually recommended in patients with gastric diseases, there are no specific indications for extraalimentary diseases. In the light of the recent findings, a revision of the current guidelines for the management of H. pylori infection may be needed.
 ...
PMID:Does H. Pylori infection play a role in idiopathic thrombocytopenic purpura and in other autoimmune diseases? 1592 55


1 2 Next >>