Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient with a history of recurrent late fetal loss associated with multiple placental infarcts and cerebrovascular ischemia at the age of 36, followed a year later by a myocardial infarction, was referred for further investigation. Coronary angiography was normal. Antinuclear factor, lupus anticoagulant, anticardiolipin antibodies, and other thrombophilia parameters were negative, but there was moderate hyperthyroidism with positive thyroid peroxidase antibodies. Platelet numbers and von Willebrand factor (vWF) were normal. Her platelets showed spontaneous aggregation that disappeared with aspirin intake. However, aggregation still was induced by low levels of ristocetin (0.3 to 0.5 mg/mL). The low-dose ristocetin aggregation in patient platelet-rich plasma (PRP) was completely blocked by neutralizing antiglycoprotein Ib (GPIb) and anti-vWF antibodies. The monoclonal anti-Fc gamma RII receptor antibody IV.3 inhibited partly, which suggests that PRP aggregation by low-dose ristocetin was elicited by vWF-immunoglobulin (Ig) complexes. Upon addition to washed human platelets, with vWF (10 micrograms/mL), purified patient Igs dose-dependently enhanced ristocetin (0.15 mg/mL)-induced aggregation between 0 and 500 micrograms/mL, an effect that disappeared again above 1 mg/mL. Aggregation was dependent on the vWF concentration and was blocked by IV.3 or neutralizing anti-GPIb or anti-vWF antibodies. The spontaneous aggregation of normal platelets resuspended in patient plasma could be inhibited totally by IV.3 and partially by neutralizing anti-GPIb or anti-vWF antibodies. Perfusion with normal anticoagulated blood, enriched with 10% of control or patient plasma, over surfaces coated with vWF showed increased platelet adhesion and activation in the presence of patient antibodies. Treatment of the patient with the antithyroid drug thiamazol and temporary corticosteroids, aspirin, and ticlopidine did not correct the platelet hypersensitivity to ristocetin. These observations suggest that some autoantibodies to vWF may both enhance vWF binding to platelets and cause platelet activation through binding to the Fc gamma RII receptor, and thereby may be responsible for a new form of antibody-mediated thrombosis.
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PMID:Recurrent arterial thrombosis linked to autoimmune antibodies enhancing von Willebrand factor binding to platelets and inducing Fc gamma RII receptor-mediated platelet activation. 953 91

Thyroid hormone acts on a wide range of tissues. In the cardiovascular system, thyroid hormone is an important regulator of cardiac function and cardiovascular hemodynamics. Although some early reports in the literature suggested an unknown extrathyroidal source of thyroid hormone, it is currently thought to be produced exclusively in the thyroid gland, a highly specialized organ with the sole function of generating, storing, and secreting thyroid hormone. Whereas most of the proteins necessary for thyroid hormone synthesis are thought to be expressed exclusively in the thyroid gland, we now have found evidence that all of these proteins, i.e., thyroglobulin, DUOX1, DUOX2, the sodium-iodide symporter, pendrin, thyroid peroxidase, and thyroid-stimulating hormone receptor, are also expressed in cardiomyocytes. Furthermore, we found thyroglobulin to be transiently upregulated in an in vitro model of ischemia. When performing these experiments in the presence of 125 I, we found that 125 I was integrated into thyroglobulin and that under ischemia-like conditions the radioactive signal in thyroglobulin was reduced. Concomitantly we observed an increase of intracellularly produced, 125 I-labeled thyroid hormone. In conclusion, our findings demonstrate for the first time that cardiomyocytes produce thyroid hormone in a manner adapted to the cell's environment.
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PMID:H9c2 cardiomyoblasts produce thyroid hormone. 1832 42

Angiogenesis therapy by bone marrow-mononuclear cell implantation (BMI) has been utilized. We found that erythroid cells played an essential role in angiogenesis by BMI. We then tried to establish a novel cell therapy by implantation of ex vivo expanded immature erythroblasts cultured from hematopoietic stem/precursor cells. Immature to mature erythroblasts were purified from human bone marrow, and mRNA expression were analyzed. Strongly expressed VEGF and PLGF in immature erythroid cells decreased according to erythroid maturation. To expand very immature erythroid cells, we established a two-step culturing system, i.e., bone marrow cells were cultured in the presence of Flt-3L, SCF and TPO for 7 days, and the cells were further cultured in the presence of SCF, IGF-I and EPO for an additional 7 days. The in vivo angiogenic effects of implantation of the ex vivo expanded cells were stronger than that of BMI in mouse limb ischemia model. Three patients with severe chronic lower limb ischemia accompanied by Burger's disease or collagen arteritis were enrolled in a pilot clinical trial of the novel cell therapy by transplantation of ex-vivo expanded immature erythroid cells. In the clinical trial, most clinical symptoms such as rest pain and skin ulcers improved in 4 weeks, and did not recur in the one-year follow-up. No adverse events were observed in any of the patients. Moreover this novel cell therapy required only a small amount of bone marrow collection. Further enrollment of patients with chronic severe lower limb ischemia is necessary to confirm the efficacy and safety of this novel cell therapy, and to estimate the necessary amount of bone marrow aspirate.
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PMID:Establishment of culturing system for ex-vivo expansion of angiogenic immature erythroid cells, and its application for treatment of patients with chronic severe lower limb ischemia. 2055 29

Stem cell therapy has recently been limited by poor engraftment and the marginal influence of the administered cells. This study aimed to enhance the survival and angiogenic capacity of human umbilical cord blood (UCB)-derived mononuclear cells (MNCs) and to demonstrate their therapeutic effects on experimental ischemia. A specific culture medium containing five growth factors (Flt-3L, EGF, TPO, FGF and IGF-1) augmented cell proliferation, adhesion potential as well as stimulated MNCs to become progenitor-like cells. In addition, qRT-PCR demonstrated that MNCs cultured with these five growth factors (5f-MNCs) markedly up-regulated multiple angiogenic, arteriogenic and anti-apoptotic factors compared with uncultured MNCs. In an ischemic hindlimb model, the injection of 5f-MNCs prevented limb loss and augmented blood perfusion, capillary density, vascular maturation and angiogenic cytokines in the affected tissues. In addition, the 5f-MNCs exhibited an increased engraftment rate and an endothelial phenotype and stimulated angiogenic factors in ischemic hindlimbs as demonstrated by flow cytometric, immunohistochemical and qRT-PCR analyses. Taken together, these data suggest that 5f-MNCs could be used as a novel therapy for the treatment of ischemic cardiovascular disease due to their increased level of engraftment and angiogenic potential.
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PMID:Combined growth factors enhanced angiogenic potential of cord blood-derived mononuclear cells transplanted to ischemic limbs. 2178 26

Oxidative stress results from either overproduction of free radicals or insufficiency of several anti-oxidant defense systems. It leads to oxidation of main cellular macromolecules and a resultant molecular dysfunction. Thyroid hormones regulate oxidative metabolism and, thus, play a role in free radical production. Studies evaluating oxidative stress in patients with hypothyroidism and hyperthyroidism have been encountered in recent years; however, oxidative status in patients with euthyroid autoimmune thyroiditis (AIT) was not investigated previously. Thirty-five subjects with euthyroid AIT and 35 healthy controls were enrolled in the study. Serum oxidative status was determined by the measurement of total anti-oxidant status (TAS), total oxidant status (TOS), ischemia-modified albumin (IMA), and oxidized-low density lipoprotein (ox-LDL) levels. Serum TAS levels were significantly lower (p<0.001), while serum TOS levels and IMA levels were significantly higher (p<0.001 and p=0.020, respectively) in patients compared to controls. In both groups, ox-LDL levels were similar (p=0.608). Serum TAS levels were negatively correlated with anti-thyroid peroxidase and anti-thyroglobulin (anti-TG) levels (rho=-0.415, p=0.001 and rho=-0.484, p<0.001, respectively). Serum TOS was positively correlated with anti-TG levels (rho=0.547, p<0.001). Further, TAS was positively correlated with free T4 levels (r=0.279, p=0.043). No correlation was observed between thyrotropin, free T3 levels, and TOS and TAS levels. These results suggest that oxidants are increased, and anti-oxidants are decreased in patients with euthyroid AIT, and oxidative/anti-oxidative balance is shifted to the oxidative side. Increased oxidative stress might have a role in thyroid autoimmunity.
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PMID:Assesment of oxidative status and its association with thyroid autoantibodies in patients with euthyroid autoimmune thyroiditis. 2515 37

The aim of this study was to investigate the specific thyroid condition and thyroid autoantibodies in adult moyamoya disease (MMD) according to clinical presentation (ischemia vs. hemorrhage stroke). In addition, a meta-analysis was performed to reveal the association between adult MMD and elevated thyroid function, or autoantibodies. Prospectively collected data on 169 consecutive patients with MMD at a single institution were analyzed. Community-based controls matched for age and sex were selected for comparison. Penalized multinomial logistic regression analysis was used for factors affecting stroke. For meta-analysis, heterogeneity was evaluated by using the I2 test. If I2 < 50%, a fixed effect model was used. Fifty-four cases (32.0%) presented with ischemic stroke and 37 cases (21.9%) with hemorrhage stroke. Hyperthyroidism had a marginally increased risk of MMD with ischemic stroke with reference value of MMD without stroke [odds ratio (OR), 2.53; P = 0.055]. Anti-thyroperoxidase antibody (TPOAb) increased the risk of MMD presenting with ischemic stroke significantly (OR, 2.99; P = 0.020). A meta-analysis revealed that adult MMD was significantly associated with elevated autoantibodies (OR, 7.663; P = 0.002) and hyperthyroidism (OR, 10.936; P < 0.001). Elevated TPOAb and hyperthyroidism may play important roles in adult MMD with ischemic stroke. Studies focusing on targeted hyperthyroidism and thyroid autoantibodies are necessary in treating adult MMD patients in the future.
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PMID:Association of Hyperthyroidism and Thyroid Autoantibodies with Moyamoya Disease and Its Stroke Event: A Population-based Case-control Study and Meta-analysis. 2935 60