Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence of amyloid P-component (AP) within cerebral amyloid deposits was investigated by means of biochemical and immunocytochemical methods. Immunoperoxidase on formalin-fixed, paraffin-embedded tissue sections from Alzheimer's Disease, Down's Syndrome, asymptomatic age-related cerebral amyloidosis, sporadic cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis-Icelandic type, and hereditary cerebral hemorrhage with amyloidosis-Dutch type revealed the presence of AP in the affected vessel walls in all cases, and in parenchymal deposits resembling neuritic plaques of Alzheimer's disease, sporadic cerebral amyloid angiopathy, and hereditary cerebral hemorrhage with amyloidosis-Dutch type. A short digestion of tissue sections with pepsin was required for immunodetection of AP in these latter structures. After extraction of leptomeningeal amyloid fibrils, AP was characterized by sodium dodecyl sulfate-polyacrylamide-gel electrophoresis, Western blot, gel chromatography, and partial amino acid sequencing. Our results indicate that: (a) AP from cerebral amyloidosis has similar biochemical properties and homologous amino terminal sequence to AP from systemic amyloidosis; (b) AP is associated to a variety of brain amyloid deposits regardless of their chemical nature. The presence of AP, a serum protein, within the brain parenchyma points to an impairment of the blood-brain barrier in these diseases.
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PMID:Isolation and characterization of amyloid P component from Alzheimer's disease and other types of cerebral amyloidosis. 296 74

In order to reduce the toxic effects of the T cell activating anti-CD3 monoclonal antibody, 145-2C11, F(ab')2 fragments were prepared by pepsin digestion. These fragments were then used as non-immunosuppressive carriers for the cytotoxic drug idarubicin (IDA), to reduce toxicity of both the monodonal antibodies (mAb) and the drug and to increase the specificity of drug delivery. The IDA-145-2C11 F(ab')2 immunoconjugate was tested for specificity by fluorometry. 145-2C11 intact antibody, 145-2C11 F(ab')2 and IDA conjugates of the antibody and F(ab')2 were used to treat CBA recipients of BALB/c vascularized cardiac allografts. Mice with hearts surviving >100 days were challenged with donor and third party (C57BL/6) skin grafts. Although both antibody and F(ab')2 blocked the binding of 145-2C11-FITC to CBA spleen cells, only the intact antibody caused sustained depletion of CD3 cells in vivo. 145-2C11 F(ab')2 blocked cell surface CD3 within 30 min, but was cleared in 24 h without depletion of CD3 cells from the spleen. In BALB/c to CBA cardiac allografts (rejected in 12-17 days), IDA-145-2C11 F(ab')2 (0.2 mg/20 g mouse i.p. at the time of transplantation) induced >100 days' allograft survival and specific tolerance, in contrast to the equivalent dose of 145-2C11 F(ab')2 (mean survival 25 days). Hearts from IDA-145-2C11 F(ab')2-treated mice at >100 days showed decreased cellular infiltration and less chronic vascular disease than long-surviving hearts from mice treated with an alternative antibody, KT3. Thus, F(ab')2 prepared from 145-2C11 provided a suitable CD3-specific, nonimmunosuppressive carrier for IDA. This immunoconjugate was more effective against both acute and chronic rejection than other conjugates or whole antibody. IDA-145-2C11 F(ab')2 is an effective, nontoxic tolerogen in the mouse cardiac allograft model.
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PMID:Idarubicin-145-2C11-F(ab')2 promotes peripheral tolerance and reduces chronic vascular disease in mouse cardiac allografts. 1063 33

We investigated the effect of hypoxia on rat osteoblast function in long-term primary cultures. Reduction of pO2 from 20% to 5% and 2% decreased formation of mineralized bone nodules 1.7-fold and 11-fold, respectively. When pO2 was reduced further to 0.2%, bone nodule formation was almost abolished. The inhibitory effect of hypoxia on bone formation was partly due to decreased osteoblast proliferation, as measured by 3H-thymidine incorporation. Hypoxia also sharply reduced osteoblast alkaline phosphatase (ALP) activity and expression of mRNAs for ALP and osteocalcin, suggesting inhibition of differentiation to the osteogenic phenotype. Hypoxia did not increase the apoptosis of osteoblasts but induced a reversible state of quiescence. Transmission electron microscopy revealed that collagen fibrils deposited by osteoblasts cultured in 2% O2 were less organized and much less abundant than in 20% O2 cultures. Furthermore, collagen produced by hypoxic osteoblasts contained a lower percentage of hydroxylysine residues and exhibited an increased sensitivity to pepsin degradation. These data demonstrate the absolute oxygen requirement of osteoblasts for successful bone formation and emphasize the importance of the vasculature in maintaining bone health. We recently showed that hypoxia also acts in a reciprocal manner as a powerful stimulator of osteoclast formation. Considered together, our results help to explain the bone loss that occurs at the sites of fracture, tumors, inflammation and infection, and in individuals with vascular disease or anemia.
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PMID:Hypoxia inhibits the growth, differentiation and bone-forming capacity of rat osteoblasts. 1652 38

Acute esophageal necrosis (AEN), also known as Gurvits syndrome, black esophagus, or acute necrotizing esophagitis, is a rare clinical entity and an unusual reason for upper gastrointestinal bleeding. It is typically described in critically ill patients with multiple medical conditions, arising from a combination of ischemic insult to the esophageal mucosa due to low-flow vascular states, corrosive injury caused by reflux of acid and pepsin, and decreased function of the mucosal barrier systems and reparative mechanisms as occurs in malnourished and debilitated physical states. Patients with AEN tend to be older men, as medical comorbidities including vascular disease, diabetes, hypertension, renal insufficiency, cardiac disease, pulmonary disease, stroke, and cirrhosis may be more common. Typically, patients present with upper gastrointestinal bleeding, and hematemesis or melena is seen in up to 90% of cases. Herein we present 3 cases of AEN in critically ill patients. We also provide a review of the literature to highlight what is currently known about this relatively uncommon esophageal disease.
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PMID:Acute Esophageal Necrosis: A View in the Dark. 3118 40