Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tremors, mental changes, opsoclonus, muscle weakness, gait ataxia, incoordination, and slurred speech developed in several employees in a Virginia chemical plant during the summer of 1974. Epidemiologic and clinical studies suggested that the chlorinated insecticide chlordecone (Kepone) was responsible. Severity of symptoms seemed directly related to dose and duration of exposure. Five sural nerve and six muscle biopsy specimens were examined by light microscopy and electronmicroscopy. The sural nerves were also evaluated by computerized morphometry, which showed considerable decrease in the number of unmyelinated fibers and lesser abnormalities of myelinated fibers. Compared with the nerves of the control subjects, those of patients may have had an increase in Reich and Elzholz bodies, and a modest increase in endoneurial collagen. There were occasional "collagen pockets," stacks of Schwann cell cytoplasmic membranes, redundant Schwann cell cytoplasmic folds, and fewer unmyelinated axons. The skeletal muscles contained increased amounts of lipofuscin and lipidlike droplets in subsarcolemmal areas and within intermyofibrillary spaces; the significance of this is unknown. Fiber size variability, type I predominance, and type grouping were present in three cases. All results strongly suggest that chlordecone is a neurotoxic agent predominantly affecting Schwann cells and unmyelinated fibers of peripheral nerves.
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PMID:Chlordecone intoxication in man. II. Ultrastructure of peripheral nerves and skeletal muscle. 7 56

BSp 73 AS is a highly invasive but scarcely metastatic cell line from a rat pancreatic adenocarcinoma. In vitro the AS-cells flatten and move actively and were originally able to form monolayers. Our highly passaged AS-cells had lost this ability and formed only two-dimensional clusters and small aggregates on plastic or glass supports. The in vitro behaviour of the As-cells, however, could be dramatically modified by biomatrices like collagen type I/III (vitrogen), Iaminin, fibronectin, basement membrane matrigel, lens capsule and bovine corneal endothelial basal lamina. On these substrata the AS-cells in most cases showed both faster and stronger attachment as well as spreading. Furthermore, degradation, alteration and penetration of the materials could be observed as well as filopodial outgrowth, secretion of membrane vesicles, modification of the cell shape and the forming of monolayers. Shaking the culture dishes decreased the attachment of the AS-cells to laminin, fibronectin and matrigel. Generally, the nonmetastatic AS-cells exhibited a rather aggressive activity in vitro. It could also be demonstrated that not only the cells alter the substratum, but also the cell phenotype is influenced by the extracellular components with which they were confronted.
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PMID:Influences of various substrata on morphology, motility, and invasiveness of rat tumour cells. I. Studies on the nonmetastatic variant BSp 73 AS. 236 89

A protocol for the biochemical study of platelet stored for transfusional use at 22 degrees C and under continuous shaking in a plastic bag highly permeable to gases and with a suitable area/volume ratio, is described. Plasmatic dextrose, lactic acid, lactic dehydrogenase activity, cellular ATP and malonyldialdehyde were monitored during the storage, as well as some acid-base indexes namely: pH, pCO2, HCO3-, pO2. The platelet functional status was checked as aggregating power induced by ADP and collagen and by beta-thromboglobulin release. The results obtained are indicative of a discrete maintenance of aerobic metabolism by platelets which are able to give up CO2 and take up O2 so that the plasmatic pH is constant during the storage. However, the malonyldialdehyde increase suggests that platelets become increasingly susceptible to peroxidative attacks. The aggregating response was dramatically reduced even on the third day of storage. The data obtained point out that, under the conditions reported, platelets can be transfused up to the third day of storage.
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PMID:Biochemical and functional changes of platelet stored for transfusional use. 244 9

A method is described for studying platelet function in human whole blood immediately after venepuncture in order to evaluate the antithrombotic potential of new pharmacological agents. In this method, platelet aggregation is quantified by measuring the fall in single platelet count, by using a whole blood platelet counter. We have investigated the platelet aggregation inhibitory effects of the new positive inotropic agents pimobendan and UD CG 212 (reported to be Ca++ sensitisers and phosphodiesterase inhibitors), alone and in combination with dipyridamole. Venous blood was drawn directly into prewarmed (37 degrees C) plastic syringes containing anticoagulants (3.2% trisodium citrate solution) plus a platelet aggregation inhibitor. Spontaneous platelet aggregation (SPA) was studied by roller mixing aliquots of blood in the collecting syringes for 6 min at 37 degrees C. Collagen induced platelet aggregation was studied by incubating aliquots of blood with 1 microgram/ml collagen on a shaking water bath for 3 min. In the absence of an inhibitor, there was a 50% fall in single platelet count due to SPA and a 65% fall was induced by collagen. Both SPA and collagen induced aggregation responses were inhibited by pimobendan (0.5-10 microM) and UD CG 212 (0.5-10 microM), in a dose dependent manner. A combination of 10 microM dipyridamole with 2 microM pimobendan or UD CG 212 was markedly a more effective inhibitor of platelet aggregation than a high dose of either inhibitor alone. It is suggested that the present method is simple and rapid, with minimal sample processing, and therefore the results may be protected from serious artifacts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Platelet aggregation inhibitory effects of the new positive inotropic agents pimobendan and UD CG 212 in whole blood. 259 Sep 3

A rare complication of nonsteroidal antiinflammatory drug (NSAID) use, particularly in patients with collagen vascular or autoimmune diseases, is aseptic meningitis. A healthy 21-year-old man receiving naproxen for muscle spasm was admitted with a chief complaint of severe headache. Approximately one week after beginning naproxen, the patient developed headache, fever (T 38.8 degrees C), shaking chills, and nuchal rigidity with occasional nausea and vomiting resulting in a 15-lb weight loss. Findings from a cerebrospinal fluid examination revealed polymorphonuclear pleocytosis and elevated protein, but no evidence of infection with bacteria, fungi, mycobacteria, or viral agents was noted. Within 36 hours of discontinuing naproxen, the meningitis-like symptoms markedly improved. Rechallenge with naproxen was not performed. In patients exhibiting meningitis-like symptoms, a thorough drug history, including that of recent or intermittent NSAID use, should be obtained.
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PMID:Aseptic meningitis associated with naproxen. 339 Nov 11

Soluble plasma inducers and inhibitors of platelet activity and fluid dynamics of the blood stream are effective modulators of platelet-vessel wall interactions. Effects of platelet activity inducers, arachidonic acid (AA) and stable prostaglandin endoperoxides analogue (U46619), on platelet disposition on the bottom of multiwell tissue culture plates coated with fibrillar calf skin collagen (CSC) have been studied by scanning electron microscopy (SEM). Both agents stimulate platelet spreading and formation of large surface-bound multilayer (thrombi-like) aggregates on a CSC substrate. AA and U46619 effects on spreading and thrombi-like aggregate formation depend on the speed of platelet suspension shaking during platelet deposition on the surface. In the absence of shaking, both inducers mainly stimulate the spreading of platelets: spread platelets fuse and form widespread sheets covering up to 50% of the CSC-coated surface. An increase in the shaking speed leads to the decrease of the platelet spreading, while the number of surface-bound thrombi-like aggregates grows, reaching the maximum at a shaking speed of 40 back and forth cycles per min. The thrombi-like aggregates mainly consist of fused platelets and always contain the basal sheet of spread platelets, which suggests the participation of the latter in aggregate attachment to the surface. Large aggregates are absent in the population of nonadherent platelets. The obtained data indicate that AA metabolites participate in platelet spreading and thrombi-like aggregate formation, the processes specific for platelet-surface interactions. The use of the suggested model for the in vitro study of platelet spreading and mural thrombi formation, and for screening of antithrombotic and thrombolytic drugs is discussed.
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PMID:Arachidonic acid and stable analogue of prostaglandin endoperoxides (U46619) induce platelet spreading and thrombi-like aggregate formation on a collagen substrate. Effect of fluid dynamics. 641 75

E-cadherin, a member of the cadherin family, plays a major role in cell-cell adhesion of normal epithelium. Recent studies have shown that reduction or loss of E-cadherin expression in carcinomas have some relationship with their clinicopathological manifestation including invasion and metastasis. In the present study, we have established cell clones with different E-cadherin expression from human esophageal cancer, TE-2, and examined their adhesive capacity and invasiveness in vitro. Cell clones with positive E-cadherin expression [ECD(+) cells] were round and formed cobblestone colonies, while cell clones negative for E-cadherin [ECD(-) cells] had spindle shapes and formed dispersed colonies. ECD(+) cells showed higher adhesive capacity than ECD(-) cells, in both an aggregation assay with gyratory shaking culture and a dissociation assay of cells passing through the micropore membrane. Monoclonal antibody against human E-cadherin (HECD1) effectively diminished the mutual adhesion of ECD(+) cells but did not affect that of ECD(-) cells. Tumor invasiveness was evaluated with organotypic raft culture which is a coculture system consisting of two layers, a collagen gel layer containing fibroblasts and overlying reconstituted stratified squamous epithelium. ECD(+) cells formed complete stratified epithelium, but ECD(-) cells did not. ECD(+) cells did not invade the collagen/fibroblast gel, but ECD(-) cells did. Furthermore, ECD(+) cells showed invasion when an antibody against E-cadherin was used. Thus, loss or dysfunction of E-cadherin diminishes intercellular adhesion and results in the acquisition of invasive capacity in the cell line we examined.
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PMID:Correlation between E-cadherin expression and invasiveness in vitro in a human esophageal cancer cell line. 832 52

The colH gene encoding 116-kDa collagenase of Clostridium histolyticum (cColH) was cloned into an Escherichia coli-Bacillus subtilis shuttle vector to develop a method for purification of recombinant collagenase (rColH). When plasmid pJCM310 containing the colH gene was introduced into B. subtilis DB104 and the transformant was grown in LB broth at 37 C, stability of the plasmid was not maintained. However, stability was partly improved by growing the transformant in a modified LB broth containing 0.5 M sodium succinate with gentle shaking at 35 C. When the transformant was grown to an optical density of 0.4 at 600 nm in this medium, pJCM310 was stable and rColH was produced in sufficient amounts. rColH was purified to homogeneity by ammonium sulfate precipitation, gel filtration and ion-exchange chromatography. The yield of rColH from an 800-ml culture was 0.53 mg and its specific activity was estimated to be 1,210 U per mg of protein. The purified rColH was capable of degrading native type-I collagen fibril from bovine achilles tendon, as was demonstrated by zymography. A comparison of the N-terminal amino acid sequence between cColH and rColH revealed that rColH has 10 extra N-terminal amino acid residues. However, the peptide mapping of rColH with V8 protease was virtually identical to that of cColH. Furthermore, the molecular mass of rColH was estimated to be 112,999 Da by mass spectrometry, coinciding with the value of 112,977 Da, which was predicted from the nucleotide sequence of the colH gene. Therefore, the recombinant B. subtilis culture is capable of serving as a useful source for enzyme purification.
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PMID:Expression of the colH gene encoding Clostridium histolyticum collagenase in Bacillus subtilis and its application to enzyme purification. 901 90

Clinical data, neuroimaging, and neuropathology of 17 patients with central nervous system tuberculosis were reported. Of this population, 12 were men, 5, women; ages ranged from 23 to 75 years (mean, 46.9). There were three HIV positive patients among them. More than a half of patients had disturbance of consciousness as initial symptom. Neurological signs were variable such as visual acuity loss, hemiparesis, paraparesis, cerebellar ataxia, and tremor, though disturbance of consciousness was the most frequent (36%). Neuroimaging (X-ray CT and MRI) revealed meningeal enhancement (53%), tuberculoma (50%), hydrocephalus, infarction or bleeding and spinal cord tuberculoma. There were three patients who showed paradoxical progression. Eleven patients were performed CSF examination, all of them revealed increased cell count (mean, 206 counts/mm3) and protein (mean, 225 mg/dl), but only 4 patients were positive on bacteriological examination including PCR. Seven patients died and 5 patients were performed autopsy. Neuropathologically, all patients showed a stage of meningitis prominent on basal brain (basal cistern and/or Sylvian fissure). Cell infiltrations including lymphocyte, monocyte, and eosinocyte were most severe around blood vessels, and observed in all cases except one which showed only fibroblast and collagen fibers indicating healed stage. In some cases, there existed epithelioid cells and Langhans giant cells, and in some cases, fibrin exudate. There were three cases having tuberculoma, one HIV case and two non-HIV cases. Center of tuberculoma in non-HIV case was formed by caseous necrosis, and tuberculoma was surrounded by granuloma constituted by epithelioid cells and Langhans giant cells with lymphocyte cell infiltration and proliferation of blood vessels. In contrast, tuberculoma of HIV case did not include granuloma, and was formed with small cells with large nucleus which surrounded arteries. Our studies, as other studies, failed to show any differences between HIV and non-HIV patients clinically, as well as on neuroimaging study. But neuropathological study suggests that mechanism of tuberculoma formation may be different between in HIV positive patients and in non-HIV patients.
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PMID:[Central nervous system tuberculosis with and without HIV infection--clinical, neuroimaging, and neuropathological study]. 1088 29

Glycoxidative modification of various body proteins, including fibronectin (FN), has been shown to change their structural and functional properties, and be implicated in pathogenesis of diabetic complications. Little is known about the role of secondary structure of glycoxidative FN (gFN) in its domain functions. gFN was prepared by incubation with 25 and 200 mM glucose in 0.2 M sodium phosphate buffer at 37 degrees C on a shaking plate under aerobic and sterile conditions for various time intervals up to 49 days, being defined as gFN25 and gFN200, respectively. Unmodified FN (uFN) was prepared by incubation in 0.2 M sodium phosphate buffer without any glucose at 4 degrees C for 49 days. The extent of glycoxidative modification was examined using a noncompetitive enzyme-linked immunosorbent assay with an antibody against N(epsilon) -(carboxymethyl)lysine (CML), one of the major glycoxidation products. The binding activities of uFN and gFN to collagen, gelatin and heparin were determined by a solid phase enzyme immunoassay or heparin-affinity HPLC. Cell attachment was estimated by the extent of adhesion of FITC-labeled smooth muscle cells to uFN or gFN. Conformational change in gFN was detected by SDS-polyacrylamide gel electrophoresis and spectroscopy (circular dichroism). CML was detected in gFN25 and gFN200 after 49 and 21 days of incubation, respectively. Levels of CML were about six-fold higher in gFN200 than in gFN25 after 49 days. Both gFN25 and gFN200 showed a significant decrease in the ability of binding to collagen and gelatin after 7 days of incubation. The binding activity for heparin was significantly decreased in both gFN25 and gFN200 after one day. Cell attachment activity was reduced to 89% and 76% of the unmodified form in both gFN25 and gFN200 after 49 days, respectively. High molecular weight materials were found in gFN25 and gFN200 after 21 and 7 days, respectively. CD spectrum showed that gFN25 had lost its native conformation after 3 days of incubation, depending upon the concentration and incubation interval of the applied glucose. These in vitro results suggest that the loss of native conformation may reduce the domain functions of gFN, including binding activity to macromolecular ligands and cell attachment, and may play a major role in the pathogenesis of diabetic complications.
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PMID:Causal relationship between conformational change and inhibition of domain functions of glycoxidative fibronectin. 1099 58


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