Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two groups of compounds, identifiable by structural similarity, have been found to interfere with the in vitro replication of arenaviruses. All 4 members of the benzimidazole group contain dipolar fused benzene and 5-membered nitrogen-containing rings and share potential chelating ability through the different bidentate structures formed with their side-chains. The biological activity of one of these compounds, metisazone, has been shown to depend on the presence of divalent metals of the first transition series, Cu(++) being the most effective. Furthermore, whereas metisazone inactivates cell-free virus, two other members of the group, HBB and 1,2-bis(5-methoxy-1H-benzimidazol-2-yl)-1,2-ethanediol, act intracellularly. The site of action of the fourth member, SKF 30097, is not known. Using murine lymphocytic choriomeningitis infections as an in vivo model, the bisbenzimidazole derivative has been found to increase life-span without interfering with virus replication. Medication with SKF 30097 or metisazone and copper (2(+)) sulfate did not significantly or reproducibly change the expected day of death of the animals. The amantadine compounds of the second group have unusual symmetric structures with a 10-carbon cage. The parent compound acts intracellularly, while the site of action of an octachloro derivative is not known. Medication with the parent compound, but not the derivative, shortened the interval between LCM infection and death of the mouse. Tissue culture and animal screening of the many available derivatives in these two groups may uncover compounds more efficacious than those already examined.
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PMID:Arenavirus chemotherapy--retrospect and prospect. 108 27

Anorexia and cachexia are major problems in patients with cancer. Such measures as anti-cancer therapy, dietary counselling or hyperalimentation are not very successful in reversing this phenomenon in the vast majority of cancer patients. Thus, several drugs have been evaluated as agents to ameliorate cancer-associated anorexia/cachexia. Cyproheptadine is an antiserotonergic drug which appears to cause slight appetite stimulation in patients. A randomised clinical trial, however, was unable to demonstrate any weight gain from this agent. Corticosteroids are frequently used in clinical practice for appetite stimulation in patients with advanced malignancies. Supporting this practice, 4 randomised clinical trials showed that corticosteroid medications can stimulate the appetites of advanced cancer patients. However, these studies were not able to show any substantial nonfluid weight gain in treated patients. Megestrol acetate is a progestational agent which appears to be a relatively potent appetite stimulant. Randomised studies in advanced cancer patients have shown both substantial appetite stimulation and improvement in the nonfluid bodyweights of patients receiving this drug. Preliminary evidence also suggests that this drug has antiemetic properties. Several clinical studies are currently ongoing to determine the effect of various doses of megestrol acetate in patients with cancer. Efforts are also ongoing to evaluate both anabolic steroids and hydrazine sulfate as drugs for the treatment of patients with cancer anorexia/cachexia. The preliminary nature of these investigations, however, precludes recommendations for the use of either of these latter 2 drugs in routine clinical practice.
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PMID:Cancer-associated anorexia and cachexia. Implications for drug therapy. 137 16

The tetradecapeptide Ac-D-F-L-A-E-G-G-G-V-R-G-P-R-V-OMe, which mimics residues 7f-20f of the A alpha-chain of human fibrinogen, has been co-crystallized with bovine thrombin from ammonium sulfate solutions in space group P2(1) with unit cell dimensions of a = 83.0 A, b = 89.4 A, c = 99.3 A, and beta = 106.6 degrees. Three crystallographically independent complexes were located in the asymmetric unit by molecular replacement using the native bovine thrombin structure as a model. The standard crystallographic R-factor is 0.167 at 2.3-A resolution. Excellent electron density could be traced for the decapeptide, beginning with Asp-7f and ending with Arg-16f in the active site of thrombin; the remaining 4 residues, which have been cleaved from the tetradecapeptide at the Arg-16f/Gly-17f bond, are not seen. Residues 7f-11f at the NH2 terminus of the peptide form a single turn of alpha-helix that is connected by Gly-12f, which has a positive phi angle, to an extended chain containing residues 13f-16f. The major specific interactions between the peptide and thrombin are 1) a hydrophobic cage formed by residues Tyr-60A, Trp-60D, Leu-99, Ile-174, Trp-215, Leu-9f, Gly-13f, and Val-15f that surrounds Phe-8f; 2) a hydrogen bond linking Phe-8f NH to Lys-97 O;3) a salt link between Glu-11f and Arg-173; 4) two antiparallel beta-sheet hydrogen bonds between Gly-14f and Gly-216; and 5) the insertion of Arg-16f into the specificity pocket. Binding of the peptide is accompanied by a considerable shift in two of the loops near the active site relative to human D-phenyl-L-prolyl-L-arginyl chloromethyl ketone (PPACK)-thrombin.
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PMID:The structure of residues 7-16 of the A alpha-chain of human fibrinogen bound to bovine thrombin at 2.3-A resolution. 156 20

Sodium pentobarbital injections followed 30 min later by d-amphetamine sulfate produce an effect over trials in the form of an increase in heart rate in response to pentobarbital in relation to rats that receive the 2 drugs 24 hr apart (long-delayed control: Revusky, Davey, & Zagorski, 1989). This study found equivalent increases in heart rate in forward and backward groups in relation to a long-delayed control regardless of whether training or testing was carried out in a heart rate recording apparatus or in the home cage, which suggests that a drug interaction due to drug administrations in forward and backward groups has yet to be eliminated in accounting for the heart rate effect. Comparison of backward and long-delayed controls in a drug-drug procedure that used a taste aversion test revealed that both forward and delayed pairings can produce attenuated aversions in relation to a backward group regardless of whether the unconditional stimulus is amphetamine (Experiment 1) or lithium chloride (Experiment 2).
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PMID:Methodological issues in drug-drug conditioning in rats: nonassociative factors in heart rate and avfail. 166 59

A new antigen associated with pancreatic cancer was prepared by immunoaffinity chromatography using Fab'-Sepharose beads. This antigen was a glycoprotein of large molecular weight (Mr greater than 8,000,000) in its native state, estimated by size exclusion chromatography on Sephacryl S400. After sodium dodecyl sulfate-polyacrylamide gel electrophoresis and blotting analysis, several cancer-associated glycoconjugates, including CA19-9, CA50, Span-1, Dupan-2, and sialyl SSEA-1, were detected on the antigenic moiety of Mr 90,000. By an enzyme immunoassay for the antigen, elevated levels were found in pooled sera obtained from patients with various malignant and non-malignant diseases and normal subjects. However, the enhanced expression of CA19-9, Lewisa, or Lewisb epitope on the antigen molecule was restricted to the pooled sera from patients with pancreatic cancer. Furthermore, antigens from pancreatic or gastric cancer expressed ligands with intense and specific reactivity for Bauhinia purpurea (BPA), peanut (PNA), and Vicia villosa (VVA) lectins. The present assay system of the antigen, using both monoclonal antibodies (CA19-9, Lewisa, and Lewisb) and lectins (BPA, VVA and PNA), will provide a useful approach to the diagnosis of pancreatic cancer.
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PMID:Preparation of pancreatic cancer-associated mucin expressing CA19-9, CA50, Span-1, sialyl SSEA-1, and Dupan-2. 168 94

The distribution of somatostatin (SST) throughout the nervous system suggests that this tetradecapeptide may play a physiological role in CNS in the mediation of analgesia. The present study was undertaken to evaluate the antinociceptive properties of intrathecal (IT) injection of SST in the comparison of morphine sulfate (MS) in a primate model. The study was conducted after institutional approval and adhered to the regulations of the animal research committee. Seven adult monkeys (Maccaca cyclopis Swinhoe) weighing 4-6 kg were used. In each animal a L5 laminectomy window was created to facilitate IT injection. No neurological damage from surgery was noted. With the monkey standing in a specially constructed cage, all animals randomly received the following agents at one-week interval: (1) MS 1 mg, IT; (2) SST 50 micrograms, IT; (3) SST 250 micrograms, IT; and (4) SST 250 micrograms, IT + intramuscular (IM) naloxone 400 micrograms. The measured withdrawal latency (HPWL) was converted to the maximal percentage effect (MPE %) for comparison. The HPWL was measured at predrug and 5, 15, 30, 45, 60, 90 and 120 min after injection. Venous blood sample was obtained every 15 min to determine the plasma SST level by radioimmunoassay (RIA) technique in group 3 only. The results showed that MS (1 mg, IT) produced potent antinociception (MPE 100%) for more than 2 h. Intrathecal SST 50 micrograms, however, induced mild antinociception (MPE 43%) for only a short period and a 5-fold larger dose (250 micrograms) did not significantly change the nociceptive threshold with MPE only up to 47%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The antinociceptive effect of intrathecal somatostatin in monkeys]. 168 26

The experiments examined amphetamine-induced locomotion and stereotyped behavior in hippocampal-ablated and control rats for 30 days following surgery. Locomotor counts, stereotypy ratings, and locomotor-time profiles showed that d-amphetamine sulfate produced a selective enhancement of locomotion (cage crosses) at the expense of stereotyped behavior in hippocampal rats relative to normal control rats. This enhancement emerged over the first 2 weeks postsurgery. To examine the role of the striatum in this amphetamine-induced effect, combined hippocampal damage and 6-hydroxydopamine-induced damage of the nucleus accumbens or caudate-putamen were used. These results suggested that amphetamine-enhanced locomotion of hippocampal rats is dependent upon the integrity of the nucleus accumbens and may reflect a change of nucleus accumbens activity relative to caudate-putamen activity. Together these findings suggest that the hippocampus may participate in the control of locomotion by projections that modulate the activity of the nucleus accumbens.
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PMID:Hippocampal modulation of nucleus accumbens: behavioral evidence from amphetamine-induced activity profiles. 190 33

Many tumour-specific antigens in gastrointestinal cancers have carbohydrate immuno-determinants. These epitopes can be identified by lectins and monoclonal antibodies. By using fluorescein-isothiocyanate (FITC)-conjugated peanut agglutinin (PNA) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) we have investigated glycoproteins carrying altered carbohydrate epitopes in normal and carcinomatous human colorectal mucosa. In normal mucosa PNA stained goblet cell glycoconjugates in the supranuclear (Golgi) distribution. After neuraminidase pretreatment PNA stained actual mucin goblet itself at all levels of the crypts. Colorectal carcinomas displayed a strong and direct binding of PNA to apical cell membranes of carcinomatous cells and intraluminal secretions. Analysis of the glycoproteins by SDS-PAGE and PNA-labelling revealed four carcinoma-associated glycoproteins (26kD, 32kD, 35kD and 50kD). In addition, four glycoproteins (29kD, 30kD, 33kD and 36kD) common to normal and carcinomatous colorectal mucosa could be identified. All of these glycoproteins differed in their molecular weight from those in red cell controls which bind PNA only after desialylation. The study shows that the expression of PNA-binding sites in colorectal carcinomas signifies a cancer-associated carbohydrate alteration. Four carcinoma-associated glycoprotein antigens could be detected by this lectin. The antigens we have identified might be useful in the isolation and purification of more selective reagents for the serologic detection of colorectal cancer.
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PMID:Identification of glycoproteins expressing tumour-associated PNA-binding sites in colorectal carcinomas by SDS-GEL electrophoresis and PNA-labelling. 243 45

Young adult CD-1 male mice were housed in individual cages throughout the study. Groups of 10 to 20 mice were given gradually increasing doses of delta-9-tetrahydrocannabinol (THC) at 6.25 to 25 mg/kg i.p., trifluoperazine (TFP) at 6 to 12 mg/kg p.o., phenobarbital sodium (PS) at 20 to 35 mg/kg p.o., morphine sulfate (MS) at 5 to 20 mg/kg i.p., methaqualone (MQ) 10 to 20 mg/kg p.o. or chlordiazepoxide (CDP) 10 to 25 mg/kg p.o. over four to six weeks to develop tolerance of these drugs. Following the development of tolerance, the drugs were withdrawn. On the fourth day of withdrawal, a young (3-4 weeks old) male mouse was introduced into the cage. When the intensity of the attack was measured by the percentage of animals that killed the intruder within four hours. The results indicated 0 to 4 percent in the controls, 50-54 percent for THC, 50 percent for TFP, 42 percent for PS and 57 percent for MS. In contrast, no killing behavior was exhibited by these mice after treatment with MQ or CDP. These data suggest that enhanced aggressive behavior, elicited by withdrawal from certain psychotropic drugs, may be measured by the killing (muricidal) behavior of isolated mice.
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PMID:The effects of chronic treatment and withdrawal of CNS depressants on aggressive behavior. 256 May 90

Colon cancer cells in culture synthesize and secrete mucin glycoproteins, which carry a number of cancer-associated antigens. However, the structures and mechanisms of biosynthetic processing are not well understood. Mucins synthesized and secreted by LS174T human colon cancer cells were compared to those in LS174T xenografts in athymic mice. Mucins radiolabeled with glucosamine or sulfate were purified by gel filtration and cesium chloride density gradient centrifugation. The mucins were of high molecular weight and were resistant to chondroitinase ABC, hyaluronidase and HNO2 treatment. They were, however, susceptible to pronase digestion and mild alkaline treatment. Using radiochemical precursors, the cellular mucin was shown to contain fucose, galactose, N-acetylgalactosamine, N-acetylglucosamine, N-acetylneuraminic acid, and sulfate. Oligosaccharides released by beta-elimination had N-acetylgalactosaminitol as the reduced amino sugar and also unreduced galactosamine, indicating that there is N-acetyl-galactosamine O-glycosidically attached to protein core and also peripheral N-acetyl-galactosamine not directly linked to protein. DEAE-cellulose chromatography of mucins showed two major peaks with both intracellular and secreted mucins, but xenograft mucins also had more acidic components. Sulfate-labeled mucins were shifted to less acidic peaks by neuraminidase digestion, which indicates that the same mucin molecules are both sialylated and sulfated. We conclude that the intracellular mucins of cultured colon cancer cells, those secreted into the medium, and those in nude mouse xenografts are chemically similar, but differ in sialic acid and sulfate content. This experimental model system, LS174T cells maintained in culture and as nude mouse xenografts, may be useful for further biosynthetic and structural studies of colon cancer mucin.
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PMID:Comparison of metabolically labeled mucins of LS174T human colon cancer cells in tissue culture and xenograft. 273 49


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