[A case of chronic hepatitis C developing drug induced intrahepatic cholestasis due to anti-inflammatory drug during interferon therapy].
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Anti-Inflammatory Agents, Non-Steroidal↗
Biomedical subjects
R Watanabe
Publications and source records attributed to R Watanabe.
Percutaneous transluminal angioplasty for renovascular hypertension 9 years after hypoplastic kidney transplantation: report of a case.
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Angioplasty, Balloon↗
[Clinical significance of serum levels of human hepatocyte growth factor in patients with acute viral hepatitis].
We studied the relationship of serum levels of human hepatocyte growth factor (hHGF) to causative viruses and clinical features in 63 patients at our hospital with serologically diagnosed acute viral hepatitis. Serum levels of hHGF were not correlated with the type of hepatitis virus (A, B, and C) during the acute phase (p < 0.60) but were correlated with results of the hepaplastin test (p < 0.01). Furthermore, the difference in serum levels of hHGF between severe (levels on hepaplastin test < 40%) and nonsevere cases of hepatitis was significant (p < 0.001), and serum levels of hHGF became normal as levels of alanine aminotransferase decreased. However, serum levels of hHGF in prolonged cases of hepatitis (time until normalization of alanine aminotransferase > 13 weeks) tended to be slightly lower than in nonprolonged cases (p < 0.47). These results suggest that serum levels of hHGF are useful to determine the prognoses of patients with severe hepatitis and to estimate the time until liver damage heals.
Acute Disease↗
[Myoglobinuria following anesthesia with enflurane and succinylcholine in an asthmatic child on theophylline].
An 8-year-old asthmatic child on theophylline was anesthetized with enflurane in nitrous oxide and oxygen. He developed a generalized muscle rigidity after intravenous succinylcholine. Although the maximum rectal temperature was 37.9 degrees C, a marked elevation in muscle-derived enzymes and myoglobinuria were observed. The relations among theophylline which is a derivative of xanthines, inhalation anesthetics, and myoglobinuria are discussed.
Anesthesia, Inhalation↗
Toward an integrated phenotype in pre-NIDDM.
The search for the genetic basis of NIDDM has magnified the need for an efficient representation of the pre-NIDDM phenotype. The overall goal is to relate specific mutations on the genome to specific changes in physiologic function which lead to NIDDM. Unfortunately, there is still not a clear understanding of the molecular cause of NIDDM in most individuals. Therefore, one must take an alternative approach: to express in quantitative terms the various tissue processes which determine the ability to regulate the blood glucose in fasting and after carbohydrate administration. A minimal list of such processes includes the provision of glucose by the liver, insulin sensitivity, insulin secretion, and glucose effectiveness. The latter function is the ability of glucose per se to enhance glucose disappearance from blood, independent of a dynamic insulin response. Approaches to measuring the list of functions which determine the glucose tolerance are reviewed: they include the minimal model method, which quantitates insulin sensitivity (Sl) and glucose effectiveness (SG), and a combined model approach, which measures insulin secretion. These methods are being developed for large populations. Such a development is important for elucidating the causes of reduced glucose tolerance in populations, and examining the relation between such causes and outcomes including diabetes and cardiovascular disease. Of particular importance for diabetes development is the characteristic hyperbolic relationship between insulin secretion and insulin action. This relationship, the "hyperbolic law of glucose tolerance' indicates that insulin secretion can only be assessed in terms of the ambient degree of insulin sensitivity. By applying this principle, it is clear that latent pancreatic islet-cell dysfunction has been underestimated, and may be significant even in subjects with impaired glucose tolerance. Finally, new explorations of insulin control of liver glucose output indicate that this process may be under the control of free fatty acids. The latter realization indicates that the insulin effect on lipolysis is what is critical for determination of glucose output in the fasting state, and that insulin resistance at the level of the adipocyte may determine the extent of fasting hyperglycaemia, and may be an important factor in the overall phenotype in prediabetic and NIDDM individuals.
Animals↗
Estimation of EDRF and nitric oxide release using [3H]GTP-labeled human platelets.
We have developed a new bioassay for endothelium-derived relaxing factor (EDRF) or nitric oxide (NO) using human [3H]guanosine triphosphate (GTP)-labeled platelets. The labeled platelets were preincubated with isobutyl-methylxanthine and co-cultured with endothelial cells and the [3H]cyclic guanosine monophosphate (cGMP) formed was isolated by ion-exchange chromatography. Endothelial cells, either in monolayer cells or in suspension, increased platelet cGMP accumulation dose-dependently, a significant increase being detected with 5000 endothelial cells or more/assay when suspended cells were used. Co-culturing with the same number of skin fibroblasts failed to elevate platelet cGMP. Preincubation of endothelial cells with bradykinin and superoxide dismutase (SOD) synergistically potentiated the increase in platelet cGMP, but was attenuated by Nomega-nitro-L-arginine, with partial restoration by L-arginine but not by D-arginine. These compounds, however, did not affect cGMP accumulation by sodium nitroprusside. Moreover, preincubation of the labeled platelets with the NO synthase inhibitor prior to EDRF assay had no effect. We conclude that [3H]GTP-labeled platelets could provide a simple, sensitive and specific bioassay for estimating EDRF or NO release.
Animals↗
What effect does controlling platelets have on atherosclerosis?
Platelets play important roles for hemostasis with activated platelets adhering to the injured vessel wall to initiate platelet aggregation. At the same time, our study revealed the cytotoxic effect on endothelial cells characterized by an increase of intracellular Ca++ and a decrease of EDRF production, which may cause plasmal infiltration including blood cells and lipids. Our clinical survey using a small dose of aspirin as an antiplatelet therapy clearly demonstrated its suppressive effect on platelet aggregation and its favorable effect on fibrinolysis. These data suggest that the therapeutic effect of aspirin in vascular disease could be applied to the prevention of thrombus formation and the protection of endothelial cells from the cytotoxic effect of activated platelets.
Adenylyl Cyclases↗
Molecular cloning and expression of rat squalene epoxidase.
Squalene epoxidase (SE) (EC 1.14.99.7) catalyzes the first oxygenation step in sterol biosynthesis and is suggested to be one of the rate-limiting enzymes in this pathway. Rat SE cDNA was isolated by selecting yeast transformants expressing rat cDNA in the presence of transformants expressing rat cDNA in the presence of terbinafine, an inhibitor specific for fungal SE. The expression of rat SE in the isolated terbinafine-resistant clone was confirmed by its survival in the presence of either terbinafine or an inhibitor specific for mammalian SE, NB-598, but not in the presence of both terbinafine and NB-598. Rat SE polypeptide deduced from the nucleotide sequence contains 573 amino acids, and its molecular weight is 63,950 Da. The amino acid sequence reveals one potential transmembrane domain, a hydrophobic segment (Leu27 to Tyr43) in the NH2-terminal region. This region also contains a beta 1-alpha A-beta 2 motif, which is the consensus sequence for an FAD binding domain, suggesting that SE is a flavoenzyme. This deduced rat SE sequence is 30.2% identical to the ERG 1 gene, which encodes SE from an allylamine-resistant Saccharomyces cerevisiae mutant. Expression of a full-length rat SE protein in Escherichia coli confirms this polypeptide as a functional SE. This is the first report of the molecular cloning of mammalian SE.
Amino Acid Sequence↗
Treatment of acute promyelocytic leukemia with all-trans retinoic acid during the third trimester of pregnancy.
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Female↗
Murine monoclonal antibody recognizing human alpha(1,3/1,4)fucosyltransferase.
We prepared a mouse monoclonal antibody, FTA1-16, that specifically recognizes human alpha(1,3/1,4)fucosyltransferase without crossreactivity to any other members of the alpha(1,3)fucosyltransferase family. The specificity was confirmed by both immunofluorescense staining of native antigens in the Golgi apparatus and Western blotting analysis, using stable transformant cells transfected with each gene of the alpha(1,3)fucosyltransferase family. Western blotting analysis on a series of human tumour cell lines from various tissues revealed that some epithelial cancer cell lines from digestive organs expressed an amount of alpha(1,3/1,4)fucosyltransferase in good correlation with expression of sialyl Lewis a antigen. Immunohistochemical staining by FTA1-16 on colon cancer tissues revealed enhanced expression of the enzyme in cancer cells in comparison to normal cells. Finally, the antigenic epitope recognized by FTA1-16 was determined using truncated recombinant peptides which were expressed in E. coli. A minimal length determined was a fragment, amino acid positions 132-153, of the alpha(1,3/1,4)fucosyltransferase.
Amino Acid Sequence↗
Inhibition of neurotropic mouse retrovirus replication in glial cells by synthetic oligo(2'-O-methyl)ribonucleoside phosphorothioates.
Synthetic oligo(2'-O-methyl)ribonucleoside phosphorothioate, FS-25, which is complementary to the splicing acceptor site of neurotropic mouse retrovirus (FrC6 virus), and non-complementary analogs including 2'-O-methylinosine homo oligomer (MIS-25), both inhibited viral infection in glial cells. In addition, FS-25 and MIS-25 partially suppressed viral production of glial cells persistently infected with FrC6 virus. Both FS-25 and MIS-25 potently inhibited reverse transcriptase activity of the FrC6 virus in a cell-free system. Addition of these compounds before or after second-round infection of the FrC6 virus inhibited the accumulation of unintegrated viral DNA. These results indicate that these compounds fundamentally inhibit retrovirus production in glial cells in the same manner in which they inhibit HIV production, by blocking several viral replication pathways including fresh infection, second-round infection, and reverse transcription of the viral genome. Our novel neurotropic retrovirus is a useful experimental model for the development of drugs against HIV infection.
Animals↗
Characterization of monoclonal antibodies recognizing neurotropic Friend murine leukemia virus.
We isolated a replication-competent, neurotropic retrovirus (FrC6 virus) and its molecular clone A8 from the NB-tropic Friend murine leukemia virus (FLV) complex. For detection and characterization of the FrC6 and A8 viruses, monoclonal antibodies (MAbs) against the FLV complex were established. Thirty MAbs, each of which reacted with the FLV-producing cell line, were tested for potential neutralizing activities; only two MAbs inhibited the proliferation of the A8 virus. These two MAbs were ineffective or had very weak neutralizing activities toward the non-neurotropic FLV strain clone 57 virus. Further characterization of MAbs by immunoprecipitation revealed that 4 MAbs recognized the envelope protein of the A8 virus. Two of these 4 MAbs recognized the surface glycoprotein gp70, requiring the conformational epitope of the virus for this recognition, while the other two MAbs, which were reactive with the transmembrane protein p15E, were conformation-independent. Both of the MAbs against gp70 distinguished neuropathogenic and non-neuropathogenic viruses to some extent, through neutralizing activity or binding activity detected by immunoprecipitation, whereas the two MAbs against p15E reacted with the viruses in a similar manner. Furthermore, one of the MAbs distinguished the viral antigen in the wall of the vacuolation that composes the spongiotic lesion induced by FrC6 viral infection of the brain.
3T3 Cells↗
Gene expression of neurotropic retrovirus in the CNS.
We isolated a neurotropic retrovirus, FrC6-V, from Friend leukemia virus complex after the adaptation of the original virus to newborn rat brain followed by the long-term infection of rat glioma cell line C6. When rats were infected with FrC6-V, the virus was isolated mainly from the brain and from the thymus of the infected animals regardless of the age of the animals at the time of inoculation. Neurological and neuropathological manifestations became apparent, however, only when the newborn rats were infected. The lesions in the brain were characterized by spongiform degeneration accompanied by the loss of neurons in the hypothalamus, cerebral cortex, and cerebellum. There was almost no inflammatory cell infiltration. In primary culture of brain, the astrocytes and the neuron specific enolase antigen-positive cells were infected with FrC6-V, but the viral antigen was not detected in neurofilament antigen-positive neurons. Furthermore, our virus inhibited the differentiation of embryonal carcinoma (EC) cell line P19 into neurons.
Animals↗
E-cadherin expression in renal cell cancer and its significance in metastasis and survival.
Decreased expression of E-cadherin (E-CD), a homotypic intercellular adhesion molecule, is considered to elicit detachment of tumour cells from primary lesions, which is the first stage of metastasis. Since renal cell cancer (RCC) shows a relatively high frequency of metastasis, we focused our interest on E-CD expression in RCC and its clinicopathological implications. We examined E-CD expression in normal kidney and RCC by immunohistochemical staining. In normal kidney, E-CD expression was localised in distal tubules and collecting ducts. In RCC, 20 of 106 primary lesions (18.9%) expressed E-CD, whereas none showed positive staining for eight metastatic lesions. There was a statistically significant correlation between loss of E-CD expression and advanced stages of RCC. Kaplan-Meier analysis showed better prognosis in the group with preserved E-CD expression than without E-CD expression (Cox-Mantel test, P = 0.022, the average follow-up was 32 months or until death). This study suggests that the patients with decreased E-CD expression may be associated with metastasis, resulting in poor prognosis. However, frequency of E-CD expression in RCC is lower than in other cancers, which may be derived from the localised distribution of E-CD expression in normal kidney.
Adult↗
Oxidation yield of the ferrous ion in a Fricke solution irradiated with monochromatic synchrotron soft X-rays in the 1.8-10 keV region.
The oxidation yield of ferrous ion in a Fricke solution was measured in the soft X-ray region from 1.8 to 10 keV. The standard Fricke solution was irradiated with monochromatic X-rays from synchrotron radiation. The yield decreased with decreasing X-ray energy, as several theoretical calculations have predicted. No significant changes were observed in the K-shell photo-absorption of the iron and sulphur contained in the standard Fricke solution. The high-LET nature of soft X-rays is discussed.
Dose-Response Relationship, Radiation↗
Simian immunodeficiency virus infection of macaque primary placental cells.
We have characterized the ability of a simian immunodeficiency virus, SIVmne strain E11S, to infect macaque placental trophoblast and Hofbauer cells. These primary placental cells were permissive to SIVmne infection, regardless of gestational age. Virus production by the infected cells was determined as time-dependent viral core antigen p27 production, followed by verification of the proviral gag/LTR DNA sequences in the infected cells using a polymerase chain reaction assay. Of more than six placentas tested, SIVmne infection of placental cells at an early gestational age (i.e., days 55 or 78) produced more than 10-fold the amount of virus core antigen p27 than did placental cells infected at a late gestational age (i.e., days 135 or 165). In addition, SIVmne infection of trophoblast cells was inhibited by SIVmac neutralizing macaque serum but not by normal serum, indicating the specificity of virus infection. Furthermore, the amount of SIV core antigen p27 produced by the virus-infected trophoblast and Hofbauer cells was shown to be dependent on the multiplicity of virus infection. Collectively, our results indicate that macaque trophoblast and Hofbauer cells can be infected by SIV and that both gestational age and viral dose may play a role in the extent of viral infection.
Animals↗
Effect of nifedipine on cyclic GMP turnover in cultured coronary smooth muscle cells.
We investigated the effects of nifedipine on cyclic GMP turnover and the pertinent enzyme activities in cultured coronary smooth muscle cells (SMC). Nifedipine at high concentrations slightly decreased basal soluble guanylate cyclase activity and inhibited the action of sodium nitroprusside (SNP) but had no effect on the particulate form of the enzyme. In contrast, nifedipine inhibited cyclic GMP hydrolysis by directly inhibiting the partially purified calmodulin-stimulated isoform of phosphodiesterase (type I PDE) with IC50 of 4.2 microM. Nifedipine > or = 1.0 microM enhanced cyclic GMP accumulation in response to 1.0 microM SNP, although nifedipine alone exerted no influence on cyclic GMP levels. Enhancement of cyclic GMP accumulation by nifedipine in response to SNP was not affected by BAY K 8644, a calcium channel agonist. These properties may be shared by other dihydropyridines since nicardipine and nisoldipine also inhibited type I PDE with similar IC50. However, some other structurally unrelated calcium channel blockers, diltiazem and verapamil, had little effect on cyclic nucleotide hydrolysis or on cyclic GMP accumulation in response to SNP. Nifedipine may synergistically enhance cyclic GMP accumulation in response to nitric oxide (NO)-releasing agents by directly inhibiting type I PDE in coronary SMC. Such effects of nifedipine may partly contribute to coronary vasodilation and prevention of coronary spasm in patients with ischemic heart disease.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
Specific deposition of passively transferred monoclonal antibodies against herpes simplex virus type 1 in rat brain infected with the virus.
The kinetics of human monoclonal antibody (anti-gB) to herpes simplex virus type 1 (HSV-1) were investigated after intravenous injection of anti-gB into an HSV-1 encephalitis animal model. Immunohistochemical study revealed specific deposition of passively transferred anti-gB in the hippocampus and thalamus of the infected rat brain, and it bound to the same neurons in which HSV-1 antigen was positively stained. To examine the macroscopic distribution of anti-gB in the infected brain, we undertook an 125I-labeled anti-gB injection study, and the same distribution of 125I-labeled anti-gB deposition was observed by brain semimicroautoradiography as in the immunohistochemical study. These results suggest that anti-gB easily permeates the capillary wall and is deposited in the inflammatory site where HSV-1-specific antigen is detectable. The use of radioisotope-labeled anti-gB injection and external brain imaging could lead to a noninvasive diagnostic tool for the early detection of HSV-1 antigen in cases of suspected HSV-1 encephalitis.
Animals↗