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Biomedical subjects

K Ohba

Publications and source records attributed to K Ohba.

At least 73 records · Page 4Linked to original sources
PubMed1997

Defective stimulation of thyroxine 5'-deiodinase activity by cold exposure and norepinephrine in brown adipose tissue of monosodium glutamate-obese mice.

In order to examine the possible change in the thyroid hormone metabolism in the monosodium glutamate (MSG)-obese mice, we determined the iodothyronine deiodinase activity of brown adipose tissue (BAT), liver and kidney of male and female mice. There was no significant difference in the type II thyroxine 5'-deiodinase (T4 5'DII) activity in BAT between MSG-obese and control mice when they were kept at the ambient temperature of 22 degrees C. T4 5'DII activity in BAT of control mice increased markedly after exposure to cold (4 degrees C) for 4 h; however, the extent of cold-induced increase in T4 5'DII activity in BAT of MSG-obese mice was greatly reduced. Injection of norepinephrine (NE) (0.8 mg/kg, s.c.) 4 h previously increased T4 5'DII activity in BAT of control mice, but NE-induced increase in T4 5'DII activity was also markedly reduced in BAT of MSG-obese mice. Both cold- and NE-induced increase in T4 5'DII activity was greater in female, although similar tendency was obtained in male mice. Type I 3,3',5'-triiodothyronine deiodinase (rT3 5'DI) activity of liver and kidney, and serum thyroxine (T4) and 3,5,3'-triiodothyronine (T3) levels in MSG-obese mice were essentially the same as those of the control male and female mice irrespective of cold exposure. These results suggest that defective stimulation of T4 5'DII activity of BAT by cold in the MSG-obese mice is due to deficient sympathetic input to BAT and/or to diminished response of BAT to NE, and may contribute to a possible cause of inability of MSG-obese mice to maintain body temperature under cold exposure.

Adipose Tissue, Brown↗
PubMed1997

Early therapy with interferon for acute hepatitis C acquired through a needlestick.

Because there is no effective neutralizing antibody or vaccine for preventing hepatitis C virus (HCV) transmission, HCV can be transmitted to health care workers through accidental needlesticks. Recently, two of our health care workers acquired HCV infection through needlestick accidents and developed acute hepatitis C. The route of transmission was confirmed by molecular evolutionary analysis with use of the E2 region of the HCV genome. After the clinical onset of acute hepatitis, the health care workers were treated with interferon (IFN) (total dose, approximately 300 megaunits). Neither individual developed chronic hepatitis. This finding raises the possibility that treatment with low-dose IFN following an accidental needlestick may be beneficial, even when it is started after the clinical onset of hepatitis.

Acute Disease↗
PubMed1997

GB virus C/hepatitis G virus infection in southern China.

The prevalence of GB virus C/hepatitis G virus (GBV-C/HGV) infection among intravenous drug users (IVDUs), patients with liver diseases, and blood donors in Nanning, southern China was studied. GBV-C/HGV RNA was detected by reverse transcription polymerase chain reaction with primers derived from the 5'-untranslated region. GBV-C/HGV RNA was detected in 64 of 85 IVDUs, 20 of 80 persons with liver disease, and 1 of 50 blood donors. Among IVDUs, GBV-C/HGV infection was associated with antibodies to hepatis C virus (HCV) and with hepatitis B surface antigen (HBsAg). Eleven nucleotide sequences were determined and analyzed by molecular evolutionary analysis. In a phylogenetic tree, the isolates were grouped in three clusters with GBV-C and HGV grouped in two clusters. These data indicate that GBV-C/HGV infection is common in China among IVDUs but uncommon among persons with liver disease without HBsAg or anti-HCV and that there is a new group of GBV-C/HGV.

Blood Donors↗
PubMed1997

New hepatitis C virus (HCV) genotyping system that allows for identification of HCV genotypes 1a, 1b, 2a, 2b, 3a, 3b, 4, 5a, and 6a.

Recent studies have focused on whether different hepatitis C virus (HCV) genotypes are associated with different profiles of pathogenicity, infectivity, and response to antiviral therapy. The establishment of a simple and precise genotyping system for HCV is essential to address these issues. A new genotyping system based on PCR of the core region with genotype-specific PCR primers for the determination of HCV genotypes 1a, 1b, 2a, 2b, 3a, 3b, 4, 5a, and 6a was developed. A total of 607 samples (379 from Japan, 63 from the United States, 53 from Korea, 35 from Taiwan, 32 from China, 20 from Hong Kong, 15 from Australia, 6 from Egypt, 3 from Bangladesh, and 1 from South Africa) were tested by both the assay of Okamoto et al. (H. Okamoto, Y. Sugiyama, S. Okada, K. Kurai, Y. Akahane, Y. Sugai, T. Tanaka, K. Sato, F. Tsuda, Y. Miyamura, and M. Mayumi, J. Gen. Virol. 73:673-679, 1992) and this new genotyping system. Comparison of the results showed concordant results for 539 samples (88.8%). Of the 68 samples with discordant results, the nucleotide sequences of the HCV isolates were determined in 23, and their genotypes were determined by molecular evolutionary analysis. In all 23 samples, the assignment of genotype by our new genotyping system was correct. This genotyping system may be useful for large-scale determination of HCV genotypes in clinical studies.

DNA Primers↗
PubMed1997

[Molecular evolutionary analysis of GB viruses and hepatitis G virus].

Recently, new blood-transfusion transmissible viruses, called hepatitis G virus(HGV) and GB virus-C(GBV-C), have been reported. It was found that two viruses were independent isolates of the same virus, the genomic structure resembled that of flavivirus family, and GBV-C/HGV was closely related to HCV. To elucidate the evolutionary relationship between hepatitis C virus(HCV) and GBV-C/HGV, we constructed the phylogenetic trees for the putative RNA helicase and the RNA-dependent RNA polymerase regions of the Flaviviridae by UPGMA. The tree showed that HCV was closely related to GB virus-B(GBV-B) and HGV was more nearer to GB virus-A(GBV-A) rather than HCV.

Amino Acid Sequence↗
PubMed1996

Tolerance to lipopolysaccharide-induced increase in vascular permeability in mouse skin.

We investigated whether tolerance develops to the lipopolysaccharide-induced increase in vascular permeability of mouse skin on pretreatment with Salmonella typhimurium lipopolysaccharide. Lipopolysaccharide-induced plasma extravasation was assessed by determining Pontamine sky blue dye accumulation in the skin where lipopolysaccharide was injected s.c. 2 h previously. When mice were pretreated with lipopolysaccharide (0.15 mg/kg i.p.), the dye leakage induced by s.c. challenge with lipopolysaccharide (400 micrograms/site) was significantly, inhibited for 2-24 h after pretreatment, indicating the development of lipopolysaccharide tolerance. At 4 h after lipopolysaccharide (0.15 mg/kg i.p.), the dose-response curve of dye leakage against the challenge dose of lipopolysaccharide shifted about 2-fold to the higher dose. The dye leakage induced by lipopolysaccharide was inhibited by pretreatment with lipopolysaccharide in a dose-dependent manner (0.05-0.15 mg/kg i.p.). Lipopolysaccharide tolerance was not seen in adrenalectomized mice. When mice were pretreated with lipopolysaccharide and NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, at the same time, the hyporesponsiveness to lipopolysaccharide challenge disappeared. However, L-NAME was ineffective to inhibit the development of lipopolysaccharide tolerance when administered 24 h after lipopolysaccharide pretreatment or just before the lipopolysaccharide challenge. Tumor necrosis factor-alpha and interleukin-1 alpha but not interleukin-6 induced a similar hyporesponsiveness to lipopolysaccharide. These results suggest that tolerance develops to the lipopolysaccharide-induced increase in vascular permeability in mouse skin after a single lipopolysaccharide administration and that endogenous glucocorticoids and NO are necessary for induction of lipopolysaccharide tolerance. Hyporesponsiveness induced by lipopolysaccharide pretreatment may be mediated by production of some cytokines such as tumor necrosis factor-alpha or interleukin-1 alpha.

Animals↗
PubMed1996

Role of nitric oxide and prostaglandins in lipopolysaccharide-induced increase in vascular permeability in mouse skin.

To examine the possible role of increased vascular permeability in the circulatory shock induced by endotoxin (lipopolysaccharide), we examined whether lipopolysaccharide elicits plasma extravasation in the skin of ddY strain mice. We also studied whether nitric oxide (NO) and prostaglandins may mediate the lipopolysaccharide-induced increase in vascular permeability. Subcutaneous injection of lipopolysaccharide (100-400 micrograms/site) induced a dose-related and delayed increase in vascular permeability at the injection site as determined by the leakage of pontamine sky blue. Concurrent administration of aminoguanidine (a putative inducible NO synthase inhibitor) (10 mg/kg, i.v.) inhibited the lipopolysaccharide (400 micrograms/site)-induced dye leakage by 71%. N(G)-Nitro-L-arginine methyl ester (an inhibitor for both constitutive and inducible NO synthase) (10 and 20 mg/kg, i.v.) inhibited the lipopolysaccharide-induced dye leakage by 36% and 54%, respectively, whereas the inactive enantiomer, N(G)-nitro-D-arginine methyl ester (10 mg/kg, i.v.), had no effect. Pretreatment with an intraperitoneal injection of dexamethasone (500 micrograms/kg) or indomethacin (a cyclooxygenase-1 and -2 inhibitor) (5 mg/kg) almost completely inhibited the response induced by lipopolysaccharide, by 96% and 84%, respectively. [N-(2-Cyclohexyloxy-4-nitrophenyl) methanesulphonamide (a cyclooxygenase-2-specific inhibitor) (0.01-1 mg/kg, i.p.) also induced a dose-related inhibition of dye leakage elicited by lipopolysaccharide: 38% and 80% suppression at the doses of 0.1 and 1 mg/kg, respectively. Cycloheximide (a protein biosynthesis inhibitor) (35 mg/kg, s.c.) suppressed the effect of lipopolysaccharide by 74%. These results suggest that the increase in vascular permeability induced by lipopolysaccharide is mediated by both NO and prostaglandins and that synthesis of inducible NO synthase and cyclooxygenase-2 may be involved in this effect of lipopolysaccharide.

Animals↗
PubMed1996

Evolutionary relationship of hepatitis C, pesti-, flavi-, plantviruses, and newly discovered GB hepatitis agents.

Two flavivirus-like viruses, GB virus-A (GBV-A) and GB virus-B (GBV-B), were recently identified in the GB hepatitis agent, and are distinct from the hepatitis A to E viruses. The putative helicase domain of GBV-A and GBV-B was found to have amino acid sequence homology with hepatitis C virus (HCV), and distantly, is also related to pestiviruses, flaviviruses, and plant viruses. A phylogenetic tree construction showed that GBVs and HCV are closely related, and they are clustered with pestiviruses, flaviviruses and plant viruses in that order.

Amino Acid Sequence↗
PubMed1996

GB virus C/hepatitis G virus infection among Japanese patients with chronic liver diseases and blood donors.

Recently, a novel hepatitis virus, GB virus C/hepatitis G virus (GBV-C/HGV), has been isolated. To elucidate the seroprevalence of chronic GBV-C/HGV infection in Japan and the phylogenetic relationship between Japanese strains and the strains previously reported, serum GBV-C/HGV RNA was detected by reverse transcription polymerase chain reaction (RT-PCR) in 203 patients with chronic liver diseases and 200 samples of voluntary blood donors. RT-PCR was performed with primers derived from the 5'-untranslated region which were conserved between GBV-C and HGV and distant from other flaviviruses including hepatitis C virus (HCV). The nucleotide sequences were determined by the dideoxy chain termination method. The phylogenetic analysis was performed by the neighbor-joining method. In 10 (4.7%) of 203 patients with chronic liver diseases and in 1 (0.5%) of 200 blood donor samples, serum GBV-C/HGV RNA was detected. Of 10 patients, 9 patients were positive for anti-HCV and negative for HBsAg, and 1 patient was positive for HBsAg and negative for anti-HCV. The phylogenetic analysis indicated that there were three major groups which were group 1 (GBV-C), group 2 (HGV), and group 3 (a group of Japanese strains). These data indicated that (1) there was a low prevalence of GBV-C/HGV infection in Japanese patients with chronic liver diseases, (2) a high proportion of patients with GBV-C/HGV infection had chronic HCV infection however, and (3) there were at least three groups in strains of GBV-C/HGV.

Adult↗
PubMed1996

Hepatitis C virus types 7, 8 and 9 should be classified as type 6 subtypes.

Tokita et al. reported the identification of hepatitis C virus type 7, 8 and 9 in Southeast Asia, based on the unweighed pair-group method with the arithmetic mean, a method that may not be appropriate when the nucleotide substitution rate is not constant over time. To determine more accurately the relationship of these proposed types 7, 8, and 9 with other types, a more appropriate approach, the neighbor-joining method, was applied to re-evaluate the phylogenetic relationship. A total of 660 HCV sequences, including the reported sequences, were collected from DNA databases. For every region, the nucleotide substitution rate was estimated by the 6-parameter method, and phylogenetic trees were constructed using the neighbor-joining method. The results of this analysis indicate that the newly proposed HCV types 7, 8 and 9 should be classified as type 6 subtypes. HCV type 6 appears to be diversified.

Evolution, Chemical↗
PubMed1996

Phylogenetic tree-based epidemiological analysis of hepatitis C virus transmission in a region of Japan with a high prevalence of infection.

Local clustering of hepatitis C virus (HCV) infection has been demonstrated in various regions in Japan. HCV genotypes have now been compared between infected individuals from districts of Saga prefecture with either a high (H district) or low (L district) prevalence of HCV-seropositivity. The prevalence of HCV genotype 1b was significantly higher (P < 0.001) in the H district (45/50; 90%) than in the L district (19/36; 52.8%). A phylogenetic tree was constructed based on the genomic sequences of viral isolates from 20 patients infected with genotype 1b in the H district. Almost all these HCV strains clustered in the same regions of the tree. With regard to risk factors for HCV transmission, the percentage of patients with a history of surgery was significantly higher in the H district than in the L district (58 versus 33.3%; P < 0.05). Of 20 patients infected with similar strains of HCV in the H district, 16 (80%) had at least one parenteral risk factor associated with medical care. These results indicate an increased transmission of similar strains of HCV in the H district as a result of nosocomial infection.

Base Sequence↗
PubMed1996

Genotype, serum level of hepatitis C virus RNA and liver histology as predictors of response to interferon-alpha 2a therapy in Japanese patients with chronic hepatitis C.

To determine whether pretreatment HCV-RNA level, hepatitis C virus genotypes, alanine aminotransferase and histology correlate with subsequent response to interferon-alpha therapy or not, serum HCV-RNA levels and genotype were determined by branched DNA signal amplification assay and genotype-specific polymerase chain reaction in 43 patients with chronic active hepatitis C. Response to recombinant interferon-alpha 2a (504 million units in total) was defined as complete and sustained CR-->SR, n = 12), complete response followed by relapse (CR-->Rel, n = 17), and no response (NR, n = 10), excluding dropouts (n = 4). Patients who showed CR-->SR had a lower HCV-RNA level (0.438 x 10(6) eq/ml) compared to CR-->Rel (2.452 x 10(6) eq/ml, p = 0.008) and NR (4.882 x 10(6) eq/ml, p = 0.009). A higher proportion of patients with CR-->SR had type 2a HCV (67%) compared to the CR-->Rel (28%) and the NR (0%). There was a trend for type 1b hepatitis C virus infection to have higher serum HCV-RNA levels. There was no correlation between pretreatment HCV-RNA level and alanine aminotransferase. However, no relation between pretreatment HCV-RNA level and liver histology was observed; a high proportion of patients with CAH2a showed CR-->SR, compared to those with CAH2b (p = 0.001). Moreover, the patients with CAH2b who had low level hepatitis C virus viremia did not show CR-->SR. These data indicate that pre-treatment serum HCV-RNA levels, genotype and liver histology are good predictors of subsequent response to interferon-alpha therapy in Japanese patients with chronic hepatitis C virus infection.

Alanine Transaminase↗
PubMed1996

Effect of S-ethylisothiourea, a putative inhibitor of inducible nitric oxide synthase, on mouse skin vascular permeability.

By dye leakage in mouse skin, we evaluated the inhibition of proinflammatory stimuli-induced plasma extravasation by a putative inhibitor of inducible nitric oxide synthase, S-ethylisothiourea. A low dose of S-ethylisothiourea (5 micrograms/kg) mimicked aminoguanidine in inhibiting the plasma extravasation elicited by lipopolysaccharide but not by 5-hydroxytryptamine or platelet-activating factor. A higher dose of S-ethylisothiourea (10 micrograms/kg) inhibited the plasma extravasation induced by 5-hydroxytryptamine slightly; however, it increased the basal dye leakage. Thus, S-ethylisothiourea may be used as a relatively specific inhibitor for inducible nitric oxide synthase in vivo.

Animals↗
PubMed1995

Bufotenine reconsidered as a diagnostic indicator of psychiatric disorders.

We have analyzed products of the serotonin-degradative pathway, in which both N-methylserotonin and bufotenine are formed in urine specimens of products with psychiatric disorders by three-dimensional HPLC with electrochemical detection. Bufotenine was detected in urine from all autistic patients with mental retardation and epilepsy (n = 18) and many autistic patients (32/47) with mental retardation. Bufotenine was detected in the urine of 15 of 18 patients with depression. Thirteen of 15 schizophrenic patients were also positive for bufotenine. N-methylserotonin was also detected in some cases of each disorder. Only two of 200 urine specimens from healthy controls were positive for bufotenine. Thus, the presence and levels of bufotenine might be useful and important markers of some psychiatric disorders.

Adult↗
PubMed1995

Endothelin-1, but not endothelin-3, suppresses lipoprotein lipase gene expression in brown adipocytes differentiated in culture.

The effect of endothelins on lipoprotein lipase activity and lipoprotein lipase mRNA levels was studied in brown adipocytes differentiated in culture. Lipoprotein lipase activity was determined in two fractions; lipoprotein lipase released by heparin (10 IU/ml, 1 h) into the medium (heparin-releasable fraction) and lipoprotein lipase activity remaining in cells (extractable fraction). Time-course studies showed that endothelin 1 (10(-7) M) progressively decreased both lipoprotein lipase fractions (heparin-releasable, extractable), until nadir at 24 h. Endothelin-1 reduced both lipoprotein lipase activities (heparin-releasable, extractable) in a concentration-dependent manner, whereas endothelin-3 did not produce any significant changes in either of them. Northern blot analysis revealed that endothelin-1 (10(-7)-10(-11) M) caused a concentration-dependent decrease in lipoprotein lipase mRNA obtained from cells on day 9. Furthermore, pretreatment of brown adipocytes with endothelin ETA receptor antagonist FR139317 antagonized the endothelin-1-induced reduction of lipoprotein lipase activity and lipoprotein lipase mRNA. These results suggest that endothelin-1 decreases lipoprotein lipase activity by inhibiting the lipoprotein lipase gene expression in brown adipocytes differentiated in culture, possibly through endothelin ETA receptors on cell membranes. Because of marked reduction of lipoprotein lipase activity and its mRNA as a marker of adipogenic differentiation, endothelin-1 may have an inhibitory role in the differentiation of brown adipocytes.

Adipocytes↗
PubMed1995

Role of eicosanoids but not nitric oxide in the platelet-activating factor-induced increase in vascular permeability in mouse skin.

We investigated the role of endogenous eicosanoids and nitric oxide (NO) in the platelet-activating factor (PAF)-induced increase in vascular permeability in mouse skin. Subcutaneous injection of PAF (45-180 pmol/site) induced a dose-related increase in vascular permeability at the injection site. The vascular permeability induced by PAF (180 pmol/site) was significantly inhibited by pretreatment with an intraperitoneal injection of 1-O-hexadecyl-2-acetyl-sn-glycero-3-phospho (N,N,N-trimethyl) hexanolamine (PAF receptor antagonist) (5 and 25 mg/kg) and indomethacin (cyclooxygenase inhibitor) (10 mg/kg), whereas it was not affected by concurrent intravenous administration of NO synthase inhibitors NG-nitro-L-arginine methyl ester (10 mg/kg) or methylene blue (100 micrograms/kg) nor by topical injection of NG-nitro-L-arginine methyl ester. The inhibitory effect of indomethacin was partially reversed by topical administration of prostaglandin E2. These results suggest that PAF increases venular permeability by activating PAF receptors and that plasma extravasation is potentiated by the release of prostanoids which cause arteriolar dilatation. However, NO is not involved in the effect of PAF in mouse skin.

Amino Acid Oxidoreductases↗