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N Ishimura

Publications and source records attributed to N Ishimura.

30 records · Page 2Linked to original sources

Nitric oxide involvement in hypoxic dilation of pial arteries in the cat.

BACKGROUND: The reactivity of cerebral arteries to different stimuli varies according to vessel size. Whether nitric oxide mediates hypoxic vasodilation is controversial. The authors considered this question by measuring the diameter of pial arteries and arterioles with or without exposure to the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME). METHODS: The cranial window technique, combined with microscopic video recording, was used in an experiment involving 20 cats anesthetized with fentanyl and midazolam. The diameters of pial arteries and arterioles were measured under the following conditions: (1) normoxia (PaO2 > 100 mmHg); (2) hypoxia (PaO2 < 45 mmHg); (3) normoxia with L-NAME infusion; and (4) hypoxia with L-NAME infusion. Changes in vessel diameter were analyzed with respect to artery size. RESULTS: Under hypoxic conditions, arteries and arterioles smaller than 200 microns were dilated significantly (P < 0.05). In arterioles smaller than 200 microns, L-NAME attenuated this hypoxic vasodilation (P < 0.05). In contrast, under normoxic conditions, L-NAME caused significant vasoconstriction in arteries larger than 100 microns but not in arteries smaller than 100 microns. CONCLUSIONS: Arteries and arterioles smaller than 200 microns are dilated by hypoxia, and nitric oxide contributes to this process. Nitric oxide synthesis may also be related to the regulation of resting vascular tone in arteries larger than 100 microns.

Animals↗

Hepatitis B virus with X gene mutation is associated with the majority of serologically "silent" non-b, non-c chronic hepatitis.

Hepatitis B virus (HBV) with X gene mutations has been a putative pathogen of chronic hepatitis without serological markers of known hepatitis viruses. The aim of this study was to reconfirm whether the HBV with the X gene mutation is associated with these serologically "silent" non-B, non-C (NBNC) chronic hepatitis, alcoholic liver disease (ALD) and autoimmune hepatitis (AIH). HBV DNA was amplified from serum and sequenced in 30 patients with NBNC chronic hepatitis in comparison with 20 patients with ALD and 5 patients with AIH. HBV DNA was identified in 21 patients (70%) in NBNC chronic hepatitis by nested polymerase chain reaction while only one patient (5%) in ALD and none in AIH showed HBV DNA. Eighteen (85.7%) of the 21 identified HBV DNAs had an identical 8-nucleotide deletion mutation at the distal part of the X region. This mutation affected the core promoter and the enhancer II sequence of HBV DNA and created a translational stop codon which truncated the X protein by 20 amino acids from the C-terminal end. All the HBV DNAs had a precore mutation at the 83rd nucleotide resulting in disruption of HBe antigen synthesis. These results indicate that HBV mutants are closely associated with the majority of serologically "silent" NBNC chronic hepatitis cases and the population of such mutant HBV DNAs is not uniform.

Adult↗

Relationship between the intrahepatic expression of interferon-alpha receptor mRNA and the histological progress of hepatitis C virus-associated chronic liver diseases.

Histological progress is one of the predictors of an unfavourable response to interferon (IFN) therapy in hepatitis C virus (HCV)-associated chronic liver diseases (CLD). The aim of the present study was to investigate whether histological progress has an association with the expression of IFN receptor (IFN-Rc) in the liver. Expression of mRNA of the IFN-Rc for IFN-alpha was investigated by reverse transcription polymerase chain reaction using liver biopsy specimens from 37 HCV-associated CLD comprising 11 liver cirrhosis (LC) and 26 chronic hepatitis (CH) cases. IFN-alpha and IFN-beta mRNA were detected in over 90% of subjects. In contrast, the detection rate of IFN-Rc mRNA in chronic persistent hepatitis, chronic hepatitis 2A, chronic hepatitis 2B and liver cirrhosis (LC) was 100, 71.4, 22.2 and 0%, respectively. The absence of IFN-Rc mRNA was significantly associated with the severity of fibrosis of the liver. These results indicated that IFN-Rc expression decreases with the histological progress of the disease, suggesting that lower expression of IFN-Rc mRNA may be partially responsible for the poor IFN response in LC.

Adult↗

Intrahepatic expression of pro-inflammatory cytokine mRNAs and interferon efficacy in chronic hepatitis C.

To investigate the relationship between intrahepatic cytokine expression and interferon (IFN) response in chronic hepatitis C [CH(C)], interleukin (IL)-1 beta, -2, -4, -6, -8, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and TNF-beta mRNAs were investigated semiquantitatively by reverse transcription polymerase chain reaction using serial liver biopsies taken before and after IFN-alpha treatment from 24 patients with CH(C), including 12 responders and 12 non-responders. Before IFN treatment, IL-2, TNF-beta, IFN-gamma and IL-8 mRNA were associated with severe hepatitis activity whereas IL-4 mRNA was associated with weak hepatitis activity, regardless of IFN response. IL-2, TNF-beta and IFN-gamma mRNAs were significantly greater in IFN non-responders. After IFN treatment a complete response to IFN was significantly associated with the disappearance of these pro-inflammatory cytokines, whereas non-responders retained the expression of cytokine mRNA as before IFN treatment. Our results indicated that IFN-alpha treatment may modulate the intrahepatic cytokine network, and this may be one mechanism of IFN-alpha that reduces hepatitis activity, aside from an anti-viral effect. A difference in cytokine network may be involved in IFN response in CH(C).

Adult↗

[The effects of preoperative drinking and H2 blocker on gastric acid secretion].

We studied the effects of preoperative drinking and H2 blocker on gastric acid secretion in 63 patients (ASA I-II, > 18yrs) scheduled for afternoon surgery. Group A (n = 20), as a control, was not permitted to eat and drink from 9 pm, the day before surgery, and was then given 500 ml of maintainance fluid before anesthesia. Group B (n = 20) fasted from 9 pm the day before surgery, and was allowed to drink clear fluids until 2hs before anesthesia. Group C (n - 23) followed the same guidelines as group B, and was given famotidine (20mg) orally at 9 pm the day before and 2hs before anesthesia. After induction, a Salem sump tube was inserted into the stomach and a gastric fluid aspiration was performed. The fluid volume and pH were measured after collection. Gastric pH was significantly higher (P < 0.001) in group C (6.4 +/- 0.9) than in groups A (3.1 +/- 1.8) and B (2.7 +/- 1.8). Fluid volume was similar in each group (A; 11 +/- 9/B; 12 +/- 9/C; 12 +/- 13ml). The dilution of gastric acid by the ingested fluid was not observed. We conclude that preoperative drinking does not affect gastric contents in elective operative patients. To reduce the risk of developing aspiration pneumonia, we recommend that every patient should receive an oral H2 blocker.

Administration, Oral↗

X gene and precore region mutations in the hepatitis B virus genome in persons positive for antibody to hepatitis B e antigen: comparison between asymptomatic "healthy" carriers and patients with severe chronic active hepatitis.

Hepatitis B virus (HBV) carriers with antibody to hepatitis e antigen comprise asymptomatic carriers (ASCs), who have low replication levels of HBV, and patients with chronic active hepatitis (CAH), who have high levels of viral replication. To investigate whether defects in the X protein might be responsible for this difference in the level of viral replication, nucleotide sequences of X and precore gene regions in serum HBV were analyzed in 19 ASCs and 9 CAH patients. All patients had a point mutation creating a stop codon in the precore region. Seventeen ASCs (87.3%) had identical mutations consisting of 4 noncontiguous 1-bp deletions or an 8-bp deletion, both of which truncate the normal X protein, whereas no CAH patient had an X gene mutation (P < .001). Thus, deletion of the X protein might be responsible for the low levels of viral replication in ASCs.

Adult↗

Gene expression of perforin and granzyme A in the liver in chronic hepatitis C: comparison with peripheral blood mononuclear cells.

Perforin and granzyme A are the major effectors of cytotoxic T cells in cell-mediated cytotoxicity. However, there has been no report on these effectors in chronic viral hepatitis. In the present study, the expression of perforin and granzyme A mRNA was investigated by the reverse transcription polymerase chain reaction method using liver biopsy specimens and peripheral mononuclear cells (PBMC) from 21 patients with chronic hepatitis C and 5 control cases. Perforin mRNA was detected only in the liver of chronic hepatitis patients but not in the control livers. Conversely, perforin mRNA was not expressed in PBMC of the patients with chronic hepatitis (P < 0.01). Granzyme A mRNA was detected both in the liver and PBMC of all the cases including control cases. These results indicated that the perforin is an important effector molecule in the hepatocyte lysis in chronic viral hepatitis C.

Base Sequence↗

The expression of IL-2, IL-4 and interferon-gamma (IFN-gamma) mRNA using liver biopsies at different phases of acute exacerbation of chronic hepatitis B.

To investigate the hypothesis that Th1 phenotype cytokines are associated with the increasing activity of hepatitis and Th2 phenotype cytokines with decreasing activity in the liver of chronic viral hepatitis, expressions of the mRNA of the cytokines IL-2, IFN-gamma and IL-4 in the liver of 23 patients with chronic hepatitis B were investigated by reverse transcription polymerase chain reaction. Patients were divided into three groups according to the phase of acute exacerbation of hepatitis as increasing (n = 9), decreasing (n = 8), and stable phase (n = 6). Both IL-2 and IFN-gamma mRNA were preferentially expressed in increasing phase than in decreasing phase (P < 0.01, P < 0.05, respectively) and associated with the high serum alanine aminotransferase (ALT) level. On the other hand, IL-4 mRNA was detected in decreasing phase with significant frequency compared with increasing phase (P < 0.05). However, expression of IL-4 mRNA was not associated with serum ALT level. Our results suggest that Th1 phenotype cytokines up-regulate and Th2 phenotype cytokines down-regulate the liver inflammation of chronic viral hepatitis.

Adolescent↗

[Preliminary studies on the retention of hydroxylated PCDF metabolites in rat blood].

We recently reported that certain hydroxylated PCB (OH-CB) metabolites were selectively retained in blood of rats experimentally dosed with PCB (Aroclor 1254), and also in blood of seals and humans environmentally exposed to PCBs. We also showed that metabolism in vivo of polychlorinated dibenzofurans (PCDFs) gave rise to a large number of hydroxylated PCDF (OH-CDF) metabolites, excreted in faeces, after oral administration to rats of PCDFs mixture (1, 2, 7, 8-tetraCDF 14%, 2, 3, 7, 8-tetraCDF 35%, 1, 2, 3, 7, 8-pentaCDF 48%). These results suggest that OH-CDFs could be present in blood. In the present study, potential retention of OH-CDF metabolites in blood (serum) was investigated in a female Wistar rat exposed to the PCDFs mixture. Serum was analyzed for the methylated OH-CDFs by gas chromatography (GC) and GC-mass spectrometry. Two major metabolites were determined in serum 1 day after oral administration. These were identified to be 3-OH-2, 4, 7, 8-tetraCDF (A) and 3-OH-2, 4, 7, 8, 9-pentaCDF (B) by comparison with synthesized reference compounds. 3-OH-2, 4, 7, 8-tetraCDF and 1, 2, 3, 7, 8-pentaCDF, respectively, via 3, 4(6, 7)-epoxide intermediate and subsequent NIH-shift of the 3(7)-chlorine to the 4(6)-position. The amounts of 3-OH-2, 4, 7, 8-tetraCDF and 3-OH-2, 4, 7, 8, 9-pentaCDF in the serum (5.72 g) analyzed accounted for 0.018% of 2, 3, 7, 8-tetraCDF and 0.003% of 1, 2, 3, 7, 8-pentaCDF dosed, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Effects of enflurane, isoflurane, and sevoflurane on renal tubular functions].

Twenty-seven patients without renal disease were divided randomly into three groups of each nine patients. Each group received either enflurane, isoflurane or sevoflurane. The renal tubular functions were examined during anesthesia and on the first postoperative day. By inhalation of 1.49 MAC hours of enflurane, 2.17 MAC hours of isoflurane or 1.29 MAC hours of sevoflurane, creatinine clearance, Na excretion rate, urine beta 2-microglobulin and urine N-acetyl-beta-D-glucosaminidase showed no significant changes during anesthesia and the during postoperative period among anesthetic agents used. These results indicate that enflurane, isoflurane or sevoflurane does not affect renal tubular function specifically under anesthesia when each was given for less than four hours.

Adult↗

[Intraoperative anoxic spells in patients with tetralogy of Fallot].

We experienced 5 cases of intraoperative anoxic spell in 48 patients with tetralogy of Fallot (TOF). One of 5 cases had tetralogy with pulmonary atresia (Type A), and the others had tetralogy alone (Type D). The patient of type A who had anoxic spells during preoperative period had been on chronic propranolol therapy. However, the patients of type D had no anoxic spells during preoperative period and one in this type had not been on beta-adrenergic blocking drugs preoperatively. One patient was anesthetized with fentanyl-diazepam-O2, and the others were anesthetized with morphine-diazepam-O2. We used mainly alpha-adrenergic drugs and sodium bicarbonate for the therapy of intraoperative anoxic spells. Concerning the intraoperative anoxic spell, we have to be aware in the management of the patients with TOF, whether the patient had anoxic spells during preoperative period or not.

Adolescent↗

Quasi-elastic light-scattering studies of conformational states of the H,K-ATPase. Intervesicular aggregation of gastric vesicles by disulfide cross-linking.

The particle size of hog gastric vesicles which contain H,K-ATPase was measured by using the method of quasi-elastic light scattering. The size of control vesicles is homogeneous as judged from its low polydispersity index. When the vesicles were treated with copper(II) o-phenanthroline (CuP), intervesicular S-S cross-linking occurred as determined by the aggregated vesicle size. The aggregation to divesicle size occurred very quickly, within 30 s, and the extent of aggregation did not depend on the extent of inactivation if the inactivation was not more than about 30%. Blocking of SH groups by 5,5'-dithiobis(2-nitrobenzoic acid) in the presence of Mg2+ prevented CuP-induced vesicular aggregation but not inactivation, indicating that S-S cross-linking rather than enzyme inactivation is the primary cause of vesicular aggregation. The presence of Mg2+ was required for the occurrence of aggregation. Nucleotides such as ADP (K0.5 = 5 microM) and 5'-adenylyl imidodiphosphate (K0.5 = 50 microM) inhibited the aggregation induced by 50 microM CuP plus 2 mM Mg2+ in a dose-dependent manner. Furthermore, K+ antagonized the effects of nucleotides. The extent of aggregation increased as the pH decreased in the pH range 6.1-7.4. Virtually no cross-linking occurred at alkaline pH (e.g., pH 8-9). These data show that vesicular aggregation can be assumed to reflect the conformational state of the responsible SH group in the native enzyme.

Adenosine Triphosphatases↗