Biomedical subjects

H Ohno

Publications and source records attributed to H Ohno.

At least 271 records · Page 15Linked to original sources

PubMed1996

Involvement of NO-ergic neural pathway in reflex tracheal dilatation during bronchoconstriction in guinea pigs.

The involvement of NOergic nerve in vagal reflex-mediated tracheal dilatation during bronchoconstriction was investigated using the guinea pig in vivo tracheo-bronchi separated preparation. Inhalation of 0.01% histamine to the bronchial site induced a biphasic, vagal reflex tracheal response, i.e., constriction followed by dilatation slightly after bronchial constriction. The reflex tracheal dilatation was inhibited by 49% by local treatment of the tracheal site with 1% propranolol. The residual dilatation in the presence of atropine and propranolol was significantly inhibited by 1% oxyhemoglobin or 1% carboxy-PTIO, NO scavengers. Cyclic GMP content in the tissue of the tracheal site during the reflex tracheal dilatation significantly increased. The increase in cyclic GMP was reduced by treatment of the tracheal site with 1% N omega-nitro-L-arginine methyl ester. These results support a hypothesis that reflex tracheal dilatation during bronchoconstriction may be mediated by not only adrenergic but also NOergic nerves in guinea pigs.

Administration, Inhalation↗

PubMed1996

Beta 2- but not beta 1-adrenoceptors mediate the adrenergic component of reflex tracheal dilatation during bronchoconstriction in guinea pigs in vivo.

Involvement of beta 1- and/or beta 2-adrenoceptors in vagal reflex-mediated tracheal dilatation during bronchoconstriction was investigated using the in vivo guinea pig tracheo-bronchi separated preparation. Inhalation of 0.01% (w/v) histamine to the bronchial site produced vagal reflex-mediated tracheal constriction followed by dilatation slightly after bronchial constriction. The latter reflex dilatation was significantly inhibited not only by 1% propranolol, a nonselective beta-adrenoceptor antagonist, but also by 0.1% butoxamine and 0.01% ICI-118,551, selective beta 2-adrenoceptor antagonists. However, 0.1% atenolol, a selective beta 1-adrenoceptor antagonist failed to inhibit the dilatation. Furthermore, the dilatation was also inhibited by 0.1% guanethidine treatment or adrenalectomy. All of noradrenaline, adrenaline and cyclic AMP contents in the tissue of the tracheal site significantly increased during the reflex tracheal dilatation after bronchoconstriction. The increase in cyclic AMP was reduced by 1% propranolol. Furthermore, local treatment of the tracheal site with 0.01% noradrenaline or 0.01% adrenaline induced tracheal dilatation, which was significantly inhibited by 0.1% butoxamine or 0.001% ICI-118,551 but not by 0.1% atenolol. These results suggest that the reflex tracheal dilatation during bronchoconstriction may be mediated by mainly beta 2-adrenoceptors activated by adrenaline released from the adrenal medulla and by noradrenaline released from the adrenergic nerve terminals.

Administration, Inhalation↗

PubMed1996

Decreased vascular sensitivity after acute exercise and chronic exercise training in rat thoracic aorta.

The effects of acute and chronic physical exercise on the sensitivity of isolated aorta to norepinephrine were investigated. After chronic exercise, the EC50 values for norepinephrine increased 3.1-fold and 2.3-fold in endothelium-intact and in endothelium-denuded aorta, respectively. The attenuated sensitivity of aorta to norepinephrine after chronic exercise was still evident in endothelium-denuded aorta, but to a lesser extent than in endothelium-intact aorta. After acute exercise, in control rats, the EC50 values increased 7.8-fold and 5.4-fold in endothelium-intact and endothelium-denuded aorta, respectively. The attenuated sensitivity of aorta to norepinephrine after an acute exercise was still evident in endothelium-denuded aorta. In trained rats, the EC50 values increased 2.3-fold and 2.6-fold in endothelium-intact and endothelium-denuded aorta, respectively. Thus, acute exercise was less effective in trained than in control rats. No significant difference in 60 mM KCl-induced tension between control and trained rats was observed with or without endothelium after acute and chronic exercise. The results suggest that levels of endothelium-dependent releasing factor may increase in response to norepinephrine after acute and chronic exercise. In addition, the attenuated sensitivity of aorta to norepinephrine after acute and chronic exercise may also result from the change(s) in the receptor sites. However, the degree of desensitization caused by acute exercise was less in the rats adapted to chronic exercise than in the sedentary control rats.

Adrenergic alpha-Agonists↗

PubMed1996

Association of Helicobacter pylori and diffuse type gastric cancer.

The major purpose of this study was to evaluate the association of Helicobacter pylori and diffuse type gastric cancer (DGC) clinicopathologically (study 1). The second aim was to investigate genetic differences of H. pylori in patients with DGC and intestinal type cancer (IGC) (study 2). The prevalence of H. pylori and the types of histopathological changes were evaluated in resected early gastric cancer (DGC; 25 patients, IGC; 25 patients). Genetic differences of H. pylori in DGC patients (n = 19) and IGC patients (n = 22) were analyzed by polymerase chain reaction (PCR) methods in terms of restriction fragment length polymorphism patterns of the ureB gene and cagA gene positive rates. All patients had evidence of H. pylori infection in the resected stomach, but the positive rate for H. pylori in the area surrounding cancer was 52% (in DGC; 56%, IGC; 48%). But in 40.0% of DGC cases (10/25), mucosal atrophy and intestinal metaplasia were rarely seen in the area surrounding cancer and the positive rate of H. pylori was 80.0% (8/10), in contrast, in 60.0% of IGC cases (15/25), atrophy and metaplasia were progressed and positive rate of H. pylori was 26.7% (4/15) in the area. UreB gene products from 89.5% of DGC cases (17/19) were unable to be digested by Spe I. 31.8% of products from IGC cases (7/22) were also unable to be digested by Spe I, but the positive rate of cagA gene in this group was higher than other groups. The high prevalence of H. pylori infection in DGC patients suggests that H. pylori plays a role in the pathogenesis of DGC, but in the stomach with DGC, it is considered atrophy and intestinal metaplasia are not so implicated in H. pylori, compared with IGC. A genetic specificity of H. pylori in DGC and IGC was indicated by the results, suggesting that H. pylori may play different roles in the pathogenesis of DGC and IGC.

Base Sequence↗

PubMed1996

Pyruvate dehydrogenase complex-catalyzed formation of N-arylacetohydroxamic acids from nitroso aromatic compounds in rat isolated cells and perfused organs.

The formation of N-arylacetohydroxamic acid derivatives from m-nitrosobenzyl alcohol (MBNO) and a nitroso derivative of chloramphenicol, 2,2-dichloro-N-[2-hydroxy-1-(hydroxymethyl)-2-(4-nitrosophenyl) ethyl]acetamide, in the presence of pyruvate was investigated with rat isolated cells (heart, kidney, liver, small intestine, lung, bone marrow and spermatozoa) and perfused organs (liver and heart). The activity in N-(m-hydroxymethylphenyl) acetohydroxamic acid (MBHA) formation was found in all the cells tested. Measurement of the kinetic parameters revealed that K(m) values of MBNO were ca. 0.3 mM and that the order of Vmax per cell was heart > kidney > liver > small intestine. In the hepatocytes, MBHA was metabolized further and the in vitro intrinsic clearance of MBHA was 1.91 +/- 0.24 ml/min/10(8) cells. In a single-pass perfusion of rat liver with MBNO, the corresponding amino, acetylamino and azoxy derivatives and unknown materials were formed in addition to MBHA. The activity in MBHA formation was increased by the addition of both diethyl maleate and paraoxon. In a recirculating perfusion of rat liver with MBNO, however, the net MBHA formation was hardly detected, because of the disposition of MBHA formed. The hepatic clearance of MBHA was 1.15 +/- 0.06 ml/min/g of liver. In a recirculating perfusion of isolated rat heart with MBNO, MBHA was formed as a major metabolite and further biotransformation was not found. The N-arylacetohydroxamic acid derivative of 2,2-dichloro-N-[2-hydroxy-1-(hydroxymethyl)-2-(4-nitrosophenyl) ethyl]acetamide was also formed in rat bone marrow cells and the isolated perfused heart. These results indicate that the formation of N-arylacetohydroxamic acids from nitroso aromatic compounds and pyruvate catalyzed by pyruvate dehydrogenase complex proceeds in virtually all mammalian tissues.

Animals↗

PubMed1996

[Differential diagnosis of tuberculous pleurisy by the measurement of cytokine concentration in pleural effusion].

Pleural fluids obtained from 26 patients with tuberculous pleurisy (T-group), 11 with parapneumonic pleurisy (B-group) and 21 with malignant pleurisy (M-group) were tested for their biologic parameters and cytokine concentrations. 1) The average age of T-group was over 10 years lower than that of M-group with a statistically significant difference. 2) The average CRP value of B-group and the positivity on PPD skin test of T-group were higher than those of the other groups, respectively. 3) Yellowish pleural fluids were mainly observed in T- and B-group, while bloody pleural fluids were mostly seen in M-group with a statistically significant difference. The average total protein amount and adenosine deaminase value in pleural fluid significantly increased in T-group. The percentage of polymorphonuclear leukocytes showed a significant increase in B-group, while lymphocytes significantly increased in T-group with a statistically significant difference. 4) Although no significant difference in concentrations of IL-1 beta, IL-2, IFN-gamma and TNF-alpha in serum was noticed among the three groups, the average concentrations of IFN-gamma and TNF-alpha in pleural fluid in T-group were significantly higher than those in the other groups. 5) TNF-alpha-mRNA of mononuclear cells in pleural fluid was strongly expressed in 3 out of 11 patients of T-group, while no expression was observed in 6 patients of M-group. In conclusion, the measurement of concentrations of two kinds of cytokines in pleural fluid, IFN-gamma and TNF-alpha, may be clinically useful for the differential diagnosis of tuberculous pleurisy from parapneumonic pleurisy and malignant pleurisy.

Adult↗

PubMed1995

Effects of hypobaric hypoxia on antioxidant enzymes in rats.

1. The present study was undertaken to investigate the effects of hypobaric hypoxia, equivalent to an altitude of 5500 m, on antioxidant enzymes in rats. 2. Malondialdehyde levels in serum, heart, lung, liver and kidney of hypobaric-hypoxic rats were all significantly higher than in control rats by day 21 of exposure (P < 0.05), indicating increased oxidative stress. 3. Superoxide dismutase (SOD) catalyses the conversion of the superoxide anion to H2O2 and O2. The concentration of immunoreactive Mn-SOD in the serum of hypobaric-hypoxic rats was raised significantly from day 5 onwards, whereas in liver and lung, it had decreased significantly by day 21 (P < 0.05). 4. Glutathione peroxidase (GSH-Px) catalyses H2O2 and certain lipid peroxides. By day 21, GSH-Px activity had increased significantly in the heart and lungs, but decreased significantly in the liver (P < 0.05). 5. Catalase catalyses H2O2. Catalase activity in the liver and kidney of hypobaric-hypoxic rats was significantly decreased on day 1 (P < 0.05) though levels then recovered. 6. Mn-SOD mRNA in the liver of hypobaric-hypoxic rats was induced during the experiment, the effect being exceptionally marked, especially during the first 3 days of exposure to hypobaric hypoxia. 7. These results suggest that the liver may be more vulnerable than the other organs tested to oxidative stress under hypobaric hypoxia.

Air Pressure↗

PubMed1995

Alterations of superoxide dismutase iso-enzyme activity, content, and mRNA expression with aging in rat skeletal muscle.

The alterations of superoxide dismutase iso-enzyme (Cu,Zn-SOD and Mn-SOD) activities, contents, and mRNA expressions with aging were studied in rat soleus muscle (SO) and extensor digitorum longus muscle (EDL). The activity and content of Cu,Zn-SOD in both muscles were significantly higher in old rats (24 months old) than in young rats (4 months old), whereas those of Mn-SOD showed no difference between young and old rats. After normalization to citrate synthase (CS) activity, however Mn-SOD/CS ratio in SO also showed the age-related increase. Moreover, the activities of other major antioxidant enzymes, glutathione peroxidase (GPX) and catalase (CAT), indicated age-related increases only in SO. As for the expressions of mRNAs for SOD iso-enzymes, that of Cu,Zn-SOD in either muscle showed no significant change with aging, unlike its activity and content, although that of Mn-SOD was decreased with aging only in EDL. Thus, aging appeared to raise the level of antioxidant enzyme system in rat skeletal muscle. However, the resistance of Cu,Zn-SOD and Mn-SOD to oxidative stress accompanied by aging was different, the former being obviously greater than the latter. Such changes also differed in muscle fiber type suggesting that fast-twitch fibers are more susceptible to age-related oxidative stress than slow-twitch fibers.

Aging↗

PubMed1995

Interaction of tyrosine-based sorting signals with clathrin-associated proteins.

Tyrosine-based signals within the cytoplasmic domain of integral membrane proteins mediate clathrin-dependent protein sorting in the endocytic and secretory pathways. A yeast two-hybrid system was used to identify proteins that bind to tyrosine-based signals. The medium chains (mu 1 and mu 2) of two clathrin-associated protein complexes (AP-1 and AP-2, respectively) specifically interacted with tyrosine-based signals of several integral membrane proteins. The interaction was confirmed by in vitro binding assays. Thus, it is likely that the medium chains serve as signal-binding components of the clathrin-dependent sorting machinery.

Adaptor Proteins, Vesicular Transport↗

PubMed1995

Developmental arrest of NK1.1+ T cell antigen receptor (TCR)-alpha/beta+ T cells and expansion of NK1.1+ TCR-gamma/delta+ T cell development in CD3 zeta-deficient mice.

The relationship between the structure of the T cell antigen receptor (TCR)-CD3 complex and development of NK1.1+ T cells was investigated. The TCR complex of freshly isolated NK1.1+ TCR-alpha/beta+ thymocytes contained CD3 zeta homodimers and CD zeta-FcR gamma heterodimers, whereas that of the majority of NK1.1- T cells did not contain FcR gamma. The function of CD3 zeta and FcR gamma in the development of NK1.1+ T cells was determined by analyzing CD3 zeta- and FcR gamma-deficient mice. The NK1.1+ T cells from wild-type and CD3 zeta-deficient mice had equal levels of CD3 expression. However, the development of NK1.1+ TCR-alpha/beta+ T cells was almost completely disrupted in thymus and spleen in CD3 zeta-deficient mice, whereas no alteration was observed in FcR gamma-deficient mice. In contrast, the number of novel NK1.1+ TCR-gamma/delta+ thymocytes expressing a surface phenotype similar to NK1.1+ TCR-alpha/beta+ thymocytes increased approximately six times in CD3 zeta-deficient mice. These findings establish the distinct roles of the CD3 zeta chain in the development of the following different thymic T cell compartments: NK1.1- TCR+, NK1.1+ TCR-alpha/beta+, and NK1.1+ TCR-gamma/delta+ thymocytes, which cannot be replaced by CD3 eta or FcR gamma chains.

Animals↗

PubMed1995

Increased growth of brown adipose tissue but its reduced thermogenic activity in creatine-depleted rats fed beta-guanidinopropionic acid.

To study the responses of thermogenic activity in brown adipose tissue (BAT) to creatine depletion, male Wistar rats were fed creatine analogue beta-guanidinopropionic acid (beta-GPA) for about 10 weeks. Compared to control rats, a marked decrease in the levels of high-energy phosphates, such as phosphocreatine and ATP, was noted in BAT of beta-GPA rats. Conversely, upward trends in other chemical components (DNA, glycogen, and total protein) in BAT as well as an increase in BAT mass were observed in beta-GPA rats, suggesting a tendency to hyperplasia of the BAT. The thermogenic activity (which was assessed by guanosine 5'-diphosphate binding to BAT mitochondria) in the mitochondria recovered from BAT of beta-GPA rats, however, was not increased in response to such changes but rather decreased. Moreover, uncoupling protein (UCP) content in the mitochondrial fraction of beta-GPA rats was significantly lower than that in control rats (the relative amounts were 77 +/- 6 and 100 +/- 4%, respectively). Nevertheless, surprisingly, the level of UCP mRNA was remarkably greater in beta-GPA rats than in control rats. These observations indicate that there is a discordance between BAT growth and activity in beta-GPA rats, thereby suggesting that a failure on and after UCP translation may be involved in the impairment of BAT thermogenic activity with creatine depletion. The impairment of BAT thermogenic activity, that is, UCP activity may indicate that uncoupling or heat production was inhibited in order to increase the ATP synthesis in BAT of beta-GPA rats in compensation for a reduction in the levels of high-energy phosphates (including ATP), with resultant hypothermia.

Adipose Tissue, Brown↗

PubMed1995

In vivo evidence for progressive activation of parathyroid hormone-related peptide gene transcription with tumor growth and stimulation of osteoblastic bone formation at an early stage of humoral hypercalcemia of cancer.

The present study was undertaken to clarify in vivo the temporal profile of parathyroid hormone-related peptide (PTHRP) gene expression as well as bone histomorphometric features as a function of tumor growth, using an athymic rat model associated with humoral hypercalcemia of malignancy (HHM). Tumor-bearing animals exhibited hypercalcemia, hypophosphatemia, and increased circulating levels of PTHRP, and died within 3 weeks. Steady-state PTHRP mRNA levels and the transcription rate of PTHRP gene in the tumors were markedly increased with tumor growth. RNAse mapping analysis revealed that both upstream and downstream promoters of the human PTHRP gene were utilized in the tumors and became progressively activated with time. Bone histomorphometric analysis showed that osteoclastic bone resorption was progressively increased throughout the course, whereas osteoblastic bone formation was stimulated more than 2-fold at a very early stage (day 6 after tumor implantation) and then markedly suppressed thereafter on day 12 and day 18 compared with age-matched control animals. These results provide in vivo evidence that PTHRP gene transcription is progressively activated with tumor growth and that activation of osteoblasts does occur at a very early phase of HHM syndrome in contrast to the marked suppression of bone formation at later stages.

Analysis of Variance↗

PubMed1995

Leucocytosis as a marker of organ damage induced by chronic strenuous physical exercise.

The effects of strenuous physical exercise on the serial changes in the haematological, biochemical and hormonal markers were investigated. A group of 14 soldiers, aged 24-36 years, took part in a military training course for about 13 weeks. After severe exercise stress, an increase (90%) in the number of peripheral blood leucocytes was observed. The degree of leucocytosis showed a close correlation with the values of some serum parameters, such as concentrations of aspartate aminotransferase (AST; r = 0.747), lactate dehydrogenase (LD; r = 0.748), blood urea nitrogen (r = 0.756), creatine kinase (CK; r = 0.637), manganese-superoxide dismutase (Mn-SOD; r = 0.508), alanine aminotransferase (ALT; r = 0.542) and uric acid (r = 0.538), and concentrations of urinary parameters, such as vanilmandelic acid (r = 0.429) and free cortisol (r = 0.437). The subjects showing prominent leucocytosis over 9500 cells.microliters-1 exhibited a lower concentration of serum cholinesterase than those who showed milder leucocytosis. The serum Mn-SOD concentration was closely correlated with the serial changes in serum concentrations of AST, ALT, LD and CK, indicating exercise-induced muscle and liver damage. The change in peripheral leucocyte number was assumed to be diagnostically informative and may be a prognostic marker, reflecting organ damage and restoration after strenuous physical exercise.

Adult↗

PubMed1995

Atypical pemphigus associated with monoclonal IgA gammopathy.

We describe a 60-year-old woman with atypical pemphigus and IgA-lambda monoclonal gammopathy. Histopathologic study of vesiculopustular lesions showed intraepidermal acantholytic and neutrophilic blisters. Direct immunofluorescence revealed intercellular IgG deposition with concurrent deposits of IgA and C3. Indirect immunofluorescence and immunoblotting studies revealed that the patient had circulating IgG anti-intercellular antibodies that recognized the 150 kd desmoglein (pemphigus foliaceus antigen) in bovine desmosome preparation. Immunoblot studies with human epidermal extract showed that the IgG of this patient exclusively reacted with the 140 kd protein (between the 150 kd human desmoglein and the 130 kd human pemphigus vulgaris antigen), the nature of which is currently unknown. The patient also had IgA anti-intercellular autoantibodies, which reacted with the desmoglein in the bovine desmosome sample but did not show any reactivity in human epidermal extract.

Antibodies, Anti-Idiotypic↗

PubMed1995

Direct evidence for the occurrence of superoxide radicals in the small intestine of the burned rat.

To determine if superoxide radicals (O2-) and related metabolites are generated in extradermal tissues of burned animals, 2-methyl-6-[p-methoxyphenyl]-3,7-dihydroimidazol [1,2-å]pyrazin-3-one (MCLA) was infused intravenously into rats, and change in the chemiluminescence (CL) intensity of the small intestine was determined by using a sensitive photodetector. When animals were challenged with burn stress of 40% total body surface area (TBSA), the CL intensity of the intestine gradually increased, reaching a maximum within 1 hour and remaining elevated for up to 3 hours. Pretreatment of animals with a long-acting superoxide dismutase (SOD) derivative (SM-SOD) significantly inhibited the increase in CL intensity. Administration of SM-SOD immediately after inducing burn injury also significantly inhibited the increase in CL. These results suggest that superoxide radicals are generated in extradermal tissues, such as the small intestine, in the early stage after burn injury.

Animals↗

PubMed1995

Class switch recombination of the immunoglobulin heavy chain gene frequently occurs in B-cell lymphomas associated with rearrangement of the BCL2 gene.

B-cell lymphomas, mainly follicular lymphomas, carrying a t(14;18) chromosomal translocation associated with rearrangement of the BCL2 gene and the immunoglobulin heavy chain (IGH) gene, share many similarities with germinal center B cells in the secondary lymphoid follicle. In the germinal center, antigen-stimulated B cells proliferate and differentiate while undergoing isotype class switching of their immunoglobulin heavy chains. To examine whether BCL2-positive lymphoma cells show class switch recombination similar to that in the germinal center B cells, we studied the genomic configurations of the IGH gene loci in 38 patients with B-cell lymphomas. Sixteen (80%) out of 20 patients with BCL2-positive lymphomas showed class switch recombination on translocated and/or productive IGH gene loci. Lymphoma cells from 7 of the 16 patients expressed the gamma-heavy chain on their surfaces, indicating functional class switching to the gamma-constant gene on the productive allele. By contrast, 6 (33%) of the 18 patients lacking the BCL2 rearrangements exhibited class switch recombination. Statistical analysis revealed that the BCL2-positive lymphomas underwent switch recombination on either allele at a significantly higher frequency than the BCL2-negative lymphomas (P = 0.0099). This indicates that follicular lymphoma, not only morphologically but also functionally, recapitulates the germinal center. We propose that the up-regulated BCL2 expression itself is capable of playing an important role in immunoglobulin class switching.

Gene Rearrangement↗

PubMed1995

Synchronous presentation of Epstein-Barr virus-associated Hodgkin's disease and adult T-cell leukemia/lymphoma (ATLL) in a patient from an endemic area of ATLL.

We report a patient from an endemic area of adult T-cell leukemia/lymphoma (ATLL), who developed lymphoma with features characteristic of Hodgkin's disease (HD). Large atypical Reed-Sternberg/Hodgkin's cells (RS/H cells) had a CD3-CD15+CD20-CD30+CD45RO- immunophenotype. Epstein-Barr virus (EBV) latent membrane protein and EBV-encoded small RNA were detected in the RS/H cells. The patient received C-MOPP/ABVD chemotherapy for the HD resulting in a partial response. However, relapse occurred and he died of disease progression associated with serious bacterial infection. Although serial lymph node biopsies revealed consistent presence of the EBV-positive RS/H cells, the background small lymphocytes showed progressive increase in pleomorphism and nuclear irregularity. The lymphocytes had the T-cell phenotype, CD3+CD4+CD7-CD8-. Southern blot analysis using DNA probes for the human T-cell lymphotrophic virus-I (HTLV-I) and the T-cell receptor beta-chain gene demonstrated expansion of the HTLV-I infected monoclonal T-cells with the disease progression. We concluded that the patient synchronously presented two independent lymphoproliferative disorders; EBV-associated HD and ATLL resulting from HTLV-I infection.

Antigens, CD↗

PubMed1995

Rapid turnover of the CD3 zeta chain independent of the TCR-CD3 complex in normal T cells.

The function of CD3 zeta in the assembly and transport of the T cell receptor (TCR)-CD3 complex was analyzed in normal T cells. The zeta chain, but not other chains in the surface TCR complex, rapidly exchanged with newly synthesized zeta. Because zeta was expressed independently from the complex, the TCR complex may be transported to the surface along the zeta turnover pathway by association with zeta. These data suggest the dynamic nature of zeta metabolism and provide the evidence that a single component in a multisubunit receptor exhibits independent metabolism from the rest of the complex.

Animals↗