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Biomedical subjects

A Ohno

Publications and source records attributed to A Ohno.

At least 55 records · Page 3Linked to original sources
PubMed1998

Effects of long-term changes in medullary osmolality on heat shock proteins HSp25, HSP60, HSP72 and HSP73 in the rat kidney.

The influence of diuresis and antidiuresis on the expression of heat shock proteins (HSP) 25, 60, 72 and 73 in the renal cortex and outer and inner medulla of Wistar rats was analysed. Medullary osmolality was reduced by long-term diuresis (3% sucrose in the drinking water for 3 weeks) and subsequently enhanced by transition to a concentrating state by giving normal drinking water again in combination with deamino-D-arginine vasopressin (dDAVP) for 5 days. Western blot analyses revealed that neither HSP73 nor HSP60 was influenced by any treatment. The HSP72 level in the medulla was markedly reduced (50%) when osmolality was lowered and increased when tonicity was high. RNAse protection assays showed that the effects on HSP72 are parallelled in general by changes in HSP72 mRNA. While levels of HSP25 were not influenced, isoelectric focusing revealed that the degree of phosphorylation of outer and inner medullary HSP25 increased following both treatments. It thus seems that HSP73 and HSP60 are not directly involved in the long-term adaptation to varying medullary osmolalities. The correlation between changes in osmolality and amounts of the major stress-inducible HSP72 in the medulla implies that medullary hypertonicity is stressful for kidney cells. Furthermore, adaptation to pronounced changes in the osmolality of the environment most likely involves phosphorylation of HSP25.

Animals↗
PubMed1998

Histomorphometric study of iliac bones in cervical myelopathy with ossification of the posterior longitudinal ligament.

To investigate whether there was any abnormal systemic bone metabolism in patients with ossification of the posterior longitudinal ligament (OPLL), we measured various histomorphometric indices of the iliac trabecular bones in 19 patients with OPLL (14 men, 5 women). For each index, the Z-score for each patient was calculated, using the SD and mean value for non-OPLL control group (n = 159) who underwent orthopaedic surgeries and had no systemic disease, age-matched for each decade. A Z-score of 1.0 meant that the observed data deviated 1 SD from the normal average, and a distribution from -2 to +2 was considered normal. All the averaged Z-scores were within +/-1.0 and there were no significant differences between the OPLL and the control groups. There was also no difference in Z-score among three types of OPLL (segmental, continuous, and mixed). From these results, we concluded that there was no common abnormal bone metabolism affecting the bone histomorphometry of the iliac bone in OPLL patients. However, in two patients, the Z-score for bone volume (BV/TV) was more than 2.0, with increased osteoid volume (OV/TV) and increased trabecular thickness, suggesting that there was some abnormal bone metabolism in these two patients with OPLL.

Adolescent↗
PubMed1998

An increase of soluble Fas, an inhibitor of apoptosis, associated with progression of COPD.

In chronic obstructive pulmonary disease (COPD) which consists of emphysema and chronic bronchitis, alveolar tissue and/or bronchiolar walls are progressively destroyed. This suggests cell death by necrosis and/or apoptosis although no direct evidence of apoptosis has been reported. It was speculated that the apoptosis-related factors are associated with the progression of COPD. Fas/Apo-1 receptor (Fas), Fas ligand (Fas-L) and soluble Fas ligand (sFas-L) are inducers, while soluble Fas (sFas) is an inhibitor of apoptosis. In this study, plasma sFas and sFas-L were measured in 19 COPD patients receiving supplemental O2 (severe COPD) and 20 COPD patients not receiving supplemental O2 (mild/moderate COPD). Twenty-two age- and sex-matched healthy volunteers (healthy controls) and 20 patients receiving supplemental O2 and with level of hypoxaemia similar to severe COPD due to other pulmonary diseases (disease controls) were also examined. Plasma sFas-L was within normal limits in all groups. Plasma sFas levels were similar among healthy controls, disease controls, and mild/moderate COPD patients, but significantly increased in severe COPD (2.6 +/- 1.1, 2.6 +/- 0.2, 2.8 +/- 0.2 and 4.8 +/- 1.0 ng ml-1, respectively). Although PaO2 was lower in severe COPD than in mild/moderate COPD, and PaCO2 was higher in severe COPD than in mild/moderate COPD, they were close between severe COPD and disease controls. Tumour necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6) and C-reactive protein (CRP) were increased in patients with COPD, but were similar in both severe and mild/moderate COPD patients. We conclude that increased plasma sFas, which is independent of hypoxaemia, and increases in PaCO2, TNF-alpha, IL-6 and inflammation, may be associated with progression of COPD.

Aged↗
PubMed1998

Effect of immunisation with Pseudomonas aeruginosa on gut-derived sepsis in mice.

The protective efficacy of immunisation with heat-killed Pseudomonas aeruginosa on murine gut-derived sepsis was evaluated. Mice were immunised intraperitoneally six times with heat-killed bacteria. This induced mean (SEM) serum IgG and IgM antibodies of 1792 (374.7) and 37.3 (8.9) ELISA units, respectively. Specific pathogen-free mice given P. aeruginosa strain D4 orally died of bacteraemia after administration of cyclophosphamide. Immunisation with heat-killed bacteria significantly increased the survival rate compared with that of control mice immunised with bovine serum albumin. Macroscopic observation revealed marked production of liver abscesses in mice immunised with bovine serum albumin but not in those immunised with heat-killed bacteria. Only low titres of antibody against the exoenzymes alkaline protease, elastase and exotoxin A were observed, and no significant difference between antibody titres to boiled and unboiled suspensions of sonicated P. aeruginosa was detected. This suggests that the main protective antibodies might be those specific to the heat stable antigen (lipopolysaccharide). Immunisation with heat-killed bacteria provided complete protection against death from gut-derived P. aeruginosa sepsis.

ADP Ribose Transferases↗
PubMed1998

Efficacies of alkaline protease, elastase and exotoxin A toxoid vaccines against gut-derived Pseudomonas aeruginosa sepsis in mice.

The protective efficacies of vaccines prepared from Pseudomonas aeruginosa alkaline protease, elastase and exotoxin A toxoids against gut-derived P. aeruginosa sepsis in mice were evaluated. Specific pathogen-free mice given P. aeruginosa strain D4 orally followed by cyclophosphamide (to promote translocation across the gut wall) died of bacteraemia. Mice immunised with one of the three individual toxoid vaccines were not significantly protected when compared to control mice immunised with bovine serum albumin. Combined immunisation with alkaline protease and elastase toxoids likewise showed no significant protective activity. However, combined immunisation with alkaline protease and exotoxin A toxoids significantly increased the survival rate, which reached 60% (compared with a 7.1% survival rate in the control group). These results show that alkaline protease and exotoxin A play important roles as pathogenic factors in gut-derived sepsis and that a combination of the two exoenzyme toxoids represents a logical candidate for vaccination against P. aeruginosa sepsis.

ADP Ribose Transferases↗
PubMed1998

Hepatocyte apoptosis and hepatic expression of transforming growth factor-beta1 mRNA during involution of hyperplastic rat liver induced by hepatocyte growth factor.

Hepatocyte apoptosis occurs during involution of hyperplastic liver induced by administration of xenobiotic compounds in rats. With this hyperplasia and involution, hepatic transforming growth factor (TGF)-beta1 is reported to be expressed to stimulate hepatocyte apoptosis. In regenerating liver after partial resection showing no hyperplasia, such expression of TGF-beta1 is also seen. However, no hepatocyte apoptosis develops despite the high levels of TGF-beta1. When rats received an intravenous injection of human hepatocyte growth factor at 12 h intervals for 14 days, the hepatic DNA content was increased 12 h after the last injection to 140% of control. This DNA content was significantly decreased at 108 and 180 h after discontinuation of treatment. At 60 h after the last injection, the number of apoptotic bodies positive for nick end-labelling of DNA in hepatocytes was significantly greater in treated rats than in control rats. Hepatocyte apoptosis was also identified electron micrographically. Hepatic TGF-beta1 mRNA levels in treated rats were significantly lower than in control rats at 12 h and then gradually increased towards control levels. We conclude that hyperplastic liver induced in normal rats by hepatocyte growth factor regresses with hepatocyte apoptosis and suppressed hepatic TGF-beta1 mRNA levels.

Animals↗
PubMed1998

In vitro and in vivo antibacterial activities of S-4661, a new carbapenem.

The in vitro and in vivo antibacterial activities of S-4661, a new 1beta-methylcarbapenem, were compared with those of imipenem, meropenem, biapenem, cefpirome, and ceftazidime. The activity of S-4661 against methicillin-susceptible staphylococci and streptococci was comparable to that of imipenem, with an MIC at which 90% of the strains tested were inhibited (MIC90) equal to 0.5 microg/ml or less. S-4661 was highly active against members of the family Enterobacteriaceae, Haemophilus influenzae, and Moraxella catarrhalis, with MIC90s ranging from 0.032 to 0.5 microg/ml. Against imipenem-resistant Pseudomonas aeruginosa, S-4661 was the most active among test agents (MIC90, 8 microg/ml). Furthermore, S-4661 displayed a high degree of activity against many ceftazidime-, ciprofloxacin-, and gentamicin-resistant isolates of P. aeruginosa. The in vivo efficacy of S-4661 against experimentally induced infections in mice caused by gram-positive and gram-negative bacteria, including penicillin-resistant Streptococcus pneumoniae and drug-resistant P. aeruginosa, reflected its potent in vitro activity and high levels in plasma in mice. We conclude that S-4661 is a promising new carbapenem for the treatment of infections caused by gram-positive and -negative bacteria, including penicillin-resistant S. pneumoniae and drug-resistant P. aeruginosa.

Animals↗
PubMed1998

Effect of interleukin-10 on gut-derived sepsis caused by Pseudomonas aeruginosa in mice.

We evaluated the protective effect of interleukin-10 (IL-10) against murine gut-derived sepsis caused by Pseudomonas aeruginosa. Gut-derived sepsis was induced by administering cyclophosphamide and ampicillin while feeding P. aeruginosa to specific-pathogen-free mice. Treating mice with recombinant human IL-10 (rhIL-10) at 1.0 or 5.0 microg/mouse twice a day following the second cyclophosphamide administration significantly increased the survival rate compared to that of control mice treated with saline; however, treatment with rhIL-10 at 0.1 microg/mouse did not result in significant protection. Bacterial counts in the liver, spleen, and blood were all significantly lower in mice treated with rhIL-10 than in saline-treated control mice. Treatment with rhIL-10 significantly suppressed tumor necrosis factor alpha, interleukin-1beta, interleukin-6, and gamma interferon levels in the serum of mice following induction of gut-derived sepsis. We also studied the effect of IL-10 on leukocyte recovery after cyclophosphamide treatment of mice. Administration of rhIL-10 intraperitoneally at 1. 0 microg/mouse significantly accelerated the recovery of leukocytes in comparison with that of the group of saline-treated controls. These results indicate that IL-10 shows a protective effect against gut-derived P. aeruginosa sepsis. We suspect that the mechanism of this effect is that IL-10 regulates in vivo production of inflammatory cytokines. Furthermore, acceleration of leukocyte recovery by IL-10 after cyclophosphamide-induced depression may also play an important role in this protection.

Animals↗
PubMed1998

In vitro and in vivo antibacterial activities of CS-834, a new oral carbapenem.

CS-834 is a prodrug of the carbapenem R-95867, developed by Sankyo Co., Ltd., Tokyo, Japan. To investigate the possibility that CS-834 may be the first carbapenem usable in an oral dosage form, its in vitro antibacterial activity (as R-95867) and in vivo antibacterial activity were compared with those of cefpodoxime proxetil, cefditoren pivoxil, cefdinir, ofloxacin, imipenem, and amoxicillin. R-95867 had high levels of activity against methicillin-susceptible staphylococci and streptococci, including penicillin-resistant Streptococcus pneumoniae, as well as Neisseria gonorrhoeae, Moraxella catarrhalis, the members of the family Enterobacteriaceae (with the exception of Serratia marcescens), Haemophilus influenzae, and Bordetella pertussis; for all these strains, the MICs at which 90% of tested strains are inhibited (MIC90s) were 1.0 microg/ml or less. Against methicillin-resistant staphylococci, enterococci, Serratia marcescens, Burkholderia cepacia, Stenotrophomonas maltophilia, and Acinetobacter calcoaceticus, R-95867 showed activity comparable to or slightly less than that of imipenem, with MIC90s ranging from 2 to >128 microg/ml. The in vivo efficacy of oral CS-834 against experimental mouse septicemia caused by gram-positive and gram-negative bacteria was better than that of comparative drugs. In murine respiratory infection models, the efficacy of CS-834 reflected not only its potent in vitro activity but also the high levels present in the lungs.

Animals↗
PubMed1998

In vivo antibacterial activities of sanfetrinem cilexetil, a new oral tricyclic antibiotic.

The in vivo antibacterial activities of a new oral trinem, sanfetrinem cilexetil (a prodrug of sanfetrinem), were evaluated in comparison with those of cefdinir and amoxicillin. Sanfetrinem cilexetil showed potent efficacy against experimental murine septicemia caused by Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli and against murine respiratory infections caused by Streptococcus pneumoniae. Likewise, in murine models of respiratory infection by penicillin-susceptible and penicillin-resistant S. pneumoniae, sanfetrinem cilexetil was more effective than amoxicillin in reducing the number of bacteria in infected lungs. These results were reflected in its potent in vitro activity and high levels in plasma.

Animals↗
PubMed1998

Serum cytokines in patients with Legionella pneumonia: relative predominance of Th1-type cytokines.

Serum samples from 14 patients with Legionella pneumonia were examined for the presence of cytokines. In spite of high levels of serum C-reactive protein in all patients during the acute phase in only four cases (one involving interleukin-1beta [IL-1beta], three involving IL-6, and none involving tumor necrosis factor alpha) was the concentration of cytokines more than 100 pg/ml. Th2 cytokines IL-4 and IL-10 were detected in only one patient each. In contrast, significant increases of serum gamma interferon (IFN-gamma) and IL-12 levels were observed during the acute phase in 6 and 11 cases, respectively. Interestingly, although serum IFN-gamma levels diminished thereafter, in seven cases IL-12 levels remained high or increased further during the convalescent phase. In an additional 22 cases clinically suspected to be but not diagnosed as Legionella pneumonia, increases of serum IL-12 levels were observed in 16 cases, whereas the remaining 6 cases showed no detectable IL-12. Our results demonstrate the relative predominance of Th1 cytokine production in Legionella pneumonia. Although the role and significance of prolonged increases in IL-12 levels in Legionella disease are unknown, our results should prompt further investigation of the host immune response in terms of Th1 and Th2 balance in legionellosis.

Cytokines↗
PubMed1998

A new peptide-N4-(acetyl-beta-glucosaminyl)asparagine amidase from soybean (Glycine max) seeds: purification and substrate specificity.

We report here the isolation and characterization of a peptide-N4-(acetyl-beta-glucosaminyl) asparagine amidase (peptide: N-glycanase) from soybean (Glycine max) seeds. The enzyme was purified to homogeneity with 6.5% yield from defatted soybean meal extract by ion-exchange chromatography, gel filtration, hydroxyapatite chromatography, and hydrophobic chromatography. The purified enzyme, designated PNGase-GM, had the apparent molecular mass of 93 kDa by SDS-PAGE and 90 kDa by gel filtration, indicating this PNGase is a monomeric protein. The enzyme showed maximal activity at pH 4.5-5.0. PNGase-GM was capable of hydrolyzing the beta-aspartylglycosylamine linkage (GlcNAc beta 1-->Asn) of various glycopeptide substrates bearing high-mannose type, hybrid type, and xylose/fucose-containing plant complex type N-glycan units, while this amidase was far less active on the glycopeptides bearing sialylated animal complex-type glycans.

Amidohydrolases↗
PubMed1998

Sarcocystis suihominis detected for the first time from pigs in Japan.

Sarcoystis suihominis was detected for the first time in Japan from the heart and diaphragm of 5 out 600 older culled breeding pigs slaughtered in Saitama Prefecture, Japan. Fresh cysts were 1,080-2,040 x 106-170 microns in size. Bradysoites measured 15 x 4 microns on average. The cyst wall was usually observed thick, 4-6 microns, and striated, but occasionally thin and smooth according to the difference in sectioning angle and in portion of cysts. Scanning electron microscopy showed that many palisade-like villar protrusions, 6-6 x 0.3-0.5 microns in size, were closely folded onto the surface of cyst. A small number of microtubules were seen in the core of protrusion. No dogs nor domestic cats fed with 20 fresh cysts each excreted oocysts or sporocysts in the feces throughout the experimental period of 30 days.

Animals↗
PubMed1998

[In vitro antibacterial activities of cefteram and other beta-lactam agents against recent clinical isolates].

In vitro antibacterial activity of the third-generation oral cephem cefteram (CFTM)--ten years after its first use in the clinical setting--against recent clinical isolates was evaluated and compared with those of other oral cephems. A total of 851 clinical isolates belonging to 13 species used in this study were collected from five medical institutions across Japan during 1996. CFTM showed excellent antibacterial activity against methicillin-susceptible S. aureus and S. pyogenes, equivalent to those of other third-generation oral cephems, except cefixime. Of the S. pneumoniae strains, a high proportion, 34.1%, were penicillin-resistant strains (PRSP), with MIC values of 2.0 micrograms/ml or above, but the MIC50 of CFTM against PRSP was 1.0 microgram/ml. CFTM and the other third-generation oral cephems showed potent antibacterial activity against E. coli, K. pneumoniae, and P. mirabilis. A few strains of E. coli, however, were highly resistant to third-generation oral cephems; that might include extended-spectrum beta-lactamase producing strains. MIC values against P. vulgaris varied significantly, depending on whether they were determined by the broth micro-dilution method or the agar dilution method; growth was observed at high concentrations in the broth micro-dilution method, in which the skip phenomenon was demonstrated, but not in the agar dilution method. The reason for this discrepancy is unknown. Most strains of S. marcescens, C. freundii, and E. cloacae demonstrated resistance to CFTM and the other third-generation oral cephems. CFTM and the other third-generation oral cephems showed excellent antibacterial activities against M. (B.) catarrhalis, N. gonorrhoeae, and H. influenzae, including ampicillin-resistant strains.

Ampicillin Resistance↗
PubMed1997

Recombinant human tissue factor pathway inhibitor as a possible anticoagulant targeting hepatic sinusoidal walls.

The expression of tissue factor pathway inhibitor (TFPI) was investigated in sinusoidal endothelial cells in the liver and endothelial cells in the lung. Northern blot analysis revealed that TFPI mRNA was expressed in the lung, but minimal in the liver. Also, immunohistochemical examination showed that TFPI was not expressed on the sinusoidal endothelial cells in contrast to marked expression on endothelial cells in the lung, suggesting that anticoagulant activity to inhibit blood coagulation induced by tissue factor is reduced in the hepatic sinusoids compared to the microvessels of other organs. When recombinant human TFPI was intravenously injected in rats, it disappeared rapidly from the circulation, but was detected by electron microscopy on the surface of sinusoidal endothelial cells and microvilli of hepatocytes in the space of Disse. In these rats, the TFPI reappeared in the circulation following an intravenous injection of heparin sodium with reduced immunohistochemical staining of the TFPI on hepatic sinusoidal walls. It is concluded that exogenous TFPI can increase anticoagulant activity on the hepatic sinusoidal walls by binding to heparinoids on the cell surface. It may act effectively even in the hepatic sinusoids with damaged endothelial cells.

Animals↗
PubMed1997

Clonotypic analysis of T cells in patients with autoimmune and viral hepatitis.

The immunopathogenesis of autoimmune hepatitis (AIH), and the role of T cells in the onset and maintenance of this disease, are still unclear. Since T cells expand clonally after stimulation by an antigen, it is important to analyze the behavior of T cells at a clonal level. We have established recently a novel system, using reverse transcriptase-polymerase chain reaction (RT-PCR) and subsequent single-strand conformation polymorphism (SSCP) that allows the identification of clonal accumulation of T cells in a lymphocyte population. Using this system, we demonstrated that oligoclonal T cells were accumulated in the liver of patients with AIH, and that identical T-cell clonotypes were detected in two different regions of the liver, although these features were also observed in cases with viral hepatitis. Only in cases with AIH, however, nearly all identical T cells were found to belong to CD8+ subset and there were very few CD4+ T cells in this population. Our results suggest that common antigens presented to CD8+ T cells in the context of HLA class I molecule are distributed diffusely in the liver of AIH. These findings also suggest that antigens recognized by CD4+ T cells may be relatively heterogeneous in the liver with AIH.

Adult↗