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Biomedical subjects

A Ohno

Publications and source records attributed to A Ohno.

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

Adverse effects of tumour necrosis factor in cyclophosphamide-treated mice subjected to gut-derived Pseudomonas aeruginosa sepsis.

To evaluate the role of tumour necrosis factor (TNF) in gut-derived sepsis, mice were given Pseudomomas aeruginosa strain D4 by bacterial suspension in their drinking water during which time ampicillin (200 mg/kg) was given to disrupt the normal indigenous bacterial flora. Cyclophosphamide was additionally administered to induce bacterial translocation of the P. aeruginosa that had colonized the gastrointestinal tract, and thereby to cause gut-derived sepsis. In this model, TNF-alpha was detected in serum from the next day after the second cyclophosphamide administration, increasing to level of 3 ng/ml in lethal conditions. Average serum TNF-alpha level was significantly higher in mice with bacteraemia than in those without bacteraemia. Treatment with 0.8 microg/kg of recombinant human TNF-alpha (rhTNF-alpha) did not affect the mortality, whereas administration of either 4 and 20 microg/kg of rhTNF-alpha significantly increased the mortality rate in comparison with saline-treated mice. Bacterial counts in liver and blood were significantly higher in 20 microg/kg of rhTNF-alpha treated mice than in saline-treated mice. Treatment with murine anti-TNF-alpha monoclonal antibody significantly reduced the mortality from septic infection. We conclude that TNF-alpha may facilitate bacterial translocation and causes deterioration of gut-derived sepsis due to P. aeruginosa in mice.

Animals↗
PubMed1997

Solute composition and heat shock proteins in rat renal medulla.

The high content of heat shock proteins (HSPs) 25 and 72 in the hyperosmotic inner medulla of the concentrating kidney has been ascribed to the high NaCl and urea concentrations in this kidney zone. To assess the effects of variations in the composition of solutes in the renal medulla on the intrarenal distribution of HSPs, rats were fed either a high- or low-Na diet for 3 weeks. These diets result in greatly differing urine and inner medullary solute composition. Sodium dodecyl sulphate polyacrylamide gel electrophoresis and Western blot techniques were used to analyse HSP25 and HSP72 in the cortex, outer medulla and inner medulla. In addition, the amounts of organic osmolytes (sorbitol, myo-inositol, betaine and glycerophosphorylcholine) and urea in the tissue were determined by high-performance liquid chromatography. Intra- and extracellular electrolyte concentrations at the papillary tip were measured by electron microprobe analysis. In the high-Na group, urine osmolality was about 1000 mosmol/kg lower than in rats fed a low-Na diet, due to lower urea concentrations. The sum of urine sodium and potassium concentrations, however, did not differ between the two groups. Neither in the outer nor in the inner medulla was the sum of the concentrations of organic osmolytes affected by the dietary treatment. The sum of sodium, potassium and chloride concentrations did not differ between the two experimental groups, neither in the interstitial nor in the intracellular compartments. However, the urea content and the amounts of HSP25 and HSP72 were significantly lower in the inner medulla of the group of rats fed a high-Na diet. Our results suggest that urea participates in the regulation of the medullary levels of the HSPs and that both HSP25 and HSP72 are components of mechanisms protecting medullary cells against the deleterious effects of high urea concentrations.

Animals↗
PubMed1997

Inhibition of angiotensin-converting enzyme modulates structural and functional adaptation to loop diuretic-induced diuresis.

The roles of elevated cell sodium concentrations and the angiotensin-aldosterone system (AAS) in the structural and functional adaptation of the distal tubule and collecting duct system to a chronic increase of sodium delivery were examined using electron microprobe and quantitative morphologic/stereologic analyses. Studies were performed on rats given the loop diuretic torasemide acutely (20 min) or chronically (12 days), either alone or in combination with the angiotensin-converting enzyme (ACE) inhibitor, enalapril. In the sodium-absorbing cells of the distal tubule and cortical collecting duct-that is, in distal convoluted tubule (DCT), connecting tubule (CNT) and principal cells-an acute increase in sodium delivery caused a significant rise in intracellular sodium concentration and rubidium uptake, the latter an index of in vivo Na,K(Rb)-ATPase activity. The elevated cell sodium concentrations returned to, or close to, control values during chronic torasemide treatment. Intracellular rubidium concentrations, measured after a 30-second rubidium exposure, were not different from controls in DCT and CNT cells but were still higher in principal cells. Since, however, the distribution space for rubidium was significantly increased in chronic torasemide animals, rubidium uptake, and hence Na,K-ATPase activity, must have increased in proportion to cell volume in DCT and CNT cells, but more than proportionately in principal cells. When ACE was inhibited during chronic torasemide, the epithelial volume of DCT and cortical collecting duct (CCD) was increased mainly by lengthening and not, as was the case in rats given torasemide alone, by thickening of the tubule wall. Adaptation of the proximal tubule exclusively by lengthening was not affected by inhibition of the ACE. These data indicate that changes in cell ion composition may participate in initiating cell processes leading to adaptation of distal nephron segments to chronically increased salt delivery. Inhibition of the ACE reverses the torasemide-induced increase in apparent Na pump density in principal cells and seems to shift the relationship between hypertrophy and hyperplasia noted in DCT and CCD after chronic torasemide in favor of hyperplasia.

Aldosterone↗
PubMed1997

In vitro and in vivo antibacterial activities of CS-940, a new fluoroquinolone, against isolates from patients with respiratory infections.

We compared the in vivo and in vitro activities of CS-940, a new fluoroquinolone, with those of a group of other drugs. The activities of CS-940 against gram-positive cocci and gram-negative rods, including methicillin-susceptible Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae, were comparable to those of tosufloxacin, with MICs at which 90% of the strains were inhibited (MIC90s) of 0.5 microg/ml or less. Against methicillin-resistant S. aureus, CS-940 was as active as tosufloxacin, with a MIC90 of 16 microg/ml. The efficacy of CS-940 against murine respiratory infections due to S. pneumoniae or Haemophilus influenzae was better than those of tosufloxacin and sparfloxacin. The efficacy of oral doses of CS-940 reflected not only potent in vitro activity but also a high transmigration ratio from the bloodstream to lung tissues.

Animals↗
PubMed1997

Immunomodulating effect of fosfomycin on gut-derived sepsis caused by Pseudomonas aeruginosa in mice.

We evaluated the protective effect of fosfomycin (FOM) and an enantiomer of fosfomycin [FOM (+); an isomer of FOM with no bactericidal activity] on murine gut-derived sepsis caused by Pseudomonas aeruginosa. Endogenous bacteremia was induced by administering cyclophosphamide (CY) and ampicillin to specific-pathogen-free mice fed P. aeruginosa. Treatment of mice with FOM at 250 mg/kg of body weight per day twice a day after the second CY administration significantly increased the survival rate compared to that for control mice treated with saline. Treatment with FOM (+) at 20 and 100 mg/kg also significantly increased the survival rate (from 30% for control mice to 80% for treated mice). The bacterial counts in the liver and blood were both significantly lower in FOM(+)-treated mice in comparison with those in liver and blood of saline-treated control mice. FOM(+) administration affected neither the bacterial colonization in the intestinal tract nor the leukocyte counts in the peripheral blood of the mice. After intravascular inoculation of P. aeruginosa, treatment of mice with FOM (+) did not enhance bacterial clearance from the blood of mice pretreated or not enhance bacterial clearance from the blood of mice pretreated or not pretreated with CY, FOM(+) significantly suppressed tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 levels in the serum of mice after gut-derived sepsis. These results indicate that both FOM and FOM(+) have protective effects against P. aeruginosa bacteremia, despite a lack of specific activity of FOM(+), and suggest that FOM may possess immunomodulating activity and that it induces a protective effect. The protective mechanism is speculated to be that FOM modulates the vivo production of inflammatory cytokines.

Adjuvants, Immunologic↗
PubMed1997

Structural analysis of N-glycans of storage glycoproteins in soybean (Glycine max. L) seed.

The structures of N-linked sugar chains (N-glycans) of storage glycoproteins in soybean seeds have been identified. Eight pyridylaminated (PA-) N-linked sugar chains were derived and purified from hydrazinolysates of the storage glycoproteins by reverse-phase HPLC and size-fractionation HPLC. The structures of the PA-sugar chains purified were first identified by two-dimensional PA-sugar chain mapping and ion-spray mass analysis, considering the results of sugar composition analysis or sequential exoglycosidase digestion. The deduced structures were further analyzed by ion-spray tandem mass spectrometry and 500 MHz 1H-NMR spectrometry. The eight structures fell into two categories; the major class (96.6%) was a typical high mannose-type, the minor class was a xylose containing-type (Man3Xyl1GlcNac2, Man3Fuc1Xyl1GlcNac2; 3.4%).

Carbohydrate Sequence↗
PubMed1997

Amino acid sequence and characterization of aldo-keto reductase from bakers' yeast.

One of the enzymes from bakers' yeast that catalyzes the reduction of alpha- and beta-keto esters has been studied. The N-terminal amino acid sequence of the enzyme shows that the enzyme belongs to the aldo-keto reductase superfamily. The substrate specificity of the enzyme is broad and resembles those of other aldo-keto reductases. The enzyme catalyzes the reduction of keto esters, aldehydes, and aldohexoses.

Alcohol Oxidoreductases↗
PubMed1997

Enteropathogenic bacteria in the La Paz River of Bolivia.

Diarrheal diseases often result from ingestion of contaminated water or food. The population of La Paz, Bolivia is directly or indirectly exposed to the sewage-contaminated La Paz River. We conducted a bacteriologic survey of the La Paz River to quantify the level of bacterial contamination, with particular reference to enteropathogens. A total bacterial count exceeding 10(6) colony-forming units (CFU)/ml, including lactose fermenting and nonfermenting, gram-negative bacilli of approximately 10(5) CFU/ml, respectively, were detected in river water samples collected near two densely populated areas. A total bacterial count of 10(5) CFU/ml was also detected at the most downstream area of the river near a sparsely populated area. At four sampling locations, several enteropathogens were detected, including five enterotoxigenic Escherichia coli (ETEC) (serotype O6, O15, and O159), two enteropathogenic E. coli (EPEC) (serotype O44), two enteroinvasive E. coli (EIEC) (serotype O29), and three Salmonella O4 group isolates. The heat-labile enterotoxin gene and the invasive toxin gene were detected in all ETEC and EIEC isolates by polymerase chain reaction analysis. Nine isolates of E. coli were found by the agar dilution method to be susceptible to ampicillin, kanamycin, nalidixic acid, tetracycline, and chloramphenicol, and ampicillin resistance was found in only two isolates of EIEC 7-4 (serotype O29) and EPEC 7-5 (serotype O44). Ampicillin resistance was coded on plasmids and transferred conjugatively to E. coli chi1037 at a frequency of 10(-5) CFU/donor by the broth mating method. Strains of Aeromonas caviae, which can cause diarrheal disease in infants, were detected in vegetables grown in fields irrigated by water from the La Paz River. The survival of nine isolates of E. coli in filtered river water was compared with that of laboratory strains (E. coli chi1037, W3110, and ATCC29577). The survival time of seven isolates, excluding two ampicillin-resistant isolates, was markedly longer than that of the laboratory strains. Our results show a high bacterial contamination of the La Paz river and suggest that such levels may contribute to the high incidence of diarrheal disease in the city of La Paz.

Bacterial Toxins↗
PubMed1997

[Regulation mechanism of glycopeptide resistance expression].

The glycopeptide antibiotics have been used to treat severe infections caused by pathogenic Gram- positive bacteria since their discovery in the 1950s. However, resistance is now emerging and spreading among enterococci. The mechanism of resistance is the synthesis of a modified cell-wall precursor, terminating in D-lactate with a lower affinity for the glycopeptides. Three glycopeptide resistance phenotype (VanA, VanB and VanC) have been distinguished on the basis of the level and inducibility of the resistance to vancomycin and teicoplanin. Especially, most attention has been focused on VanA resistance because of a high-level resistance. VanA-resistance has been associated with five genes (vanR, vanS, vanH, vanA, vanX) on the transposon Tn 1546, which usually resides on a plasmid. Synthesis of VanH, VanA and VanX is regulated at the transcriptional level by the VanR-VanS two-component regulatory system. The VanH dehydrogenase and the VanA ligase, which is D-Ala-D-Ala ligase of altered substrates specificity, catalyze the synthesis of the depsipeptide D-alanyl-D-lactate. The VanX dipeptidase hydrolyzes the dipeptide D-alanyl-D-alanine produced by the host ligase.

Anti-Bacterial Agents↗
PubMed1997

p21 expression as a predictor for favorable prognosis in squamous cell carcinoma of the lung.

Although p21 WAF1/Cip1 expression has been detected immunohistochemically in non-small cell lung cancer (NSCLC), the associations between p21 expression and clinical characteristics are unknown. To determine the association between p21 expression and clinical features, p21 expression was immunohistochemically analyzed in paraffin-embedded tumor samples from 137 patients with curatively resected NSCLC. p21 expression, indicating normal p21 function, was detected in 48 (35.0%) of the 137 patients with curatively resected NSCLC and was detected more frequently in patients with stage I or II disease (40.2%) than in those with stage IIIA disease (22.5%; P = 0.0483). There was no difference in the positive rate between squamous cell carcinoma [SCC; 15 of 48 (31.3%)] and adenocarcinoma [30 of 77 (39.0%)]. For SCC, patients with tumors expressing p21 survived longer than did those with tumors negative for p21 expression; however, the corresponding survival time was not significant for adenocarcinoma. On the other hand, p53 expression, detected in 58 (42.3%) of these patients, did not act as any predictor for prognosis in either SCC or adenocarcinoma. Our findings suggest that the presence of p21 expression is associated with favorable prognosis in SCC and may be useful in obtaining candidates for adjuvant therapies from among patients with SCC.

Adenocarcinoma↗
PubMed1996

Blood coagulation in the hepatic sinusoids as a contributing factor in liver injury following orthotopic liver transplantation in the rat.

Blood coagulation equilibrium in the hepatic sinusoids may be deranged after orthotopic liver transplantation, since tissue factor activity increases in Kupffer cells and thrombomodulin expression disappears in sinusoidal endothelial cells in orthotopically transplanted rat liver. The presence of sinusoidal blood coagulopathy and its contribution to the development of early graft failure following orthotopic liver transplantation were investigated in rats. Orthotopic liver transplantation was performed using livers preserved in cold UW solution, according to the method of Kamada, in rats. Abnormalities in the hepatic sinusoids were evaluated electron-microscopically. Anticoagulation therapy was done using antithrombin III concentrate infused immediately and 12 hr after operation. Fibrin deposition and endothelial cell destruction in the hepatic sinusoids were observed in transplanted rats 5 hr after operation. In these rats, plasma antithrombin III activity was decreased to less than 40%o of normal levels, and massive hepatic necrosis developed with increased plasma thrombin-antithrombin III complex concentration 24 hr after operation. Anticoagulation therapy significantly attenuated the extent of hepatic necrosis, with normalization of plasma antithrombin III activity and further increase in plasma thrombin-antithrombin III complex concentration. A hypercoagulative state exists after orthotopic liver transplantation in rats. Fibrin deposition in the hepatic sinusoids associated with this state may contribute to the development of early graft injury.

Animals↗
PubMed1996

Heat shock proteins HSP25, HSP60, HSP72, HSP73 in isoosmotic cortex and hyperosmotic medulla of rat kidney.

The distribution of heat shock proteins (HSP) HSP60, HSP73, HSP72 and HSP25 in the isoosmotic cortex and the hyperosmotic medulla of the rat kidney was investigated using Western blot analysis and immunohistochemistry. HSP73 was homogeneously distributed throughout the whole kidney. The level of HSP60 was high in the renal cortex and low in the medulla. HSP25 and HSP72 were present in large amounts in the medulla. Only low levels of HSP25 and almost undetectable amounts of HSP72 were found in the cortex. HSP25 exists in one nonphosphorylated and several phosphorylated isoforms. Western blot analysis preceded by isoelectric focussing showed that HSP25 predominates in its nonphosphorylated form in the outer medulla but in its phosphorylated form in cortex and inner medulla. Although this intrarenal distribution pattern was not changed during prolonged anaesthesia (thiobutabarbital sodium), a shift from the nonphosphorylated to the phosphorylated isoforms of HSP25 occurred in the medulla. The characteristic intrarenal distribution of the constitutively expressed HSPs (HSP73, HSP60, HSP25) may reflect different states of metabolic activity in the isoosmotic (cortex) and hyperosmotic (medulla) zones of the kidney. The high content of inducible HSP72 in the medulla most likely is a consequence of the osmotic stress imposed upon the cells by the high urea and salt concentrations in the hyperosmotic medullary environment.

Anesthetics↗
PubMed1996

Large spleno-caval shunt not accompanied by cirrhosis or encephalopathy.

A 40-year-old man with a large spleno-caval shunt through the azygos vein is described. This was considered a rare case, because the patient had no accompanying advanced liver disease, or episodes of hepatic encephalopathy. During checks after abnormal liver function test results, a shunt vessel was detected incidentally by ultrasonography. Computed tomography, magnetic resonance imaging, and angiography demonstrated that it was a large shunt between the splenic vein and superior vena cava through the coronary and azygos veins. The patient was a hepatitis B virus carrier and was positive for anti-HBe, and had a history of heavy drinking. However, on laparoscopic examination, the liver was not cirrhotic and the biopsy revealed only mild chronic hepatitis without bridging fibrosis. There were no esophageal varices or hepatosplenomegaly. On hemodynamic evaluation, the wedge hepatic vein pressure was slightly elevated and hepatic blood flow was reduced to half the normal value. Despite the large portal-systemic shunt, the patient had no history or signs of hepatic encephalopathy. The clinical features of this rare case are discussed.

Adult↗
PubMed1996

Low malignant intraductal carcinoma on the hard palate: a variant of salivary duct carcinoma?

A rare, minor salivary gland tumour of the hard palate in a middle-aged woman was presented. The small (1.0 X 0.5 cm in diameter) hemispherical tumour was well circumscribed with a fine papillomatous surface. Histopathologically, tumour cells with eosinophilic cytoplasm and a large nucleus were single-strand cuboidal and columnar cells, which showed intraductal growth exhibiting a cribriform pattern. The histological features were distinct from adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma because the tumour lacked the neurotropic infiltration, cord-like proliferation and targetoid arrangement. The tumour could not be identified as a typical salivary-duct carcinoma because Roman bridging, papillary projection, and severe cell atypia were not found. Tumour cells were negative for PAS, Alcian blue, mucicarmine, p53, c-erbB-2, CEA, S-100 protein, alpha-smooth muscle actin, lactoferrin or vimentin. About 5% of the tumour cells were positive for proliferating cell nuclear antigen. Taking these factors into account, together with the clinical features, the name low malignant intraductal carcinoma seems appropriate.

Female↗
PubMed1996

Intraosseous carcinoma arising from mandibular ameloblastoma with progressive invasion and pulmonary metastasis.

A 60-year-old woman, who had undergone curettage of a mandibular ameloblastoma about 20 years before, presented with recurrence of an ameloblastoma in the mandibular symphysis. This tumor was removed by a marginal resection. About 2 years later, the tumor recurred in the right mandibular ramus, and the patient underwent right mandibulectomy. About 6 months later, the tumor again recurred. Radical resection was performed, but invasion of the infraorbital region and cranial base was noted. An anterior craniotomy was then performed and the lesion removed. Histologically, proliferation of squamous cells associated with atypia was seen, and ameloblastic features were no longer observed. Metastasis to the lung was noted 1 year later.

Ameloblastoma↗
PubMed1996

Role of adhesion molecules in the development of massive hepatic necrosis in rats.

Massive hepatic necrosis develops after endotoxin administration in rats pretreated with heat-killed Propionibacterium acnes as a result of microcirculatory disturbance caused by endothelial cell destruction by activated macrophages in the hepatic sinusoids. Immunohistochemical hepatic expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen 1 alpha (LFA-1 alpha) and the effect of monoclonal antibodies against both adhesion molecules on liver necrosis provoked after endotoxin administration was studied in these rats. There were increased stains of ICAM-1 in endothelial cells and LFA-1 alpha in macrophages in the hepatic sinusoids in Propionibacterium acnes-pretreated rats compared with normal rats. Such stains were further increased soon after endotoxin administration, followed by development of hepatic necrosis. Monoclonal antibodies against both adhesion molecules significantly attenuated the extent of liver injury compared with controls, without affecting the infiltration and activation of hepatic macrophages. Polyclonal antibodies against polymorphonuclear leukocytes eradicated circulating neutrophils, but did not change such liver injury, although gum arabic, which suppressed macrophage activation, attenuated the extent of liver injury. Thus, adhesion between endothelial cells and activated macrophages in the hepatic sinusoids via ICAM-1 and LFA-1 alpha is essential for the initiation of massive hepatic necrosis of this type. Contribution of neutrophils seems less likely.

Animals↗
PubMed1996

Direct evidence for antipseudomonal activity of macrolides: exposure-dependent bactericidal activity and inhibition of protein synthesis by erythromycin, clarithromycin, and azithromycin.

Several previous investigators have reported that long-term administration of certain macrolides is efficacious in patients with persistent pulmonary Pseudomonas aeruginosa infections, even though the clinically achievable concentrations of these medications are far below their MICs. In the present study, we examined how sub-MICs of macrolide antibiotics affect the viability of and protein synthesis in several strains of P. aeruginosa. We report that 48 h, but not 12 or 24 h, of growth on agar containing a clinically achievable concentration of azithromycin (0.5 microgram/ml, 1/128 the MIC) significantly reduces the viability of strain PAO-1. Similar effects were seen with erythromycin and clarithromycin at 2 micrograms/ml (1/128 and 1/64 the respective MICs), whereas josamycin, oleandomycin, ceftazidime, tobramycin, minocycline, and ofloxacin had no effect on viability, even following 48 h of incubation with concentrations representing relatively high fractions of their MICs. The bactericidal activity of azithromycin seen following 48 h of incubation was not limited to strain PAO-1 but was also seen against 13 of 14 clinical isolates, including both mucoid and nonmucoid strains. Although viability was not decreased prior to 48 h, we found that 4 micrograms of azithromycin per ml inhibits protein synthesis after as little as 12 h and that protein synthesis continues to decrease in a time-dependent manner. We likewise found that P. aeruginosa accumulates azithromycin intracellulary over the period from 12 to 36 h. These results suggested that sub-MICs of certain macrolides are bactericidal to P. aeruginosa when the bacteria are exposed to these antibiotics for longer periods. Exposure-dependent intracellular accumulation of the antibiotic and inhibition of protein synthesis may partially account for the antipseudomonal activity of macrolides over relatively prolonged incubation periods.

Anti-Bacterial Agents↗