Biomedical subjects

M Ohta

Publications and source records attributed to M Ohta.

At least 415 records · Page 23Linked to original sources

PubMed1996

Portal hypertension activates the nitric oxide synthase genes in the esophageal mucosa of rats.

BACKGROUND & AIMS: Nitric oxide is associated with hyperdynamic circulation and development of collaterals in portal hypertension. The aim of this study was to investigate whether NO synthase is activated in the portal-hypertensive esophagus. METHODS: In esophageal specimens after portal ligation or sham operation, the expression of constitutive and inducible NO synthase messenger RNA was assessed by reverse transcription-polymerase chain reactions. NO synthase protein at 14 postoperative days was visualized with immunofluorescence staining with specific antibodies against constitutive and inducible NO synthase. RESULTS: The esophageal muscularis mucosae and epithelium overlying large submucosal veins in portal-hypertensive rats were significantly thinner than in controls (muscularis mucosae, 24.3% thinner, P < 0.01; epithelium, 23.0% thinner, P < 0.05). Expression of NO synthase proteins in endothelia of submucosal veins was significantly higher in portal-hypertensive rats than in controls (constitutive NO synthase, 17.6%; inducible NO synthase, 18.0% increased over controls, respectively; P < 0.01). Expression of both constitutive and inducible NO synthase messenger RNA in portal-hypertensive rats was significantly increased (constitutive NO synthase, 10-fold; inducible NO synthase, 20-fold at 14 days vs. controls; P < 0.01). CONCLUSIONS: Portal hypertension triggers overexpression of NO synthase messenger RNA and protein in the rat esophageal mucosa. This phenomenon, combined with the thinness of muscularis mucosae and epithelium, may facilitate development and rupture of esophageal varices.

Animals↗

PubMed1996

Decreased ureagenesis from alanine, but not from ammonia and glutamine, in the perfused rat liver after partial hepatectomy.

Ureagenesis from ammonia, alanine, and glutamine in the liver after partial hepatectomy (PH) was determined by using the liver-perfusion system. The maximum rate of ureagenesis from ammonium chloride (10 mmol/L) in hepatectomized (HX) rats at 24 hours after surgery was obtained in the presence of ornithine, lactate, and pyruvate, and it was almost identical to that in sham-operated (SO) rats. The rate of urea production from glutamine (1 mmol/L or 10 mmol/L) in HX rats was significantly lower than that of SO rats with a concomitant decrease in hepatic glutaminase activities. However, the rate of urea synthesis from glutamine (1 mmol/L) in the presence of added ammonia (0.5 mmol/L) was accelerated approximately 10-fold, and the significant difference in the rate of urea formation between HX and SO rats was abolished. This result indicates that there is enough glutaminase to generate ammonia from glutamine in the liver of HX rats. The rate of urea production from alanine (1 mmol/L or 10 mmol/L) in HX rats was significantly decreased at 24 hours following surgery, while that of SO rats was increased. The decreased formation of urea from alanine was not seen at 72 and 120 hours after the operation. These results suggest that during the proliferation phase of liver regeneration, a reduction of ureagenesis from alanine facilitates the remnant liver to make nonessential amino acids such as aspartate. This metabolic alteration might be related to the proliferation of liver cells.

Alanine↗

PubMed1996

Population of hepatic macrophages and response of perfused liver to platelet-activating factor during production of thioacetamide-induced cirrhosis in rats.

The response of hepatic macrophages and the effects of platelet-activating factor (PAF) in perfused liver were studied during production of experimental cirrhosis induced by thioacetamide (TAA) in female Sprague-Dawley rats. Within 4 weeks of TAA administration (300 mg/L drinking water), an increase in hepatic macrophage population and enlargement in cell size preceded the alterations characteristic of cirrhosis. During 12 weeks of TAA administration, the changes in hepatic macrophages were maintained and cirrhosis of the micronodular type developed with a marked increase in hydroxyproline content. Although TAA treatment for 4 weeks had no effect on oxygen consumption or hepatic portal pressure in the perfused liver, the increment in hepatic portal pressure and decrement in oxygen consumption induced by PAF in TAA-treated rats were double those in control rats. The amounts of prostaglandin D2 (PGD2) and thromboxane B2 (TxB2) in perfusate induced by PAF were seven- and fivefold greater, respectively, in TAA-treated rats than in control rats. Zymosan mimicked the effects of PAF. These results are consistent with the hypothesis that hepatic macrophages and PAF play important roles in the development of cirrhosis induced by TAA.

Animals↗

PubMed1996

Distribution of and age-related changes in ciliary neurotrophic factor protein in rat tissues.

We developed a sensitive enzyme-linked immunosolvent assay for measuring ciliary neurotrophic factor (CNTF) and examined age-related changes in the CNTF contents of a variety of rat tissues during postnatal development. CNTF contents were substantially higher in the sciatic nerve and spinal cord than in the other tissues tested, the kidney coming third. In all the tissues except the sciatic nerve (90 ng/g), the CNTF content was less than 1 ng/g at 1 week of age, then gradually increased. It was highest at 5 weeks of age in the sciatic nerve (3171 ng/g), spinal cord (118 ng/g), and kidney (36.8 ng/g), after which it slowly decreased. In contrast, the maximum in the brain stem (9 ng/g) and cerebellum (3.6 ng/g) was at 8 weeks of age, whereas in skeletal muscle it was at 2 weeks of age (14.6 ng/g). These findings indicate that CNTF functions in the postnatal development of the rat.

Aging↗

PubMed1996

Use of metronidazole gel to control malodor in advanced and recurrent breast cancer.

Intolerable malodor emanating from ulcerated tumors as a result of anaerobic infection is a serious problem in the management of advanced and recurrent breast cancer. Metronidazole can control this malodor, but its oral use may cause adverse reactions. We therefore formulated a metronidazole gel, since no equivalent preparation is commercially available in Japan, and used it in five female patients (four with advanced cancer and one with recurrent cancer) admitted to our hospital between March 1994 and July 1995. The patients were aged between 47 and 71 (median: 59) years, and the duration of morbidity in the four patients with advanced cancer ranged from 10 months to four years. In three patients, the tumors were larger than 10 cm x 10 cm. Metronidazole gel was applied to the surface of ulcerated tumors once or twice daily. Independent assessments by the patient, doctor and nurse were unanimous, and revealed that the malodor was alleviated in one patient after three days, and removed in four patients after two to five (median: four) days of metronidazole gel treatment. Culture of swabs showed a decrease or disappearance of anaerobic colonies. Adverse reactions characteristic of metronidazole did not occur. The topical use of metronidazole in a gel form will improve the quality of life for patients with malodorous ulcerated tumors and facilitate intensive treatment of the underlying disease.

Administration, Topical↗

PubMed1996

Bilateral tumor-like invasive xanthelasma palapebrarum in the superior palpebra.

We describe a very rare case of bilateral xanthelasma. Pathologically, xanthoma cells invaded the dermis, subcutaneous tissues, orbicularis muscle, orbital septum, orbital fat, and palpebral levator. Clinically, diplopia was present. Although considerable improvement was noted in appearance after surgical removal of as much of the tumors as possible, an increase in and a recurrence of the remaining tumors were observed at a later date following the operation.

Adult↗

PubMed1996

Role of cholecystokinin (CCK)-A receptor for pancreatic growth after weaning: a study in a new rat model without gene expression of the CCK-A receptor.

This work extends a recent observation that Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which have been established as an animal model of non-insulin-dependent diabetes mellitus, show no expression of the cholecystokinin (CCK)-A receptor gene in the pancreas. The CCK-A receptor is known to be involved in regulating pancreatic exocrine function and growth. We examined the growth of the pancreas in terms of wet weight, enzyme compositions, and protein and DNA contents at 5-6 and 24-25 weeks of age in OLETF rats and control (Long-Evans Tokushima; LETO) rats. The pancreatic wet weight increased significantly with age in both OLETF and LETO rats but was significantly lower in OLETF rats than in LETO rats. The total DNA contents in the whole pancreas (cell numbers) were comparable for both strains and increased significantly with age. However, the ratio of protein content to DNA content (the cell size) significantly increased with age in LETO rats, with no increase in OLETF rats. The changes in chymotrypsin, amylase, and insulin with respect to age were in the same direction in both strains: a decrease or no change in total and/or cellular contents of chymotrypsin and insulin and increases in amylase. These results suggest that the CCK-A receptor plays some role in the increase in cell size associated with normal growth of the pancreas from 5 to 25 weeks of age (after weaning).

Aging↗

PubMed1996

Crystallization of an R-form lipopolysaccharide from Klebsiella pneumoniae.

An R-form lipopolysaccharide (LPS) from Klebsiella pneumoniae strain LEN-111 (03-:K1-) formed crystals, whose shapes were elongated hexagonal plates, trapezoid plates, and rhomboid plates, and whose greatest dimensions were 3.1 x 0.8 microns, when it was suspended in 50 mM Tris buffer at pH 8.5 containing 5 mM MgCl2 and kept at 4 C for as long as 870 days. K. pneumoniae LEN-111 synthesized LPS molecules possessing incomplete repeating units of the O-antigenic polysaccharide portion besides the R-form LPS because of a leaky characteristic, but crystals consisted exclusively of the R-form LPS. Although the size of crystals was not large enough for X-ray analysis and limited crystallographic information was available, it was suggested that the crystals consist of hexagonal lattices with an alpha axis of 4.62 A and c axis of 79.8 +/- 2.6 A. The present results showed that R-form LPS lacking the O-antigenic polysaccharide portion tends to form crystals during long-term incubation in Tris buffer at pH 8.5 containing MgCl2 at 4 C.

Crystallography, X-Ray↗

PubMed1996

Crystallization of synthetic Escherichia coli-type lipid A.

Synthetic Escherichia coli-type lipid A formed hexagonal plate crystals when it was precipitated by the addition of 2 volumes of 95% ethanol containing 375 mM MgCl2 and incubated in 70% ethanol containing 250 mM MgCl2 at 4 C for 10 days. Analyses of crystals by electron diffraction and synchrotron X-ray diffraction showed that crystals consist of hexagonal lattices with the lattice constant (a side of the lozenge as a unit cell on the basal plane) of 4.62 angstrom and the longitudinal axis (perpendicular to the basal plane) of 49.3 +/- 1.3 angstrom. Results suggest that the previous finding that various kinds of R-form lipopolysaccharides crystallized but free lipid A isolated by acid hydrolysis from Re lipopolysaccharide did not crystallize under the same experimental conditions (Kato et al, J. Bacteriol., 172:1516-1528, 1990) is due to structural changes of lipid A occurring during the procedure of isolation of free lipid A.

Crystallization↗

PubMed1996

Complications of percutaneous transhepatic catheterization of the portal venous system in patients with portal hypertension.

We report here complications of percutaneous transhepatic catheterization of the portal venous system in 170 Japanese patients with portal hypertension. All patients underwent percutaneous transhepatic portography and percutaneous transhepatic obliteration of oesophagogastric varices was also performed in 29 patients. After retraction of the catheter, the puncture canal was plugged with gelatin sponge in 150 subjects and with one steel coil in 20 others. The overall complication rate was 16.5%. Intraperitoneal bleeding occurred in 10.6% of patients and 2.9% required blood transfusion. In these patients with intraperitoneal bleeding, the gelatin sponge was used for plugging after retraction of the catheter, while in the 20 patients with a steel coil plug, haemoperitoneum never occurred. Right pleural effusion was recognized in 3.5% of patients, intraperitoneal bile leakage in 1.8% and deterioration of liver function due to arteriovenous fistula in 0.6%. By univariate and multivariate analyses, female gender was the only risk factor for intraperitoneal bleeding among 150 patients investigated by percutaneous transhepatic catheterization of the portal venous system with gelatin sponge plugging. Intraperitoneal bleeding is the most important complication in patients with portal hypertension; it is difficult to predict intraperitoneal bleeding before retraction of the catheter in patients for whom gelatin sponge is used. Thus, for patients undergoing percutaneous transhepatic catheterization of the portal venous system, close follow up is recommended.

Adult↗

PubMed1996

Gigantic aneurysm in the thoraco-abdominal aorta of an infant.

We report the case of a boy with a gigantic aneurysm in the thoraco-abdominal region which was detected by a chest X-ray taken prior to surgical correction of ptosis of the eyelids at 11 months of age. At 18 months, he successfully underwent aneurysm exclusion and bypass grafting. A biopsy from the thoracic aorta revealed medial degeneration with conspicuous smooth muscle cell involvement. Laboratory examination showed altered elastase activity in the granulocytes and whole blood. The present case may represent a unique form of aneurysm in infancy.

Aortic Aneurysm, Abdominal↗

PubMed1996

Multifocal outbreaks of metallo-beta-lactamase-producing Pseudomonas aeruginosa resistant to broad-spectrum beta-lactams, including carbapenems.

A total of 3,700 Pseudomonas aeruginosa isolates were collected from 17 general hospitals in Japan from 1992 to 1994. Of these isolates, 132 carbapenem-resistant strains were subjected to DNA hybridization analysis with the metallo-beta-lactamase gene (blaIMP)-specific probe. Fifteen strains carrying the metallo-beta-lactamase gene were identified in five hospitals in different geographical areas. Three strains of P. aeruginosa demonstrated high-level imipenem resistance (MIC, > or = 128 micrograms/ml), two strains exhibited low-level imipenem resistance (MIC, < or = 4 micrograms/ml), and the rest of the strains were in between. These results revealed that the acquisition of a metallo-beta-lactamase gene alone does not necessarily confer elevated resistance to carbapenems. In several strains, the metallo-beta-lactamase gene was carried by large plasmids, and carbapenem resistance was transferred from P. aeruginosa to Escherichia coli by electroporation in association with the acquisition of the large plasmid. Southern hybridization analysis and genomic DNA fingerprinting profiles revealed different genetic backgrounds for these 15 isolates, although considerable similarity was observed for the strains isolated from the same hospital. These findings suggest that the metallo-beta-lactamase-producing P. aeruginosa strains are not confined to a unique clonal lineage but proliferated multifocally by plasmid-mediated dissemination of the metallo-beta-lactamase gene in strains of different genetic backgrounds. Thus, further proliferation of metallo-beta-lactamase-producing strains with resistance to various beta-lactams may well be inevitable in the future, which emphasizes the need for early recognition of metallo-beta-lactamase-producing strains, rigorous infection control, and restricted clinical use of broad-spectrum beta-lactams including carbapenems.

Blotting, Southern↗

PubMed1996

Molecular aspects of high-level resistance to sulbactam-cefoperazone in Klebsiella oxytoca clinical isolates.

Nine Klebsiella oxytoca strains which demonstrated resistance to the combination of sulbactam and cefoperazone were isolated from geographically separate hospitals in Japan in 1995. Among them, K. oxytoca SB23 showed high-level resistance to sulbactam-cefoperazone (MIC > 128 micrograms/ml) and aztreonam (MIC, 128 micrograms/ml). The sulbactam-cefoperazone resistance was not transferred from strain SB23 to Escherichia coli CSH2 by conjugation, beta-Lactamase RbiA, produced by strain SB23, was purified, and the molecular mass was estimated to be 29 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Kinetic parameters for RbiA revealed that cefoperazone and aztreonam were hydrolyzed efficiently by this enzyme. Moreover, ceftazidime and imipenem were also hydrolyzed weakly by RbiA, although strain SB23 did not show any resistance to these agents. Clavulanate, sulbactam, and tazobactam failed to block the hydrolysis of cefoperazone by RbiA. The structural gene of RbiA (blaRBI) was cloned and sequenced, and the deduced amino acid sequence of RbiA demonstrated high-level similarities to those of the beta-lactamases found in K. oxytoca D488, E23004, and plasmid-mediated MEN-1, which have been classified into Bush functional group 2be. Although RbiA demonstrates high-level molecular similarity to the enzymes in group 2be, from an enzymological point of view, this enzyme might be differentiated from the enzymes in that group. Hybridization analysis revealed that beta-lactamase genes highly similar to blaRBI were generally encoded on the chromosome of the sulbactam-cefoperazone-resistant clinical isolates of K. oxytoca tested in the study, despite their different derivations. This observation suggests that sulbactam-cefoperazone-resistant A. oxytoca strains which produce RbiA-type beta-lactamases have been proliferating in many hospitals in Japan.

Amino Acid Sequence↗

PubMed1996

PCR detection of metallo-beta-lactamase gene (blaIMP) in gram-negative rods resistant to broad-spectrum beta-lactams.

We applied PCR to the rapid detection of the metallo-beta-lactamase gene, blaIMP, in clinically isolated gram-negative rods. A total of 54 high-level ceftazidime-resistant strains (MICs, > 128 micrograms/ml) were subjected to PCR analyses with the blaIMP-specific primers, since the blaIMP-bearing clinical isolates tested in our previous study always demonstrated high-level resistance to ceftazidime. Twenty-two blaIMP-positive strains including 9 Pseudomonas aeruginosa, 9 Serratia marcescens, 2 Alcaligenes xylosoxidans, 1 Pseudomonas putida, and 1 Klebsiella pneumoniae strains were newly identified from 18 different hospitals in Japan. These strains were mostly isolated from urine samples and showed high-level resistance to almost every cephem, while their levels of resistance to carbapenems were diverse. The PCR analyses with novel integrase gene-specific (intI3) and acc(6')-Ib gene-specific primers suggested that the integron structure found in a large plasmid harbored by S. marcescens AK9373 was also well conserved among blaIMP-positive strains. These results imply that the blaIMP gene cassettes have been dispersing into various gram-negative rods with the help of the newly identified integron element. Thus, the PCR-aided rapid detection will be helpful for the early recognition of emerging blaIMP-positive clinical isolates which demonstrate consistent resistance to beta-lactams.

Alcaligenes↗

PubMed1996

Pulsed Doppler echocardiographic assessment of changes in pulmonary artery pressure during oxygen breathing.

To validate the use of pulsed Doppler echocardiography in detecting changes in pulmonary artery pressure (PAP), several parameters of flow velocity profiles of the right ventricular outflow tract were compared with changes in PAP and pulmonary vascular resistance measured directly by cardiac catheterization. The study was performed in 33 patients with chronic pulmonary disease (chronic obstructive pulmonary disease or pulmonary fibrosis) or pulmonary thromboembolism, during room air and 100% oxygen breathing. Inhalation of 100% oxygen for 15 min significantly reduced PAP in patients with mild pulmonary hypertension (20 < or = mean PAP < or = 24 mm Hg; control: 21.3 +/- 1.3, O2: 17.9 +/- 2.2 mm Hg, p < 0.05) and those with severe pulmonary hypertension (mean PAP > or = 25 mm Hg; control 44.9 +/- 16.8, O2: 35.4 +/- 13.5 mm Hg, p < 0.05). It also significantly reduced the pulmonary vascular resistance and cardiac output in both groups. The ratio of acceleration time to right ventricular ejection time (AT/RVET), a parameter measured by Doppler echocardiography, correlated significantly with mean PAP during room air (r = 0.73, p < 0.0001) and oxygen breathing (r = 0.64, p < 0.0001). Furthermore, AT/RVET increased significantly in patients with mild pulmonary hypertension and those with severe pulmonary hypertension. Our results suggest that the Doppler technique provides a clinically useful, noninvasive index for assessing changes in PAP during oxygen breathing in patients with pulmonary hypertension complicating chronic pulmonary disease or pulmonary thromboembolism.

Administration, Inhalation↗

PubMed1996

Effect of teprenone on portal hypertensive gastric mucosa.

Teprenone (geranylgeranylacetone) is a gastric mucosal protective drug used clinically in Japan for treatment of gastric ulcers and gastritis. Its effect on portal hypertensive (PHT) gastric mucosa which has impaired defensive mechanisms is not known. In 20 PHT and 20 sham-operated rats, we studied the effects of teprenone or placebo on: (1) portal pressure; (2) gastric pH; (3) gastric mucosal blood flow using laser doppler flowmetry, and (4) hexosamine content in gastric mucosa. The gastric mucosal blood flow was significantly higher in the PHT + teprenone group than in the PHT + placebo group (463 +/- 75 and 381 +/- 82 perfusion units, respectively; p < 0.05). The hexosamine content was significantly lower in PHT rats than in sham-operated controls (12.6 +/- 2.3 vs. 14.3 +/- 2.2 micrograms/mg, respectively). Teprenone treatment significantly increased the gastric mucosal hexosamine concentration in both sham-operated and PHT rats (17.2 +/- 3.1 and 15.6 +/- 3.6 micrograms/mg, respectively). These effects of teprenone, combined with its known prostaglandin-stimulating action, suggest a potential role for this agent in the treatment of PHT gastric mucosal abnormalities.

Animals↗

PubMed1996

A rare case of arteriosclerosis obliterans without prominent risk factors complicated by idiopathic thrombocytopenic purpura. A case report.

An eighty-four-year-old man was admitted to the hospital because of pain at rest in the lower extremities. On physical examination, trophic changes of the skin and petechiae in the limbs were observed. Computed tomographic scan of the abdomen showed focal renal infarctions and calcification of the descending aorta. Moreover, radionuclide imaging of the arterial system revealed complete obstructions of the two right iliac arteries and the left external iliac artery, where collateral flows were observed. Laboratory examination showed a severe thrombocytopenia caused by immunoglobulin G (IgG)-type autoantibody against platelets. He was diagnosed as having arteriosclerosis obliterans complicated by idiopathic thrombocytopenic purpura, although no known risk factors promoting atherosclerosis other than age were evident. In such a case with hemorrhagic diathesis, a hemorheologic agent and the vasodilator prostaglandin could confer advantages in relieving and controlling the ischemic leg pain without hemorrhagic complications. Moreover, small doses of the initial prednisolone therapy for ITP might also be recommended to avoid thrombus formations in the atherosclerotic lesions.

Aged↗

PubMed1996

IR and NMR analyses of hardening and maturation of glass-ionomer cement.

It has been reported that the silicate phase as well as the cross-linking of the polycarboxylic acid by aluminum and calcium ions played an important role in the hardening of glass-ionomer cement. The objective of this study was to investigate the structural change during hardening of the cements by means of infrared (IR) spectroscopy and solid-state nuclear magnetic resonance (NMR) spectroscopy and to confirm the role of the silica phase in the hardening of the cement. For that purpose, we measured the change in compressive strength of an experimental glass-ionomer cement, two commercial glass-ionomer cements, and a polycarboxylate cement and carried out 29Si and 27Al NMR analyses of the cement samples after the strength measurement. In the IR spectra during hardening, a characteristic band of the silicate network around 1000 cm-1 shifted toward high frequency with time. The spectrum after hardening was similar to that for a hydrated amorphous silica structure. The 27Al NMR analysis showed that Al3+ ion was tetrahedrally coordinated by oxygen in the original glass, but a part of the Al3+ ion was octahedrally coordinated after hardening to form Al polyacrylate gel. The chemical shift of Si in the 29Si NMR spectra also changed during hardening. The variation in the chemical shift reflected the structural change in the silicate network. The initial increase in compressive strength of the cement was mainly caused by polycarboxylate gel formation. However, it was concluded that the reconstruction of the silicate network contributed to the increase in strength with time during the period after the gelation by cross-linking was completed.

Compressive Strength↗