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Biomedical subjects

M Otsuki

Publications and source records attributed to M Otsuki.

At least 145 records · Page 8Linked to original sources
PubMed1996

Mutation in DNA gyrase of norfloxacin-resistant clinical isolates of Neisseria gonorrhoeae.

BACKGROUND AND OBJECTIVES: Recently a rapid decrease in the susceptibility of Neisseria gonorrhoeae isolates to fluoroquinolones has occurred and gonococcal fluoroquinolone resistance is now a significant problem in the treatment of gonorrhoea in Japan. Thus, in order to investigate the quinolone resistance mechanisms in clinical isolates of N gonorrhoeae we studied an alteration in the DNA gyrase subunit A (GyrA) which is well-known as a common mechanism of bacterial quinolone resistance. MATERIALS AND METHODS: Four clinical isolates of N gonorrhoeae resistant to norfloxacin and 5 strains susceptible to norfloxacin, including 2 clinical isolates and 3 WHO reference strains, were tested in this study. To identify mutations in the GyrA genes of gonococcal strains, polymerase chain reaction and direct DNA sequencing were performed. RESULTS: A single base change (serine codon TCC changed to phenylalanine codon TTC), which resulted in an amino acid change in GyrA at position 91, was identified in all 4 norfloxacin-resistant strains for which the MICs of norfloxacin ranged from 1.0 to 8.0 micrograms/ml, while no mutation within GyrA was detected in 5 norfloxacin-susceptible strains for which the MICs of norfloxacin ranged from 0.004 to 0.063 microgram/ml. CONCLUSIONS: The results from this study suggest that the serine-91 to phenylalanine substitution in GyrA is probably an essential mutation in fluoroquinolone resistance in clinical isolates of N gonorrhoeae.

Animals↗
PubMed1996

Defect in pancreatic exocrine and endocrine response to CCK in genetically diabetic OLETF rats.

Clinical as well as experimental studies in insulinopenic diabetes mellitus have demonstrated abnormal pancreatic exocrine responses to cholecystokinin (CCK). In the present study, we examined pancreatic exocrine and endocrine function in the recently developed genetically diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats and compared them with those in the control Long-Evans Tokushima Otsuka (LETO) rats of the same age. Stepwise increasing doses of CCK octapeptide (CCK-8; 0.027-7.0 nmol.kg-1.h-1) evoked a characteristic biphasic dose-response curve for pancreatic juice and protein output in the LETO rats, whereas the OLETF rats were totally insensitive to CCK-8 stimulation. However, the responsiveness and the sensitivity to both carbamylcholine and secretin were similar in the two groups. Intraduodenal infusion of casein (500 mg/h) failed to stimulate pancreatic exocrine secretion in the OLETF rats despite a greater CCK response than in the LETO rats (peak response: 8.43 +/- 0.97 vs 5.12 +/- 0.30 pmol/l in LETO, P < 0.01). Intravenous infusion of CCK-8 (4.4 nmol.kg-1.20 min-1) caused a significant increase in serum insulin concentrations and a concomitant decrease in glucose levels in the LETO rats but not in the OLETF rats. On the other hand, an intravenous bolus injection of 1.1 mmol/kg glucose caused a greater insulin release in the OLETF rats than in the LETO rats. In contrast, gastric acid secretion in the OLETF rats was significantly high in basal and in response to intravenous infusion of CCK-8 compared with that in the LETO rats. Four subcutaneous injections of 20 micrograms/kg caerulein at hourly intervals over 3 h induced acute pancreatitis in the LETO rats but did not elicit any significant increase in serum amylase or lipase activities and pancreatic wet weight or histological evidence of acute pancreatitis in the OLETF rats. These results indicate that the exocrine and endocrine pancreas of the recently developed genetically diabetic OLETF rats are totally and specifically insensitive to exogenous and endogenous CCK stimulation, whereas parietal cells in these rats are sensitive to CCK stimulation.

Acute Disease↗
PubMed1996

Generalized peritonitis caused by spontaneous intraperitoneal rupture of the urinary bladder.

We report a case of generalized peritonitis caused by spontaneous intraperitoneal rupture of the urinary bladder. A 74-year-old female was admitted with abdominal pain and biochemical findings of acute renal failure (ARF). She had recently complained of macrohematuria. She had a past history of radiotherapy for uterine cervical cancer and Parkinson's disease treated with levodopa and amantadine. We diagnosed this case as intraperitoneal rupture of the bladder by cystogram. Biochemical findings of ARF might have resulted from urine reabsorption. Intraperitoneal rupture of the bladder should be considered in all cases of peritonitis, especially in patients with urological symptoms and features of ARF.

Aged↗
PubMed1996

Intrahepatic portosystemic venous shunt: report of two cases assessed by helical computed tomography.

BACKGROUND: Three-dimensional (3D) anatomic analysis was carried out, using helical computed tomography (helical CT), to evaluate its usefulness in two cases of large intrahepatic portosystemic venous shunt (IPSVS). METHODS: Case 1, a 74-year-old man with type-C hepatitis, underwent hepatic angiography to confirm suggested IPSVS of the left hepatic lobe in 1994. Case 2, a 62-year-old woman with liver cirrhosis associated with type-B hepatitis, was hospitalized for evaluation of suspected hepatocellular carcinoma in 1994. Hepatic angiography disclosed a large IPSVS in the right hepatic lobe. Retrospective evaluation of CT showed that the size of this shunt had increased over the 5 years 3D anatomic analysis was carried out, and the shunt vessels were clearly demonstrated. CONCLUSION: 3D anatomic analysis using helical CT was less invasive and useful for evaluating large IPSVS.

Aged↗
PubMed1996

Enlarging splenic vein aneurysm associated with stagnation of splenic venous blood flow.

We report a case of splenic vein aneurysm (SVA) that was enlarged during a 17-month follow-up. A 62-yr-old female with liver cirrhosis was followed up in our hospital. Real-time ultrasonography initially detected aechoic space at the middle part of the splenic vein, confirmed as SVA by contrast-enhanced computed tomography, magnetic resonance imaging and angiography. Magnetic resonance imaging showed the stagnation of blood flow in SVA, which suggests the presence of hypertension in the portal venous system. Moreover, SVA enlarged in parallel with the development of esophageal varices. These observations suggest that the persistent stagnation of blood flow in the portal venous system may have played a major role in the increase in size of the SVA in this case.

Aneurysm↗
PubMed1996

[Motor initiation difficulty of right upper extremity induced by tactile-stimulation after infarction in the left anterior cerebral artery territory].

We report a patient who manifested motor initiation difficulty of the right upper extremity, which was caused by tactile-stimulation on his right palm or back. The patient was a 62-year-old right-handed man, who showed reduction of spontaneous speech, slight paresis in the right lower extremity, and left unilateral ideomotor apraxia. He initially showed grasping reflex in the right hand, which disappeared in a month. MRI revealed infarction in the left medial frontal lobe and anterior-half of the corpus callosum. He complained that he was not able to initiate to move his right hand after his right palm or back touched something. He showed no paresis, no abnormal muscle tonus, no involuntary movement. Detailed examination revealed that it was an initiation disturbance caused by tactile-stimulation on his right palm or back. We concluded that this phenomenon, motor initiation difficulty, is one of the disturbances among motor process such as motor initiation, maintainance, and termination. The medial frontal lobe seems to manage the execution of motor process, therefore, lesions in the frontal lobe cause disturbance of motor process. And tactile-stimulation has a close relation to the reaction through the medial frontal lobe, thus, frontal lobe lesion may cause a misinteraction which retrieves a wrong reaction from a certain stimulation.

Arm↗
PubMed1996

[In vitro and in vivo antibacterial activities of sulopenem, a new penem antibiotic].

The in vitro and in vivo antibacterial activities of sulopenem, a new penem, were evaluated in comparison with imipenem (IPM), meropenem (MEPM), ceftazidime (CAZ) and flomoxef (FMOX). Sulopenem had broad and potent antibacterial spectra against Gram-positive and Gram-negative bacteria, including Enterococcus faecalis, Proteus vulgaris, Morganella morganii, Enterobacter spp. and Citrobacter freundii. Sulopenem showed concentration-dependent bactericidal activities against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Acinetobacter calcoaceticus. Morphological observation using phase-contrast microscope revealed that sulopenem induced spherical cell formation with E. coli and K. pneumoniae at lower concentrations and bacteriolysis at higher concentrations. Therapeutic efficacies of sulopenem against systemic infections in mice were almost equal to those of imipenem against Streptococcus pneumoniae. While its therapeutic efficacies were superior to those of meropenem, ceftazidime and flomoxef against S. aureus and S. pneumoniae, they were inferior to those of imipenem/cilastatin against S. aureus, K. pneumoniae and A. calcoaceticus.

Animals↗
PubMed1996

Pharmacological profile of a new serine derivative cholecystokinin receptor antagonist TP-680 on pancreatic, biliary and gastric function.

The in vivo pharmacological effects of the newly developed serine derivative [(R)-1-[3-(3-carboxypyridine-2-yl)thio-2-(indol-2-yl) carbonylamino]propionyl-4-diphenyl-methyl-piperazine] (TP-680), a cholecystokinin type-A (CCK-A) receptor antagonist, on pancreatic, biliary and gastric function were examined in rats and mice. The i.v. infusion of TP-680 in rats caused a parallel rightward shift of the entire dose-response curve for cholecystokinin octapeptide (CCK-8)-stimulated pancreatic exocrine secretion without altering the maximal response (ID50 = 480 nmol/kg). TP-680 also antagonized CCK-8-stimulated pancreatic secretion in mice (ID50 = 600 nmol/kg). Secretion of pancreatic juice and protein elicited by intraduodenal infusion of casein was also antagonized by TP-680. The CCK antagonism produced by i.v. TP-680 persisted for 16 h. Specificity for CCK was demonstrated by the inability of TP-680 (1000 nmol/kg) to antagonize either secretin- or bombesin-stimulated pancreatic secretion in rats. Moreover, specificity for CCK-A receptor was also demonstrated by the inability of TP-680 to antagonize pentagastrin-stimulated gastric acid secretion. Administered i.v., TP-680 was highly potent in antagonizing CCK-8-induced inhibition of gastric emptying (ID50 = 40 nmol/kg) but was less potent in antagonizing the contractile effects of CCK-8 on the gallbladder in mice (ID50 = 4000 nmol/kg). TP-680 also antagonized gallbladder contraction elicited by p.o. administered peptone. In the absence of exogenously administered CCK-8, TP-680 had no effect on any of the assay systems studied, which indicates a lack of CCK-like agonist properties. These results indicate that TP-680 is a potent, competitive and specific CCK-A receptor antagonist with long duration of action. The selectivity of TP-680 action depends on anatomical location of the CCK receptors (gastric emptying > pancreatic secretion > gallbladder contraction). This may provide a potentially valuable new tool for evaluating the role of CCK as a physiological mediator of GI function and its possible involvement in pathological states.

Animals↗
PubMed1996

[Effect of high dose interferon alpha-2b therapy for chronic hepatitis C].

We evaluated the efficacy of high dose interferon therapy in 122 patients with chronic hepatitis C between 1992 and 1995. They received 612 to 836 mega-units (MU) of recombinant interferon alpha-2b as a total dose during a 6-month treatment in our hospital. Fifty one patients (41.8%) achieved complete response (CR) which was defined as persistent normalization of serum aminotransferase levels and disappearance of serum HCV-RNA for more than 6 months after the end of interferon administration. However, there were no CR in patients with genotype II and in those with serum HCV-RNA levels above 1.5 Meq/ml, quantified by branched DNA probe assay. The rate of CR was not increased even if a total dose of IFN administration was increased from 612 MU to 836 MU. These results indicate that some new regimen of interferon therapy is necessary for these cases with high titer of serum HCV-RNA and genotype II to increase the rate of CR.

Adult↗
PubMed1996

[Relation between defect in comprehension and frontal lobe lesion].

We assessed anatomical findings and language defects in 14 right handed patients who had fluent aphasia following left frontal lobe lesion. From the onset of aphasia all of the patients showed fluent speech and excellent repetition but difficulty in word finding and impairment in language comprehension. We administered to all of the patients the Western Aphasia Battery, a 50-item pointing task using line drawings representing single words selected from among common Japanese words for language training for aphasics, and the Token Test. Anatomical analysis was performed using brain CT and/or MRI. The patients were divided into three groups on the basis of the extent of impairment in comprehension of single words: one group showed no impairment, another showed slight impairment and the other showed severe impairment. The lesion site differed among the groups. Each group had a different lesion site. We concluded the following: first, lesions in Brodmann's areas 6 and 9 produce impairment in comprehension of single words, with lesions extending to anterior to Broca's area producing more impairment than those without the extending lesions. Second, lesions in the frontal lobe produce impairment in comprehension of complex sentences.

Adult↗
PubMed1995

In vivo pharmacological study of spermine-induced neurotoxicity.

Spermine-induced neurotoxicity and its pharmacological manipulation was studied in the rat striatum in vivo. Spermine (50, 100, 250 nmol) was injected into the striatum and the volume of damage quantified by computer-based image analysis. Spermine produced a dose-dependent increase in the volume of damage. Co-administration of MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate; dizocilpine, 60 nmol), 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (25, 40 nmol) and pretreatment with pentobarbital (40 mg/kg, i.p.) significantly reduced the volume of damage induced by 100 nmol spermine. MK-801 (30 nmol) was also effective in reducing the damage induced by 50 nmol spermine. Treatment with a specific inhibitor of nitric oxide synthase, N omega-nitro-L-arginine methyl ester (50 mg/kg, i.p., twice daily for 10 days) was ineffective. These results suggest an involvement of both N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors in the cascade of spermine-induced neurotoxicity.

Animals↗
PubMed1995

Pericardiac metastasis from advanced gastric cancer.

A 64-year-old man complaining of anterior chest pain, weight loss, and neck tumors was found to have advanced gastric cancer with pleuritis carcinomatosa and multiple lymph node and bone metastases. The patient was treated with combination chemotherapy consisting of mitomycin C (MMC), tegafur (UFT), and lentinan, and then with MMC and 5-fluorouracil (5FU) instillation into the pleural spaces after pleural drainage. With these treatments, the primary tumors and cancerous ulcers of the stomach improved markedly, and the lymph node enlargement and pleural effusion disappeared completely. Afterwards pericardiac metastasis complicated by cardiac tamponade occurred, but repeated pericardiocentesis and administration of MMC into the pericardiac cavity effectively eliminated the effusion. These treatments appeared potentially useful for advanced gastric cancer with generalized metastases including pericardiac involvement. However, the patient died of cardiac tamponade with massive pericardiac bleeding, probably due to the repeated pericardiocentesis and/or the administration of anticancer drugs.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

A case of mesenteric venous thrombosis after endoscopic variceal band ligation.

A rare case of isolated superior mesenteric venous thrombosis (MVT) after endoscopic variceal band ligation (EVL) is reported. A 64-year-old woman with a history of idiopathic portal hypertension presented at the emergency room with vomiting, increasing cramping abdominal pain, and low-grade fever. She had undergone EVL for esophageal varices 4 months before and had had intermittent attacks of mild abdominal pain after the EVL. Ultrasonogram of the abdomen demonstrated marked concentric wall thickening of the ileal loop. Enhanced computed tomographic (CT) scan revealed a central lucency in the lumen of the superior mesenteric vein, surrounded by a high-density vein wall, corresponding to a thrombus. An isolated MVT and venous collateral network in the splanchnic area were confirmed by angiography. Supportive therapy, i.e., water and electrolyte replacement, and anticoagulation improved the clinical condition and radiologic status. This case of MVT after EVL suggests a possible relationship between EVL and MVT. It is necessary for clinicians to be aware of this relationship for the early diagnosis of MVT.

Endoscopy↗
PubMed1995

Chronic oral administration of synthetic trypsin inhibitor camostate reduces amylase release from isolated rat pancreatic acini.

In the present study, we examined stimulus-secretion coupling in pancreatic acini prepared from rats given synthetic protease inhibitor camostate at a dose of 200 mg/kg body wt by an orogastric tube once a day for 10 d. Camostate treatment significantly increased pancreatic weight, protein, DNA, and enzyme contents. In acini prepared from the camostate-treated rats, responsiveness to both CCK-8 and carbamylcholine was greatly decreased with no shift in the dose-response curves compared to control acini prepared from saline-treated rats. There were no major changes in the affinity for both high- and low-affinity sites of CCK receptors, but there was a significant reduction in the capacity of low-affinity site based on acinar protein. Responsiveness to secretin in the camostate-treated rat acini was also significantly reduced compared with that in the controls. However, amylase release from the camostate-treated rat acini in response to an increase in intracellular calcium levels induced by the calcium ionophores A23187 or to an increase in intracellular cyclic 3',5'-monophosphate (cyclic AMP) levels caused by 8 bromo cyclic AMP was not significantly different from the control rat acini, suggesting that both Ca(2+)-dependent tyrosine kinase and nucleotide-activated kinases are not impaired. On the other hand, the responsiveness to phorbol ester TPA, which stimulates amylase secretion via a calcium-independent cascade by activating protein kinase C directly, was reduced in the camostate-treated rat acini compared with the controls. These results suggest the possibilities that the reduced amylase secretion in the camostate-treated rats is owing to alterations in both the transmembrane signal transduction and the phosphorylation of regulatory proteins by the Ca(2+)-independent, protein kinase C-dependent mechanisms.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Effects of tetraprenylacetone on pancreatic exocrine secretion and acute pancreatitis in two experimental models in rats.

The effects of tetraprenylacetone (TPN), an acyclic polyisoprenoid with antiulcer actions, on pancreatic exocrine secretion, and its preventive and therapeutic effects on acute pancreatitis in two experimental models were studied in rats. Intraduodenal administration of TPN (0, 100, 200, and 400 mg/kg/h) caused dose-dependent increases in pancreatic juice and bicarbonate output without increasing protein output and plasma cholecystokinin (CCK) concentrations. TPN-stimulated pancreatic exocrine secretion was completely abolished by antisecretin serum but it was not by CCK receptor antagonist loxiglumide (50 mg/kg/h). In acute pancreatitis induced by four subcutaneous injections of 20 micrograms/kg cerulein at hourly intervals over, 3 h, TPN (400 mg/kg) given by an oral route either 1 h before the first cerulein injection or immediately after the last injection significantly reduced the increases in serum amylase and lipase activities and pancreatic wet wt. Pretreatment with TPN caused histologic improvements, whereas posttreatment failed to ameliorate histologic alterations. In severe type of acute pancreatitis induced by retrograde intraductal injection of 1.0 mL/kg of 4% sodium taurocholate, TPN exerted no apparent beneficial effects on biochemical and histologic alterations of acute pancreatitis. It is concluded that TPN given by an oral route stimulates pancreatic exocrine secretion through an increase in endogenous secretin release and causes beneficial effects on the experimental model of mild acute pancreatitis in rats.

Acute Disease↗
PubMed1995

Antibacterial properties of AM-1155, a new 8-methoxy quinolone.

AM-1155 is a new 8-methoxy quinolonecarboxylic acid with a broad spectrum of antibacterial activity. It inhibited more than 90% of clinical isolates of methicillin-susceptible Staphylococcus aureus, streptococci, Enterococcus faecalis, most of the Enterobacteriaceae, Acinetobacter calcoaceticus and Haemophilus influenzae at the concentration of 0.39 mg/L. AM-1155 was 2- to 16-fold more active than ciprofloxacin against Gram-positive organisms including methicillin-resistant staphylococci. The antibacterial activity of AM-1155 was almost equal to that of sparfloxacin against a wide range of Gram-positive and Gram-negative species. AM-1155 also showed a good activity against anaerobes. The protective efficacy of AM-1155 against experimental systemic infections with Gram-positive and Gram-negative pathogens in mice was almost equal or superior to that of sparfloxacin. AM-1155 was 5- to 28-times more effective than ciprofloxacin, in terms of ED50 at one week, in staphylococcal and streptococcal infections.

Animals↗