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Biomedical subjects

K Ochi

Publications and source records attributed to K Ochi.

At least 127 records · Page 7Linked to original sources

Clinical trial with a protease inhibitor gabexate mesilate in acute pancreatitis.

To evaluate whether early administration of protease inhibitors could improve mortality and morbidity in acute pancreatitis (AP), we made a retrospective analysis of 23 patients with severe AP and 88 with mild to moderate AP who were treated in our institute and four affiliated medical centers during the 10-y period from 1980 to 1990. Intravenous infusion of a protease inhibitor, Gabexate Mesilate (FOY), was started within 24 h from onset of AP (early administration) in 17 patients with severe AP and 51 with mild to moderate AP. The remaining patients were put on FOY later than 24 h from onset of AP (late administration). Comparison of the mortality and morbidity between the two groups, early vs late administration of FOY, led to the following conclusions: (1) Early administration of FOY significantly improved mortality (29.4 vs 83.3%) in severe AP, although the improvement in mortality was not directly proportional to the shortening of the time lag between the onset of AP and the start of FOY, and (2) earlier administration of FOY brought about significantly earlier recovery of abdominal pain, hyperamylasemia, and leucocytosis in mild to moderate AP.

Acute Disease↗

Polyacrylamide gel electrophoresis analysis of ribosomal protein AT-L30 as a novel approach to actinomycete taxonomy: application to the genera Actinomadura and Microtetraspora.

Actinomycete ribosomal protein AT-L30 exhibits electrophoretic mobility that is specific for each genus. On the basis of this fact, we analyzed ribosomal AT-L30 proteins from 26 type strains of species belonging to the genera Actinomadura and Microtetraspora. The electrophoretic mobilities of AT-L30 preparations from these strains, as determined by two-dimensional polyacrylamide gel electrophoresis, revealed that they could be divided into two groups, one group with relative electrophoretic mobilities of 14.0 to 41.5 and another group with relative electrophoretic mobilities of -6.5 to 0. The first group corresponded to the genus Actinomadura, and the second group corresponded to the genus Microtetraspora. Partial amino acid sequencing of AT-L30 preparations from several strains proved that we were indeed dealing with the specified protein homologous to ribosomal protein L30 of Escherichia coli. Our results strongly supported the conclusions of previous work and thus proved the efficacy of ribosomal protein analysis as a novel approach for taxonomy of actinomycetes.

Actinomycetales↗

Pleiotropic effects of a relC mutation in Streptomyces antibioticus.

Ochi (Agric. Biol. Chem. 51:829-835, 1987) has isolated a relaxed mutant of Streptomyces antibioticus, designated relC49, relC49 accumulates significantly lower levels of ppGpp than the parent stain, IMRU3720. At its maximum, the ppGpp level in relC49 was only one-fourth that observed in strain IMRU3720. Interestingly, a burst of ppGpp synthesis between 18 and 22 h of growth in IMRU3720 coincided with the onset of actinomycin production in that strain. As shown previously, the activity in protein synthesis of ribosomes from strain IMRU3720 decreases with the age of the culture. The decrease in activity was less pronounced in cultures of relC49. relC49 mycelium contains reduced levels of phenoxazinone synthase, a key enzyme involved in actinomycin biosynthesis. The rel mutation prevents the normal increase in the activity of one of the other enzymes required for production of the antibiotic, 3-hydroxyanthanilate-4-methyltransferase, and a third enzyme, actinomycin synthetase I, appears to be completely absent from relC49 mycelium. Levels of phenoxazinone synthease mRNA were examined by RNA dot blotting with the cloned phenoxazinone synthase gene as a probe. mRNA levels for phenoxazinone synthase were dramatically reduced in relC49 compared with strain IMRU3720. These results are discussed in terms of the possible regulation of the onset of actinomycin production by ppGpp.

Dactinomycin↗

Long-term follow-up of electrocochleogram in Ménière's disease.

Serial electrochochleogram (ECochG) recordings were obtained over a long time span from 24 patients with Ménière's disease showing dominant negative SP. The long-term fluctuation of responses (especially SP) was evaluated. Dominant -SP or abnormally increased SP/AP ratio has been unchanged over long periods in most operated or nonoperated patients. It is assumed that the generation of -SP dominance may chiefly result from the malfunction of hair cells, which may be caused by abnormal changes in inner ear fluids associated with endolymphatic hydrops or by other unknown disturbances in the cochlea. The mechanical factor of basilar membrane displacement can hardly be considered as a main cause of SP abnormality.

Audiometry, Evoked Response↗

[Aging and exocrine pancreatic function evaluated by the recently standardized secretin test].

The authors studied the relationship between aging and exocrine pancreatic function by the secretin test which was recently standardized by the Japanese Society of Gastroenterology. Pancreatic juice was collected at 10 min intervals for 60 minutes after a bolus intravenous injection of secretin (Secrepan, Eisai Co., Ltd., 100 U/body) through a quadruple-lumen doudenal tube equipped with double balloons. Exocrine pancreatic function was evaluated by three parameters: secretory volume, maximal bicarbonate concentration or bicarbonate output, and enzyme (amylase and lipase) output. Control subjects consisted of 65 outpatients presenting with mild vague abdominal symptoms who fulfilled the following three criteria: 1) good general condition with no known diseases; 2) no abnormality in the liver, bile duct, pancreas, kidney and metabolism judged from blood chemistry, urine and stool analysis, upper GI series, abdominal ultrasonography (US), and endoscopic retrograde cholangiopancreatography (ERCP); 3) alcohol consumption less than 25 g/day. Control subjects were divided into three groups: 15 subjects below 40 years of age (group A), 32 subjects from 40 to 65 years (group B), and 18 subjects of 65 years and above (group C). Nineteen patient with chronic pancreatitis were also studied. The group C showed significantly lower values in secretory volume, bicarbonate output, and enzyme output than group A and B. Enzyme output showed a gradual decrease with aging. However, secretory volume and bicarbonate output showed a gentle convex curve with a peak around age 40 and a rather steep down-slope after late 50s. The degree of the decrease was significantly more marked in volume and bicarbonate output than in enzyme output in group C.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A relaxed (rel) mutant of Streptomyces coelicolor A3(2) with a missing ribosomal protein lacks the ability to accumulate ppGpp, A-factor and prodigiosin.

A relaxed (rel) mutant was found among 70 thiopeptin-resistant isolates of Streptomyces coelicolor A3(2) which arose spontaneously. The ability of the rel mutant to accumulate ppGpp during Casamino acid deprivation was reduced 10-fold compared to the wild-type. Analysis of the ribosomal proteins by two-dimensional PAGE revealed that the mutant lacked a ribosomal protein, tentatively designated ST-L11. It was therefore classified as a relC mutant. The mutant was defective in producing A-factor and the pigmented antibiotic prodigiosin, in both liquid and agar cultures, but produced agarase normally. Production of actinorhodin, another pigmented antibiotic, was also abnormal; it appeared suddenly in agar cultures after 10 d incubation. Although aerial mycelium still formed, its appearance was markedly delayed. Whereas liquid cultures of the parent strain accumulated ppGpp, agar cultures accumulated only trace amounts. Instead, a substance characterized only as an unidentified HPLC peak accumulated intracellularly in the late growth phase, just before aerial mycelium formation and antibiotic production. This substance did not accumulate in mutant cells. It was found in S. lividans 66 and S. parvulus, but not in seven other Streptomyces species tested. The significance of these observations, and the relationship of the mutant to earlier rel isolates of Streptomyces is discussed.

Anthraquinones↗

Streptomyces relC mutants with an altered ribosomal protein ST-L11 and genetic analysis of a Streptomyces griseus relC mutant.

Several relaxed (rel) mutants have been obtained from Streptomyces species by selecting colonies resistant to thiopeptin, an analogue of thiostrepton. Using two-dimensional gel electrophoresis, I compared the ribosomal proteins from rel and rel+ pairs of S. antibioticus, S. lavendulae, S. griseoflavus, and S. griseus. It was found that all of the Streptomyces rel mutants thus examined had an altered or missing ribosomal protein, designated tentatively ST-L11. These rel mutants therefore could be classified as relC mutants and were highly sensitive to erythromycin or high temperature. A relC mutant of S. griseus was defective in streptomycin production, but phenotypic reversion of this defect to normal productivity was found at high incidence among progeny of the relC mutant. This phenotypic reversion did not accompany a reappearance of ribosomal protein ST-L11, and furthermore the ability of accumulating ppGpp still remained at a low level, thus suggesting existence of a mutation (named sup) which suppresses the streptomycin deficiency phenotype exhibited by the relC mutant. Genetic analysis revealed that there is a correlation between the rel mutation and the inability to produce streptomycin or aerial mycelia. The sup mutation was found to lie at a chromosomal locus distinct from that of the relC mutation. It was therefore concluded that the dependence of streptomycin production on the normal function of the relC gene could be entirely bypassed by a mutation at the suppressor locus (sup). The suppressing effect of the sup mutation on the relC mutation was blocked when the afs mutation (defective in A-factor synthesis) was introduced into a relC sup double mutant. It is proposed that the sup gene or its product can be direct or indirect target for ppGpp.

Anti-Bacterial Agents↗

The tsr gene-coding plasmid pIJ702 prevents thiopeptin from inhibiting ppGpp synthesis in Streptomyces lividans.

Streptomyces lividans normally accumulated high levels of ppGpp during nutritional shift-down. Its accumulation was, however, severely inhibited when a small amount of thiopeptin (an analogue of thiostrepton) was included in the transfer medium. In contrast, a S. lividans strain, which harbours the plasmid pIJ702 carrying the tsr gene resist to thiopeptin through methylation of the 23S rRNA, was still capable of accumulating ppGpp in the presence of large amounts of thiopeptin. These results indicate that the rRNA methylation resulting from the action of tsr gene prevents thiopeptin not only from inhibiting cell-growth but also from inhibiting ppGpp synthesis. The results also indicate that the observed accumulation of ppGpp during nutritional shift-down was associated with ribosomal function, as has been shown in E. coli and B. subtilis.

Anti-Bacterial Agents↗

Prognosis and prognostic factors in chronic pancreatitis.

To evaluate the prognosis and prognostic factors of chronic pancreatitis, 84 patients with alcoholic chronic pancreatitis and 51 with nonalcoholic chronic pancreatitis have been followed for 1-21 years (average of 7.1 years). The follow-up period was defined as the period from diagnosis to death in those who died and to the present in those still alive. The following conclusions were obtained. (1) Patients with alcoholic chronic pancreatitis showed a significantly higher mortality rate (26.2%) and cancer death rate (8.3%) than the age- and sex-matched population. In patients with nonalcoholic chronic pancreatitis, however, the difference did not reach the level of statistical significance, although both rates tended to be higher. (2) Patients with alcoholic chronic pancreatitis showed a significantly poorer prognosis than those with nonalcoholic chronic pancreatitis. (3) Frequent causes of death in chronic pancreatitis were cancer (11 cases) and diabetes-associated conditions (renal failure in three cases, intractable pneumonia in one, hypoglycemic shock in two, and myocardial infarction in two). Death directly from pancreatitis was observed in four. (4) Unfavorable prognostic factors in alcoholic chronic pancreatitis included heavy drinking, continuance of drinking after diagnosis, smoking, insulin-dependent diabetes, and an advanced age. In nonalcoholic chronic pancreatitis, however, patients' age was the only significant prognostic factor; smoking did not reach the level of statistical significance, although it tended to lead to a poorer prognosis.

Adult↗

Heterogeneity of ribosomal proteins among Streptomyces species and its application to identification.

The ribosomal proteins from 11 Streptomyces strains representing various numerical taxonomic clusters were compared by two-dimensional PAGE. The protein patterns were specific for each species and were unaffected by acridine dye treatment, suggesting genetic stability of ribosomal proteins. An attempt was made to identify one strain of Streptomyces by both traditional taxonomic methods and analysis of the ribosomal protein patterns. Both methods identified the strain as Streptomyces lavendulae, and protein pattern analysis also showed that Streptomyces avidinii was closely related to this species. The practical application of ribosomal protein patterns in Streptomyces taxonomy was therefore demonstrated.

Bacterial Proteins↗

Cefotiam disposition in markedly obese athlete patients, Japanese sumo wrestlers.

Markedly obese athletes like Japanese sumo wrestlers may frequently suffer various traumas which result in the prophylaxis or treatment of posttraumatic infection with antibiotics. However, appropriate dosage regimens in this group of patients have not been fully known for many antibiotics. Therefore, we studied the kinetic disposition of cefotiam, a parenteral, broad-spectrum cephalosporin with activity against gram-positive and -negative bacteria, after an intravenous dose (2 g) infused over 30 min into 15 sumo wrestler patients with an excess body weight (130 to 220% of ideal body weight) and 10 control patients with a normal weight (90 to 102% of ideal body weight). Mean (+/- standard deviation) clearance and steady-state volume of distribution were significantly greater in the sumo wrestler than in the control group (38.3 +/- 9.4 versus 23.5 +/- 6.0 liters/h, P less than 0.001, and 30.2 +/- 8.0 versus 17.9 +/- 6.1 liters, P less than 0.001). Mean elimination half-life was slightly but significantly longer in the sumo wrestler than in the control group (0.91 +/- 0.14 versus 0.74 +/- 0.20 h, P less than 0.05). However, mean residence time did not differ between the two groups (0.79 +/- 0.10 versus 0.75 +/- 0.14 h). The statistical differences in clearance and volume of distribution between the two groups disappeared when these kinetic parameters were corrected for body surface area, but not for total body weight or ideal body weight. The results suggest that the dosage calculation of cefotiam, a hydrophilic antibiotic, should be made on the basis of body surface area in morbidly obese athlete or sumo wrestler patients. However, whether this recommendation should extend to other nonathlete obese subjects remains to be determined.

Adult↗

Reaction of (R)-(-)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato)platinum( II) with guanosine.

The reaction of a new antitumor platinum complex, (R)-(-)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +)platinum(II) (1) with guanosine at room temperature in an aqueous solution was followed by proton nuclear magnetic resonance (1H-NMR) spectroscopy and high performance liquid chromatography (HPLC) at intervals. Both techniques showed that a new compound was formed by displacement of the 1,1-cyclobutanedicarboxylate moiety of 1 with two guanosines, and its 1H-NMR spectrum and HPLC chromatogram were proved to be identical with those of [(R)-(-)-2-aminomethylpyrrolidine]bis(N7-guanosine)platinum(II) (2), which was obtained upon successive treatment of (R)-(-)-2-aminomethylpyrrolidinedichloroplatinum(II) (3) with AgNO3 and 2 mol eq of guanosine in water. The binding sites of the platinum to the two guanosine moieties in 2 were confirmed by the pH dependence of the two G-H8 signals.

Carboplatin↗

Inhibitory effect of calcitonin on pure human pancreatic secretion.

The inhibitory effect of calcitonin on human pancreatic secretion was evaluated to examine whether the different results reported earlier between humans, cats and dogs can be ascribed to the different sensitivity of these species to calcitonin, as suggested by some investigators. Pancreatic juice was obtained by endoscopic cannulation of the pancreatic duct from 11 patients with relapsing pancreatitis during intravenous infusion of secretin (1 U/kg/h) plus caerulein (0.04 microgram/kg/h). After steady secretion was attained 20 min after the beginning of collection, five 2-min fractions were obtained before, and ten 2-min fractions were obtained after intravenous infusion of calcitonin (1 IU/kg/h). The pre- and post-calcitonin fractions from each patient were compared by Student's t-test. Calcitonin inhibited the secretory volume (26.8 to 65.6%) and bicarbonate secretion (21.4 to 62.0%) in 8 patients, and amylase (48.4 to 89.5%) and lipase secretion (47.4 to 90.5%) in all patients. The present studies reconfirmed that prominent inhibition of enzyme secretion occurs in humans. A new finding was that significant inhibition of the secretory volume and bicarbonate secretion occurs in humans. The inhibitory effects of calcitonin in humans did not appear to differ from those in cats and dogs, when evaluated similarly with the use of pure pancreatic juice.

Aged↗

[Aging and exocrine pancreatic function].

To evaluate the effect of aging on exocrine pancreatic function, fecal chymotrypsin activity (FCA) was measured by a photometric method in 62 healthy controls (20 to 87 years old, average 51.0 years), 42 patients with non-pancreatic diseases (31 to 83 years old, average 56.1 years), 40 controls in an old-age home (63 to 92 years old, average 77.6 years), 20 patients with definite chronic pancreatitis (17 to 72 years old, average 53.5 years) and five patients with pancreatic cancer (60 to 76 years old, average 65.4 years). Exocrine pancreatic function showed a significant decrease with aging as indicated by: (a) a significant inverse correlation between aging and FCA in the 62 healthy controls (r = -0.56, p less than 0.001), in the 42 patients with non-pancreatic diseases (r = -0.59, p less than 0.001), and also in the 40 controls in an old-age home (r = -0.52, p less than 0.001); and (b) a significantly lower FCA in the 21 healthy controls aged 65 or more (designated as the B group of healthy controls) than the 41 healthy controls aged less than 65 (designed as the A group of healthy controls). The 40 controls in an old-age home showed significantly lower FCA than the B group of healthy controls. This result was ascribed to the fact that the former group consisted of significantly older subjects than the latter. No significant difference was found in FCA between patients with chronic pancreatitis, those with pancreatic cancer, the B group of healthy controls, and the controls in an old-age home.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Exocrine pancreatic function test by endoscopic retrograde aspiration of pure pancreatic juice.

The validity of endoscopic retrograde aspiration of pure pancreatic juice (PPJ) as an exocrine pancreatic function test was evaluated in terms of coefficients of variation in control subjects, reproducibility on repeated examinations, and sensitivity for detecting patients with chronic pancreatitis (CP). PPJ was obtained from, nine control subjects, four patients with suspected CP and 13 with CP. PPJ was collected from within the pancreatic duct by endoscopic retrograde catheterization of the papilla at 2-min intervals for 20 minutes after a bolus intravenous injection of secretin (1U/kg) and then for further 20 minutes after a bolus intravenous injection of CCK-PZ (1U/kg). It was recognized that endoscopic aspiration of PPJ was at least as useful and reliable as the traditional pancreozymin secretin test. Useful parameters included 10-min secretory volume and 10-min bicarbonate output after secretin stimulation, and 10-min enzyme output after CCK-PZ stimulation (lipase output showed higher sensitivity than amylase output). Maximal bicarbonate concentration showed poorer reproducibility and sensitivity despite better coefficients of variation. Lower limits in controls (mean-1.5SD) were 22.5ml for 10-min secretory volume, 2.7mEq for 10-min bicarbonate output, 24.5 x 10(3)U for 10-min amylase output and 3.4 x 10(3)IU for 10-min lipase output.

Adult↗

The organic matrix of urinary uric acid crystals.

We have demonstrated that urinary uric acid crystals contain an organic matrix within the crystalline boundaries, morphologically similar to that of uric acid stones. Among several glycosaminoglycans in urine, heparan sulfate was almost exclusively identified in this matrix, as in that of uric acid stones. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showed that several proteins in urine were incorporated in this matrix on a selective basis; two of which were albumin and Tamm-Horsfall mucoprotein. An affinity of uric acid or urate for selective urinary macromolecules in a liquid phase was supposed to be the origin of this matrix. But the proteins in the uric acid stone matrix were not separated by SDS-PAGE. Therefore we could not conclude whether the organic matrix of urinary uric acid crystals is similar to that of uric acid stones.

Crystallization↗