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Biomedical subjects

M Shibata

Publications and source records attributed to M Shibata.

At least 703 records · Page 39Linked to original sources

Mechanism of interference between influenza A/WSN and B/Kanagawa viruses.

Simultaneous infection of MDCK cells with influenza viruses A/WSN and B/Kanagawa resulted in mutual interference with virus protein synthesis and in significant suppression of A/WSN growth. When infection by one virus preceded the other by 1 or 2 h, growth of the superinfecting virus was selectively inhibited at the level of transcription. Interference by the pre-infecting virus was strongly dependent on the expression of the viral genome but not on haemagglutinin activity. When the replication of both virus types was restricted to primary transcription by cycloheximide, the only translation products following removal of the drug were those of the preinfecting virus. This result was not affected by blocking secondary transcription by actinomycin D. These findings suggest that intertypic interference occurs at the level of primary transcription. This concept was supported further by the observation that a ts mutant of A/WSN (ts-65) with a defect in primary transcription interfered only with superinfection by B/Kanagawa at the permissive temperature.

Animals↗

Isolation of Rickettsia tsutsugamushi antigenically different from Kato, Karp, and Gilliam strains from patients.

Rickettsia tsutsugamushi strains from three recent patients of Tsutsugamushi disease in Niigata Prefecture were isolated primarily in mice and then in L cell cultures. By this procedure, low virulent strains to mice, as well as high virulent ones, could be isolated and cultivated serially in L cell cultures, suggesting the usefulness of L cells for isolation of this species of rickettsia. Each newly isolated strain was identified as a member of R. tsutsugamushi from the results of cross immunological tests and morphological observation. On the other hand, it was recognized that one of these rickettsiae showed immunological properties distinguishable from the prototype strains of Kato, Karp, and Gilliam by the cross complement fixation test, and also had low virulence in mice.

Animals↗

Production of leukocidin by clinical isolates of Pseudomonas aeruginosa and antileukocidin antibody from sera of patients with diffuse panbronchiolitis.

The ratio of leukocidin-producing strains to clinical isolates of Pseudomonas aeruginosa was investigated together with the production of protease, elastase, and exotoxin A. We also examined whether these strains contain the common antigen which resides in the cell wall. By using the agar gel diffusion test with specific antisera, we found that 87 of 90 (96.7%) of clinical isolates produced leukocidin. Protease, elastase, and exotoxin A were also produced at high percentages. The common antigen was found to exist in all strains. Next, to estimate antileukocidin antibody in the sera of patients, we used an enzyme-linked immunosorbent assay with horseradish peroxidase-protein A. The sera of 39 patients with diffuse panbronchiolitis (DPB) were investigated for antileukocidin antibody. The mean antileukocidin titer in the sera of 17 DPB patients who were not infected with P. aeruginosa and 5 DPB patients who were transiently infected with the bacteria was about the same as the mean antileukocidin titer in the sera of 11 healthy controls, whereas the mean antileukocidin titer in the sera of 17 DPB patients who were persistently colonized was significantly higher than that in healthy controls. These results indicate that leukocidin was produced at the local site of infection in DPB patients.

Antibodies, Bacterial↗

Immunological and genomic analyses of two serotypes of avian paramyxovirus isolated from wild ducks in Japan.

A total of 11 avian paramyxoviruses isolated from migrating feral ducks in Niigata, Japan, were characterized by serological and genomic analyses. Hemagglutination inhibition and immuno-double-diffusion tests with antisera specific for the isolated hemagglutinin-neuraminidase polypeptides of reference strains indicated that, of these, eight isolates possessed hemagglutinin-neuraminidase antigen closely related to that of duck/Hong Kong/D3/75, and the remaining three isolates possessed antigen closely related to that of duck/Hong Kong/199/77. RNA analysis of the eight isolates identified serologically as duck/Hong Kong/D3/75 by oligonucleotide mapping revealed that these isolates were genetically very similar to each other but different from the reference strain and isolates reported previously. The oligonucleotide maps of duck/Hong Kong/199/77-like isolates appeared to be very similar to each other, suggesting the same origin, but not to the duck/Hong Kong/199/77 virus.

Animals↗

[Studies on sulbactam/cefoperazone in the field of pediatrics].

Microbiological, pharmacokinetic and clinical studies on sulbactam/cefoperazone (SBT/CPZ) were carried out in the field of pediatrics. Antimicrobial activity The MIC80 of SBT/CPZ was 6.25 micrograms/ml for clinically isolated 24 strains of S. aureus (24 beta-lactamase producing strains), 0.39 micrograms/ml for 17 strains of S. pyogenes, 3.13 micrograms/ml for 24 strains of E. coli (22 beta-lactamase producing strains), 3.13 micrograms/ml for 22 strains of K. pneumoniae (22 beta-lactamase producing strains), 1.56 micrograms/ml for 22 strains of P. mirabilis and 0.20 microgram/ml for 15 strains of H. influenzae (13 beta-lactamase producing strains). In comparison with CPZ in respect to the MIC, SBT/CPZ exhibited synergistic effect on 31 strains out of 81 beta-lactamase producing strains (included 6 strains of S. aureus, 9 of E. coli, 5 of K. pneumoniae and 11 of H. influenzae) which was scarcely observed against 43 non-beta-lactamase producing strains. Absorption and excretion Serum levels and urinary excretion of SBT/CPZ were studied in 7 children aged 5 to 12 years. The mean serum concentration of SBT at 15 minutes following a single intravenous injection of 10 mg/kg of SBT/CPZ was 14.2 micrograms/ml and that of CPZ was 30.4 micrograms/ml. The mean urinary recovery rates at 6 hours following the intravenous injection were 57.8% and 18.3%, respectively. The mean serum concentrations of SBT and CPZ after 1-hour infusion of 10 mg/kg of SBT/CPZ were 10.9 micrograms/ml and 17.6 micrograms/ml, respectively. The urinary recovery rates of SBT and CPZ at 7 hours after the infusion were 100.0% and 27.7% on average, respectively. The mean serum levels of SBT and CPZ at 15 minutes after a single intravenous injection of 20 mg/kg of SBT/CPZ were 25.6 micrograms/ml and 66.0 micrograms/ml, respectively and urinary elimination until up to 6 hours were 72.5% on average for SBT and 21.1% for CPZ. Clinical study SBT/CPZ was used for the treatment of a total of 20 pediatric patients aged 1 month to 14 years to evaluate its clinical effectiveness, bacteriological efficacy and adverse effects. The clinical efficacy in 6 patients with acute pneumonia, 3 with staphylococcal scalded skin syndrome, 2 each with acute purulent tonsillitis and acute pyelonephritis, 1 each with acute purulent lymphadenitis, acute sinusitis, acute bronchitis, peritonitis and acute enteritis was judged to be excellent in 15 cases and good in 3 cases with an efficacy ratio of 100%. The clinical efficacy in 6 patients whose infections were caused by beta-lactamase producing strains was judged to be excellent in all the cases.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗

[Fundamental and clinical evaluation of ceftriaxone in the pediatric field].

Fundamental and clinical evaluation of ceftriaxone (Ro 13-9904, CTRX) was performed in the pediatric field. Antibacterial activity The MIC80 of CTRX against clinical isolates such as S. aureus (23 strains), S. pyogenes (23 strains), E. coli (20 strains), K. pneumoniae (23 strains), H. influenzae (15 strains) and P. aeruginosa (23 strains) were 6.25 micrograms/ml, 0.024 microgram/ml, 0.20 microgram/ml, 0.05 microgram/ml, less than or equal to 0.006 microgram/ml and 12.5 micrograms/ml, respectively. The antibacterial activity of CTRX was therefore poor against S. aureus and P. aeruginosa, but quite excellent against S. pyogenes, E. coli, K. pneumoniae and H. influenzae. Compared with cefotaxime (CTX), cefoperazone (CPZ), cefmetazole (CMZ), cefazolin (CEZ) and ceftazidime (CAZ), CTRX was the highest in the antibacterial activity against H. influenzae, next to CTX against S. pyogenes, E. coli and K. pneumoniae, similar to CTX, CPZ and CAZ against S. aureus and similar to CTX against P. aeruginosa. Absorption, Excretion The mean serum levels of CTRX after an intravenous one shot injection with about 20 mg/kg in 3 children aged 10 to 14 years were 160.0 +/- 23.3 micrograms/ml after 1/4 hour, 134.3 +/- 27.5 micrograms/ml after 1/2 hour, 115.0 +/- 33.2 micrograms/ml after 1 hour, 95.3 +/- 28.4 micrograms/ml after 2 hours, 75.3 +/- 14.5 micrograms/ml after 4 hours, 30.3 +/- 13.5 micrograms/ml after 12 hours and 8.2 +/- 3.1 micrograms/ml after 24 hours, while the half-life time was 5.92 +/- 0.43 hours on the average. The mean urinary levels were 1,060 +/- 461 micrograms/ml from 0 to 2 hours, 309 +/- 122 micrograms/ml from 2 to 4 hours, 375 +/- 83 micrograms/ml from 4 to 6 hours, 237 +/- 77 micrograms/ml from 6 to 12 hours and 122 +/- 23 micrograms/ml from 12 to 24 hours, the mean urinary recovery rate up to 24 hours being 38.9 +/- 13.6%. The concentration in the cerebrospinal fluid The mean levels of CTRX in the cerebrospinal fluid of the patients with purulent meningitis were 4.30 +/- 4.22 micrograms/ml 1 hour after an intravenous one shot injection with 42 to 51 mg/kg, 4.64 +/- 3.53 micrograms/ml after 3 1/2 hours to 6 hours, 3.79 +/- 2.15 micrograms/ml after 7 1/2 hours to 12 hours and 1.79 +/- 0.23 microgram/ml after 19 hours.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

[Fundamental and clinical studies on ceftazidime in the field of pediatrics].

Fundamental and clinical studies were carried out on ceftazidime ( CAZ ), a new cephalosporin, in the field of pediatrics. 1. Antimicrobial activity MICs of CAZ were determined for clinical isolates of 24 strains of S. aureus, 15 of S. pyogenes, 8 of H. influenzae, 22 of E. coli, 20 of K. pneumoniae, 18 of P. mirabilis, 3 of P. morganii, and 21 of P. aeruginosa, and compared with those of the control drugs, i.e. CEZ, CXM, CMZ, CTX, LMOX and CMX. For P. aeruginosa, CPM, CFS and GM were also employed as the control drugs. CAZ was as active as CTX, LMOX and CMX, its MICs distributing in the range not higher than 0.10 microgram/ml for H. influenzae, 0.78 microgram/ml for E. coli, 0.39 microgram/ml for K. pneumoniae, 0.10 microgram/ml for P. mirabilis, and 0.10 microgram/ml for P. morganii in all the strains. Against P. aeruginosa, CAZ showed MICs in the range between 0.39 and 3.13 micrograms /ml, which showed activity higher than that of CTX, LMOX , CPM, CMX and GM, and comparable to that of CFS. Against S. pyogenes, CAZ was as active as all the control drugs except for LMOX , its MICs for all strains tested being 0.20 microgram/ml or below. Against S. aureus, CAZ was slightly more active than LMOX , but less active than the other control drugs, its MICs being relatively high ranging from 6.25 to 50 micrograms/ml. 2. Pharmacokinetics After a one-shot intravenous injection of CAZ 20 mg/kg, serum levels and urinary excretion were studied in 3 children aged 6 to 9 years, and CSF levels were determined in 2 children aged 6 to 7 years with aseptic meningitis. The mean serum levels of CAZ were 85.3 micrograms/ml at 1/4 hour, 53.3 micrograms/ml at 1/2 hour, 32.0 micrograms/ml at 1 hour, 16.1 micrograms/ml at 2 hours, 5.3 micrograms/ml at 4 hours, and 2.0 micrograms/ml at 6 hours, with the mean half-life of 1.18 hours. The mean urinary levels were 9,700 micrograms/ml at 0 to 2 hours, 803 micrograms/ml at 2 to 4 hours, 540 micrograms at 4 to 6 hours, and the mean urinary recovery rate during the first 6 hours was 83.9%. The CSF levels at 1 hour after intravenous injection were 0.44 microgram/ml in acute stage and 0.10 to 0.22 microgram/ml in convalescent stage. 3. Clinical study Thirty-one pediatric patients with bacterial infections were treated with CAZ , and the clinical efficacy, bacteriological response, and side effects were evaluated.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

Effects of 12-O-tetradecanoylphorbol-13-acetate on carcinogenesis in the heterotopically transplanted rat urinary bladder.

12-O-Tetradecanoylphorbol-13-acetate (TPA), a potent promoter of mouse skin carcinogenesis, was tested for possible tumor-enhancing effects on urinary bladder carcinogenesis using the heterotopically transplanted bladder (HTB) model. Weekly administration of TPA at 1.0 microgram/week to N-methyl-N-nitrosourea-initiated HTBs did not increase tumor incidence, but instead, resulted in a significantly high incidence of nodulopapillary hyperplasia, an early neoplastic lesion, suggesting possible tumor enhancement by TPA. In addition, administration of a high dose of TPA with or without a carcinogen treatment led to the development of numerous finger-like epithelial projections on the luminal surface of the HTBs. Evidence indicates that epithelial projections are formed as a result of proliferation of intermediate cells. Whether these structures evolve into true neoplastic lesions is at present unknown.

Animals↗

Effects of three sweeteners on rat urinary bladder carcinogenesis initiated by N-butyl-N-(4-hydroxybutyl)-nitrosamine.

The effects of three sweeteners, sodium saccharin, aspartame and stevioside, on urinary bladder carcinogenesis in rats initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were evaluated. Male F344 rats were given 0.01% BBN in their drinking water for 4 weeks and then the test sweeteners in their diet for 32 weeks. All surviving rats were sacrificed after 36 weeks, and examined histologically. Treatment with sodium saccharin significantly increased the incidence and extent of preneoplastic lesions, papillary or nodular (PN) hyperplasia, in rats treated with BBN for 4 weeks. Administration of 5% aspartame or 5% stevioside in the diet did not, however, affect the incidence or extent of PN hyperplasia in BBN-treated rats. No preneoplastic or neoplastic lesions of the urinary bladder were observed in rats treated with the test sweeteners only. The results with sodium saccharin were consistent with those in our previous experiments. The data also suggest that aspartame and stevioside do not promote bladder carcinogenesis.

Animals↗

Carcinogenicity of captafol in B6C3F1 mice.

The potential carcinogenicity of captafol in B6C3F1 mice was examined. Captafol was given at levels of 0 (control), 0.075, 0.15 or 0.3% in the diet to a total of 203 males and 203 females for 96 weeks, after which time the animals were returned to basal diet for a further 8 weeks. Mice surviving 42 weeks or longer were included in the effective numbers. Males and females given 0.3% captafol showed increased cumulative mortalities in the final quarter period of the experiment. Significant increases in the development of neoplastic lesions were found in the heart, spleen, forestomach, small intestine and liver of mice of both sexes treated with captafol. Tumors induced by captafol were, histologically, hemangioendothelioma in the heart, hemangioma or hemangioendothelioma in the spleen, papilloma and squamous cell carcinoma in the forestomach, adenoma and adenocarcinoma in the small intestine, and hyperplastic nodule and hepatocellular carcinoma in the liver. These results demonstrate a broad-spectrum carcinogenicity of captafol in B6C3F1 mice.

Animals↗

[Formalin-induced minor tremor response as an indicator of pain].

Formalin which was said to produce prolonged pain and inflammation was injected subcutaneously into the back of guinea pigs, and minor tremor pain response (MTP-response) was measured using the MT-pick up, integrator and digital volt meter. The MTP-response curve showed a biphasic pattern. Immediately after injection, the MTP-response curve showed a significant peak which lasted for about 2 min (the first phase) and subsequently dipped rapidly, and after 5 min, it began to rise slowly again and had a peak at 30 min (the second phase). Morphine (6 mg/kg, s.c.) inhibited completely the first and second phases. Levallorphan (1.2 mg/kg), however, reversed the inhibitory effect of morphine at the first phase, but not at the second phase. Aspirin (200 mg/kg, i.p.), aminopyrine (100 mg/kg, s.c.) and pentazocine (5 mg-10 mg/kg, s.c.) inhibited significantly the formalin-induced MTP-response at both phases. Pyridinol carbamate (200 mg/kg, i.p.) and hydrocortisone (25 mg/kg, i.p.) had no effect on the MTP-response at the first phase, but inhibited it at the second phase. There was a parallelism between the time course of the vascular permeability induced by formalin and that of the second phase of MTP-response. From these results, it is suggested that the first phase of MTP-response is derived from the direct effect of formalin on free nerve endings, while the second phase is derived from the inflammation. Since two kinds of pain features were differentiated in this method, the relationships with so-called "immediate pain" and "delayed pain" were discussed. Furthermore, this method can be utilized to assess pain and the action of analgesics objectively and quantitatively.

Aminopyrine↗

A role of elementary interactions between nucleic-acid base and amino-acid side chains in specificity of ribonuclease.

Several X-ray structures of model crystals that contain hydroxyl group and nucleic-acid bases suggest that hydroxyl group interacts preferentially with pyrimidines than with purines through hydrogen bonds. This explains a role of Thr 45 and Ser 123 at the B1 site of RNAase A. The stacking energies of nucleic-acid bases with the protonated imidazolyl group are estimated to be in the order of C greater than A greater than G greater than U from 1H-NMR spectra and CNDO/2 calculations. Such interactions, in addition to hydrogen bondings, would stabilize the binding of substrates at the B2 site.

Amino Acids↗

Interferon-inducing, pyrogenic and proclotting enzyme of horseshoe crab activation activities of chemically synthesized lipid A analogues.

Interferon-inducing, pyrogenic and proclotting enzyme of horseshoe crab activation activities of chemically synthesized lipid A analogues were investigated and compared with the same activities of a natural lipid A. These analogues are nonphosphorylated, C-1 or C-4' monophosphorylated and C-1,4' bisphosphorylated derivatives of beta-1,6-linked D-glucosamine disaccharide possessing both ester-bound and amide-bound fatty acid substituents. Fatty acid substituents of the analogues are tetradecanoyl (C14), (R)-3-hydroxytetradecanoyl (C14-OH) or (R)-3-tetradecanoyloxytetradecanoyl [C14-O-(C14)] groups. The biological activities of the samples were assayed after solubilization with triethylamine and complexing with bovine serum albumin. Interferon-inducing activity was exhibited by both the C-1 monophosphorylated compounds examined. Ester-bound and amide-bound fatty acid substituents of these compounds are both C14 or C14 and C14-OH, respectively. Nonphosphorylated, C-4' monophosphorylated and C-1,4' bisphosphorylated compounds possessing the same fatty acid substituents as those of the C-1 monophosphorylated compounds showed no detectable interferon-inducing activity. C-4' monophosphorylated compounds possessing C14-OH as ester-bound and C14-OH or C14-O-(C14) as amide-bound fatty acid substituents exhibited interferon-inducing activity, but nonphosphorylated compounds possessing the same fatty acid substituents did not. None of the analogues exhibited significant pyrogenicity nor proclotting enzyme of horseshoe crab activation activity under the conditions employed in this study.

Animals↗

Electric convulsive therapy (ECT) increases plasma and red blood cell haloperidol neuroleptic activities.

In nine schizophrenic patients (five males and four females) on haloperidol treatment, plasma and red blood cell (RBC) haloperidol neuroleptic activities were measured before and after ECT by radioreceptor assay. Five patients randomly selected from these patients also served as controls on another occasion and neuroleptic activities in plasma and RBC were examined before and after the premedication only. All patients given ECT showed a considerable increase in plasma and RBC haloperidol neuroleptic activities after ECT (% increase in plasma neuroleptic activity, 28-409%; mean + SD, 136 +/- 155%, P less than 0.005, Wilcoxon test; % increase in RBC neuroleptic activity, 11-121%; mean + SD, 59 +/- 40%, P less than 0.005). However, no significant increase was observed for either plasma or RBC haloperidol neuroleptic activity, when patients were examined after premedication only. It was suggested that ECT induced a transient redistribution of haloperidol. It remains to be studied whether this phenomenon is causally related to the previous observation that the combination therapy of ECT and neuroleptics is more effective in the treatment of schizophrenia than ECT alone.

Adult↗

Inter- and intramolecular stacking interaction between indole and adeninium rings.

Crystals of 1,9-dimethyladeninium-indole-3-acetate (1:1) complex (I) and 9-(3-indol-3-ylpropyl)-1-methyladeninium iodide (II), an inter- or intramolecular model for the stacking interaction between the tryptophanyl residue and the methylated (or protonated) adenine base, were subjected to X-ray analyses. Nearly parallel stacking and interplanar spacing near to 3.4 A were observed between the indole and adeninium rings of both crystals. In particular, one of the two stacking pairs formed in I showed the existence of a partial charge-transfer interaction in their ground states. On the basis of the molecular orbital consideration, the mutual orientation between these stacked aromatic rings is considerably governed by the orbital interaction between the highest occupied molecular orbital of the indole ring and the lowest unoccupied one of the adeninium ring. The ring stacking observed in II was stabilized by the strong coupled dipole-dipole interaction. Absorption, fluorescence, and proton nuclear magnetic resonance spectra indicated the existence of a stacking interaction in the aqueous solutions of I and II, as well as in their crystalline states. The biological implication for the observed stacking interactions has been discussed.

Adenine↗

X-ray structural studies and physicochemical properties of cimetidine polymorphism.

Four crystalline forms of cimetidine, three anhydrous (forms A, B, and D) and a monohydrate (form C), obtained by slow evaporation of aqueous solutions of varying concentrations were characterized by IR spectroscopy, X-ray powder patterns, dissolution rates in deionized water, and thermal analyses. Among the three anhydrous forms of cimetidine, form A was thermodynamically more stable than the others. The structural conversion of form C into form A on dehydration was confirmed by IR spectroscopy and X-ray powder patterns. The structures of forms C and D were determined using X-ray diffraction. Form D was of spirally curled conformation; it was linked in a head-to-tail arrangement with the neighboring molecules via intermolecular hydrogen bonds between the imidazole nitrogen and guanidine nitrogen atoms. Form C was characterized by its folded conformation due to the weak stacking interaction between the imidazole and guanidine moieties; there was stabilization by double hydrogen bond formation with neighboring molecules and via water molecules of crystallization. The dissolution rate constant in deionized water for form C was approximately 1.29, 1.70, and 1.90 times greater than those measured for forms A, D, and B, respectively. There was a similar relationship among the four forms with respect to the rates of inhibition of stress ulceration. Regarding the molecular conformations of the crystalline forms and the rates of inhibition of stress ulceration, the gauche orientation of the guanidine group relative to the imidazole ring would be the conformation necessary for effective binding to the histamine H2-receptor. The compactly folded conformation of form C appears to be optimal for binding to the active site of the receptor and for clinical efficacy.

Animals↗