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Biomedical subjects

H Shimada

Publications and source records attributed to H Shimada.

At least 487 records · Page 27Linked to original sources
PubMed1995

Construction and evaluation of a virG thyA double mutant of Shigella flexneri 2a as a candidate live-attenuated oral vaccine.

A virG thyA double mutant of Shigella flexneri 2a was constructed as a candidate live-attenuated oral vaccine. In the keratoconjunctivitis model it did not provoke any adverse reaction by itself on guinea pigs' eyes and completely protected them from provoking keratoconjunctivitis. When (2.7-4.8) x 10(10) of the vaccine was inoculated intragastrically after 1 day fasting in cynomolgus monkeys three times at weekly intervals, a watery stool was observed at 40% as a side-effect. Upon intragastric challenge after 1 day fasting with 7.5 x 10(9) of the virulent strain four weeks after the last vaccination, a statistically significant difference was obtained in the mortality rate but not in the morbidity rate between the vaccine and the control group, although the clinical findings were less severe in the vaccine group than in the control group. These results together with the histopathological and immunological findings indicate that the vaccine deserve further detailed studies.

Animals↗
PubMed1995

Effects of dithiocarbamates and cadmium on the enzymatic activities in liver, kidney and blood of mice.

The effects of N-benzyl-D-glucamine dithiocarbamate (BGD), diethyldithiocarbamate (DDTC), and N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD) on the enzymatic activities in mice were studied. The mice were given i.v. injections of these chelating agents (1 mmol/kg) and 3 h later the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltranspeptidase (gamma-GTP), alkaline phosphatase (ALP), leucine aminopeptidase (LAP), and cholinesterase (ChE) in the liver, kidney, and blood were determined. These enzymatic activities were little changed by treatment with these chelating agents. Cadmium (Cd) administration markedly decreased the activities of AST and ALT in the liver and kidney and greatly increased these enzymatic activities in blood. The changes in the enzymatic activities by treatment with Cd were prevented by injection of BGD (1 mmol/kg). These results indicate that BGD, DDTC, and HBGD were not toxic to the liver or kidney of mice and that BGD treatment protected against the acute hepatic and renal toxicity induced by Cd.

Alanine Transaminase↗
PubMed1995

Dominant and differential deposition of distinct beta-amyloid peptide species, A beta N3(pE), in senile plaques.

We analyzed an amino-terminal modification of beta-amyloid (A beta) peptide in brain, using anti-A beta antibodies that distinguish distinct molecular species. Examination of cortical sections from 28 aged individuals with a wide range in senile plaque density revealed that a molecular species distinct from the standard A beta is deposited in the brain in a dominant and differential manner. This modified A beta peptide (A beta N3(pE)) starts at the 3rd aminoterminal residue of the standard A beta, glutamate, converted to pyroglutamate through intramolecular dehydration. Because plaques composed of A beta N3(pE) are present in equivalent or greater densities than those composed of standard A beta bearing the first amino-terminal residue (A beta N1) and because deposition of the former species appears to precede deposition of the latter, as confirmed with specimens from Down's syndrome patients, the processes involved in A beta N3(pE) production and retention may play an early and critical role in senile plaque formation.

Adult↗
PubMed1995

Effect of aging on spontaneous micronucleus frequencies in peripheral blood of nine mouse strains: the results of the 7th collaborative study organized by CSGMT/JEMS.MMS. Collaborative Study Group for the Micronucleus Test. Environmental Mutagen Society of Japan. Mammalian Mutagenesis Study Group.

The spontaneous frequencies of micronucleated reticulocytes (MNRETs) were examined monthly over the life spans of animals belonging to nine mouse strains for the 7th collaborative study organized by the CSGMT/JEMS.MMS. Both sexes of the BDF1 strain and females of the A/J strain showed a statistically significant increase in mean spontaneous MNRET frequency in their last month of life, suggesting the possibility of strain-specific, age-dependent chromosomal instability. SAMP6/Tan, an accelerated senescence-prone strain, showed the same tendency, although it was not statistically significant. The other strains studied, ddY, CD-1, B6C3F1, SAMR1, and MS/Ae, did not show significant age-related differences in mean of MNRET frequencies. More extensive statistical analyses are underway, and the outcomes will be reported separately.

Aging↗
PubMed1995

IL-4 upregulates Fc epsilon RI alpha-chain messenger RNA in eosinophils.

By using the reverse transcription polymerase chain reaction and Southern blot hybridization, we demonstrated that Fc epsilon RI alpha-chain (Fc epsilon RI alpha) messenger RNA was expressed in eosinophils purified from the peripheral blood of patients with allergic rhinitis and that this expression was enhanced by IL-4. However, studies in which flow cytometry or immunostaining was used did not reveal the expression of Fc epsilon RI alpha protein on eosinophils from peripheral blood. Neither IL-4 alone nor the combination of IL-4 and other cytokines could induce detectable Fc epsilon RI alpha protein; nevertheless, they do express Fc epsilon RI alpha mRNA. Double-labeling immunostaining on cryostat sections of nasal mucosa clearly demonstrated that some Fc epsilon RI alpha-positive cells were eosinophil cationic protein-positive, which confirms their eosinophilic nature. Not all the eosinophil cationic protein-positive cells express on Fc epsilon RI alpha signal. Considering that Fc epsilon RI alpha mRNA was detectable in four of five samples of eosinophils from those patients with nasal allergy and that only one of five eosinophil samples from normal subjects expressed Fc epsilon RI alpha mRNA, the level of Fc epsilon RI expression may be correlated with the activation of eosinophils. It seems very likely that some other unidentified factors are required for the process from the expression of Fc epsilon RI alpha mRNA to that of Fc epsilon RI as a protein.

Adolescent↗
PubMed1995

Growth hormone effects on wound healing in malnourished animals: a histological study.

Systemic growth hormone (GH) markedly improves celiotomy wound strength in protein malnourished (PM) animals. This study was undertaken to analyze the effect of GH as a basis for anatomically understanding. Adult female Spraque-Dawley rats were divided into normally nourished controls, PM and GH-treated PM groups. Protein malnutrition was achieved by feeding 5.5% protein restricted chow every other day for eight weeks before surgery. Controls were fed 23.4% protein chow. All animals were fed 23.4% protein chow postoperatively. Rat-GH was injected subcutaneously twice daily (1.0 mg/day) for three days prior to and five days after 5 cm midline celiotomy. Bursting strength of the wound was measured at 3, 6 and 14 days postoperatively. Histologic wound specimens (hematoxylin and eosin) were obtained from each group. Wound strength of malnourished rats was significantly less than that of normal controls at six days after operation (p < 0.001). With administration of growth hormone, the wound strength was significantly improved. Histologically, there was no difference between groups on day 3. On day 6 the normal control group showed a decrease in the early inflammatory cell infiltrate with concurrent development of granulation tissue and a dense proliferation of fibroblasts. The PM wound showed fatty infiltration, a very narrow band of poorly formed granulation tissue and a sparse fibroblastic proliferation. The GH-treated PM group showed a combination of histologic findings. Fatty infiltration, similar to that in malnourished non-treated animals, was still evident but there was also a dense proliferation of capillary channels and fibroblasts comparable to normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Toxicity of quinolone antimicrobial agents.

An approach to minimization of toxicity of a new compound is to elucidate the mechanisms of toxicity of analogous compounds and to clarify their structure-toxicity relationships. A problem with this approach, however, is that such elucidation remains difficult. For quinolones, some improvements in this mechanistic approach have been achieved in the central nervous system (CNS), particularly with regard to their interaction with non-steroidal anti-inflammatory drugs (NSAIDs), and in genotoxicity and phototoxicity studies, particularly in comparison with other toxicities, such as to the cardiovascular, gastrointestinal, bone, reproductive, and developmental systems. This review concentrates on a description of the known effects of quinolones on various organ systems in experimental animals and humans. Given the logarithmic increase in the synthesis of new quinolones, it is questionable whether these drugs share similar safety and efficacy. Nevertheless, this mechanistic approach to the investigation and minimization of toxicity has produced satisfactory results to date and deserves to be continued.

4-Quinolones↗
PubMed1995

Genomic organization of 251 kDa acetyl-CoA carboxylase genes in Arabidopsis: tandem gene duplication has made two differentially expressed isozymes.

Acetyl-CoA carboxylase (ACCase) catalyzes the carboxylation of acetyl-CoA, forming malonyl-CoA a key intermediate in the biosynthesis of fatty acids and a variety of secondary metabolites. Based upon amino acid sequences conserved among rat, chicken, and E. coli ACCases, PCR-primers were used to amplify a genomic fragment which codes for an ACCase of Arabidopsis. The resulting fragment was used for isolation of genomic and cDNA clones. We have determined the complete cDNA sequence coding for an Arabidopsis ACCase consists of 2,254 amino acids with the molecular mass of 251 kDa. This enzyme contains no recognizable plastid transit-peptide sequence. Therefore, this ACCase is presumably the cytosolic isozyme. Southern analysis indicates that there are two ACCase genes in the Arabidopsis genome. Surprisingly, the results of RFLP analysis and physical mapping of the isolated genomic clones demonstrate that these two genes, acc1 and acc2, are contiguously located within a 25-kbp genomic region near the middle of chromosome 1. Both genes are transcriptionally active, as transcripts from each gene were detected by reverse transcription-PCR analysis using gene-specific primers. The acc1 and acc2 transcripts accumulate in leaves and seedlings but only the acc1 transcript accumulates in developing siliques, unexpectedly. The differences in the expression patterns may be indicative of the differential role of the two genes.

Acetyl-CoA Carboxylase↗
PubMed1995

Prolonged interference of blue dye "patent blue" with pulse oximetry readings.

Several blue dyes were reported to interfere with the accurate determination of oxygen saturation by pulse oximetry. However, in previous reports the interferences were observed only for a short duration. We have experienced a case in which the interference by a blue dye, "patent blue" continued for a long time. It was suggested that the blue dye, when it was injected intra-arterially and in an anaemic patient, interfered with the pulse oximetry measurement to a greater extent.

Catheterization, Peripheral↗
PubMed1995

Involvement of an AP-1 complex in zone-specific expression of the CYP11B1 gene in the rat adrenal cortex.

The CYP11B1 gene, which encodes steroid 11 beta-monooxygenase, which is responsible for the synthesis of cortisol and corticosterone, the major glucocorticoids in mammals, is expressed specifically in the zona fasciculata of the adrenal cortex. We have analyzed the promoter region of the rat CYP11B1 gene by using a transient-expression system with adrenocortical Y1 cells and have identified a positive regulatory region. The region contained two adjacent sites for the binding of Y1-cell nuclear proteins: the binding site for an AP-1 transcription factor composed of JunD and a Fos-related protein, and the site for Ad4-binding protein (Ad4BP). The binding of the AP-1 factor to the regulatory region had a suppressive effect on that of Ad4BP in the nuclear extracts. Mutational analyses revealed that the transcriptional activation of the CYP11B1 gene promoter in Y1 cells was attributable to the AP-1 site but not to the Ad4 site. Subsequently, nuclear extracts of the zona fasciculata cells from the rat adrenal cortex were found to contain both AP-1 factor and Ad4BP, whose binding properties to the regulatory region were almost identical to those of the two factors in the Y1-cell nuclear extracts. Moreover, immunohistochemical analyses of rat adrenal cortices showed that the AP-1 factor was present in the nuclei of CYP11B1-expressing cells in the zona fasciculata but not in the nuclei of cells in the other zones. From these results, we propose that the AP-1 transcription factor found in this study plays an important role in the zone-specific expression of the CYP11B1 gene in rat adrenal cortex.

Animals↗
PubMed1995

Interleukin-5 upregulates intercellular adhesion molecule-1 gene expression in the nasal mucosa in nasal allergy but not in nonallergic rhinitis.

The effect of interleukin-5 (IL-5) on intercellular adhesion molecule-1 (ICAM-1) gene expression in human nasal mucosa was studied using the method of gene expression quantification. Recombinant human IL-5 was shown to induce ICAM-1 gene expression in the nasal mucosa of patients with nasal allergy, but not in the mucosa of non-allergic patients. The peak level of ICAM-1 gene expression was seen 6 h after IL-5 stimulation. In the nasal mucosa of patients with nasal allergy, IL-5 might act not only as an eosinophil chemotactic factor, but also as an enhancement factor for the expression of adhesion molecules, thereby accelerating eosinophil appearance. The results also suggest that the nasal mucosa of patients with nasal allergy somehow favors adhesion molecule induction by IL-5.

Adolescent↗
PubMed1995

Manipulation of the lighting schedule can modify the pharmacological effects of theophylline in chick embryos.

The effect of the lighting schedule on the pharmacological action of theophylline was studied in chick embryos. Fertile eggs of White Leghorns were incubated and investigated, on two occasions, under constant light conditions or under constant dark conditions. A single injection of theophylline 2.14, 4.29, 8.57 and 17.14 mg/egg into the air sac of fertile eggs was carried out on the 16th day of incubation. Electrocardiograms (ECGs) were recorded 0 to 60 min after drug injection. After drug injection, heart rate increased under constant light conditions, but decreased under dark conditions. In addition, arrhythmia was produced by theophylline, 17.14 mg/egg, under constant dark conditions. These results indicate that the manipulation of the lighting schedule may have a marked influence on the pharmacological effects of theophylline in chick embryos.

Animals↗
PubMed1995

Rhodiocyanosides A and B, new antiallergic cyanoglycosides from Chinese natural medicine "si lie hong jing tian", the underground part of Rhodiola quadrifida (Pall.) Fisch. et Mey.

Two new antiallergic cyanoglycosides named rhodiocyanosides A and B were isolated from the Chinese natural medicine "Si Lie Hong Jing Tian" (Shiretsukoukeiten in Japanese), the underground part of Rhodiola quadrifida (Pall.) Fisch. et Mey., together with two new glycosides, octyl alpha-L-arabinopyranosyl(1-6)-beta-D-glucopyranoside and gossypetin 7-O-beta-D-glucopyranosyl(1-3)-alpha-L-rhamnopyranoside. Their chemical structures were determined on the basis of chemical and physicochemical evidence. Rhodiocyanosides A and B exhibited inhibitory activity on the histamine release from rat peritoneal exudate cells sensitized with anti-DNP IgE. In addition, rhodiocyanoside A was found to inhibit the PCA reaction in rats.

Animals↗
PubMed1995

[Effect of FRG-8813, a new histamine H2-receptor antagonist, on gastric mucus production in rats].

We examined the effect of FRG-8813, a new histamine H2-receptor antagonist, on 1% NH3-induced gastric mucosal lesions and basal gastric mucus production in rats. The effect of FRG-8813 (10 mg/kg) given orally was investigated macroscopically and histochemically compared with that of 16,16-dimethyl prostaglandin E2 (dmPGE2, 2 micrograms/kg) or capsaicin (Cap, 10 mg/kg) in the fundic gland area. FRG-8813, dmPGE2 and capsaicin inhibited the NH3-induced mucosal lesions, and stimulated the mucus secretion 5 min after the administration. Chemical deafferentation abolished the gastroprotective effect of FRG-8813 or Cap and attenuated the increase by FRG-8813, dmPGE2 or Cap in mucus secretion seen after 5 min. These results suggest that FRG-8813 exerts its effect on gastric mucus production partially through the capsaicin-sensitive afferent nerves, like the mechanism involved in gastroprotection, and that the increase in mucus production by FRG-8813 is at least in part responsible for the gastroprotection.

16,16-Dimethylprostaglandin E2↗
PubMed1995

[Experimental studies of physiological and pathological effects induced by systemic hypoxia and the hypoxia-reoxygenation model in rats].

We attempted to make a basic model to investigate a series of factors that induce histological changes in systemic hypoxia-reoxygenation injuries. At first, we set the experimental conditions for hypoxia and the hypoxia-reoxygenation models as follows: respiration volume: 1.5 ml/stroke, respiratory frequency: 80 times/min, oxygen concentration: 14%. Next, Male SPF Wistar rats were anesthetized with pentobarbital sodium. For artificial ventilation, a cannula was inserted in the trachea and connected to the rodent ventilator through two flow meters to allow mixing of 100%N2 and 95%O2-5%CO2 gases at a desired ratio. The influence of hypoxia-reoxygenation was studied and evaluated histologically and biochemically. The rats were placed under the hypoxic condition for either 3 or 6 hr. Then, oxygen partial pressure was restored to 21% followed by reoxygenation for either 3 or 6 hr. Then the rats were sacrificed, and the pituitary, adrenals, heart, stomach and kidneys were removed. The results were as follows: 1) GPT activities were increased by a load of hypoxia, but no influence of reoxygenation was detected. 2) Under the condition of experimental hypoxia, the weights of the pituitary and adrenals increased significantly. 3) The histological findings indicated that 6-hr hypoxia followed by 3-hr reoxygenation induced hypoxia-reoxygenation injuries mostly affecting the anterior pituitary and adrenal medulla.

Adrenal Glands↗
PubMed1995

The uricosuric effect in rats of E5050, a new derivative of ethanolamine, involves inhibition of the tubular postsecretory reabsorption of urate.

N-[3-[4'-(2",6"-Dimethylheptyl)phenyl]butanoyl]ethanolamine (E5050), a newly synthesized compound, was shown recently to induce uricosuria in humans via inhibition of the postsecretory reabsorption of urate. We examined the effects of this compound on urate excretion in rats loaded with oxonate and compared these effects with those of the uricosuric drugs trichlormethiazide and probenecid. When administered i.p., E5050 (0.3-15 mg/kg) increased the urinary excretion rate of urate and the ratio of urate clearance to inulin clearance in a dose-dependent manner, while the urine volume increased only slightly, and the glomerular filtration rate and plasma urate level were not changed. No paradoxical effect on urate excretion was observed. In contrast, trichlormethiazide and probenecid had a biphasic effect on urate excretion. In a pyrazinoic acid suppression test, the uricosuric effect of E5050 was completely inhibited by pretreatment with pyrazinoic acid. In a phenolsulfonphthalein (PSP) test, E5050 did not affect urinary PSP excretion, while probenecid strongly decreased such excretion. Thus, E5050 also appears to be uricosuric in rats.

Animals↗