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Biomedical subjects

H Shimada

Publications and source records attributed to H Shimada.

At least 685 records · Page 38Linked to original sources

Purification and characterization of a nuclease from Lentinus edodes.

An endonuclease with 3'-nucleotidase activity (nuclease Le1) was purified from fruit bodies of Lentinus edodes in a single band on sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The apparent molecular weight of nuclease Le1 was about 27000. The nuclease was inactivated in the presence of ethylenediaminetetraacetic acid (EDTA) and reactivated by the addition of Zn2+. Hydrolysis of poly U by the nuclease showed many intermediate size oligomers prior to the formation of 5'-uridine monophosphate (UMP). Therefore, it was concluded that nuclease Le1 was a Zn(2+)-endonuclease similar to P1-nuclease from Penicillium citrinum. The nuclease was very sensitive to ionic strength, but pH-profiles of the hydrolysis of four 3'-nucleotides were very similar to those of P1 nuclease from P. citrinum.

Amino Acid Sequence↗

[Effects of 3-hydroxymethyl-2-methylimidazo [2, 1-b] benzothiazole (NIK-228) on gastric acid secretion and various experimental peptic ulcers in rats].

We examined the antisecretory and antiulcer activities of NIK-228 in rats. Male Wistar rats (200 to 250 g) were used under 24 to 48 hr fasted (without water) conditions. NIK-228 and famotidine were administered orally 1 hr before pylorus ligation, stress or each ulceration inducer. Both NIK-228 (10 to 100 mg/kg) and famotidine (0.3 to 3 mg/kg) dose-dependently inhibited gastric secretion in pylorus ligated rats. Water-immersion stress-, indomethacin- or pylorus ligation (Shay)-induced gastric ulcers were dose-dependently inhibited by NIK-228 (10 to 100 mg/kg), but only water-immersion stress and indomethacin induced ulcers were dose-dependently inhibited by famotidine (0.03 to 3 mg/kg). Ethanol- and 0.6 N HCl-induced gastric lesions were remarkably inhibited by NIK-228 (ED50 = 2.7 and 5.6 mg/kg), but tended to be inhibited also by famotidine (0.3 to 3 mg/kg). Cysteamine-induced duodenal ulcer was inhibited significantly by NIK-228 (30, 100 mg/kg) or famotidine (3 mg/kg). NIK-228 may produce its antiulcer effects via antisecretory and cytoprotective effects. These results suggest that NIK-228 has antisecretory and antiulcer activities.

Administration, Oral↗

[Evaluation of HCl-induced gastric mucosal lesions using a computer image processing system].

Oral administration of HCl (0.2 N, 0.4 N, 0.6 N, 0.8 N) solution produced congestive or hemorrhagic gastric mucosal lesions in rats. Lesion areas were differentiated into two areas (i.e., brown area and black area) macroscopically. Then, fine observations were performed on two areas using a computer image processing system (CIPS) and histological techniques. Cell necrosis from the mucosal surface to the middle mucosal layer were observed in the brown area, and gastric mucosal necrosis that reached to a deeper layer were observed in the black area. These results indicate that histological degree of lesion may be reflected in the macroscopic changes. Concerning the concentration of HCl, over 0.4 N HCl solution induced mucosal lesions, but HCl solution (0.4 N HCl) only produced a brown area. Maximum changes in the mucosal surface were observed at 30 min to 1 hr by 0.6 N HCl and at 15 to 30 min by 0.8 N HCl. Therefore, the best condition for evaluating the preventive effects of anti-ulcer agents is 30 min after treatment by 0.6 N HCl solution and 15-30 min after treatment by 0.8 N HCl solution. These results suggest that this technique may provide both quantitative and qualitative information on histological changes.

Animals↗

[Effects of NIK-228 on gastric acid secretion in rats using the congo red sprayed method].

We have reported the antiulcer activities of a new compound that we named NIK-228 (3-hydroxy-methyl-2-methylimidazo [2, 1-b] benzothiazole). In the present report, we studied the antisecretory effects of NIK-228 on basal and stimulated gastric acid secretion using the Congo red sprayed method. Male Wistar rats (200 to 250 g) were used after 24 hr of fasting (without water). NIK-228, atropine and cimetidine were administered orally or intravenously 1 hr before operation for Congo red spraying. NIK-228 (100 mg/kg, p.o.), atropine (5 mg/kg p.o.) and cimetidine (100 mg/kg, p.o.) all inhibited basal gastric acid secretion. Oral administration of NIK-228 and atropine inhibited gastrin, 2-deoxy-D-glucose (2-DG) and bethanechol-induced acid secretion, but didn't inhibit histamine-induced acid secretion. Cimetidine inhibited all of histamine, gastrin, 2-DG and bethanechol-induced acid secretion. In vagotomized rats, oral and intravenous administration of atropine both inhibited bethanechol-induced acid secretion, but NIK-228 was not inhibited. These results suggested that antisecretory effects of NIK-228 were caused by the central vagal systems.

Animals↗

Double response to Stroop stimuli.

To reexamine Klein's 1964 findings we carried out two experiments on the double response made to Stroop stimuli. In Exp. 1 incongruent color-word stimuli were presented on a CRT online with a microcomputer. A color-word card was used in Exp. 2. Subjects were asked to read words before naming colors or, conversely, to name colors before reading words. An analysis of variance (the task x the type of task) was performed on response times in both experiments. Two main effects and interactions were nonsignificant. Some subjects made an error-like reverse-order response on the double-response task. The present findings do not support Klein's findings or the competition explanation of the Stroop effect.

Adult↗

[Pigmented neuron/non-pigmented neuron ratio of the substantia nigra in relation to ageing and pathological conditions].

Based on 45 normal cases aged from 32 to 106 years of age, a morphometric study revealed that, despite decrease in the number of both pigmented neurons (PN) and the non-pigmented neurons (NN) with advancing age, the ratio (PN/NN) did not change (4.8). It is well-known that both the substantia nigra and the striatum send fibers to each other. McGee demonstrated that the ratio of the number of large neurons to that of small neurons was constant, irrespective of different ages, although number of both neurons decreased with ageing. It was therefore apparent that this phenomenon in the putamen was the same as in the substantia nigra. It could be considered that "balanced depopulation of different neurons" in the nucleus of the strio-nigral circuit contribute to support normal extrapyramidal functions. Additionally, the centenarian cases showed larger numbers of both PN and NN than younger case. It was likely that they could be classified as so-called "excellent" centenarians. On the other hand, idiopathic Parkinson's disease (15 cases) showed that while the same number of NN remained as in age-matched controls, PN showed marked depopulation. Olivopontocerebellar atrophy of the sporadic type (OPCA, 10 cases) and progressive supranuclear palsy (PSP, 5 cases) showed a decrease in number of both PN and NN. However, NN in PSP showed much more decrease than OPCA. NN sends fibers to the pontine tegmentum as well as the thalamus, and PSP shows marked atrophy of the brainstem tegmentum. In this connection, it was considered that marked decrease of NN in PSP could be related to tegmental atrophy.

Adult↗

Quantitative study of neurofibrillary tangles in subdivisions of the hippocampus. CA2 as a special area in normal aging and senile dementia of the Alzheimer type.

The frequency of neurofibrillary tangles (NFTs) in relation to aging was examined in five regions of the hippocampus of 139 normal controls (60 to 106 years) and 14 patients with senile dementia of the Alzheimer type (SDAT). The regions were CA4, CA3, CA2 and CA1, the latter being subdivided into CA1a (the region near CA2) and CA1b (the region near the subiculum). Only CA2 showed no correlation of NFTs with normal aging. CA2 in SDAT was the site most vulnerable to NFT formation. Therefore, it is considered that CA2 is a special region in both normal aging and SDAT. CA1 was characterized by the early appearance of large amounts of NFT, and was the most reliable marker of senile change related to aging. Like CA1, both CA3 and CA4 showed an increase of NFTs with normal aging, but their aging process was far less marked. In addition, statistical analysis based on a "normal" distribution was considered to be unsuitable for quantitative study of senile change, because no histogram of NFTs in any subdivisions for any age showed such a distribution.

Aged↗

An autopsy case of pancreatic duct cell carcinoma associated with ossification.

A case of pancreatic duct cell carcinoma with ossification was reported. A 71-year-old female died of pancreas carcinoma with liver and diffuse lymph node metastasis. Computed tomography (CT) revealed a punctate calcification of the body of the pancreas. At autopsy, the carcinoma occupied almost all of the pancreas, and histological examination revealed a moderately to well-differentiated adenocarcinoma with mucin production in the glands. The whole of the pancreas was examined microscopically by multiple-step sections, and mature ossification was found in the body, corresponding to its CT localization. Around the ossification were found cancer cells with massive mucin in the cytoplasm, capillary proliferation, scattered necrosis and mesenchymal cells, which were thought to be fibroblasts. But neither cartilage nor calcification was found. The pathogenesis of ossification was believed to be associated with metaplastic changes of mesenchymal cells. This is the fourth case of pancreatic carcinoma with ossification, and the second case of pancreatic duct cell carcinoma with mature bone formation to have been reported.

Adenocarcinoma↗

Comparison of the effectiveness of dithiocarbamates on the excretion and distribution of cadmium in mice.

Sodium N-benzyl-D-glucamine dithiocarbamate (BGD), sodium N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD), and sodium N-p-methoxybenzyl-D-glucamine dithiocarbamate (MeOBGD) were evaluated for their efficacy in the distribution and excretion of cadmium in mice exposed to cadmium. Mice were injected i.p. with 109CdCl2 (1 mg Cd/kg and 74 kBq of 109Cd/mouse) and 30 min or 24 h later, they were injected i.p. with chelating agents (5% of an LD50). The results of this study indicated that the injection of HBGD to mice pretreated with cadmium can remove cadmium from the body without redistribution of cadmium to the brain, testes, and heart more effectively than that of BGD or MeOBGD.

Animals↗

Novel anticoagulant peptides from the functional site of human placental anticoagulant protein.

Histidine-containing peptides SHLRKV and DHTLIR, corresponding to placental anticoagulant protein-I (PAP-I) residues 204-209 and 266-271, respectively, are included in the functional site of PAP-I and exhibit anticoagulant activity, but the peptides in which alanine is substituted for histidine do not. However, the peptide KHALKG, corresponding to the region from Lys-97 to Gly-102, did not exhibit an anticoagulant activity, showing that it is not included in the functional site. These findings thus suggest that His-205 and His-267 are involved in the Ca(2+)- or the phospholipid-binding site of PAP-I but that His-98 is not.

Amino Acid Sequence↗

[Morphological observation of the mitral annulus fibrosus (II)].

In 1986, Hutchins observed a high incidence of the disjunction of the mitral annulus fibrosus in mitral valve prolapse syndrome. However, we could not prove his view in our previous study using one section in each case. In this study, the types of mitral annulus fibrosus were analyzed in plural sections. Autopsy hearts of nine aged cases were used for examination of the mitral annulus fibrosus in five to eight longitudinal sections from the posterolateral wall. The types of the mitral annulus fibrosus were classified as; Type A (the mitral valve attaches to the left ventricle), Type B (the valve attaches to the left atrium), Type C (the atrialis layer of the valve continues to the left atrium, while the fibrosa layer continues to the left ventricle), and type D (mitral annulus calcification). A1-3 and B1-3 are subtypes. In the nine cases there were no consistent patterns in type distributions. All sections showed Type A1 (Case 2), Type A1 to A3 (Case 5), and Type B1 to B3 (Case 8). In other cases, a combination of Type A and B (Case 4, 6, 7, 9), and inclusion of Type C (Case 1) and Type D (Case 3) were found. The location of the middle scallop of the posterior mitral leaflet corresponded to the section of the previous study. Among three cases of Type A in the middle scallop, two showed Type A in every section. Among five cases of Type B in the middle scallop, only one case showed Type B in every section. Other four cases showed various combinations with the other types. A case of Type D in the middle scallop showed also Type B and Type C. The conclusion of this study was that in 1/3 of the cases, the type of the mitral annulus fibrosus was consistent, but in the other 2/3 they were not consistent. In other words, one section is not necessarily representative of the morphology of the mitral annulus fibrosus in each case.

Aged↗

Effect of (+/-)-2-(dimethylamino)-1-[[o-(m-methoxyphenethyl)phenoxy] methyl]ethyl hydrogen succinate on experimental models of peripheral obstructive disease.

Peripheral obstructive disease in tail or hind limb was experimentally induced by intravenous injection of kappa-carrageenin or intra-arterial injection of sodium laurate in rats, and the suppressive effect of (+/-)-2-(dimethylamino)-1-[[o-(m-methoxyphenethyl)phenoxy] methyl]ethyl hydrogen succinate (MCI-9042, CAS 125926-17-2) on the peripheral obstructive diseases was examined. The injection of kappa-carrageenin induced a thrombotic infarction of the tail vessel in rats. The administration of MCI-9042 dose-dependently suppressed the peripheral infarction with an ED50 value of 16 mg/kg p.o. Ticlopidine, a reference antiplatelet drug, did not affect the peripheral infarction even at 50 mg/kg p.o. Cyproheptadine, however, an S2-serotonergic antagonist, potently suppressed the peripheral infarction with an ED50 of 3.5 mg/kg p.o. After the injection of sodium laurate into the femoral artery in rats peripheral lesions of the paw were generated and extended. MCI-9042 significantly prevented the progression of the disease at doses of 10 mg/kg p.o. and above. When the daily administration of MCI-9042 was started from 1 day after the laurate injection, it was also effective as well as by pretreatment. Ticlopidine was significantly effective only at 100 mg/kg p.o. as pretreatment. From the present study, it is considered that platelet-derived serotonin plays an important role in the development of peripheral obstructive disease and MCI-9042 suppressed the disease through its S2-serotonergic antagonism.

Animals↗

Evaluation of the Shimada classification in advanced neuroblastoma with a special reference to the mitosis-karyorrhexis index: a report from the Childrens Cancer Study Group.

Histopathology of 46 cases of Stage III and Stage IV neuroblastoma collected at the Childrens Cancer Study Group Pathology Center was reviewed independently by two pathologists to formulate essential steps in the determination of the mitosis-karyorrhexis index (MKI), to assess interobserver concordance, and to evaluate prognostic significance of the Shimada classification system. "Absolute" agreement (obtained after the review by both pathologists) or "consensus" agreement (obtained after the second review of cases with initial discrepancy) was achieved with respect to category of MKI in 93% of 40 stroma-poor neuroblastomas and prognostic subgrouping in 98% of the total cases. This classification system distinguished favorable from unfavorable prognostic subgroups significantly (P = 0.0002), and the prognostic effects were largely unaltered when adjusted for age and stage of the patients (P = 0.0005) in this series.

Adolescent↗

Subtypes and proportions of cerebrovascular disease in an autopsy series in a Japanese geriatric hospital.

Of 1721 consecutive autopsies performed on patients over 60 years of age in Tokyo Metropolitan Geriatric Hospital, 550 (32% of all autopsied cases) revealed symptomatic cerebrovascular lesions. Among the 550 patients, intracranial hemorrhage was found in 19%, cerebral infarction in 75%, and coexisting cerebral hemorrhage and cerebral infarction in 6%. Twenty-eight percent of the cerebral infarctions were embolic infarctions of cardiac origin, half of which were caused by nonvalvular atrial fibrillation, and 69% were non-embolic infarctions of cardiac origin. Progressive subcortical vascular encephalopathy accounted for 15% of the cerebral infarctions. Two-thirds of all lobar cerebral hemorrhages were amyloid angiopathy-related. Nonvalvular atrial fibrillation is the most important cardiac source of embolic stroke. Progressive subcortical vascular encephalopathy is one of the characteristic features of ischemic lesions, and cerebral amyloid angiopathy is an important cause of lobar cerebral hemorrhage in the aged.

Age Factors↗

A human testis-specific mRNA for phosphoribosylpyrophosphate synthetase that initiates from a non-AUG codon.

Two highly homologous subunits for phosphoribosylpyrophosphate synthetase are encoded by human X-linked genes, PRPS1 and PRPS2 (Taira, M., Kudoh, J., Minoshima, S., Iizasa, T., Shimada, H., Shimizu, Y., Tatibana, M., and Shimizu, N. (1989b) Somat. Cell Mol. Genet. 15, 29-37). These genes are expressed in most tissues, whereas an additional unique mRNA (1.4 kilobases) is present in the testes of rats as well as mice and humans (Taira, M., Iizasa, T., Yamada, K., Shimada, H., and Tatibana, M. (1989a) Biochim. Biophys. Acta 1007, 203-208). In this paper, cDNA cloning revealed that the human testis-specific mRNA was encoded by an autosomal gene, termed PRPS3. RNA blot analysis showed that the expression of this gene began at 4 weeks of age in rats, coinciding with the reported appearance of primary spermatocytes. A cDNA clone of PRPS3 was sequenced and found to encode a predicted product of 317 amino acids which was highly homologous to those of PRPS1 and PRPS2 (94.3% and 91.2% identities, respectively). However, the PRPS3 cDNAs lacked an ATG initiator for translation at the expected position, and instead contained an ACG triplet. In vitro transcription/translation studies, combined with in vitro site-directed mutagenesis experiments, suggested that the ACG codon at this position did serve as a start codon. Analysis of amino-terminal sequence of the radiolabeled PRPS3 product, prepared by in vitro translation, supported the predicted sequence starting with Pro-1, and, in addition, this product was labeled with N-formyl[35S]methionyl-tRNAi. These results suggested that the synthesis of the nascent polypeptide could initiate with methionine at the position corresponding to the ACG codon.

Amino Acid Sequence↗