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Biomedical subjects

M Hashimoto

Publications and source records attributed to M Hashimoto.

At least 775 records · Page 43Linked to original sources
PubMed1991

Protective effect of WEB 1881 FU on AF64A (ethylcholine aziridinium ion)-induced impairment of hippocampal cholinergic neurons and learning acquisition.

The effect of continuous administration of 4-aminomethyl-1-benzylpyrrolidin-2-one-hemifumarate (WEB 1881 FU) on cerebral cholinergic neurons was studied using rats treated with ethylcholine aziridinium ion (AF64A), a neurotoxic choline analog. AF64A (2.0 nmol, administered i.c.v.) caused a significant decrease in the hippocampal acetylcholine (ACh) content. This decrease in hippocampal ACh content was accompanied by a reduction of choline acetyltransferase (CAT) activity. Under these experimental conditions, the latency of the passive avoidance response of rats, determined with a step-through method, was strongly decreased as compared with that of sham-operated rats. Although treatment with WEB 1881 FU (50 mg/kg per day, administered orally for 7 days) from immediately after the administration of AF64A did not affect the AF64A-induced decrease of ACh in the hippocampus, 100 mg/kg per day of WEB 1881 FU (orally for 7 days) significantly suppressed the AF64A-induced declines in hippocampal ACh content and CAT activity. The AF64A-induced reduction in latency of the passive avoidance response was also significantly antagonized by the treatment with 100 mg/kg per day of WEB 1881 FU (administered orally for 7 days) from immediately after the administration of AF64A. Continuous administration of WEB 1881 FU (100 mg/kg per day, orally for 7 days) from 7 days after the treatment with AF64A also had a significant inhibitory effect on the AF64A-induced decrease in ACh content in the hippocampus. These results suggest that WEB 1881 FU may have protective actions on the destruction of hippocampal cholingergic neurons as well as memory impairment induced by AF64A administration.

Acetylcholine↗
PubMed1991

[Clinical experience of expandable metallic stent placement for malignant biliary obstruction].

Expandable metallic stents of modified Gianturco design were used in nine cases of malignant biliary obstruction. Stents were placed through a percutaneous transhepatic approach without any severe complications. Initial patency was obtained seven of nine patients. Of these seven patients, recurrent jaundice was observed in three within four weeks. One patient had recurrent stenosis after four months due to ingrowth of the tumor. Although the expandable metallic stent offers several theoretical advantages over currently available stents, a disadvantage is that tumors may grow through the spaces between the legs of the wire or grow over the stent. We found that multi-modal treatment combined with radiation therapy was indispensable to maintain the patency of the stent in malignant biliary obstruction.

Aged↗
PubMed1991

Isolation of estrogen receptor-binding sites in human genomic DNA.

Total genomic DNA digested by restriction enzymes was mixed with the DNA-binding domain of the estrogen receptor (ER-DBD) that was expressed in Escherichia coli and the fragments that bound to it were selected by nitrocellulose filter. These fragments were cloned into a plasmid vector and amplified. This selection process was repeated six times and five fragments ranging from 0.2 to 2 kb were isolated. Interestingly, each of these fragments had a perfect palindromic estrogen responsive element (ERE) (GGT-CANNNTGACC). More surprisingly, one of the fragments was found to be derived from the same locus as a fragment obtained by another similar but independent experiment. The results indicate that the ER-DBD region can bind by itself specifically to the perfect palindromic ERE with a 3 base pair spacing but it does not bind strongly enough to the half palindromic EREs or to the imperfect palindromic EREs. Chloramphenicol acetyltransferase assay has shown that some of these fragments have estrogen-dependent enhancer activity, suggesting the existence of a target gene near these fragments. The method described here may be generally applicable for screening and isolation of other transcription factor-binding sites in genomic DNA.

Amino Acid Sequence↗
PubMed1991

Action site of circulating interleukin-1 on the rabbit brain.

Interleukin-1 (IL-1) is now generally accepted as an endogenous pyrogenic mediator of fever induction. IL-1 induces fever by means of activation of arachidonate metabolism in the brain. However, whether circulating IL-1 enters the brain or not, further, the question of where is the action site of circulating IL-1 on the brain, have not been clearly demonstrated. In the present study, to investigate the site of action of circulating IL-1 on the brain, recombinant rabbit interleukin-1 beta (IL-1 beta) was labeled with colloidal gold, injected into the carotid artery of anesthetized rabbits and traced in the brain tissue by means of electron microscopy. Dose-dependent increase in colonic temperature was induced by intravenous injection of used IL-1 in rabbits, while heated IL-1 beta lost the pyrogenicity. Injection of solution of colloidal gold per se did not affect the colonic temperature of afebrile conscious rabbits. However, the IL-1/gold conjugates induced fever; IL-1 beta retained its pyrogenic potency even after labeling with gold. By electron microscopy, the IL-1/gold conjugates were observed on the surface and in the vesicle of endothelial cells of the capillary in the region of the anteroventral third ventricle. This implies that circulating IL-1 acts, as the initial step to induce fever, on the endothelium in that region.

Animals↗
PubMed1991

Expression of mRNA for activin-binding protein (follistatin) during early embryonic development of Xenopus laevis.

Follistatin is a specific activin-binding protein and is supposed to control activin functions. During Xenopus embryonic development, activin is thought to act as a natural mesoderm-inducing factor. We isolated here the Xenopus follistatin cDNA from Xenopus ovary cDNA library and studied the expression of Xenopus follistatin gene during the course of early embryonic development. The Xenopus follistatin has an 84% homology at the level of deduced amino acid sequence with human and porcine follistatin. Its 3.5 kb mRNA is first expressed at the gastrula stage, when the expression of activin mRNA becomes first detectable, and increased thereafter. Another species of 2 kb mRNA become detectable from early neurula and also increased dramatically in tadpole. These results suggest that the follistatin acts also as a regulator of activin in inductive interactions during amphibian embryonic development.

Amino Acid Sequence↗
PubMed1991

Characterization and mechanism of fever induction by interleukin-1 beta.

To investigate the relation of arachidonate metabolism to the induction of fever by interleukin-1, indomethacin was administered in either an intracerebroventricular (icv) or a subcutaneous (sc) route in conscious rabbits. Fever induced by icv administration of recombinant human interleukin-1 beta (rhIL-1 beta) was depressed by either icv or sc pretreatment with indomethacin. Fever induced by intravenous (iv) administration of rhIL-1 beta was significantly inhibited, though initial small increase in colonic temperature still remained, and was completely depressed by combination of icv and sc pretreatment with indomethacin. Intracerebroventricularly administered recombinant rabbit IL-1 beta (rrIL-1 beta) induced dose-dependent increases in colonic temperature, which was depressed by sc pretreatment with indomethacin. There is little species specificity between human and rabbit IL-1 beta, in terms of the pyrogenic potency and the inhibitory effect of sc indomethacin on fever induced by icv IL-1 beta. Further, fever caused by icv administration of sodium arachidonate was significantly depressed by sc pretreatment with indomethacin. These results show that the inhibitory effect of indomethacin, administered either icv or sc, on IL-1 beta-induced fever is similar to that of IL-1 alpha-induced fever reported previously. This suggests that the site of arachidonate metabolism significantly involved in the mechanism of fever induction by IL-1 is easily accessible to the brain from the blood.

Animals↗
PubMed1991

PAF inhibitory activity of diketopiperazines: structure-activity relationships.

FR900452, a natural product isolated from the culture broth of Streptomyces phaeofaciens No. 7739, was found to inhibit PAF-induced rabbit platelet aggregation with an IC50 of 3.7 x 10(-7)M. FR900452, 1-methyl-3-[1-[5- methylthiomethyl-6-oxo-3-(2-oxo-3-cyclopenten-1-yli- dene)-2-piperazinyl]ethyl]-2-indoline, has an oxocylopentylidene group incorporated as a vinylogous amide in a diketopiperazine skeleton. This unique structure led us to synthesize diketopiperazine derivatives, 3-arylalkyl- 6-substituted-piperazine-2,5-diones. Their observed PAF inhibitory activity suggest that the D-D configuration of diketopiperazine is an important factor for anti-PAF activity and that the hydrophobic aromatic portion may play a specific role in the binding of the diketopiperazine to the PAF receptor.

Animals↗
PubMed1991

Lymphocytic adenohypophysitis: an immunohistochemical study.

Lymphocytic adenohypophysitis is a rare inflammatory disorder of the anterior pituitary gland. In some cases, there is evidence of concurrent autoimmune disease. We present the case of a 39-year-old woman who developed visual disturbance during the early postpartum period. Magnetic resonance imaging revealed an intrasellar mass with suprasellar extension. Study of the tumor tissue showed diffuse infiltration of the entire pituitary gland by lymphocytes and plasma cells. Immunohistochemical examination revealed that the majority of the infiltrating lymphocytes were T cells that might have modulated the immunoreaction to the anterior pituitary gland. We suggest that the disorder is related to cell-mediated immunity as well as humoral immunity.

Adult↗
PubMed1991

Age-related increase in the uptake of acetylated low density lipoprotein into cultured endothelial cells from rat aorta.

A simple and reliable method for the separation of endothelial cells from the thoracic aorta of rats was established in the present study. The cultured endothelial cells separated by this improved explantation method showed typical characteristics of endothelial cells, morphology of cobblestone monolayer, immunoreactivity against antibodies to Von Willebrand's factor and angiotensin I converting enzyme, and the ability to uptake acetylated low density lipoprotein (LDL) labeled with 1,1'-dioctadecyl-1-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI-Ac-LDL). The purity of the cultured endothelial cells separated by this method was over 98%, and the cells were maintained in culture for 3-4 months. Age-related changes of the uptake of DiI-Ac-LDL into the endothelial cells were then estimated by using the cultured endothelial cells separated from the aortas of young (4-8 weeks old) and old (95-100 weeks old) rats. When fluorescent DiI-Ac-LDL-labeled endothelial cells were sorted and analyzed by a cell sorter, the fluorescence intensity of the cultured cells from old rats was stronger than that of the cells from young rats. Therefore, the present results show that the uptake of the acetylated LDL into the endothelial cells increases with rat aging, and suggest the age-related increase in the acetyl LDL receptor in the endothelial cells of the rat aorta.

Acetylation↗
PubMed1991

Cross-adaptive response in Escherichia coli caused by pretreatment with H2O2 against formaldehyde and other aldehyde compounds.

A cross-adaptive response (CAR), defined as a reduction of the effects of an agent by pretreatment with another agent, was demonstrated when E. coli WP2 cells were pretreated with hydrogen peroxide (H2O2) followed by challenging treatment with aldehyde compounds. Pretreatment with a sublethal dose (60 microM) of H2O2 for 30 min made WP2 cells resistant to the killing effects of formaldehyde (FA), and 4 other mutagenic aldehydes: glutaraldehyde, glyoxal, methyl glyoxal and chloroacetaldehyde. CAR was also observed in WP2uvrA (uvrA-) and ZA12 (umuC-) cells, but not in ZA60 (recA-) and CM561 (lexA- (Ind-] cells. A role of recA and lexA in CAR was further suggested by the lack of beta-galactosidase induction in recA- and lexA- cells by H2O2. CAR and beta-galactosidase induction, however, were found to be separate events since CAR was recovered by introducing the recA+ gene into lexA- cells, but no induction of beta-galactosidase by H2O2 was observed in cells with the same gene transfer. These results suggest that H2O2 has the capacity to induce a function which reduces the killing effects of aldehydes, and the function is controlled by the recA gene without involvement of SOS response.

Acclimatization↗
PubMed1991

Effects of bestatin (Ubenimex) on human T-cell colony formation.

The antitumor action of bestatin is considered to be an indirect action mediated by T-cells. Therefore, we investigated the effects of bestatin on the differentiation and proliferation of human precursor T-cells using a colony formation technique. Bestatin did not increase the overall number of T-cell colonies, but it significantly increased in CD4+ cell and significantly decreased in CD8+ cell subpopulations. It also induced CD4+.8+ cells. These findings indicated that bestatin acts on precursor T-cells to induce the differentiation of these cells into CD4+ cells.

Adult↗
PubMed1991

Orbitozygomatic temporopolar approach for a high basilar tip aneurysm associated with a short intracranial internal carotid artery: a new surgical approach.

For two cases of a high basilar tip aneurysm accompanied by a short intracranial internal carotid artery, the orbitozygomatic temporopolar approach consisting of an en bloc fronto-orbitozygomatic temporal craniotomy and temporopolar approach was carried out. On angiograms, the height of the bifurcation of an elongated basilar artery and the length of the intracranial internal carotid artery from the interclinoid line between the anterior and posterior clinoid process were 20 mm and 6 mm in Case 1, and 18 mm and 5 mm in Case 2, respectively. The skin flap was separated subfascially to preserve the frontotemporal branch of the facial nerve. The fronto-orbitozygomatic temporal bone flap was made, and a part of the basal bony structures of the orbital roof, the sphenoid ridge, and the temporal bone were removed. The basilar tip aneurysm could be seen and clipped easily by upward and oblique viewing from below through the wide operative space consisting of the less retracted internal carotid and middle cerebral arteries, the oculomotor nerve, the tentorial hiatus, and the emptied anterior temporal fossa obtained by partial division of the temporal bridging veins. The operative procedure is presented in detail and compared with other surgical approaches that have been described previously.

Basilar Artery↗
PubMed1991

Missing Y chromosome in Ph1-negative chronic myeloid leukemia with bcr rearrangement. Evidence for a bcr-abl recombination on chromosome 22 by in situ hybridization.

In a case of Philadelphia chromosome (Ph1)-negative chronic myeloid leukemia (CML) without the Y chromosome, we investigated the differences, at the molecular level, from Ph1-positive CML. Using Southern blot analysis and in situ hybridization studies, we could demonstrate a rearrangement within the breakpoint cluster region (bcr), and the location of a bcr-abl fusion gene on chromosome 22. To our knowledge, this is the first case of Ph1-negative CML with a loss of the Y chromosome in which the molecular abnormalities are shown to be identical with those in Ph1-positive CML.

Chromosome Aberrations↗
PubMed1991

Pharmacokinetics of haloperidol decanoate in rats.

Plasma levels of haloperidol decanoate and haloperidol after intramuscular administration of haloperidol decanoate in rats showed good fits with a multi-compartment model which was constituted by combination of 2-compartment models for the disposition of haloperidol and for its ester decanoate through the process of hydrolysis of the ester. Calculated parameters indicated that most of intramuscularly administered haloperidol decanoate is absorbed in blood after hydrolysis to haloperidol and the absorption is rate-limiting. Regional lymph node levels suggested that the intramuscularly administered ester was absorbed via the lymphatic system where the hydrolysis to haloperidol probably occurred. Thus, slow entrance and hydrolysis of haloperidol decanoate in the lymphatic system was considered to be the cause of sustained plasma levels of the active principle after intramuscular administration of haloperidol decanoate.

Animals↗
PubMed1991

Functional and structural domains of the sixth component (C6) of human complement.

The effects of serine protease inhibitors, diisopropyl fluorophosphate (DFP) and phenylmethanesulfonyl fluoride (PMSF), on hemolytic activity of C6 were reinvestigated. C6 was inactivated in a range of 1-10 mM by both of the inhibitors as previously reported. Limited proteolytic digestion was also studied to elucidate the functional and structural domains of C6. The major fragments produced by trypsin, plasmin, or lysyl endopeptidase could not be separated unless disulfide bonds were disrupted, but Staphylococcus aureus V8 protease yielded several fragments, each of which was not linked by disulfide bond. When C6 labeled with [3H]DFP was subjected to limited digestion with V8 protease, a fragment with a molecular weight of 38 kilodaltons (kDa) was mainly labeled and other fragments of 53 kDa and 26.4 kDa were also faintly labeled, while fragment 35 kDa wasn't labeled, indicating specific domains reactive with DFP. On the other hand, when C6 with or without DFP treatment was digested with V8 protease and those fragments were incubated with C5 and subjected to sucrose density ultracentrifugation, fragments 53, 38, 35 and 27.5 kDa interacted with C5 in both cases. These results suggest that C6 modified by DFP can interact with C5, and the amino-terminal sequences of fragment 38 and 35 kDa suggest the binding domain of C6 with C5 takes place within the two short consensus repeats.

Complement C6↗
PubMed1991

The response to acoustic stimulation and the changes in brain amine levels after repeated administration of beta-phenylethylamine in rats.

Reverse tolerance to stereotyped behavior was induced after repeated administration of beta-phenylethylamine (PEA) (50 mg/kg, i.p., daily for 10 days) in rats. The reverse tolerance was maintained for at least 4 weeks after the last administration. We studied the effects of acoustic stimulation on locomotor activity 2 days and 4 weeks after withdrawal from PEA and measured the changes in brain monoamine levels 4 weeks after the withdrawal. Locomotor activity during acoustic stimulation was increased in the saline treated group, and this response was unaffected after repeated PEA treatment. Four weeks after withdrawal, significant increases in noradrenaline levels in the cerebral cortex and decreases in 5-hydroxytryptamine levels in the hypothalamus were found. The effects of acoustic stimulation on locomotor activity and the changes in brain monoamine levels were different from those of methamphetamine treatment obtained in our previous study. In conclusion, it may be suggested that the response to acoustic stimulation after repeated PEA administration in rats cannot be a model for abnormal responsiveness to environmental stimulation that is observed in chronic paranoid schizophrenics.

Acoustic Stimulation↗