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Biomedical subjects

M Hashimoto

Publications and source records attributed to M Hashimoto.

At least 91 records · Page 5Linked to original sources

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

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

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

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

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

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

Bombesin and bradykinin increase inositol phosphates and cytosolic free Ca2+, and stimulate DNA synthesis in human endometrial stromal cells.

The present studies were carried out to investigate the effect of several growth factors on human endometrial stromal cells. In human endometrial stromal cells, bombesin and bradykinin provoked an increase in intracellular free Ca2+ and in labelled inositol phosphates when pre-incubated with [3H]myoinositol. Some or possibly all of the initial increase in intracellular free Ca2+ represented a mobilization of Ca2+ from intracellular stores and the second phase of the response depended on Ca2+ influx from the extracellular medium. [3H]Thymidine was added to human cultured endometrial stromal cells with bombesin, bradykinin, epidermal growth factor (EGF), prostaglandin F2 alpha, vasopressin and platelet-derived growth factor. Bombesin, bradykinin and EGF stimulated the incorporation of [3H]thymidine into DNA in quiescent cells. In conclusion, bombesin and bradykinin are growth factors which activate phospholipase C in human endometrial stromal cells, while EGF stimulates DNA synthesis without the activation of phospholipase C.

Bombesin

The role of the paraventricular nucleus and pituitary gland in morphine analgesia.

The authors investigated the analgesic effects of small morphine doses injected into the paraventricular nucleus (PVN) of normal rats and hypophysectomized (Hx) rats. An injection cannula was stereotactically inserted into the PVN or third ventricle. On the 5-7th postoperative day, morphine (7 micrograms) was injected and the pain threshold (paw lick latency: PLL) was measured using a hot plate analgesia meter (52.0 +/- 0.1 degrees C). PVN morphine injection caused significantly longer PLL than the control (physiological saline) in both normal and Hx rats. Ventricular morphine injection did not increase PLL over the control. PVN is a site of morphine action. The analgesia induced by PVN morphine injection was not affected by hypophysectomy, or induced by leaking of morphine into the third ventricle.

Analgesia

Subependymoma of the lateral ventricle--case report.

A 56-year-old male presented with mild gait disturbance and short-term memory disturbance. Computed tomographic scans revealed an isodense mass with a large cyst in the left lateral ventricle, extending to the right. The tumor was removed totally via the left frontal transcortical approach. Light microscope examination found clusters of isomorphic cells separated by a dense fibrillar matrix. No ependymal rosettes or blepharoplasts were found. Some cluster cells had positive immunoperoxidase staining for glial fibrillary acidic protein and S-100 protein. Electron microscope observation found tumor cells with gap junctions and zonula adherens resembling the junctional complexes of normal ependymal cells, many microvilli and cilia, and long processes containing abundant glial fibrils. Such "transitional cells" may be important in establishing the origin of subependymoma.

Adenocarcinoma

Effects of insulin and myo-inositol on embryo growth and development during early organogenesis in streptozocin-induced diabetic rats.

We have previously shown that myo-inositol depletion in the embryonic tissue at a critical stage of organogenesis has a crucial role in hyperglycemia-induced embryopathy. This study tested whether myo-inositol depletion in early organogenesis contributes to the pathogenesis of streptozocin-induced diabetic embryopathy. Rats were made diabetic by streptozocin administration before conception, and the diabetic rats were treated with diet supplemented by 2% myo-inositol or insulin from 6 to 11 gestational days during the period of maximum teratological susceptibility. In each group on the 11th gestational day, growth retardation and incidence of malformations were recorded, and myo-inositol and sorbitol content in the embryonic and extraembryonic tissues were examined. In diabetic rats, the myo-inositol content of the embryos was decreased by 36% (P less than 0.01) compared with control rats, and there was growth retardation (crown-rump length 3.37 +/- 0.04 vs. 3.87 +/- 0.03 mm, P less than 0.01; somite no. 27.5 +/- 0.2 vs. 29.1 +/- 0.2, P less than 0.01) and a significantly increased incidence of the neural lesions (17.6 vs. 1.9%, P less than 0.01). Insulin treatment resulted in near normalization of maternal serum glucose and complete restoration of myo-inositol content in the embryos with significant improvement of the growth retardation (crown-rump length 3.55 +/- 0.06 vs. 3.37 +/- 0.04 mm, P less than 0.05; somite no. 28.2 +/- 0.13 vs. 27.5 +/- 0.2, P less than 0.05) and a significantly lowered incidence of neural lesions (2.5 vs. 17.6%, P less than 0.01) compared with those of the untreated diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Synthesis and inhibitory activity of acyl-peptidyl-pyrrolidine derivatives toward post-proline cleaving enzyme; a study of subsite specificity.

Several pyrrolidine derivatives have been synthesized and examined for their inhibitory activity on post-proline cleaving enzymes from Flavobacterium meningosepticum and bovine brain. Almost all the compounds tested in this study inhibited the activity of both enzymes at low IC50 values (from nM to microM) but a specificity difference was observed with alkylacyl-peptidyl-pyrrolidine derivatives which strongly inhibited only the bacterial enzyme. The most effective inhibitors have a proline residue on their P2 sites and a substituted or unsubstituted phenoxybutyryl moiety on their P3 sites. Thus phenoxybutyryl-prolyl-pyrrolidine is the most effective partial structure of the inhibitors. The best inhibitors found were: 4-(4-benzylphenoxy)butyryl-prolyl-pyrrolidine for bacterial enzyme (IC50 1.4 nM) and 4-phenylbutyryl-thioprolyl-pyrrolidine for bovine brain enzyme (IC50 67 nM). In the passive avoidance test, using amnesic rats experimentally induced with scopolamine, the pyrrolidine derivatives which had potent inhibitory activity toward post-proline cleaving enzymes also showed strong anti-amnesic activities at doses of 1-5 mg/kg, i.p.

Acylation

[Investigation of postoperative adjuvant chemotherapy in patients with transitional cell carcinoma of the upper urothelium. Nara Urooncology Research Group (NUORG)].

During the 5 years from January, 1985 to December, 1989, 88 patients with transitional cell carcinoma of the renal pelvis and/or ureter were operated curatively in the Department of Urology, Nara Medical University and the affiliated hospitals. There were 66 males and 22 females (3:1) and the mean age was 66.0 years old ranging from 34 to 82. Staging of the renal pelvic and ureteral cancer of each patient was determined by General Rule for Clinical and Pathological Studies on Renal Pelvic and Ureteral Cancer established jointly by Japanese Urological Association and The Japanese Society of Pathology in 1990. The over-all survival rates at 1 and 3 years were 91.2% and 74.0%, respectively. The 3 year survival rates of TS and TE were 80.5% and 41.7%. As for grading, the 3-year survival rates were 75.0% for G1, 70.1% for G2, and 75.2% for G3, respectively. The stage of the tumors affected the prognosis. Of 88 patients 26 (Group 1) received cisplatin based combination chemotherapy as a postoperative adjuvant therapy, and the remaining 62 (Group 2) received no such cytotoxic adjuvant chemotherapy. The 3-year survival rates were 63.3% in Group 1 and 78.9% in Group 2, however mean age of Group 1 was significantly younger than that of Group 2. In spite of the age matched trial, there were no significant differences in survival rates between both groups. Adverse effects of cisplatin based combination chemotherapy included gastrointestinal symptom, fatigue, alopecia and leukopenia, however no serious toxicity was seen. These results suggest that prospective randomized trial would be clarified the efficacy of postoperative adjuvant chemotherapy for patients with renal pelvic and/or ureteral cancer.

Adult

WF-2421, a new aldose reductase inhibitor produced from a fungus, Humicola grisea.

WF-2421 is a novel aldose reductase inhibitor produced by Humicola grisea. WF-2421 was purified from the culture filtrate by successive ion exchange chromatography and the chemical structure was assigned to be alpha-formamido-5'-(2-formamido-1-hydroxyethyl)- beta,2',6-trihydroxy-3-biphenylpropanoic acid (1) on the basis of spectroscopic evidence. The IC50 value of WF-2421 was 3 x 10(-8) M against partially purified aldose reductase of rabbit lens.

Aldehyde Reductase

Human papillomavirus type 31 DNA detected in part of the dysplasia but in no part of the squamous metaplasia in a specimen taken from one patient.

Using in situ hybridization, human papillomavirus (HPV 6, 16, 18, 31, 33) DNAs were detected in a cervical severe dysplasia accompanied by squamous metaplasia. It was found that, only HPV 31 DNA was harbored in the cervical severe dysplasia, but HPV DNAs were not identified in a lesion of squamous metaplasia. The in situ hybridization method will be of use, therefore, when dysplasia with squamous metaplasia or other lesions are examined for HPV DNA. In a cervical smear, HPV 31 DNA could be detected on the nuclei of dysplastic cells, so this method is applicable to cervical smears. If squamous metaplasia is to be considered as a precursor lesion to cervical dysplasia, the HPV DNA harbored in the dysplasia must also be detected in the accompanying squamous metaplasia. Our results suggested that not all squamous metaplasias were involved with HPV, as far as we were able to detect using five types of HPV DNA probe.

Adult