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Biomedical subjects

M Hashimoto

Publications and source records attributed to M Hashimoto.

At least 829 records · Page 46Linked to original sources

Changes in the hormone receptors of human breast carcinoma xenografts in nude mice by treatment with cytotoxic agents.

We examined the effect of chemotherapeutic agents on the estrogen receptors (ER) of breast carcinomas in vivo using human breast carcinoma strains (Br-10, T-61) serially transplanted into nude mice. When the tumor size reached approximately 1 X 1 X 1 cm, mitomycin C (MMC) at doses of 1, 2 and 4.5 mg/kg and cyclophosphamide (CPA) at a dose of 120 mg/kg, were administered once intraperitoneally, and the ERs of the tumors were measured sequentially by the dextran-coated charcoal method. Four days after the MMC administration at above doses, the binding sites of ER in Br-10 were not reduced and binding affinity was not affected. When the changes in ER content with time after the treatment with 4.5 mg/kg MMC and 120 mg/kg CPA were investigated, the ER content was found to be stable until 4 days after the treatment with both drugs, although the growth of T-61 had been significantly inhibited by the drugs. From these findings, it seems reasonable to initiate chemotherapy before endocrine therapy, since the chemotherapeutic agents did not reduce the ER content of the breast cancer strains.

Animals↗

Immunoreactive circulating alpha-interferon is low in Sjögren's syndrome.

Circulating alpha-interferon in plasma of 26 patients with Sjögren's syndrome was 0.069 +/- 0.034 ng/ml, a significant decrease compared with 0.119 +/- 0.051 ng/ml for age- and sex-matched healthy subjects (P less than 0.01) and compared with values previously found for healthy donors at ages 1-89 years. The results indicate the inability of Sjögren's syndrome patients to maintain circulating alpha-interferon.

Adult↗

Pharmacokinetics of a novel quinolone, AT-4140, in animals.

The pharmacokinetics of 5-amino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(cis-3,5-dimethyl-1- piperazinyl)-4-oxoquinoline-3-carboxylic acid (AT-4140) in experimental animals given a single oral dose of 5 mg/kg were studied. The mean peak levels of AT-4140 in plasma of mice, rats, dogs, and monkeys were 0.25, 0.50, 1.14, and 0.49 micrograms/ml, respectively, with mean elimination half-lives of 5.0, 3.8, 8.0, and 11.7 h, respectively. The oral bioavailability of AT-4140 calculated from the ratio of the areas under the concentration-time curve after oral and intravenous administration was 77% in dogs. The levels of AT-4140 in tissue in mice and rats were 1 to 11 times higher than the levels in plasma and 4 to 9 times higher than those of ciprofloxacin in mice. The mean 24-h biliary recovery of AT-4140 in rats was 5.6% of the dose and became 21.3% after beta-glucuronidase treatment. The mean 48-h urinary recoveries of AT-4140 in mice, rats, dogs, and monkeys were 6.7, 12.9, 8.6, and 12.7%, respectively, of the dose and were 7.8, 16.3, 8.9, and 18.9%, respectively, after beta-glucuronidase treatment. The pharmacokinetics of AT-4140 may be characterized by its good tissue penetration and its long half-life in plasma and tissues.

Administration, Oral↗

Salivary proline-rich protein polymorphisms in Chinese, Malays and Indians in Singapore.

Salivary proline-rich protein (PRP) polymorphism, PRH1, PRH2, Ps, Pm (PmF), PmS and Gl, were investigated in three ethnic groups in Singapore: Chinese, Malays and Indians. The phenotype and gene frequencies were presented and comparison with other ethnic groups was made. The As protein, which was recently found in Japanese but not in Caucasians as a new allelic product of the PRH1 locus, was also observed in Chinese and Malays but not in Indians. Another allelic product (Ps4) of Ps protein polymorphism was found in Malays but not in Chinese and Indians. The results indicate the usefulness of salivary PRP polymorphism as markers in population genetic studies.

Alleles↗

Abnormality of platelet membrane glycoprotein GPIIb in a myelodysplastic syndrome with 3q inversion presenting with marked dysmegakaryopoiesis.

Platelet membrane glycoproteins were analyzed in a case of myelodysplastic syndrome with inv(3) (q21q26) presenting with prominent dysmegakaryopoiesis by three different labelling techniques for surface proteins. Markedly decreased level of platelet membrane glycoprotein GPIIb was observed in the patient's platelets by terminal sialic acid labelling method, whereas no significant changes in the levels of glycoproteins including GPIIb could be detected either by penultimate galactose labelling or by tyrosine/histidine labelling. These results indicate a decreased sialylation of GPIIb in the patient's platelets, implying aberrant process in thrombopoiesis in the disease.

Bone Marrow Examination↗

Correlation between levels of plasma adenosine triphosphate and stress to the fetus at delivery.

Adenosine triphosphate (ATP) and its metabolites are released from intracellular stores and levels of ATP in the plasma are affected by hypoxia and by exercise. We examined levels of plasma ATP in the fetus at the time of obstetrical delivery. The arterial (ACB), venous cord (VCB) and maternal venous blood (MVB) samples were collected immediately after clamping of the cord. ATP was determined by the bioluminescence method. The levels of plasma ATP were significantly higher in ACB than in VCB or in MVB. There were significant correlations between the levels of ATP in ACB and in VCB, between the levels in ACB and in MVB and between the levels in MVB and in VCB. In case of delivery by elective cesarean section, the levels of ATP in ACB were significantly higher than those in ACB of the fetus delivered vaginally. We found a significant correlation between the levels of plasma ATP in ACB and PO2 in VCB, though there was no significant correlation between the levels of ATP and pH and PCO2. These observations suggest that ATP in ACB may be of fetal origin, that the levels decrease concomitantly in response to stress during vaginal delivery and correlate with the oxygen supplied from the placenta.

Adenosine Triphosphate↗

[Behavioral characteristics associated with acoustic stimulation and the neurochemical alterations of monoaminergic systems in rat brain at the steady state of repeated methamphetamine administration].

Behavioral characteristics associated with acoustic stimulation and the neurochemical alterations of monoaminergic systems in rat brain at the steady state of repeated methamphetamine administration were investigated. We confirmed that reverse tolerance in stereotyped behavior was constructed up to the 28th day after repeated intermittent pretreatment with increasing doses of MAP (2.5, 5, and 7.5 mg/kg x 3 and 10 mg/kg x 2, every other day). During acoustic stimulation, locomotor activity in the saline group was significantly increased, but the activity after the stimulation was completely suppressed. In contrast to the saline group, locomotor activity was not influenced by the acoustic stimulation in the MAP group, suggesting that behavioral hyporesponsiveness to acoustic stimulation was induced by MAP treatment. Two days after the last injection, the contents of 5-hydroxytryptamine (5-HT) and 5-hydroxyphenylacetic acid (5-HIAA) in the cerebral cortex, midbrain + thalamus, hypothalamus and striatum were significantly decreased. These changes were maintained up to the 28th day after the drug withdrawal in the cerebral cortex and the midbrain + thalamus. From these results, the persistence of behavioral hyporesponsiveness to acoustic stimulation might be associated with long-lasting reduction of 5-HT synthesis.

Acoustic Stimulation↗

Venous angioma: follow-up study and therapeutic considerations.

Ten patients with cerebral venous angioma (VA) were followed up for 12 to 106 months. Seven VAs were found as a result of intracerebral hemorrhage and the others were found incidentally. Among three VAs cauterized or partially excised, one disappeared but two were unchanged on follow-up angiography. Another VA, treated by irradiation following evacuation of the hematoma, gradually reduced in size on angiography. In the remaining six VAs treated conservatively, follow-up angiography demonstrated no visible change. During the follow-up period, bleeding from VA was encountered in one patient who had previously suffered from intracerebral hemorrhage. Prevention of bleeding from VA is considered important; however, complete extirpation of VA is difficult since the resectable area of normal brain parenchyma including the VA is very limited. From our experience, radiation therapy is believed to be useful when VA is considered to carry the risk of hemorrhage.

Adult↗

Antibodies to interleukin 2 in sera of autoimmune-prone mice.

Autoimmune-prone mice spontaneously develop the disease characterized by autoantibodies to a wide variety of antigens. In the present study, we have demonstrated that IgG antibodies to interleukin 2 (IL-2) are to be found in serum of autoimmune mice in association with ageing. These antibodies can neutralize the biological activity of IL-2 and thus play an important role in the etiopathogenesis of autoimmune disease.

Aging↗

Synthesis and inhibitory activity of acyl-peptidyl-prolinalderivatives toward post-proline cleaving enzyme as nootropic agents.

Several prolinal derivatives were synthesized and examined for their inhibitory activity on post-proline cleaving enzymes from Flavobacterium meningosepticum and bovine brain and their possible properties as nootropic agents. Almost all the compounds tested inhibited the activity of both enzymes at low IC50 values of the order of nM, but a specificity difference was observed with alkylacyl-prolinal derivatives which strongly inhibited only the bacterial enzyme. Prolyl-prolinal derivatives were the most effective inhibitors for both enzymes. In the passive avoidance test using amnesic rats experimentally induced with scopolamine, the prolinal derivatives that have potent inhibitory activity toward post-proline cleaving enzymes showed also strong anti-amnesic activities at dose of 10-1000 micrograms/kg, i.p. Some of the compounds showed a bell-shape dose dependency. These results suggest that the post-proline cleaving enzymes play an important role in the regulation of learning and memory consolidation in the brain and inhibitors of these enzymes are suggested as possible candidates for nootropic agents, particularly for an anti-amnesic drug.

Amino Acid Sequence↗

Changes in the components and content of biological water in the brain of experimental hydrocephalic rabbits.

Changes in biological water components and their respective content in the cortical gray matter and periventricular white matter were studied in rabbits rendered hydrocephalic by intracisternal kaolin injection. There was no change in either total water content or free or bound water content in the cortical gray matter at the various stages of hydrocephalus development. While there was no significant change in total water content in the periventricular white matter at any stage of hydrocephalus, free water content was significantly elevated and bound water content was decreased at the acute and subacute stages, with a return to relatively normal levels at the chronic stage. It is concluded that in the periventricular white matter, free water enters the brain across the ependymal lining during the acute and subacute stages of experimental hydrocephalus with a simultaneous reduction in the bound water and that there is some recovery at the chronic stage. It is suggested that alternative drainage pathways may develop in chronic hydrocephalus allowing drainage of free water in the periventricular white matter, which in turn permits bound water to return to relatively normal levels.

Animals↗

[Observation on implants of porous hydroxyapatite granules in periodontal osseous defects].

UNLABELLED: The purpose of this study was to observe the regeneration of the periodontal tissue using porous hydroxyapatite granules in experimental periodontal lesions. The upper lateral incisors of three Macaca fuscatae were extracted. After a 12-week recovery period, three wall infrabony defects were surgically prepared on the distal surface of the central incisors. In order to accumulate the plaque and cause inflammation, a wire with dental floss was placed inside the defects for a period of four weeks and then removed. Flap operations were performed and porous hydroxyapatite granules were placed into the defects. Twelve weeks after surgery, the samples were taken out and fixed in glutaraldehyde solution. They were embedded in polyester resin and undecalcified sections were prepared. The specimens were stained with toluidine blue and observed under light microscope. RESULTS: 1) The implanted area was divided into three distinctive zones. The first zone was located distally and occupied two-thirds of the total area. A large quantity of osseous tissue was detected. The second zone was situated near the root and presented only a small quantity of osseous tissue; Fibrous connective tissue predominated in the third zone adjacent to the root. 2) Bone apposition and resorption caused by physiologic mobility and movement of the teeth were observed. These results suggest that the elimination of the functional forces is advisable during the healing period whenever hydroxyapatite granules are placed into the periodontal defect.

Animals↗

WS-7528, a new isoflavanone with estrogen activity isolated from Streptomyces sp. No. 7528. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities.

WS-7528, produced by Streptomyces sp. No. 7528, was extracted from cultured broth, purified by solvent extraction followed by chromatography on silica gel and then isolated as pale yellow powder (C16H14O5, mp 95-98 degrees C). WS-7528 inhibited estrogen binding to its receptor protein in rat uterine cytosol. The IC50 value of WS-7528 for partially purified rat uterine cytosol receptor was 5.7 x 10(-8) M. This compound was found to induce the growth of the estrogen dependent cell line MCF-7. WS-7528 was tested orally and subcutaneously in immature rats to confirm its effect on the growth of the uterus. WS-7528 has also weak anti-inflammatory activity on the carrageenin paw edema of the rat model.

Animals↗

A novel antifungal antibiotic, FR-900848. I. Production, isolation, physico-chemical and biological properties.

Streptoverticillium fervens produced a new antibiotic, FR-900848, which has a high specific activity against filamentous fungi. Purified by solvent extraction and column chromatography, the compound appears as colorless crystals. Its structure is C32H43N3O6, which consists of 5'-amino-5'-deoxy-5,6-dihydrouridine with an unsaturated fatty acid having unprecedented four serial and one isolated cyclopropane rings.

Animals↗