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Biomedical subjects

M Yamamura

Publications and source records attributed to M Yamamura.

At least 109 records · Page 6Linked to original sources

Changes in striatal dopamine metabolism after microsphere embolism in rats.

BACKGROUND AND PURPOSE: Dopamine plays an important role in striatal function. The present study was undertaken to elucidate the pathophysiological changes in striatal dopamine metabolism after microsphere embolism. METHODS: Microspheres (48 microns) were injected into the right internal carotid artery of rats. Extracellular levels of dopamine and its metabolites were measured by in vivo microdialysis with the aid of high-performance liquid chromatography. In vivo striatal tyrosine hydroxylation and turnover (catabolism) rate of dopamine were estimated on the first and third days after the embolism. These were estimated by measuring tissue dopa or dopamine content in the presence of either an aromatic L-amino acid decarboxylase inhibitor or a tyrosine hydroxylase inhibitor, respectively. RESULTS: In the microdialysis study, a 190-fold increase in the release of dopamine from the right striatum was observed 40 minutes after microsphere embolism, whereas the striatal dopamine metabolites decreased during the first 180 minutes after the embolism. Microsphere embolism decreased the striatal dopamine content throughout the experiment (28 days), whereas it increased tissue dopamine metabolites on the first day, followed by a decline in the metabolites on the third day or later. The in vivo turnover rate of dopamine decreased both on the first and third days, whereas the in vivo tyrosine hydroxylation decreased only on the third day after the embolism. CONCLUSIONS: The results suggest that microsphere embolism induces severe damage to striatal dopaminergic metabolism 3 to 28 days after the embolism. Dopamine synthesis may be more resistant to the embolism-induced ischemic insults than its catabolism.

3,4-Dihydroxyphenylacetic Acid↗

Regulation of heat production of brown adipocytes via typical and atypical beta-adrenoceptors in the rat.

Previous studies in our laboratory demonstrated that microcalorimetry is an appropriate method for estimating the physiological function of isolated rat brown adipocytes. In the present study, to elucidate the mode of action of typical and atypical beta-adrenoceptors on heat production of this cell, the effect of novel adrenergic beta 3-agonists was compared with that of other typical adrenergic reagents by direct microcalorimetry. Isoproterenol and beta 3-agonists, BRL37344, ICI215001, and CGP12177, increased heat production in a dose-dependent manner, however, phenylephrine had no effect. Propranolol and pindolol did not increase the heat production but attenuated the effect of isoproterenol and BRL37344 in a dose-dependent manner. Molar IC50 values of propranolol and pindolol for BRL37344 were about 10(-5) and 3 x 10(-6) M, respectively, whereas those of the two antagonists for isoproterenol were about 3 x 10(-7)M. The pA2 values by Schild analysis of propranolol vs. isoproterenol and BRL37344 were 7.91 and 6.13, respectively. These results suggest that heat production may be regulated via both beta 3- and typical beta-adrenoceptors in brown adipocytes.

Adipose Tissue, Brown↗

[Trial of combined cytosine arabinoside with granulocyte colony-stimulating factor therapy or refractory acute myeloid leukemia].

Thirteen cases, including 10 relapse cases, of refractory acute myeloid leukemia (AML) (aged 17-70, median 46) by cytosine arabinoside (Ara-C) combined with granulocyte colony-stimulating factor (G-CSF) simultaneously to enhance the sensitivity to Ara-C. Low dose Ara-C (10-40 mg/day) combined with G-CSF was administered in most of them. Complete (CR) and partial remission (PR) were achieved in 5 and 4 patients, respectively, and response (CR + PR) rate was 69.2%. We obtained 5 CRs and 3 PRs in 10 patients with relapsed AML. However, CR and PR duration was short in all cases. None of the 3 patients with MO, AML transformed from myelodysplastic syndrome (MDS), and de novo AML with trilineage myelodysplasia (TMDS) had any response. There was no leukemic colony formation in the culture medium containing G-CSF in the nonresponding patients. The combination therapy caused severe myelosuppression, and most patients experienced prolonged neutropenia, and suffered from infections. In some patients enhanced chemosensitivity of leukemic cells induced by G-CSF was indicated but, the effect of this approach must be determined by large scale controlled studies.

Adolescent↗

Leukocytapheresis therapy with leukocyte removal filter for inflammatory bowel disease.

Leukocytapheresis (LCAP) with a leukocyte removal filter was administered to 44 patients with inflammatory bowel disease (IBD), diagnosed as ulcerative colitis (UC) in 25 and Crohn's disease (CD) in 19. Clinical and blood examinations showed no side effects in any of the patients. During intensive therapy, clinical improvement was recognized in 21 of the 25 UC patients (84%), 8 of whom had an excellent response, and in 16 of the 19 CD patients (84.2%), 4 of whom had an excellent response. The clinical improvement continued throughout the maintenance therapy in 19 of the UC patients (76%) and in 12 of the CD patients (63.2%). In both the UC and the CD patients, flow cytometry study showed that those who had improved generally had high values for the percentages of HLADR+, HLADR+CD3+, HLADR+CD8+, and CD11a+CD8+ cells before the first LCAP, and that these values decreased to near the normal range after both intensive and maintenance therapy. In the patients who showed poor response, in contrast, the values had been at or near normal before the initial LCAP administration. The clinical improvement and the findings on flow cytometry suggest that LCAP exerts an immuno-modulatory effect and is an effective therapy for patients with IBD in whom conventional drug treatments have failed.

Case-Control Studies↗

IL-12 regulates T helper type 1 cytokine responses in human infectious disease.

We investigated the role of IL-12 in regulating T cell and cytokine responses in human infectious disease by using the spectrum of leprosy as a model. Tuberculoid patients mount strong T cell responses to Mycobacterium leprae, with production of the type 1 cytokines IL-2 and IFN-gamma in lesions; whereas lepromatous patients manifest weak T cell responses to M. leprae, with production of the type 2 cytokines IL-4 and IL-10 in lesions. We found expression of IL-12 p40 mRNA, as measured by PCR amplification, and IL-12 p70, as measured by immunohistochemistry, to be 10-fold greater in tuberculoid lesions than in lepromatous lesions. The ability of M. leprae to stimulate release of IL-12 from monocytes was inhibited by rIL-4 and rIL-10. M. leprae-induced T cell proliferation in tuberculoid patients was blocked by the addition of neutralizing Abs to IL-12. Furthermore, rIL-12 stimulated proliferation of CD4+ type 1 T cell clones from tuberculoid lesions, but not CD8+ type 2 T cell clones from lepromatous lesions; however, both responded to rIL-2, rIL-12 augmented M. leprae-specific T cell proliferation in lepromatous patients, thereby causing the selective expansion of CD4+ T cells and increasing T cell IFN-gamma production. These data indicate that IL-12 is an important mediator in the generation of the type 1 cytokine response in human infectious disease.

Base Sequence↗

[Studies on angiotensin I converting enzyme (ACE): inhibitory effect of imidapril, a novel ACE inhibitor (II). Inhibition of various tissue ACEs ex vivo].

The antihypertensive mechanism of imidapril was investigated in relation to its inhibition of ACE activities in the serum, thoracic-abdominal aorta, lung, kidney, heart and brain from adult spontaneously hypertensive rats (SHRs). In comparison with normotensive rats (NTRs), the ACE activities in the aorta, heart, brain and lung were higher, while those in the serum and kidney were considerably lower. Imidapril (2 mg/kg) showed remarkable inhibitions within 6 hr in all tissues, except for the brain, after a single oral administration. Consecutive administration of imidapril (2 mg/kg/day) for 30 days produced inhibitions in all tissues. The inhibitions in the serum, aorta and lung were greater, and the duration of inhibition in the aorta, brain and lung were longer. Blood pressure declined gradually until 6 hr, and the reductions were significant at 24 hr after the single and chronic administrations. Imidapril (0.5 mg/kg, ineffective on normal blood pressure) inhibited ACE activities in NTRs similarly. Enalapril at the same dose exhibited less ACE inhibition and antihypertension. These results suggest that the ACE inhibition in the serum, lung and aorta by imidapril correlate with the antihypertension in SHRs; especially, the lung and vascular ACE inhibitions play an important role in the duration of antihypertension in SHRs.

Administration, Oral↗

Impaired interleukin-8-dependent chemotaxis by synovial fluid polymorphonuclear leukocytes in rheumatoid arthritis.

The accumulation of polymorphonuclear leukocytes (PMN) in synovial fluid is a common feature of rheumatoid arthritis (RA). We studied the chemotactic response of PMN obtained from the synovial fluid and from the peripheral blood of patients with RA using a modified Boyden's method, in which interleukin-8 (IL-8) or N-formyl-methionyl-leucyl-phenylalanine (FMLP) was used as a chemotactic agent. The IL-8-induced response of peripheral blood PMN from 15 patients with RA did not differ from that of 15 healthy controls. A decreased chemotactic response to IL-8 was, however, observed in PMN from the synovial fluid of 12 patients with RA compared with peripheral blood cells of the same individual. This defective chemotactic ability of PMN was inversely correlated with the number of infiltrating cells in the synovial fluid. We also obtained similar results with FMLP. These results indicate that the chemotactic ability of PMN may be reduced after migrating to the synovial fluid.

Adult↗

[Structural changes in jaw bone marrow after hemorrhagic infiltration].

UNLABELLED: Normal saline solution flushing of the inner mandible was done on twelve dogs, to confirm the effect of hemorrhagic infiltration that occurs in the fatty marrow. Histological examinations were performed at 1 hour, 5 days, 10 days, 2 weeks, 1 month and 3 months. RESULTS: 1. Marrow extrusion occurred at approximately 1 atm (injection pressure). 2. At 1 hour, marrow cavities located between the 2 injection holes with the exception of the extraction sites were filled with infiltrated blood cells. Fatty marrow was moderately replaced by the infiltrated blood cells in the extraction cavities and outer distal areas of the injection holes. 3. A sequence of histogenetic events occurred. The area of bone formation gradually expanded in the fibrous tissue area. 4. Expansion of the bone formation area was almost completed at 2 weeks. Most of the original marrow was transformed into thin trabeculae-forming areas, and hematopoiesis and sinusoidal capillaries formed in the new marrow. These conditions at 2 weeks were similarly maintained at 1 month. 5. At 3 months, the number of trabeculae, sinusoidal capillaries and hematopoietic area decreased, with the increase of adipose cells. 6. These results indicate that the area of fatty marrow where the hemorrhagic infiltration occurred was transformed into the bone formation area, and the marrow activates particularly high between the period of 2 weeks and 1 month.

Animals↗

[Clinical experiences of granulocyte colony stimulating factor for granulocytopenia after AC bypass].

We have successfully treated 3 cases of granulocytopenia, using Granulocyte Colony Stimulating Factor (G-CSF) after AC bypass surgery. All cases were male, aged 68, 75 & 54 years old, and underwent AC bypass surgery without transfusion except in case 1. Granulocyte cell counts decreased to 135/mm3 on 39th post-operative days (POD) in case 1, 624/mm3 on 13 rd POD in case 2, and 514/mm3 on 20th POD in case 3. In case 1, 300 micrograms of G-CSF was given intravenously for 3 days. In case 2, 100 micrograms of G-CSF for 1 day and 50 micrograms for 3 days was given subcutaneously, and in case 3, 100 micrograms of G-CSF was also given subcutaneously for 2 days. And their granulocyte cell counts all increased within few days. G-CSF is effective for patients with granulocytopenia after AC bypass surgery, but we need more experiences to know the best way of administration.

Aged↗

Role of nuclear histone-H1 kinase in regeneration of rat liver.

The activities of nuclear histone-H1 kinase and C-kinase as well as the amount of phosphate bound to histone-H1 following partial hepatectomy were studied in rat. It was found that the nuclear histone-H1 kinase activity increased twice within 80 h, first 20 to 30 h, and second at 50 to 70 h after partial hepatectomy. The timing of increase of the enzyme activity correlated with increased amount of bound phosphate. On the other hand, the increase of the C-kinase activities occurred between 5 and 15 h after partial hepatectomy. Antibodies raised against human cdk2, human cyclin-A and mouse cdc2 kinase showed no detectable effect on the nuclear histone H1 kinase activity. These results suggest that phosphorylation of histone-H1 in liver regeneration may be catalysed by a putative kinase(s).

Animals↗

Effects of cytotoxic factors of Helicobacter pylori on superoxide generation in situ in the rabbit stomach.

OBJECTIVE: To evaluate the effect of certain cytotoxic products of Helicobacter pylori on superoxide generation in situ and on the infiltration by polymorphonuclear cells into the gastric mucosa. The agents studied were ammonia, a culture supernatant of H. pylori, and N-formyl-methionyl-leucyl-phenylalanine (FMLP), a chemotactic factor. METHODS: One or two of these agents were dripped onto rabbit gastric epithelium. The number of polymorphonuclear cells in gastric mucosa were counted histologically. Superoxide generation was measured by a chemiluminescence method, using a Cypridina luciferin analog, 2-methyl-6-phenyl-3,7-dihydroimidazo[1,2-alpha]pyrazin-3-one , a chemiluminescence probe that responds to the generation of superoxides and singlet oxygen radicals. Bovine erythrocyte copper zinc superoxide dismutase was dripped to confirm that the increase in photon counts was a direct consequence of the generation of superoxides. RESULTS: The greatest infiltration of polymorphonuclear cells into the gastric mucosa was observed with the administration of 1 mmol/l FMLP followed by 5.9 mmol/l ammonia, and 10 mmol/l FMLP followed by 59 mmol/l ammonia. There was no increase in the number of polymorphonuclear cells in the other experiments. Increased chemiluminescence was observed in conjunction with the infiltration of polymorphonuclear cells and was inhibited by superoxide dismutase. CONCLUSIONS: Acute gastritis and superoxide generation in situ were induced by ammonia after pretreatment with FMLP.

Ammonia↗

[Constipation].

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Constipation↗

[Constipation].

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Constipation↗

[A case of coronary artery bypass grafting without cardiopulmonary bypass in a patient of both coronary ostial stenosis due to Takayasu's arteritis].

A 61-year-old female admitted with the diagnosis of both coronary ostial stenosis & the severe calcified aorta due to Takayasu's arteritis. She underwent coronary artery bypass grafting successfully, using the right internal thoracic artery to RCA & the left internal thoracic artery to LAD, without cardiopulmonary bypass. Coronary artery bypass grafting without cardiopulmonary bypass is one of the useful surgical technique for the patient with the severe calcified aorta due to Takayasu's arteritis.

Cardiopulmonary Bypass↗

Simultaneous occurrence of adenomas in stomach, duodenal bulb, and colon: disappearance of gastric and duodenal adenomas during oral administration of 5'-deoxy-5-fluorouridine.

The present report concerns a patient who was first diagnosed as having adenoma in the duodenal bulb and subsequently was discovered to have adenomas in the stomach and colon. Surgical procedures including endoscopic resection could not be carried out because the patient had advanced liver cirrhosis. Follow-up colonoscopy no longer detected any polyp in the colon. Ultrasonography demonstrated a slowly growing hypoechoic mass in the liver, which was indicative of hepatocellular carcinoma. Then, single chemotherapy with oral administration of 5'-deoxy-5-fluorouridine was initiated. Surprisingly, repeated esophagogastroduodenoscopy revealed gradual regression of the gastric and duodenal tumors. Findings from the endoscopy and biopsy materials 10 months after the start of therapy showed disappearance of the gastric and duodenal adenomas. Despite enlargement of the hepatic mass, no recurrence of gastric and duodenal tumors has been noted during the past 1 1/2 yr.

Adenoma↗