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Biomedical subjects

M Murakami

Publications and source records attributed to M Murakami.

At least 235 records · Page 13Linked to original sources
PubMed2000

Homeostasis of alpha beta TCR+ T cells.

Cytokines contribute to T cell homeostasis at all stages of T cell existence. However, the particular cytokine involved varies as T cells progress from a naïve through an activated to a memory state. In many cases the important cytokines are members of the interleukin 2 subfamily of the short-chain type I cytokines. A case is made for the idea that the evolutionary divergence of the short-chain family allowed for concurrent divergence in leukocytes.

Animals↗
PubMed2000

Acute abdomen without cutaneous signs of varicella zoster virus infection as a late complication of allogeneic bone marrow transplantation: importance of empiric therapy with acyclovir.

Two patients complained of severe abdominal pain as the first sign of varicella zoster virus infection about 1 year after allogeneic BMT. In case 1, eruptions, found on the face and chest on admission, became vesicular and dispersed on the third hospital day. Though acyclovir (ACV) was immediately started, he died on the fourth day. In case 2, skin rash was never observed during the clinical course. Laparotomy on the third hospital day revealed many hemorrhagic spots on the liver surface and mucous membrane of the upper GI tract, indicating disseminated visceral disease. Empiric therapy with ACV was successful.

Abdominal Pain↗
PubMed2000

Late onset cyclosporine-induced cerebral blindness with abnormal SPECT imagings in a patient undergoing unrelated bone marrow transplantation.

A 23-year-old woman underwent HLA-matched unrelated BMT for CML. She developed cerebral blindness on day 81. Brain magnetic resonance imaging revealed hyperintensity on a T2-weighted image in the white and gray matter of the right frontal and both occipital lobes. Single-photon emission computed tomography (SPECT) was consistent with a decrease in radionuclide uptake in these areas, suggesting a vasoconstrictive mechanism. A diagnosis of CsA-induced encephalopathy was made and CsA was discontinued. Her vision recovered completely after 24 h and abnormal imaging resolved within 2 weeks. This case demonstrates late onset CsA-induced cerebral blindness with the previously unreported abnormalities on SPECT.

Aged↗
PubMed2000

Cell membrane changes of structure and function in protein kinase inhibitor-induced polyploid cells.

Exogenous cyclic AMP has been thought to be a chemical without marked pharmacological effect until now, as it is not capable of penetrating the cell membrane in most eucaryotic cells. The present study obtained results consistent with those of most previous studies, showing that exogenous cyclic AMP itself did not interfere with the cell cycle even at the high dose of 100 microM. However, it was found that K252a, a potent inhibitor of protein kinases including protein kinase C, induced DNA re-replication, i.e. DNA synthesis at a elevated DNA ploidy in cells that had not undergone cytokinesis (leading to polyploidization), and that exogenous cyclic AMP markedly potentiated the K252a-induced polyploidization at a very low dose similar to the effective dose of membrane-permeable cyclic AMP analogue dibutyryl cyclic AMP. These findings suggested that the cell membrane changed during the formation of polyploid cells. This supposition was confirmed by scanning electron microscopy to observe structural changes and by determination of cellular attachment to investigate functional changes.

Animals↗
PubMed2000

Mast cell tryptase from pig lungs triggers infection by pneumotropic Sendai and influenza A viruses. Purification and characterization.

A novel trypsin-type serine proteinase, which processes the precursors of the envelope fusion glycoproteins of pneumotropic Sendai and human influenza A viruses, was purified to homogeneity from pig lungs. On SDS/PAGE, the purified enzyme gave a protein band corresponding to about 32 kDa, and has an apparent molecular mass of 120 kDa, as determined by gel permeation chromatography. Immunohistochemical staining with antibodies against this enzyme revealed that the enzyme is located in pig lung mast cells. The N-terminal 44-amino-acid sequence of the enzyme exhibits about 80% identity with those of mast cell tryptases from other species. Of the inhibitors tested, di-isopropyl fluorophosphate, antipain, leupeptin, benzamidine and a few proteinaceous inhibitors, such as mucus protease inhibitor and aprotinin, inhibited this enzyme activity. Heparin stabilized the enzyme, but high-ionic-strength conditions did not, unlike for human mast cell tryptase. The purified enzyme efficiently processed the fusion glycoprotein precursor of Sendai virus and slowly processed hemagglutinin of human influenza A virus, and triggered the infectivity of Sendai virus in a dose-dependent manner, although human mast cell tryptase beta and rat mast cell tryptase (rat MCP-7) from lungs did not process these fusion glycoproteins at all. These results suggest that mast cell tryptase in pig lungs is the possible trigger of the pneumotropic virus infections.

Amino Acid Sequence↗
PubMed2000

KRH-594, a new angiotensin AT1 receptor antagonist, ameliorates nephropathy and hyperlipidaemia in diabetic spontaneously hypertensive rats.

1. We examined whether KRH-594, a new angiotensin AT1 receptor antagonist, ameliorates the progression of diabetic nephropathy and hyperlipidaemia in streptozotocin (STZ)-induced diabetic unilateral nephrectomized spontaneously hypertensive rats (DM-1K-SHR) or not. 2. The oral administration of KRH-594 (3 and 10 mg/kg per day) and candesartan cilexetil (1 mg/kg per day) for 16 weeks significantly reduced systolic blood pressure, urinary albumin and urinary total protein in DM-1K-SHR. 3. In a histological study, KRH-594 (3 and 10mg/kg per day) and candesartan cilexetil (0.3 and 1 mg/kg per day) dose-dependently improved glomerulosclerosis and the hyalin cast of tubules in DM-1K-SHR kidneys. Both KRH-594 (10 mg/kg per day) and candesartan cilexetil (0.3 and 1 mg/kg per day) dose-dependently inhibited cardiac hypertrophy. 4. KRH-594 (3 and 10 mg/kg per day), but not candesartan cilexetil, dose-dependently reduced the levels of triglyceride, total cholesterol and phospholipids in DM-1K-SHR. 5. These results suggest that KRH-594 improves diabetic complications, such as nephropathy and hyperlipidaemia, with hypertension.

Albuminuria↗
PubMed2000

Ileal carcinoid tumor complicating carcinoid heart disease and secondary retroperitoneal fibrosis.

A 70-year-old man with metastatic liver tumors showed carcinoid syndrome with clinical symptoms of facial flushing, palpitation, dyspnea, and an itching sensation. Regurgitation of the tricuspid and aortic valves was observed by echocardiography. An elevated serum level of serotonin and a high urine excretion of serotonin metabolites were confirmed. Autopsy confirmed a serotonin-immunoreactive 1 cm ileal carcinoid tumor with metastasis to the liver, bone and peritoneum. The tumor cells were argyrophilic but not argentaffin, and showed erythrophagocytosis in the primary lesion. All the four heart valves and bilateral atrial endocardium showed fibromyxoid thickening, indicating the association of carcinoid heart disease. Desmoplastic reaction with deposition of sulfated acid mucopolysaccharides was also observed in the retroperitoneal space (secondary retroperitoneal fibrosis). Stenosis of the bilateral ureters and inferior mesenteric artery provoked hydronephrosis and lethal ischemic necrosis of the left-sided colon, respectively. Rarity of functioning ileal carcinoid tumor and pathogenesis of systemic fibroplasia are discussed.

Aged↗
PubMed2000

Primary primitive neuroectodermal tumor of the kidney.

Primitive neuroectodermal tumor (PNET) is a small round cell sarcoma that mainly develops in the central nervous system and soft tissues of childhood; however recently, primary occurrence of this tumor in the kidney has been reported. We experienced one case of PNET primarily arose in the kidney without metastasis. The patient was a 28-year-old man whose chief complaint was abdominal pain, especially on exercise. On computed tomography scan and magnetic resonance imaging, a solid lesion was found in the left kidney, and a left nephrectomy was performed based on the diagnosis of a tumor in the left kidney. The tumor was within the parenchyma of lower end of left kidney protruding into the abdominal cavity. Histologically, diffuse proliferation of primitive small round cells with rosette formation was found. Immunohistochemically, MIC2 gene product, neuron-specific enolase and S-100 protein were positive. No metastasis to the regional lymph nodes was found. From these observations, the tumor was diagnosed as PNET primarily arising in the left kidney. Although chromosome analysis was not performed, EWS-FLI1 chimera gene was identified by reverse transcriptase-polymerase chain reaction on the freshly frozen specimen and fluorescence in situ hybridization on paraffin sections.

12E7 Antigen↗
PubMed2000

Mismatched clinicopathological response after concurrent chemoradiotherapy for thoracic esophageal cancer.

We have been treating patients with operable thoracic esophageal cancer according to our own protocol. It includes the initial concurrent chemoradiotherapy (CRT) followed by continuous CRT or surgery. Patients with good response to initial chemoradiotherapy were allowed to continue chemoradiotherapy, whereas the others were treated with surgery. However, there were two cases which showed discrepancies in the clinicopathological response. Both patients received initial chemoradiotherapy, including two courses of cisplatin (100-120 mg), 5-fluorouracil (750-1000 mg for 4 days) and radiation (44-50 Gy). On completion of the initial chemoradiotherapy, all diagnostic imaging modalities including barium swallow, esophagoscopy, endoscopic ultrasonography and thoracic computed tomography strongly implicated residual tumor with a reduction rate of 40-50%. The patients underwent radical esophagectomy 15-20 days after initial chemoradiotherapy. Pathological specimens only revealed thickening of the esophageal wall due to inflammatory change without residual carcinoma. These facts suggest the current limitations of diagnostic images in evaluating the response to chemoradiotherapy.

Aged↗
PubMed2000

Effect of teprenone on gastric mucosal injury induced by Helicobacter pylori in rats.

The aim of this study was to investigate the protective effect of gastric mucus against Helicobacter pylori-induced gastric mucosal injury, measuring intramucosal mucus and the surface hydrophobicity. Male Sprague-Dawley rats' stomachs were exposed to H. pylori suspension (1 x 10(5) ml) plus 1 ml of urea solution (400 mg/dl) with gastric ischemia (withdrawal of 3 ml of blood) for 60 min, 60 min after pretreatment with teprenone (CAS 6809-52-5) (50 mg/rat, intragastric). The control rats were treated in the same manner without pretreatment with teprenone. A high concentration of intragastric ammonia was generated 60 min after administration of H. pylori plus urea in both the control and the teprenone-pretreated rats. A reduction in transmucosal potential difference, formation of hemorrhagic gastric lesions, and impairment in both intramucosal mucus and surface hydrophobicity were observed in the corpus of the control rats. However, the pretreatment with teprenone prevented such a reduction in potential difference and the development of gastric lesions against ammonia through the preservation of gastric mucus. The preservation of gastric mucus might protect gastric mucosa against attacks by H. pylori, suggesting that the mechanism of H. pylori-associated gastric injury is associated with the decrease in gastric mucus.

Animals↗
PubMed2000

Serum levels of soluble IL-2 receptor, IL-12, IL-18, and IFN-gamma in patients with acute graft-versus-host disease after allogeneic bone marrow transplantation.

BACKGROUND: Acute graft-versus-host disease still represents the major factor that limits successful allogeneic bone marrow transplantation. Cytokines released by type 1 T-helper cells are thought to play a pivotal role in acute graft-versus-host disease. OBJECTIVE: This study was performed to investigate whether the serum levels of soluble IL-2 receptor, IL-12, IL-18, and IFN-gamma were associated with the manifestation of acute graft-versus-host disease. METHODS: Serum cytokine levels were measured by sandwich ELISA in 18 patients who underwent allogeneic bone marrow transplantation. RESULTS: Serum levels of soluble IL-2 receptor, IL-12, IL-18, and IFN-gamma were increased in patients in whom acute graft-versus-host disease developed. However, only serum soluble IL-2 receptor levels were significantly related to disease severity. Serum levels of IL-12 and IL-18, both of which are mainly produced by activated macrophages, were increased in different phases of acute graft-versus-host disease, especially grade I. Serum levels of soluble IL-2 receptor and IFN-gamma were significantly elevated in patients with fever. CONCLUSION: Serum levels of soluble IL-2 receptor were more closely related to the severity of acute graft-versus-host disease than those of IL-12, IL-18, and IFN-gamma.

Acute Disease↗
PubMed2000

Relationship between amylase and fluid secretion in the isolated perfused whole parotid gland of the rat.

Whole gland perfusion technique was applied to rat parotid glands to assess whether amylase affects fluid secretion. Control perfusion without any secretagogue evoked no spontaneous secretion. Carbachol (CCh 1 microM) induced both amylase and fluid secretion with distinctive kinetics. Fluid secretion occurred constantly at 40-120 microliter/g-min (average plateau was 60 microliter/g-min), whereas amylase secretion exhibited an initial peak (10 mg maltose/30 s per g wet w. of the gland), followed by a rapid decrease to reach a plateau level of 1 mg maltose/30 s later than 1.5-2 min. Isoproterenol (Isop 1 microM) alone did not induce fluid secretion although it evoked amylase secretion as measured in isolated perfused acini. Addition of Isop during CCh stimulation evoked a rapid and large rise in amylase secretion to 15 mg maltose/30 s accompanied by the increase in oxygen consumption. However, the fluid secretion exhibited a rather gradual decrease. These findings suggest that control of salivary fluid secretion is independent of the amylase secretion system induced by CCh and/or Isop. Morphological observations carried out by HR SEM and TEM revealed exocytotic profiles following Isop stimulation. CCh stimulation alone seldom showed -exocytotic profiles, suggesting a low incidence of amylase secretion during copious fluid secretion. Combined stimulation of CCh and Isop induced both vacuolation and exocytosis along intercellular canaliculi. During washout of secretagogues, lysosomal digestion of excess membrane took place.

Amylases↗
PubMed2000

Transduction ion channels directly gated by sugars on the insect taste cell.

Insects detect sugars and amino acids by a specialized taste cell, the sugar receptor cell, in the taste hairs located on their labela and tarsi. We patch-clamped sensory processes of taste cells regenerated from the cut end of the taste hairs on the labelum of the flashfly isolated from the pupa approximately 20 h before emergence. We recorded both single channel and ensemble currents of novel ion channels located on the distal membrane of the sensory process of the sugar receptor cell. In the stable outside-out patch membrane excised from the sensory processes, we could repeatedly record sucrose-induced currents for tens of minutes without appreciable decrease. An inhibitor of G-protein activation, GDP-beta-S, did not significantly decrease the sucrose response. These results strongly suggested that the channel is an ionotropic receptor (a receptor/channel complex), activated directly by sucrose without mediation by second messengers or G protein. The channel was shown to be a nonselective cation channel. Analyses of single channel currents showed that the sucrose-gated channel has a single channel conductance of approximately 30 pS and has a very short mean open time of approximately 0.23 ms. It is inhibited by external Ca(2+) and the dose-current amplitude relation could be described by a Michaelis-Menten curve with an apparent dissociation constant of approximately 270 mM. We also report transduction ion channels of the receptor/channel complex type directly gated by fructose and those gated by L-valine located on the sensory process.

Algorithms↗
PubMed2000

Conserved smooth muscle contractility and blood pressure increase in response to high-salt diet in mice lacking the beta3 subunit of the voltage-dependent calcium channel.

Voltage-dependent calcium channels are crucially important for calcium influx and the following smooth muscle contraction. Beta subunits of these channels are known to modify calcium currents through pore-forming alpha subunits. Among the four reported independent beta subunits, the beta3 subunit is expressed in smooth muscle cells and thought to compose L-type calcium channels in the tissue. To determine the role of the beta3 subunit in the cardiovascular system, we have analyzed beta3-null mice. Electrophysiological examinations proved the existence of dihydropyridine (DHP)-sensitive. L-type calcium channels in the smooth muscle cells. Beta3-null mice show no apparent changes in smooth muscle contraction and sensitivity to DHP, and normal blood pressure when they are raised on a normal diet, but the 13 subunit deficient mice show elevated blood pressure in response to a high-salt diet, with significant reductions in plasma catecholamine concentrations. Our finding strongly suggests a close relationship between voltage-dependent channels and high blood pressure.

Animals↗
PubMed2000

Greater than normal expression of the collagen-binding stress protein heat-shock protein-47 in the infarct zone in rats after experimentally-induced myocardial infarction.

BACKGROUND: The heat-shock protein with relative molecular mass 47,000 (HSP47) can bind to procollagen molecules in the endoplasmic reticulum, and acts as a molecular chaperone during the processing and secretion of procollagen. OBJECTIVE: To test our hypothesis that HSP47 is expressed in the myocardial infarct zone. METHODS: We induced myocardial infarction in male Sprague-Dawley rats by ligation of left coronary artery. The expression of HSP47 was examined by Northern blotting, in-situ hybridization, Western blotting and immunohistochemistry. The time-dependent change in the distribution of HSP47 messenger RNA (mRNA) signal was compared with the changes in expression of alpha 1(I) and alpha 1(III) collagen mRNA by in-situ hybridization. The hypoxic induction of HSP47 in cultured cardiac fibroblasts was examined by Northern-blot analysis. RESULTS: Northern blotting demonstrated that the expression of HSP47 mRNA had increased on day 2, reaching a maximum level around day 14 (induced 3.5-fold compared with the preligation hearts) and was maintained at a high level up to day 28. In-situ hybridization analysis revealed HSP47 mRNA signals in spindle-shaped mesenchymal cells located between surviving myocytes in the infarct's peripheral zone 24 h after the ligation, and in the entire infarct zone on day 14. The sequential changes in distribution of HSP47 mRNA signal were identical to those of the alpha 1(I) and alpha 1(III) collagen mRNA. Western blotting demonstrated that expression of HSP47 protein in the infarct zone had increased. Immunofluorescent staining revealed positivity for HSP47 in the infarct's peripheral zone on day 2 and in the entire infarct zone on day 14. Northern blotting revealed that the expression of HSP47 mRNA in cultured cardiac fibroblasts in hypoxic cultures was greater than that in normoxic cultures. CONCLUSION: The present data demonstrated that an increase in expression of HSP47 is produced by spindle-shaped mesenchymal cells in the infarct zone. Expression of HSP47 mRNA was concurrent with the expression of collagen mRNA of types I and III. Hypoxia is one of the factors which induces expression of HSP47.

Animals↗
PubMed2000

The role of osteopontin in the development of granulomatous lesions in lung.

Osteopontin (OPN) has been shown to be expressed by cells in granulomas of various origins, but whether it plays a functional role in granuloma formation is not known. Here we used a cardiomyopathic hamster (TO2) model, to test the hypothesis that OPN contributes functionally to granuloma development. We immunized cardiomyopathic and normal hamsters by subcutaneous injection of bovine serum albumin in complete Freund's adjuvant, and assessed various tissues for both OPN RNA expression and granuloma formation. Cardiomyopathic hamsters expressed OPN, and formed granulomatous lesions, in heart tissue in both immunized and untreated animals. In addition, immunization induced expression of OPN in lung and lymph nodes of cardiomyopathic (but not normal) hamsters, and also induced granuloma formation in these organs. To test whether OPN expression could play a functional role in inducing granulomas, we produced an adenoviral vector containing the murine OPN gene, and introduced this vector intratracheally into the lungs of normal hamsters. The OPN-containing vector, but not the control vector, induced pulmonary granuloma formation. These studies provided direct in vivo evidence that OPN can contribute functionally to the formation of granulomatous lesions, and suggest that OPN expression may be a common factor involved in formation of granulomas of various origin.

Adenoviridae↗
PubMed2000

Chemopreventive effect of bovine lactoferrin on 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in male F344 rats.

The modifying effects of dietary feeding of bovine lactoferrin (bLF) on tongue carcinogenesis initiated with 4-nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats. The activities of phase II detoxifying enzymes, glutathione S-transferase (GST) and quinone reductase (QR), polyamine content and ornithine decarboxylase (ODC) activity in the tongue were also examined for mechanistic analysis of possible modifying effects of bLF on carcinogenesis. At 7 weeks of age, all animals except those treated with bLF alone and untreated rats were given 20 ppm 4-NQO in drinking water for 8 weeks to induce tongue neoplasms. Starting 7 days before 4-NQO exposure, experimental groups were fed experimental diets containing bLF (0.2% and 2%) for 10 weeks ("initiation feeding"). Starting 1 week after the cessation of exposure to 4-NQO, the other experimental groups given 4-NQO and a basal diet were fed the experimental diets for 22 weeks ("postinitiation feeding"). At week 32, the incidence and multiplicity of tongue neoplasms in the "initiation feeding" groups of 0.2% and 2% bLF and the "post-initiation feeding" group of 0.2% bLF were lower than those of the 4-NQO alone group, but without statistical significance. However, "post-initiation feeding" of 2% bLF caused a significant reduction in the incidence (20% vs. 55%, P=0.02418) and multiplicity (0.25+/-0.54 vs. 0.70+/-0.71, P<0.05) of tongue squamous cell carcinoma (by 64%, P=0.02418). bLF treatment elevated liver and tongue GST activities and liver QR activity. The "post-initiation feeding" with 2% bLF significantly decreased QR activity, proliferating cell nulcear antigen-positive index and ODC activity in the tongue. In addition, feeding with bLF decreased tongue polyamine content. These results suggest that bLF, when given at the 2% dose level during the post-initiation phase, exerts chemopreventive action against tongue tumorigenesis through modification of cell proliferation activity and/or the activities of detoxifying enzymes.

4-Nitroquinoline-1-oxide↗