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Biomedical subjects

H Murakami

Publications and source records attributed to H Murakami.

At least 217 records · Page 12Linked to original sources
PubMed1999

Pilot study of schistosomiasis control in Poyang lake region.

AIM: To perform a longitudinal survey of the control of schistosomiasis in Fanhu Village hyperendemic for schistosomiasis, Poyang Lake region of Jiangxi Province from 1992 to 1996. METHODS: Annual mass chemotherapy and health education were implemented in all investigated individuals, in 1996, artesunate was used in high risk population in transmission season as a prophylactic measure. RESULTS: The prevalence of S. japonicum infection reduced from 26.0% in 1992 to 10.7% in 1994, the intensity of infection (geometric mean of EPG of feces) in residents decreased from 1.92 in 1992 to 0.55 in 1994, and the morbidity indicators such as hepatomegaly and splenomegaly in the cases also have been improved significantly after chemotherapy. In 1995, both the infection rate and intensity of infection of schistosomiasis were recurred from 10.7% and 0.55 in 1994 to 18.4% and 1.04 respectively due to the floods. In 1996, the infection rate reduced to 5.0% and the intensity of infection also decreased to 0.25 due to the additional measure. CONCLUSION: A mass chemotherapy in conjunction with health education and oral artesunate for preventing reinfection in transmission season is effective for the control of schistosomiasis in lake regions.

Adolescent↗
PubMed1998

Consensus phosphorylation sites of human GABA(c)/GABArho receptors are not critical for inhibition by protein kinase C activation.

The mechanism of inhibition of human GABA(C)/GABArho receptors by protein kinase C (PKC) activation was investigated in Xenopus oocytes. Phorbol 12-myristate 13 acetate (PMA), a potent PKC activator, at 25 nM inhibited the currents through GABArho2 receptors, which have one consensus phosphorylation site by PKC in the predicted intracellular loops. The time-courses and amplitudes of inhibition were not significantly different from those occurring through GABArho1 receptors, which have six such sites. The inhibitory effect of PMA was also observed after removing each consensus phosphorylation site in both GABArho1 and rho2 receptors by site-directed mutagenesis. These results suggest that phosphorylation of consensus sites in the intracellular loops is not involved in the inhibition of human GABA(C)/GABArho receptors by PKC activation.

Animals↗
PubMed1998

Human genes for KNSL4 and MAZ are located close to one another on chromosome 16p11.2.

KNSL4 (Kid; kinesin-like DNA-binding protein) is a member of the kinesin family that is involved in spindle formation and the movements of chromosomes during mitosis and meiosis. Myc-associated zinc finger protein (MAZ) participates in both the initiation and the termination of transcription of target genes. We isolated genomic DNA clones that encoded KNSL4 and MAZ from a human cosmid library. Sequence analysis revealed that the two genes were very close to one another. The distance between the two genes was only 1. 2 kb, and this intervening 1.2-kb region was extremely GC-rich. The gene for KNSL4 spanned 16 kb and consisted of 14 exons and 13 introns, while the gene for MAZ spanned 6 kb and consisted of 5 exons and 4 introns. The two genes were mapped to chromosome 16p11.2 by fluorescence in situ hybridization.

Chromosome Mapping↗
PubMed1998

Genomic organization and expression of a human gene for Myc-associated zinc finger protein (MAZ).

We have cloned and characterized the genomic structure of the human gene for Myc-associated zinc finger protein (MAZ), which is located on chromosome 16p11.2. This gene is transcribed as an mRNA of 2.7 kilobases (kb) that encodes a 60-kDa MAZ protein. A 40-kb cosmid clone was isolated that includes the promoter, five exons, four introns, and one 3'-untranslated region. All exon-intron junction sequences conform to the GT/AG rule. The promoter region has features typical of a housekeeping gene: a high G + C content (88. 4%); a high frequency of CpG dinucleotides, in particular within the region 0.5 kb upstream of the site of initiation of translation; and the absence of canonical TATA and CAAT boxes. An S1 nuclease protection assay demonstrated the presence of multiple sites for initiation of transcription around a site 174 nucleotides (nt) upstream of the ATG codon and such expression was reflected by the promoter activity of a MAZ promoter/CAT (chloramphenicol acetyltransferase) reporter gene. Cis-acting positive and negative elements controlling basal transcription of the human MAZ gene were found from nucleotides (nt) -383 to -248 and nt -2500 to -948. Moreover, positive and negative autoregulatory elements were also identified in the regions from nt -248 to -189 and from nt -383 to -248 after co-transfection of HeLa cells with plasmids that carried the MAZ promoter/CAT construct and the MAZ-expression vector. Our results indicate that the 5'-end flanking sequences are responsible for the promoter activities of the MAZ gene.

Amino Acid Sequence↗
PubMed1998

Organ and development related difference in tissue norepinephrine concentrations in Dahl rats.

To determine organ and development related differences in tissue norepinephrine concentration (tNE) in Dahl salt-sensitive (S) and -resistant (R) rats, we measured the tNE of 16 organs, including the heart (left ventricle), kidney, cerebrum, brain stem, stomach, jejunum, ileum, colon, spleen, pancreas, liver, aorta, lung, bone, salivary gland, and muscle, at 1, 3, 5, 7, 9, 11 weeks old. Large differences were found in tNE among the organs of both S and R rats, ranging from 4.0 +/- 1.1 ng/g tissue (the bone of S rats) to 1234.8 +/- 32.5 ng/g tissue (the salivary gland of R rats). tNE in R rats increased development-dependently in 12 of 16 organs, but did not significantly change in the other three organs, and decreased in the bone. On the other hand, the development-dependent increase in tNE was suppressed in S rats, and the tNE values of S rats were significantly lower than those of R rats in 14 of 16 organs. To eliminate the baroreflexive effects on tNE, another group of 5-week-old S and R rats were subjected to sinoaortic denervation (SAD) or the sham operation. The tNE was measured in 10 organs in these animals at 9 weeks old. SAD did not alter the tNE in most of the organs in both S and R rats. There was no significant differences in mean arterial pressure (MAP) between S and R rats with baroreceptor intact at 9 weeks old. SAD slightly but significantly increased MAP in S rats, whereas not in R rats. There was no significant differences in plasma NE concentration (pNE) between S and R rats with the baroreceptor intact. SAD did not alter pNE in S or R rats. These results demonstrate that variations of the tNE were dependent on the organ and development. Many organs of S rats had lower tNE than those of R rats. The developmental-dependent increases in tNE in S rats were suppressed, compared with those in R rats. These tNE behaviors in S rats may not be related to blood pressure or baroreflex sensitivity, but might be involved in an abnormal sympathetic nerve activity.

Animals↗
PubMed1998

Role of endogenous endothelin in the development of graft arteriosclerosis in rat cardiac allografts: antiproliferative effects of bosentan, a nonselective endothelin receptor antagonist.

BACKGROUND: The purpose of this study was to determine whether endothelin-1 (ET-1) contributes to the development of graft arteriosclerosis and whether the orally active nonpeptide endothelin receptor antagonist bosentan, which blocks both ETA and ETB receptors, can protect against this pathologic damage. METHODS AND RESULTS: Recipient male Lewis rats were divided into three groups; group 1 received heterotopic heart transplantations from Lewis donors and groups 2 and 3 received transplantations from Brown-Norway donors; group 3 recipients also received bosentan orally at the dose of 20 mg/kg per day for 120 days. All recipients were given cyclosporine and were euthanized at examination 120 days after transplantation. Plasma ET-1 levels were significantly higher in group 2 than in group 1 (6.99+/-0.91 and 4.15+/-.83 pg/mL, respectively). Strong ET-1 immunoreactivity was seen in both the thickened neointima and the media of the coronary arteries in group 2 but not in group 1. The mean ratio of the coronary luminal area to the total vascular area in group 2 (19.0+/-11.7%) was significantly lower than that in group 1 (34.2+/-9.9%) and was significantly increased in group 3 (33.2+/-9.2%). CONCLUSIONS: These results show that local upregulation of ET-1, mainly in the thickened neointima and the media of the coronary arteries, may play an important role in the pathogenesis of graft arteriosclerosis by stimulating ETA receptors, ETB receptors, or both. Orally active bosentan might be a useful agent for the clinical prevention of graft arteriosclerosis.

Actins↗
PubMed1998

Reconstitution of F1-ATPase activity from Escherichia coli subunits alpha, beta and subunit gamma tagged with six histidine residues at the C-terminus.

An engineered gamma subunit of Escherichia coli F1-ATPase with extra 14 and 20 amino acid residues at the N- and C-termini (His-tag gamma), respectively, was overproduced in E. coli and purified. Six histidines are included in the C-terminal extension. The reconstituted F1 containing alpha, beta, and His-tagged gamma exhibited sixty percent of the wild-type ATPase activity. The reconstituted alphabeta His-tag gamma complex was subjected to affinity chromatography with nickel-nitrilotriacetic acid (Ni-NTA) agarose resin. ATPase activity was eluted specifically with imidazole. These results implied that the tag sequence protruded to the surface of the complex and did not seriously impair the activity. The reconstituted alphabeta His-tag gamma complex, even after its binding to the resin, exhibited ATPase activity suggesting that the gamma subunit, when fixed to a solid phase, may rotate the alphabeta complex. This system may provide a new approach for analysis of the rotation mechanisms in F1-ATPase.

Bacterial Proteins↗
PubMed1998

Alternatively spliced forms of cyclin D1 modulate entry into the cell cycle in an inverse manner.

Alternative splicing of cyclin D1 gene mRNA has recently been demonstrated. The novel transcript shows no splicing at the downstream exon 4 boundary and encodes a protein with an altered carboxyl-terminal domain that is a cyclin D1 variant; exon 5 is not included in the coding sequence which terminates downstream of exon 4. We here produced cells that exogenously express each form of cyclin D1 and analysed their cell cycle regulation. We found that (1) alternative splicing forms of cyclin D1 modulated entry into the cell cycle in an inverse manner; (2) both splicing forms suppressed cell growth; and (3) cells overexpressing form [a] were inhibited from entry into and completion of the S phase, although form [b]-expressing cells showed no reduction of G1- to S transition. We also found that overexpression of either cyclin D1 form upregulated Rb gene products, suggesting that this upregulation may be one of the causes of growth suppression in cyclin D1 overexpressing cells.

Alternative Splicing↗
PubMed1998

Myeloid-specific transcriptional activation by murine myeloid zinc-finger protein 2.

Myeloid zinc finger protein 2 (MZF-2) is a zinc-finger transcription factor that is expressed in myeloid cells, particularly in the cells committed to the neutrophilic lineage. Here we examine the ability of murine MZF-2 (mMZF-2) to activate transcription. The mMZF-2 protein binds to a DNA element (MZF-binding site) through its zinc-finger domain. When the intact mMZF-2 was cotransfected with a reporter gene, it did not activate transcription. However, N-terminal deletion mutants greatly enhanced transcription specifically in myeloid cells. Furthermore, in an in vivo competition assay, the middle region of MZF-2 inhibited the mMZF-2-mediated transcription activation. These results suggest that mMZF-2 is a transcriptional factor that can specifically work in myeloid cells and can be divided into at least three functional domains. The N-terminal domain inhibits transactivation by masking the effect of the activation domain. The middle region recruits a coactivator, which is responsible for myeloid-specific transcriptional activation. The C-terminal zinc-finger domain functions as a DNA-binding domain.

Animals↗
PubMed1998

Angiotensin II-nitric oxide interaction on sympathetic outflow in conscious rabbits.

Increasing evidence suggests that endogenous NO inhibits sympathetic outflow in anesthetized animals. However, in a recent study from this laboratory, we were unable to find any evidence of increased renal sympathetic nerve activity (RSNA) in response to blockade of NO synthesis in conscious rabbits. Because angiotensin II (Ang II) increases sympathetic outflow, one factor for this discrepancy may be the difference in the resting level of Ang II, which may be lower in well-trained conscious animals. In the present study, the effects of blockade of NO synthesis with Nomega-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg IV) on resting RSNA with and without a background intravenous infusion of Ang II (10 ng.kg(-1).min(-1)) was investigated in conscious rabbits. Intravenous administration of L-NAME (30 mg/kg) caused an increase in mean arterial blood pressure (MAP, from 80.4+/-2.9 to 92.8+/-2.5; P=.0001) and a decrease in RSNA (from 100+/-0% to 53.4+/-8.6%, P=.0016). When the elevated blood pressure was returned to control by infusion of hydralazine (0.01 to 0.06 mg.kg(-1).min(-1)), RSNA returned to the level before L-NAME administration. During a sustained infusion of Ang II (10 ng.kg(-1).min(-1)), L-NAME increased MAP from 89.2+/-2.9 to 109.0+/-4.3 mm Hg (P=.0101) and decreased RSNA from 100.0+/-0% to 53.7+/-7.5% (P=.0013). Under this circumstance, however, when the MAP was returned to the level that existed before the administration of L-NAME, RSNA increased significantly above the level that existed before the administration of L-NAME (164.5+/-17.7% versus 100+/-0%, P=.0151). The enhancement of the sympathetic response by Ang II was completely blocked by the AT1 receptor antagonist, losartan. In contrast, during a background infusion of phenylephrine, which increased MAP to the same level as produced by Ang II, L-NAME had no effect on RSNA when MAP was returned to the control level. Nomega-Nitro-D-arginine methyl ester had no effect on MAP and RSNA. Intravenous infusion of Ang II alone for 75 minutes had no effect on RSNA when MAP was returned to control levels. These data suggest that an elevated level of Ang II is critical for the inhibitory effect of NO on sympathetic outflow in conscious rabbits and imply that these two substances have a major impact on the regulation of sympathetic outflow.

Angiotensin II↗
PubMed1998

Sinoaortic denervation produces sodium retention in Dahl salt-sensitive rats.

The role of the arterial baroafferent signals in sodium (Na) homeostasis was examined in salt-sensitive rats. Sodium balances, water balances, and systolic arterial pressure (SAP) were measured for 3 weeks in sinoaortic denervated (SAD) or sham denervated (Sham) Dahl salt-sensitive (S) and salt-resistant (R) rats fed a standard-salt diet (0.4% NaCl). In R rats, there was no significant difference in Na balance, water balance, or SAP between the SAD and Sham animals. In the S rats, urinary Na excretion was suppressed in the SAD but not in the Sham animals, resulting in Na retention. SAD significantly increased SAP and mean arterial pressure. High salt challenge (8% NaCl diet) markedly increased SAP and Na and water balances in both S-SAD and S-Sham rats. However, no significant difference was found in SAP or cumulative Na and water balances between S-SAD and S-Sham rats. These results suggest that the baroafferent signals may have some role on the regulation of Na balance in salt-sensitive animals under a standard-salt condition, although a high-salt load masked the baroafferent-dependent sodium excretion.

Animals↗
PubMed1998

The gain of the hepatorenal reflex in anesthetized dogs.

To determine the overall gain of the hepatorenal reflex, hypertonic NaCl solutions were infused into the portal vein or inferior vena cava of anesthetized dogs at a rate of 0.01 ml/kg/min for 30 min and the urinary Na excretion measured. Infusion of 2.25% NaCl into either the portal vein or inferior vena cava had no effect. Portal infusion of 4.5% or 9% NaCl produced an increase of 36 +/- 16 or 40 +/- 17 microeq/kg/30 min, respectively, while inferior vena caval infusion had no effect. With 13.5% NaCl infusion, a significant increase in the natriuretic response was seen with portal venous infusion, with no significant difference between portal venous and inferior vena caval infusion. Thus, the difference in the natriuretic response between portal venous and inferior vena caval infusion was dependent on the degree of input; when an appropriate input was given, natriuresis was induced only by portal venous infusion, probably mediated by the hepatorenal reflex. The gain of the hepatorenal reflex was calculated from the output divided by the input. When 4.5% or 9% NaCl was infused into the portal vein, the 2-h gain of the hepatorenal reflex was 0.38 +/- 0.15 or 0.34 +/- 0.14, respectively.

Animals↗
PubMed1998

Calcium-dependent Ret activation by GDNF and neurturin.

Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) define a new family of neurotrophic factors that play crucial roles in survival and differentiation of various neurons. Recent studies demonstrated that GDNF and NTN use a multicomponent receptor system in which glycosyl-phosphatidylinositol (GPI)-linked cell surface proteins and Ret receptor tyrosine kinase function as the ligand-binding and signalling components, respectively. In the present study, we investigated the role of Ca2+ ions for biochemical and biological activities of Ret because Ret has a unique structure of the extracellular domain with the cadherin-like motif. The results demonstrated that Ca2+ ions might be required for the complex formation of Ret and GDNF or NTN that induces Ret oligomerization and autophosphorylation. Full morphological differentiation of neuroblastoma cells by these neurotrophic factors was also Ca2+-dependent. These findings thus suggested that, in addition to GPI-linked cell surface proteins, Ca2+ ions are components of the signal transducing complex formed by Ret and GDNF protein family.

Calcium↗
PubMed1998

Coincidental occurrence of pernicious anemia and mycosis fungoides in two elderly males.

We experienced two rare cases of pernicious anemia that presented in the course of mycosis fungoides in elderly males. Pernicious anemia has recently been reported to be caused by autoimmune gastritis that produces autoantibodies to gastric parietal cells and intrinsic factor. Immunological abnormalities in mycosis fungoides are reported to induce autoimmune diseases (i.e., autoimmune hemolytic anemia, anti-phospholipid antibody syndrome, arthritis, myasthenia gravis, necrotizing vasculitis, and vitiligo); the pernicious anemia in our two patients may have been closely related to the mycosis fungoides.

Aged↗
PubMed1998

Mechanisms of development of multiple endocrine neoplasia type 2 and Hirschsprung's disease by ret mutations.

The ret proto-oncogene encodes a receptor tyrosine kinase whose ligands belong to the glial cell line-derived neurotrophic factor (GDNF) protein family. Its germline mutations are responsible for the development of multiple endocrine neoplasia (MEN) types 2A and 2B and Hirschsprung's disease (HSCR). MEN2A and MEN2B mutations result in the constitutive activation of Ret by different molecular mechanisms. MEN2A mutations involve cysteine residues present in the Ret extracellular domain and induce disulfide-linked Ret dimerization on the cell surface. MEN2B mutations were identified in methionine 918 in the tyrosine kinase domain and activate Ret without dimerization, probably due to a conformational change of its catalytic core region. In contrast to MEN2 mutations, HSCR mutations represent loss of function mutations. We found that most of HSCR mutations detected in the extracellular domain impair the Ret cell surface expression. More interestingly, ret mutations in cysteines 618 and 620 were reported in several families who developed both MEN2A and HSCR. It was suggested that these mutations might have two biological effects on Ret function, leading to the development of different clinical phenotypes in the same patients.

Drosophila Proteins↗
PubMed1998

Immunohistochemical examination of c-Met protein expression in astrocytic tumors.

Hepatocyte growth factor/scatter factor (HGF/SF), which has various physiological functions, and its receptor c-Met, the human c-met proto-oncogene product, are thought to be determinant in the pathological processes of various malignancies. To investigate the possible role of HGF/SF in the progression of development of astrocytic tumors, we examined the expression of c-Met in these tumors. Immunohistochemistry using the streptavidin-biotin peroxidase complex method and immunofluorescence double staining with anti-c-Met polyclonal and anti-glial fibrillary acidic protein monoclonal antibodies were performed. Positive c-Met expression was detected in 31 of the 42 astrocytic tumors and some of the control cases analyzed. c-Met-positive cells showed morphological characteristics of astrocytes. Especially in the cases of high-grade tumors, c-Met positivity was abundant in cells in both vascular-rich and peripheral regions of the tumors but not in the cells with distinctly malignant features. Immunofluorescence double staining revealed that the c-Met-positive cells were in part of astrocytic origin. We suggest that c-Met-positive cells are affected by some factors in the lesions where the pathological processes are in a state of development. Our studies indicated that c-Met expression might take part in glioma invasion but not in the development of malignancy.

Astrocytes↗
PubMed1998

Inappropriate microvascular constriction produced transient ST-segment elevation in patients with syndrome X.

OBJECTIVES: The aim of this project was to study the responsible site(s) and underlying cardiac disease(s) of patients with transient ST-segment elevation and normal coronary angiograms. BACKGROUND: Transient ST-segment elevation has been demonstrated in patients with variant angina or unstable angina. In those patients, epicardial coronary arteries, not microvessels, are always the responsible site for the transient ST-segment elevation. METHODS: This study consisted of three cases with a transient ST-segment elevation and normal coronary angiograms. Treadmill testings were performed before coronary angiography in all cases. Coronary angiography was undertaken during the control state and during ST-segment elevation and, when possible, a Doppler guide wire was positioned in the left anterior descending artery (LAD). Coronary responses to vasodilators were observed. Finally, cardiac biopsy was performed and pathologic observation was conducted. RESULTS: All three cases had significant ST-segment depression during treadmill testing in II, III, aVF and V4-6 leads; however, no angiographic coronary stenosis was demonstrated and vasospasm was not provoked. A transient ST-segment elevation associated with chest pain was observed in V1-5 leads, but normal coronary angiograms during ST-segment elevation were observed in every case. Coronary blood flow (CBF) velocity profile remained normal during ST-segment elevation. In one case, vasodilator responses to the LAD during ST-segment elevation were also measured. A 0.5 mg intracoronary injection of nitroglycerin increased CBF velocity (220%), but ST-segment elevation was not normalized and chest pain persisted. A 10 mg intracoronary injection of papaverine (PVN) further increased CBF velocity up to 340%, and this normalized ST-segment elevation and relieved chest pain quickly. Either endothelium-dependent coronary flow reserve (CFR) measured with a 100 microg intracoronary infusion of acetylcholine, or flow-dependent CFR by a 10 mg intracoronary injection of PVN was reduced in one of two cases measured. Pathologic findings supported syndrome X as the underlying cardiac disease in all cases. CONCLUSIONS: These findings suggested a new clinical implication involving transient ST-segment elevation mimicking variant angina and normal coronary angiograms in patients with syndrome X. The major responsible site for this phenomenon was suggested to be coronary arterioles of less than 200 microm in diameter.

Acetylcholine↗