Biomedical subjects

H Murakami

Publications and source records attributed to H Murakami.

At least 289 records · Page 16Linked to original sources

PubMed1997

High plasma immunoreactive leptin level in essential hypertension.

Insulin resistance, the most important factor in metabolic syndrome X, has been considered to raise blood pressure. Recently it was reported that insulin resistance was related to an elevated plasma level of leptin, which is an adipocyte-specific ob gene product and which plays a role in food intake suppression, thermogenesis, and energy expenditure through the activation of the hypothalamus. However there are no reports that deal with the relationship of insulin resistance to plasma leptin and blood pressure. To evaluate the role of leptin in essential hypertensives, two groups of subjects who were carefully matched for body mass index (BMI) were studied; 22 normotensives (NT, age: 46.5 +/- 2.6 years, BMI: 23.9 +/- 0.4 kg/m2, male/female: 14/8) and 45 mild-to-moderate essential hypertensives (EHT, age: 51.9 +/- 2.0 years, BMI: 24.5 +/- 0.4 kg/m2, male/female: 21/24). We applied the euglycemic hyperinsulinemic glucose clamp technique to all subjects and insulin sensitivity was evaluated as the M value. EHT showed a significantly lower M value (160.2 +/- 7.4 v 184.3 +/- 7.3 mg/m2/min, P < .05) and higher basal plasma immunoreactive leptin level (7.6 +/- 0.8 v 5.0 +/- 0.8 ng/mL, P < .05) than NT, despite the fact that there was no significant difference between NT and EHT in age, gender, or BMI. The relationship between mean blood pressure and leptin showed a significant positive correlation in all of the subjects (r = 0.31, P < .05), suggesting that leptin may be related to a pathophysiology of essential hypertension.

Adult↗

PubMed1997

Tiludronate inhibits protein tyrosine phosphatase activity in osteoclasts.

Signaling pathways mediated by tyrosine phosphorylation and dephosphorylation have been reported to be involved in the regulation of cytoskeletal organization in osteoclasts, the principal cells responsible for bone resorption. We examined the effects of tiludronate [(4-chlorophenyl)thiomethylene bisphosphonate] on the cytoskeleton and the balance of phosphotyrosine levels in osteoclast-like multinucleated cells (OCLs) formed in cocultures of mouse osteoblastic cells and bone marrow cells. When OCLs were placed on plastic dishes in the presence of 10% fetal bovine serum, they formed a ringed structure of F-actin dots (actin ring) within 2 h. Tiludronate did not inhibit the process of actin ring formation, but it disrupted preformed actin rings in a time- and a dose-dependent manner. Western blot analysis using an antiphosphotyrosine antibody revealed that tyrosine phosphorylation of certain proteins in OCLs was stimulated by tiludronate added to the purified OCLs. Tyrosine kinase activity of the p60c-src immunoprecipitated from cell lysates of the purified OCLs was not affected by tiludronate directly added to the kinase assay. OCL lysates stimulated dephosphorylation of tyrosine-phosphorylated substrates such as phosphoneuroprotein 14 and epidermal growth factor receptors. Like sodium orthovanadate, an inhibitor of protein tyrosine phosphatases, tiludronate dose-dependently inhibited tyrosine dephosphorylation of those substrates induced by OCL lysates. These findings suggest that tiludronate disrupts the preformed actin rings and suppresses bone-resorbing activity by inhibiting protein tyrosine phosphatases in osteoclasts.

Actins↗

PubMed1997

Bisphosphonate tiludronate increases bone strength by improving mass and structure in established osteopenia after ovariectomy in rats.

We examined the mechanical properties of bone in ovariectomized rats treated with tiludronate. 186 Sprague-Dawley (SD) rats, 6 months of age, were assigned to 13 groups and were maintained for 3-9 months after surgery. Ovariectomy (ovx) groups were given tiludronate orally at the respective doses of 0 (vehicle), 12.5 (low), 25 (medium), and 50 (high) mg/kg body weight daily for 3 months beginning 3 months after surgery. Rats were killed at 0 (start), 3, 6, and 9 months. Whereas bone mineral density (BMD) values of the midfemur did not increase after ovx, the values in the sham-operated groups increased age-dependently. Bending moment to failure of the femur in the sham group was larger than that of the ovx control group at 9 months. In the ovx control groups, the ultimate compressive load values of the third lumbar body were reduced compared with those in the sham groups at 3 months and thereafter. Although serum osteocalcin levels were decreased in the medium- and high-dose tiludronate groups, both serum PTH and 1,25(OH)2D levels were increased only in the high-dose group. Femoral BMD, mechanical properties, and the cortical bone area were increased by the high dose at 9 months. Lumbar ultimate compressive load and the circumscribing cortical shell area in the high-dose group were increased at 6 months and thereafter. The trabecular number values were maintained at 6 and 9 months by the high dose. These data demonstrate that tiludronate administration increased the mechanical properties of bone by preserving the age-dependent increases in the cortical bone mass and three-dimensional structure of trabecular bone. These effects seemed to be due to reduced bone turnover by the agent.

Animals↗

PubMed1997

Calcium hydroxide ameliorates tobramycin toxicity in cultured chick tibiae.

Results from this laboratory have shown that bone metabolism is directly related to extracellular pH and that high concentrations of tobramycin released from impregnated polymethylmethacryrate (PMMA) beads has pH-dependent toxic effects on bone. In the present study, beneficial effects of calcium hydroxide-impregnated PMMA were investigated regarding tobramycin toxicity and bone metabolism in chick embryo tibiae in vitro. Also using Ca(OH)2 as a pH regulator, the antibiotic efficacy of tobramycin-impregnated PMMA was evaluated with respect to inhibition of Staphylococcus aureus growth. When Ca(OH)2 was added to PMMA beads containing tobramycin, the beads released hydroxyl and calcium ions into the culture medium and released more antibiotic than beads containing only tobramycin. Bone metabolism (glycolysis, total protein synthesis, and collagen synthesis) was enhanced by Ca(OH)2-impregnated beads with or without tobramycin. Additionally, bacterial growth was inhibited more strongly when S. aureus was incubated with tobramycin- and Ca(OH)2-impregnated PMMA disks than with disks containing only tobramycin. This study demonstrates the feasibility of adding Ca(OH)2 to tobramycin-impregnated PMMA beads as a regulator of local pH and a promoter of bone metabolism for protection of bone when high concentrations of tobramycin are used to treat osteomyelitis. It also suggests that lower concentrations of antibiotic may be effective if Ca(OH)2 and tobramycin are administered simultaneously.

Animals↗

PubMed1997

Development of DNA diagnostic methods for the detection of new fish iridoviral diseases.

A new disease of epidemic proportions caused by fish viruses within the Iridoviridae family inflicts serious damage on red sea breams (Pagrus major) and striped jack (Caranx delicatissimus) populations grown in aquacultures in Japan. A partial segment of the fish iridoviral DNA was directly amplified using the polymerase chain reaction (PCR) with synthetic primers designed from well conserved nucleotide sequences between the frog virus 3 (Ranavirus) and the silkworm iridescent virus type 6. The deduced amino acid sequence from the nucleotide sequence of the PCR fragment demonstrates a high correlation with a partial sequence from the frog virus 3. Using the PCR method with specific primers, we could detect three of four different known types of fish iridoviruses in diseased fishes. To construct more reliable detection methods specific for this viral family, DNA fragments which can specifically hybridize with all of the four known iridoviridae viral DNAs were screened from the genomic library of one iridoviridae strain. The hybridization assay, using a specific fragment which contains regions which are highly homologous with a characterized partial sequence from the frog virus 3, proved to be a reliable diagnostic tool for fish iridoviral diseases.

Animals↗

PubMed1997

A novel form of the myeloid-specific zinc finger protein (MZF-2).

BACKGROUND: Myeloid cell development is controlled by tissue-specific transcription factors. Human myeloid zinc finger protein (MZF-1) is a putative transcription factor containing 13 zinc fingers, and has been suggested that it regulates the development of neutrophilic granulocytes. RESULTS: Here, we have isolated the murine and human cDNAs which encode a novel form of MZF protein (MZF-2). Murine and human MZF-2 proteins consisted of 814 and 775 amino acids, respectively, and have identity of 75.3% between them. The C-terminal half of human MZF-2, carrying the zinc finger domains, was completely identical with that of human MZF-1, whereas the N-terminal half of MZF-2 was different from the corresponding region of human MZF-1, and was coded by distinct exons. MZF-2 mRNA was expressed in myeloid cells, particularly in the cells committed to the neutrophilic lineage, and down-regulated by G-CSF. CONCLUSIONS: MZF-1 and MZF-2 mRNAs seem to be produced by the alternative use of two different transcription initiation sites. The distinct N-terminal half of MZF-2 carries two characteristic domains, a leucine-rich domain called LeR and an acidic domain, which suggests a unique function of MZF-2 in neutrophil development.

Amino Acid Sequence↗

PubMed1997

The outcome of early surgical management of ruptured posterior circulation aneurysms.

Since 1990, early surgery within 3 days following subarachnoid hemorrhage has been performed routinely in our hospital even for ruptured posterior circulation aneurysms. Our experience with early surgical management of 25 patients with posterior circulation aneurysms, including two patients who underwent endovascular surgery, is reported. Fourteen patients had an aneurysm on the basilar, the posterior cerebral or superior cerebellar artery (BA), and 11 patients had an aneurysm on the vertebral or posterior inferior cerebellar artery (VA). The mortality and morbidity of the BA group were 7% and 29%, respectively, and those of the VA group were 27% and 9%, respectively. In BA, the incidence of symptomatic vasospasm and hydrocephalus was definitely high compared with VA, and the outcome in elderly patients was significantly unfavorable. Early surgery for posterior circulation aneurysms to prevent rebleeding might be considered in selected cases.

Adult↗

PubMed1997

A WD repeat protein controls the cell cycle and differentiation by negatively regulating Cdc2/B-type cyclin complexes.

In the fission yeast Schizosaccharomyces pombe, p34(cdc2) plays a central role controlling the cell cycle. We recently isolated a new gene named srw1(+), capable of encoding a WD repeat protein, as a multicopy suppressor of hyperactivated p34(cdc2). Cells lacking srw1(+) are sterile and defective in cell cycle controls. When starved for nitrogen source, they fail to effectively arrest in G1 and die of accelerated mitotic catastrophe if regulation of p34(cdc2)/Cdc13 by inhibitory tyrosine phosphorylation is compromised by partial inactivation of Wee1 kinase. Fertility is restored to the disruptant by deletion of Cig2 B-type cyclin or slight inactivation of p34(cdc2). srw1(+) shares functional similarity with rum1(+), having abilities to induce endoreplication and restore fertility to rum1 disruptants. In the srw1 disruptant, Cdc13 fails to be degraded when cells are starved for nitrogen. We conclude that Srw1 controls differentiation and cell cycling at least by negatively regulating Cig2- and Cdc13-associated p34(cdc2) and that one of its roles is to down-regulate the level of the mitotic cyclin particularly in nitrogen-poor environments.

Amino Acid Sequence↗

PubMed1997

Molecular cloning of a pig homologue of membrane cofactor protein (CD46).

Organs of transgenic pigs that express human complement regulatory proteins are under assessment as an alternative to transplantation. A major barrier to the transplantation of pig organs is the hyperacute rejection caused by pre-existing antibodies and complement. Pig cells are very susceptible to human complement, presumably because pig cell-surface complement regulatory proteins are inefficient against it. Expression of human complement regulatory proteins, such as decay-accelerating factor and membrane cofactor proteins (MCP or CD46), by means of transgenes would confer resistance to human complement upon pig cells, thereby preventing hyperacute rejection. To express sufficient levels of human complement regulatory proteins at appropriate sites, regulatory elements of genes of pig membrane-bound complement regulatory proteins would be useful. To obtain their cDNAs, we transfected human cells with a pig cDNA library, selected cells by incubation with pig complement and rescued the plasmids. We cloned a cDNA for the pig homologue of MCP, pMCP. The cDNA encoded a predicted protein of 363 amino acids with 42% amino acid identity with human MCP. The pMCP consisted of four short consensus repeats, a Ser/Thr/Pro-rich domain, and transmembrane and cytoplasmic domains. Recombinant soluble pMCP that lacked transmembrane and cytoplasmic domains had factor I cofactor activity in C3b cleavage, indicating that it is functionally, as well as structurally homologous to MCP. FACS analysis with anti-pMCP mAb demonstrated that pMCP is expressed on all blood leukocytes, erythrocytes, and on endothelial and epithelial cell lines.

Amino Acid Sequence↗

PubMed1997

Synergistic actions of pentobarbital and dihydropyridine Ca2+ antagonists on guinea pig isolated thoracic aorta.

In order to elucidate the mechanism(s) behind the interactions between barbiturates and Ca2+ antagonists, the effects of pentobarbital combined with three structurally diverse types of Ca2+ antagonist on CaCl2-induced contractile responses of the guinea pig thoracic aorta in Ca(2+)-free and 40 mM K+ medium and the effects of pentobarbital on Ca2+ antagonist binding to guinea pig aortic membranes were investigated. The dihydropyridine derivatives isradipine (10(-10)-10(-8) M) and nifedipine (10(-10)-10(-8) M) inhibited CaCl2-induced contractions concentration-dependently. Treatment with both pentobarbital (10(-4) M) and dihydropyridine Ca2+ antagonists (10(-9) M) shifted the CaCl2 concentration-response curves to the right significantly compared with those after treatment with the Ca2+ antagonists and pentobarbital alone. However, no synergistic effects of pentobarbital (10(-4) M) with other types of Ca2+ antagonist (verapamil (10(-7) M) and diltiazem (10(-6) M)) were observed. The binding of [3H]isradipine (2 x 10(-9) M) to guinea pig aortic membranes was increased significantly by simultaneous pentobarbital treatment, but no such effect was observed with [3H]verapamil (10(-8) M) or [3H]diltiazem (2 x 10(-8) M). These findings suggest that the synergistic contractile effects of pentobarbital and dihydropyridines were, in part, due to enhancement of dihydropyridine binding to guinea pig aortic membranes (L-type Ca2+ channels) by pentobarbital and that the interactions between pentobarbital and Ca2+ antagonists may be structurally specific.

Animals↗

PubMed1997

[Clinical and diagnostic characteristics of Legionella pneumonia].

We have characterized clinical and diagnostic features in 18 cases of Legionella pneumonia. Age average of patients was 62.0 years old (male:female = 14:4) and underlying diseases were observed in 12 patients. Legionella pneumonia were diagnosed in 3, 5, 8 and 9 cases by culture, serum antibody measurement, urinary antigen detection and PCR, respectively. Sixteen cases were caused by L. pneumophila, while the other 2 cases were L. bozemanii pneumonia and L. pneumophila or L. dumoffii pneumonia. Chest X-rays of those patients showed multiple pneumonia shadows in 14 cases, alveolar shadows in 10 cases, pleural effusion in 5 cases. Blood-gas analysis on admission indicated hypoxemia in all cases with abnormal A-a DO2. Laboratory findings showed abnormal data in WBC, CRP, LDH, CPK and liver function tests (ex. GOT, GPT) in most cases. Serum antibody testing showed positive by 5 weeks after onset of pneumonia, but 10 cases of Legionella pneumonia diagnosed by other techniques were judged to be negative. In urinary antigen detection test, 6 and 2 cases showed positive 1 and 4 weeks after onset of pneumonia, respectively. Macrolide antibiotics were administered in all cases during the episode, but delay of macrolide administration was observed in 3 of 4 cases of dead outcome. Serum antibody measurement, urinary antigen detection and PCR, in addition to culture to bacteria, may be required for exact diagnosis of Legionella infection.

Adult↗

PubMed1997

Angiotensin II blockade [corrected] enhances baroreflex control of sympathetic outflow in heart failure.

Enhanced sympathetic outflow is seen in both patients with congestive heart failure and animals with experimental heart failure. In a previous study, we demonstrated that the baroreflex control of heart rate was impaired in conscious rabbits with pacing-induced heart failure and that this impairment was partially restored by blockade of angiotensin II type 1 (AT1) receptors. In the present study, we determined the interaction between the renin-angiotensin system and baroreflex control of renal sympathetic nerve activity in normal conscious rabbits and conscious rabbits with pacing-induced heart failure before and after AT1 receptor blockade. Heart failure was induced by rapid ventricular pacing at a rate of 360 to 380 beats per minute for an average of 16.7 +/- 0.6 days. To generate baroreflex curves, we altered arterial pressure by administering phenylephrine and sodium nitroprusside. A sigmoidal logistic function was fit to renal sympathetic nerve activity-mean arterial pressure relationships for analysis of several components of baroreflex function. AT1 receptors were blocked by intravenous administration of the specific antagonist L-158,809. In normal rabbits, there was no significant difference in any parameter of baroreflex function before and after blockade of AT1 receptors. In contrast, blockade of AT1 receptors enhanced baroreflex sensitivity in heart failure rabbits. The maximal gain increased to 5.0 +/- 0.7% renal sympathetic nerve activity/mm Hg from 2.6 +/- 0.3 (P < .05). Although L-158,809 had no effect on baseline renal sympathetic nerve activity in normal rabbits, analysis of the data in the heart failure rabbits indicated that baseline renal sympathetic nerve activity was reduced from 33 +/- 5% to 17 +/- 4% after L-158,809 administration after adjustment for changes in arterial pressure. These data suggest that angiotensin II plays a role in baroreflex impairment in this model of heart failure and may be in part responsible for the depressed baroreflex sensitivity observed in heart failure.

Angiotensin II↗

PubMed1997

Asp905Tyr polymorphism of protein phosphatase 1 G subunit gene in hypertension.

A possible pathogenic polymorphism in the gene for the G subunit of the glycogen-associated regulatory form of protein phosphatase 1 (PP1 G subunit), causing an Asp-to-Tyr substitution at codon 905 (Asp905Tyr), has been reported to be associated with insulin resistance and hypersecretion of insulin in the white population. Since marked heterogeneity has been reported in the association of mutations of candidate genes with essential hypertension between Japanese and other ethnic groups, we investigated the association of Asp905Tyr with essential hypertension in Japanese subjects. The frequency of the Tyr allele in Japanese control subjects (0.70) was much higher than that in the Danish population (0.10, P<1x10(-8)), indicating that the Tyr allele, previously reported as a rare variant in white subjects, is a common allele in our population. The genotype distribution in Japanese hypertensive patients (n=109; Asp/Asp=0.09, Asp/Tyr=0.39, Tyr/Tyr=0.52) was not significantly different (chi2=0.7, df=2, P>.6) from that in normotensive control subjects (n=148; Asp/Asp=0.12, Asp/Tyr=0.36, Tyr/Tyr=0.52). Among subjects with different PP1 G subunit genotypes, there was no difference in blood pressure, serum cholesterol, plasma glucose and insulin levels, and glucose disposal rate estimated by the euglycemic hyperinsulinemic clamp test. These data indicate that the Asp905Tyr polymorphism of the PP1 G subunit is not associated with essential hypertension, nor with insulin resistance and/or hyperinsulinemia in Japanese patients with essential hypertension, suggesting that the polymorphism plays little if any role in susceptibility to insulin resistance or hypertension.

Aged↗

PubMed1997

Noninvasive detection of iliac artery disease and prediction of its severity from Doppler spectral analysis in common femoral artery.

The direct interrogation of iliac artery disease (IAD) with color-coded duplex scanning is limited by the presence of intestinal gas or obesity. The purposes of this study were to examine the diagnostic accuracy of duplex ultrasound (DUS) analysis of spectral waves in common femoral artery (CFA) for detection of IAD and to predict its severity. DUS and arteriography were performed in 107 lower extremities in this study. The following were calculated from the CFA spectral waves obtained by DUS: peak systolic velocity (PSV), acceleration (PSV/pulse rise time), and deceleration (PSV/pulse decay time). In patients with isolated IAD, the treadmill exercise test was also performed to evaluate the ischemic severity expressed as recovery rate of ankle pressure index five minutes after exercise (RR-API). Forty-six lower extremities with IAD and 61 without IAD were diagnosed by arteriography. PSV was significantly reduced in lower extremities with IAD (109.5 +/- 32.7 vs 59.8 +/- 32.9 cm/s, P < 0.05). The deceleration detected IAD with a greater specificity and sensitivity vs acceleration (100.0 vs 82.0% and 97.8 vs 82.6%, respectively). Moreover, the acceleration and deceleration significantly correlated with the RR-API (r = 0.589, P < 0.05 and r = 0.779, P < 0.01, n = 14, respectively). The present evaluation is a simple and accurate technique to augment other examinations for detection of IAD and to assess its ischemic severity.

Angiography, Digital Subtraction↗

PubMed1997

Detection of interleukin 6-producing cells among various organs in normal mice with an improved enzyme-linked immunospot (ELISPOT) assay.

The enzyme-linked immunospot (ELISPOT) assay is an efficient technique for the enumeration of single cells secreting antibodies or cytokines. To assess mice interleukin 6 (IL-6)-secreting cells at a single cell level, a highly sensitive ELISPOT assay with 5-bromo-4-chloro-3-indolylphosphate p-toluidine salt and nitroblue tetrazolium chloride (BCIP/NBT) as a gel-substrate has been developed. The IL-6 specific ELISPOT assay thus developed with an ordinary plastic ELISA plate is as efficient as the previous IL-6 specific ELISPOT assay system which uses a nitrocellulose coated plate, and is much more economic and convenient. We demonstrated with this newly devised ELISPOT assay that the ratio of IL-6 producing cells in the resident peritoneal exuded cells was highest in normal BALB/c mice, and a few IL-6 secreting cells were detected in all organs we tested, namely the spleen, bone marrow, Peyer's patch, axillary lymph node and thymus.

Animals↗

PubMed1997

A functioning black adenoma of the adrenal gland.

A 53-year-old female had clinical and laboratory findings suggestive of Cushing's syndrome. In contrast to the Cushing's syndrome caused by cortical adenoma, a high level of urinary 17-ketosteroids (17-KS) was also noted. Imaging studies revealed a right adrenal tumor. Right adrenectomy was performed; the surgical specimen revealed a black adenoma consisting of compact cells with numerous pigments which seemed to be lipofuscin in nature. The present case indicates that black adenoma as well as adrenocortical carcinoma should be suspected, when patients with Cushing's syndrome show an increased level of urinary 17-KS excretion.

17-Ketosteroids↗

PubMed1997

Acute myeloid leukemia accompanied by multiple thrombophlebitis.

A 66-year-old woman suffering from fever and thrombophlebitis was referred to our hospital. A peripheral blood examination revealed hyperleukocytosis with 96% blast cells and thrombocytopenia. The patient was diagnosed as having acute myeloid leukemia (AML) accompanied by disseminated intravascular coagulation (DIC). A marked decrease in protein C (PC) antigen and activity were observed. In this case, PC levels were lower than those observed in AML with DIC. Induction therapy for leukemia and treatment of DIC were started on the first day of hospitalization. The patient achieved complete remission, with PC antigen and activity levels normalized.

Aged↗

PubMed1997

Cerebellar infarction with hydrocephalus caused by spontaneous extracranial vertebral artery dissection--case report.

A 38-year-old male suffered sudden onset of rotational vertigo without headache. Consciousness disturbance developed on the 3rd day after the onset. Computed tomography showed cerebellar infarction with obstructive hydrocephalus. External ventricular drainage was performed. Angiography showed bilateral extracranial vertebral artery dissection. Antiplatelet therapy was given. Repeat angiography showed improvement of the dissection. His neurological deficits completely resolved. Vertebral artery dissections may cause both lateral medullary or cerebellar infarction and hydrocephalus due to the cerebellar infarction manifesting as various symptoms so careful evaluation and treatment are required.

Adult↗