Search PubMed⌕ Search

Biomedical subjects

K Murakami

Publications and source records attributed to K Murakami.

At least 541 records · Page 30Linked to original sources
PubMed1995

Recombinant human soluble thrombomodulin reduces endotoxin-induced pulmonary vascular injury via protein C activation in rats.

Adult respiratory distress syndrome (ARDS) is a serious complication of disseminated intravascular coagulation (DIC) or multiple organ failure. To determine whether recombinant soluble human thrombomodulin (rsTM) may be useful in treating ARDS due to sepsis, we investigated the effect of rsTM on lipopolysaccharide (LPS)-induced pulmonary vascular injury in rats. The intravenous administration of rsTM prevented the increase in pulmonary vascular permeability induced by LPS. Neither heparin plus antithrombin III (AT III) nor dansyl Glu Gly Arg chloromethyl ketone-treated factor Xa (DEGR-Xa), a selective inhibitor of thrombin generation, prevented LPS-induced vascular injury. The agents rsTM, heparin plus AT III, and DEGR-Xa all significantly inhibited the LPS-induced intravascular coagulation. Recombinant soluble TM pretreated with a monoclonal antibody (moAb) that inhibits protein C activation by rsTM did not prevent the LPS-induced vascular injury; in contrast, rsTM pretreated with a moAb that does not affect thrombin binding or protein C activation by rsTM prevented vascular injury. Administration of activated protein C (APC) also prevented vascular injury. LPS-induced pulmonary vascular injury was significantly reduced in rats with leukopenia induced by nitrogen mustard and by ONO-5046, a potent inhibitor of granulocyte elastase. Results suggest that rsTM prevents LPS-induced pulmonary vascular injury via protein C activation and that the APC-induced prevention of vascular injury is independent of its anticoagulant activity, but dependent on its ability to inhibit leukocyte activation.

Animals↗
PubMed1995

AQ-0145, a newly developed histamine H3 antagonist, decreased seizure susceptibility of electrically induced convulsions in mice.

We studied the effect of AQ-0145, a newly developed histamine H3-receptor antagonist, on electrically induced convulsions in mice. AQ-0145 significantly decreased the durations of each convulsive phase. The anticonvulsant effect of AQ-0145 was antagonized by mepyramine (pyrilamine) and ketotifen, centrally acting histamine H1-receptor antagonists. Thus, the blockade by histamine H1 antagonists of the AQ-0145-induced decrease in seizure susceptibility indicated that histamine released by AQ-0145 from the histaminergic nerve terminals interacts with the histamine H1 receptors of postsynaptic neurons. These findings fully support the hypothesis that the central histaminergic neuronal system is involved in the inhibition of seizures. It is suggested that the neuropharmacological data on histamine H3 ligands may provide clinical candidates for the CNS disorders in which histamine plays important roles in mental and behavioral functions. In this study, it was suggested that AQ-0145 was a new clinical candidate of H3 ligands.

Adamantane↗
PubMed1995

[Catalase].

Explore the source record for details and available documents.

Catalase↗
PubMed1995

Study of JA300 as agent having high transglycosylation activity.

Escherichia coli JA300 as the strain catalyzing transglycosylation of nucleic acids has so strong activity. We scrutinized where the high faculty of this strain come from. Using PCR methods with our primer pair MI-1 (up; GTT GAA TTC GCC TTT GTT ATG TCA C) and MI-2 (down; GTT CCG CTA ACG GAA CAC CTA GGC CT), we isolated deoD (the coding region of PNPase) of JA300. Nucleotide sequence analysis indicated that deoD of JA300 is definitely same as that of parent strain K12. The fact that the transcription of deoD of JA300 is more active than that of K12 was also revealed after the analysis by Northrn blot hybridization. These data may suggest that the varieties of gene concerning regulation contribute to the difference of PNPase activity between them.

Base Sequence↗
PubMed1995

In vitro selection of RNA aptamers that can bind specifically to Tat protein of HIV-1.

The Tat protein of human immunodeficiency virus interacts specifically with its target RNA sequence, TAR, and activates viral gene expression at the early stage of infection. Here, we have used in vitro genetic selection strategy to determine what sequence or structural motifs might exist between RNA's that interact specifically with the Tat protein. Starting from a RNA pool that has a 120 base random sequence core, aptamers that bind specifically to the Tat protein were selected by repeating 11 rounds of selection and amplification. A comparative analysis of 64 aptamers that were isolated from the 11th generation revealed two main sequence classes. Interestingly, one of these two classes of aptamers had minimum of one U residues in bulge loop and 2 specific adjacent base pairs. This region is very much homologous to the core sequence of TAR RNA that is essential for the specific Tat-TAR interactions. Further analyses of the sequences from the 11th generation should reveal what kind of RNA structures are required in order to show a high affinity for the Tat protein.

Base Sequence↗
PubMed1995

Effectiveness of daily living abilities (DLA) as a tool for evaluating vocational competencies: study of non-disabled workers aged 45 and over.

A questionnaire survey was conducted on 28-55 items of daily living abilities (DLA) linked to 13 basic vocational competencies such as memory, learning, planning, judgement, muscular power and concentration covering a total of 505 non-disabled blue collar male workers aged 45 and over. Results of the survey were as follows, (1) The 457 subjects were grouped into five groups ranging from normal to unsound groups according to the degree of DLA; (2) The reduction of DLA has directionality to two factors, memory and muscular power; (3) DLA provide clues for aging; (4) Among basic vocational competencies, muscular power showed the highest performance with a small standard deviation, while concentration scored low points with a large standard deviation (p < .05); (5) No age difference was found in planning ability, coordination, muscular power, physical tolerance, manual dexterity, and sense of equilibrium, while subjects aged 65 or over showed significantly low figures for learning ability, agility and concentration (p < .05); Since the findings showed various characteristics of vocational competencies and the aging process precisely in blue collar workers aged 45 and over, we assumed that the DLA survey is one of the alternatives for evaluating workers vocational competencies.

Activities of Daily Living↗
PubMed1994

Pharmacological properties of YM-26365, a low molecular weight, orally active renin inhibitor.

This report describes the pharmacological properties of a novel renin inhibitor (YM-26365: (3R)-3-[3-[(1S)-1-cyclohexylmethyl-2-hydroxy-3- [(1-methyl-5-tetrazolyl)thio]propyl]ureido]-1-methyl-5-phenyl- 2,3-dihydro-1H-1,4-benzodiazepin-2-one) with molecular weight 577 and no peptide bonds. YM-26365 inhibited human plasma renin with an IC50 value of 2.9 x 10(-6) M, but did not affect plasma renin from dogs, rabbits, and rats at 10(-4) M. YM-26365 inhibited not only human renin, but also cathepsin D with an IC50 value of 1.7 x 10(-5) M. This compound competitively inhibited the reaction between recombinant human renin and N-acetyl tetradecapeptide with a Ki value of 1.1 x 10(-6) M. In pithed spontaneously hypertensive rats, YM-26365 at 10 mg/kg i.v. significantly antagonized the pressor response to recombinant human renin, but did not affect responses to angiotensin II, angiotensin I, norepinephrine, or arginine vasopressin. Similarly, oral administration of YM-26365 (10 and 30 mg/kg) to pithed spontaneously hypertensive rats caused a shift to the right of the recombinant human renin dose-pressor response curve. Systemic bioavailability as determined on the basis of the ratio of the total area under the plasma concentration-time curve after 3 mg/kg i.v. and 30 mg/kg orally to rats was 9.6%. These results demonstrate that YM-26365 is a weak but orally absorbed, low molecular weight renin inhibitor.

Administration, Oral↗
PubMed1994

Angiotensinogen-deficient mice with hypotension.

The renin-angiotensin system is an enzymatic cascade that produces a potent vasoconstrictor octapeptide angiotensin II, through its physiologically inactive intermediate decapeptide angiotensin I, from their precursor angiotensinogen. In the present study, we generated angiotensinogen-deficient mice by homologous recombination in mouse embryonic stem cells. These mice do not produce angiotensinogen in the liver, resulting in the complete loss of plasma immunoreactive angiotensin I. The systolic blood pressure of the homozygous mutant mice was 66.9 +/- 4.1 mm Hg, significantly lower than that of wild-type mice (100.4 +/- 4.4 mm Hg). This profound hypotension in angiotensinogen-deficient mice demonstrates an indispensable role for the renin-angiotensin system in maintaining blood pressure.

Angiotensin I↗
PubMed1994

A cell type-dependent enhancer core element is located in exon 5 of the human angiotensinogen gene.

We have recently characterized a cell type-dependent downstream enhancer that is contained within an 832-bp B2 sequences spanning the exon 5 and 3'-flanking region of the human angiotensinogen gene and have localized one of core elements to a 24-bp region in the 3'-flanking region. In the present study, we functionally dissected the 5'-half of B2 region and identified an additional cell type-dependent enhancer core element composed of the 80-bp sequences (+1399 to +1478) in the exon 5. Electrophoretic mobility shift assays demonstrated that the element interacts with two HepG2 cell-specific and several ubiquitous nuclear factors. These results, together with our previous results, suggest that the 80-bp exon 5 enhancer core element as well as 24-bp region plays an important role in the downstream enhancer effect.

Angiotensinogen↗
PubMed1994

Neuroectodermal tumors expressing c-, L-, and N-myc in transgenic mice that carry the E1A/E1B gene of human adenovirus type 12.

Adenovirus early 1 (E1) region gene products, including E1A and E1B, are required for transformation of primary cultured rodent cells. In order to investigate in vivo action of the E1 region, we established a line of transgenic mice carrying the oncogenic E1A and E1B genes of human adenovirus type 12 under control of the human angiotensinogen promoter. Histopathological analyses indicated that transgenic mice heritably develop neuroectodermal tumors arising from the pelvic region with varying degrees of incidence. The transgene was expressed in the neuroectodermal tumors as well as in TNT-1 cells, a cell line established from the tumors, where the human angiotensinogen promoter was constitutively active. The high level expression of c-, L-, and N-myc without gene amplification was notable in the original tumors and TNT-1 cells, but not in another tissue examined. The co-expression of the three sets of myc family genes in both the original tumors and the established cell line provided the possibility that the target cells for transformation may belong to a specific cell type that expresses all these oncogenes during development.

3T3 Cells↗
PubMed1994

Identification of cell type-dependent enhancer core element located in the 3'-downstream region of the human angiotensinogen gene.

We previously demonstrated that the 3.8-kilobase DNA fragment containing exons 4 and 5 of the human angiotensinogen (hAG) gene enhances the expression of chloramphenicol acetyltransferase gene, under control of the hAG promoter, in human hepatoma HepG2 cells. In the present study, to define regulatory elements of the hAG gene, we have functionally dissected this downstream region and localized a cell type-dependent enhancer to the 832-base pair sequence containing the exon 5 and 3'-flanking region. Further deletion analyses revealed that the 24-base pair core DNA fragment present in the 3'-flanking region was responsible for this enhancement. Electrophoretic mobility shift assay demonstrated that the 3'-enhancer core element interacts specifically with two nuclear factors from the HepG2 cells, one of which is an uncharacterized factor (human angiotensinogen enhancer factor-1: hAEF-1), the other is an AP-3-related factor. Mutation analyses indicated that the disruption of hAEF-1 binding alone completely impaired the enhancer activity of the core element. These results suggested that the downstream enhancer core element interacting with hAEF-1 plays an important role in activating the angiotensinogen promoter in a cell type-dependent manner.

Angiotensinogen↗
PubMed1994

Extracorporeal shock wave lithotripsy (ESWL) for biliary stones: a nationwide survey in Japan.

To assess the current status of extracorporeal shock wave lithotripsy (ESWL) for the treatment of gall-stones in Japan, we conducted a nationwide survey by sending a questionnaire to 251 institutions using this therapy. Replies were obtained from 50 institutions. The use of ESWL was investigated over the period from its introduction up to October 1992. ESWL was performed on 2,760 of 10,058 patients with gallstones (27.4%). The stones were completely pulverized in 1,021 of these 2,760 patients (37.0%). Complete disappearance was limited to single gallstones less than 20 mm in maximum diameter. A comparison in the number of ESWL sessions revealed no significant difference between the patients with and without a good response. Choledocholithiasis was resolved completely in 44.0% of 157 patients who underwent ESWL for this condition and intrahepatic stones were cured in 18.7% of 32 patients. Therefore, ESWL may be a useful form of conservative therapy for biliary calculi.

Cholelithiasis↗
PubMed1994

A truncated bone morphogenetic protein receptor affects dorsal-ventral patterning in the early Xenopus embryo.

Bone morphogenetic proteins (BMPs), which are members of the transforming growth factor beta (TGF-beta) superfamily, have been implicated in bone formation and the regulation of early development. To better understand the roles of BMPs in Xenopus laevis embryogenesis, we have cloned a cDNA coding for a serine/threonine kinase receptor that binds BMP-2 and BMP-4. To analyze its function, we attempted to block the BMP signaling pathway in Xenopus embryos by using a dominant-negative mutant of the BMP receptor. When the mutant receptor lacking the putative serine/threonine kinase domain was expressed in ventral blastomeres of Xenopus embryos, these blastomeres were respecified to dorsal mesoderm, eventually resulting in the formation of a secondary body axis. These findings suggest that endogenous BMP-2 and BMP-4 are involved in the dorsal-ventral specification in the embryo and that ventral fate requires induction rather than resulting from an absence of dorsal specification.

Amino Acid Sequence↗