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Biomedical subjects

Y Murakami

Publications and source records attributed to Y Murakami.

At least 325 records · Page 18Linked to original sources
PubMed1998

Tumor accumulation of poly(vinyl alcohol) of different sizes after intravenous injection.

The body distribution and tumor accumulation of polymers were evaluated using poly(vinyl alcohol) (PVA) which has the simplest chemical structure among water-soluble polymers, similar to poly(ethylene glycol). To study the effect of polymer size on the tumor accumulation, we used not only water-soluble PVA with different molecular weights but also PVA microgels prepared through gamma-irradiation of aqueous PVA solutions. The PVA specimens in the aqueous solution were intravenously injected to mice carrying a tumor mass at their footpad. Both types of PVA (water-soluble and microgel) of larger size were retained in the blood circulation for longer time periods and excreted more slowly from the kidney than those of smaller size. The plasma half-life period of PVA became longer with increasing size both for the water-soluble and microgel PVA, indicating that the body fate of PVA is governed only by the size. Both the water-soluble PVA and PVA microgels were accumulated in tumor tissue to a significantly greater extent than in normal tissue. The size dependence of the plasma half-life period and tumor accumulation was similar between the water-soluble PVA and the PVA microgels and the tumor accumulation became maximum around the size of 60 nm both for water-soluble and microgel PVA. A pharmacokinetical study demonstrated that the tumor uptake rate index of PVA decreased with the increase in PVA size. On the other hand, the greater the size, the larger the value of the area under the blood concentration-time curve (AUC). In addition, the PVA around 60 nm in diameter showed the smallest liver clearance. It was concluded that the balance between the uptake rate and the AUC as well as the liver clearance resulted in the maximum accumulation of PVA with the size of 60 nm.

Animals↗
PubMed1998

Mapping of the human genes encoding cyclin H (CCNH) and the CDK-activating kinase (CAK) assembly factor MAT1 (MNAT1) to chromosome bands 5q13.3-q14 and 14q23, respectively.

Cyclin-dependent kinases (CDKs), which play a key role in cell cycle control, are activated by the CDK-activating kinase (CAK), which activates cyclin-bound CDKs by phosphorylation at the specific threonine residue. Mammalian CAK contains three components: CDK7, cyclin H, and an assembly factor called MAT1. The CDK7-cyclin H-MAT1 complex is tightly associated with a multiprotein complex TFIIH, which plays a dual role in transcription and DNA repair. Here, we have determined chromosomal localizations of the human genes encoding cyclin H (CCNH) and MAT1 (HGMW-approved symbol MNAT1) to chromosome bands 5q13.3-q14 and 14q23, respectively, by using fluorescence in situ hybridization, somatic cell hybrid analyses, and mapping to the human YAC contigs.

Animals↗
PubMed1998

Hemolysis complicating coil occlusion of patent ductus arteriosus.

We report on 5 patients who developed hemolysis (the Hemolysis group) following coil occlusion for PDA, and compare their data to 66 cases which were not complicated by hemolysis despite residual leak (the No Hemolysis group). A significant leak with a heart murmur was more frequent in the Hemolysis group than in the No Hemolysis group. The ratio of the sum of the loop diameter of coils to the minimal diameter of the ductus (C/D) in those who developed persistent hemolysis that needed a second intervention (2.2+/-0.4) was significantly smaller than in the No Hemolysis group (3.1+/-1.1). Persistent hemolysis can occur if a significant residual shunt remains after implantation of coils with small C/D. As this complication may be avoided by complete closure or, if not complete, a minimal leak, we should be careful to make residual leaks as small as possible by the use of multiple coils.

Anemia, Hemolytic↗
PubMed1998

Constitutive activation of Jak-2 and Tyk-2 in a v-Src-transformed human gallbladder adenocarcinoma cell line.

It is well known that v-Src phosphorylates various substrates on tyrosine residue and associates with tyrosine-phosphorylated proteins as well as proline-rich ligands through its SH2 and SH3 domains, respectively, thereby inducing oncogenic transformation. A signal pathway from the cell surface to genes in the nucleus, the Jak/STAT (signal transducers and activators of transcription) pathway, has been shown to be involved in the signal transduction mechanism mediated by many cytokines and growth factors. Although a member of the STAT family, STAT3 has been reported to be constitutively activated in several v-Src-transformed cells, and it still remains unknown whether Jak molecules, which act upstream of STATs, are involved in the v-Src-induced activation mechanism of STAT3. In this study, we analyzed activations of both Jak and STAT molecules using v-Src-transformed HAG-1 cells derived from a human gallbladder adenocarcinoma. STAT3 was found to be constitutively activated in v-Src-transformed HAG-1 cells, but not in either non-transformed mock-transfected or activated c-H-ras-transfected HAG-1 cells, even though the other known STAT molecules are expressed. Furthermore, both Jak-2 and Tyk-2 were constitutively activated only in v-Src-transformed HAG-1 cells. Association of v-Src with either STAT3 or the Jak molecules was not observed. No change of this activation was detected by either interferon (IFN)-alpha2a or IFN-gamma, which had shown inhibitory effects on the growth of v-Src-transformed HAG-1 cells. These results raise the possibility that Jak-2 and Tyk-2 are both activated by v-Src, thereby contributing to the constitutive activation of STAT3 in the v-Src-transformed cells.

DNA-Binding Proteins↗
PubMed1998

Cloning and sequence analysis of the poly (3-hydroxyalkanoic acid)-synthesis genes of Pseudomonas acidophila.

Pseudomonas acidophila can grow with CO2 as a sole carbon source by the possession of a recombinant plasmid that clones genes that confer chemolithoautotrophic growth ability derived from the H2-oxidizing bacterium Alcaligenes hydrogenophilus. H2-oxidizing bacteria produce poly(3-hydroxybutyric acid) (PHB) from CO2, but recombinant P. acidophila can produce the more useful biopolymer poly(3-hydroxyalkanoic acid) (PHA). In this study, the pha genes of P. acidophila were cloned and a sequence analysis was carried out. A gene library was constructed using the cosmid vector pVK102. A recombinant cosmid carrying the pha genes was selected by the complementation of a PHB-negative mutant of Alcaligenes eutrophus H16. The resulting recombinant cosmid pIK7 contained a 14.8-kb DNA insert. Subcloning was done. and the recombinant plasmid pEH74 was selected by hybridization with the A. eutrophus H16 pha genes. Escherichia coli possessing pEH74 produced PHB, indicating that pEH74 contained the pha genes of P. acidophila. The nucleotide sequences of the PHA-synthesis genes phaA (beta-ketothiolase), phaB (acetoacetyl-CoA reductase), and phaC (PHA synthase) in pEH74 were determined. The homologies of phaA, phaB, and phaC between P. acidophila and A. eutrophus H16 were 64.7, 76.1 and 56.6%, respectively.

Acetyl-CoA C-Acyltransferase↗
PubMed1998

Properties of a cold-active protease from psychrotrophic Flavobacterium balustinum P104.

Protease activity was detected in the culture medium of Flavobacterium balustinum P104 grown at 10 degrees C, which was isolated from salmon (Oncorhynchus keta) intestine. The enzyme, designated as CP-70 protease, was purified to homogeneity from the culture broth by ion exchange and gel filtration chromatographyies. The molecular mass of the protease was 70 kDa, and its isoelectric point was close to 3.5. Maximal activity toward azocasein was observed at 40 degrees C and from pH 7.0 to 9.0. The activity was strongly inhibited by phenylmethylsulfonyl fluoride, suggesting that the enzyme is a serine protease. The N-terminal amino acid sequence was Asp-Thr-Arg-Gln-Leu-Leu-Asn-Ala-Asn-Ser-Asp-Leu-Leu- Asn-Thr-Thr-Gly-Asn-Val-Thr-Gly-Leu-Thr-Gly-Ala-Phe-Asn-Gly-Gly-Asn. A search through the database for sequence homology yielded no significant match. The initial cleavage sites for oxidized insulin B-chain were found to be the Glu13-Ala14 and Phe24-Phe25 bonds. The result of the cleavage pattern of oxidized insulin B-chain suggests that CP-70 protease has a broader specificity than the other cold-active proteases against the peptide substrate.

Amino Acid Sequence↗
PubMed1998

Glucocorticoid regulation of adrenomedullin in a rat model of endotoxic shock.

Wistar rats were injected intravenously with bacterial lipopolysaccharide (LPS) and developed endotoxic shock with severe hypotension. This was accompanied by significantly elevated concentrations of adrenomedullin (AM) in the plasma and expression of high levels of AM mRNA in the lung. Pretreatment of the rats with dexamethasone (DEX) prevented hypotension caused by LPS administration, but plasma AM concentrations and AM mRNA levels in the lung remained elevated. Adrenalectomized (ADX) rats developed a more severe form of circulatory shock in response to a low-dose of LPS. This was accompanied by only a slight increase in circulating AM in the plasma. However, pretreatment of ADX rats with DEX caused substantial elevations of plasma AM concentrations and expression of AM mRNA in the lung. Our studies demonstrate that glucocorticoid upregulates the expression and secretion of AM in vivo, and endogenous glucocorticoid is required for increased AM secretion under certain conditions such as endotoxic shock.

Adrenal Glands↗
PubMed1998

Properties of calcium channels coupled to endogenous glutamate release from the vascularly perfused rat stomach in vitro.

We have demonstrated that both high-K+ and electrical stimulation of the vagus nerves release endogenous glutamate from the vascularly-perfused rat stomach in a calcium-dependent manner. In the present study, we examined properties of calcium channel subtypes mediating endogenous glutamate release from the stomach. Application of 50 mM KCl elicited a release of glutamate, and this release was abolished in calcium-free medium. The release of glutamate was significantly inhibited by both omega-agatoxin IVA, a P/Q-type calcium channel antagonist, and isradipine, an L type calcium channel antagonist. Omega-conotoxin GVIA, an N type calcium channel antagonist and flunarizine, a nonselective T-type calcium channel antagonist were without effect. In contrast to this case of glutamate, omega-conotoxin GVIA induced a marked inhibition in the release of gastric noradrenaline. The combined treatment with omega-agatoxin IVA plus isradipine produced a marked synergistic inhibition of the glutamate release. This inhibition was, however, much less than that by cadmium. The present results suggest that P/Q and L type calcium channels coexist to regulate the release of gastric glutamate. Furthermore, it is possible that unidentified calcium channels other than P/Q and L type channels are also involved in the release of glutamate in the stomach.

Animals↗
PubMed1998

Adrenomedullin regulation by thyroid hormone in the rat.

To investigate the effect of thyroid hormone on adrenomedullin (AM) changes during hyper- and hypothyroid states, we evaluated plasma AM concentrations and AM mRNA levels in lung tissue from hyper- and hypothyroid rats. AM peptide concentrations were significantly higher in plasma from hyperthyroid rats and lower in plasma from hypothyroid rats compared with control rats. AM mRNA transcripts were significantly increased in lung tissue from hyperthyroid rats and significantly decreased in lung tissue from hypothyroid rats compared with normal rats. These changes are paralleled alterations in AM production in cultured rat vascular smooth muscle cells, in which AM is regulated at the transcriptional level by thyroid hormone. Thus, thyroid hormone positively regulates AM production in vivo.

Adrenomedullin↗
PubMed1998

A monomeric human C4b-binding protein (C4bp) more efficiently inactivates C3b than natural C4bp: participation of C-terminal domains in factor I-cofactor activity.

We designed a cDNA construct encoding an artificial membrane molecule consisting of all 8 short consensus repeats (SCRs) of human monomeric C4b-binding protein (C4bp) followed by DAF's GPI anchor, named mC4bp, and expressed the protein on swine endothelial cells (SEC). At the same level of expression, mC4bp protected host cells as effectively as DAF, the most potent complement (C) regulator on the membrane. This result was unexpected from the reported functional properties of natural multimeric C4bp. Here, we investigated the mechanism whereby mC4bp has potent cell-protective activity. Our results were as follows: (1) mC4bp serves more efficiently as a methylamine-treated C3 (C3ma)-inactivating factor I-cofactor than natural C4bp and as efficiently as MCP as a methylamine-treated (C4ma)-inactivating cofactor by fluid-phase cofactor assay: (2) the potency of C3ma inactivation by mC4bp and factor I is quite high compared to those of other cofactors: (3)blocking studies using mAbs against C4bp suggested that both the 48 kDa N-terminal fragment and the C-terminal domain near the portion responsible for bundle formation participate in the high C3ma-inactivating capacity of mC4bp. Thus, acquiring high C3ma-inactivating capacity secondary to monomeric alteration leads to high C regulatory activity of mC4bp. These results infer that mC4bp differs from C4bp in its potent factor I-cofactor activity and is a good candidate as a safeguard against hyperacute rejection of xenografts.

Complement C3b Inactivator Proteins↗
PubMed1998

Thromboxane A2 is involved in the nitric oxide-induced central activation of adrenomedullary outflow in rats.

The central effect of 3-morpholinosydnonimine, a nitric oxide donor, on the sympatho-adrenomedullary system was investigated in urethane-anesthetized rats. Intracerebroventricular administration of 3-morpholinosydnonimine (100, 250 and 500 microg/animal) induced a marked elevation of adrenaline levels and a slight elevation of noradrenaline levels in the plasma. These 3-morpholinosydnonimine (250 microg/animal)-induced elevations of catecholamines were abolished by intracerebroventricular treatments with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-l-oxyl 3-oxide (750 microg/animal), a nitric oxide scavenger, and indomethacin (500 microg/animal), a cyclo-oxygenase inhibitor, but not with superoxide dismutase (250 units/animal), a superoxide anion scavenger. Furthermore, the 3-morpholinosydnonimine (250 microg/animal)-induced elevation of plasma adrenaline levels was abolished by intracerebroventricular treatments with thromboxane A2 synthase inhibitors [furegrelate (100, 250 and 1000 microg/animal) and carboxyheptyl imidazole (500 microg/animal)], and also with thromboxane A2 receptor blockers [(+)-S-145 (100, 250 and 1000microg/animal) and SQ29548 (8microg/animal)]. The elevation of noradrenaline levels was, however, not attenuated by these thromboxane A2-related test agents. The present results indicate that nitric oxide but not peroxynitrite markedly activates central adrenomedullary outflow. Thromboxane A2 in the brain is probably involved in this central activation of adrenomedullary outflow.

Animals↗
PubMed1998

Psychosomatic aspects of patients complaining of dizziness or vertigo with orthostatic dysregulation.

Eighty-five patients (26 males and 59 females) with orthostatic dysregulation who visited our clinic complaining of dizziness or vertigo between December, 1990 and August, 1996 were analyzed using the Japanese Edition Cornell Medical Index-Health Questionnaire and the Yatabe-Guilford Personality Test. The condition of OD was most commonly noted in 29 patients (34.1%) with dizziness or vertigo of indeterminate etiology, followed by in 14 (16.5%) with Meniere's disease, in ten (11.8%) with hypotension and CNS disorder each, and in 22 (25.9%) with other disorders. The percentage classed as Type III (possible neurotic) or Type IV (probable neurotic), was 46.1% in males and 47.4% in females. The percentage classed as Type B or Type E, suggestive of emotional or psychological disturbance, was 38.5% in males and 37.3% in females. There was good correlation between the Japanese Edition Cornell Medical Index-Health Questionnaire and the Yatabe-Guilford Personality Test results as to psychosomatic aspects. We conclude that, in the treatment of patients with orthostatic dysregulation, it is necessary to consider both physical and psychological aspects of the condition.

Adult↗
PubMed1998

Baló's concentric sclerosis in a 4-year-old Japanese infant.

We report the youngest known case with Baló's concentric sclerosis (Baló's disease), a variant of multiple sclerosis. This 4-year-old Japanese boy was diagnosed by clinical manifestations and by characteristic findings on magnetic resonance imaging (MRI). Dexamethasone was given intravenously, 3 mg twice daily for 10 days. The clinical manifestations were resolved within 2 weeks, and the MRI findings were markedly improved after 3 weeks. Following the initiation of steroid therapy, he showed remarkable clinical and physical improvement. It cannot be excluded that the clinical improvement resulted from the steroid therapy.

Brain↗
PubMed1998

Cerebral oxygenation and hemodynamics during hyperventilation and sleep in patients with Rett syndrome.

We continuously monitored changes in cerebral oxygenation and hemodynamics in the frontal lobes of six patients with Rett syndrome during the awake state, which is associated with hyperventilation (HV) and breath-holding (BH), and during sleep by near-infrared spectroscopy. We also monitored three adult volunteers during simulated episodes of HV and BH. In patients with Rett syndrome, the oxygenated hemoglobin (HbO2) and total hemoglobin (HbT) decreased significantly during HV and BH in the awake state compared with the sleep state. The HbO2 and HbT decreased gradually in adult volunteers in response to prolonged episodes of HV and BH. Further studies are required to investigate the relationship, if any, between the discovered continuous decreases in HbO2 and HbT during the awake state and the brain damage seen in patients with Rett syndrome.

Brain Chemistry↗
PubMed1998

Quantitative evaluation of nutritional pathways for the posterior cruciate ligament and the lateral collateral ligament in rabbits.

The cruciate ligament of the knee receives its nutrition from a direct vascular supply and by permeation of nutrients from the synovial fluid. The contributions of these two routes as nutritional pathways are not known in detail. In this study, we injected [3H]methyl glucose as a tracer intravenously or directly into the knee of rabbits. Tracer concentrations in plasma, synovial fluid, the posterior cruciate ligament (PCL), and the lateral collateral ligament (LCL) were analysed by a pharmacokinetic compartment model. The contribution of [3H]methyl glucose permeation from the synovial fluid during steady state was calculated at 44.3% in the PCL and at 39.0% in the LCL. Although these results indicated that more than half the nutrition for both ligaments is provided by its vascular supply, synovial fluid permeation is also an important transport route for small molecules for the PCL and the LCL, which is an extra-articular structure.

Animals↗
PubMed1998

Multiple personality disorder in Japan.

The aim of this study was to determine whether the features of multiple personality disorder (MPD) in Japan are similar to those in North America, although a wide disparity exists in the prevalence of MPD between the two areas. In order to describe the features of MPD in Japan, we obtained clinical data from MPD case reports, including two of our own cases, published in Japanese academic journals and compared it with the data from other countries. The cases in Japan differed significantly from those in North America in the mean number of personalities and prevalence of sexual and/or physical abuse.

Adult↗
PubMed1998

Immunohistochemical analysis of Ki-67 antigen and Bcl-2 protein expression in prostate cancer: effect of neoadjuvant hormonal therapy.

OBJECTIVE: To determine differences in the immunohistochemical (IHC) expression of Bcl-2 protein and Ki-67 antigen in patients with prostatic cancer who underwent radical prostatectomy with or without neoadjuvant hormonal therapy. MATERIALS AND METHODS: Ki-67 antigen and Bcl-2 protein were detected by IHC using MIB-1 and Bcl-2 antibodies in prostatectomy specimens from 28 patients who received hormonal therapy before surgery (group 1) and 51 patients who did not (group 2). RESULTS: In group 2, the mean MIB-1 index increased with increasing grade of tumour, from 11.6% in low-grade to 24.7% in high-grade tumours (P = 0.002). Bcl-2 expression did not correlate with either tumour grade or stage. In group 1, there were no correlations between Bcl-2 expression or MIB-1 index and tumour grade or stage. More tumours in group 1 were Bcl-2-positive (16 of 28, 57%) than were tumours in group 2 (11 of 51, 22%; P = 0.003). The mean (SD) MIB-1 index of tumours in group 2 [15.6 (14.4)%], was significantly greater than that of tumours in group 2 [6.8 (7.5)%; P = 0.004]. CONCLUSIONS: These results indicate that Bcl-2 positivity is increased by androgen ablation therapy and conversely, that the proliferative activity of cancer cells is significantly reduced. The expression of Bcl-2 protein may play a role in the ability of prostate cancer cells to survive in an androgen-deprived environment.

Aged↗