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Biomedical subjects

Y Morikawa

Publications and source records attributed to Y Morikawa.

At least 37 records · Page 2Linked to original sources

Membrane relocation but not tight binding of human immunodeficiency virus type 1 Gag particles myristoylated in Escherichia coli.

Expression of human immunodeficiency virus Gag protein and the N-terminal matrix (MA) domain in Escherichia coli yielded spherical structures in the cytoplasm. When human N-myristoyltransferase was coexpressed, both Gag and MA were fully myristoylated and spherical structures were relocated in close proximity to the cytoplasmic membrane. However, neither myristoylated Gag nor MA exhibited tight binding to E. coli membrane, suggesting that myristoylation in E. coli did not confer membrane affinity on Gag despite the relocation. Our data also suggest that the morphogenetic pathway of Gag particles in prokaryotic cells differs from that in eukaryotic cells despite biochemical similarities of in the form of Gag expressed.

Acyltransferases↗

Birth weight, childhood growth, and cardiovascular disease risk factors in Japanese aged 20 years.

To determine whether birth weight and childhood growth, especially rate of height increase, are independently related to major cardiovascular disease risk factors in adult life, the authors conducted a 20-year follow-up study in a Japanese population, using the record-linkage method. From medical checkup data for babies and for residents aged 20 years in Ishikawa, Japan, the authors obtained 20-year follow-up data (1985-1994) on 4,626 participants (2,198 men and 2,428 women) born in 1965-1974. Using multiple linear regression analysis, the authors estimated that a 1-standard-deviation higher birth weight was significantly associated with systolic blood pressure that was lower by 1.6 mmHg in men and by 1.0 mmHg in women, and with a serum cholesterol level that was lower by 0.07 mmol/liter in men and by 0.04 mmol/liter in women, after adjustment for current weight and rate of height increase. Moreover, after adjustment for birth weight and current weight, a 1-standard-deviation higher rate of height increase from age 3 years to age 20 years was significantly associated with systolic blood pressure that was lower by 0.7 mmHg in men and by 0.5 mmHg in women, and with serum cholesterol that was lower by 0.09 mmol/liter in men and by 0.05 mmol/liter in women. The results suggest that lower birth weight and lower rate of height increase during childhood are independently associated with increases in blood pressure and serum cholesterol in adult life.

Adult↗

Necrotizing tracheobronchitis in patent ductus arteriosus-dependent cyanotic congenital heart disease.

We report 2 patients with necrotizing tracheobronchitis (NTB) associated with patent ductus arteriosus-dependent cyanotic congenital heart disease. The pathologic findings suggest that hypotension and decreased tracheo-bronchial perfusion were the major contributing factors in the development of NTB. Necrotizing tracheobronchitis developed in infants with pulmonary atresia and Ebstein's anomaly with pulmonary stenosis. Both infants required prostaglandin E1 infusion from early infancy, and presented with sudden onset of dyspnea and hypercapnea. In one infant, NTB developed prior to mechanical ventilation. In the other infant, NTB developed after 4 days of mechanical ventilation. Care of both infants involved minimal pressures and FiO(2), adequate humidification, and optimal temperature of inspired gases; these factors probably did not play a role in the development or worsening of NTB. Both infants had hypotension and hypoxemia. These factors could have contributed to the development of NTB because of decreased perfusion pressure and tissue hypoxia. As the area of necrosis and its severity correlated with the area of blood supply served by the specific feeding arteries, we speculate that tissue hypoperfusion was the major cause of NTB.

Bronchitis↗

L-Sorbose induces cellulase gene transcription in the cellulolytic fungus Trichoderma reesei.

L-Sorbose has previously been assumed to stimulate cellulase formation in an indirect manner, different from that of sophorose in Trichoderma reesei. Through Northern blot analysis however, L-sorbose was found to regulate coordinately six cellulase genes (including eg13, whose behavior has not been studied so far) at transcriptional level, as is the case with sophorose in T. reesei strains PC-3-7 and QM9414. Dot blot analysis showed that the proportions of each cellulase mRNA to cbh1 mRNA, the largest amount of mRNA transcribed in T. reesei, did not change when L-sorbose or sophorose was used as an inducer in the PC-3-7 and QM9414 strains. cbh2 and egl1 mRNAs were about 45-60% and 20-30% of the cbh1 transcript, whereas small amounts of mRNA, 1-2% of cbh1, were observed on other endoglucanase genes. Furthermore, the PC-3-7 strain showed an enhanced level of cellulase gene transcription, about two- and four- to six-fold higher than that of the QM9414 strain with sophorose and L-sorbose, respectively.

Cellulase↗

Acute reversible renal failure with macroscopic hematuria in Henoch-Schönlein purpura.

A Japanese girl aged 5 years 4 months developed macroscopic hematuria and acute renal failure (ARF) 8 days before the appearance of purpura rash. A renal biopsy undertaken during the acute phase of illness revealed many red blood cells in the tubular lumina with no apparent glomerular lesions. ARF showed improvement without dialysis therapy. A second renal biopsy was performed 2.5 months later because of the prolonged proteinuria and hematuria. Sclerotic change and crescent formation were demonstrated in 30% and 20% of glomeruli, respectively. Red blood cell casts in the tubular lumina were completely resolved. It is likely that the tubular change was involved in the development of ARF at the onset of illness. Although ARF during or after episodes of macroscopic hematuria has been observed in IgA nephropathy, it may occur as an uncommon complication in Henoch-Schönlein nephritis, which is a common glomerulonephritis in children.

Acute Kidney Injury↗

Halothane but not isoflurane attenuates interleukin 1beta-induced nitric oxide synthase in vascular smooth muscle.

BACKGROUND: Inducible nitric oxide synthase (iNOS) is induced by endotoxin or cytokines, such as interleukin (IL)-1, through a protein synthesis pathway. Halothane reportedly inhibits protein synthesis in various tissues. The aim of the current study was to examine the effect of halothane on the IL-1beta-evoked induction of NOS in vascular smooth muscle. METHODS: After removal of the endothelium, arterial rings of rat aorta were mounted in an isometric force recording system. The effects of halothane (1.0-3.0%) or isoflurane (3.0%) on IL-1beta (20 ng/ml)-induced inhibition of the contractile responses to KCl (30 mM) and phenylephrine (10(-9)-10(-5) M) were studied. The cyclic guanosine monophosphate and cyclic adenosine monophosphate contents were determined by radioimmunoassay. Expression of iNOS and iNOS mRNA were measured by Western or Northern blot analysis, respectively. RESULTS: Halothane (1.0-3.0%) but not isoflurane (3%) significantly reduced the ML-1beta-induced inhibition of contraction in a concentration-dependent manner. The cyclic guanosine monophosphate content of the vascular smooth muscle increased significantly after a 5-h exposure to IL-1beta. Halothane at 3.0% significantly inhibited the increase in cyclic guanosine monophosphate content induced by IL-1beta. Halothane had no effect on cyclic adenosine monophosphate content. IL-1beta-induced expression of iNOS and iNOS mRNA in the rat aorta were inhibited significantly by halothane. CONCLUSION: The current study demonstrated that halothane but not isoflurane inhibits IL-1beta-stimulated hyporesponsiveness to vasoconstrictive agents in vascular smooth muscle and that this inhibitory effect of halothane involves the inhibition of iNOS mRNA expression. Thus, these findings suggest that halothane may have some sites to affect nitric oxide-signaling pathway.

Adenylyl Cyclases↗

Perinatal development of the rat kidney: proliferative activity and epidermal growth factor.

The immunolocalization of proliferating cell nuclear antigen (PCNA), epidermal growth factor (EGF) and its receptor (EGFR) was examined in the perinatal rat kidney. As the index of proliferative activity, PCNA-positive cell ratios in glomeruli and proximal tubules were determined. The PCNA-positive ratios in both glomeruli and proximal tubules decreased significantly during the perinatal period and tended to decrease as the glomerular developmental stage proceeded as well. PCNA-positive cells were seen predominantly in the nephrogenic zone of the kidney throughout the period examined. They were noted in the collecting ducts of the nephrogenic zone and were rarely seen in those of the central zone of the kidney. On the other hand, PCNA-positive cells were noted in the straight portion of the proximal tubules and were rarely seen in the convoluted one. EGF-positive cells were seen in the proximal tubules, distal tubules and collecting ducts, though EGF-positive cells in the proximal tubules decreased after birth. EGFR-positive cells were seen along the entire length of the proximal tubules and collecting ducts as well as in immature glomeruli, not in mature ones. These results indicate that marked cell proliferation occurs in the collecting ducts in the peripheral area and in the proximal tubules in the central area of the kidney, that the proliferative activity decreases with age during the perinatal days and that EGF plays an important role in the proliferation of glomerular cells, and in both proliferation and maturation of the cells in the proximal tubules and collecting ducts.

Animals↗

Influence of adenine-induced renal failure on tryptophan-niacin metabolism in rats.

To discover the role of the kidney in tryptophan degradation, especially tryptophan to niacin, rat kidneys were injured by feeding a diet containing a large amount of adenine. The kidney contains very high activity of aminocarboxymuconate-semialdehyde decarboxylase (ACMSD), which leads tryptophan into the glutaric acid pathway and then the TCA cycle, but not to the niacin pathway. On the other hand, kidneys contain significant activity of quinolinate phosphoribosyltransferase (QPRT), which leads tryptophan into the niacin pathway. The ACMSD activity in kidneys were significantly lower in the adenine group than in the control group, while the QPRT activity was almost the same, however, the formations of niacin and its compounds such as N1-methylnicotinamide and its pyridones did not increase, and therefore, the conversion ratio of tryptophan to niacin was lower in the adenine group than in the control group. The contents of NAD and NADP in liver, kidney, and blood were also lower in the adenine group. The decreased levels of niacin and the related compounds were consistent with the changes in the enzyme activities involved in the tryptophan-niacin metabolism in liver. It was concluded from these results that the conversion of tryptophan to niacin is due to only the liver enzymes and that the role of the kidney would be extremely low.

3-Hydroxyanthranilic Acid↗

Attachment of Malassezia pachydermatis to the ear dermal cells in canine otitis externa.

To investigate the predominance of Malassezia pachydermatis (M. pachydermatis) as a causative agent of canine otitis externa, ear cerumen samples were observed for adhesion of M. pachydermatis to the cornified epithelial cells by light and electron microscopes. The yeasts appeared not to adhere to the cornified epithelial cells directly, but they seemed to exist in the proximity of the epithelial cells with an electron opaque halo-like space around them. Polysaccharide and lipid staining techniques were conducted to identify the substances existing in that space. Lipid substances, not saccharides, were observed around the yeasts and the cornified epithelial cells. These results suggested that in the canine ear canal malassezia yeast attachment to the cornified epithelial cells is mediated by lipids.

Animals↗

Development of endoscopic surgery for the minimally invasive treatment of digestive and other diseases.

Minimally invasive surgery has rapidly changed the performance of surgical practice in a wide range of surgical specialities in the last decade of the 20th century. The marked progress in endoscopic surgery has been conducted especially in general and digestive surgery. The Department of Surgery, School of Medicine, Keio University has contributed to the development and establishment of endoscopic surgery in every subspeciality of general and digestive surgery. Our achievements include the development of original methods for laparoscopic wedge gastrectomy and endoscopic thyroidectomy, establishment of surgical techniques in endoscopic surgery for esophageal, gastric, colorectal and hepatobiliary diseases, and the introduction of robotics and tele-communicative technologies to endoscopic surgery.

Digestive System Surgical Procedures↗

Sickness absence and shift work among Japanese factory workers.

To investigate the effect of shift work on long-term sickness absence (more than 7 calendar days), an 8-year follow-up study was carried out in a factory in Japan. The participants were male employees aged 18-54 years who were engaged in manufacturing sites. Shift patterns were classified by the number of non-daytime working days during the previous one-year. The causes of sickness absence were classified into three groups, 1) causes except injury, diseases of the musculoskeletal system and connective tissue, 2) injury, 3) diseases of the musculoskeletal system and connective tissue. The analysis of long-term sickness absences was based on the first occurrence. The age-adjusted incidence of sickness absence among shift workers who were on non-daytime shifts more than two-thirds of working days during the previous one year was significantly higher than that among other workers. After adjusting for confounding factors, a significant high risk still existed for this group of workers taking sickness absence for all causes and causes except for injury and the musculoskletal disorders. These findings suggest that shift workers who are engaged on a particular shift schedule are more likely to take leave due to sickness.

Accidents, Occupational↗

A novel low-density lipoprotein receptor-related protein mediating cellular uptake of apolipoprotein E-enriched beta-VLDL in vitro.

We report here the identification of a novel member of the low-density lipoprotein receptor (the LDL receptor) family through signal sequence trap screening of a mouse lymphocyte cDNA library. The protein was termed LDL receptor-related protein 9 (LRP9). LRP9 is a type I membrane protein predicted to contain 696 amino acids with a calculated molecular mass of 74 764 Da. The NH(2)-terminal half of LRP9 contains two CUB domains separated by a single ligand-binding repeat. The second CUB domain is followed by a cluster of three additional ligand-binding repeats and a transmembrane domain. The COOH-terminal intracellular region contains a proline-rich region. LRP9 mRNA was expressed in the liver, kidney, lung, and heart at high levels, and in the spleen and brain at low levels. In situ hybridization analysis of mouse liver, kidney, and brain detected LRP9 transcripts in hepatocytes, sinusoidal lining cells, peritubular capillaries, choroid plexus, ependyma of the third ventricle, pia matter, and hippocampus. In particular, high levels of expression were observed in the vascular walls. Apolipoprotein E (apoE)-enriched beta-VLDL stimulated cellular cholesteryl ester formation in ldl-A7/LRP9. These results raise the possibility that this newly identified receptor, which is expressed in the liver, may play a physiological role in the uptake of apoE-containing lipoproteins.

Adult↗

Biochemical characterization of casein kinase II as a protein kinase responsible for stimulation of HIV-1 protease in vitro.

The physiological significance of casein kinase II (CK-II) on the protease (PR) activity of recombinant HIV-1 PR (rPR) was biochemically investigated in vitro. We found that (i) the purified rPR (p11) functions as a phosphate acceptor of CK-II; (ii) the PR activity of rPR is stimulated approximately 2.9-fold after its full phosphorylation by recombinant human CK-II (rhCK-II) in a manner similar to that observed for recombinant HIV-1 reverse transcriptase (rRT); and (iii) this stimulation is completely inhibited by two polyphenol-containing anti-oxidant compounds [quercetin and epigallo-catechin gallate (EGCG)] at 0.1 microM or a glycyrrhetinic acid derivative (oGA) and catechin at 10 microM without significant effect on the PR activity of rPR. These results suggest that (i) CK-II may be a host mediator responsible for stimulation of PR and RT in HIV-1-infected cells; and (ii) the selective inhibition of the CK-II-mediated stimulation of HIV-1 PR and RT by potent CK-II inhibitors may be involved in their anti-HIV-1 effects at the cellular level.

Amino Acid Sequence↗

TROY, a newly identified member of the tumor necrosis factor receptor superfamily, exhibits a homology with Edar and is expressed in embryonic skin and hair follicles.

In a signal sequence trap screening of the murine brain, we identified a new member of the tumor necrosis factor receptor superfamily designated TROY. TROY is a type I membrane protein of 416 amino acids with characteristic cysteine-rich motifs in the extracellular domain and a tumor necrosis factor receptor-associated factor (TRAF) 2 binding sequence in the cytoplasmic domain of 223 amino acids. In fact, activation of nuclear factor kappaB was induced by the overexpression of TROY and inhibited by dominant negative forms of TRAF2, TRAF5, and TRAF6, indicating that TRAFs and nuclear factor kappaB are involved in the signal transduction of TROY. We also cloned a cDNA for a human counterpart, which showed a 75% homology with mouse TROY at the amino acid level. The extracellular domain of TROY exhibits an extensive homology with that of Edar, a receptor that specifies hair follicle fate. TROY mRNA is strongly expressed in brain and embryo and moderately expressed in the heart, lung, and liver but not the spleen. In the embryo, the expression level is particularly strong in the skin. Interestingly, in situ hybridization analysis of the embryo showed that TROY mRNA was exclusively expressed in the epithelium of many tissues. On the other hand, in neonatal mice, TROY is expressed in hair follicles like Edar as well as in the cerebrum, suggesting pleiotropic functions of TROY in development as well as in the adult mice. The Troy gene is located near the waved coat (Wc) locus, a mutant related to abnormalities in skin and hair.

Amino Acid Sequence↗

In vitro processing of human immunodeficiency virus type 1 Gag virus-like particles.

Human immunodeficiency virus (HIV) Gag proteins are assembled into virus particles and then cleaved by the virion-associated HIV protease. Concomitant with Gag processing, doughnut-like HIV particles (the immature form) are converted to particles containing condensed cores (the mature form). Here we describe the in vitro processing of immature HIV Gag virus-like particles (VLP) by exogenously added HIV protease. Following delipidization, sequential processing of immature VLP showed that the matrix (MA)/capsid (CA) junction was cleaved faster than the CA/nucleocapsid (NC) junction, an altered order of processing when compared with authentic processing. When the in vitro processed VLP were analyzed on density gradients, most of the MA, CA-p15 intermediate, and NC were detected as a highly multimeric form, equivalent to the unprocessed VLP. In contrast, CA was found as a monomer dissociated from the multimeric CA-p15 following cleavage of the CA/NC junction. Electron microscopy revealed that the in vitro processing was accompanied by conversion of the doughnut-like particles to particles containing condensed cores and spherical outer shells. The cores, however, lacked core shells, which are normally observed for authentic HIV, suggesting that the in vitro processing of immature VLP failed to produce core shells.

Animals↗

CSF phosphorylated tau protein and mild cognitive impairment: a prospective study.

Cerebrospinal fluid (CSF) tau protein phosphorylated at both Thr231 and Ser235 sites (CSF/phospho-tau(231-235)) and total tau (CSF/total-tau) were quantified by sandwich ELISA in 20 patients with mild cognitive impairment (MCI) who eventually developed AD on follow-up as well as seven memory complainers with no objective memory loss. 13/20 (65%) of the MCI patients had high CSF/total-tau and detectable levels of CSF/phospho-tau(231-235), whereas these markers were low and under a detectable level in all of the memory complainers. Although either a total-tau, phospho-tau measurement or a combination of these can help in predicting if MCI will develop AD, our results suggest that the pathogenic steps of AD may be at the stage that finally leads to an accumulation of abnormally phosphorylated tau and neuron death, at least in some brain areas, when MCI patients present with the earliest detectable clinical symptoms of dementia.

Aged↗