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Biomedical subjects

H Chiba

Publications and source records attributed to H Chiba.

At least 91 records · Page 5Linked to original sources
PubMed1999

Rhodopeptins, novel cyclic tetrapeptides with antifungal activities from Rhodococcus sp. III. Synthetic study of rhodopeptins.

Total syntheses of cyclo (-Gly-L-Lys-L-Val-(R)-3-aminododecanoyl-); LV9nA and its diastereomer cyclo (-Gly-L-Lys-L-Val-(S)-3-aminododecanoyl-); LV9nB, congeners of rhodopeptin B5 on beta-amino acid moiety, were achieved. The beta-amino acid moiety was prepared as a racemate by the thermal Michael addition of an amine to alpha,beta-unsaturated ester. The racemic beta-amino acids were converted to their L-Valylamide derivatives and the obtained diastereomers were separated. Coupling of both diastereomers, L-Val-beta-amino acids with Gly-L-Lys gave linear tetrapeptides, and tetrapeptides were cyclized by diphenylphosphoryl azide (DPPA) method between C-terminus of beta-amino acid and N-terminus of Gly to give cyclic tetrapeptides. The deprotected cyclic tetrapeptides, LV9nA and LV9nB, both exhibited almost the same antifungal activity as the naturally obtained rhodopeptins. Furthermore, comparison of the 1H NMR spectra of two congeners and rhodopeptin B5 suggested that the stereochemistry of beta-amino acid moiety in natural rhodopeptin B5 has (R)-configuration.

Antifungal Agents↗
PubMed1998

Surfactant proteins A and D: disease markers.

The abundant and restricted expression of surfactant proteins SP-A and SP-D within the lung makes these collectins specific markers for lung diseases. The measurement of SP-A and SP-D in amniotic fluids and tracheal aspirates reflects lung maturity and the production level of the lung surfactant in infants with respiratory distress syndrome (RDS). The SP-A concentrations in bronchoalveolar lavage (BAL) fluids are significantly decreased in patients with acute respiratory distress syndrome (ARDS) and also in patients at risk to develop ARDS. The prominent increase of these proteins in BAL fluids and sputum is diagnostic for pulmonary alveolar proteinosis (PAP). The concentrations of SP-A and SP-D in BAL fluids from patients with idiopathic pulmonary fibrosis (IPF) and interstitial pneumonia with collagen vascular diseases (IPCD) are rather lower than those in healthy controls and the SP-A/phospholipid ratio may be a useful marker of survival prediction. SP-A and SP-D appear in the circulation in specific lung diseases. Their serum concentrations significantly increase in patients with PAP, IPF and IPCD. The successive monitoring of serum levels of SP-A and SP-D may predict the disease activity. The serum SP-A levels increase in patients with ARDS. SP-A is also a marker for lung adenocarcinomas and can be used to differentiate lung adenocarcinomas from other types and metastatic cancers from other origins, and to detect metastasis of lung adenocarcinomas.

Enzyme-Linked Immunosorbent Assay↗
PubMed1998

Induced potential model for muscular contraction mechanism, including two attached states of myosin head.

The model for myosin head motion along an actin filament as proposed by Mitsui & Chiba [(1996). J. theor. Biol. 182, 147-159] is here modified so that it can explain the isometric tension and isotonic velocity transients having the same parameter values as the stationary filament sliding. The modified model differs in that a myosin head forms a complex with two actin molecules in an actin filament and has two attached states in the complex instead of three. Thus an incremental step in the myosin head motion is equal to the F-actin monomer repeat (5.46 nm). Muscle properties concerning the stationary filament sliding are calculated with new parameters in a manner similar to that of Mitsui-Chiba, with the results being qualitatively similar to theirs. In studying the transient phenomena, a quantitative expression is given for the potential energy of the myosin head in the complex, and two rate constants are applied to the kinetics of the head. The time course of tension recovery after a quick length change is determined by calculating the statistical distribution of the head in the two attached states, which conforms to experimental observations by Ford et al. [(1977). J. Physiol. 269, 441-515]. The tension variations T1/T0 and T2/T0 calculated with parameters determined from the analysis of stationary filament slidings are in fairly good agreement with the experimental data by Ford et al. The model suggests that a large fluctuation exists in the relative position between the actin and myosin filaments even when the load on a muscle is kept constant. Taking this fluctuation into account explains the characteristics of the isotonic velocity transient observed by Civan & Podolsky.

Actins↗
PubMed1998

Actinin-4, a novel actin-bundling protein associated with cell motility and cancer invasion.

Regulation of the actin cytoskeleton may play a crucial role in cell motility and cancer invasion. We have produced a monoclonal antibody (NCC- Lu-632, IgM, k) reactive with an antigenic protein that is upregulated upon enhanced cell movement. The cDNA for the antigen molecule was found to encode a novel isoform of nonmuscle alpha-actinin. This isoform (designated actinin-4) was concentrated in the cytoplasm where cells were sharply extended and in cells migrating and located at the edge of cell clusters, but was absent from focal adhesion plaques or adherens junctions, where the classic isoform (actinin-1) was concentrated. Actinin-4 shifted steadily from the cytoplasm to the nucleus upon inhibition of phosphatidylinositol 3 kinase or actin depolymerization. The cytoplasmic localization of actinin-4 was closely associated with an infiltrative histological phenotype and correlated significantly with a poorer prognosis in 61 cases of breast cancer. These findings suggest that cytoplasmic actinin-4 regulates the actin cytoskeleton and increases cellular motility and that its inactivation by transfer to the nucleus abolishes the metastatic potential of human cancers.

Actinin↗
PubMed1998

Mouse P450RAI (CYP26) expression and retinoic acid-inducible retinoic acid metabolism in F9 cells are regulated by retinoic acid receptor gamma and retinoid X receptor alpha.

We have cloned a mouse cDNA homolog of P450RAI, a cytochrome P450 belonging to a new family (CYP26), which has previously been isolated from zebrafish and human cDNAs and found to encode a retinoic acid-inducible retinoic acid hydroxylase activity. The cross-species conservation of the amino acid sequence is high, particularly between the mouse and the human enzymes, in which it is over 90%. Like its human and zibrafish counterparts, the mouse P450RAI cDNA catalyzes metabolism of retinoic acid into 4-OH-retinoic acid, 4-oxo-retinoic acid, 18-OH-retinoic acid, and unidentified water-soluble metabolites when transfected into COS-1 cells. Retinoic acid-inducible retinoic acid metabolism has previously been observed in F9 murine embryonal carcinoma cells and some derivatives lacking retinoid receptors. We were interested in determining whether P450RAI could be responsible for retinoic acid metabolism in F9 cells and in studying the effect of retinoid receptor ablation on P450RAI expression. In wild-type F9 cells and derivatives lacking RAR gamma, RAR alpha, and/or RXR alpha, we observed a direct relationship between the level of retinoic acid metabolic activity and retinoic acid-induced P450RAI mRNA. These experiments, as well as others using synthetic receptor subtype-specific retinoids, suggest that the RAR gamma and RXR alpha receptors mediate the effects of retinoic acid on the expression of the P450RAI gene.

Amino Acid Sequence↗
PubMed1998

Significance of membrane glycoproteins in platelet interaction with oxidized low-density lipoprotein.

The significance of three platelet membrane glycoproteins, (CD62p, CD63, and CD36) was studied in platelet interaction with native and copper-oxidized plasma low-density lipoproteins (LDL). Native LDL acquired platelet-activating ability only after oxidation. Flow-cytometric studies showed that CD62P and CD63 were rapidly expressed on platelets at a low concentration of oxidized LDL, indicating that they are more sensitive markers than platelet aggregation for detection of platelet activation by oxidized LDL. CD36 was found to be contributing to the binding and activation of platelets with oxidized LDL, but not to the binding of platelets with native LDL. Although the presence of oxidized LDL in plasma is known, its effect on platelet function remains to be studied.

Antigens, CD↗
PubMed1998

Neonatal hyperbilirubinemia and mutation of the bilirubin uridine diphosphate-glucuronosyltransferase gene: a common missense mutation among Japanese, Koreans and Chinese.

We analyzed the bilirubin uridine diphosphate-glucuronosyltransferase (B-UGT) gene in 42 Japanese newborns with hyperbilirubinemia and determined that 21 infants were heterozygous while 3 was homozygous for Gly71Arg. Allele frequency of Gly71Arg was 0.32 in newborns with hyperbilirubinemia, which was significantly higher than 0.13 in healthy Japanese controls. This mutant allele is also prevalent among Korean and Chinese healthy controls with a frequency of 0.23 in both populations. However, this mutation was not detected in 50 healthy German controls. These data suggest that the high frequency of the Gly71Arg mutation of the B-UGT gene is associated with high incidence of neonatal hyperbilirubinemia in Japanese, Korean and Chinese populations.

Alleles↗
PubMed1998

'Alice in Wonderland' syndrome as a precursor of depressive disorder.

A 54-year-old Japanese businessman who was found to exhibit the 'Alice in Wonderland' syndrome and went on to develop a depressive disorder is described. Lengthening and shortening of time experience continued intermittently for about 3 months, and metamorphopsia, distortion of body image, and the quick-motion phenomenon (alteration in time sense) persisted for almost 2 days without interruption. There were no abnormal physical findings. The authors review studies on 'Alice in Wonderland' syndrome and suggest that depressive illness may be a causal factor.

Body Image↗
PubMed1998

Familial hypercholesterolemia with cholesteryl ester transfer protein deficiency.

A 21-year-old male was clinically diagnosed with familial hypercholesterolemia (FH) by the manifestations of hypercholesterolemia, tendon xanthoma and family history of premature coronary heart disease. Low density lipoprotein receptor gene was analyzed in attempt to determine a possible point mutation. The normal sequence was partially preserved, and the patient was genetically diagnosed as a heterozygote of FH. In addition, screening for two cholesteryl ester transfer protein (CETP) gene mutations common to Japanese revealed the patient to be a heterozygote of CETP deficiency. A complication of two influential mutations for atherosclerotic ailments was genetically ascertained.

Adult↗
PubMed1998

Diminished kidney function and nephrocalcinosis in rats fed a magnesium-deficient diet.

The effect of a magnesium-deficient diet on kidney function was studied in young male rats. The rats were fed a purified diet with a magnesium content of either 20.5 (control diet) or 2.6 mmol/kg (magnesium-deficient diet) for 21 d. In rats fed the magnesium-deficient diet, kidney wet and dry weights were significantly increased, and calcium and phosphorus concentrations in the kidney were significantly higher than in rats fed the control diet. Upon histological examination, an increase in the mesangial matrix of the glomeruli and injury to the brush border of the proximal tubules were observed in rats fed the magnesium-deficient diet. Also, a deposition of calcium was observed in the tubules of the corticomedullary junction and medulla of these rats. Total protein and albumin concentrations in serum were significantly decreased in rats fed the magnesium-deficient diet. Urinary albumin excretion was significantly higher, and N-acetyl-beta-D-glucosaminidase activity in the urine was significantly increased in rats fed the magnesium-deficient diet. These findings indicate diminished glomerular and proximal tubular functions. We suggest that a magnesium-deficient diet not only induces nephrocalcinosis, but it also diminishes kidney function.

Acetylglucosaminidase↗
PubMed1998

Effects of iron and copper supplementation on the formation of thiobarbituric acid-reactive substances and phosphatidylcholine hydroperoxide in the livers of iron- and copper-deficient rats.

Free radicals and lipid peroxide formation are related to tissue damage. This damage is thought to be associated with various diseases. To accurately assess the degree of lipid hydroperoxidation in biological materials, three different thiobarbituric acid (TBA) assay methods and the measurement of phosphatidylcholine hydroperoxide (PCOOH) by the chemiluminescence-HPLC (CL-HPLC) method were compared. Iron and copper deficiencies in rats reduced the contents of these metals. The addition of iron and copper to liver homogenates produced dose-dependent increases and decreases in TBARS, respectively. TBARS measured by the Shinnhuber method slightly increased with the addition of copper. The measurement of PCOOH was less affected by the addition of these metals. TBARS did not reflect lipid peroxidation when different concentrations of metals were present in the samples. The TBARS level is thus not a suitable marker for the assess of lipid peroxidation. PCOOH, accumulated as a primary peroxidation product from membrane phospholipids in the liver, was found to be a more appropriate marker for the estimating hepatic lipid peroxidation in the iron- and/or copper-deficient condition.

Animals↗
PubMed1998

[Apolipoprotein E immunoreactivities in normal human ovary and ovarian neoplasms].

An immunohistochemical study on localization of apoE in normal human ovary and various ovarian neoplasms was performed using polyclonal anti-human apoE antibody. In the normal tissues, apoE immunoreactivity was found in folliculus (theca interna and stratum granulosum), and most intensely in a corpus luteum. The stroma cells were not stained. Among various ovarian tumours, positive staining was found in granulosa cell tumour, teratoma and dysgerminoma. Close relationship between apoE and steroid synthesis was suggested by the distribution of apoE in the studied tissues. The present results show that an immunohistochemical study for apoE may be helpful for the diagnosis of steroid producing tumours.

Apolipoproteins E↗
PubMed1997

Specific and redundant functions of retinoid X Receptor/Retinoic acid receptor heterodimers in differentiation, proliferation, and apoptosis of F9 embryonal carcinoma cells.

We have generated F9 murine embryonal carcinoma cells in which either the retinoid X receptor (RXR)alpha and retinoic acid receptor (RAR)alpha genes or the RXRalpha and RARgamma genes are knocked out, and compared their phenotypes with those of wild-type (WT), RXRalpha-/-, RARalpha-/-, and RARgamma-/- cells. RXRalpha-/-/ RARalpha-/- cells were resistant to retinoic acid treatment for the induction of primitive and parietal endodermal differentiation, as well as for antiproliferative and apoptotic responses, whereas they could differentiate into visceral endodermlike cells, as previously observed for RXRalpha-/- cells. In contrast, RXRalpha-/-/RARgamma-/- cells were defective for all three types of differentiation, as well as antiproliferative and apoptotic responses, indicating that RXRalpha and RARgamma represent an essential receptor pair for these responses. Taken together with results obtained by treatment of WT and mutant F9 cells with RAR isotype- and panRXR-selective retinoids, our observations support the conclusion that RXR/ RAR heterodimers are the functional units mediating the retinoid signal in vivo. Our results also indicate that the various heterodimers can exert both specific and redundant functions in differentiation, proliferation, and apoptosis. We also show that the functional redundancy exhibited between RXR isotypes and between RAR isotypes in cellular processes can be artifactually generated by gene knockouts. The present approach for multiple gene targeting should allow inactivation of any set of genes in a given cell.

Animals↗
PubMed1997

Amino-terminus truncated apolipoprotein E is the major species in amyloid deposits in Alzheimer's disease-affected brains: a possible role for apolipoprotein E in Alzheimer's disease.

Amyloid deposits in Alzheimer's disease (AD) are composed of amyloid beta protein (A beta) and many other components called amyloid-associated proteins. Apolipoprotein E (apoE) is one of the most important amyloid-associated proteins. The role apoE plays in AD, however, is yet to be determined. In this study, we present the biochemical and histochemical nature of apoE in AD-affected brains using four monoclonal antibodies (mAbs) against apoE and newly established antibodies against the amino-terminal (anti-apoE-N), and carboxyl-terminal regions (anti-apoE-C) of apoE. Competitive ELISA and Western-blot analysis combined with thrombolytic digestion of apoE indicated that our four mAbs recognized at least two different epitopes within a 22-kDa amino-terminal domain of apoE. Using these mAbs and an anti-A beta mAb, double immunostaining showed that the majority of amyloid deposits were stained by both anti-apoE and anti-A beta mAbs, but the minority of them were detected only by either anti-apoE or anti-A beta mAbs. Differences in staining properties between anti-apoE-N and anti-apoE-C were that anti-apoE-C recognized both amyloid deposits and astrocytes similar to anti-apoE mAbs, but anti-apoE-N strongly stained only astrocytes. Preliminary semi-quantitative determinations of apoE in CSF and brain homogenate showed that the amount of apoE increased in AD and Creutzfeldt-Jakob disease brains compared to normal samples. Our immunological data, using antibodies specific for the amino and carboxyl termini of apoE, suggest that apoE may, in some circumstances, initiate plaque formation, and that apoE in amyloid deposits has at least part of its amino termini cleaved out.

Alzheimer Disease↗
PubMed1997

A novel type of binding specificity to phospholipids for rat mannose-binding proteins isolated from serum and liver.

Mannose-binding protein (MBP) belongs to the collectin subgroup of C-type lectins with specificity for mannose and N-acetylglucosamine sugars. We investigated whether rat MBPs isolated from serum (S-MBP) and liver (L-MBP) interact with phospholipids using antibody against each MBP. Both S- and L-MBPs bound to phosphatidylinositol coated onto microtiter wells in a concentration- and a Ca2+-dependent manner. L-MBP also bound to phosphatidylglycerol and weakly to phosphatidylserine. MBPs interacted with liposomes composed of these lipids. S- and L-MBPs bound to phosphatidylinositol 4-monophosphate. L-MBP also bound to cardiolipin. These results provide evidence for a novel type of ligand binding specificity for MBPs, and raise the possibility that phospholipids are ligands for collectins.

Acute-Phase Proteins↗