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Biomedical subjects

K Mimura

Publications and source records attributed to K Mimura.

At least 19 recordsLinked to original sources
PubMed1998

Galactocerebroside and not glucocerebroside or ceramide stimulate epidermal beta-glucocerebrosidase activity.

Glycosphingolipids including glucocerebroside (GluCer) and galactocerebroside (GalCer) have been recognized as bioreguratory lipids by our group and others. In addition, our recent study demonstrated that GalCer corrects dry skin conditions in humans. The processing of stratum corneum lipids, which occurs when beta-glucocerebrosidase (beta-GluCer'ase) changes GluCer to ceramide (Cer), is required to form the epidermal permeability barrier. We herein investigated the effects of GluCer, GalCer and Cer on the processing of GluCer to Cer by assaying epidermal beta-GluCer'ase in mice (155%, P < 0.01) when compared to vehicle treated controls, while neither GluCer nor Cer had this effect. Studies using inhibitors of beta-GluCer'ase or beta-galactosidase and measuring the optimum pH of the enzyme verified that GalCer specifically activated beta-GluCer'ase. We confirmed that GalCer significantly increased beta-GluCer'ase activity in the outer epidermal fraction (172%, P < 0.01) and that the activation of beta-GluCer'ase is not due to a direct activating effect of GalCer on the enzyme. Furthermore, the induction of beta-GluCer'ase activity by GalCer was also observed in cultured normal human deratinocytes (123%, P < 0.01). Finally, acylceramide content in stratum corneum was increased in mice treated with GalCer (194%, P < 0.0005). These results indicate that GalCer appears to affect the Cer construct in the stratum corneum by the activation of beta-GluCer'ase, which ultimately contribute to an enhancement of barrier formation.

Animals↗
PubMed1998

Comparative study of 5' UTR and NS3R primers for the detection of GB virus C/hepatitis G virus RNA in Japanese.

AIMS/BACKGROUND: Many epidemiological studies of new hepatitis viruses, including GB virus C (GBV-C) and hepatitis G virus (HGV), have used polymerase chain reaction (PCR) primers designed for the third nonstructural region (NS3R). However, a homology study of GBV-C and HGV genomes revealed that the 5' untranslated region (5'UTR) was more conserved than NS3R. METHODS: We attempted to detect GBV-C/HGV using PCR primers corresponding to the 5' UTR, and compared its incidence to that derived from NS3R primers. Furthermore, PCR products amplified using the 5' UTR primers were sequenced and subjected to phylogenetic analysis. RESULTS: In patients with chronic hepatitis C, the prevalence of GBV-C/HGV by PCR with the NS3R and 5' UTR primers was 5.1% (4/78) and 17.9% (14/78), respectively, and in patients on hemodialysis, it was 0% (0/81) and 5.9% (5/85), respectively. We could not detect GBV-C/HGV in patients with non-A-C liver disease. The incidence of GBV-C/HGV by 5' UTR primers was higher than by NS3R primers. After DNA sequencing at 5' UTR, phylogenetic analysis showed two types of GBV-C/HGV, Jap and HGV types. CONCLUSION: 5' UTR primers proved highly sensitive for detection of GBV-C/HGV and were superior to the NS3R primers.

5' Untranslated Regions↗
PubMed1998

Cytogenetic analysis of de novo acute myeloid leukemia with trilineage myelodysplasia in comparison with myelodysplastic syndrome evolving to acute myeloid leukemia.

Characteristics of karyotypes were analyzed in de novo acute myeloid leukemia (AML) with trilineage myelodysplasia (AML/TMDS) at initial diagnosis and compared with myelodysplastic syndrome (MDS) cases that had evolved to AML (MDS/AML). Abnormal karyotypes were seen in 11 of 19 patients with AML/TMDS and 13 of 16 MDS/AML cases. Trisomy 8 was observed in 3 AML/TMDS cases as a sole anomaly and was also present in 3 MDS/AML cases but not as a sole finding. Although MDS/AML frequently displayed monosomies or long-arm deletions of chromosome 5, 7 and 9, only one case exhibited long-arm deletion (of chromosome 7) in AML/TMDS. Two or more chromosome aberrations were found in some cases in both groups. These findings suggest that AML/TMDS had passed through several preleukemic stages at diagnosis, as has been well documented in MDS and MDS/AML. Additionally, clonal evolution may have already occurred in AML/TMDS, as MDS transformed to AML is associated with clonal evolution.

Acute Disease↗
PubMed1998

[Squamous cell lung cancer with minimal-change nephrotic syndrome].

We report a case of squamous cell lung cancer with nephrotic syndrome. A 69-year-old man was admitted because of proteinuria and microhematuria. A plain chest X-ray film on admission showed a large mass in the left-lower lung field. The patient was given a diagnosis of minimal-change-nephrotic syndrome and squamous cell lung cancer. We first treated the nephrotic syndrome with glucocorticoid therapy, and then treated the lung cancer with chemo-radiotherapy. This reduced the lung cancer, alleviated the proteinuria, and completely resolved the nephrotic syndrome. Nephrotic syndrome is generally associated with malignant lymphoma and other nonepithelial neoplasms. As the underlying disease, epithelial neoplasms are less common, but lung cancer is one of the most widely reported. Histologically, most cases of cancer-associated nephrotic syndrome exhibit membranous nephropathy; Minimal-change nephrotic syndrome is rare. Deposits of immunocomplex on glomerular basement membrane are considered to play a pathogenic role in membranous nephropathy. However, the pathogenesis of minimal-change nephrotic syndrome is different.

Aged↗
PubMed1997

Differences in the angiogenesis of benign and malignant ovarian tumors, demonstrated by analyses of color Doppler ultrasound, immunohistochemistry, and microvessel density.

BACKGROUND: To clarify the differences in angiogenesis between benign and malignant ovarian tumors, the authors examined the immunohistochemical characteristics and the density of tumor vessels in both tumor groups. Intratumoral vascularization was observed preoperatively by transvaginal color Doppler ultrasound. METHODS: The authors examined 106 patients with ovarian tumors preoperatively for the presence or absence of intratumoral blood flow and evaluated the blood flow waveforms of tumor vessels in patients showing intratumoral vascularization, using a resistance index (RI). The characteristics of both smooth muscle and endothelial cells in the vessels of each tumor were immunohistochemically assessed, using monoclonal antibodies against smooth muscle actin (SMA) and CD34 (an endothelial cell marker). The microvessel density (MVD) identified by CD34 was also evaluated in each tumor. RESULTS: Intratumoral blood flow was found in 64 of 106 patients (60.4%). The tumors in 44 of these 64 patients were histopathologically benign, and the tumors in 20 were malignant. The malignant tumors showed a low RI (mean, 0.39 +/- 0.09) compared with benign tumors (mean, 0.62 +/- 0.12) (P < 0.001). The vessels of malignant tumors significantly demonstrated poor SMA expression and intense CD34 expression compared with the vessels of benign tumors. However, no significant differences were observed in MVD between the benign and malignant tumors. CONCLUSIONS: In this study, immunohistochemical analysis demonstrated that low resistance to blood flow in vessels within malignant ovarian tumors may be associated with a poorly developed muscular coat in the tumor vessels, compared with that observed in benign tumors. The difference in the angiogenic natures of benign and malignant ovarian tumors showing intratumoral blood flow may thus be correlated with the endothelial cell activity of the tumor vessels and not the MVD.

Actins↗
PubMed1997

Intrinsically aged epidermis displays diminished UVB-induced alterations in barrier function associated with decreased proliferation.

Ultraviolet (UV) irradiation of the skin induces a variety of responses in the epidermis, including sunburn cell formation, epidermal hyperplasia, and a dose-dependent permeability barrier abnormality, an effect that appears to be dependent upon both UVB-induced hyperplasia and T-cell activation. Since intrinsically aged epidermis displays decreased epidermal turnover, diminished inflammatory response to various stimuli, including UVR, and impaired immune function, we investigated the effects of UVB on both epidermal barrier function and proliferation in hairless mice of increasing chronologic age (27, 61, and 90 wk). After a single UVB exposure (0.15 J/cm2 7.5 MED), a barrier abnormality developed (i.e., increased transepidermal water loss; TEWL), after a delay of > or = 48 h, regardless of age. In young mice (27 wk old), TEWL levels peaked at 72-96 h (9.9-fold over untreated controls), whereas increased epidermal [3H]thymidine incorporation preceded the peak TEWL increase (i.e., approximately 570% increase over controls at 48 h). In contrast, the UVB-induced increased in both TEWL and DNA synthesis were significantly diminished, with decreased epidermal hyperplasia evident, in intrinsically aged versus young mouse epidermis. Baseline epidermal thickness decreased with animal age (i.e., 16.8 +/- 3.1 vs. 27.9 +/- 0.7 microm for 90- vs. 27-wk-old animals, respectively; p < 0.02), suggesting that the diminished barrier response with aging reflects an attenuation of events subsequent to initial UVB exposure, rather than an increase in the UV dose delivered. These results demonstrate that (i) murine epidermis becomes less sensitive to UVB-induced barrier alterations with age and (ii) decreased DNA synthesis after UVB correlates with the age-related decrease in barrier dysfunction.

Animals↗
PubMed1997

Propionyl coenzyme A carboxylase is required for development of Myxococcus xanthus.

A dcm-1 mutant, obtained by transposon mutagenesis of Myxococcus xanthus, could aggregate and form mounds but was unable to sporulate under nutrient starvation. A sequence analysis of the site of insertion of the transposon showed that the insertion lies within the 3' end of a 1,572-bp open reading frame (ORF) designated the M. xanthus pccB ORF. The wild-type form of the M. xanthus pccB gene, obtained from a lambdaEMBL library of M. xanthus, shows extensive similarity to a beta subunit of propionyl coenzyme A (CoA) carboxylase, an alpha subunit of methylmalonyl-CoA decarboxylase, and a 12S subunit of transcarboxylase. In enzyme assays, extracts of the dcm-1 mutant were deficient in propionyl-CoA carboxylase activity. This enzyme catalyzes the ATP-dependent carboxylation of propionyl-CoA to yield methylmalonyl-CoA. The methylmalonyl-CoA rescued the dcm-1 mutant fruiting body and spore development. During development, the dcm-1 mutant cells also had reduced levels of long-chain fatty acids (C16 to C18) compared to wild-type cells.

Amino Acid Sequence↗
PubMed1997

Interstitial muscle insulin and glucose levels in normal and insulin-resistant Zucker rats.

To study interstitial insulin and glucose concentrations, microdialysis was performed in the medial femoral muscles in normal SD rats as well as in insulin-resistant obese Zucker rats during a euglycemic insulin clamp. [14C]inulin was given (0.1 mCi/rat) as a constant subcutaneous infusion 24 h before the insulin clamp. Insulin infusion rates were 5-8 mU x kg(-1) x min(-1) (low rate) for 140 min and 10-20 mU x kg(-1) x min(-1) (high rate) for another 100 min. The relationship between insulin and [14C]inulin dialysate recoveries was evaluated in vivo and in vitro in plasma to calculate interstitial insulin concentration. Relative microdialysis recovery of interstitial insulin in vivo was 3.0 +/- 0.3% (mean +/- SE, n = 68). In normal SD rats, plasma and interstitial insulin concentrations were identical when plasma insulin was < or =250 mU/ml, whereas interstitial insulin was lower when plasma insulin was > or =350 mU/ml. Half-maximal glucose infusion rate was achieved in the presence of plasma and interstitial insulin concentrations of approximately 140 mU/ml, whereas maximal glucose disposal was seen at interstitial insulin concentrations of approximately 325 mU/ml, corresponding to approximately 500 mU/ml in plasma. In electrically stimulated and contracting (1 Hz) normal muscle with markedly increased blood flow, the dialysate insulin concentration was significantly higher at high rates, but not at low rates, of insulin infusion. In insulin-resistant obese Zucker rats, the interstitial insulin concentration was similar to that in plasma, even at pharmacological concentrations. The glucose infusion rate was significantly lower in the obese Zucker rats at both insulin infusion rates than in the lean animals. The glucose content in dialysates from skeletal muscle was equal in both obese and lean rats during the low insulin infusion rate. During the high insulin infusion rate, dialysate glucose concentrations decreased significantly in both groups but were significantly higher in the obese Zucker rats. The data suggest that transport of insulin and glucose diffusion across the capillary wall are rate limiting for insulin as well as for glucose metabolism in muscle in normal rats. This does not appear to be the case in the insulin-resistant obese Zucker rats, where the reduced insulin responsiveness in muscle is due to muscular cellular defects rather than an inhibited transcapillary delivery of insulin.

Animals↗
PubMed1997

[Insulin secretin and resistance accompany immobilization of the aged patient].

Physical activity is known to increase glucose tolerance and insulin sensitivity. To examine the influence of physical inactivity on insulin sensitivity in aged people, insulin sensitivity and secretion was measured by using a two-step euglycemic glucose clamp, a glucagon tolerance test (GTT), an oral glucose tolerance test (OGGT) and urinary CPR excretion in 11 aged patients immobilized in bed for more than 12 weeks. The results were compared with those of nine healthy mobile aged controls. The muscle volume of the immobilized patients decreased by 20-25% compared with that of the controls, and insulin sensitivity decreased 50% in each step. These results mean that the immobilized patients had decreased insulin sensitivity and responsiveness, even when there was muscle atrophy. The glucose and insulin responses in both the GTT and OGTT showed that there was a slight decrease in the initial response of insulin in the immobilized patients and was in the controls compared with adolescent controls. There was no difference in the initial response of insulin between the immobilized patients and the aged controls. The ratio of impaired glucose tolerance in the OGTT was 4/11 of the immobilized patients and 3/9 of the controls. Total insulin secretion was increased and insulin sensitivity and responsiveness was decreased in the immobilized patients. This suggests that the decreased insulin sensitivity was compensated for increased by insulin secretion in the immobilized patients.

Aged↗
PubMed1997

Effect of beraprost sodium on the increased transendothelial permeation of albumin induced by high concentration of glucose.

To determine whether a decrease in prostacyclin production is involved in the increase in endothelial permeability induced by a high concentration of glucose, we evaluated the effect of beraprost sodium, a stable prostacyclin analog, on the transendothelial permeation of albumin in cultured aortic cells. Permeation of albumin across an endothelial cell monolayer was significantly greater when the cells were cultured with a high concentration of glucose (400 or 800 mg/dl) than when they were cultured with 100 mg/dl glucose. No significant change in the permeation of albumin was observed when cells were cultured with 100 mg/dl glucose as compared with 100 mg/dl glucose plus 700 mg/dl mannitol. The addition of beraprost sodium to the culture medium completely restored the increase in the permeation of albumin brought about by 400 mg/dl glucose. These results suggest that increased transendothelial permeation of albumin by high glucose may be due in part to a decrease in prostacyclin production by the endothelial cells. Beraprost sodium may restore the endothelial barrier function affected by a high concentration of glucose.

Albumins↗
PubMed1996

Age-related changes in branched-chain fatty acid concentration of the skin surface lipid from hairless mouse.

Age-related changes in branched chain fatty acid (BCFA) concentration were studied with the skin surface lipid from hairless mice. A large proportion of BCFA was present in the cholesterol ester (CE) and wax diester (WDE) fraction of the skin surface lipid from hairless mice. The concentration of iso-series BCFA was highest at infancy and decreased with advancing age in both CE and WDE fraction. The concentration of anteiso-series BCFA appeared to be constant throughout the experiment.

Age Factors↗
PubMed1996

Effect of a chemically-synthesized acylglucosylceramide, epidermoside, on normal human keratinocyte differentiation.

Epidemosides (N-(0-linoleoyl)-(1)-hydroxy fatty acyl sphingosyl glucose) are found exclusively in the epidermis not in dermis, and are thought to play important role in forming the mammalian epidermal permeability barrier. A species of epidermoside isolated from guinea pig epidermis and named lipokeratinogenoside has been shown to enhance fetal rat keratinocyte differentiation. In the present investigation, we studied the effects of a chemically synthesized equivalent of human epidermoside on the viability and differentiation of cultured human keratinocytes (HK Cells). The chemically-synthesized epidermoside was not toxic to cultured HK Cells at concentrations of 0.01 to 10 micrograms/ml. When 10 micrograms/ml of the chemically-synthesized epidermoside was added to keratinocyte growth medium containing 1.2 mM Ca2+, HK Cells showed a 5.6-fold increase of keratin content compared to the vehicle treated control at 144 h of cultivation, and they also displayed morphological changes suggestive of differentiation. A similar increase of cellular keratin content was observed in HK cells treated with tetradecanoyl phorbol-13 myristyl-12 acetate (TPA), an agent known to enhance the differentiation of keratinocytes. Lipokeratinogenoside also increased the keratin content of cultured HK cells. These results suggest that epidermosides have an ability to enhance keratinocyte differentiation. Epidermoside could thus be a key molecule, not only as a constituent of the epidermal permeability barrier, but also as a regulator of keratinocyte differentiation.

Animals↗
PubMed1996

Changes in glycerophospholipid profile in experimental nephrotic syndrome.

We investigated changes in the glycerophospholipids in kidney tissue and its various intracellular fractions in rats with nephrotic syndrome induced by puromycin aminonucleoside. The ethanolamine plasmalogen, 1-O-alk-1'-enyl-2-acyl-GPE (EP), was increased in kidney tissue obtained from the puromycin-treated animals. A similar increase was found in the mitochondria and endoplasmic reticulum (microsomes) of this tissue. These increases were not found in the liver. Since platelet-activating factor (PAF) is known to be produced in increased amounts in inflammatory disorders, it is suggested that the higher plasmalogen found in rat kidneys during experimental nephrotic syndrome might be derived from increased levels of this autacoid. The increase in PAF may also result in the elevation of plasma PAF-acetylhydrolase (AH) activity observed in these animals.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1996

Increased expression of a brain/embryo-type myosin heavy chain isoform (MIIB2) in mesangial proliferative glomerulonephritis.

Proliferation of mesangial cells is frequently found in glomerulonephritis, such as IgA glomerulonephritis. Recent reports suggest that a brain/embryo-type myosin isoform (MIIB2) is involved in cell proliferation. We have studied the expression of MIIB2 in renal biopsy samples from patients with various renal diseases and in the renal tissues from the rat model of mesangial proliferative glomerulonephritis induced with anti-Thy 1.1 antibody. Immunohistochemical analysis of the biopsy samples using an anti-brain-type myosin heavy chain-specific monoclonal antibody (HBM1) indicated that 92% of the samples from patients with IgA glomerulonephritis contained a significant population of mesangial cells that reacted with the antibody. Most of the samples from patients with other types of proliferative glomerular diseases also contained HBM1-reactive mesangial cells, while none of the samples from patients with non-proliferative glomerular diseases contained a significant population of HBM1-reactive mesangial cells. The expression of a brain/embryo-type myosin heavy chain isoform (MIIB2) in the mesangial cells began at five days after injection of anti-Thy 1.1 antibody and peaked at the tenth day. On the other hand, the expression of the proliferating cell nuclear antigen in the mesangial cells was induced at two days after injection of anti-Thy 1.1 antibody and was maximal at the fourth day. These results indicate that the expression of the MIIB2 isoform by mesangial cells is accelerated in proliferative glomerulonephritis and suggest that the myosin isoform is involved in the phenotypic transformations of the glomerular tissues rather than in the cell proliferation.

Adolescent↗
PubMed1995

Side-chain structure is critical for the transport of sterols from lysosomes to cytoplasm.

Macrophages take up and metabolize negatively charged liposomes containing free cholesterol efficiently, resulting in a massive accumulation of cholesteryl esters and triacylglycerols in their cytoplasm (Nishikawa, K., Arai, H. and Inoue, K. (1990) J. Biol. Chem. 265, 5226-5231). This system was used to assess the effects of structural variation of sterol on the intracellular transport and the metabolism of endocytosed sterols by the cells. Liposomes containing phytosterols with an extra one (campesterol) or two (beta-sitosterol, stigmasterol, fucosterol) carbons at the C-24 position of the cholesterol side-chain were endocytosed as efficiently as those containing cholesterol without exhibiting any apparent toxicity on the cells. Esterification of endocyotosed phytosterols was, however, extremely low; campesterol esterification was only 20% that of cholesterol and either beta-sitosterol or stigmasterol was not esterified appreciably. A morphological study showed that the endocytosed phytosterols were accumulated in the phagolysosomes of the cells. Blocking of esterification of endocytosed cholesterol by an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor did not lead to cholesterol accumulation in the phagolysosomes. These data suggest that accumulation of endocytosed phytosterols in phagolysosomes is not a consequence of the inability of the cell to esterify sterols in the endoplasmic reticulum. In the light of these observations, we conclude that cultured macrophages can discriminate between sterols that differ only by a methyl or ethyl group at the C-24 position at their lysosomal compartment.

Animals↗
PubMed1995

Chinese hamster ovary cells expressing a novel type of acetylated low density lipoprotein receptor. Isolation and characterization.

Macrophage scavenger receptors mediate the recognition of a wide range of negatively charged macromolecules including acetylated low density lipoproteins (AcLDL). Chinese hamster ovary (CHO) cells were cultured in the presence of increasing concentrations of simvastatin, a cholesterol biosynthesis inhibitor, and AcLDL as the sole source of exogenous lipoproteins. The cells surviving under these conditions specifically bound 125I-labeled AcLDL with high affinity and degraded them via an endocytic pathway. Unexpectedly, the association and degradation of 125I-labeled AcLDL by these CHO cells were not inhibited by dextran sulfate, fucoidan, and polyinosinic acid, competitors of macrophage scavenger receptors, but were completely inhibited by maleylated bovine serum albumin. Furthermore, these cells effectively took up negatively charged liposomes containing acidic phospholipids such as phosphatidylserine and phosphatidic acid, whereas CHO cells expressing macrophage scavenger receptors did not. AcLDL and negatively charged liposomes were cross-competed with each other. Northern blot analysis using the cDNA for the macrophage scavenger receptor revealed that these CHO cells did not express this receptor. From these observations, we conclude that the isolated CHO cells express a novel type of AcLDL receptor, which is distinct from macrophage scavenger receptors with respect to ligand specificity and competitor sensitivity.

Albumins↗