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Biomedical subjects

M Adachi

Publications and source records attributed to M Adachi.

At least 19 recordsLinked to original sources
PubMed1996

SPONASTRIME dysplasia: report on a female patient with severe skeletal changes.

We report on a 6-year-old girl with SPONASTRIME dysplasia, characterized by short-limbed dwarfism, a relatively large head, midfacial hypoplasia, a saddle nose, moderate deformities of the vertebral bodies, striated metaphyses, and normal intelligence. She showed severe skeletal changes including marked delay of epiphyseal ossification, evident metaphyseal dysplasia, and osteopathia striata more pronounced than in most of the previously reported patients with this disorder. The patient we describe and a male patient reported by Camera et al. [1994: Pediatr Radiol 24:322-324] are likely to represent the severely-affected end of the clinical spectrum of the disorder. These finding thus rule out the X-linked mode of inheritance of the disorder proposed by Camera et al. [1994: Pediatr Radiol 24: 322-324]. Alternatively, the two severely-affected patients may represent a variant form of the disorder. There is evidence that SPONASTRIME dysplasia is a genetically heterogeneous disorder.

Bone Diseases, Developmental↗
PubMed1996

Interleukin-2 (IL-2) upregulates BAG-1 gene expression through serine-rich region within IL-2 receptor beta c chain.

BAG-1 is a Bci-2-binding protein which functions in protection from apoptotic cell death. Here we provide evidence for interleukin-2 (IL-2)-mediated upregulation of BAG-1 expression. In hematopoietic cell line BAF-B03 F7 cells, gene transfer mediated expression of the IL-2R beta c chain is sufficient to confer proliferation and cell survival responses to IL-2. In these IL-2R beta c-expressing cells, BAG-1 mRNA was dramatically induced by IL-2. The IL-2-mediated induction of BAG-1 expression required the activation of tyrosine kinase(s) and was sensitive to rapamycin as the induction of bcl-2 expression was. Analysis of the transfectants which express mutant IL-2R beta c chains or mutant Janus family protein tyrosine kinase Jak3 lacking the kinase domain showed that the IL-2-mediated BAG-1 gene expression required the serinerich region within the IL-2R beta c chain, but Jak3 activation was dispensable. The signaling pathway for BAG-1 gene expression thus highly resembles that for bcl-2 gene expression, strongly suggesting that their induction shares the same signaling pathway. In addition, deletion of the serine-rich region led to loss of IL-2-mediated protection from apoptotic cell death. Taken together, these studies demonstrate that the serine-rich region of the IL-2R beta c chain mediates the coordinated expression of bcl-2 and BAG-1 genes, thereby contributing to suppression of apoptosis.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1996

Constitutively enhanced nbl expression is associated with the induction of internucleosomal DNA cleavage by actinomycin D.

Previous studies have found nbl expression to transiently rise and fall during glucocorticoid-induced thymic apoptosis. This induction of apoptosis is blocked by the transcriptional inhibitor actinomycin D. However, actinomycin D can trigger apoptosis in other cell types, e.g., HL-60 cells. This study found that internucleosomal DNA cleavage typical of apoptosis is induced by actinomycin D in cell lines such as HL-60 which constitutively express high levels of nbl above a certain "threshold." In contrast, "DNA ladder" formation was not induced by actinomycin D in cell lines with low constitutive nbl expression. Enhanced nbl expression therefore appears to be associated with apoptosis which is either blocked or induced by actinomycin D.

Amnion↗
PubMed1996

Synthesis and structure--activity relationships of fused imidazopyridines: a new series of benzodiazepine receptor ligands.

2-Arylimidazo[4,5-c]quinolines and analogous fused imidazopyridines were synthesized and evaluated as benzodiazepine receptor ligands. Affinity to the receptors was greatly affected by the bulkiness of the aryl group at the 2-position, compared to the pyrazoloquinolines such as CGS-9896. Derivatives with an isoxazole moiety at the 2-position showed high binding affinity and in vivo activity. In the imidazo[4,5-c]quinoline series, substitution at the 6-position decreased or abolished activity. Most derivatives with an unsubstituted isoxazolyl group showed antagonist or inverse agonist activity except for the 7-halo analogues, which exhibited agonist activity. On the other hand, 5-methylisoxazol-3-yl or 3-methylisoxazol-5-yl derivatives generally exhibited agonist activity. A similar substitution effect on the isoxazole moiety was observed in the imidazopyridines fused with a nonaromatic ring. From the detailed pharmacological evaluation, S-8510, 2-(3-isoxazolyl)-3,6,7,9-tetrahydroimidazo[4,5-d]pyrano++ +[4,3-b]pyridine monophosphate, possessing weak inverse agonist activity was selected as a therapeutic candidate for the treatment of some symptoms of senile dementia.

Animals↗
PubMed1996

Expression of dominant negative mutant SHPTP2 attenuates phosphatidylinositol 3'-kinase activity via modulation of phosphorylation of insulin receptor substrate-1.

To clarify the role of protein-tyrosine phosphatase (PTPase) containing Src homology 2 regions (SHPTP2) in insulin signaling, either wild-type or mutant SHPTP2 (delta PTP; lacking full PTPase domain) was expressed in Rat 1 fibroblasts overexpressing human insulin receptors. In response to insulin, phosphorylation of insulin receptor substrate 1 (IRS-1), IRS-1-associated PTPase activities and phosphatidylinositol (PI) 3'-kinase activities were slightly enhanced in wild-type cells when compared with those in the parent cells transfected with hygromycin-resistant gene alone. In contrast, introduction of delta PTP inhibited insulin-induced association of IRS-1 with endogenous SHPTP2 and impaired both insulin-stimulated phosphorylation of IRS-1 and activation of PI 3'-kinase. Furthermore, decreased content of p85 subunit of PI 3'-kinase was also found in mutant cells. Consistently, the insulin-stimulated mitogen-activated protein kinase activities and DNA synthesis were also enhanced in wild-type cells, but impaired in mutant cells. Thus, the interaction of SHPTP2 with IRS-1 may be associated with modulation of phosphorylation levels of IRS-1, resulting in the changes of PI 3'-kinase and mitogen-activated protein kinase activity. Furthermore, an impaired insulin signaling in mutant cells may be partly reflected in a decreased content of p85 protein of PI 3'-kinase.

Animals↗
PubMed1996

Correlation of KAI1/CD82 gene expression with good prognosis in patients with non-small cell lung cancer.

As part of our evaluation of members of the transmembrane 4 super-family as possible prognostic predictors, we performed a retrospective study on the expression of the recently identified KAI1 gene by tumors of the lung. This gene, which is identical to CD82, suppresses tumor metastasis of prostate cancer, and its decreased expression may be involved in malignant progression. We used reverse transcription-PCR to analyze tumor tissues from 151 lung cancer patients; 74 tumors were stage I, 17 were stage II, and 60 were stage III. Our results indicate that while 35 patients had tumors in which the KAI1/CD82 gene was conserved (positive), 116 patients had tumors with reduced gene expression (negative). The overall survival rate of patients with KAI1/CD82-positive tumors was significantly higher than that of patients with KAI1/CD82-negative tumors (77.4% versus 38.5%; P=0.002). Furthermore, the overall survival rate of patients with KAI1/CD82-positive adenocarcinoma was also much higher than that of individuals whose adenocarcinoma had reduced KAI1/CD82 expression (73.4% versus 27.1%;P=0.009). Multivariate analysis with the Cox regression model indicated that KAII/CD82 positivity correlated best with the overall survival rate, except for lymph node status. Our data suggest that high KAII/CD82 gene expression by tumors of the lung may be associated with a good prognosis. These findings complement our earlier studies on MRP-1/CD9, another member of the transmembrane 4 superfamily, whose reduced expression in non-small cell lung cancer appears to be a factor of poor prognosis. This set of observations suggests that assessment of the expression status of KAI1/CD82 and MRP-1/CD9 by tumors may provide prognostic information on the clinical behavior of lung cancer.

Age Factors↗
PubMed1996

Enhanced and accelerated lymphoproliferation in Fas-null mice.

Fas is a 45-kDa membrane protein that transduces an apoptotic signal. The mouse lymphoproliferation (lpr) mutation is a leaky mutation of Fas. In this study, we examined lymphocyte development in Fas-null mice generated by gene targeting. The Fas-/- mice progressively accumulated abnormal T cells (Thy1+, B220+, CD4-, and CD8-) and developed lymphadenopathy and splenomegaly, which were much more accelerated and pronounced than those in lpr mice. In addition, the Fas-null mice showed lymphocytosis, accompanied by lymphocytic infiltration in the lungs and liver. The number of apparently normal B cells also increased, and large amounts of immunoglobulins, including anti-DNA antibodies, were produced. Thymic clonal deletion, assessed by deletion of T cells reactive to mouse endogenous superantigens, was apparently normal in the Fas-/- mice, whereas the peripheral clonal deletion of mature T cells against a bacterial superantigen was impaired. These results suggested that Fas plays a decisive role in peripheral clonal deletion but not in negative selection in the thymus.

Animals↗
PubMed1996

Effects of 8-(N-N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8) on skinned myocardial fibres of the rat: reversible inhibition of calcium release from the sarcoplasmic reticulum.

The effects of 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-3), which is reported to inhibit the release of intracellularly stored Ca2+ in skeletal and smooth muscles, were examined in ventricular myocardia of the adult rat. In skinned papillary muscle fibres with functional sarcoplasmic reticulum (SR) preserved, application of 100 or 300 microM TMB-8 during the Ca2+ loading period had no significant effect on the peak tension of subsequent caffeine-induced contraction, but when applied during exposure to caffeine, concentration-dependent reduction of the peak tension was observed. At 1000 microM, TMB-8 reduced the peak tension of caffeine-induced contraction when applied either during Ca2+ loading or during exposure to caffeine. TMB-8 had no substantial influence on the Ca(2+)-tension of skinned fibres without functional SR. In isolated papillary muscle preparations, TMB-8 prolonged the action potential duration and decreased the maximum rate of rise of potential, leading to abolition of contraction at 100 microM. In conclusion, TMB-8 may be a useful pharmacological tool for inhibiting Ca2+ release from SR, but only in skinned myocardial preparations.

Action Potentials↗
PubMed1996

Ill-defined focal low attenuation in the posterior internal capsule: a normal CT finding.

Although many pathological changes in the internal capsule may lead to neurological deficits, we often encounter ill-defined focal low attenuation in the posterior limb of the internal capsule (PIC) on CT in patients with no neurological disturbance. Brain CT studies of 141 patients without neurological deficits were reviewed to investigate the position of the focal low attenuation by analysis of a profile density curve. Nine patients with lacunar infarcts only within the posterior internal capsule were also studied. The focal low attenuation areas were ill-defined and bilaterally symmetrical, without mass effect. They were seen consistently within the posterior limb of the posterior internal capsule. Correlation between the distribution of these foci and the position of lacunar infarcts in the posterior internal capsule in nine patients with neurological deficits suggests that they may be related to the corticospinal tract.

Adult↗
PubMed1996

The direct effect of interferon-gamma on human eosinophilic leukemia cell lines: the induction of interleukin-5 mRNA and the presence of an interferon-gamma receptor.

The EoL-1 and EoL-3, human eosinophilic leukemia cell lines, have been used as models for studying the maturation and the function of human eosinophils. We investigated the effects of interferon-gamma (IFN-gamma) on superoxide anion (O2-) production of these cell lines and interleukin-5 (IL-5) mRNA expression in the EoL-1. O2- was measured by chemiluminescence of MCLA, one of cypridina luciferin analogs. The O2- production of fMLP-stimulated EoL-1 and EoL-3 was increased by the IFN-gamma treatment. IL-5 mRNA expression was detected in the IFN-gamma-treated EoL-1 by reverse transcription-polymerase chain reaction (RT-PCR). Further, we examined IFN-gamma receptor 1 mRNA expression in these cell lines and peripheral blood eosinophils by means of northern blot hybridization. IFN-gamma receptor 1 mRNA was detected in the EoL-3 and the IFN-gamma-treated EoL-1. A weak expression of IFN-gamma receptor 1 mRNA was detected in peripheral blood eosinophils isolated from a patient with eosinophilia. These results suggest that IFN-gamma may act on eosinophils directly through its receptor.

Antigens, CD↗
PubMed1996

High intraocular pressure-induced ischemia and reperfusion injury in the optic nerve and retina in rats.

PURPOSE: The purpose of this paper is to describe the damage caused to the retina and the axons of the optic nerve by acute ischemia-reperfusion injury and the extent to which optic nerve damage correlates with the duration if ischemia due to high intraocular pressure (IOP). METHODS: Acute ischemia in the retina and optic disc was induced in albino rats by increasing the IOP to 110 mmHg for a period of 45-120 min. Thereafter, the eyes were reperfused at normal IOP after 7 days. The retina and optic nerve were examined by light and electron microscopy, and morphometrical counts of the optic nerve axons were performed. RESULTS: After 45 min of ischemia, electron microscopic examination revealed swelling of mitochondria and degeneration of neurotubules on axons in cross sections of the optic nerve. The axonal counts in eyes subjected to 45 min of ischemia were 29% lower than in control eyes. After 60 min of ischemia, there were distinct disruptions of mitochondria and degeneration of the axons. After 90 min of ischemia, numerous axons showed degeneration with disordered myelin sheaths. Neuronal cell death was seen in the retina, mainly in the ganglion cell layer. CONCLUSION: Damage to the retinal ganglion cell layer and the optic nerve was evident after only 45 min of ischemia in normal eyes. This experiment suggests that seriously injured eyes must be protected from high IOP; if IOP elevation is required during vitrectomy, it is essential to reduce the duration of interruption of blood flow to a minimum.

Animals↗
PubMed1996

Fluoride analysis of apatite crystals with a central planar OCP inclusion: concerning the role of F- ions on apatite/OCP/apatite structure formation.

To study the roles of F- ions in the formation of apatite crystals embedding octacalcium phosphate (OCP) lamella in the center of apatite (Ap), a range of the Ap/OCP/Ap lamellar-mixed crystals were synthesized under various concentrations of fluoride ion (F-) from 0. 1-1.0 ppm at pH 6.5 and 37 degrees C. The products were analyzed for the F- incorporation, F- distribution, and the amount of OCP and Ap by chemical analysis, X-ray diffraction (XRD), electron probe microanalysis (EPMA), and nuclear magnetic resonance (NMR) techniques. The F- content and the amount of apatite in the crystalline product increased with an increase in the F- concentration in solution, whereas the amount of OCP and the yield of total product decreased. EPMA indicated that F- ions are distributed in the crystals almost homogeneously. The combined analysis suggested that a low-substituted fluoridated hydroxyapatite (FHAp) grew on a small amount of F--containing OCP or on a surface-reaction layer of OCP, which has accumulated a small amount of F-. The roles of F- ions were hypothesized as the reduction of the growth rate and/or the critical thickness in the a*-axis direction of OCP, the enhancement of hydrolysis of OCP, and the activation of the growth of FHAp, resulting in thinner OCP lamella and thicker apatite lamella in the a*-axis direction with an increase in F- concentration.

Apatites↗
PubMed1996

High prevalence of small LDL particles in non-insulin-dependent diabetic patients with nephropathy.

To determine whether small-sized low density lipoprotein (LDL) is associated with a high incidence of coronary heart disease in diabetic nephropathy, we measured the LDL particle size in non-insulin-dependent diabetes mellitus (NIDDM) patients with various degrees of albuminuria (n = 95) and age-, weight-matched non-diabetic control subjects (n = 31). The diabetic subjects were divided into three groups, normoalbuminuric, microalbuminuric and macroalbuminuric NIDDM, based on the amount of albuminuria. The average diameter of LDL particles was determined by non-denaturing polyacrylamide gradient (2-16%) gel electrophoresis. The plasma lipid and lipoprotein concentrations were comparable between the non-diabetic controls and normoalbuminuric NIDDM, whereas the plasma triglyceride, very-low-density lipoprotein (VLDL) or LDL concentration was significantly increased in diabetic nephropathy. The mean LDL particle size was significantly smaller in microalbuminuric NIDDM compared with the controls or normoalbuminuric NIDDM, and the LDL size was further decreased in macroalbuminuric NIDDM. The incidence of small LDL (diameter < 255 A) was remarkably increased in microalbuminuric (58%) and macroalbuminuric NIDDM (67%) compared to the control (13%) and normoalbuminuric NIDDM (27%). Corresponding to the decreased LDL size, the cholesterol content of the LDL was significantly depleted in NIDDM with nephropathy. The high prevalence of small LDL in diabetic nephropathy was also observed even when hypertriglyceridemic or hypertensive subjects were excluded from each group. The increment in triglyceride-rich lipoprotein (d < 1.006) after oral fat-loading was increased, and postheparin lipoprotein lipase activity was decreased significantly in diabetic nephropathy. These abnormalities were significantly associated with LDL particle size. Multivariate regression analysis revealed that the amount of albuminuria was closely associated with the average LDL particle size, and this association was independent of the plasma triglyceride level. Neither insulin resistance nor glycemic control was directly associated with LDL particle diameter. The present study indicates that LDL particles become smaller in diabetic nephropathy, and this may be associated primarily with abnormal triglyceride metabolism. However, in addition to hypertriglyceridemia, other metabolic abnormalities caused by diabetic nephropathy may also be involved in the pathogenesis of small LDL particles.

Aged↗
PubMed1996

Apoptosis of cultured microglia by the deprivation of macrophage colony-stimulating factor.

Promotion of microglial proliferation and differentiation by colony-stimulating factors (CSFs) and disappearances of microglia at the late neonatal stage by decreasing of CSFs have been reported. In this study, the effects of the deprivation of macrophage CSF (M-CSF) on enriched microglia in cultures were examined by cytochemical methods including in situ nick-end labeling for DNA fragmentation, and Carrazi's hematoxylin nuclear staining. When M-CSF was deprived from the culture medium: (1) at least 40% of the cells were weakly labeled by nick-end within 3 h and more than 70% of the cells were clearly labeled by 16 h; and (2) nuclear condensation or fragmentation, and formation of apoptotic bodies were observed within 48 h. LeY-positive immunoreactivity, identified as a characteristic of cells undergoing apoptosis, was observed on cells positively labeled by nick-end and condensed nucleus, and ones budding apoptotic bodies. From these results, it is conceivable that microglia undergo apoptosis when M-CSF is deprived from the culture medium and, therefore, require CSFs for their survival. This in vitro phenomenon suggests that one of the mechanisms of microglial disappearance in vivo after synaptogenesis may be due to apoptosis by decreasing level of CSFs.

Animals↗
PubMed1996

Subcellular distribution of protein kinase C in the living outer hair cell of the guinea pig cochlea.

Immunohistochemical staining using isoform-specific antibodies and intracellular localization using fluorescent probes for protein kinase C (PKC) were evaluated in the cochlear outer hair cell (OHC). Among three isoforms of classic PKC, PKC alpha was selectively stained in the fixed OHC as well as inner hair cells under a surface preparation method. Two types of fluorescent probes to detect subcellular localization of PKC were observed with a confocal laser scanning microscopy in the present study, fim-1 diacetate which binds to the ATP-competitive catalytic domain of PKC and Bodipy FL C12-phorbol acetate which binds to specific site localized to the first cysteine-rich loop of the C1 region in the regulatory domain. High fluorescence intensity of both dyes was observed in subcuticular and subsynaptic regions, infracuticular network, and along the lateral wall. The displacement experiments to evaluate binding specificity were performed by incubating Bodipy FL C12-phorbol acetate in the presence of 10 microM phorbol 12-myritate 13-acetate (PMA) and the fluorescence was totally disappeared. For the acute treatment of phorbol ester, cells were preincubated with 1 microM PMA 30 min before loading with fim-1 diacetate. The brightest area in the plasma membrane became much larger as compared with untreated cells, which suggests a dramatic translocation of PKC to the plasma membrane. The biological functions involving PKC in the OHC are discussed.

Adenosine Triphosphate↗
PubMed1996

Expression of IL-6, IL-8, and RANTES on human bronchial epithelial cells, NCI-H292, induced by influenza virus A.

Bronchial epithelial cells are primary sites of airway viral infection, and these cells may play an important role in the pathogenesis of respiratory diseases. It has recently been reported that bronchial epithelial cells express RANTES. RANTES attracts monocytes, T cells, eosinophils, and basophils; it can also activate eosinophils. To determine whether viral infection induces RANTES expression on bronchial epithelial cells, we infected a bronchial epithelial cell line, NCI-H292, with influenza virus A (H3N2). We then examined the concentration of RANTES in the culture medium of infected cells by ELISA and assessed expression of the gene for RANTES by the reverse-transcriptase polymerase chain reaction. We also investigated the concentrations of IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor in the medium of infected cells, because some virus infections have been reported to induce expression of these cytokines on bronchial epithelial cells, but there are few data concerning influenza virus infection. Small amounts of IL-6 and IL-8 were detected in the medium of uninfected cells. RANTES was not detected in the medium of uninfected cells. After influenza virus infection, significant amounts of IL-6, IL-8, and RANTES were released into the culture medium of infected cells, and RANTES messenger RNA was detected from infected cells. Granulocyte-macrophage colony-stimulating factor was not detected in the medium of uninfected and infected cells. These results suggest that influenza virus infection may stimulate production of IL-6, IL-8, and RANTES from human bronchial epithelial cells and that these cytokines may contribute to the pathogenesis of airway inflammatory diseases caused by influenza virus infection.

Base Sequence↗