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Biomedical subjects

Y Koga

Publications and source records attributed to Y Koga.

At least 271 records · Page 15Linked to original sources
PubMed1993

Improving effect of acetylcholine receptor agonists on a deficit of 2-deoxyglucose uptake in cerebral cortical and hippocampal slices in aged and AF64A-treated rats.

The aim of the present study was to determine whether the facilitation of 2-deoxyglucose (2-DG) uptake in the cerebral and hippocampal slices by nicotinic and muscarinic receptor agonists is compromised in the aged rat brain. For this, the effects of the nicotinic receptor agonist nicotine, the muscarinic receptor agonists oxotremorine and McN-A-343, and the ACh esterase inhibitors physostigmine and NK247 on 2-DG uptake in the brain slices of young (2-month-old) and aged (24-26-month-old) rats were tested. The decrements of 2-DG uptake in the cortical slices of aged rats were significantly attenuated by treatment with oxotremorine, nicotine and amiridine. In contrast, the metabolic responsivity of hippocampal slices to these drugs was reduced. To assess whether age-related changes in 2-DG uptake may be due to deficits in cholinergic function, we tested these drugs on the decrements of 2-DG uptake in ethylcholine aziridinium (a neurotoxic analog of choline) injected rats. The reductions of 2-DG uptake by injection of ethylcholine aziridinium was attenuated by oxotremorine but not by physostigmine. The present results reveal that metabolic decrements in the cerebral cortex from aged or ethylcholine aziridinium-injected rats were attenuated by muscarinic and nicotinic receptor agonists, suggesting that the muscarinic and nicotinic receptor mechanism in the cerebral cortex may be involved in cholinergic drug-induced functional recovery in aged rats.

Acetylcholine↗
PubMed1993

Facilitation of 2-deoxyglucose uptake in rat cortex and hippocampus slices by somatostatin is independent of cholinergic activity.

2-Deoxyglucose (2-DG) uptake is an index of regional glucose utilization which reflects predominantly activity in the axonal terminal of neuronal pathways. The present experiments showed that somatostatin elevated 2-DG uptake in rat cortex and hippocampus slices. Treatment with somatostatin-14 and somatostatin-28 markedly enhanced 2-DG uptake, whereas the amino-terminal fragment of somatostatin-28 did so only slightly. This effect appeared to be mediated by an interaction with somatostatin receptors because cyclo-somatostatin, a somatostatin antagonist, abolished the effect of somatostatin-14. The increase in 2-DG uptake caused by somatostatin-14 was blocked by the calcium channel antagonist, nifedipine, but not by tetrodotoxin, suggesting that the action of somatostatin does not require the initiation of impulse activity, somatostatin enhanced the KCl-induced release of acetylcholine, suggesting that a cholinergic mechanism is involved in the somatostatin-induced cellular responses. We therefore examined whether acetylcholine receptor antagonists block the somatostatin-induced increase in 2-DG uptake. Neither muscarinic nor nicotinic receptor antagonists affected the somatostatin-14-induced response. The present results suggest that somatostatin has a stimulatory effect on energy metabolism and that this effect is independent of acetylcholine receptor mechanism.

Animals↗
PubMed1993

Fine mapping of mitochondrial RNAs derived from the mtDNA region containing a point mutation associated with MELAS.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a mitochondrial disorder associated with heteroplasmic point mutations in the mitochondrial tRNA(Leu)(UUR) gene. While previous studies have shown that the MELAS mutation at nt-3243 results in impairments in mitochondrial protein synthesis and respiratory chain function, it was not clear whether these were associated with structural alterations in mature RNAs derived from transcription of the region containing the mutation. We have performed fine mapping and high-resolution. Northern analysis of RNAs from cybrids derived from two MELAS patients harboring the nt-3243 mutation. No differences in the size or steady-state levels of transcripts from the 16S rRNA, tRNA(Leu)(UUR), or ND 1 genes (which are contiguous in the mtDNA) were observed between cell lines containing mutated or wild-type mtDNAs. Therefore, it is not likely that the protein synthesis defects observed in cybrids with the MELAS-3243 mutation are directly caused by qualitative alterations in either transcription termination or processing of these mitochondrial RNAs.

Base Sequence↗
PubMed1993

A simple quantitative in vitro assay for thymocyte adhesion to thymic epithelial cells using a fluorescein diacetate.

Recent data verified the role of thymocyte adhesion to thymic epithelial cells (TEC) in T cell development. In order to measure this cellular event as one of routine examinations in immunological studies, a simple quantitative assay in in vitro setting is required. Labeling thymocytes with fluorescein diacetate (FDA) was used to measure quickly and with certainty the adhesion ability of BALB/c thymocytes to TEC cells, a thymic epithelial cell line derived from BALB/c mouse thymic stroma. Thymocytes stained with FDA at the concentration of 2.5 micrograms/ml gave a strong fluorescent intensity (FI) easily detectable in a spectrophotometer and showed the same phenotypical and functional features as unstained cells. As it was confirmed that the cell number correlated well with FI, the number of cells adhering to TEC in wells of a 96-well microplate could be estimated. The major advantage of using FDA was that it took only a few seconds to measure FI of one sample. In contrast, to count the number of adherent cells with conventional methods using a light microscope or radioisotopes required much longer time and care to avoid radiological hazards. Moreover, cell viability and FI of FDA-labeled thymocytes changed little for 24 h, and lysates of FDA-positive cells demonstrated the same FI as living cells. These results indicate that many samples could be applied for FI measurement at the same time after in vivo or in vitro experiments.

Animals↗
PubMed1993

Right common iliac arterio-intestinal fistula caused by tubercular peritonitis: report of a case.

A 59-year-old female was admitted with massive hematemesis and melena. A hematological examination revealed that the red blood cell count was 1.31 x 10(6)/mm3, Hb 3.4 g/dl, and Hct 12%. No source of bleeding was found by an emergency endoscopic examination of the esophagus, stomach and duodenum, or by superior mesenteric angiography. At laparotomy a right common iliac arterio-intestinal fistula was found. The microscopic examination of this part of the ileum, including the fistula, revealed the presence of tubercular peritonitis. An extra-anatomic bypass graft using a prosthetic graft was performed between the left and right femoral arteries because reconstruction of the right common iliac artery was impossible.

Blood Vessel Prosthesis↗
PubMed1993

The effect of adult thymectomy on immune response to infection with Listeria monocytogenes in mice.

The role of adult thymus in in vivo immune response to infection with Listeria monocytogenes was examined using euthymic mice and adult-thymectomized (ATx) mice which had been thymectomized 2 weeks before. Numbers of T cells in peritoneal cavities and spleens were increased at 2 weeks after inoculation of L. monocytogenes, whereas such increases of T cells were several times higher in euthymic mice than in ATx mice. In flow-cytometric analysis of peritoneal exudate cells, a significant increase of CD3+CD4-CD8- cells bearing gamma/delta type T cell receptor was noted in euthymic mouse after infection compared to ATx mouse. Neither assay of antigen-specific T cell proliferation nor analysis of cell cycle exhibited any superiority of T cells obtained from euthymic mice to those obtained from ATx mice. These findings suggest that the enlargement of T cell population in euthymic mice is attributed largely to T cells which emigrate from the thymus after inoculation of L. monocytogenes. Moreover, in vivo protective immune response against secondarily challenged L. monocytogenes was achieved more efficiently in euthymic mice than in ATx mice, as shown by the clearance of the bacteria from organs and the survival rate of infected mice. Our results indicate the importance of adult thymus-dependent increase of T cells in eliminating the facultative intracellular bacteria such as L. monocytogenes.

Animals↗
PubMed1993

Roles of the splenic cytokines and arachidonic acid metabolites in severe hepatic injury after lipopolysaccharide injection in chronically alcohol-fed rats.

We examined the early changes after lipopolysaccharide (LPS) injection in chronically alcohol-fed rats with or without splenectomy. Administration of 2 mg/kg body weight LPS caused severe hepatic injury. The plasma aspartate aminotransferase (ASAT) activity was significantly higher in sham-operated rats 8 hr after LPS injection than in splenectomized rats. The plasma tumor necrosis factor (TNF) activity was also significantly higher 1 hr after LPS injection in sham-operated rats than in splenectomized rats. The plasma thromboxane (TX) B2/6-keto-prostaglandin (PG) F1 alpha ratio increased in sham-operated rats after LPS injection. Therefore, the balance of arachidonic acid metabolites was in a hypercoagulated state in sham-operated rats after the LPS injection. Neutrophil infiltration into liver tissue increased in sham-operated rats after the LPS injection. The cytokines and arachidonic acid metabolites released from the spleen after LPS injection in alcohol-fed rats may play important roles in severe hepatic injury.

Animals↗
PubMed1993

Clinical and pathological features, and the mechanism of development in severe alcoholic hepatitis, especially in comparison with acute type fulminant hepatitis.

Among the patients with alcoholic hepatitis, the patients with severe alcoholic hepatitis (SAH) were distinguished by clinical course, laboratory data and histological findings. The aim of this study was to clarify the clinicopathological features, pathological condition and pathogenesis of SAH. Twenty-four SAH patients were compared with 55 patients with acute type fulminant hepatitis (FH) and the other types of alcoholic liver disease. SAH showed a very poor prognosis with a survival rate of 25% and was complicated by multiple organ failure earlier than FH. IgA class lipid A antibody, endotoxin (Et) and tumor necrosis factor-alpha (TNF-alpha) levels in the blood well reflected the pathological condition and severity of SAH. The white blood cell count in the peripheral blood was thought to be the simplest indicator for the prediction of the prognosis of SAH. In conclusion, SAH involves hyper-endotoxemia due to dysfunction of the reticuloendothelial system in the liver, and cytokines including TNF-alpha and neutrophils play an important role in the severity of liver injury.

Adult↗
PubMed1993

Down-regulation of CD4 molecules by the expression of Nef: a quantitative analysis of CD4 antigens on the cell surfaces.

Nef is one of the non-structural genes encoded by human immunodeficiency viruses. The protein product is associated with the cellular and plasma membranes, and is synthesized soon after entry of the virus. However, little is known about its functions relevant to viral replication and cytopathogenesis. CD4 is considered to be a crucial molecule for the signal transduction and maturation of T cells, and also serves as the receptor for HIV-1. It has been suggested that the down-regulation of cell surface CD4 by Nef proteins is somehow controversial. In order to evaluate the effects of Nef on the CD4 molecule, we constructed a CD4+ monocytoid cell line in which the HIV-1 nef gene was placed under the transcriptional control of the human metallothionein IIA promoter. The analysis of this cellular clone showed that CD4 on the cell surface was down-regulated when Nef proteins were induced. The amount of CD4 antigens on the cell surface correlated inversely with the level of Nef protein expression. This down-regulation of CD4 antigens by Nef was found to occur at the post-translational level. These results showed that the nef gene could modulate the pathophysiology of AIDS by altering the surface CD4 expression.

Blotting, Southern↗
PubMed1993

Failure characteristics of osteoporotic vertebral bodies monitored by acoustic emission.

The third lumbar vertebrae of nine elderly subjects (average age, 81.4 +/- 6.7 years) graded osteoporotic and the second to fifth lumbar vertebrae of a 37-year-old man graded as normal were used to investigate microdamage accumulation during quasi-static compression loading with an acoustic emission detection system. Mechanical parameters (apparent elastic modulus, stress, and strain) and acoustic emission event count rates were measured simultaneously. The normalized mean value of any mechanical parameters of normal group was significantly high with respect to that of osteoporotic group. The normalized mean value of cumulative acoustic emission event counts to maximum stress of the normal vertebrae was substantially small with respect to that of the osteoporotic vertebrae (p < 0.0005, z-test). Postloading microradiographs displayed fracture lines adjacent to the end plates in six vertebrae of osteoporotic group. These results are consistent with the hypotheses that microdamages of osteoporotic vertebral bodies are generated and accumulate at lower strains than those of normal vertebrae at a specific site.

Adult↗
PubMed1993

Induction of interleukin 2-responsiveness in thymocytes of the transgenic mice carrying lck-transgene.

The role of lck gene in T cell proliferation and differentiation was investigated with transgenic mice carrying human lck cDNA whose expression was regulated by the promoter of mouse H-2Kb and the enhancer element of mouse IgH. RNase protection assay revealed that the lck transgene was expressed in the thymus and spleen, whereas immunoblot analysis demonstrated that amounts of p56lck in freshly isolated lymphoid organs were almost equal between transgenic mice and negative littermates. Cell-surface marker analyses of the thymocytes and peripheral lymphocytes revealed no remarkable difference between both groups. Notable finding is that the thymocytes from transgenic mice showed a significant proliferative response to the stimulation with IL-2, but not the thymocytes from negative littermates. Further analysis revealed that CD4+8- single positive thymocytes proliferated in response to IL-2. While surface expression levels of IL-2R alpha and IL-2R beta of these CD4+8- thymocytes from transgenic and control mice were almost equal before stimulation with IL-2, the expression of IL-2R beta was induced only in transgenic thymocytes after stimulation with IL-2. Immunoblot analysis demonstrated that the expression of p56lck of transgenic thymocytes was not down-regulated at 4 hr after stimulation with IL-2, whereas p56lck of control ones were not detectable any more at 4 hr after stimulation with IL-2. Moreover, in vitro kinase assay substantiated such unchanged expression of p56lck in the thymocytes from transgenic mice: the kinase activities of p56lck did not decrease in thymocytes from transgenic mice after stimulation with IL-2, while kinase activities of control ones were significantly down-regulated by stimulation of IL-2. These results suggested that a significant proliferative response found in the thymocytes from lck-transgenic mice after the stimulation with IL-2 was caused by a constitutive expression of p56lck in these thymocytes even after the stimulation. Our findings, therefore, support a possibility that p56lck may play a role in the IL-2R-mediated signaling system in CD4+8- thymocytes.

Animals↗
PubMed1993

A study of borderline personality disorder from the viewpoint of ego functions.

Twenty-eight Borderline Personality Disorder patients (BPD) (by DSM-III-R) were compared with 19 neurotic patients by consulting clinical charts and an interview. The clinical features and ego functions were examined. The results brought this conclusion: (1) Disorders of ego functions of BPD covered a wide range, and were especially noted in object relations. Brief psychotic experiences, depressive experiences, and impulsiveness were the characteristics of the clinical features of BPD. An examination chiefly from the viewpoint of ego functions brought two more conclusions: (2) BPD could be partly included in the schizophrenia spectrum and the affective disorder spectrum, (3) BPD can be divided into two: (a) A Core Group with impulsiveness, (b) A Serious Group with impulsiveness, and brief psychotic experiences and/or depressive experiences.

Adolescent↗
PubMed1993

Ether polar lipids of methanogenic bacteria: structures, comparative aspects, and biosyntheses.

Complete structures of nearly 40 ether polar lipids from seven species of methanogens have been elucidated during the past 10 years. Three kinds of variations of core lipids, macrocyclic archaeol and two hydroxyarchaeols, were identified, in addition to the usual archaeol and caldarchaeol (for the nomenclature of archaeal [archaebacterial] ether lipids, see the text). Polar head groups of methanogen phospholipids include ethanolamine, serine, inositol, N-acetylglucosamine, dimethyl- and trimethylaminopentanetetrol, and glucosaminylinositol. Glucose is the sole hexose moiety of glycolipids in most methanogens, and galactose and mannose have been found in a few species. Methanogen lipids are characterized by their diversity in phosphate-containing polar head groups and core lipids, which in turn can be used for chemotaxonomy of methanogens. This was shown by preliminary simplified analyses of lipid component residues. Core lipid analysis by high-pressure liquid chromatography provides a method of determining the methanogenic biomass in natural samples. There has been significant progress in the biosynthetic studies of methanogen lipids in recent years. In vivo incorporation experiments have led to delineation of the outline of the synthetic route of the diphytanylglycerol ether core. The mechanisms of biosynthesis of tetraether lipids and various polar lipids, and cell-free systems of either lipid synthesis, however, remain to be elucidated. The significance and the origin of archaeal ether lipids is discussed in terms of the lipid composition of bacteria living in a wide variety of environments, the oxygen requirement for biosynthesis of hydrocarbon chains, and the physicochemical properties and functions of lipids as membrane constituents.

Euryarchaeota↗
PubMed1993

Fatal acute hepatitis B virus infection while receiving immunosuppressants after renal transplantation.

A 47-year-old man with acute hepatitis B virus (HBV) infection who had been receiving immunosuppressants after renal transplantation developed progressive liver failure. During the clinical course (approximately 7 months), anti-HBc IgM antibody and HBV-DNA polymerase levels remained high, but the serum alanine aminotransferase (ALT) level was consistently less than 150 K.U. Histopathologic examination of the liver showed submassive hepatic necrosis without significant inflammation accompanied by marked fibrosis. Most hepatocytes showed strong nuclear expression of HBc antigen by immunohistochemical staining and electron microscopy revealed numerous intranuclear core-like particles. Hepatitis B virus infection in immunosuppressed individuals occasionally insidiously progresses, resulting in liver failure. The clinical course of such patients thus merits close scrutiny.

Acute Disease↗
PubMed1993

Proton magnetic resonance spectroscopy of astrocytic tumors: an in vitro study.

Water-soluble metabolites extracted from 20 astrocytic tumors (11 glioblastomas, 3 anaplastic astrocytomas, and 6 low-grade astrocytomas) and four normal brains were measured qualitatively and quantitatively using in vitro high-resolution proton magnetic resonance (1H-MR) spectroscopy. MR spectra from tumors exhibited characteristic patterns according to malignancy, presumably reflecting the metabolism of gliomas. Concentrations of choline-containing compounds, inositol, alanine, and glycine increased according to the malignancy, while that of total creatine decreased. In particular, glycine concentration was very high in glioblastoma, and an immunohistochemical study using anti-glycine antibody demonstrated that glycine was mainly distributed in glioma cells, not in proliferative endothelial cells. The ratios of choline-containing compounds and glycine to total creatine are useful parameters for grading gliomas, and the ratio of glycine to total creatine is useful for the differential diagnosis of glioblastoma from metastatic tumor. Such indications appearing in in vivo 1H-MR spectroscopy might provide clinically useful information on tumor metabolism and malignancy, and help assess the effects of radiation therapy and chemotherapy on gliomas.

Antibodies, Monoclonal↗
PubMed1993

Alterations in beta-adrenergic receptor density and cyclic-AMP level in the myocardium of rats chronically treated with alcohol.

An impaired function of the myocardial beta-adrenergic receptor system has been reported in patients with end-stage heart failure and this impairment has been postulated to be a factor in further deterioration of cardiac contractile function. As ventricular dysfunction is often associated with prolonged alcohol abuse, we investigated whether or not chronic administration of ethanol could induce alterations in the beta-adrenergic receptor adenylate-cyclase system in rats. Male Wistar rats of 8 weeks of age received 33% ethanol in drinking water for 3 months. As compared with control rats drinking water, the ethanol-treated rats showed weight loss and an increase in the heart/body weight ratio. Chronic ethanol increased myocardial contents of norepinephrine and epinephrine, possibly resulting from sympathoadrenal activation. The beta-adrenergic receptor density (Bmax) of the myocardial membrane was significantly decreased in the ethanol-treated rats (27.7 +/- 9.9 vs 39.0 +/- 6.0 fmol/mg protein, p < 0.01), while the affinity (Kd) did not differ between the two groups. The myocardial content of cyclic-AMP was also reduced in the ethanol rats (865 +/- 59 vs 1055 +/- 83 pmol/g w.w., p < 0.01). These observations indicate that chronic ethanol administration depresses the function of the beta-adrenergic receptor adenylate-cyclase system. The decreased beta-adrenergic receptor density was partly attributed to down-regulation due to increased sympathetic stimulation. This impaired function may contribute to the cardiac contractile dysfunction observed in chronic alcoholics.

Animals↗