Search PubMed⌕ Search

Biomedical subjects

Y Kobayashi

Publications and source records attributed to Y Kobayashi.

At least 415 records · Page 23Linked to original sources
PubMed2000

Enhanced hepatic lipid peroxidation in patients with primary biliary cirrhosis.

OBJECTIVE: The mechanisms responsible for hepatic injury have not been fully clarified in primary biliary cirrhosis (PBC). It has recently been suggested that hepatic lipid peroxidation may be involved in the pathogenesis of PBC. The aims of the current study were to determine whether patients with PBC have evidence of enhanced hepatic lipid peroxidation and to evaluate its relationship to clinicopathological features. METHODS: Immunohistochemical detection of 4-hydroxynonenal (HNE) protein adducts was performed in the liver biopsies of 20 patients with PBC. Histological stages of PBC were evaluated. Orcein or Victoria blue staining was performed for detection of copper-associated proteins. The size of bile ducts was defined as the smallest diameter between the subepithelial basement membranes. RESULTS: All 20 patients had immunodetectable HNE protein adducts in the cytoplasm of damaged, but also intact, biliary cells. The mean diameter of bile ducts with HNE protein adducts was smaller than those without the adducts (61.0 +/- 1.9 vs 122.5 +/- 24.4 microm, respectively, p < 0.01). Out of 20 patients, 6 (30%) also had immunodetectable HNE protein adducts in hepatocytes preferentially located around the portal tracts. Most of the patients with hepatocytic HNE protein adducts had copper-associated protein granules in hepatocytes around the portal tracts and were classified as histological stage 3, whereas all of the patients without the adducts lacked copper-associated protein granules and were classified as histological stage 1 or 2. The patients with hepatocytic HNE protein adducts had higher levels of serum total bilirubin than did those without the adducts (2.9 +/- 0.9 vs 0.7 +/- 0.1 mg/dl, respectively, p < 0.01). CONCLUSIONS: Hepatic lipid peroxidation can occur in PBC and may be an early event in bile duct destruction. At advanced stages of PBC, hepatocellular lipid peroxidation may play a role in hepatocyte injury during cholestasis.

Aldehydes↗
PubMed2000

Inflammation and atherosclerosis. Atherosclerotic lesions in Takayasu arteritis.

Takayasu arteritis is a chronic vasculitis, mainly involving the aorta and its main branches as well as the coronary and pulmonary arteries, causing stenosis and/or obstruction due to thrombus formation or dilatation due to aneurysmal formation and/or rupture of the involved arteries. These characteristic anomalies resulted from ischemia of retinal arteries due to the obstruction of cervical vessels. In Western countries this disease is also known as "pulseless disease," because the pulse is frequently absent due to the obstruction of subclavian or branchial arteries. The pathogenesis of this morbid condition is still unknown. Epidemiologically, it is found mostly in female patients and is more prevalent in Asian and Latin American countries. Affected areas consist of a mixture of both active, productive inflammatory lesions, and old fibrous lesions. Autoimmune processes stimulated by viral infection and other unknown causative factors may play an important role under these pathophysiological conditions because HLA analysis revealed a statistically significant high frequency of haplotype A24-B52-DR2 in these patients in Japan. Documentation of atherosclerotic complications in young female patients with Takayasu arteritis who are generally free from traditional atherosclerosis risk factors may be clinical evidence that inflammation is indeed an important risk factor in atherogenesis.

Arteries↗
PubMed2000

Cloning of murine glycosyl phosphatidylinositol anchor attachment protein, GPAA1.

Glycosyl phosphatidylinositols (GPIs) are used to anchor many proteins to the cell surface membrane and are utilized in all eukaryotic cells. GPI anchoring units are attached to proteins via a transamidase reaction mediated by a GPI transamidase complex. We isolated one of the components of this complex, mGPAA1 (murine GPI anchor attachment), by the signal sequence trap method. mGPAA1 cDNA is about 2 kb in length and encodes a putative 621 amino acid protein. The mGPAA1 gene has 12 small exons and 11 small introns. mGPAA1 mRNA is ubiquitously expressed in mammalian cells, and in situ hybridization analysis revealed that it is abundant in the choroid plexus, skeletal muscle, osteoblasts of rib, and occipital bone in mouse embryos. Its expression levels and transamidation efficiency decreased with differentiation of embryonic stem cells. The 3T3 cell lines expressing antisense mGPAA1 failed to express GPI-anchored proteins on the cell surface membrane.

3T3 Cells↗
PubMed2000

Increase in peripheral blood flow due to extraocular direct irradiation of visible light in rats.

We have conducted experiments to clarify the existence of extraretinal photosensitivity in mammals through the measurements of skin blood flow variation due to light irradiation. We found that blood flow shows a synchronized transient increase with a irradiation-nonirradiation sequence. The action spectrum of the phenomenon was found to show peaks at approximately 410-420 nm, 540-550 nm, and 570- 580 nm. These peaks coincide with the specific optical absorption peaks of B and Q (alpha,beta) bands in sixfold coordinated ferruos-heme complexes such as nitric oxide (NO)-Hb. The blood flow increase in the irradiated duration disappears when the rats are intraperitoneally injected with 1H-[1,2,3]oxydiazolo[4,3-a] quinoxalin-1-one (ODQ), which is an inhibitor of guanylate cyclase, and N(G)-monomethyl-L-arginine acetate and N(G)-nitro-L-arginine methyl ester, which are inhibitors of NO synthase. On the basis of the present results, we propose a photochemical model of the photosensitivity mechanism where optical absorption of the sixfold coordinated ferrous heme-NO complex plays a main role.

Animals↗
PubMed2000

Immunocytochemical and immunoelectron-microscopic study of somatotrophs in ICR and nonobese diabetic mice.

Somatotrophs (GH cells) were classified immunoelectron microscopically into three types mainly on the basis of the size of secretory granules in the mouse pituitary of ICR strain. Type I cells contained large secretory granules. Type II cells contained both large secretory granules and small secretory granules. Type III cells contained small secretory granules. All three types of GH cells were found from the neonatal ages to adult. The relative proportion of three types did not change with age, and no sex differences in the relative proportion of the cell types were detected. Type I cells predominate in all age groups observed. In 60-day-old male mice percentages of each type were as follows: type I 93.7 +/- 0.1%, type II 5.4 +/- 0.8%, and type III 0.9.0 +/- 0.4% (n = 5), and in 60-day-old female mice type I 95.2 +/- 0.1%, type II 2.7 +/- 0.5%, and type III 2.1 +/- 0.9% (n = 5). The maximum diameters of the large secretory granules increased from 7 to 60 days of age. The small secretory granules similarly increased in size in female mice, but those in male mice did not change. In the diabetic female mice of the nonobese diabetic (NOD) strains, GH cells in diabetic mice became smaller, and the number and size of secretory granules decreased, indicating diminished GH secretion. However, the relative proportion of each subtype of GH cells did not differ irrespective of the occurrence of diabetes.

Animals↗
PubMed2000

Myelodysplastic syndrome with clonal eosinophilia accompanied by eosinophilic pulmonary interstitial infiltration.

We report a case of de novo myelodysplastic syndrome with clonal eosinophilia (MDS-Eo) and eosinophilic pulmonary interstitial infiltration, confirmed by autopsy. Cytogenetic study using Giemsa banding identified 47,XY,+1,der(1;7)(q10;p10),+8 in the marrow cells. Simple Giemsa staining revealed the same chromosomal aberration in metaphase spreads with eosinophilic granules, indicating the clonal proliferation of eosinophils. To our knowledge, our case is the 6th reported case of MDS-Eo with cytogenetically confirmed clonal eosinophilia, and the first autopsy of MDS-Eo. A review of the literature combined with our findings suggests that this type of chromosomal aberration might be involved in the as yet unknown pathogenesis of MDS-Eo.

Aged↗
PubMed2000

Scleroderma associated with anemia and thrombocytopenia that responded well to cyclosporin.

A 55-year-old woman came to our hospital because of cutaneous sclerosis of the limbs in September 1996, and was diagnosed with scleroderma based on a skin biopsy. In August 1997, the cutaneous sclerosis became progressive (hemoglobin level, 4.3 g/dl; platelet count, 7 x 10(9)/l). The laboratory results were positive for the direct Coombs test, bone marrow aspiration showed a dry tap, and the bone marrow biopsy showed marked fatty marrow. Indium-111 bone marrow scintigraphy showed a markedly decreasing uptake. These findings indicated bone marrow hypoplasia associated with hemolytic anemia. After prednisolone therapy (60 mg) was initiated, the direct Coombs test became negative but the blood cell count did not increase. Then, 300 mg of cyclosporin was initiated and anemia and thrombocytopenia improved. The cyclosporin dosage was gradually decreased and the patient's hematological condition was good, although the cutaneous sclerosis changed only a little. This is a rare and interesting case of a patient with scleroderma associated with bone marrow insufficiency and hemolysis who responded well to cyclosporin.

Anemia, Hemolytic↗
PubMed2000

An optimal condition of bronchial cell proliferation stimulated by insulin-like growth factor-I.

BACKGROUND: It is known that growth hormones such as insulin-like growth factor-I (IGF-I) and several kinds of cytokines are involved in the regeneration process of injured epithelial cells in chronic respiratory inflammatory diseases such as bronchial asthma. Repetitive degeneration/regeneration processes of the airway epithelial layer is supposed to be responsible for the remodeling and irreversible organic changes of the airway in bronchial asthma. The purpose of this study is to establish a simple and reliable in vitro method for studying airway epithelial cell growth and proliferation using IGF-I. METHOD: By altering the number of cultured epithelial cells (strain NCI-H(292)), culture duration before stimulation with IGF-I, concentration of IGF-I, and duration of IGF-I stimulation, the optimum conditions for epithelial cell growth was determined. The epithelial cell growth was evaluated using [methyl-(3)H]thymidine uptake. RESULT: Among various culture conditions, the epithelial cells cultured at 1 x 10(3) cells/well for 24 h followed by 24 h of stimulation by 10(-8) M of IGF-I showed the highest growth. CONCLUSION: The method for the evaluation of epithelial cell growth established in this study requires a small number of cells and has no complicated procedure. This simple model enables us to investigate the effect of various substances on bronchial epithelial cell growth in the presence of IGF-I.

Bronchi↗
PubMed2000

Telomerase activity in giant condyloma acuminatum.

A 46-year-old male came to our hospital 1 month after noticing a 2-cm penile tumor. Since malignant findings such as atypical cells and mitosis were not observed in the frozen sections obtained at operation, the pathological diagnosis of this tumor was giant condyloma acuminatum. This tumor was analyzed by a telomeric repeat amplification protocol method, and telomerase activity was revealed. For comparison, a case of squamous cell carcinoma and a case of condyloma acuminatum were examined. Telomerase activity was observed in our case and in the case of squamous cell carcinoma. To our knowledge, this is the first case of telomerase activity in giant condyloma acuminatum ever reported. In addition to the histological examination, measurement of telomerase activity may provide valuable objective diagnostic information on evaluating the degree of malignancy of giant condyloma acuminatum and in obtaining a differential diagnosis between the benign and malignant.

Biomarkers, Tumor↗
PubMed2000

Primary malignant lymphoma of the central nervous system presenting with ascites and pleural effusion.

A 70-year-old woman was admitted to our hospital owing to ascites and pleural effusion. Though malignant cells (B-cell type lymphoma) were detected in both the ascites and pleural effusion, neither lymph node swelling nor a tumor was detected upon chest, abdominal and pelvic computed tomography (CT). After weekly THP-COP therapy for 8 weeks, the ascites and pleural effusion completely disappeared. Two years after the first admission, she was re-admitted because of a disturbance of consciousness, and a brain tumor was detected on CT scan. The immunohistological and genetic data for the brain tumor were identical to those of the malignant cells in the pleural effusion and ascites detected 2 years previously. Whereas the symptoms at onset of a primary lymphoma of the central nervous system (CNS) are usually neurological ones, in this rare case of primary CNS lymphoma, the symptoms at onset were the ascites and pleural effusion without neurological symptoms.

Aged↗
PubMed2000

Release of endothelins and platelet-activating factor by a rat pleural mesothelial cell line.

Thrombin is a multifunctional serine protease. It is generated in inflammatory processes and induces the proliferation and chemotaxis of a variety of cells including mesothelial cells (MTCs). MTCs are epithelial cells derived from the mesoderm, as are the vascular endothelial cells. Since thrombin acts on endothelial cells to produce platelet-activating factor (PAF) and endothelin (ET)-1, it was hypothesized that MTCs also produce PAF and ET via the action of thrombin. Rat pleural MTC (RMTC, 4/4 R.M.-4) monolayers were cultural in tissue culture dishes for various periods. The supernatants were fractionated by means of high-performance liquid chromatography to determine the ET isoforms and PAF species present. Immunoreactive ET was measured using an enzyme-linked immunosorbent assay, and PAF was measured by means of a bioassay using a platelet aggregometer. ET-1, ET-2 and ET-3 were detected in RMTC-conditioned medium, and the predominant isoforms were ET-1 and ET-2. RMTCs mainly released C16:0 PAF into the supernatant. Immunoreactive ET and PAF were released via the action of thrombin. Synthetic PAF significantly induced secretion of ET, but the PAF receptor antagonists, WEB2086 and E6123, failed to modulate thrombin-induced ET release. These results indicate that thrombin acts on pleural rat mesothelial cells to release ET and PAF, which may play a role in the development of pleurisy.

Animals↗
PubMed2000

A common downstream signaling activity of osteoclast survival factors that prevent nitric oxide-promoted osteoclast apoptosis.

Treatment with NO-releaser NOC18 significantly promoted apoptosis in murine osteoclast-like cells, with a transient increase in caspase-3-like protease activity. In contrast, the apoptosis was protected against by caspase inhibitors, most efficiently with the broadly acting caspase specific inhibitor z-Asp-CH2-DCB, indicating involvement of multiple caspases in progression of the apoptosis. Among osteoclast survival factors examined, calcitonin completely protected against morphologically defined-apoptosis and the increase of caspase-3-like protease activity. The effect of calcitonin was mimicked by treatment of cells with (Bu)2cAMP and forskolin, and abolished by protein kinase-A inhibitor H-89. Independently from the PKA activation, colony stimulating factor-1, interleukin-1beta and the receptor activator of NF-kappaB ligand also protected against the apoptosis but were less effective than calcitonin. All survival factors investigated inhibited conversion of procaspases-3 and -9 to their mature forms in the cells. Thus, downstream antiapoptotic signaling activity from each factor overlapped in inhibition of caspases. However, how this was attained seemed to be different from each other. Typically, only colony stimulating factor-1 up-regulated expression of endogenous caspase inhibitor protein, X-linked inhibitor of apoptosis (XIAP), in the osteoclast-like cells.

Animals↗
PubMed2000

Effects of fujibitol, a remedy for nasal symptoms, on experimental allergic rhinitis in rats.

The effects of Fujibitol, a preparation of crude drugs in wide clinical use for treatment of chronic rhinitis and empyema, on experimental allergic rhinitis in rats were studied. Fujibitol inhibited nasal allergic symptoms, i.e. sneezing and nasal rubbing, induced by antigen in sensitized animals. An increase in dye leakage into the nasal cavity induced by antigen was also inhibited by Fujibitol. On the other hand, no inhibitory effects were observed on either the nasal allergic symptoms or increase in dye leakage into the nasal cavity induced by histamine. However, Fujibitol was effective in inhibiting histamine release from the nasal cavity induced by antigen. Oxatomide used as positive control drug showed potent inhibitory effects on nasal symptoms and dye leakage into the nasal cavity induced by histamine and antigen. These results suggested that Fujibitol showed a remarkable protective effect against experimental rhinitis induced by antigen via inhibition of histamine release from the nasal cavity.

Animals↗
PubMed2000

Antiallergic effect of apple polyphenols on the allergic model mouse.

We studied here the antiallergic effect of apple condensed tannins (ACT) administered orally to a type I allergy model mouse transplanted with an IgEL a2 hybridoma secreting anti-2,4,6-trinitrophenyl (TNP) immunoglobulin E (IgE). The oral administration of ACT significantly inhibited the ear swelling responses at 1 h after antigen-stimulation with picryl chloride. The response was dose dependent within 0.1 to 10 mg/mouse. The inhibition of the ear swelling response reached the maximal level (90% inhibition) when ACT was administered 2 h before the antigen challenge. These findings suggest that ACT has an antiallergic effect on type I allergic symptoms.

Animals↗
PubMed2000

Occurrence of a novel cannabimimetic molecule 2-sciadonoylglycerol (2-eicosa-5',11',14'-trienoylglycerol) in the umbrella pine Sciadopitys verticillata seeds.

The umbrella pine Sciadopitys verticillata seeds were found to contain a substantial amount (16.7 nmol/g) of sciadonic acid (all-cis-5,11,14-eicosatrienoic acid)-containing 2-monoacylglycerol, i.e., 2-sciadonoylglycerol (2-eicosa-5',11',14'-trienoylglycerol). Because the structure of 2-sciadonoylglycerol closely resembles that of 2-arachidonoylglycerol, the endogenous natural ligand for the cannabinoid receptor, we examined whether or not 2-sciadonoylglycerol exhibits cannabimimetic activity using NG108-15 neuroblastomaxglioma hybrid cells which express the cannabinoid CB1 receptor. We found that 2-sciadonoylglycerol induces rapid transient elevation of intracellular free Ca2+ concentration in NG108-15 cells through a cannabinoid CBI receptor-dependent mechanism similar to the case of 2-arachidonoylglycerol, yet the activity of 2-sciadonoylglycerol was apparently lower than that of 2-arachidonoylglycerol. The activity of 2-sciadonoylglycerol was detectable from 3-10 nM, reaching a maximum at around 10 microM. To our knowledge, this is the first report showing the occurrence of a cannabimimetic monoacylglycerol in higher plants.

Arachidonic Acid↗
PubMed2000

[Studies on organofluorine compounds: an overview of our 30 years].

This review article covers our research activities over 30 years in organofluorine chemistry. The followings are briefly summarized researches in this memorandum: (1) Trifluoromethylation of organic halides with trifluoromethyl copper complex and its application to trifluoromethylated nucleosides, (2) a systematic study on reactivity of aromatic trifluoromethyl compounds, (3) valence bond isomers of aromatic compounds stabilized by the trifluoromethyl groups, and (4) synthesis of fluorinated bioactive compounds which involve vitamin D3, arachidonic acid and its metabolites, and retinal.

Chemistry, Organic↗