Biomedical subjects

S Nagata

Publications and source records attributed to S Nagata.

At least 307 records · Page 17Linked to original sources

PubMed1996

Selective increase of V beta 2+ T cells in the small intestinal mucosa in Kawasaki disease.

The current study tested the hypothesis that the gastrointestinal tract could be one of the primary sites of entry for etiologic agents in Kawasaki disease (KD). In an attempt to elucidate the pathogenic role of certain superantigenic agents in KD, T cell receptor V beta expression by T cells in the small intestinal mucosa of KD patients was investigated using MAb on frozen tissue sections. Twelve Japanese patients with KD and eight controls were enrolled in the study. The numbers of cells stained by an immunofluorescence from each study group were counted and analyzed statistically by the t test. The occurrence of V beta 2+ T cells was found to be selectively increased in the small intestinal mucosa of patients in the acute phase of KD compared with controls (p < 0.01). In our previous study, five kinds of streptococci and two kinds of staphylococci, not detected in control patients, were isolated from the lumen of the jejunum of KD patients. These data suggest that the increased occurrence of V beta 2+ T cells in the jejunal mucosa of KD patients may be caused by exotoxins acting as superantigens produced by bacteria colonizing the small intestinal mucosa of these patients.

Child, Preschool↗

PubMed1996

Microbiologic studies on the small intestine in Kawasaki disease.

In an attempt to elucidate the etiology of Kawasaki disease (KD), the microflora of the small intestine was investigated in 15 Japanese KD patients. The range of bacterial species adhering to the lumen of the jejunum of KD patients was quite different from that of controls. A wider variety of bacteria was isolated from jejunal biopsies in the acute phase of KD as compared with those from control children. Gram-positive cocci were isolated from KD patients predominantly. Notably, five kinds of streptococci and two kinds of staphylococci were isolated only from KD patients. Further investigation of the microflora of the small intestine of KD patients may provide clues to clarify the pathogenesis of this disease.

Child, Preschool↗

PubMed1996

Food antigen activates intraepithelial and lamina propria lymphocytes in food-sensitive enteropathy in mice.

Morphologic and immunologic changes in the gut mucosa of food-hypersensitive mice, from a study model generated by feeding ovalbumin (OVA) to female BALB/c mice after intraperitoneal injection of cyclophosphamide (CY), were investigated in an effort to clarify the mechanisms of food-sensitive enteropathy. Villous atrophy, crypt hyperplasia, and increased numbers of intraepithelial lymphocytes (IEL) were confirmed in the antigen-challenged OVA-sensitive mice as seen in food-sensitive enteropathy in humans, whereas no significant morphologic changes were observed in the nontreated control group or groups treated with OVA or CY alone. IEL and lamina propria lymphocytes (LPL) were isolated from the intestinal mucosa before and after the antigen challenge, and surface markers were analyzed by FACScan. After the antigen challenge, the numbers of CD8+ cells increased among the IEL, and the occurrence of both CD4+ and CD8+ cells increased among the LPL. The numbers of Thy-1+ cells and TCR- alpha/beta + cells increased among both the IEL and LPL, and LFA-1 expression was enhanced in both of these lymphocyte populations. The proliferative response of IEL and LPL to OVA increased in a dose-dependent manner after the antigen challenge in the OVA-sensitive mouse model. These results indicate that IEL and LPL, possibly those that have migrated from peripheral blood, are activated by orally administered antigens and cause mucosal damage in the food-sensitive enteropathy.

Animals↗

PubMed1996

Absence of lysosomal cleavage in the cytotoxicity mechanism of an immunoconjugate composed of anti-alpha-fetoprotein monoclonal antibody and vindesine analog.

The effect of lysosomal enzyme inhibition on the cytotoxic activity of an immunoconjugate composed of anti-alpha-fetoprotein monoclonal antibody and vindesine analog (VDS) was studied in vitro using human tumor clonogenic assay (HTCA). Addition of the lysosome enzyme inhibitors, leupeptin and ammonium chloride, to the HTCA system had little influence on the cytotoxicity of this immunoconjugate. In separate experiments, no released VDS was detected by HPLC after incubation with the supernatant of rat liver homogenate without inhibitor. These results show that the immunoconjugate may bypass the lysosomal process and exert its activity as an intact or similar form.

Ammonium Chloride↗

PubMed1996

New algorithms for real-time, 24 hr continuous and noise-adjusted power spectral analysis of heart rate and blood pressure fluctuations in conscious rats.

The effective combination of C+2 and assembler could realize real-time power spectral analysis of various fluctuation indexes simultaneously. The blood pressure (BP) waveform indexes (WIs) analyzed simultaneously were heart rate (HR), systolic blood pressure (SBP), mean blood pressure (MBP) and diastolic blood pressure (DBP). Power amplitudes (very low frequency, VLFamp; low frequency, LFamp; and high frequency, HFamp) were evaluated by accurate BP waveform recognition, accurate automatic rejection of outliers, baseline adjustment in periodograms and digital filtering of each amplitude. In the in vivo experiments, the amplitudes were changed in a dose-dependent manner by methylatropine (HR-VLFamp, HR-LFamp and HR-HFamp), phentolamine (HR-LFamp, SBP-VLFamp, SBP-LFamp and SBP-HFamp) and propranolol (HR-LFamp and SBP-LFamp). The absolute correlation coefficients of the amplitude and the change in each parameter were more than 0.96. In conclusion, this real-time, noise-adjusted power spectral analysis system for investigating HR and BP fluctuations enabled us to accurately evaluate autonomic nerve activity in conscious rats. Moreover, unlike other systems, this system was able to detect the biphasic changes in SBP-HFamps caused by phentolamine.

Algorithms↗

PubMed1996

3-Hydroxyisobutyrate dehydrogenase from Pseudomonas putida E23: purification and characterization.

The NAD(+)-dependent 3-hydroxyisobutyrate dehydrogenase [EC 1.1.1.31] was purified to homogeneity from Pseudomonas putida E23. The enzyme was a tetramer (molecular mass, 120 kDa) consisted of identical subunits (molecular mass, 30 kDa). The enzyme was specific for NAD+ (Km, 0.44 mM). The maximal activity was obtained at about pH 10. The enzyme was specific for the L-isomer of 3-hydroxyisobutyrate. In addition to L-3-hydroxyisobutyrate, L-serine, 2-methyl-DL-serine, and 3-hydroxypropionate were substrates. The Km for L-3-hydroxyisobutyrate, L-serine, 2-methyl-DL-serine, and 3-hydroxypropionate were 0.12, 18, 44, and 83 mM, respectively. The enzyme was inhibited by p-chloromercuribenzoate, HgCl2, and AgNO3, but not by EDTA, alpha,alpha'-dipyridyl, and o-phenanthroline. The N-terminal 26 amino acid sequence was compared with the sequences deduced from the enzyme genes of rat liver and Pseudomonas aeruginosa.

Alcohol Oxidoreductases↗

PubMed1996

cDNA cloning and expression of the Xenopus homologue of the neural adhesion molecule, contactin (F3/F11).

Contactin (F3/F11) is an immunoglobulin superfamily cell surface glycoprotein predominantly expressed in the nervous system. To examine the structure and tissue distribution of Xenopus contactin, a cDNA clone was isolated based on the amino acid sequences conserved among chicken and mammalian contactin proteins. The conceptual translate of the cDNA consists of 1005 amino acid residues that have 70% identity to those of chicken and mammalian contactin. Northern blot hybridization using a labeled cDNA fragment revealed specific expression of 6.5 kb mRNA in the brain. Monoclonal and polyclonal antibodies prepared to the recombinant Xenopus contactin peptides detected a single 135 kD band on Western blots of the brain and spinal cord extracts. Differential extraction and phosphatidylinositol-specific phospholipase C (PI-PLC) digestion experiments showed that the immunoreactive 135 kD proteins bind, at least in part to the membrane by GPI anchor. On brain tissue sections, strong contactin immunoreactivities were detected on nerve fibers of a subset of cerebral and cerebellar neurons. These results suggest that the basic structure and tissue distribution of Xenopus contactin are similar to those in other vertebrates.

Amino Acid Sequence↗

PubMed1996

[A retrospective analysis of the outcomes of patients with aneurysmal subarachnoid hemorrhages: a focus on the prognostic factors].

The authors report a clinical analysis of the outcomes of aneurysmal subarachnoid hemorrhages in 112 patients. Cerebral angiography was conducted on 85 patients. Clipping or wrapping of the aneurysm was performed on 81 patients. The overall good outcome (GR and MD in the Glasgow Outcome Scale) ratio and mortality rate were 43% and 34%, respectively. The good outcome ratio and mortality rate in operative cases were 59% and 12%, respectively. With regard to the timing of the operation, 77 cases (95%) underwent early operation and 4 cases (5%) underwent delayed operation. The good outcome ratio of patients with grade I to III at surgery using the Hunt and Kosnik grading system was 74%. There was no difference in outcome between the patients with a ruptured aneurysm in the anterior circulation and those with one in the posterior circulation. The retrospective analysis of the overall outcomes showed the risk factors as being: age over 70 years, cerebral atherosclerosis, poor grade on Hunt and Kosnik grading system and symptomatic vasospasm. Preoperative bleeding of the aneurysm, severe brain swelling at surgery, and postoperative symptomatic vasospasm were factors which worsen the outcome of surgically treated patients. Patients with more than 2 factors showed worse outcomes than those with only one factor. The utilization of these prognostic factors should be important to improve the outcome of patients with aneurysmal subarachnoid hemorrhage.

Adult↗

PubMed1996

[A case of mucoepidermoid carcinoma underwent middle and lower sleeve bi-lobectomies with carinal reconstruction].

A case of mucoepidermoid carcinoma was successfully resected by bronchoplasty with carinal resection. A 36-year-old male complaining cough and sputum was admitted to our hospital. Bronchofiberscopical examination revealed a tumor mass occluding the truncus intermedius. The tumor seemed to invade the carina, but the orifice of the right upper lobe bronchus was intact. The results of the pathological examination of the biopsy specimen showed mucoepidermoid carcinoma. Sleeve middle and lower lobe bi-lobectomies with carinal reconstruction were successfully performed. The postoperative course was uneventful. The patient is alive 5 year and 5 months after operation without recurrent tumor.

Adult↗

PubMed1996

Elevated levels of soluble Fc epsilon RII/CD23 and antibodies to Epstein-Barr virus in patients with Sjögren's syndrome.

To clarify how Epstein-Barr virus (EBV) infection is responsible for Sjögren's syndrome (SjS) we measured both IgG and IgM antibodies to viral capsid antigen (VCA) of EBV in the sera of normal healthy subjects and patients with SjS. Anti-VCA IgG was detectable in all controls and patients however, anti-VCA IgG titers in the sera of SjS patients were significantly higher than those of the controls (p < 0.01). No anti-VCA IgM was detected in the sera of controls whereas anti-VCA IgM was detected in the sera from 10 out of the 13 patients with SjS. This suggests that SjS might be associated with EBV. The serum levels of sCD23 (IgE-binding factor) were also measured to assess the differential state in patients with SjS. The sCD23 level of normal individuals was 211.26 +/- 12.01 micrograms/L (value is mean +/- SE), and was 443.77 +/- 71.94 micrograms/L in the 13 patients with SjS. The mean sCD23 level in the 9 patients with SjS without any complication was 360.67 +/- 35.63 micrograms/L. In the patients with SjS, sCD23 levels were significantly higher than those in the normal individuals (p < 0.01).

Antibodies, Viral↗

PubMed1996

[Psychosomatic effect of a health program on obese employees].

A 12-week training period including exercise and diet was undertaken to determine the effects of a newly developed health program on the physical and phychological parameters in 24 obese employees of a certain company. The association between a number of somatic parameters and psychological variables, including the attitude toward better health, and the level of mental health (General Health Questionnaire) were analysed before, immediately or 1 year after the program. After the program, significant overall improvements were found in several physical parameters. Those who had higher initial levels of attitudes toward better health showed greater exercising/dieting achievements during the program. Furthermore, these considerable health-related attitudes seemed to be concerned with higher HDL levels preceding the program, and minor improvements in diastolic blood pressure due to the program. The GHQ scores tended to increase in proportion to decreased exercising/ dieting achievements during the program and undesirable lifestyle that ignored any form of exercising.

Adult↗

PubMed1996

A death factor--the other side of the coin.

Fas is a cell-surface protein belonging to the tumor necrosis factor (TNF) receptor family, whereas the Fas ligand (FasL) is a member of the TNF family. FasL binds to Fas, which results in target cell apoptosis. A family of cysteine proteases is sequentially activated to proceed the Fas-induced apoptosis, whereas Bcl-2 inhibits the process. FasL is expressed in activated T cells and natural killer (NK) cells, and works as an effector of these cytotoxic cells to remove the cells infected by virus, or cancer cells. The Fas system is also involved in peripheral clonal deletion, and/or the activation-induced suicide of T cells to down-regulate the immune reaction. Mouse mutations of lymphoproliferation (lpr) and generalized lymphoproliferative disease (gld), which cause lymphadenopathy and splenomegaly, and accelerate autoimmune disease, are loss-of-function mutations in the Fas and FasL genes, respectively. Moreover, the Fas-null mice established by gene targeting showed hyperplasia in the liver, suggesting that the Fas system is involved in turn-over of senescent hepatocytes.

Animals↗

PubMed1995

Apoptosis by a cytosolic extract from Fas-activated cells.

Fas is a type I membrane protein and its activation by binding of the Fas ligand or an agonistic anti-Fas antibody induces apoptosis in Fas-bearing cells. In this report we prepared lysates from cells treated with anti-Fas antibody. The lysates induced apoptotic morphological changes in nuclei from normal mouse liver, accompanied by DNA degradation. The apoptosis-inducing activity was quickly generated in cells by anti-Fas antibody and was found in the soluble cytosolic fraction. Induction of the activity in cells was inhibited by a tetrapeptide, acetyl-Tyr-Val-Ala-Asp-chloromethylketone, a specific inhibitor of interleukin-1 beta converting enzyme. Addition of COS cell lysates containing Bcl-2 to the assay significantly inhibited the apoptotic process, indicating that the in vitro process reflected apoptosis that occurs in intact cells.

Animals↗

PubMed1995

Distinct signal transduction through the tyrosine-containing domains of the granulocyte colony-stimulating factor receptor.

The receptor for granulocyte colony-stimulating factor (G-CSFR) is a hemopoietic growth factor receptor, which mediates proliferation and differentiation signals. The cytoplasmic region of G-CSFR carries four tyrosine residues in its C-terminal half. We constructed mutant receptors in which each tyrosine residue of G-CSFR was mutated to phenylalanine. Two mutant receptors (Tyr703 and Tyr728) neither transduced the growth-inhibitory signal nor induced the neutrophil-specific myeloperoxidase (MPO) gene. The Tyr703 mutant did not induce morphological changes in cells, whereas transformants expressing the Tyr728 mutant adhered to plates with a macrophage-like morphology upon G-CSF stimulation. Mutation of the most distal tyrosine residue (Tyr763) abolished the ability of G-CSFR to stimulate the tyrosine phosphorylation of a cellular protein with an M(r) of 54 kDa. These results indicated that the regions around the three tyrosine residues of G-CSFR play essential and distinct roles in signal transduction.

Animals↗

PubMed1995

Structure of the gene encoding the mouse pituitary adenylate cyclase-activating polypeptide receptor.

The PACAP-R gene, encoding the mouse pituitary adenylate cyclase-activating polypeptide receptor (PACAP-R), has been isolated and its structural organization has been determined. PACAP-R spans more than 50 kb and is divided into 18 exons. PACAP-R contains two alternative exons encoding the putative third intracellular loop, as found in the rat PACAP-R. The proximal promoter region is highly G+C rich and lacks an apparent TATA box, but contains a CCAAT box and two potential Sp1-binding sites.

Animals↗

PubMed1995

Different modes of sensory neuropeptides and nitric oxide involvement in relaxation of guinea-pig vessels.

This study investigated involvement of calcitonin-gene-related peptide (CGRP), substance P (SP) and nitric oxide (NO) in transmural nerve stimulation (TNS)-induced non-adrenergic, non-cholinergic (NANC) relaxation in isolated guinea pig anterior mesenteric artery (AMA) and posterior caval vein (PCV). Effects of cyclo-oxygenase-generated eicosanoids were blocked with indomethacin (10(-5) M) and so were adrenergic and cholinergic responses with phentolamine (3 x 10(-6) M), propranolol (10(-6) M) and atropine (10(-6) M). In both vessels precontracted by U-46619, TNS induced relaxation, which was almost completely abolished by capsaicin pretreatment (10(-6) M, 15 minutes). In AMA, a CGRP1 receptor antagonist (human CGRP8-37, 10(-5) M) significantly attenuated the relaxation, while did both human CGRP8-37 (10(-5) M) and neurokinin-1 receptor antagonists (spantide, 2 x 10(-5) M and FK888, 3 x 10(-6) M) in PCV. NG-nitro-L-arginine methyl ester (10(-4) M) did not significantly attenuate either the NANC-or CGRP-induced relaxation in AMA. However, it significantly did attenuate both the NANC-and SP-induced relaxation, and it also considerably attenuated CGRP-induced relaxation although insignificantly, in PCV. Thus, CGRP could be significantly responsible for the NO-independent NANC relaxation in AMA, whereas both CGRP and SP could additionally relax PCV in a NO-dependent manner.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1995

Age-related increase in peptidylarginine deiminase in the male rat pituitary.

We have measured the activity of peptidylarginine deiminase (EC 3.5.3.15) in male Wistar rat pituitaries at various ages. Pituitaries obtained from 3- and 9-month-old rats showed negligible activities. The mean enzyme activity increased appreciably by 18 months and markedly by 24 months accompanied with actual increases in the enzyme content. The peptidylarginine deiminase mRNA content showed a similar but more gradual increase appreciable from 9 months. Many enzyme-positive cells were present in the pars distalis of 24-month-old male pituitaries. Most of the enzyme-positive cells coincided with lactotrophs. The pituitary prolactin content showed a gradually increasing profile resembling that of the enzyme mRNA, but the serum prolactin concentration did not increase significantly. Neither the serum 17 beta-estradiol content nor the pituitary estrogen receptor content showed significant variation that could account for the marked increase in the pituitary enzyme content between 18 and 24 months of age. These data suggest possible presence of other factors regulating the enzyme content in old male pituitaries.

Aging↗

PubMed1995

Involvement of an ICE-like protease in Fas-mediated apoptosis.

Fas is a type-I membrane protein that transduces an apoptotic signal. Binding of Fas ligand or agonistic anti-Fas antibody to Fas kills the cells by apoptosis. Studies in the nematode Caenorhabditis elegans have suggested that proteases such as interleukin-1 beta-converting enzyme (ICE) or the product of the C. elegans cell-death gene ced-3 are involved in apoptotic signal transduction. The activity of ICE can be inhibited by the product of crmA, a cytokine-response modifier gene encoded by cowpox virus. We report here that expression of crmA inhibits cytotoxicity induced by anti-Fas antibody or tumour necrosis factor (TNF). We have found a specific ICE inhibitor tetrapeptide (acetyl-Tyr-Val-Ala-Asp-chloromethylketone) that also prevents apoptosis induced by anti-Fas antibody. These results suggest an involvement of an ICE-like protease in Fas-mediated apoptosis and TNF-induced cytotoxicity.

Amino Acid Sequence↗