[Application of complement inactivator gene for control of heterograft rejection].
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Animals↗
Biomedical subjects
M Okamoto
Publications and source records attributed to M Okamoto.
Oral administration of lipopolysaccharides activates B-1 cells in the peritoneal cavity and lamina propria of the gut and induces autoimmune symptoms in an autoantibody transgenic mouse.
About a half of the antierythrocyte autoantibody transgenic (autoAb Tg) mice, in which almost all B cells are detected in the spleen, lymph nodes, and Peyer's patches, but not in the peritoneal cavity, suffer from autoimmune hemolytic anemia. The occurrence of this disease is strongly linked to production of autoAb by activated peritoneal B-1 cells in the Tg mice. In this study, we have shown that oral administration of lipopolysaccharides (LPS) activated B-1 cells in the lamina propria of the gut as well as the peritoneal cavity in the healthy Tg mice and induced the autoimmune symptoms in all the Tg mice. The activation of peritoneal and lamina propria B-1 cells by enteric LPS is found not only in the anti-RBC autoAb Tg mice and normal mice but also in the aly mice which congenitally lack lymph nodes and Peyer's patches. These results suggest that B-1 cells in the two locations may form a common pool independent of Peyer's patches and lymph nodes, and can be activated by enteric thymus-independent antigens or polyclonal activators such as LPS. The induction of autoimmune hemolytic anemia in the Tg mice by enteric LPS through the activation of B-1 cells in the lamina propria of gut and in the peritoneal cavity suggests that B-1 cells and bacterial infection may play a pathogenic role in the onset of autoimmune diseases.
Administration, Oral↗
Enhanced expression of group II phospholipase A2 in human hepatocellular carcinoma.
Enzyme activity, protein contents, and mRNA contents of group II phospholipase A2 (PLA2) in hepatocellular carcinoma (HCC) surgically obtained from 8 patients were compared with those in either its neighboring liver tissues or control liver tissues. The PLA2 specific activity towards the mixed micelles of 1-palmitoyl-2-oleoyl-phosphatidylglycerol and cholate was significantly greater in the tumor tissues (6.62 +/- 1.46 nmol/min/mg) than those in the surrounding liver tissues (1.33 +/- 0.22 nmol/min/mg) and controls (0.43 +/- 0.04 nmol/min/mg). The results of immunoblot analysis using a specific anti-human group II PLA2 antibody and of Northern blot analysis using a human group II PLA2 cDNA as a probe demonstrated that group II PLA2 was responsible for the increased enzyme activity. The contents of immunoreactive group II PLA2 in the tumor tissues (8.81 +/- 1.24 ng/mg) were significantly higher than those in the surrounding liver tissues (1.74 +/- 0.27 ng/mg); those in the control tissues were below the analytical range of the method used. The group II PLA2 mRNA was also significantly increased in the tumor tissues, compared with that in the surrounding liver tissues, whereas it was not detectable in the controls. This indicates that group II PLA2 in HCC is induced at the pretranslational level.
Carcinoma, Hepatocellular↗
Chondroitin sulfate proteoglycans protect cultured rat's cortical and hippocampal neurons from delayed cell death induced by excitatory amino acids.
Protective effects of chondroitin sulfate proteoglycans (CSPGs) from rat's brain against delayed cell death induced by excitatory amino acids were examined in cultured neurons of the rat. CSPGs reduced delayed neuronal death induced by 10 min exposure to glutamate at a concentration between 100 microM and 1 mM when lactate dehydrogenase activity of culture medium was assayed 24 h after the exposure. CSPGs also protected neuronal death induced by 200 microM N-methyl-D-aspartate (NMDA), kainate or 100 microM alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). CSPGs reduced death of cortical and hippocampal neurons even when they were administered at 2 h, but not 6 and 12 h, after the exposure to glutamate. These results indicate that CSPGs may have a neuroprotective action against acute noxious conditions in the brain.
Amino Acids↗
A protective action of chondroitin sulfate proteoglycans against neuronal cell death induced by glutamate.
The role of chondroitin sulfate proteoglycans (CSPGs) on excitotoxic cell death and long-term survival of neurons were investigated in primary cultured neurons of the rat cortex. Soluble CSPGs were prepared from 10-day-old and adult rat brains by the ion-exchange chromatography on DEAE-Sephacel. CSPGs were added to the culture medium on culture day 4, and glutamate neurotoxicity was examined on culture day 7 by both microscopic cell count and measurement of lactate dehydrogenase activity in culture media. The effect on long-term survival was evaluated by counting viable neurons until culture day 28. CSPGs and core proteins, but not glycosaminoglycan chains (GAGs), protected cultured neurons from excitotoxic cell death induced by 24 h exposure to 1 mM glutamate, but CSPGs did not promote the long-term survival of neurons. The neuroprotective effect of CSPGs and core proteins was dose-dependent with ED50 about 10 microM hexuronate and 2 micrograms/ml protein respectively. This effect was not considered to be due to adsorption of glutamate by CSPGs because [3H]glutamate was not adsorbed by CSPGs added to the culture medium. Based on these findings, we suggested that CSPGs may exert their neuroprotective action through molecular interactions with the binding sites on neuronal membrane, neurotrophic factors, or other extracellular matrix molecules and may be involved in the pathogenesis of neuronal cell death in acute pathological conditions and chronic degenerative diseases of the brain.
Animals↗
Eclosion hormone-mediated signal transduction in the silkworm abdominal ganglia: involvement of a cascade from inositol(1,4,5)trisphosphate to cyclic GMP.
The neuropeptide eclosion hormone triggers ecdysis behavior in lepidopteran insects. We have previously shown that the eclosion hormone stimulates the formation of two intracellular second messengers, cGMP and inositol(1,4,5)trisphosphate in the abdominal ganglia of Bombyx mori. In order to elucidate the intracellular signaling pathway involving these second messengers, we studied the eclosion hormone-mediated signal transduction using saponin-treated abdominal ganglia. We obtained the following results; i) eclosion hormone activated nitric oxide synthase, ii) the eclosion hormone-induced cGMP increase was inhibited by various enzyme inhibitors such as NG-nitro-arginine; a nitric oxide synthase inhibitor, EGTA; a calcium chelating reagent, W-5; a calmodulin inhibitor and compound 48/80; a phospholipase C inhibitor and iii) the inositol(1,4,5)-trisphosphate stimulated the formation of cGMP, in the Bombyx abdominal ganglia. Based on these findings we tentatively propose a hypothetical pathway: The signal initially triggered by eclosion hormone and eclosion hormone receptor complex induces activation of phospholipase C which produces inositol(1,4,5)trisphosphate. Inositol(1,4,5)trisphosphate increases intracellular Ca2+, followed by subsequent activation of nitric oxide synthase through the formation of Ca(2+)-calmodulin complex. The reaction product, nitric oxide acts on soluble guanylate cyclase to stimulate cGMP formation which induces the ecdysis behavior in Bombyx pharate adults.
Amino Acid Oxidoreductases↗
Lysis of autologous tumor cells by large granular lymphocytes in patients with acute leukemia in complete remission: correlation between lytic activity and clinical outcome.
In order to evaluate the effect of specific immune response on prognosis in acute leukemia, we investigated the correlation between the lysis of autologous tumor cells (ATC) by lymphocytes and prognosis. Peripheral mononuclear cells (PMC) from most patients with acute leukemia in complete remission (CR) do not exhibit cytotoxic activity against fresh-frozen ATC, although they have adequate cytotoxic activity against K562 cells. When the large granular lymphocyte (LGL) fraction was used in this study, we observed lysis of ATC in 17 (43.6%) of 39 patients with acute leukemia (12 (42.9%) of the 28 patients with acute myelogenous leukemia (AML) and 5 (45.5%) of the 11 patients with acute lymphocytic leukemia (ALL)). With regard to prognosis, the lytic activity of the LGL fraction did not reflect the duration of CR. The median CR duration in AML patients was 13 months for the lysis-positive group and 11 months for the lysis-negative group. No significant correlation was also found between lytic activity of the LGL fraction and overall survival in each patient. However, the lysis-positive group tended to have a longer survival, the median overall survival being 48 months for the lysis-positive group vs 12 months for the lysis-negative group. The prolonging of overall survival in the lysis-positive group was attributed to a high rate of induction of second remissions in this group. Long-term patient survival in the two groups did not differ.
Adolescent↗
Quantitation of rCBF by 99mTc-hexamethylpropyleneamine oxime single photon emission computed tomography combined with 133Xe CBF.
A simple, noninvasive method of measuring CBF that uses single photon emission computed tomography (SPECT) of 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) and whole-brain CBF obtained by 133Xe clearance technique was developed. SPECT data were normalized to the count density of HMPAO uptake in the whole brain and then converted to the absolute units of CBF by multiplying average CBF in the whole brain obtained by 133Xe. Mean CBF values in healthy volunteers (n = 12) were 49 +/- 7 and 30 +/- 5 ml 100 g-1 min-1 for gray matter and white matter, respectively, with a global flow value of 45 +/- 5 ml 100 g-1 min-1. The mean flow value was 19 +/- 7 ml 100 g-1 min-1 for the core of the infarct and 31 +/- 5 ml 100 g-1 min-1 for the contralateral region (n = 13). CBF values were reproducible for all brain regions. The method was convenient to use and suitable for the routine measurement of regional CBF in normal and pathologic states.
Cerebrovascular Circulation↗
Treatment of ureteral stones by extracorporeal shock wave lithotripsy: with ureteral catheter or in situ?
Many authors recommend that stone manipulation or catheter placement be attempted before SWL of ureteral stones. We tried to insert ureteral catheters before SWL on the unmodified Dornier HM3 machine in all patients treated for solitary ureteral stones between April 1986 and December 1991, succeeding in 77.5% (n = 395) of those for whom adequate follow-up is available for analysis. The stone-free rates with SWL alone in the series of 510 patients were 93% in patients with catheters and 75% in patients without catheters. An additional 6% of the patients in both groups became stone free with the aid of ureteroscopy. Eventually, only 0.5% of the patients with a catheter and 1.7% of the patients without a catheter had residual fragments. Among patients with a ureteral catheter after any procedure, 58.7% had no need for pain relief medication and no fever; the figure in the patients treated without a catheter was 74.4%. Although the success rate of SWL for ureteral stones is higher with a ureteral catheter in place, the incidence of complications also is higher. We recommend trying in situ SWL initially for patients with a ureteral stone.
Body Temperature↗
CA125-producing adenocarcinoma of the seminal vesicle.
A case of primary seminal vesicle carcinoma is reported. The tumor was a CA125-producing adenocarcinoma consisting of fine papillary-tubular, intricate branching or anastomosing glandular structures and was composed of small cuboidal, but occasionally hobnailed, cells with mostly clear, but occasionally granular, cytoplasm. Some tumor cells showed evidence of secretion of seromucinous materials into the interpapillary and cystic space. Immunohistochemically, almost half of the tumor cells expressed a positive reaction with anti-CA125, a common serological marker for ovarian epithelial carcinomas; however, no tumor cells expressed any other serological tumor markers such as carcinoembryonic antigen, alpha-fetoprotein, human chorionic gonadotropin, prostatic specific acid phosphatase, or prostatic specific antigen. The patient showed a high level of serological CA125, which fluctuated parallel with the growth, removal and recurrence of the tumor. The morphological and immunohistochemical findings suggested a close relationship between the present tumor and clear cell carcinoma of the ovary, which is thought to be of a Müllerian-Wolfian duct origin.
Adenocarcinoma↗
Protection by dexamethasone from a lethal infection with Listeria monocytogenes in mice.
The effects of dexamethasone (DEX) on a lethal infection with Listeria monocytogenes were studied in mice. Mice were completely protected against the lethal infection when treated with 3.3 mg per kg of DEX. The effect was observed only when DEX was injected before infection. The control mice died from day 3 to day 5 of infection, whereas DEX-treated mice could eliminate L. monocytogenes cells from the organs by day 11 of infection. High titres of endogenous tumour necrosis factor (TNF), interleukin-6 (IL-6) and gamma interferon (IFN-gamma) were induced in the bloodstreams and organs of the drug-free mice. DEX suppressed IL-6 production, but augmented TNF and IFN-gamma production within 24 h of infection, whereas production of all three endogenous cytokines was suppressed in the DEX-treated mice on day 3 of infection when the control mice began to die. These results suggest that DEX shows a protective effect on a lethal infection with L. monocytogenes in mice and that regulation of production of endogenous cytokines might be involved in the effect of DEX.
Animals↗
Effects of aging on acute toxicity of nicotine in rats.
Acute toxicity of nicotine was examined in old (24 months) and young (6 weeks) Wistar rats. There were no significant age differences in the mortality and convulsive responses induced by an intraperitoneal injection of nicotine (24.5 mg/kg). The lethal nicotine levels in blood and cortex and the latent period to death in old rats were larger than those in young rats. Cortical and blood nicotine levels 15 min. after the nicotine injection in old rats were also higher than those in young rats. Nicotine significantly increased dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels in striatum and hippocampus in young rats, but not those in old rats. Moreover, nicotine-induced elevations in blood levels of corticosterone in old rats were also less than those in young rats. On the other hand, the cytochrome P-450 content, the nicotine oxidase activity and the flavin-containing monooxygenase activity in liver showed age-related decreases in the young, the middle-aged (12 months) and the old rats. These results indicate that the acute toxicity of nicotine in old rats reflects the decreases in hepatic nicotine metabolism and in brain sensitivity to nicotine.
Aging↗
Host resistance to an intragastric infection with Listeria monocytogenes in mice depends on cellular immunity and intestinal bacterial flora.
Suckling and adult mice were infected intragastrically with different doses of viable Listeria monocytogenes. The 50% lethal dose for the intragastric infection was 10(3.7) CFU for suckling mice, while adult mice were highly resistant and the 50% lethal dose was more than 10(9.3) CFU. When adult mice were infected intragastrically with 5 x 10(8) CFU of L. monocytogenes, no mice died. However, 35% of adult mice died when they were treated with cyclosporin A 1 day before infection. Although mice did not die when treated with an L. monocytogenes-resistant broad-spectrum cephalosporin, sodium cefbuperazone, before and during infection, the number of L. monocytogenes bacteria increased in the feces. The sodium cefbuperazone treatment of mice resulted in superinfection, i.e., a marked decrease of Escherichia coli and an increase of Enterococcus spp. in the intestines. Furthermore, host resistance against the intragastric infection markedly decreased when the mice were treated with both drugs. The growth of L. monocytogenes was augmented in the spleens, mesenteric lymph nodes, Peyer's patches, and feces, and the mortality of the mice was 65%. These results suggest that both cellular immunity and the intestinal bacterial flora are required for host resistance against oral L. monocytogenes infection.
Animals↗
Increased group II phospholipase A2 in colonic mucosa of patients with Crohn's disease and ulcerative colitis.
The immunochemical protein content of group II phospholipase A2 (PLA2) and PLA2 enzymatic activity were measured for colonic mucosal biopsy samples obtained from patients with either Crohn's disease of the colon or ulcerative colitis, and control patients without inflammatory bowel disease. Immunoreactive group II PLA2 (IR-PLA2 II) content and PLA2 activity in actively inflamed colonic mucosa of Crohn's disease patients were significantly higher than those in inactively inflamed mucosa of Crohn's disease patients and the colonic mucosa of controls. IR-PLA2 II content and PLA2 activity in severely inflamed mucosa of ulcerative colitis patients were significantly higher than those in the colonic mucosa of the controls. Mucosal PLA2 enzymatic activity was closely correlated with mucosal IR-PLA2 II content in patients with Crohn's disease and ulcerative colitis. These results suggest that an increase in PLA2 enzymatic activity in inflamed colonic mucosa of Crohn's disease and ulcerative colitis was mainly attributed to increased protein content of group II PLA2, and that an increase in mucosal group II PLA2 may be involved in the pathogenesis of intestinal inflammation of Crohn's disease and ulcerative colitis.
Adolescent↗
Three year follow up study of national influenza vaccination practices in Japan.
STUDY OBJECTIVE: To evaluate new national influenza vaccination practices which were started in 1987 under a revised law in Japan. DESIGN: This was a three year, nonrandomised cohort study with information collected by questionnaire between 1989 and 1991. SETTING: Eight primary schools in the city of Yonago, Tottori, Japan. These schools were selected from 23 schools in the city. PARTICIPANTS: Altogether 4251 pupils (1355 boys and 2896 girls) in years 1-4 of the eight primary schools were included in this study, and followed up. Three years later, data for 1619 pupils (768 boys and 851 girls) were obtained and analysed. MAIN RESULTS: The one-winter seasonal incidence rates of influenza-like disease were 13.4%, 29.9%, and 10.3% in 1989, 1990, and 1991 respectively. The incidence rate of influenza-like disease in fully vaccinated pupils was significantly lower than that in unvaccinated pupils in 1990, but not in 1989 or 1991. Stepwise multiple regression analysis showed that the incidence of influenza-like disease had a statistical relationship with the frequency of vaccination and the school year (R2 was 0.0148). Standardised parameters of the frequency of vaccination and the school frequency of vaccination and the school year were -0.089 and -0.080 respectively. CONCLUSIONS: The preventive effects of influenza vaccine are not strong. There must be some unknown factors that affect the incidence of influenza. This vaccine is useful for pupils in the early school years who seem to have less resistance. All pupils should not be inoculated with the vaccine to reduce influenza transmission in the community or school.
Child↗
Decreased cerebrovascular dilatory capacity in subjects with asymptomatic periventricular hyperintensities.
BACKGROUND AND PURPOSE: The clinical significance of the periventricular hyperintensity incidentally found on magnetic resonance images of the brain is questionable. We evaluated resting cerebral blood flow and cerebrovascular dilatory capacity of subjects with asymptomatic periventricular hyperintensities to study their cerebral hemodynamics. METHODS: Magnetic resonance imaging of the brain was performed in 28 asymptomatic subjects with cerebrovascular risk factors to determine the severity of periventricular hyperintensity. Mean gray matter flow was computed by a 133Xe-clearance technique in subjects at rest and after the administration of 1 g acetazolamide. Flow values were correlated with the scores for periventricular hyperintensity. RESULTS: Resting gray matter flow was not significantly correlated with the severity of periventricular hyperintensity for the whole brain (rs = -.364), whereas flow after acetazolamide loading (rs = -.783, P < .001) and the absolute value of increased flow (rs = -.567, P < .01) were significantly and negatively correlated with the severity of periventricular hyperintensity. CONCLUSIONS: A decrease in vasodilatory capacity and compensatory vasodilation occur in the cerebral cortex of subjects with asymptomatic periventricular lesions and maintain cerebral blood flow.
Aged↗
A novel substrate for insulin-sensitive serine/threonine kinase in intact cells.
We have studied insulin-stimulated threonine phosphorylation of cellular proteins by immunoblotting and immunoprecipitation using antiphosphothreonine antibody (anti-P-Thr). A 50-kilodalton protein (p50) was found to be greatly phosphorylated on threonine residues upon insulin stimulation in intact rat hepatoma cells (Fao) and Chinese hamster ovary cells overexpressing human insulin receptor (CHO-HIR). Insulin induced threonine phosphorylation of this protein in a dose-dependent manner, with an ED50 of 3-6 x 10(-9) M. The 50-kilodalton phosphoprotein (pp50) was detectable 20 min after exposure of the cells to insulin, and phosphorylation reached a maximum after 90 min. Immunoprecipitation of pp50 with anti-P-Thr required extraction of the cellular proteins with sodium dodecyl sulfate and dithiothreitol, and subcellular fractionation of the cells revealed that pp50 is present in the membrane fraction, implying that pp50 is a protein integrated into the membrane component in the cells. Tryptic phosphopeptide mapping of the pp50 was distinct from that of the insulin receptor beta-subunit. Phosphoamino acid analysis of the pp50 demonstrated that insulin increased phosphorylation, mainly of threonine and moderately of serine, whereas pp50 did not contain phosphotyrosine. Cycloheximide, a protein synthesis inhibitor, did not affect the insulin-induced appearance of pp50 in the cells. pp50 was not detectable in A431 cells and KB cells stimulated by epidermal growth factor. These data suggest that p50 is a novel endogenous substrate for insulin-sensitive serine/threonine kinase in intact cells.
Animals↗
Infectivities of four isolates of Taenia taeniaeformis to various rodents.
Taenia taeniaeformis were isolated from Norway rats captured at Sapporo (SRN isolate) and Kuala Lumpur, Malaysia (KRN) and from Bedford's gray red-backed voles at Toubetsu (TCR) and Abuta (ACR). SRN, KRN and TCR isolates showed similar degree of infectivity to various rodents in which cysticerci with hooks were obtained in laboratory rats, white tuberous lesions in mice and no cysts or lesions in Mongolian gerbils and voles. Contrary to this, inoculation with ACR isolate eggs resulted in strobilocerci formation in the liver of voles, but no cysts were observed in rats, mice or gerbils. This host specificity of ACR isolate to voles suggests that it might be a new species of Taenia.
Animals↗