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Biomedical subjects

H Oshima

Publications and source records attributed to H Oshima.

At least 271 records · Page 15Linked to original sources

[Abnormal calcium metabolism in myotonic dystrophy: increased level of serum 1,25(OH)2D concentration and augmented intestinal calcium absorption].

Myotonic dystrophy (MyD) is a multisystemic disorder characterized by muscle weakness, myotonia, cataract and frontal baldness. Several endocrinological abnormalities are also known in this disorder. Although presence of bone changes, such as hyperostosis, has been frequently reported in MyD patients, there have been few published papers in which calcium metabolism was precisely examined. The present study was designed to elucidate the possibility of the presence of abnormal calcium metabolism in MyD by using the oral calcium tolerance test. Ten patients with MyD, 11 patients with other neuromuscular disorders (non-MyD) and 9 healthy control subjects were investigated according to the method of Broadus et al. Increments of serum and urinary calcium levels after oral calcium load (1 gram) were determined as indices of intestinal calcium absorption. There were no significant differences in basal plasma calcium and phosphate levels among the three groups. Plasma 1,25(OH)2D level in MyD (38.0 +/- 11.8 pg/ml, Mean +/- SD) was significantly higher than those in the other two groups (normal subjects 21.8 +/- 7.0; P less than 0.01, non-MyD 21.8 +/- 12.0; P less than 0.01), respectively. In contrast, plasma 25(OH)D and 24, 25(OH)2D levels were not significantly different among these groups. Fasting urinary calcium excretion in both MyD (0.151 +/- 0.069 mg/100 ml GF) and non-MyD (0.141 +/- 0.077) was significantly higher than that in normal subjects (0.064 +/- 0.048). Calcemic response in MyD (1.08 +/- 0.20 mg/dl) was significantly increased when compared with that in normal subjects (0.72 +/- 0.34, P less than 0.02) and non-MyD (0.54 +/- 0.31, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Urinary trehalase as an early indicator of cadmium-induced renal tubular damage in rabbit.

The significance of urinary trehalase as a possible early indicator of renal disorder was examined using Cd-treated rabbits, which received 1 mg/kg Cd thrice weekly for 3 months subcutaneously. The results showed that urinary trehalase increased significantly from 1 week after treatment, earlier than LAP, ALP, proteinuria and glucosuria, with no changes in plasma trehalase level. A marked decrease in trehalase activity in renal brush border membranes prepared from Cd-treated rabbits was observed. It was also confirmed by immunohistological techniques that Cd treatment resulted in a marked decrease in specific fluorescence compared with controls. Ouchterlony double diffusion analysis demonstrated that urine and renal brush border extracts formed precipitation lines against anti-renal trehalase IgG, indicating that urinary trehalase and renal trehalase had the same antigenicity. Therefore, the facts presented here would suggest that urinary trehalase originated from the renal brush border, indicating its superiority as a diagnostic tool over other indicative indicating its superiority as a diagnostic tool over other indicative enzymes like LAP and ALP in detecting injury to renal proximal tubular cells in the early stage.

Animals↗

Antigens associated with various cytotoxic activities of murine peripheral macrophages.

BCG- or glucan-elicited murine peripheral macrophages released a cytotoxin in the presence of loach egg lectin, whereas proteose peptone-, glycogen-, or thioglycollate-elicited or resident macrophages did not. The macrophages that released cytotoxin coincided with those that showed lectin-dependent macrophage-mediated cytolysis (LDMC) in response to loach egg lectin. The cytotoxin released by BCG-elicited macrophages in response to loach egg lectin had a molecular weight of 55 K daltons. The macrophages that released cytotoxin and other cytotoxic macrophages such as those that showed LDMC- and antibody-dependent macrophage-mediated cytolysis (ADMC) were examined by using several antibodies to surface antigens of macrophages. The results showed that murine peripheral macrophages could be divided into three types. Resident macrophages (Type I) which had common macrophage antigens (Mac-1 and B12) showed only LDMC in response to wheat germ agglutinin. Some elicited macrophages (Type II) were asialo GM1-positive and showed both ADMC and LDMC in response to wheat germ agglutinin. Activated macrophages (Type III) showed LDMC in response to loach egg lectin and cytotoxin-release, but had no antigen detectable with monoclonal anti-macrophage antibody (C14). These three types of macrophages were clearly distinguished diagrammatically by their roof-shaped, rocket-shaped and irregular-shaped profiles of activities and antigens. These data suggest that several selected surface antigens of macrophages are associated with distinct cytotoxic stages of peripheral macrophages.

Animals↗

Testicular control of prostaglandin E2 production in rat vas deferens.

Orchidectomy decreased and testosterone (T) replacement restored prostaglandin E2 (PGE2) concentrations in adult rat vas deferens. To explain this finding, phospholipase A (PLase-A) and PG synthetic activity were studied in vas tissue from 9-week-old rats orchidectomized with or without T replacement as well as in rats in which the cauda epididymidis was ligated. PG synthetic activity fell to 3% of intact levels in 14-day castrate rats and was restored to normal by T replacement. Although vas PLase-A activity was also significantly (P less than 0.01) reduced to 38% of the control level in 14-day castrate rats, this change appears in part to reflect a castration-related increase in endogenous phospholipid concentrations. Further, T replacement only partially restored PLase-A activity to 59% of intact levels. Ligation of the cauda epididymidis in intact rats reduced vas PLase-A activity to castrate levels without altering vas T concentration. These results demonstrate both a direct effect of T on the biosynthesis of PGs in rat vas deferens as well as a paracrine effect, which appears to be mediated by a factor(s) other than T. These data suggest the existence of a new mechanism through which testicular products contribute to the function of the vas deferens.

Animals↗

Priming effect of interferons and interleukin 2 on endogenous production of tumor necrosis factor in mice.

The effects of interferons (IFNs) and interleukin 2 (IL 2) on endogenous production of tumor necrosis factor (TNF) were investigated in mice. Production of serum TNF was triggered by iv injection of OK-432 and tested by in vitro cytotoxicity assay. Injection of recombinant IFN-gamma with OK-432 and tested by in vitro cytotoxicity assay. Injection of recombinant IFN-gamma with OK-432 or of IFN-alpha/beta, recombinant IFN-beta, recombinant IFN-alpha A/D or recombinant IL 2 six hours before OK-432 enhanced TNF production about 10-fold, which indicated priming actions of these compounds in TNF production. These findings suggest that these compounds could also be used as priming agents for endogenous production of TNF in cancer patients.

Animals↗

Endogenous production of TNF in mice long after BCG sensitization.

The effect of tuberculin-antigen protein (PPD: purified protein derivatives) on the priming of tumor necrosis factor (TNF) a long time after sensitization with bacillus Calmette-Guérin (BCG) was investigated in mice. Mice were infected intravenously (i.v.) with 4 X 10(7) colony-forming units (CFU) of BCG per mouse, and the TNF activity triggered by 15 micrograms lipopolysaccharide (LPS) was assayed with time using L-929 cells. The activity was maximal 4 weeks after sensitization and decreased to the control level after 10 weeks. The i.v. injection of 10 micrograms of PPD per mouse enhanced the TNF production triggered by LPS in mice even 10-20 weeks after sensitization. This enhancement was unexpectedly quite transient, being maximal 3 h after PPD treatment. The activity was comparable to that in mice 4 weeks after sensitization of BCG (without PPD). The enhancing effect of PPD was observed in the dose range of 0.1-10 micrograms/mouse, and 10 micrograms of PPD significantly enhanced the TNF activity triggered by even 0.6 microgram LPS. These findings indicate that priming of sensitized animals with some antigens followed by triggering with LPS induces a significant endogenous production of TNF even a long time after antigen sensitization. The possible application of these findings for inducing endogenous production of TNF in human patients by use of tuberculin allergy is discussed.

Animals↗

Induction by heterologous fibrinogen of release of TNF-like cytotoxic factor from murine macrophages.

In an attempt to find nontoxic triggering agents to release cytotoxin from primed macrophages of mice, the abilities of eight plasma components to induce release of cytotoxin from J-774.1, a murine macrophage-like cell line, were examined. Heterologous, but not homologous, fibrinogen and fibrin were found to enhance the release of cytotoxin. The fibrinogen and fibrin did not contain any lipopolysaccharide (LPS) as tested with polymyxin B. Thus, heterologous fibrinogen and fibrin could be useful as nontoxic triggering agents.

Animals↗

Endogenous production of TNF in mice with immune complex as a primer.

C3H/He mice were immunized i.v. with sheep red blood cells (SRBC), and then the effect of i.v. challenge with SRBC on the priming of endogenous production of tumor necrosis factor (TNF) was investigated. Mice were immunized i.v. with 10(8) SRBC/mouse, and their serum TNF activity, triggered by 3 micrograms lipopolysaccharide (LPS) per mouse, was assayed by an in vitro cytotoxicity test using L-929 cells. Anti-SRBC antibodies were induced maximally in 2 weeks, but the acquired immunity did not affect TNF triggering. However, 9-10 weeks after the primary challenge, when there was still a relatively high antibody titer in the serum, i.v. rechallenge with 10(8) SRBC/mouse transiently enhanced the TNF activity triggered by LPS to about 10 times that in normal control mice. This priming effect of SRBC challenge was antigen specific, because challenge with horse red blood cells (HRBC) had no effect. SRBC opsonized with anti-treated with anti-SRBC antiserum or sonicated SRBC had no effect. These findings suggest two ways of facilitating the triggering of endogenous TNF production: booster challenge of immunized animals with the corresponding antigens makes them ready for TNF triggering, and direct injection of immune complexes, even into normal animals, makes them ready for triggering of TNF. The possible application of these findings for inducing endogenous TNF production in human cancer patients by use of immune complexes is discussed.

Animals↗

[Clinical effectiveness of short-term administration of norfloxacin in acute urethritis].

Thirty patients with acute urethritis were treated with short-term administration of norfloxacin. The drug was administered randomly in two regimens: Two 400 mg oral doses for a single day or three 200 mg oral doses for three days. For gonorrheal urethritis, the efficacy rates of one and three-day administrations were 75 and 90%, respectively. For non-gonorrheal urethritis, they were 75% each. No adverse effects were observed. The results indicate that short-term administration of norfloxacin is useful in the treatment of acute urethritis, especially for gonorrheal urethritis.

Acute Disease↗

Studies of the human testis. XX--Effect of NADH on 17 alpha-hydroxypregnene C17-20 lyase activity.

A study of the cofactor requirements of C17-20 lyase was carried out using human testis tissue obtained at the time of orchiectomy for treatment of prostatic carcinoma. Washed microsomal fractions were prepared from frozen human testes using a KCl containing buffer. The preparation revealed dose-dependent activity of C17-20 lyase in the presence of either NADPH or commercial or purified NADH. The Km of NADH for the enzyme was of the order of 10(-3) M and the Km of NADPH was determined as 1.6 X 10(-5) M. NADH also provided synergistic enhancement of NADPH-mediated lyase activity, and decreased the Km of NADPH for the lyase but did not change the Vmax of NADPH-mediated lyase activity. Carbon monoxide inhibited both NADH and NADPH-mediated lyase activities indicating that both activities are catalyzed by cytochrome P-450. Cations including Ca2+, Mg2+ and Mn2+ were found to inhibit the NADPH-mediated lyase activity but enhanced the lyase activity in the presence of NADH. The results indicate both the presence of NADH-mediated C17-20 lyase activity and the synergistic effect of NADH on NADPH-mediated lyase activity in the human testis.

Aged↗

An analysis of the age-related decline in testicular steroidogenesis in the rat.

The effect of aging in rats on serum and intratesticular testosterone levels, microsomal steroidogenic enzyme activities and microsomal cytochrome P-450 was studied. Serum testosterone levels were highest in 11-wk-old rats, declined at age 16 wk and further declined between ages 7 and 21 mo. Intratesticular testosterone levels in 21-mo-old rats were significantly lower than those of the other groups. The activity of 17 alpha-hydroxylase and C17-20 lyase, as well as cytochrome P-450, decreased significantly in 21-mo-old rats. The activity of 17 beta-hydroxysteroid oxidoreductase increased from 11 wk to 16 wk of age and then declined by 21 mo of age to the levels of 11-wk-old animals. Similar changes in delta 5-3,3-hydroxysteroid dehydrogenase coupled with delta 5-delta 4 isomerase activities were observed, but were not statistically significant. These results suggest that the decline in testosterone production in old rats is predominantly a result of decreased oxygenase activity. Inasmuch as oxygenases are gonadotropin dependent, our results support the hypothesis that gonadotropin deficiency is the major factor responsible for Leydig cell dysfunction in old rats. Further, the decline in the ratio of 17 alpha-hydroxylase to C17-20 lyase with aging suggests that other factors affect these enzymes as well as the reduction in cytochrome P-450.

Aging↗