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Biomedical subjects

K Ohta

Publications and source records attributed to K Ohta.

At least 739 records · Page 41Linked to original sources

Transport and distribution of copper injected into an albumin-deficient (analbuminemic) rat.

Copper (Cu) concentrations in blood, liver, kidney, spleen and pancreas of an albumin-deficient (Nagase analbuminemic) rat (NAR) were compared with those of a control (Sprague-Dawley) rat (SDR). Cu concentrations were significantly higher in the blood and significantly lower in the liver of the NAR strain than those of the SDR strain in female control (saline-injected) groups at 8 weeks old. Female NAR and SDR 8-week-old rats were injected i.p. with Cu at a single dose of 2.0 mg/kg body wt and killed 18 hr later. Concentrations of Cu and other essential elements in the blood, liver, kidney, spleen and pancreas were determined simultaneously by inductively coupled plasma-atomic emission spectrometry. Cu concentration in the liver was significantly lower in the NAR than in the SDR strain suggesting a role for albumin as a carrier protein of free Cu ions in the blood. The effects of Cu loading on other essential elements (Zn, Fe, Ca, Mg, P) were also compared between the NAR and SDR strains.

Animals↗

Inherited deficiency of the seventh component of complement associated with meningococcal meningitis: lack of serum bactericidal activity against Neisseria meningitidis in a girl with C7 deficiency and HLA studies of a C7-deficient Japanese family.

An 8-year-old girl with meningococcal meningitis lacked serum complement activity. The seventh component of complement (C7) could not be detected in her serum by either functional or immunochemical analysis. The levels of the other components were within the normal range. Her serum complement activity was restored by the addition of purified C7. Her fresh serum showed a total absence of bactericidal activity against Neisseria meningitidis, group Y, but her serum bactericidal activity was restored by the addition of purified C7. The restoration of her serum bactericidal activity was completely inhibited in the presence of Mg2+ EGTA. These findings suggest that restoration of the bactericidal activity of her serum against N. meningitidis might be mediated by the specific antibody against N. meningitidis and the reconstituted complement system in her serum. Heterozygous deficiency of C7 was found in 10 of her family members. Genetic studies showed that the mode of inheritance might be an autosomal codominant trait. No genetic linkage between deficiency of C7 and the HLA system was found.

Blood Bactericidal Activity↗

Regional distributions of thiobarbituric acid-reactive products, activities of enzymes regulating the metabolism of oxygen free radicals, and some of the related enzymes in adult and aged rat brains.

Regional distributions of thiobarbituric acid-reactive products, activities of enzymes regulating metabolism of oxygen free radicals, and some of the related enzymes were studied in 10 areas of adult and aged rat brains. Thiobarbituric acid-reactive products were lower in cerebral cortex, septal area, hippocampus, caudate-putamen, and substantia nigra compared with other areas studied in adult rats; however, they increased significantly in the former areas with aging. A slight but significant reduction in superoxide dismutase activity was noted in frontal cortex, septal area, caudate-putamen, and substantia nigra with aging. Glutathione peroxidase and reductase activities were highest in caudate-putamen and in substantia nigra. Glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities were lowest in cortical areas. Phosphofructokinase activity was lowest in septal area and hippocampus in aged rats. Glyceraldehyde-3-phosphate dehydrogenase activity showed only small regional and evolutional changes. Lactate dehydrogenase activity declined with age in most of the areas studied. sn-Glycerol-3-phosphate dehydrogenase activity showed small changes with aging except in hippocampus, where 40% reduction was noted. Generally, cerebral cortical areas, hippocampus, and septal areas were not particularly enriched in enzymes regulating the metabolism of oxygen free radicals. The results were discussed in relation to the role of free radicals in aging.

Aging↗

Interrelationship between pituitary and ovarian hormones in normal and neoplastic growth of mammary glands of mice.

While prolactin is a key hormone for normal and neoplastic mammary gland growth, the participation of ovarian estrogen and progesterone is essential for these processes under the normal physiological conditions. Prolactin exerts its influence directly to the glands and indirectly through its luteotropic effects by stimulation of ovarian progesterone secretion. Furthermore, the action of prolactin, whether in promoting normal growth and function or enhancing the progression of neoplastic foci, depends upon the circulating levels of other mammotropic hormones as well as the level of prolactin itself. Presence of estrogen and prolactin is essential for manifestation of progesterone effects on mammary gland growth. Estrogen acts on the mammary glands directly by modulating mammary cell responsiveness to prolactin and indirectly by stimulating pituitary prolactin secretion. While data have been accumulated on the effects of growth hormone on mammary gland growth, the significance of these findings is still unknown. Neoplastic potential of mammary cells is largely dependent upon the susceptibility of the cells to mammotropic hormones.

Animals↗

Purification and characterization of an enzyme produced by Treponema denticola capable of hydrolyzing synthetic trypsin substrates.

An enzyme from Treponema denticola that hydrolyzes a synthetic trypsin substrate, N-alpha-benzoyl-L-arginine-p-nitroanilide (BAPNA), was purified to near homogeneity, as judged by gel electrophoresis. The molecular weight of the enzyme was estimated to be ca. 69,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and ca. 50,000 by gel filtration on Sephadex G-100. The pH optimum for the hydrolysis of BAPNA was around 8.5. The enzyme was heat labile and irreversibly inactivated at low pH values. Enzyme activity was enhanced by Ca2+, Mg2+, and Ba2+ but inhibited by Mn2+, Hg2+, Co2+, and Zn2+. Metal chelators and sulfhydryl reagents had no effect on this activity. The enzyme was inhibited by certain protease inhibitors such as diisopropyl fluorophosphate, N-alpha-p-tosyl-L-lysine chloromethyl ketone, phenylmethylsulfonyl fluoride, L-1-tosylamide-2-phenylethylchloromethyl ketone, alpha-1-antitrypsin, and soybean trypsin inhibitor. The Km values for BAPNA and N-alpha-benzoyl-L-arginine ethyl ester were 0.05 and 0.12 mM, respectively, and the Vmax values were higher than those observed with trypsin. Although the purified enzyme hydrolyzed some low-molecular-weight synthetic trypsin substrates, it did not hydrolyze casein, hemoglobin, azocasein, azocoll, bovine serum albumin, or gelatin. Thus, this enzyme is probably not a protease but is capable of hydrolyzing ester, amide, and peptide bonds involving the carboxyl group of arginine and lysine.

Benzoylarginine Nitroanilide↗

Antigenic characteristics and serological identification of 10 black-pigmented Bacteroides species.

Strains of 10 black-pigmented Bacteroides species were serologically characterized using absorbed and unabsorbed rabbit antisera. An agglutination test using intact cells or heated cells (100 degrees C for 60 min) from each species and unabsorbed antisera revealed only homologous reactions with little or no reactivity in heterologous assays. Immunodiffusion tests using sonicated antigen demonstrated that Bacteroides gingivalis, B. endodontalis, B. asaccharolyticus, B. macacae, and B. levii are antigenically distinct. Strains of B. gingivalis, B. endodontalis, and B. asaccharolyticus were also clearly identified by the indirect immunofluorescent antibody method. B. intermedius, B. corporis, B. loescheii, B. melaninogenicus, and B. denticola possessed common antigens; however, species-specific antigens detectable with immunoabsorbed antisera were also demonstrated. B. intermedius strains isolated from the human oral cavity included at least two serogroups. In each black-pigmented Bacteroides species, lipopolysaccharide constituted one of the species-specific antigens.

Agglutination Tests↗

IgG1 antibodies to house dust mite (Dermatophagoides farinae) and late asthmatic response.

Thirteen asthmatic patients sensitive to mite were challenged by inhalation of an extract of mites (Dermatophagoides farinae). Seven showed dual bronchial reactions and 5 showed isolated immediate responses. No patient showed an isolated late reaction. Six of seven patients with dual reaction had higher IgG1 antibodies than the 5 patients with isolated immediate reaction when examined before the challenge. A similar result was obtained in terms of levels of immune complex. IgE, IgG4 and total IgG antibodies were not predictive for late reaction. These results suggest that there is a close correlation of the presence of high IgG1 antibodies with a propensity to develop late asthmatic responses. The meaning of this observation is discussed.

Adult↗

Granulomatous pneumonitis induced by bacille Calmette-Guérin in the mouse and its treatment with cyclosporin A.

Granulomatous pneumonitis was induced intravenously by an injection of BCG, and changes in the population of cells from bronchoalveolar lavage (BAL) fluid were examined. Increased lymphocytes in BAL fluid, especially Lyt-1 positive T-lymphocytes, were observed after the development of granulomatous pneumonitis. Cyclosporin A (Cy A) administered for 5 days before and for 5 days after BCG injection clearly suppressed development of the granuloma. The BAL cell count and cell population became almost the same as those in naive animals. The increase in the number of Lyt-1 positive T cells was abrogated by Cy A treatment. These results suggested the important role of Lyt-1 positive T cells in the development of granulomas and the possible beneficial effect of Cy A in human granulomatous lung diseases.

Animals↗

[Toxicity studies of VP 16-213 (I)--Acute toxicity in mice, rats and rabbits].

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was examined for its oral, subcutaneous or intravenous acute toxicity using Slc : ICR mice, Crj : CD (Sprague-Dawley) rats and JW-NIBS rabbits of both sexes. The summarized results obtained are as follows: A mode of manifestation of toxic effects was classified into immediate-type symptoms predominantly caused by the carrier and delayed-type symptoms predominantly caused by VP regardless of animal species and routes of administration, excluding the case of intravenous dosing to rabbits. Referring to the delayed-type toxic signs, depilation, diarrhea and suppression of body weight increase were observed for mice and rats regardless of administration routes, and diarrhea was noted in rabbits by oral route. Necropsy of three species of animals and histopathology on rabbits revealed thymic and splenic atrophy in mice and rats as well as thymic atrophy and inflammatory changes of intestine in rabbits dying by oral administration. The drug-related cause of death for mice and rats seemed to be due to the cytocidal action of VP as an oncostatic drug, but the cause of death for rabbits by oral administration was considered to be somewhat different from that for mice and rats. LD50 values (mg/kg) were as follows, showing oral toxicity in rabbits being rather potent as compared with that in mice or rats: (table; see text).

Administration, Oral↗

[Toxicity studies of VP 16-213 (V)--Intravenous three-month toxicity in rats].

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered intravenously to Crj : CD (Sprague-Dawley) rats of both sexes at dose levels of 0.05, 0.15, 0.5 and 1.5 mg/kg/day for three months with the object of examining its toxicity and the reversibility of toxic effects. For the purpose of comparison, vincristine (abbr. to VCR) was administered in the same manner at a dose level of 0.02 mg/kg/day. The summarized results obtained are as follows: VP 1.5 mg/kg brought anemia as well as suppression of body weight increase and food intake, and 0.5 and 1.5 mg/kg increased water consumption. However, no drug-related deaths occurred. VP 0.5 and 1.5 mg/kg predominantly decreased red blood cell count and white blood cell count accompanied with lowered lymphocyte fraction which was agreeable to the findings on bone marrow. VP 1.5 mg/kg increased platelet count. VP 1.5 mg/kg lowered total serum protein content and elevated A/G ratio. VP 0.15 mg/kg and higher decreased testicular weight; 0.5 and 1.5 mg/kg brought thymic atrophy, suppression of spermatogenesis, tubular atrophy and hydropic change in testis. VP 1.5 mg/kg induced decrease of sperms in number and appearance of giant cells in epididymis. Above-described changes excluding the findings on testis and epididymis were shown to be generally reversible. Most of the findings for a reference drug, VCR, were qualitatively comparable to those for VP. Based on these results, the non-effect dose level of VP under the present experimental condition was estimated to be 0.05 mg/kg/day against male rats and 0.15 mg/kg/day against female rats.

Anemia↗

[Toxicity studies of VP 16-213 (II)--Oral one-month subacute toxicity in rats].

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered orally to Crj : CD (Sprague-Dawley) rats of both sexes at dose levels of 3, 10, 30 and 100 mg/kg/day for one month with the object of examining its subacute toxicity and the reversibility of toxic effects. The summarized results obtained are as follows: VP 30 mg/kg suppressed body weight increase and feed intake, and brought soft stool. VP 100 mg/kg decreased body weight and feed intake, and induced diarrhea, depilation and so forth. Furthermore, half of the animals at this dose level died showing systemic debility and emaciation. VP 30 and 100 mg/kg predominantly decreased red blood cell count as well as white blood cell count accompanied with lowered lymphocyte fraction. VP 10 mg/kg and higher lowered total serum protein content and serum alkaline phosphatase activity, and elevated A/G ratio. VP 10 mg/kg and higher caused thymic atrophy and a decrease in testicular weight; 30 and 100 mg/kg brought suppression of spermatogenesis; and 100 mg/kg predominantly induced appearance of giant cells in epididymis, hypoplasia of bone marrow, ileocecitis, and atrophy of prostate, seminal vesicle and splenic germinal centers. Above-described changes excluding exacerbation of the findings on testis and epididymis were shown to be generally reversible. Based on these results, the no-effect dose level of VP under the present experimental condition was estimated to be 3 mg/kg/day against rats of both sexes.

Administration, Oral↗

[Reproduction studies of VP 16-213 (I)--Oral administration to rats prior to and in the early stages of pregnancy].

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered orally to male Crj : CD (Sprague-Dawley) rats for 64 days and to female rats of the same strain for 15 days prior to mating at dose levels of 1, 3 and 10 mg/kg/day. These animals were then mated under the consecutive administration of this drug and the females confirmed to be copulated were further dosed from day 0 through 7 of gestation. The summarized results obtained are as follows: VP 10 mg/kg suppressed the body weight increase in females from day 8 of pre-mating through day 20 of gestation, but did not affect the body weight in males. VP 10 mg/kg decreased the organ weights of testes, epididymides and thymus in males and induced atrophy of these organs macroscopically, but did not affect their reproductive performances. As for fetuses, VP 10 mg/kg elevated the mortality and induced anophthalmia, microphthalmia and dilated lateral ventricles, as well as suppressed their growth and the ossification processes of sternums, sacral and coccygeal vertebrae, metacarpus, thoracic vertebrae and pubis. Based on these results, the no-effect dose level of VP under the present experimental condition was estimated to be 3 mg/kg/day against parent rats of both sexes and their offspring.

Administration, Oral↗

[Reproduction studies of VP 16-213 (II)--Oral administration to rats during the period of fetal organogenesis].

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered orally to pregnant Crj: CD (Sprague-Dawley) rats from day 7 through 17 of gestation at dose levels of 1, 3 and 10 mg/kg/day. The summarized results obtained are as follows: VP 10 mg/kg suppressed the maternal body weight increase from day 12 through 20 of gestation. VP 10 mg/kg brought the inhibition of fetal growth accompanied by the lowered values in body weight and body length. Furthermore, the elevated incidences of skeletal anomalies and unossified 5th and 6th sternums, as well as retarded ossification of thoracic vertebrae were also noted in this dose level. VP 10 mg/kg induced anophthalmia, microphthalmia and dilated lateral ventricles in fetuses (F1), as well as unilateral anophthalmia in offspring (F1). VP 10 mg/kg increased the days required for opening of eyelids and descending of testes in offspring (F1), but failed to affect their learning ability, motility, motor activity or emotional development. VP 10 mg/kg suppressed the growth of genital organs in F1 rats of both sexes, but failed to affect their reproductive ability or gestation period. As for F2 newborns derived from F1 rats whose dams had ever received VP 10 mg/kg during the period of fetal organogenesis, the number of implantations and survivors as well as birth indexes lowered due to changes in these items restricted to a few litters. Based on these results, the no-effect dose level of VP under the present experimental condition was estimated to be 3 mg/kg/day against dams and their offspring.

Administration, Oral↗

[Reproduction studies of VP 16-213 (III)--Oral administration to rabbits during the period of fetal organogenesis].

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered orally to pregnant JW-NIBS rabbits from day 6 through 18 of gestation at dose levels of 0.3, 1, 3 and 10 mg/kg/day. The summarized results obtained are as follows: VP 3 and 10 mg/kg elevated the maternal mortality dose-responsively. VP 3 mg/kg and lower doses failed to affect the fetal growth and ossification processes, and did not induce drug-dependent external and visceral anomalies as well as skeletal variations and anomalies. Based on these results, the no-effect dose levels of VP under the present experimental condition were estimated to be 1 mg/kg/day against dams and 3 mg/kg/day against fetuses.

Administration, Oral↗

[Reproduction studies of VP 16-213 (IV)--Oral administration to rats during the perinatal and lactation periods].

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered orally to female Crj: CD (Sprague-Dawley) rats from day 17 of gestation through postpartum day 20 at dose levels of 1, 3 and 10 mg/kg/day. The summarized results obtained are as follows: VP 10 mg/kg induced thymic atrophy in dams. VP failed to affect the parturition of dams. VP 10 mg/kg lowered the viability of newborns (F1) on postpartum day 3 and increased the days required for descending of testes, but failed to affect the growth of genital organs, learning ability, motility motor activity or emotional development. VP 10 mg/kg brought a transient suppression of body weight increase in pregnant F1 rats, but failed to affect their reproductive ability and parturition. F2 newborns derived from F1 rats whose dams had ever received VP during the prenatal and lactation periods showed no changes in observation items at birth. Long-term rearing F1 rats derived from VP-treated dams manifested no delayed toxicity including carcinogenicity. Based on these results, the no-effect dose level of VP under the present experimental condition was estimated to be 3 mg/kg/day against dams and their offspring.

Administration, Oral↗

[Reproduction studies of VP 16-213 (VI)--Intravenous administration to rats during the perinatal and lactation periods].

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered intravenously to female Crj: CD (Sprague-Dawley) rats from day 17 of gestation through postpartum day 20 at dose levels of 0.05, 0.2 and 0.8 mg/kg/day. The summarized results obtained are as follows: VP 0.2 and 0.8 mg/kg suppressed the body weight increase and brought thymic atrophy in dams. VP failed to affect the states of birth of newborns (F1). In F1 offspring, VP 0.8 mg/kg increased the days required for testicular descending and vaginal opening, and suppressed the body weight increase, but failed to affect the growth of genital organs, reproductive ability, learning ability, motility, motor activity or emotional development. F2 newborns derived from F1 rats whose dams had ever received VP during the prenatal and lactation periods showed no changes in observation items at birth. Based on these results, the no-effect dose level of VP under the present experimental condition was estimated to be 0.05 mg/kg/day against dams and 0.2 mg/kg/day against their offspring.

Animals↗