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Biomedical subjects

M Katsumata

Publications and source records attributed to M Katsumata.

At least 91 records · Page 5Linked to original sources
PubMed1985

[Clinical studies on lenampicillin in the therapy of skin and soft tissue infections].

Clinical evaluation of newly developed oral ampicillin prodrug lenampicillin (LAPC, KBT-1585) applied to patients with superficial purulent infection at a dosage of 750 approximately 1,500 mg daily was conducted. Additionally, as part of the basic study, transition of the compound to the human skin tissue was observed. With regard to transition to human skin tissue in 11 presurgery dermatitis cases, 250 mg or 500 mg of LAPC was administered to 2 approximately 3 hours before surgery. Comparison was made between concentrations in serum and in skin tissue. Results in the case of 250 mg application showed serum concentration to be 1.28 approximately 3.32 micrograms/ml, and in skin tissue, 0.13 approximately 0.82 micrograms/g. At 500 mg, serum concentration was found to be 2.23 approximately 10.05 micrograms/ml, with skin tissue concentration at 0.45 approximately 1.34 micrograms/g. Rate of clinical efficacy in the treatment of the 183 cases of superficial purulent infection was 79.2%. By grouping of the infections (Table 3), high efficacy rates were obtained in the second group, at 85.7%; in the third at 88.9%; and in the fourth group at 96.4%. Evaluation of usefulness from the standpoint of safety was 77.6%. Good results were obtained in the third group with 88.9%; and in the fourth group with 96.4%. LAPC's efficacy rates against individual strains of bacteria in simple infection are as follows: Staphylococcus aureus, 74.6%; Staphylococcus epidermidis, 76.3%; GPC, 100%; anaerobes, 87.5%. In polymicrobial infections the rate was 84.6%. The rate of efficacy against all strains of bacteria was 76.0%. Adverse reactions were found in 13 cases (14 incidences) out of 193. The rate of incidence was 7.3%, with allergic response accounting for 5 cases, digestive tract disorders, 7 cases, and mouth odor, 1 case. There were 5 cases (6 incidences) of abnormal deviation of laboratory findings. In all cases, abnormal deviations were mild and their relation to the drug was unclear.

Administration, Oral↗
PubMed1984

H-2 influences phenytoin binding and inhibition of prostaglandin synthesis.

We have reported that susceptibility to glucocorticoid- and phenytoin-induced cleft palate and glucocorticoid receptor levels in mice are influenced by the H-2 histocompatibility complex on chromosome 17. Phenytoin competes with glucocorticoids for the glucocorticoid receptor and inhibits production of prostaglandins and thromboxanes. In this paper we have investigated whether, as in the case of glucocorticoids, phenytoin receptor levels and phenytoin-induced inhibition of prostaglandins are influenced by H-2 in a variety of mouse tissues. Using congenic strains varying only in the H-2 region, but otherwise having either the A/Wy(A) or B10(B) genetic background, we demonstrate here that phenytoin receptor content in the lung and liver is significantly higher in the strains with H-2a (A/Wy and B10.A) than in their corresponding H-2b partners (A.BY and B10). The H-2 complex also influences phenytoin-induced inhibition of the release of 3H-arachidonic acid and prostaglandin biosynthesis from thymocytes, prelabeled with 3H-arachidonic acid. Thus, these results suggest a similar genetic and biochemical pathway for the teratogenic action of both phenytoin and glucocorticoids.

Animals↗
PubMed1984

Glucocorticoid-induced phospholipase A2-inhibitory proteins mediate glucocorticoid teratogenicity in vitro.

Dexamethasone induces the synthesis of a phospholipase A2-inhibitory protein (PLIP) of molecular weight approximately equal to 55,000 from calf thymus and PLIPs of molecular weights 55,000, 40,000, 28,000, and 15,000 from A/J mouse thymus and from 12-day embryonic B10. A mouse palates. Sufficient quantities of calf thymus PLIP and of the 15,000 molecular weight mouse thymus and palate PLIPs were prepared and tested as inhibitors of programmed cell death in the medial-edge epithelium of single mouse embryonic palatal shelves in culture. All of the proteins tested prevent the loss of the medial-edge epithelium and, thus, produce the teratogenic effects of glucocorticoids in the palatal culture model. This teratogenic action of both PLIP and glucocorticoids is reversed by arachidonic acid, the precursor of prostaglandins and thromboxanes, suggesting that PLIP mediates the effects of glucocorticoids by inhibiting phospholipase A2.

Animals↗
PubMed1982

Diphenylhydantoin: an alternative ligand of a glucocorticoid receptor affecting prostaglandin generation in A/J mice.

Evidence for the binding of 5,5-diphenylhydantoin and glucocorticoids to a common receptor is presented for pulmonary and hepatic cytosols and thymocytes of A/J female mice. The 5,5-diphenylhydantoin-protein complex is absorbed by DNA cellulose, and is incorporated into nuclei, 5,5-Diphenylhydantoin, like glucocorticoids, inhibits the production of prostaglandins in thymocytes. Thus a common receptor is probably responsible for the inhibitory and teratogenic effects of these drugs.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

An H-2 linked difference in the binding of dexamethasone to murine hepatic cytosol receptor. A possible role of endogenous modifier(s).

The binding of dexamethasone to its receptor in hepatic cytosol preparations from pregnant mice of four congenic and recombinant strains, C57BL/10, B10.A, B10.A(2R) and B10.A(5R), which have almost identical genetic backgrounds other than the H-2 complex, on day 12 of gestation was analyzed by plotting the binding of ligand against cytosol concentration. The plots of C57BL/10 and B10.A(5R) mice were straight lines, but those of the strains B10.A and B10.A(2R) were upward concave curves. The curvature probably did not result from denaturation of the receptor, as indicated by the time course of the dexamethasone binding and by the fact that at a lower concentration of the ligand, at which the receptor would be less stable, there was less curvature than at a higher concentration of the ligand. The curvature can be explained by the presence of endogenous modifier(s) using an analogy from enzymology. Mathematical analysis, partial removal of the modifier(s) by gel filtration, and mixing of the cytosols from the two types of strains indicated the presence of an unsaturated amount of a modifier(s) in the cytosol of the B10.A and B10.A(2R) strains, and the presence of a saturated amount of the cytosol of the C57BL/10 and B10.A(5R) strains. Thus, the H-2 complex contains a gene(s) which regulates the level of a modifier(s) in hepatic cytosol which affects the binding of glucocorticoid to its hepatic cytosolic receptor.

Animals↗
PubMed1981

Influence of H-2-linked genes on glucocorticoid receptors in the fetal mouse palate.

The binding of 3H-dexamethasone to cytosolic receptors in fetal jaws and in cytosols and nuclei of primary cell cultures of fetal palates was studied in various congenic strains of mice. The amount of specific binding was greater in palatal tissues from B10.A and B10.A(2R) mice than in B10 or B10.A(5R) preparations. These differences were not observed in the liver. Since the strains with higher levels of glucocorticoid receptor are known to be more susceptible to cortisone-induced cleft palate than the strains with low receptor levels, it is suggested that quantitative variation in receptor levels may be involved in determining H-2-linked differences in cleft-palate susceptibility. Whether or not this is the case, it appears that an H-2-linked gene affects the quantity of a cytosolic glucocorticoid-binding protein which translocates to the nucleus.

Animals↗
PubMed1980

Quantitative variation in hormonal receptors and clefting in the mouse.

Evidence has been presented that there is a quantitative variation of fetal palatal glucocorticoid receptor levels which correlates with susceptibility to cortisone-induced cleft palate in a variety of inbred strains of mice. This is consistent with what is known about the mechanism of action of glucocorticoids in most tissues. It may be stated with some reservation that there may be a gene(s) in or near the H-2 locus which regulates, in part, both susceptibility and receptor levels. There is at least one non H-2 gene which is involved in this regulation. Susceptibility to phenytoin-induced cleft palate may be also regulated in part by an H-2 associated gene. These studies have raised more questions than they have answered and hopefully may lead to some new light in the mechanism of this animal model of the congenital defect of cleft palate with future work.

Animals↗
PubMed1978

Prepubertal diagnosis of steroid 5 alpha-reductase deficiency.

The diagnosis of 5 alpha-reductase deficiency was proven in two prepubertal patients with male pseudohermaphroditism (MPH). Both had a 46-XY karyotype and were reared as females; one child had been castrated in infancy. Clitoromegaly, urogenital sinus, and short vaginal pouch were present in both; inguinal gonads were palpable in one. The diagnosis was made biochemically by observing characteristic changes in five parameters: 1) abnormally high testosterone to dihydrotestosterone (T:DHT) ratio after hCG stimulation (35 and 53 vs. normal, 11 +/- 3), 2) abnormally high 5 beta-T metabolites in urine (8.1 and 6.0 vs. normal, less than 1),3) deficient conversion of T to DHT during [3H] T infusion (0.3 and 0.4% vs. normal, 5.3 +/- 3), 4) deficient conversion of [14 C] T to 5 alpha-reduced metabolites by nongenital skin fibroblasts (2.2 and 1.9 pmol/microgram DNA/nmol substrate vs. 68.4+/- 7.8 Pmol/microgram DNA/nmol substrate in normal controls), and 5) deficient conversion of [14C]T to DHT in genital skin slices. The fact that this syndrome represents a defect in T metabolism rather in in T binding is demonstrated by the observation that binding of [3H]DHT to cytosol of skin fibroblasts was normal (4.2 dpm/micrograms DNA vs. normal male values of 3.7 +/- 0.64). Thus, the present report suggests that 5 alpha-reductase deficiency can be diagnosed during childhood and even after castration by metabolic studies of nongenital skin fibroblasts and determination of the conversion ratio of [3H]T to [3H]DHT in plasma.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1976

A mathematical analysis of the substrate effect observed in 3beta-hydroxysteroid dehydrogenase reactions of rat testicular microsomes.

The substrate effect in enzyme reactions has been explained mostly in terms of an additional substrate binding site on the enzyme other than the catalytic site. A rate equation for the reaction is introduced according to the steady state mechanism as follows: v = (Ps3+Qs2+Rs)/(s3+Ls2+Ms+N), were the six parameters, L,M,N,P,Q, and R, can be determined by the least-squares method from the experimental points. The v vs. s curve has an asymptote parallel to the s abscissa, and can be classified into one of four types. The type A curve has an intersection with the asymptote and an apparent maximum velocity; the curve descends toward the asymptote. Type B has no intersection and no stationary point; the curve ascends toward the asymptote. Type C has two intersections and two stationary points, an apparent maximum velocity and a minimum velocity; the curve ascends toward the asymptote. Type D has no intersection and two stationary points; the curve ascends toward the asymptote. The equation was applied to the 3beta-hydroxysteroid dehydrogenase [EC 1.1.1.145] reaction of rat testicular microsomes. The conversion of 3beta-hydroxyandrost-5-ene-17-one was represented by type C, with an apparent maximum velocity of 0.338 nmole/min/mg protein at 0.912 muM of the substrate concentration, minimum velocity of 0.108 nmole/min at 16.6 muM, and saturating velocity of 0.169 nmole/min at infinite concentration of the substrate. The converson of 3beta-hydroxypregn-5-ene-20-one was of type B, having two inflexion points, 0.320 nmole/min at 2.735 muM and 0.814 nmole/min at 12.39 muM, and a saturating velocity of 3.80 nmoles/min at infinite concentration of the substrate.

Animals↗