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Biomedical subjects

T Ishimaru

Publications and source records attributed to T Ishimaru.

At least 145 records · Page 8Linked to original sources

Structures of fibrostatins, new inhibitors of prolyl hydroxylase.

The structures of six inhibitors of prolyl hydroxylase, fibrostatins A, B, C, D, E and F produced by a strain of Streptomyces, were deduced to be 1, 2, 3, 4, 5 and 6, respectively, from chemical and spectroscopic evidence, especially from extensive 13C NMR studies including selective decoupling and low power selective decoupling experiments monitored by 13C-1H long-range couplings. These compounds are the first naturally occurring 2,6,7- or 3,6,7-tri-substituted or 2,3,6,7-tetra-substituted 5-hydroxy-1,4-naphthoquinone inhibitors possessing N-acetyl-L-cystein-S-yl moieties in the molecule.

Cysteine↗

HTLV-I carrier mothers with high-titer antibody are at high risk as a source of infection.

High-titer antibody against HTLV-I in carrier mothers is proposed as a secondary parameter for risk of viral transmission to the children via milk. For titration of antibodies, a less expensive modified gelatin particle agglutination assay (approximately 40% of the standard cost) was developed. None of 11 carrier mothers with antibody titers of less than 4000 had carrier children, whereas 11 out of 17 mothers with titers of 256,000 or higher had carrier children. The antibody titer was correlated with antigen-bearing cells detectable in cultures of peripheral blood T-lymphocytes, which was previously described as a marker of risk for transferring HTLV-I to children.

Antibodies, Viral↗

Effects of atomic bomb radiation on the differentiation of B lymphocytes and on the function of concanavalin A-induced suppressor T lymphocytes.

The differentiation of peripheral blood B lymphocytes into immunoglobulin-producing cells (Ig-PC) by pokeweed mitogen (PWM) and the function of concanavalin A (Con A)-induced suppressor T lymphocytes were examined to elucidate the late effects of atomic bomb radiation. A total of 140 individuals, 70 with an exposure dose of 100 rad or more and an equal number with an exposure dose of 0 rad matched by sex and age, were selected from the Nagasaki Adult Health Study (AHS) sample. Both the differentiation of peripheral blood B lymphocytes into Ig-PC by PWM and the function of Con A-induced suppressor T lymphocytes tended to be more depressed in the exposed group than in the control group, but a statistically significant difference could not be observed between the two groups. The function of Con A-induced suppressor T lymphocytes tended to decrease with age, but a statistical significance was detected only for percentage suppression against IgM-PC.

Adult↗

[Fundamental and clinical studies on aztreonam in the gynecological field].

Aztreonam (AZT), a new monocyclic beta-lactam antibiotic was studied on clinical efficacy for infectious disease in gynecological field. At about 80 minutes following intravenous injection of 1 g dose of AZT, it penetrated well into internal genital organs at therapeutic levels. Moreover it transferred very fast and enough into intrapelvic dead space exudate, and its level was kept still as high at 12 hours after administration. AZT was given to 20 women affected with gynecological infectious disease. The outcome of AZT therapy was as follows: effective in 5 out of 6 patients (83.3%) administered intravenously and in all of 14 patients (100%) received intramuscularly. Notable adverse effects or abnormal laboratory findings were not observed except 1 case of diarrhea and 2 cases of transient and slight elevation of serum CPK and transaminases. Based on these results, we may conclude that AZT is a highly effective and a very safe antibiotic for the treatment of infectious disease in gynecological field.

Adult↗

[Monitoring of follicles by ultrasonography during induction with HMG-HCG treatment--especially on the prevention of side effects].

Estrogen levels are a useful indicator to use in predicting of ovarian hyperstimulation syndrome (OHSS) which is one of the side effects of HMG-HCG therapy. However, the quantitative assay of estrogens entails cumbersome time-consuming procedures. The present study represents our attempt to establish criteria for predicting the occurrence of OHSS by the use of ultrasonography (USG), a diagnostic procedure that can be performed quickly and conveniently. The subjects were 40 anovulatory women (79 cycles) receiving HMG-HCG therapy. Each patient had USG performed at the time of switching to HCG in a regimen of sequentially administered gonadotropins and was measured for maximum follicular diameter (FD) and total of vertical follicular area (FA) to correlate measurements of these parameters with simultaneously determined serum estradiol (E2) levels. A study was also made of relationships of FD and FA with ovulation and OHSS. The results are summarized as follows: No distinct correlation was observed between FD and E2 (r = 0.3794). It should be noted, however, that the therapy was successful in inducing ovulation in those cases in which the patient was switched to HCG from HMG when FD was 18mm or above. There was a significant correlation between FA and E2 (r = 0.8113, p less than 0.001). FA was thus proven to well reflect E2 levels and hence to be a parameter of the predictive value for OHSS. All but one (with moderate OHSS) of 26 cases showing evidence of OHSS had FA values of more than 6.0cm2, while those developing severe OHSS invariably.(ABSTRACT TRUNCATED AT 250 WORDS)

Amenorrhea↗

[Dihydrotestosterone formation (5 alpha-reductase activity) in cultured human skin fibroblasts].

Testosterone secreted from the testis is converted to dihydrotestosterone (DHT) in target tissues by 5 alpha-reductase and DHT exerts its action on the nucleus. Since skin is one of the target tissues of androgen we established a system for culturing human skin fibroblasts, and we investigated the conversion of testosterone to DHT in genital and nongenital skin fibroblasts obtained from males as well as from females. In our system, fibroblasts were incubated with 0.1 microM 1, 2-3H testosterone, and labeled metabolites were separated by thin layer chromatography. DHT formation was linear for 6 hours and the rate of DHT formation correlated with the growth phase of the fibroblasts. In the course of serial subculture, DHT formation did not change between the 3rd and 10th subculture in four cell strains. DHT formation in nongenital skin fibroblasts did not differ significantly between males and females. Fibroblasts obtained from male genital skin produced significantly greater amounts of DHT than those from male or female nongenital skin. Furthermore, DHT formation in genital skin fibroblasts did not differ between normal males and hypogonadal males. These data suggest that genital skin is the target tissue where testosterone strongly converts to DHT and the difference of male secondary sexual characteristic appearance between males and females may not depend on the sensitivity of the target tissues to androgen but on the secretion rate of androgen.

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

Temporal analysis of a dose-response relationship: leukemia mortality in atomic bomb survivors.

A data analysis that incorporates time dependencies is demonstrated for the dose response of leukemia mortality in the atomic bomb survivors. The time dependencies are initially left unspecified and the data on leukemia mortality--up to the end of 1978--are used to infer them. Several findings based on T65 revised doses (T65DR) are obtained. First, it is shown that the fits to the data of time-dependent L (linear in gamma dose)-Q (quadratic in gamma dose)-L (linear in neutron dose), L-L, and Q-L dose-response models are significantly improved (P less than 0.001) by using the corresponding time-dependent dose-response models. Second, it is shown that the increased risk of leukemia mortality due to gamma irradiation decreases in time while the increased risk due to neutron exposure decreases more slowly, if at all, in time. Consequently, relative biological effectiveness (RBE) of neutrons is shown to increase in time (P = 0.002) and the current definition of RBE as a time-independent quantity is therefore challenged. It is demonstrated with time-dependent models that the L-L model has a poor fit (P = 0.01) to the data for the first 7 years of study, but has an adequate fit for the remaining 21 years. In contrast the Q-L model has an adequate fit for the entire follow-up period (P greater than 0.30).

Adult↗

[Developmental studies on the palatine bone in the human skull. With special references to the development of its nasal surface].

For the purpose of these studies 83 cases of fetus skulls and 4 cases of adult skulls were used and the following results were obtained; The palatine bone was found to ossify in a fetus between the middle of the second month and that of the third month. The pyramidal process and conchal crest were first observed in a 9.0 cm fetus. The orbital process, sphenoidal process, sphenopalatine notch and nasal crest were first found in a 16.0 cm fetus. The ethmoidal crest was first found in a 20.0 cm fetus. The posterior nasal spine was first found in a 33.0 cm fetus. The anterior part of the palatal surface of the horizontal plate was found to cover the posterior part of the nasal surface of the palatine process of the maxilla so as to form two layers one above the other. However, the covered surface gradually reduced in size finally to make the transverse palatine suture between the maxilla and the palatine bone in the adult. The transverse length of the horizontal plate was almost equal to its antero-posterior length up until the fifth month fetus, while the former was constantly longer than the latter in the fetus older than the sixth month. The perpendicular plate was constantly longer than the horizontal plate in the fetus older than the fourth month. The metrical comparison between the fetus and the adult revealed that the most well-developing part of the palate bone was the height of the perpendicular plate, which developed 10.9 times longer than that of the fourth month fetus. The rest of the part developed 4.5-5.5 times longer than that of the fourth month fetus.

Adult↗

An autopsy case of 17 alpha-hydroxylase deficiency with malignant hypertension.

This is the first autopsy case of male 17 alpha-hydroxylase deficiency with malignant hypertension. The subject had hypertension, hypokalemic alkalosis, and pseudohermaphroditism. At age 21, 17 alpha-hydroxylase deficiency was diagnosed by low urinary excretion of 17-hydroxysteroids, low secretion rate of cortisol, and low plasma testosterone level in association with high urinary excretion of pregnanediol and high plasma progesterone and corticosterone. Urinary excretion of aldosterone and PRA were suppressed, and plasma ACTH was elevated. Hypertension and hypokalemic alkalosis were normalized with dexamethasone therapy. After missing 5 yr of follow-up, malignant hypertension developed, and PRA and aldosterone were elevated. Histological examination revealed some characteristic arteriolar lesions as in malignant nephrosclerosis. Juxtaglomerular hyperplasia and an increase of renin granules were observed, which reflected high PRA. Abnormal histological findings of endocrine organs were observed in the breast, the pituitary gland, the adrenal glands, and the testis.

Adrenal Hyperplasia, Congenital↗

Synthetic cephalosporins. The synthesis and antibacterial activities of 7-[2-(2-(amino-1,3,4-thiadiazol-5-yl)acetamido]-cephalosporins.

Synthesis and antibacterial activities of 7-[2-(2-amino-1,3,4-thiadiazol-5-yl)acetamido]-cephalosporins and their derivatives having the methoxyimino group at the 2-position of the 7-acyl moiety are described. These compounds are of interest as structural analogues of potent antibiotics, 7-[2-(2-aminothiazol-4-yl)acetamido]cephalosporins. 7-[2-(2-Amino-1,3,4-thiadiazol-5-yl)acetamido]cephalosporins showed comparable activity with cefazolin. Introduction of methoxyimino group to the 7-side chain resulted in a lowering of activity.

Anti-Bacterial Agents↗

Investigation of circular asymmetry in cancer mortality of Hiroshima and Nagasaki A-bomb survivors.

Data on Hiroshima and Nagasaki A-bomb survivors are used to investigate, for each city, possible circular asymmetry in cancer mortality around the hypocenter. Using the Cox regression method and controlling for age ATB, sex, followup year, distance from the hypocenter, and type of shielding, it is found that in Hiroshima cancer mortality was significantly higher in the westerly direction from the hypocenter. Mortality from stomach cancer, leukemia, and colon cancer were higher in the westerly direction. In Nagasaki, only lung cancer exhibited circular asymmetry, and was significantly higher in the westerly direction. For various reasons, the results tend to support the possibility of an asymmetry in radiation dose in Hiroshima, but not in Nagasaki. Also, possible asymmetry in nondose variables associated with cancer is suggested in both cities, particularly in variables associated with lung cancer. Indications for future work and implications for future dose-mortality investigations are discussed.

Age Factors↗