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Biomedical subjects

Y Kitamura

Publications and source records attributed to Y Kitamura.

At least 721 records · Page 40Linked to original sources

Computation of statistical secondary structure of nucleic acids.

This paper presents a computer analysis of statistical secondary structure of nucleic acids. For a given single stranded nucleic acid, we generated "structure map" which included all the annealing structures in the sequence. The map was transformed into "energy map" by rough approximation; here, the energy level of every pairing structure consisting of more than 2 successive nucleic acid pairs was calculated. By using the "energy map", the probability of occurrence of each annealed structure was computed, i.e., the structure was computed statistically. The basis of computation was the 8-queen problem in the chess game. The validity of our computer programme was checked by computing tRNA structure which has been well established. Successful application of this programme to small nuclear RNAs of various origins is demonstrated.

Biological Evolution↗

In vitro demonstration of deleterious effect of steel mutation on spermatogenesis in mice.

The effect of the steel mutation on spermatogenesis was investigated by using organ culture. Cultured cryptorchid testes from C57BL/6- +/+ mice showed an effective differentiation of type A spermatogonia in response to an increased concentration of bovine serum. In contrast, the cryptorchid testes from C57BL/6- Sld/+ mice showed only limited differentiation of type A spermatogonia even in the highest concentration of serum tested. The type A spermatogonia of mutant mice showed the normal mitotic response but did not differentiate further. The findings reported here are the first in vitro demonstration of the deleterious effects of the steel mutation on testicular germ cell differentiation and suggest that the effect of the steel mutation is expressed in Sertoli cells, the only supporting element in seminiferous tubules, or germ cells themselves.

Alleles↗

Pituitary abnormalities detected by high resolution computed tomography with thin slices in primary hypothyroidism and Turner syndrome.

Pituitary hyperplasia, microadenoma or an empty sella was detected in three children with primary hypothyroidism and three with Turner syndrome with the use of high resolution contrast-enhanced computed tomography (CT) with thin slices. Hyperplasia or microadenoma of the pituitary gland frequently occurs secondary to primary hypothyroidism and gonadal dysgenesis, and recognition of these results may eliminate unnecessary surgery in favor of hormone replacement therapy. High resolution contrast-enhanced CT, especially coronal CT, with thin slices is very helpful in demonstrating these pituitary abnormalities.

Adenoma↗

Augmentation of aromatase activity by FSH in ovaries of fetal and neonatal mice in organ culture.

The stimulative effect of FSH on aromatase activity was investigated in ovaries of fetal (on days 17 and 18 of gestation) and neonatal mice (on days 0, 3, 6 and 9 after birth). Two to six ovaries, were cultured for 48 h in 2 ml of Medium 199 supplemented with insulin (5 micrograms/ml) and [1 alpha, 2 alpha, 6 alpha, 7 alpha, beta-3H]4-androstene-3,17-dione (0.35 microM) in the presence or absence of porcine FSH (0.5 units/ml) and the amount of [3H]oestradiol-17 beta and [3H]oestrone produced was estimated. In the presence of FSH, aromatase activity per ovary, which was found in all fetal and neonatal ovaries examined, increased with age. In the absence of FSH, however, the production of oestrogens could be demonstrated only in ovaries from 3- to 9-day old mice. FSH increased the aromatase activity by up to 10-fold. In spite of the stimulative effect of FSH on aromatase activity, FSH exerted no significant effect on DNA synthesis of the ovaries. The formation of primordial follicles could not be observed histologically in ovaries of fetal mice on day 17 of gestation, although the ovaries of 6- and 9-day old mice contained multilayered follicles. These results show that FSH stimulates the aromatase activity of the mouse ovary even before the formation of primordial follicles and that the stimulative effect of FSH on ovarian aromatase is not due to the proliferation of ovarian cells.

Androstenedione↗

Inhibition of luteinizing hormone secretion during quiescent interval of testicular androgen production in immature mice.

We reported [1] that the proliferation of seminal vesicle cells in mice takes place largely in the neonatal (days 0-15) and pubertal (days 25-35) periods and that between neonatal and pubertal proliferations, a quiescent interval of cell proliferation due to markedly diminished secretion of androgens occurs. The present study was carried out to investigate the mechanism for this quiescent interval of Leydig cell activity. Serum LH concentrations were moderate (0.29 ng NIH-LH-S1/ml) at 8 days of age, low (0.13 ng/ml) at 18 days, and high (0.78-0.60 ng/ml) at 30, 40 and 60 days. The LH level on day 18 was almost the same as that found in hypophysectomized adult mice (0.12 ng/ml). These changes with age in serum LH concentrations paralleled those for serum total androgen (testosterone plus 5 alpha-androgens) concentrations. The injection of HCG (1 IU/day) or LH releasing hormone (0.1 or 0.4 microgram/6h) for 1 or 2 days resulted in significant and marked increases on day 18 in testicular and serum androgen levels and/or the proliferation of seminal vesicle cells measured with 5-[125I]iodo-2'-deoxyuridine uptake by the whole seminal vesicles. These findings lead to the hypothesis that the quiescent interval of testicular androgen production due to inhibition of pituitary LH secretion occurs around day 20 in mice.

Aging↗

Friend erythroleukaemia cell mutants defective in viral gene expression.

Cellular mutants defective in the expression of viral polypeptides were isolated from the Friend erythroleukemia cell line 745a by immunoselection with anti-ecotropic murine leukaemia virus serum in the presence of complement. The mode of appearance of the antiserum-resistant cells showed an interesting pattern which is discussed in the text. One of the mutants obtained contained no detectable gp70 or p15(E) while retaining gPr90env; defects appeared to reside in the processing of the gPr90env to gp70 and p15(E). In another type of mutant, gPr90env was not detected. All these mutants retained spleen focus-forming virus (SFFV)-specific gp55 and gag precursor Pr68gag. The mutants superinfected with the helper virus produced the helper and SFFV also, indicating that these mutations did not affect the replication of the exogenously infecting virus.

Animals↗

Effects of ovariectomy on the ultrastructure of the parathyroid gland of the golden hamster.

Ultrastructural changes of the parathyroid glands of ovariectomized golden hamsters were investigated. In the parathyroid glands there is a decrease in the area of each cell occupied by the Golgi complex, in the number of prosecretory granules and in the tortuosity of plasma membrane as compared with those of the control golden hamsters. In addition, the area occupied by lipid droplets appears to be increased and the number of secretory granules in the peripheral cytoplasm and large vacuolar body appears to be decreased compared to those of the control animals. These features suggest that the synthesis and release of parathyroid hormone may be suppressed in many chief cells of the ovariectomized golden hamsters.

Animals↗

[Concentration of antibiotics (cefoperazone) in human brain, brain tumor tissue and cerebrospinal fluid].

The transfer of cefoperazone (CPZ) into cerebrospinal fluid (CSF), brain or brain tumor tissue was studied in 13 cases with brain tumor, chronic subdural hematoma and benign intracranial hypertension in 1982. The peak values of CPZ in serum came up immediately after its rapid intravenous administration and then decreased exponentially. The concentration of CPZ in CSF started to increase with a long delay of about 60 min. The average peak level in CSF remained 21.6 micrograms/ml and corresponded to 10.3% of the peak level in serum. The best transfer of chloramphenicol into CSF has been reported, while that of CPZ would be one of the next. The CPZ levels in CSF showed a slower decay than in serum. The concentration of CPZ in brain reached the peak level in less than 30 min and the average peak level was 36.5 micrograms/g cerebral tissue. The brain to blood rate of the CPZ concentration was 11.1%. The CPZ levels in the brain showed a rapid decrease like the transition of antibiotic levels in serum. The antibiotic levels in brain tumors were divided into two groups. The one showed sharp peak about one tenth of the values in serum. The other was of a slowly increasing type.

Adult↗

Interleukin-1 restores the impaired cytotoxic T lymphocyte generation in beige mutant mouse.

Spleen cells from C57BL/6 beige mouse showed significantly lower cytotoxic T lymphocyte (CTL) generation in vitro against allogeneic target cells as compared with spleen cells from the wild type, whereas the heterozygous littermate showed a response similar to that of the wild type. In contrast, the responsiveness of beige spleen cells in the mixed lymphocyte reaction against allogeneic stimulator cells was in the normal range, suggesting that beige spleen cells recognize allogeneic stimulator cells to the same extent as spleen cells from normal mouse, resulting in a significant proliferation. The addition of interleukin 1 (IL-1)-containing supernatant from lipopolysaccharide-stimulated J774.1 cells to the culture of spleen cells from beige mouse stimulated with allogeneic cells restored the impaired CTL generation in a dose-dependent manner. The molecules responsible for restoration of the impaired CTL response co-migrated with IL-1 on gel filtration. The addition of purified interleukin 2(IL-2) also augmented the induction of CTL from beige spleen cells. However, the magnitude of augmentation by IL-2 was appreciably lower than that of augmentation by IL-1. These results suggest that the role of IL-1 in the induction of CTL is not only to provide a signal for activated amplifier T cells to release IL-2, but also to magnify otherwise low responsiveness of CTL-precursors and/or CTL-helpers. Moreover, intraperitoneal injection of IL-1 without allo-antigenic stimulation was able to restore the in vitro CTL responsitivity to allo-antigen but not the natural killer cell activity, indicating that IL-1 has a therapeutic potential in vivo for preferentially correcting impaired CTL generation associated with beige mutation.

Animals↗

Poor response of Wv/Wx mice to a grafted neutrophilia-inducing, colony-stimulating-factor-producing tumor.

Although mice possessing two mutant genes at the W locus have a defect in multipotential hematopoietic stem cells that form macroscopic colonies in the spleen of irradiated mice, the number of neutrophils in the blood of these mutant mice is normal or nearly normal. We investigated neutrophil production using the NFSA fibrosarcoma of C3H mouse origin, which induces neutrophilia accompanied by production of a neutrophil-macrophage colony-stimulating factor by the tumor. When the NFSA tumor was transplanted to (C57BL/6 X C3H/He)F1-Wv/Wx or to congenic +/+ mice, neutrophilia developed in mice of both genotypes. However, there was a significant difference between the degree of neutrophilia that developed in them; there was a 107-fold increase in the +/+ mice, but only a 28-fold increase in the Wv/Wx mice four weeks after tumor transplantation. This result is consistent with the concept that doubly heterozygous W mice have multipotential stem cells with diminished ability to respond to stimulation. The unperturbed condition may not provide a sufficient stimulus to demonstrate the defect in neutrophil production in doubly heterozygous W mutant mice.

Anemia↗

[Significance of cell-to-cell interaction for migration and proliferation: an application of W and Sl mutant mice for cancer research].

A double gene dose of mutant alleles at either W or Sl locus of mice produces the pleiotropic effects of macrocytic anemia, depletion of mast cells, lack of hair pigmentation, and sterility. Although the phenotypic expression of these two mutations is very similar, underlying mechanisms are quite different. The depletion of erythrocytes, mast cells and melanocytes in W/Wv mice is attributed to a defect in their precursor cells. In fact, the transplantation of bone marrow cells from congenic +/+ mice normalizes the number of erythrocytes and mast cells in the W/Wv mice. The donor origin of erythrocytes and mast cells was confirmed by using genetic markers. In contrast, the depletion of erythrocytes, mast cells and melanocytes in the Sl/Sld mice is due to a defect of microenvironment in which precursor cells differentiate into erythrocytes, mast cells and melanocytes. Although the sterility of both W/Wv and Sl/Sld mice is attributed to the depletion of germ cells, the mechanisms of germ-cell depletion have not been clarified. Since phenotypes of W/Wv and Sl/Sld mice seem to result from defects in cell-to-cell interactions, and since cell-to-cell interactions seem to play important roles for development of cancer, the author introduced these mutant mice as tools for cancer research.

Animals↗

Intraclonal conversion from papilloma to carcinoma in the skin of Pgk-1a/Pgk-1b mice treated by a complete carcinogenesis process or by an initiation-promotion regimen.

Skin tumors were produced by either a complete carcinogenesis process or an initiation-promotion regimen in C57BL/6 X C3H/HeHa F1-Pgk-1b/Pgk-1a mice which carried X-chromosome inactivation mosaicism for the phosphoglycerate kinase gene. In the complete carcinogenesis process, 200 nmol of 7,12-dimethylbenz(a)anthracene were applied once weekly; in the initiation-promotion regimen, a single application of 200 nmol of 7,12-dimethylbenz(a)anthracene was followed by twice weekly applications of 17 nmol of 12-O-tetradecanoylphorbol-13-acetate. Most papillomas produced by either procedure contained only one type of phosphoglycerate kinase, suggesting the monoclonal origin of papillomas. When the carcinoma developed at the same place where the papilloma was observed, the phosphoglycerate kinase type of most carcinomas was consistent with that of the original papillomas. This suggests that the malignant tumor develops as a result of the intraclonal conversion from the benign tumor.

9,10-Dimethyl-1,2-benzanthracene↗

Presence of colony-promoting activity-responsive cells as a separate compartment of granulocytic cell lineage in mice.

A population of cells that responds to colony-enhancing factor has been reported to constitute the most immature subpopulation in the compartment of granulocyte/macrophage progenitors (GM-CFC). A similar colony-promoting activity (CPA) was found in the supernatant of long-term cultures of murine bone marrow cells. Here, some characteristics of the cells responsive to CPA were studied. The CPA-responsive cells in the spleen and bone marrow of W/WV mice were as numerous as in +/+ litter-mates. The concentration of CPA-responsive cells was independent of those of other cell populations, namely pluripotent stem cells (CFU-S), pluripotent precursor cells in vitro and GM-CFC in the spleen and bone marrow. Seeding efficiency in the spleen of irradiated mice and the cell-cycle state of CPA-responsive cells also differed from those of CFU-S and GM-CFC. Accordingly, the target of CPA appears to constitute a separate compartment in the progenitor populations of granulocytic lineage.

Animals↗

Favorable effect of dimethyl sulfoxide on secondary amyloidosis in juvenile rheumatoid arthritis.

A girl with secondary amyloidosis as a complication of juvenile rheumatoid arthritis was administered dimethyl sulfoxide by topical application to the skin. Her gastrointestinal symptoms and massive proteinuria improved. Decreased left ventricular function and creatinine clearance also improved remarkably. The favorable effect of dimethyl sulfoxide in this single patient deserves further study in a controlled trial.

Adolescent↗

Growth-stimulative effect of estrogen on androgen-dependent Shionogi carcinoma 115.

The stimulative effect of 17 beta-estradiol on the growth of androgen-dependent Shionogi carcinoma 115 and estrogen receptor in the tumor were studied. The incorporation of 17 beta-[3H]estradiol following a single injection of 17 beta-[3H]estradiol into tumor-bearing animals was 5- to 20-fold higher in the tumor than in the spleen and blood. Scatchard plot analyses showed that the tumor cytosol possessed a 17 beta-estradiol-binding site having a high affinity for 17 beta-estradiol [Kd 1.1 +/- 0.1 nM (S.E.)]. Competition experiments demonstrated that the 17 beta-estradiol binding was specific only for estrogenic compounds. Using sedimentation coefficient obtained by high-salt sucrose gradient (4.0S) and Stokes radius obtained by gel chromatography on Sephadex G-200 (46 A), the molecular weight of 17 beta-estradiol-binding component in the tumor cytosol was estimated to be 76,400. In castrated DS mice, a slight but significant increase in growth of s.c. grafted tumors was found by daily s.c. injections of either 17 beta-estradiol or 10 micrograms per mouse of testosterone propionate. Growth of the tumor maintained by 10 micrograms of testosterone propionate was augmented markedly by the addition of 4 micrograms of 17 beta-estradiol, and the growth approached the level induced by 100 micrograms of testosterone propionate. Simultaneous injections of bromocryptine inhibited an increase in 17 beta-estradiol-induced prolactin secretion but had no effect on the 17 beta-estradiol-enhanced tumor growth. These results demonstrate for the first time the stimulative effect of estrogen on the growth of androgen-dependent Shionogi carcinoma 115. The tumor contains typical estrogen receptor, which might be able to transmit estrogen signal to tumor cell nuclei with regard to tumor growth.

Androgens↗

Radiosensitivity of mouse seminal vesicle cells which show proliferative response to androgen and estrogen.

Injections of either androgen or estrogen have been shown to induce proliferation of epithelial cells in the seminal vesicle of castrated mice. Uptake of 5-[125I]iodo-2'-deoxyuridine [( 125I]IdUrd) by the whole seminal vesicle was used as an index for cell proliferation. Although uptake of [125I]IdUrd induced by androgen was about four times as great as that induced by estrogen, both values decreased with a similar pattern after irradiation. Uptake of [125I]IdUrd showed a dose-dependent decrease up to 1000 rad; the values remained unchanged until 4000 rad. Uptake of [125I]IdUrd by the radiosensitive cell population was calculated by subtracting [125I]IdUrd uptake attributable to the radioresistant cell population from total [125I]IdUrd uptake. Androgen- and estrogen-responsive cells were equally sensitive to irradiation. Recovery of androgen-responsive cells from radiation-induced decrease was examined with or without androgen stimulation. Although recovery occurred without androgen, it was significantly enhanced by androgen stimulation following irradiation. Irradiation seems useful for investigation of kinetic characteristics of epithelial stem cells in the seminal vesicle of mice.

Androgens↗