Biomedical subjects

M Kosaka

Publications and source records attributed to M Kosaka.

At least 109 records · Page 6Linked to original sources

PubMed1993

Activin A suppresses proliferation of interleukin-3-responsive granulocyte-macrophage colony-forming progenitors and stimulates proliferation and differentiation of interleukin-3-responsive erythroid burst-forming progenitors in the peripheral blood.

We examined the effects of activin A on the proliferation and differentiation of immature hematopoietic progenitors prepared from peripheral blood (PB) using methylcellulose and liquid-suspension culture. In a kinetic analysis, colony formation by PB granulocyte-macrophage colony-forming unit (CFU-GM) was delayed in a dose-dependent manner by the addition of activin A only when stimulated with interleukin-3 (IL-3), but not when stimulated with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), or stem cell factor (SCF) plus G-CSF. DNA-synthesizing CFU-GM was increased by IL-3, but this effect was abolished by activin A. In contrast, PB erythroid burst-forming unit (BFU-E) was accelerated by the addition of activin A only when exposed to IL-3 plus erythropoietin (Epo), but not when exposed to Epo or Epo plus SCF. DNA-synthesizing BFU-E was increased by IL-3 and activin A, alone and additively in combination. In a mixed culture of myeloid and erythroid progenitors, activin A increased the numbers of BFU-E and CFU-Mix colonies at concentrations of 1 and 10 ng/mL and decreased the number of CFU-GM colonies in a dose-dependent manner. However, in a liquid-suspension culture of erythroid progenitors, activin A decreased total cell count and the percentage of hemoglobin-containing cells only when cells were exposed to IL-3 plus Epo. These results indicate that activin A suppresses the proliferation of IL-3-responsive CFU-GM progenitors and stimulates the proliferation and differentiation of IL-3-responsive BFU-E progenitors, and suggest that activin A acts as a commitment factor of immature hematopoietic progenitors for erythroid differentiation.

Activins↗

PubMed1993

Suppression of tumorigenicity in temperature-sensitive mutants of embryonal carcinoma cells by induction of cell differentiation at non-permissive temperature.

The temperature-sensitive (ts) mutants of cell differentiation derived from the mouse teratocarcinoma cell line F9, when exposed to non-permissive temperature, undergo stem-cell differentiation concomitant with a transient retardation of cell-cycle progression. By incubating these mutant strains at non-permissive temperature, we were able to study the relationship between cell differentiation and tumorigenicity. Upon exposure to non-permissive temperature, the mutant cells undergo extensive differentiation and lose their ability to initiate tumors in vivo, but retain their in vitro proliferative potential. Our data suggest that the loss of tumorigenicity is not caused by altered proliferative potential, but rather by cell differentiation. We therefore suggest that the loss of proliferative potential and the onset of cell differentiation in teratocarcinoma F9 cells are 2 independent events which can be genetically dissected, and that there is (a) crucial step(s) in the differentiation pathway at which these ts mutant cells lose their tumorigenicity.

Alkaline Phosphatase↗

PubMed1993

Changes in Hox1.6, c-jun, and Oct-3 gene expressions are associated with teratocarcinoma F9 cell differentiation in three different ways of induction.

To obtain information on the mechanism of teratocarcinoma cell differentiation, the expression of genes having a specific role in gene regulation was examined using three different methods of inducing differentiation: drug treatments with retinoic acid (RA) and sodium butyrate, and a genetic approach using ts mutants. The RAR-beta and MK genes were induced specifically by RA treatment, which indicates that these two genes are solely RA responsive. By contrast, a change in c-jun, Hox1.6, and Oct-3 gene expression was observed in all three methods of F9 cell differentiation. These findings suggest that these three genes, whether down-or up-regulated, play an important and key role during teratocarcinoma cell differentiation.

Animals↗

PubMed1993

The induction of jun genes during the reversible changes induced with sodium butyrate on the differentiation of F9 cells.

Sodium butyrate (NaB) induces the phenotypic changes and differentiation markers in embryonal carcinoma F9 cells (Kosaka et al., Exp. Cell Res. 192, 46, 1991). However, the effects are rapid and reversible and different from those induced with retinoic acid (RA). We examined the expression of jun genes during differentiation induced with NaB and compared it with that of RA induction. Although c-jun expression was induced with RA, rapid and predominant induction of junB expression was specifically observed with NaB, which is regulated by both transcriptional and post-transcriptional mechanisms. These results suggest that the mechanism of differentiation induced with NaB differs from that of RA; the former may be mediated by the junB gene and the latter by c-jun.

Animals↗

PubMed1993

[Correlates associated with desire by caregivers to transfer elderly from home care to institutions].

A questionnaire survey was performed on 183 caregivers of elderly listed on a roster for utilization of day service or short stay service in nursing homes in order to elucidate the following; actual conditions of care at home; percentage desiring to transfer to institutionalized care in hospital, nursing homes and geriatric intermediate care facilities, reasons for continuing care at home; and factors relating to desire for transferring to institutionalized care. Results are as follows; Major items of troubles expressed by caregivers were; "high stress and mental fatigue" (55.7%), "unable to freely go out from home" (54.1%), and "loss of personal time" (46.4%), "heavy burden from food preparation, body discharge disposal and bathing of the elderly" (40.0%). 41.5% of caregivers expressed desire for transfer of elderly to institutional care. Of those who desire transfer to hospital care, 21.1% were continuing home care due to non-availability of appropriate hospital, 44.7% because of inability to meet the demand for assisting in the nursing of the elderly during hospitalization, 26.3% because they were turned away by the hospital. Where transfer to nursing homes was desired but not realized, 20.0% reported lack of nursing homes nearby. Where desire was for transfer to geriatric intermediate care facilities, lack of such facilities was reported by 37.5%. Analysis was performed to elucidate the factors that determine whether a caregiver would demand a transfer to an institutions. Main factors were age of caregiver, family relationships, family finance, the frequency of occurrence of problems with home care, and whether or not they themselves would accept institutional care when that time came. Main factors associated with the cared elderly desiring institutional care were eating ability, speaking ability and mental status score. Analysis of the problems related to desire to transfer to institutional care showed their factors such as whether or not there was room available for home care, financial family burden, perceived interference with personal time by the home care, and perception of appropriateness of coping with symptom change of elderly, all have significant relationships.

Adult↗

PubMed1993

[Exposure to DMTP by sprayers and the urinary excretion of metabolites].

Exposure in vinyl hothouses to DMTP (0,0-dimethyl-s-(2-methoxy-1,3,4-thiadiazol-5(4H)-onyl-(4)-m ethyl)- dithiophosphate) was studied in 5 spray-operators and one assistant worker. To determine the level of exposure to DMTP, concentrations in the atmosphere, concentration in atmosphere near the operators breathing zone, skin levels from penetration through the operator's clothing, and urinary excretion of metabolites of DMTP (2,3-dihydro-5-methoxy-3-methyl-sulphonyl methyl-1,3,4-thiadiazol-2-one and 2,3-dihydro-5-methoxy-3-methyl-sulphinyl methyl-1,3,4-thiadiazol-2-one) were measured. The results were as follows; 1. DMTP concentrations in the atmosphere were 10.0-18.0 micrograms/m3, and concentrations in the atmosphere near the operators breathing zone were 5.4-33.6 micrograms/m3 during spraying. 2. Metabolites of DMTP were detected in all sprayers. Levels were 1.5 to 31.6 micrograms/day for the sulphonyl-metabolite. But it was not detected in the assistant sprayer. 3. Urinary concentrations of the DMTP metabolite were maximum 15-20 h after spraying. 4. Amount of DMTP adherent on the skin was estimated to be 0.4 to 71.3 micrograms for spray-operators. Variations resulted from differences in condition of protective clothing. 5. DMTP appeared to be absorbed not only through the respiratory system, but also through the skin.

Female↗

PubMed1993

Serum concentration and localization in tumor cells of proteasomes in patients with hematologic malignancy and their pathophysiologic significance.

The pathophysiologic significance of proteasomes in hematologic malignancies was examined by comparison of the proteasome levels in normal subjects and patients with benign liver diseases. The serum proteasome level measured by enzyme-linked immunosorbent assay was found to be positively correlated with the tumor burden of the patients with hematologic malignancies such as acute leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, and myeloma. Immunohistochemical staining showed that proteasomes were strongly expressed in these tumor cells, especially in the nuclei. These data suggest that the elevated levels of serum proteasomes in these patients are derived from tumor cells, reflect the tumor burden, and so provide prognostic information. However, in patients with benign liver diseases, serum proteasome levels correlated with serum alanine aminotransferase activities, suggesting that in hematologic malignancies associated with liver injury some of the serum proteasomes may originate from hepatocytes. The marked production of proteasomes by malignant blood cells may be involved in transformation and proliferation of these cells.

Autoimmune Diseases↗

PubMed1992

The existence of activin A/erythroid differentiation factor and its inhibitor in human serum: comparison of normal and chronic renal failure sera.

Activin A/EDF, initially found as a differentiation inducer of murine Friend erythroleukemia, also has a stimulatory effect on erythropoiesis in vitro and in vivo. Here we proved activin A/EDF activity in human serum. The activin A/EDF level in 18 normal human serum samples was measured by a specific bioassay and was found to be 8.3 +/- 4.6 ng/ml, indicating that there exists sufficient activity to affect erythropoiesis in normal serum. In contrast, activin A/EDF activity was reduced in the chronic renal failure patients and 23/26 serum samples examined showed levels below 1.2 ng/ml. Further analysis using HPLC revealed that chronic renal failure serum actually contained as much activin A/EDF as normal serum, and that the difference between normal and patient serum existed in the content of a specific inhibitor of activin A/EDF. This observation suggests the possibility that the inhibitor is participating in the regulation of activin A/EDF activity in vivo in chronic renal failure patients and also the possibility of activin A/EDF could be utilized in the therapy of the anemia of such patients.

Activins↗

PubMed1992

Teratocarcinoma F9 cells induced to differentiate with sodium butyrate produce both tissue-type and urokinase-type plasminogen activators.

Sodium butyrate (NaB) can induce teratocarcinoma cell differentiation as retinoic acid (RA). However, the function of these two agents seems to be a little different [Kosaka et al., Exp Cell Res, 192:46-51, 1991]. F9 cells treated with NaB synthesize both tissue-type (tPA) and urokinase-type (uPA) plasminogen activator, though RA induces only tPA production. Urokinase-type PA is demonstrated to exist in association with membrane and to localize its activity to the close environment of the cell surface. This may cause the specific cell morphology and characteristics of differentiated F9 cells induced with NaB.

Animals↗

PubMed1992

Expression of c-kit protooncogene is stimulated by cAMP in differentiated F9 mouse teratocarcinoma cells.

Protooncogene c-kit, a transmembrane tyrosine kinase receptor, was recently shown to map to the dominant white spotting locus (W) of the mouse. W mutations affect melanogenesis, gametogenesis, and hematopoiesis during development and in adult life. In order to determine the regulation of the c-kit gene in cell differentiation, we investigated its expression during the differentiation of F9 cells. Undifferentiated F9 cells and F9 cells treated with retinoic acid (RA) alone or dbcAMP alone showed little expression of c-kit mRNA if any. The subsequent addition of dbcAMP to F9 cells treated with RA markedly increased the expression of c-kit mRNA. Furthermore, the effect of dbcAMP on c-kit expression is reversible. In differentiated cells treated with RA, c-kit gene expression is induced by agents such as forskolin or theophylline, which are known to elevate cellular cAMP level. These results indicate that the expression of the c-kit gene is regulated by the level of intracellular cAMP in differentiated F9 cells induced by RA.

Animals↗

PubMed1992

Primary adult T-cell lymphoma of the breast.

A case of primary adult T-cell lymphoma (ATL) of the breast is described. A 69-year-old woman presented with a painless, rapidly growing lump in her left breast. Staging procedures demonstrated no sign of generalized disease. Following a Patey's mastectomy, 10 courses of adjuvant chemotherapy (CHOP) were successfully administered. The light microscopic, immunohistochemical and molecular genetic analyses of the surgical specimen revealed a primary ATL. Seropositive mothers who breast-feed their children may facilitate the accumulation of T cells carrying HTLV-I in their breasts and thereby increase their risks of developing breast ATL.

Aged↗

PubMed1992

[Occupational skin hazards in hairdressers and their etiologic factors--results of mass health examination at health centers].

From 1986 to '88, mass health examinations for skin disorders among hairdressers were performed in 4 Health Centers in Osaka Prefecture. Among 306 female hairdressers examined, the prevalence of skin lesions was 49.0%, consisting of skin lesions of hands and arms alone 22.9%, nail lesion alone 13.7%, and both 12.4%. Characteristic features of the skin lesions were dryness, roughness, thickening of epidermis, redness, hyperkeratinization, scales, desquamation, etc. In the case of nails, thinning, onycholysis, onychoschisis, pitting, transverse grooves and onychorexis were characteristic. The relationship between prevalence of skin disorders and site of lesions to history or category of work was studied. For the prevention of these skin hazards, improved chemicals, equipment, and hygienic education are necessary. Periodical health-checks including participation by a dermatologist, and health supervision should be continued with cooperation between Health Centers and beauty salons, because these businesses are principally small-size enterprises.

Adolescent↗

PubMed1992

[Clinical significance of serum erythropoietin levels in patients with multiple myeloma].

Serum erythropoietin (Epo) levels were measured in 53 patients with multiple myeloma (MM), 49 normal subjects and 53 patients with some hematological diseases including aplastic anemia (AA), iron deficiency anemia, etc. to study the significance of erythropoietin in anemia of MM. The serum Epo level was 72.0 +/- 94.4 mIU/ml (mean +/- SD) in MM patients, which was significantly higher than in normal subjects (24.1 +/- 6.1 mIU/ml), but lower than in AA patients (7069.9 +/- 9406 mIU/ml). A significant inverse correlation was found between the hemoglobin (Hb) levels and the logarithmic values of serum Epo levels (r = -0.543, p < 0.05) in MM patients. This inverse correlation was stronger (r = -0.636, p < 0.05) in MM patients without renal dysfunction than in whole MM patients, while no correlation was observed in MM patients with renal dysfunction. These results indicate that MM patients with renal dysfunction have a low ability to synthesize Epo and that the supplemental therapy of recombinant Epo is effective to improve their anemia. In addition, the circadian rhythm of serum Epo level was lower in the morning than in the afternoon in both MM patients and normal controls. Serum Epo levels after chemotherapy in MM patients were elevated temporarily and then decreased in spite of no change of blood Hb level.

Adult↗

PubMed1992

c-myc and p53 gene expression in the differentiation of temperature-sensitive mutants of teratocarcinoma F9 cells.

We have previously reported the isolation of several temperature-sensitive (ts) mutants of F9 cells. Further investigations showed that some mutants were induced to differentiate at non-permissive temperature of cell growth, accompanied by changes in the expression of various genes, whereas others were not. During the differentiation induced by shifting up to the non-permissive temperature, a rapid and transient decrease in both c-myc and p53 mRNA levels and rapid induction of c-jun mRNA were observed. These changes were specific in differentiation-inducible mutants and were not observed in a non-inducible mutant. In both types of mutants, the level of c-myc mRNA decreased in association with growth retardation at the non-permissive temperature. The p53 mRNA, however, showed specific increase in the differentiation-inducible ts mutants. These observations suggest distinct roles for p53 and c-myc from proliferation to differentiation in teratocarcinoma stem cells.

Animals↗

PubMed1992

[Malignant histiocytosis with T cell receptor and immunoglobulin gene rearrangements].

A case of malignant histiocytosis with rearrangements of both T-cell receptor and immunoglobulin genes. The patient was a 69 year-old woman suffering from high fever, which was unresponsive to the administration of various antibiotics and steroids for more than two weeks. Laboratory findings on admission revealed disseminated intravascular coagulopathy and liver dysfunction. The bone marrow examination showed an increased number of giant cells. Some of the giant cells had phagocytosis of various blood cells and were cytochemically stained with non-specific esterase, but not with myeloperoxidase and PAS. Immunohistochemical study revealed that alpha 1-antitrypsin alpha 1-antichymotrypsin, lysozyme and CD15 were all detected in the cytoplasm of some giant cells while CD30 was not detected. Of interest was the rearrangements of the T-cell receptor, Ig heavy chain and kappa chain genes on bone marrow mononuclear cells demonstrated by Southern blot analysis.

Aged↗

PubMed1992

[Health effects and personal protection in pest control workers using organophosphorus insecticides].

One hundred and sixteen pest control workers (16 termite control workers (Sprayer I), 46 cockroach or fly-control workers (Sprayer II) and 56 both termite and cockroach or fly-control workers (Sprayer III)) were surveyed by a questionnaire and health examinations. Variety and quantity of pesticide used, personal usage of protective devices (respirator, gloves, work clothes, under wear), and conditions related to bathing were studied by a questionnaire. Relationships between protective devices and blood cholinesterase activity (ChE) were also analyzed. Significant findings were as follows: Most of the pest control operators wore gum gloves and gas masks when involved in termite control. However in the case of cockroach or fly-control, 38% did not wear gloves, and for respiratory protection 44% wore gas masks while 25% of them did not even use any form of respirators. In spite of having better protective practices than sprayers II and III, sprayer I showed significantly lower plasma ChE activity than both sprayer II and III. Plasma ChE activity in sprayers who put on simple respirators tended to be lower than those using gas masks. Plasma ChE activity was also significantly lower in those workers who had less frequent changes of work clothes compared to those with more frequent.

Adult↗

PubMed1992

[A study on work and daily life factors affecting the health of taxi drivers].

In order to elucidate factors affecting taxi drivers health, a questionnaire survey was performed on 5523 taxi drivers and health examinations were conducted on 311 taxi drivers from among them. Analysis by a method of multivariate analysis called Quantification II was performed with dependent variables being blood pressure, the number of subjective symptoms and fatigue on rising, and independent variables being work and daily life conditions. The major results of this survey were as follows: 1) A tendency for hypertension risk to increase with degree of obesity, and both employment as a taxi driver for 1-4 years and over twenty years of taxi driving were positively associated with increase in risk for hypertension. 2) Common factors to all types of work shifts which were related to an increase in the number of subjective symptoms were irregularity of meals, insufficient rest on off days, large number of years engagement at taxi driving, frequent frightening experiences while driving and comparatively short driving distance in one shift. 3) Common factors to all types of work shifts that were connected with fatigue at the time of rising were insufficient rest on off days and long years engagement in taxi driving.

Activities of Daily Living↗

PubMed1991

[Effect of growth hormone on immune function in normal and hypophysectomised rats].

The effect of growth hormone (GH) on immune function was studied using normal and hypophysectomised male Wistar rats. Hypophysectomy was performed by the auditory approach at 4 weeks of age. Normal and hypophysectomised rats were treated with saline or 0.4IU/body GH daily during 7 to 11 weeks of age. Histological features of the thymus and spleen and immunological parameters including blood cell counts, lymphocyte subsets, serum immunoglobulin levels, splenic natural killer activity, and mitogen-induced splenic lymphocyte proliferation were examined in the rats at 11 weeks of age. In hypophysectomised rats, the counts of peripheral white blood cells (5,513 +/- 813/microliters), lymphocytes (4,838 +/- 737/microliters), Th/i cells (2,237 +/- 329/microliters), and B cells (1,400 +/- 509/microliters), Th/i/Ts/c ratio (1.78 +/- 0.27), splenic T cell subsets (pan T: 51.0 +/- 4.3%, Th/i: 31.6 +/- 3.0%, Ts/c: 23.9 +/- 2.7%), and serum IgG level (2,148 +/- 470mg/l) were significantly decreased as compared with normal rats. Natural killer activity (17.8 +/- 4.6%) and mitogen-induced proliferation of T cells (Con A: 47.1 +/- 15.7, PHA: 51.6 +/- 12.5) were also suppressed. Hypoplasia of the thymus and spleen was observed in parallel to retarded growth of the rats. In contrast, GH supplement to the hypophysectomised rats resulted in increases in growth and lymphoid tissue, and the restoration of the counts of peripheral white blood cells (6,850 +/- 840/microliters), lymphocytes (6,211 +/- 731/microliters), Th/i cells (2,909 +/- 304/microliters), and B cells (1,947 +/- 402/microliters), Th/i/Ts/c ratio (2.04 +/- 0.34), serum IgG level (3,414 +/- 1,326mg/l), and natural killer activity (25.7 +/- 4.7%). However, splenic lymphocyte subsets and mitogen-induced proliferation of T cells were not recovered by GH treatment for 4 weeks. GH administered to normal rats increased serum IgG level (4,982 +/- 1,496mg/l) but did not affect other immunological parameters. These results indicate that humoral and cell-mediated immune function are impaired in hypophysectomised rats, but GH supplement administered to them restored most of the impaired immune function, suggesting that GH plays an important role in the development of immune function.

Animals↗