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Biomedical subjects

M Kosaka

Publications and source records attributed to M Kosaka.

At least 19 recordsLinked to original sources

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

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

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

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

[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

[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

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

[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

[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

[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

[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

Reversible effects of sodium butyrate on the differentiation of F9 embryonal carcinoma cells.

We have studied effects of sodium butyrate on embryonal carcinoma F9 cell differentiation. In the presence of sodium butyrate, F9 cells underwent rapid and drastic morphological changes and expressed marked increases in mRNA levels of various differentiation markers. When sodium butyrate was removed from the cultures, all the examined phenotypes of F9 cell differentiation rapidly reverted to the characteristics of undifferentiated stem cells. However, under the same conditions, when cycloheximide or actinomycin D was added to the cultures, such phenotypic reversion was not observed, but high mRNA levels of the differentiation markers as well as altered cell morphology were retained. These results indicated that the effects of sodium butyrate on induction of teratocarcinoma cell differentiation were reversible and that de novo syntheses of some mRNA(s) and protein(s) were necessary for the reversion of differentiated cells to stem cells.

Animals

Treatment of myelodysplastic syndromes with orally administered 1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate.

1-beta-D-Arabinofuranosylcytosine-5'-stearylphosphate (fosteabine) was administered orally to patients with myelodysplastic syndromes (MDS); refractory anemia with excess of blasts (RAEB), RAEB in transformation, acute leukemia derived from RAEB and chronic myelomonocytic leukemia, in an early phase II study in a multi-institutional study. Among 62 evaluable patients, 2 patients achieved a complete remission, 6 a good response and 8 partial response by daily oral administration of 100-200 mg of fosteabine. The overall response rate was 25.8%. The response rates were almost the same among the four subtypes of MDS. Responses were reached 2-23 weeks (median, 8 weeks) after the start of therapy and continued for 3-50 weeks (median, 10 weeks). Major side effects were myelosuppression and gastrointestinal toxicities. In spite of the disadvantages, such as unpredictable absorption, this newly developed orally administrable cytarabine analogue will be a useful drug in the treatment of MDS.

Adult

[Assessment of occupational exposure to p-tert-butylphenol in synthetic resin factories].

Two cases of occupational vitiligo were observed in a resin factory where p-tert-butylphenol (PTBP) has been used as a starting material or an intermediate of synthetic resin. In this resin factory (A shop) and another resin factory (B shop), occupational exposure to PTBP was assessed in workers charging this chemical into the reaction vessel by means of a gas-chromatographic measurement of the environmental PTBP concentration and their urinary PTBP excretion. Assessment in A shop was made after the working condition was partly improved. Geometrical mean values of 8 h-time-weighted-average (8 h-TWA) of PTBP in air near the charger's breathing zone (personal air) were 0.215 mg/m3 in A shop and 2.12 mg/m3 in B shop. Continuous measurements of PTBP concentration in some stationary air of the shops showed that the maximum environmental PTBP values occurred during charging. Urinary PTBP concentration was increased to the maximum values 2 to 4 h after charging of this chemical and then rapidly decreased. Biological half-lives of urinary PTBP were estimated as 4.4 h in A shop and 4.8 h in B shop. The urinary PTBP concentration was correlated to 8 h-TWA of PTBP in the personal air. In particular, PTBP in urine collected at the end of the shift showed an excellent correlation to PTBP in the personal air (r = 0.84, n = 9, A shop; r = 0.88, n = 11, B shop). These results indicate that biological monitoring using urinary PTBP concentration is a suitable means of assessing exposure to this alkylphenol and the urine collected at the end of shift is the best sample for monitoring. In addition, the present environmental and urinary PTBP values were compared with those described in the literature and the relation of the occupational vitiligo with PTBP exposure is discussed.

Chemical Industry

Rotatostereoradiography: a new radiodiagnostic method--development of a new three-dimensional radiodiagnostic device and evaluation in neurosurgical clinics.

The rotatostereoradiographic device uses an x-ray tube coupled with an image intensifier rotating through a 180 degree arc in 2.25 seconds. The rapidly rotating x-ray tube allows 180 degree-arc angiograms to be obtained with a single injection of contrast medium. Subtracted fluoroscopic angiograms can be viewed immediately after injection of the contrast medium with digital recording. These three-dimensional images are displayed on side-by-side monitors stereoscopically. The mortality and morbidity of subarachnoid hemorrhage can only be greatly reduced by surgical treatment of unruptured aneurysms and arteriovenous malformations detected by a wide survey of subarachnoid hemorrhage. Such a wide survey would be possible utilizing intra-arterial digital subtraction angiography via the ascending aorta and this new three-dimensional radiodiagnostic method. A fluoroscopic device must be used to allow easier manipulation of the catheter from the axillary or brachial artery.

Adult

[A study of dental status and its contributing factors in mentally retarded persons institutionalized in welfare facilities].

Two hundred and forty-one mentally retarded persons, institutionalized in three private welfare facilities in Oita Prefecture, were assessed for dental status and tooth brushing ability. Information on their life style was also obtained by a questionnaire completed by their supervisors in the facilities. 1) Dental status of mentally retarded subjects was found to be inferior compared to the general Japanese population studied in the survey of dental disease in 1987 by the Ministry of Health and Welfare. Inferior dental status was characterized by a low score for filled teeth and a high score for missing teeth. 2) Both low tooth brushing ability and low intelligence quotient were associated with their poor dental status. 3) Discrepancy between supervisor assessment of tooth brushing ability and actual ability was observed. 4) Periodontitis was observed in young epileptics taking antiepileptic medication at a high rate. However there was no association between the taking of antiepileptic medication and missing teeth score. These results indicate a necessity for more active dental services including the teaching of tooth brushing and early treatment by dentists and supervisors.

Adolescent

Effects of erythroid differentiation factor (EDF) on proliferation and differentiation of human hematopoietic progenitors.

The effects of erythroid differentiation factor (EDF) on normal human hematopoietic progenitor cells were examined by bone marrow colony assay. Addition of EDF to the erythroid colony assay system enhanced erythroid burst-forming unit (BFU-E)-derived colony formation, and this effect disappeared on removal of adherent cells. Conditioned medium of EDF-treated monocytes also enhanced BFU-E colony formation, whereas conditioned medium of EDF-treated T cells did not. In contrast, EDF inhibited erythroid colony-forming unit (CFU-E) colony formation dose-dependently, although it had no effect on colony formation by myeloid cells. These data show that EDF has a specific effect on human hematopoietic progenitors of the erythroid lineage. The results also indicate that EDF enhanced BFU-E colony formation by stimulating adherent cells to produce factors with burst-promoting activity (BPA), but suppressed CFU-E colony formation by promoting differentiation of these cells.

Activins