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Biomedical subjects

M Kosaka

Publications and source records attributed to M Kosaka.

At least 145 records · Page 8Linked to original sources
PubMed1989

In vivo treatment with erythroid differentiation factor (EDF/activin A) increases erythroid precursors (CFU-E and BFU-E) in mice.

The in vivo effect of human EDF on erythroid precursors (CFU-E and BFU-E) was investigated in normal and bled mice. In anemic (bled) mice, EDF treatment led to significant dose-dependent rises in the CFU-E and BFU-E levels of bone marrow. An elevation in the level of CFU-E was also seen in the spleen. In normal mice, a significant elevation in the level of bone marrow BFU-E was observed. Thus, EDF has an effect on erythropoiesis in anemic and normal mice in vivo.

Activins↗
PubMed1989

Isolation of mutants showing temperature-sensitive cell growth from embryonal carcinoma cells: control of stem cell differentiation by incubation temperatures.

Embryonal carcinoma(EC) cells, the undifferentiated stem cells of teratocarcinomas, have many properties in common with pluripotent embryonic cells, and thus provide an excellent system for studying the early events involved in embryonic development and stem cell differentiation. We have isolated three novel mutants with temperature-sensitive(ts) cell growth that were able to differentiate at a non-permissive temperature for cell growth. These mutations affect the progression of the cell cycle, leading to the transient accumulation of cells in a specific phase, the S phase, of the cell cycle, which is likely to be the primary cause of stem cell differentiation of EC cells at non-permissive temperature. Isolation of these mutants strongly supports the notion that there is a close association between the inhibition of DNA synthesis and EC cell differentiation.

Animals↗
PubMed1989

Inhibition of DNA synthesis causes stem cell differentiation: induction of teratocarcinoma F9 cell differentiation with nucleoside analogues of DNA-synthesis inhibitors and their inducing abilities counterbalanced specifically by normal nucleosides.

Nucleoside analogues inhibiting DNA synthesis can induce cell differentiation in teratocarcinoma cells. We have examined how their abilities to induce F9 cell differentiation were specifically counterbalanced by their corresponding normal nucleosides. We have also compared the differentiation inducing ability of the wild type F9 cells with that of its thymidine kinase-less mutant using plasminogen activator, as a differentiation marker, which is expressed at a very early stage of endodermal cell differentiation and can be assayed quantitatively. The results obtained were clearly explainable by the conventionally accepted action mechanisms of the nucleoside analogues, thus strongly suggesting that their abilities to induce cell differentiation were direct consequences of the inhibition of DNA synthesis; thus this confirms the notion that a close association exists between the inhibition of DNA synthesis and the induction of teratocarcinoma stem cell differentiation.

Animals↗
PubMed1989

Cell-mediated suppression of human hematopoiesis: evaluation by limiting-dilution analysis of hematopoietic progenitors.

We have used limiting-dilution clonal analysis (LDA) in microwells to study the inhibitory effects of T lymphocytes (T-cells) or natural killer (NK) cells on human marrow progenitor cell growth. In four subjects with normal hematopoiesis, the growth of progenitors showed single-hit kinetics both before and after T-cell removal, indicating that, in the presence of colony-stimulating activity, T-cell have no effect on progenitor growth. In a patient with marrow hypoplasia associated with thymoma, hypogammaglobulinemia, and an increased number of suppressor T-cells (Good's syndrome), the progenitor growth deviated from linearity, demonstrating the presence of cells with suppressor activity. After T-cells were removed from this sample, the progenitor growth showed single-hit kinetics. The suppressive action of E-rosette-positive cells with NK or cytotoxic activities was also suggested in a patient with severe combined immune deficiency and in a patient with T gamma lymphocytosis. Poor progenitor-cell growth in three other patients with aplastic anemia was not significantly altered by T-cell removal. Thus, LDA of human hematopoietic progenitors is useful for evaluating cell-mediated interactions affecting hematopoiesis. This method may facilitate elucidation of mechanisms of myelosuppression in clinical settings.

Anemia, Aplastic↗
PubMed1989

Urinary metabolite levels in workers handling p-tert-butylphenol as an index of personal exposure.

Occupational exposure to p-tert-butylphenol (PTBP) was studied in a workplace where workers were engaged in packing this alkylphenol in bags or transporting the bags by fork-lift. The geometrical mean of eight-hour-time-weighted-average (8 h-TWA) value for personal ambient PTBP level of the packers was 0.39 mg/m3 (n = 15), higher than that of the carriers (0.10 mg/m3, n = 5). Amounts of PTBP collected in the respirators used by the workers were in proportion to the 8 h-TWA values but lower than the estimated theoretical amounts; considerable amounts of PTBP were assumed to be absorbed through the respiratory tract. The urine excreted during the latter half of the shift showed the highest levels of PTBP (geometrical mean: packer, 5.07 micrograms/ml, n = 20; carrier, 3.03 micrograms/ml, n = 8). When the workers were away from the workplace, PTBP levels decreased; most was excreted within 24 h. Correlation between the urinary PTBP levels and 8 h-TWA values was significant (r = 0.46, n = 19, P less than 0.05), but its extent was weak. The total amounts of urinary PTBP excreted for 24 h after the start of the shift were two to three times higher than the estimated respiratory absorption of PTBP; PTBP was assumed to be absorbed not only through the respiratory tract but also through intact skin. It was concluded that the personal ambient PTBP level is not a suitable index for personal exposure, and biological monitoring via the PTBP level in the urine excreted at the end of the each shift is useful for the evaluation of personal exposure.

Air Pollutants, Occupational↗
PubMed1989

Tetramer Bence Jones protein in the immunoproliferative diseases. Angioimmunoblastic lymphadenopathy, primary amyloidosis, and multiple myeloma.

The authors report the clinical features and the results of immunochemical studies of patients with angioimmunoblastic lymphadenopathy, primary amyloidosis, and multiple myeloma, each of whom had in the serum and urine multiple forms of Bence Jones protein (BJP). The BJPs were isolated and purified and were shown by electrophoretic, gel filtration, and ultracentrifugal analyses to exist as tetramers and dimers. The components in two cases were kappa type and in one lambda type. The kappa tetramers consisted of two covalent dimers and the lambda tetramer two noncovalently bound dimers present in both serum and urine.

Aged↗
PubMed1989

Inhibition of fibrin monomer polymerization by Bence Jones protein in a patient with primary amyloidosis.

The mechanism of inhibition of fibrin monomer polymerization was studied in a patient with primary amyloidosis. Thrombin and reptilase times of the patient's purified fibrinogen (Fbg) were remarkably prolonged, and polymerization of the patient's fibrin monomer was disturbed. Fbg-Bence Jones protein (BJP) complex was demonstrated by immunoelectrophoresis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis on the patient's purified Fbg. The patient's BJP not only prolonged the thrombin time of normal Fbg but also inhibited the polymerization of normal fibrin monomer. These results suggested that in this patient fibrin monomer polymerization was inhibited by binding of BJP to Fbg.

Aged↗
PubMed1989

[Effects of propiverine hydrochloride and its metabolites on isolated guinea pig urinary bladder].

The effects of P-4 and its active metabolites in human blood and urine and the effects of 1-methyl-4-piperidyl diphenylpropoxyacetate N-oxide [P-4(N----O)], 1-methyl-4-piperidyl benzilate N-oxide [DPr-P-4(N----O)] and 1-methyl-4-piperidyl benzilate (DPr-P-4) on isolated guinea pig urinary bladder were investigated. At doses of 10(-6) or 10(-5) M, P-4 shifted the dose-response curve for acetylcholine (ACh) to the right, and at a dose of 10(-5) M, it also inhibited the maximum response of ACh. At doses of 10(-5) M or more, P-4(N----O) inhibited the maximum response of ACh. DPr-P-4(N----O) or DPr-P-4 shifted the dose-response curve for ACh to the right at doses of 10(-6)-10(-4) M or at doses of 10(-7)-10(-5) M. P-4 at doses of 10(-6) M or more inhibited the KCl (100 mM)-induced contraction in a dose-dependent manner, and its potency was quite equal to that of terodiline. The inhibitory effect of P-4(N----O), DPr-P-4(N----O) and DPr-P-4 in the KCl (100 mM)-induced contraction were weaker than that of P-4. P-4 and P-4(N----O) had a dose-dependent inhibitory effect on K+-induced 45Ca influx in isolated guinea-pig urinary bladder.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1989

[Urinary alkylphosphate levels as an index of exposure to organophosphorus insecticides in pest control operators].

In pest control operations, organophosphorus compounds (OP) have been sprayed as insecticides, blood cholinesterase (ChE) activities and urinary alkylphosphate levels were measured for both OP-sprayers (n = 102) and non-sprayers (n = 35) in pest control companies, and the relationship between the analytical results and spraying conditions was investigated. Plasma ChE activities of the OP-sprayers and of the non-sprayers, as well as blood cell ChE activities of the OP-sprayers, were significantly lower than those of employees of chemical factories who served as controls (n = 103). Urinary alkylphosphates were not detected in the controls at all but were detected in 83% of the sprayers and in 57% of the non-sprayer employees of pest control companies. A significant negative correlation (r = -0.34, n = 137, p less than 0.01) between the plasma ChE activities and urinary total alkylphosphate levels was observed in employees of pest control companies. In the case of the employees whose urinary total alkylphosphate levels were 0.1 mumol/g creatinine or more, the plasma ChE activities were 25% decreased compared to the control group. The OP-sprayers showed significantly higher urinary total alkylphosphate levels than the non-sprayers. The OP-sprayers were further divided into two groups. One was sprayers engaged in both cockroach- or fly-control and termite-control operations (sprayers I, n = 54) and the other was sprayers engaged in only cockroach- or fly-control operations (sprayer II, n = 48).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Relationship between exposure to chlorpyrifos and concentration of urinary alkylphosphates in termite control workers].

Chlorpyrifos (O, O-diethyl-3,5,6-trichloro-2-pyridinyl phosphorothioate; CP) has been used for insecticide to prevent infestation of termites. A study was made on occupational exposure to CP of termite control workers engaged in spraying this organophosphorus insecticide. Workers were engaged in two types of spraying; that is spraying CP under floor and spraying CP around house. All the under-floor sprayers wore respirators during spraying. CP levels in air near the breathing zone, contact amounts of CP with skin, and urinary alkylphosphates levels were higher in the under-floor sprayers than in the around-house sprayers. The personal ambient CP levels of the under-floor sprayers were 0.012 to 0.145 (8 h-TWA, mg/m3) lower than the threshold limit value (0.2 mg/m3) proposed by ACGIH. A maximum diethylphosphate (DEP) excretion was observed in the first urine collected the next day, while the highest diethylthiophosphate (DETP) was excreted in the last urine in the working day. In the excretion amount, DEP was higher than DETP. Amounts of CP collected in respirators used by the under-floor spraymen averaged 0.76 mg/respiratory comparable to their estimated theoretical value of 0.69 mg/m3. The urinary total alkylphosphate (DEP + DETP) level was more closely correlated with the contact amount of CP with skin (r = 0.86) than with the personal ambient CP level (r = 0.05). These results indicate that 1) respiratory absorption of CP was prevented by the use of respirator; 2) the urinary alkylphosphates were mainly derived from the dermal absorption of CP; and 3) biological monitoring using urinary alkylphosphates levels is an useful index for CP exposure.

Chlorpyrifos↗
PubMed1989

[A case of Hodgkin's disease exhibiting erythrodermia probably due to allergic reaction to vinca alkaloids].

A 58-year-old man with Hodgkin's disease exhibited erythrodermia due to allergic reaction to vincristine sulfate (VCR) and vindesine sulfate (VDS). However, chemotherapy could be continued by changing VCR and VDS to etoposide without allergic symptom. Clinical observation strongly suggested that erythrodermia was due to the use of vinca alkaloids in this patient. Hematological and neurological side effects have been well known for VDS and VCR, but erythrodermia has not yet been reported as being caused by these agents. It is often difficult to differentiate drugs as a cause of an allergic reaction when several drugs are used together. Therefore, it is important to collect all the cases showing the effects of drugs.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Isolation and storage of peripheral blood hematopoietic stem cells for autotransplantation into children with cancer.

Peripheral blood stem cells (PBSC) were collected for autotransplantation by a total of 46 continuous-flow leukaphereses in 17 children with various types of cancer in whom the stem-cell pool had been expanded by chemotherapy. As the cells collected by leukapheresis were contaminated with many visible cell clumps, platelets, and erythrocytes, they were separated from the platelet-rich plasma (PRP) by slow-speed centrifugation and fractionated on a discontinuous gradient of Percoll. All the hematopoietic progenitors (CFU-GM, CFU-GEMM) in the starting samples were recovered at the interface of 40% and 60% Percoll solutions largely free of other cellular components and with a substantial reduction in volume. The separation and freezing procedures could be completed within three hours after obtaining cells by leukapheresis. After their fractionation and storage, these PBSC were shown to be able to reconstitute normal hematopoiesis in ten children with poor prognosis leukemia or neuroblastoma for whom no HLA-compatible marrow donors were available and who had been subjected to marrow-ablative therapy. This separation procedure is simple, efficient, and readily available and can be used for children as a routine procedure for PBSC autotransplantation.

Adolescent↗
PubMed1989

A cluster of human T-lymphotropic virus type-I carriers found in the southern district of Tokushima Prefecture.

Since we had experience of eight patients with adult T-cell leukemia lymphoma from 130 cases of non-Hodgkin's lymphoma between 1978 and 1986, a sero-epidemiological survey of anti human lymphotropic virus type-I (HTLV-I) antibody was performed using a gelatin particle agglutination test, an enzyme-linked immunosorbent assay and an indirect immunofluorescence assay for 2,190 adults (768 men and 1,422 women) aged between 21 and 86 years, in the southern district of Tokushima Prefecture. The inconclusive data obtained using the above mentioned methods have been re-examined by western blotting analysis using enzyme-labelled anti IgM and anti IgG. There was an overall prevalence rate of 6.0% (132/2, 190) but higher rate were found in village C (10.9%) and village D (14.2%). These two villages together with town K (6.1% seropositive) form one community unit with a small population in a mountain area, which could be prone to producing a cluster of HTLV-I carriers. Town G with 8.0% sero-positivity is on the Pacific Ocean coast neighboring one of the endemic areas in the eastern section of Kohchi Prefecture. Interestingly, only IgM antibody was detected in 17 of 137 carriers (13%), all females who had never had a blood transfusion, suggesting them to h ave been in a sort of immunodeficient state, as reported in cases of HTLV-I infection. In 13 of 29 HTLV-I carriers (44.8%) from villages C and D, the viral antigen was detected in 1-9% (0.41 +/- 0.19%) of the peripheral blood mononuclear cells after being cultured with phytohemagglutinin for three days. The data indicate that those carriers had evidently been infected with the HTLV-I virus.

Adult↗
PubMed1989

[Effect of propiverine hydrochloride on the function of the bladder in dogs].

Propiverine hydrochloride (P-4) is a new derivative of benzilic acid. The effect of P-4 on the function of the bladder in anesthetized dogs was studied in comparison with flavoxate, which is clinically used for the treatment of pollakiuria. P-4 (4 mg/kg, i.v.) caused a significant increase in maximum vesical volume (Vmax), which was estimated by a cystometrogram. A similar effect was also observed following intravenous administration of verapamil (1 mg/kg), while flavoxate (4 mg/kg, i.v.) caused no significant changes in Vmax. P-4 significantly decreased the frequency of rhythmic bladder contractions at doses higher than 1 mg/kg, i.v., whereas flavoxate first revealed a significant decrease at 4 mg/kg, i.v. Thus the inhibitory effect of P-4 on the micturition movements of the bladder is more potent than that of flavoxate. These findings indicate that P-4 is a useful drug for the treatment of pollakiuria.

Animals↗
PubMed1988

Direct determination of the blood concentration of halogenated anesthetic agents by gas chromatography.

The direct determination by gas chromatography of blood levels of anesthetic agents has been difficult because of the water content of blood. In the present study, the method of Yokota et al. (1967) was modified by improving the packing materials of the column, the blood sample vaporizer and the flow-path during analysis. As a result, accurate and reproducible determination of halothane, enflurane and isoflurane dissolved in blood was achieved. With this system, blood in which halothane, enflurane and isoflurane had been dissolved could be analyzed without changing the column between samples. Moreover, each sample was prepared in less than 10 min, and more than 100 consecutive determinations could be made with excellent reproducibility. The coefficient of variation was less than 3.8%.

Chromatography, Gas↗
PubMed1987

[Studies on the immunoregulation of anti-thyroglobulin antibody synthesis by lymphocytes in the patients with Hashimoto's disease and Graves' disease].

Anti-thyroglobulin antibody (aTg) synthesis by the lymphocytes in the peripheral blood and the thyroid gland were studied in patients with Hashimoto's disease (HD) or Graves' disease (GD), all in euthyroid states, to clarify the mechanism of autoantibody synthesis. The ability of the lymphocytes to synthesize aTg was analyzed in the culture system of lymphocytes incubated in a concentration of 1 X 10(6) cells/ml for 7 days at 37 degrees C in 5% CO2-95% air. The B cells alone were also cultured in the absence of T cells or PWM to estimate their abilities on spontaneous aTg synthesis. The regulatory functions of T cells on aTg synthesis by B cells were investigated in cross-combination cultures of B cells and an equal number of T cells. The concentration of aTg and total IgG in cultured medium were measured by sensitive enzyme immunoassay developed by us, and the capacity on aTg synthesis was expressed as aTg/IgG ratio (aTg%). The surface markers of lymphocytes in the peripheral blood and the thyroid gland were determined by flowcytometry using mouse monoclonal antibodies (CD3, CD4, CD8, OKIa1, CD20 and Leu7). These results were obtained as follows: 1) All the lymphocytes from the peripheral blood, thyroid gland and bone marrow of HD patients synthesized much more aTg (3.1 +/- 1.6, 2.2 +/- 0.9, 1.5 +/- 0.5%, respectively) than those from normal peripheral blood lymphocytes (1.0 +/- 0.9%). This hyper-function of aTg synthesis by the lymphocytes in HD patients was caused by the presence of activated B cells and the predominance of helper T cells. 2) Both the lymphocytes from the peripheral blood and the thyroid gland in GD patients synthesized the same level of aTg (0.7 +/- 0.7%) as in normal subjects. However, the lymphocytes from bone marrow and lymph nodes, which were indicated by Benner et al. to play a main role in antibody synthesis after immunization with antigen, were involved in aTg synthesis (1.8 +/- 1.2, 5.4 +/- 1.1%, respectively). 3) There was no correlation between aTg synthesis and CD4+/CD8+ ratio of the peripheral blood lymphocytes in AITD patients. These results suggest that aTg synthesis in HD patients is an expression of abnormal immune reaction due to the presence of aTg specific activated B cells and dysfunction of regulatory T cells, and that aTg production by the lymphocytes from the bone marrow and lymph nodes in GD patients is resulted from a normal immune response to the high level of thyroglobulin in the blood.(ABSTRACT TRUNCATED AT 400 WORDS)

Autoantibodies↗