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Biomedical subjects

M Kosaka

Publications and source records attributed to M Kosaka.

At least 19 recordsLinked to original sources
PubMed1996

A new approach to analysis of human sweating.

In human skin transplanted to the back of 3 strains of immuno-deficient mice the function of the eccrine sweat glands of the human transplant was tested by topical intradermal application of pilocarpine, adrenaline and atropine + pilocarpine. Sweat responses were observed in pre-selected fields of observation by means of video macroscope. The iodine starch reaction served as an indicator for the appearance of sweat sport and permitted the evaluation of areas wetted by sweat in the field of observation. Among 9 animals tested, the hybrids between the CB-17-scid mouse and the BALB/cA-nu mouse (BALB/cA-nu,scid) seemed to exhibit the most consistent sweating response to local pharmacological stimulation. According to histological examination, eccrine sweat glands were preserved in human skin transplanted into the back skin of the BALB/cA-nu,scid mouse strain. The heterologous, human skin graft provides a novel model permitting, independent of the normal sweat gland innervation, the analysis of molecular receptors of sweat gland cells by which the actions of natural transmitters and pharmacological agents are transduced.

Animals↗
PubMed1996

Analysis of circulating hematopoietic progenitors in patients with chronic renal failure under hemodialysis.

Circulating hematopoietic progenitors were analyzed in patients with chronic renal failure (CRF) under hemodialysis (HD) by methylcellulose culture containing interleukin-3 (IL-3) to clarify the differences in hematopoiesis between patients with and without CRF-associated anemia and between good responder whose hematocrit (Ht) was preserved in more than 25% under erythropoietin (Epo) treatment and poor responders whose Ht remained less than 25% even under Epo treatment. The numbers of peripheral blood (PB) erythroid burst-forming units (BFU-E) and granulocyte-macrophage colony-forming units (CFU-GM) in HD patients without Epo treatment, whose Ht levels were greater than 30%, were similar to those in normal subjects. However, these numbers in HD patients who required Epo treatment were significantly lower than those in normal subjects. The number of PB BFU-E in HD patients who showed a poor response to Epo was significantly lower than that in HD patients who showed a good response to Epo. The number of PB BFU-E was well correlated with the number of PB CFU-GM in all groups of HD patients. There also existed a definite correlation between these numbers and the Ht levels in HD patients without Epo treatment, but not those in HD patients with Epo treatment. The sensitivity of PB BFU-E to IL-3 was lower in HD patients who showed a poor response to Epo than in the other HD patients and normal subjects. These findings indicate that hematopoiesis in HD patients with CRF associated anemia is suppressed in both the erythroid and myeloid lineage at primitive stages, and that the lower sensitivity of PB BFU-E to IL-3 in HD patients with a poor response to Epo may be associated with this poor response. In addition, the level of the serum transferrin receptor (sTfR) in HD patients without severe anemia was higher than that in normal subjects and HD patients who required Epo treatment, indicating that erythropoiesis in HD patients who do not require Epo treatment is more active than that in normal subjects and other HD patients.

Case-Control Studies↗
PubMed1996

Immunohistochemical localization of activin A and follistatin in human tissues.

We immunohistochemically investigated the localization of activin A and follistatin in various human tissues with specific antibodies to recombinant human (rh-) activin A and rh-follistatin. Specific immunostaining of activin A was detected in Leydig and Sertoli cells of the testis. In the ovary, granulosa cells of mature follicle and luteal cells of the corpus luteum stained for activin A. Immunoreactive activin A was present in somatotrophs of the pituitary gland and insulin-positive B cells of the pancreatic islets. Immunoreactivity for activin A was also found in thyroid follicular cells, adrenocortical cells, neuronal cells of the cerebrum and monocytoid cells in the bone marrow. Follistatin, an activin-binding protein, was immunostained in the same tissues as activin A. These findings indicated that activin A and follistatin are widely distributed in human tissues, suggesting that activin plays important roles as a common regulator in various tissues under the control of co-existing follistatin.

Activins↗
PubMed1996

Human betacellulin, a member of the EGF family dominantly expressed in pancreas and small intestine, is fully active in a monomeric form.

Betacellulin (BTC) was found to be expressed mainly in human pancreas and small intestine. This finding suggests that BTC possesses some specific function distinguished from the other members of epidermal growth factor (EGF) family. To clarify this function, the released form of human BTC has been expressed in E.coli, purified, and characterized. The recombinant human BTC was produced as an inclusion body. This material was dissolved in guanidine-HCl under reducing conditions, refolded, and purified through sequential liquid chromatography. Purified BTC was electrophoresed under reducing conditions and a molecular size of 18 kDa was determined, which is the supposed size of a dimer of the peptide. However, chemical analysis failed to show a covalently linked dimer. The molecular mass of BTC analyzed by mass spectrometry revealed it to be 9 kDa, which is consistent with theoretical value for a monomer. Recombinant BTC showed growth promoting activity for mouse fibroblasts and rat aortic smooth muscle cells which was equivalent to EGF On the other hand, BTC was found to exhibit a growth inhibitory effect on the cells overexpressing EGF receptor.

3T3 Cells↗
PubMed1996

[Advances in the pathogenesis, biology, and management of multiple myeloma].

There have been several advances in our understanding and management of multiple myeloma (MM). Firstly, somatic mutations without intraclonal variation have been detected in Ig genes of malignant plasma cells, indicating that the major oncogenic events yielding continuous proliferation of the myeloma stem cell occur in a cell selected by contact with antigen in the lymphoid follicles. Secondly, interleukin-6 supplied by autocrine and paracrine secretion has been identified as a major cytokine for the emergence of the tumor clone. Thirdly, myeloablative chemoradiotherapy with autologous peripheral blood stem cell rescue has been shown to induce complete remission and to improve prognosis, although disappointingly few patients benefit from it. An improved strategy, such as anti IL-6 and/or anti IL-6R administration with biological therapy directed to suppress the myeloma cell growth is necessary as rational therapy.

Animals↗
PubMed1996

[Association between dental erosion and exposure to acids in a chemical factory].

An examination of dental erosion status and a semi-quantitative assessment of exposure to acids were carried out for 134 workers in a chemical factory in Osaka Prefecture, and an association between the dental erosion and the exposure to acids was discussed. 1) Percentage of workers with dental erosion of grade + or more among the subjects was 30.6%. 2) Most of the erosion was observed in the front teeth. There were more eroded teeth in the upper jaw than in the lower jaw. 3) The workers were divided into 4 groups according to job type at the time of the examination: production, research, clerical work and others. The production workers, those routinely handling a large amount of various kinds of acids, was the highest proportion of workers with eroded teeth. Because some of the clerical workers had previously handled acids, this group of workers included a larger number of those with dental erosion than the other two groups. 4) More than half of the workers who had been engaged in production had eroded teeth including those of grade +/- 5) The intensity of exposure to acids, as a semi-quantitative index for cumulative exposure to acids, was calculated in each worker from a score for the job type and its duration. A significant association was observed between the intensity and the manifestation of dental erosion.

Acids↗
PubMed1996

Localization and imaging of human plasmacytoma xenografts in severe combined immunodeficiency mice by a new murine monoclonal antibody, anti-HM1.24.

We have examined the localization in the tumor of anti-HM1.24, a murine monoclonal antibody which is specific for human plasma cell-associated antigen. The biodistribution and imaging were compared in severe combined immunodeficiency mice bearing human plasmacytoma (RPMI 8226) xenografts after intravenous injection of radiolabeled anti-HM1.24. The mean tumor uptake of 1 microCi of 125I-labeled anti-HM1.24 was 2.98% injected dose per g of tissue (%ID/g) at day 1 and increased to 5.50% ID/g at day 4, whereas tumor uptake values of control IgG was always less than 1.36% ID/g. The tumor localization indices ranged between 2.35 and 6.03 at day 1 to 4 after injection. Anti-HM1.24 showed no evidence of targeting to normal tissues except a splenic uptake, however, splenic targeting was abolished by the blocking of Fc receptors in the reticuloendothelium. In most cases, tumor-to-tissue ratios were greater than 2 at day 4, indicative of tumor selectivity for anti-HM1.24. Radioimaging with 10 microCi of 131I-labeled anti-HM1.24 showed that 25% of the total-body count were localized in the tumor and the tumors could be visualized without subtraction techniques at day 4. Furthermore, the penetration and binding of anti-HM1.24 to the tumor cells were confirmed by autoradiographic studies. These findings indicate that anti-HM1.24 is a potent agent for detection and targeting of human plasmacytoma.

Animals↗
PubMed1995

Recombinant human pancreatic ribonuclease produced in E. coli: importance of the amino-terminal sequence.

Human pancreatic ribonuclease 1 (hRNase 1) in the mature form has been produced in E. coli using T7 expression system. The recombinant hRNase 1 protein was solubilized from the inclusion bodies, refolded in glutathione redox system, and purified through chromatographic procedures by utilizing cation-exchange and reversed-phase columns. The ribonucleolytic activity of recombinant hRNase 1 was examined on yeast RNA and cytidylyl-3',5'-adenosine revealing the distinctive ribonucleolytic activity. The activity was perfectly inhibited by human placental RNase inhibitor. Truncation of 7 amino acid residues in the amino-terminal sequence resulted in much reduction in ribonucleolytic activity and in affinity to human placental RNase inhibitor with the disintegration of secondary structures of the protein observed by circular dichroism spectra. The present study has revealed the important contribution of the amino-terminal sequence of hRNase 1 to the characteristics of the protein.

Amino Acid Sequence↗
PubMed1995

Molecular cloning and expression of human ribonuclease 4 cDNA.

A cDNA coding for human ribonuclease 4 was isolated from a pancreas cDNA library and sequenced. This cDNA (996 bp) includes an entire open reading frame encoding mature protein (119 aa) following signal peptide (28 aa). Expression of mature protein in Escherichia coli showed an apparent molecular mass of about 16 kDa, which was slightly lower than the mature form of human RNase 1, in SDS-PAGE.

Amino Acid Sequence↗
PubMed1995

Frequent somatic mutations in D and/or JH segments of Ig gene in Waldenström's macroglobulinemia and chronic lymphocytic leukemia (CLL) with Richter's syndrome but not in common CLL.

V(D)J recombination and somatic hypermutations are developmentally regulated during B-cell differentiation; therefore, DNA analysis of the Ig gene delineates the cellular origin of B-cell neoplasms. We analyzed the third complementarity-determining region and adjacent regions of the Ig heavy-chain gene of tumor cells from 7 patients with Waldenström's macroglobulinemia (WM) and from 10 patients with B-cell chronic lymphocytic leukemia (CLL), 2 of whom progressed to high-grade non-Hodgkin's lymphoma (NHL), ie, Richter's syndrome (RS). There were no intraclonal variations resulting from VH replacements or ongoing somatic mutations in both WM and CLL. We found replacement mutations in the D and/or JH segments in all patients with WM and in 4 of the 10 patients with CLL, including the 2 RS patients. Replacement mutations were clustered in codon 102 of the JH segment. Preferential utilization of the JH4 gene was found in WM (5 of 7 [71.4%]) and in CLL (7 of 10 [70.0%]), and DXP family genes in CLL (5 of 10 [50.0%]). In conclusion, WM and CLL with RS are generated under the influence of antigenic stimulation and selection. However, the majority of CLL may arise from a distinct subpopulation that has the restricted repertoire of nonmutated Ig genes.

Adult↗
PubMed1995

Induction of teratocarcinoma F9 cell differentiation with cis-diammine dichloroplatinum(II) (CDDP).

cis-Diammine dichloroplatinum(II) (CDDP) is the salt of a platinum compound which has been noted to have a wide spectrum of activity against malignant disorders. We have studied the effects of CDDP on embryonal carcinoma F9 cell differentiation. In the presence of this agent in vitro, the cells showed rapid morphological changes, a marked increase in the mRNA expression of various differentiation markers accompanied by a loss of tumorigenicity. These results indicate that the differentiation of F9 cells is induced with CDDP.

Animals↗
PubMed1995

The kinetics of induction of Hox1.6 and C-jun mRNA during three different ways of inducing differentiation in teratocarcinoma F9 cells.

Changes in Hox1.6 and c-jun gene expression were examined upon F9 cell differentiation that was induced by three independent methods: a drug treatment with retinoic acid (RA), that with sodium butyrate (NaB), and a genetic approach using the ts mutant. To obtain further information on the mechanism of teratocarcinoma cell differentiation we have examined the kinetics of the induction of Hox1.6 and c-jun mRNA whose gene products have been demonstrated to have specific roles in gene regulation. Expression of Hox1.6 mRNA was induced more rapidly than c-jun mRNA by all the above three inducing methods. Furthermore, protein synthesis was not required for the induction of Hox1.6 mRNA as well as of c-jun mRNA synthesis in all three methods. The data suggested that the transcriptional increase in the Hox1.6 mRNA was a primary response and could play an important role in F9 cell differentiation.

Butyrates↗
PubMed1995

Macrophage colony-stimulating factor-producing malignant histiocytosis.

We describe a patient with malignant histiocytosis who had a prominent neutrophilia uncommonly observed in this disease. Serum concentration of macrophage colony-stimulating factor (M-CSF) was markedly elevated, and correlated with clinical symptoms and neutrophil counts during clinical course. Moreover, M-CSF was detected in the cytoplasm of malignant histiocytes of the lymph node and bone marrow by immunohistochemical staining. These results indicate that the neutrophilia observed in this patient was caused by M-CSF produced by the malignant histiocytes.

Adult↗
PubMed1995

Suppression of haematopoiesis by IgG autoantibodies from patients with systemic lupus erythematosus (SLE).

The inhibiting activity of serum on haematopoiesis has been described in patients with SLE. To explore further the features of serum inhibitor, we first examined the suppression of granulocytic and erythroid colony formation in vitro by serum from patients with SLE using methylcellulose culture. The potent inhibiting activity was demonstrated in six of 20 patients. All of these six patients were associated with leukocytopenia and/or anaemia. Five of 10 sera from patients with active SLE suppressed the colony formation of both burst-forming units of erythrocyte (BFU-E) and colony-forming units of granulocyte/macrophage (CFU-GM), and one serum suppressed BFU-E only. IgG fraction isolated from sera with inhibiting activity suppressed colony formation without complement involvement. The elimination of monocytes and lymphocytes from target mononuclear cells did not affect the suppression by the IgG fractions. The suppressive effect was completely eliminated after incubation of the IgG fractions with progenitor-enriched mononuclear cells. Flow cytometric analysis showed these IgG bound to CD34+ haematopoietic progenitor cells, but not to CD33+ cells. These data suggest that (i) the inhibitor of colony formation in serum was observed in IgG fraction; (ii) its suppressive effect on colony formation was mediated by neither monocytes and lymphocytes nor complements; and (iii) IgG fraction could bind to primitive haematopoietic progenitor cells and suppress the growth of these cells. Thus, IgG autoantibodies to primitive haematopoietic progenitor cells are demonstrated to be present in the sera of a significant proportion of active SLE patients with anaemia and leukocytopenia and to suppress the progenitor cell growth.

Adolescent↗
PubMed1995

Effects of activin A on deoxyribonucleic acid synthesis, iodine metabolism, and cyclic adenosine monophosphate accumulation in porcine thyroid cells.

We have recently shown the presence of activin A in human thyroid cells. To determine whether activin A affects the growth and function of the thyroid, we investigated its effects on DNA synthesis, iodine metabolism, and cAMP accumulation in cultured porcine thyroid cells. Activin A increased DNA synthesis. This effect was abolished by addition of follistatin but additively enhanced by epidermal growth factor. In contrast, activin A significantly reduced uptake and release of iodide by the thyroid and also TSH-induced cAMP accumulation but did not inhibit the cAMP accumulation induced by forskolin. These data indicate that activin A stimulates thyroid growth irrespective of cAMP accumulation and inhibits thyroid function.

Activins↗
PubMed1995

Multiple myeloma: new evidence and insights from the immunoglobulin heavy chain gene and phenotypes.

DNA analysis of the Ig genes has been utilized to delineate the stages of differentiation of normal and malignant B-lineage cells, since the mechanisms involved in V(D)J recombination, somatic hypermutations, and class switch are developmentally regulated. Somatic mutations which result in amino acid substitutions are observed frequently in the Ig variable region genes in multiple myeloma (MM), but there is no intraclonal variation. This fact suggests that the target cell of malignant transformation in MM is a B-lineage cell which already has undergone antigenic selection. This B-lineage cell probably corresponds to a pre-plasma cell or a plasma cell rather than a memory B cell. Tumour cells which share an identical third-complementarity-determining-region (CDR3) sequence with the myeloma cells can be detected from the various fractions representing different stages of B-cell differentiation, such as CD34+, CD20+CD10+, CD20+CD21+, CD20+CD19- cells from the peripheral blood. Thus, the tumour cells in MM are composed of immunophenotypically heterogeneous subpopulations at various stages of differentiation, similar to normal B-lineage cells. These results imply that there is an analogous developmental pathway between the normal B-lineage cells and the tumour cells of MM. Dedifferentiation to the stem cell level may be essential to the malignant transformation in MM.

Base Sequence↗
PubMed1995

[Clinical significance of measurement of a novel basement membrane-associated collagen levels in serum].

We measured serum levels of a basement membrane-associated collagen(BMC) by enzyme linked immunosorbent assay using two recently produced monoclonal antibodies (named JK-199 and JK-135) to evaluate that's clinical significance. JK-199 reacted with alpha 1 (IV) chain in triple helical region of type IV collagen and JK-132 is considered to react with an unidentified alpha (IV) related collagen chain. BMC was determined in sera of patients with chronic liver diseases (n = 27), healthy volunteers (n = 30) and in random serum samples of in- or outpatients of our hospital (n = 1125). The degree of fibrosis of the chronic liver diseases was estimated by computed image analysis for the biopsy specimens. BMC levels in sera of healthy volunteers as 0-40ng/ml. Serum BMC levels were significantly higher than that in healthy volunteers in chronic active hepatitis 2A (56.9 +/- 27.9ng/ml; mean +/- SD), 2B (80.9 +/- 39.1ng/ml) and liver cirrhosis (114.5 +/- 26.6ng/ml). Serum BMC levels showed positive correlation with fibrosis area/total area(%) in biopsy specimens of chronic liver diseases (r = 0.678; p < 0.001). Total 149 samples (from 127 patients) of 1125 random serum samples (13.2%) showed increased BMC and 70 of 127 patients with abnormal high BMC (55.1%) had liver diseases. These results suggest that serum BMC increases mainly in patients with liver diseases, especially with progression of chronic liver diseases.

Adult↗