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M Kosaka

Publications and source records attributed to M Kosaka.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1995

[Advances in biology and pathogenesis of multiple myeloma].

Plasma cell malignancy, multiple myeloma, is the prototype of monoclonal terminal-differentiated B cell proliferation that reveals a monoclonal Ig in the serum and/or urine of the majority of patients. New insights into the biology and pathogenesis of this entity are based on careful research to a complex cytokine network including TNF beta, IL-1 beta, and IL-6, many oncogene products such as bc1-2 protein, H-ras p-21 protein, and RB-1 product, and cell surface antigens associated with myeloma cells. The recent understanding on the mechanism for acquisition of IgV region diversity during B cell development has clarified the origin of the clonogenic cell in multiple myeloma. Further identification of new prognostic parameters as well as new therapeutic agents is necessary for the rational therapy of this refractory malignancy.

Aged↗
PubMed1994

A novel membrane antigen selectively expressed on terminally differentiated human B cells.

A monoclonal antibody (MoAb) that defines a novel terminal B-cell-restricted antigen, termed HM1.24, was developed against a human plasma cell line. The MoAb, designated anti-HM1.24, reacted with five different human myeloma cell lines, as well as with monoclonal neoplastic plasma cells obtained from the bone marrow or peripheral blood of patients with multiple myeloma or Waldenström's macroglobulinemia. The HM1.24 antigen was also expressed by mature Ig-secreting B cells (plasma cells and lymphoplasmacytoid cells) but not by other cells contained in the peripheral blood, bone marrow, liver, spleen, kidney, or heart of normal individuals or patients with non-plasma-cell-related malignancies. The anti-HM1.24 MoAb bound to human myeloma RPMI 8226 cells with an affinity constant of 9.2 x 10(8) M-1, indicating approximately 84,000 sites/cell. By immunoprecipitation assay under reducing conditions, this MoAb identified a membrane glycoprotein that had a molecular weight of 29 to 33 kD. Our studies indicate that the HM1.24-related protein represents a specific marker of late-stage B-cell maturation and potentially serves as a target antigen for the immunotherapy of multiple myeloma and related plasma cell dyscrasias.

Animals↗
PubMed1994

Nucleotide sequence encoding human pancreatic ribonuclease.

A cDNA coding for human pancreatic ribonuclease was isolated from a pancreas cDNA library and sequenced. This cDNA (1620 bp) includes an entire open reading frame encoding mature protein (128 aa) following a signal peptide (28 aa) as well as 5'- and 3'-untranslated regions.

Amino Acid Sequence↗
PubMed1994

An S-alkylating reagent with positive charges as an efficient solubilizer of denatured disulfide-containing proteins.

A novel S-alkylating reagent, N-(3-bromopropyl)-N,N,N',N',N'-pentamethyl-1,3-propanedi(ammonium bromide) (TAP2-Br) which carries two positive charges in the molecule, was prepared to increase the solubility or to decrease the hydrophobicity of cysteine-containing denatured proteins (or peptides). S-Alkylation with TAP2-Br introduces two positive charges per cysteine residue, which will effectively shift the net charge of a protein in the positive direction. Disulfide-containing proteins, such as hen egg-white lysozyme, RNase A, BSA, and soybean trypsin inhibitor (Kunitz type), were reduced and S-alkylated with TAP2-Br to evaluate the potential of this reagent compared with other S-alkylating reagents such as monoiodoacetic acid, bromosuccinic acid and (3-bromopropyl)trimethylammonium bromide. The solubilities of these denatured proteins in the pH range of 2-10 indicated that S-alkylation with TAP2-Br effectively solubilized not only basic proteins (lysozyme and RNase) but also an acidic protein containing a fairly large number of cysteine residues (BSA). Moreover, the retentions of cysteine-containing tryptic peptides derived from lysozyme on reversed-phase HPLC were greatly reduced by S-alkylation with TAP2-Br. These results indicate that TAP2-Br is very useful to increase the solubility of some cysteine-containing denatured proteins and to decrease the hydrophobicity of peptides containing cysteine residue(s).

Alkylating Agents↗
PubMed1994

Cellular origin and extent of clonal involvement in multiple myeloma: genetic and phenotypic studies.

The cellular origin and extent of clonal involvement in multiple myeloma (MM) are controversial. The third-complementarity-determining region (CDR3) of the immunoglobulin heavy chain gene is the target region of VH replacements and somatic mutations. We analysed the CDR3 sequences of myeloma cells from eight newly diagnosed and three relapsed patients in order to elucidate the target cell of malignant transformation in MM. We also examined the extent of clonal involvement in MM using a CDR3 clone-specific nucleic acid probe. The peripheral lymphocytes from the five MM patients were separated into fractions such as CD34+, CD20+CD10+, CD20+CD21+, CD20+CD19- and CD2+ cells. Amplified CDR3 DNAs from these subpopulations were hybridized with the probe specific to each patient's tumour cells. We found no evidence of ongoing VH replacements or somatic mutations in CDR3 in MM. However, frequent nucleotide mutations in D and JH segments were observed. Circulating malignant cells were detected in the CD34+ and all of the CD20+ subpopulations, but not in the CD2+ fraction. MM is a neoplasm originating from a B-lineage cell which has already undergone antigen-dependent selection. Nevertheless, the tumour cells are composed of heterogeneous subpopulations at various stages of differentiation, similar to normal B-lineage cells. Conversely, T cells were not involved in MM. These results imply that there is an analogous developmental pathway between the normal B-lineage cells and the tumour cells of MM.

Aged↗
PubMed1994

Ten-year survival and prognostic factors in multiple myeloma. Japan Myeloma Study Group.

Among 1119 Japanese patients with symptomatic multiple myeloma diagnosed between 1965 and 1981, 38 (3.4%) survived more than 10 years. Younger age, low tumour mass (absence of severe anaemia, hypercalcaemia, renal failure, and multiple bone lesions), low plasma cell percentage in bone marrow, mature and intermediate myeloma according to Greipp's criteria, and a positive response to subsequent treatment, were related to long-term survival according to univariate analysis. Multivariate logistic regression analysis indicated younger age and low tumour mass as pretreatment characteristics to be related to long-term survival. Prognostic factors proposed applicable to myeloma were also related to 10-year survival.

Aged↗
PubMed1994

Combination chemotherapy with MCNU, vindesine, melphalan, and prednisolone (MCNU-VMP therapy) in induction therapy for multiple myeloma. Japan Myeloma Study Group.

From January 1988 until December 1990, 99 previously untreated patients with multiple myeloma (MM) were enrolled in a randomized prospective study comparing two combination chemotherapies with and without MCNU as induction therapy for MM; 49 patients with vindesine, melphalan and prednisolone (VMP therapy) versus 50 patients with MCNU, vindesine, melphalan and prednisolone (MCNU-VMP therapy). Seventy-two evaluable patients (34 patients in the VMP group, 38 in the MCNU-VMP group) were analyzed. The response rate was slightly higher with MCNU-VMP than with VMP (81.6% vs. 64.7%). In 43 responders (21 patients in the VMP group and 22 in the MCNU-VMP group) who were treated with the same regimen as the induction therapy to maintain remission, the remission duration was significantly longer in patients treated with MCNU-VMP than in those treated with VMP (median > 10.1 vs. 8.0 months, P = 0.018), particularly in patients with PS 3-4. The remission duration in the MCNU-VMP group was also slightly longer in the patients with stage III disease and who were older than 65 years. The median survival time showed no significant difference between the VMP group (20.3 months) and the MCNU-VMP group (> 15 months). Leukopenia, thrombocytopenia and nausea/vomiting were found to be somewhat severe in the MCNU-VMP group. In summary, MCNU-VMP therapy is effective as induction therapy for MM.

Adult↗
PubMed1994

[Caregiving burden of elderly caregivers who provide at home care for infirm elderly].

In order to elucidate the degree of feeling burdened and factors affecting caregiving burden of elderly caregivers, a questionnaire survey was performed on 241 female caregivers of infirm elderly. The surveyed group consisted of 138 caregivers under 60 years of age (young group) and 103 aged 60 and over (old group). The major results of this survey were as follows, 1) Conditions perceived as unfavorable in the old group were related to caregiving assistants, number of the family members and health condition of the caregiver. 2) Greater number of infirm elderly with serious ADL problems and higher average body weight of the elderly cared for were seen for the old group than the young group. 3) The old group had a larger number of problem incidents and expressed more eager desire for transfer of elderly to institutional care than providing the young group. 4) A feeling of burden in daily care appeared larger for night care, body discharge disposal and bathing care of the elderly and was more frequent in those above 70 than under 70 years of age. 5) Hours in bed were longer and range of movement by wheel chair was more limited for infirm elderly as the caregiver's age increased. These results suggest that the above-mentioned unfavorable conditions in elderly caregivers promote a state of becoming bedridden and a lowering of ADL ability of infirm elderly.

Activities of Daily Living↗
PubMed1993

Effect of erythroid differentiation factor on maintenance of human hematopoietic cells in co-cultures with allogenic stromal cells.

The effect of erythroid differentiation factor (EDF) on the maintenance of human hematopoietic progenitors in a microenvironment was examined by co-culture of adherent- and E rosette-depleted mononuclear cells from the bone marrow (BM) or peripheral blood (PB) with allogenic stromal cells. EDF had no effect on colony formation of erythroid burst-forming units (BFU-E) from the BM cultured without a stromal layer. The number of BFU-E cultured with the stromal layer was decreased less in the presence of EDF than in its absence. This activity of EDF was also observed when the mononuclear cells were separated from the stromal layer by a filter membrane. These data suggest that EDF facilitates maintenance of the number of BFU-E through a humoral factor(s) secreted by the stromal layer. The number of BM erythroid colony-forming units (CFU-E) was decreased on addition of EDF, which promotes differentiation of CFU-E. The number of PB CFU-E was increased irrespective of the presence or absence of EDF over 2 weeks, suggesting that BFU-E, which are more abundant in PB than in BM, differentiate to supply CFU-E. However, the addition of EDF resulted in less increase of PB CFU-E, indicating that it inhibited the proliferation of CFU-E progenitors to suppress colony formation. On the other hand, CFU-GM was consistently decreased by addition of EDF to this culture system. These data indicate that EDF acts as a commitment factor and/or a promoter of erythroid progenitors in a hematopoietic microenvironment.

Activins↗