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Biomedical subjects

H Nagumo

Publications and source records attributed to H Nagumo.

33 records · Page 2Linked to original sources
PubMed1998

Synergistic augmentative effect of interleukin-10 and CD27/CD70 interactions on B-cell immunoglobulin synthesis.

Interleukin-10 (IL-10) is a potent cytokine that regulates immunoglobulin synthesis by B cells. CD27/CD70 interactions by direct cell-to-cell contact are also needed to produce substantial amounts of immunoglobulin. We have investigated the effects of IL-10 and CD27/CD70 interactions on the immunoglobulin synthesis. In the presence of IL-10 stimulation, the production of IgG, IgM and IgA was increased synergistically by the addition of CD27 ligand (CD70)-transfectants in a dose-dependent manner, which was completely blocked by anti-CD70 monoclonal antibody. In contrast, CD70-transfectants additively enhanced the immunoglobulin production in the presence of IL-2, IL-4, or IL-6. The synergistic enhancement of the immunoglobulin production by IL-10 and CD70-transfectants was remarkable in highly purified CD27+ B cells, but there was no immunoglobulin production in CD27- B cells. Furthermore, by the addition of CD70-transfectants, the synthesis of IgG1, IgG2, IgG3 and IgG4 was also enhanced in the presence of IL-10. On the other hand, IL-10 diminished CD27 expression in B cells. B-cell proliferation was augmented by CD70-transfectants with IL-10 or IL-10 plus IL-2. The addition of IL-2 further augmented the immunoglobulin production which was synergistically enhanced by IL-10 and CD27 triggering. Taken together, the co-operative response to IL-10 and CD27/CD70 interactions regulates B-cell immunoglobulin production.

Adult↗
PubMed1997

B cell subpopulations separated by CD27 and crucial collaboration of CD27+ B cells and helper T cells in immunoglobulin production.

B cell immunoglobulin production is regulated by helper T cells through direct interaction and secreted cytokines. In the present study, we functionally analyzed CD27 in cord and peripheral blood B cells. Adult peripheral blood B cells were separated into CD27+ and CD27- cells, which differed in their morphology. Cord blood B cells did not express CD27, and CD27 expression on peripheral blood B cells increased with age. Only CD27+ B cells had the ability to produce immunoglobulin, which was increased by contact with a tumor necrosis factor-related transmembrane ligand, CD70. Adult peripheral blood CD27+ B cells can be further subdivided into two discrete subtypes: IgD- CD27+ and IgD+ CD27+ B cells. IgD- CD27+ B cells produce IgG, IgM and IgA, whereas IgD+ CD27+ B cells predominantly produce IgM. The addition of activated CD4+ CD45RO T cells expressing CD70 caused down-regulation of CD27 expression on activated B cells, and this down-modulation was completely blocked by anti-CD70 monoclonal antibody, indicating direct T-B cell contact via CD27/CD70. The triggering via CD27 and CD40 additively increased the immunoglobulin production under Staphylococcus aureus Cowan strain plus interleukin-2 stimulation. Taken together, our findings demonstrate that peripheral blood B cells are separated into subpopulations by CD27 and IgD expression and that CD27+ B cells produce large amounts of immunoglobulin by interaction with the CD70 molecule.

Adult↗
PubMed1997

Analysis of the tumor staining obtained by preoperative IV-DSA for breast cancer patients: density and metastasis correlation.

We examined the density of tumor enhancement on intravenous digital subtraction angiography (IV-DSA) in patients with breast cancer in relation to disease-free survival. The subjects of the present study consisted of 103 patients with invasive ductal carcinoma measuring 5 cm or less treated from July 1988 to September 1993. In the 103 patients, 15 had distant metastasis. The region of interest was set in the areas enhanced by IV-DSA of the breast. The maximum density (MAX) was calculated by the time-density curve. When the patients were divided according to three classes of MAX, i.e., 0-5.0 pixels (group A, n = 23), 5.1-9.0 pixels (group B, n = 50), 9.1 pixels or more (group C, n = 30), disease-free survival was highest in group A followed by group B and C, respectively. The disease-free survival rate in group C was significantly lower than that of group A or B (p < 0.05). Thus, high values of MAX were associated with low rates of disease-free survival. Since the value of MAX was found to be independent from other prognostic factors by multivariate analysis, these results indicate that MAX has a close correlation with metastasis or recurrence of breast cancer, making IV-DSA a promising prognostic factor.

Adult↗
PubMed1997

Activation of phorbol ester responsive form of protein kinase C zeta in association with Ca(2+)-induced differentiation of primary cultured mouse epidermal cells.

In primary cultured mouse epidermal cells, protein kinase C (PKC) zeta consists of multiple forms: a low salt-eluted PKC zeta (1-PKC zeta, 79 and 85 kDa) and a high salt-eluted PKC zeta (h-PKC zeta, 79 and 85 kDa) by anion-exchange column chromatography (K. Nishikawa et al., Cell. Signal. 7, 491-504, 1995). In the present study, PKC isozyme-specific responses during terminal differentiation of epidermal cells, which were induced by the increase of Ca(2+)-concentration in culture medium, were examined. After 24 hr-treatment with 1.8 mM Ca2+, 79-kDa 1-PKC zeta in the particulate fraction was apparently shifted to the 85-kDa form. The phosphatidylserine-dependent kinase activity of this 1-PKC zeta was increased in association with the shift. These results suggest the pivotal role of 1-PKC zeta in the particulate fraction in the Ca(2+)-induced epidermal cell differentiation processes.

Amino Acid Sequence↗
PubMed1996

Relation between Locoregional Hyperthermic Area Detected by Contact Thermography and the Maximum Density of Tumor Stain Obtained by IV-DSA in Breast Cancer Patients.

We studied the significance of the locoregional hyperthermic area observed by contact thermography in relation to the maximum density of tumor enhancement obtained by IV-DSA. The subjects were 34 patients with primary breast cancer. The thermal difference between the locoregional hyperthermic area and the surrounding mammary tissues was obtained, and the maximum density of tumor stain on IV-DSA was calculated from the time-density curve. Twenty-three (67.6%) patients had a locoregional hyperthermic area corresponding to the tumor. The higher the degree of thermal difference between the hyperthermic area and the surrounding tissues, the higher the maximum density of tumor enhancement. As the maximum density of tumor stain is considered to reflect the vascularity of the tumor, the degee of the locoregional hyperthermic area obtained by thermography may also reflect tumor vascularity.

Journal Article↗
PubMed1995

Selectivity of action of staurosporine on Ca2+ movements and contractions in vascular smooth muscles.

We examined the effects of staurosporine, a protein kinase inhibitor, on Ca2+ movements and contractions due to KCl and 12-deoxyphorbol 13-isobutyrate (DPB), which are thought to activate myosin light chain kinase and protein kinase C, respectively. In rabbit aortae, staurosporine inhibited contractions due to KCl (65.4 mM) and DPB (1 mu M) with IC50 values of 140.5 +/- 1.3 nM and 13.3 +/- 1.3 nM, respectively. Calphostin C, a putative inhibitor of protein kinase C, inhibited DPB-induced contraction with much less effect on the KCl-induced one. On the other hand, wortmannin, an inhibitor of myosin light chain kinase, was 4 times more potent on KCl-induced contraction than the DPB-induced one. Staurosporine at 100 nM decreased the rise in cytosolic Ca2+ due to KCl, whereas wortmannin did not affect it. In rabbit cerebral arteries permeabilized with beta-escin, staurosporine at 100 nM, but not 30 nM, inhibited Ca2+ -induced contraction in the presence of 1 mM ATP. The results indicate that staurosporine preferentially inhibits a contraction dependent on protein kinase C than that dependent on myosin light chain kinase in vascular smooth muscles. Its ability to inhibit KCl-induced contraction involves inhibition of voltage-dependent Ca2+ channels.

Alkaloids↗
PubMed1995

The presence of phorbol ester responsive and non-responsive forms of the zeta isozyme of protein kinase C in mouse epidermal cells.

The possible involvement of zeta isozyme of protein kinase C (PKC zeta) in phorbol ester-induced signal transduction was investigated in mouse epidermal cells. Western blot analysis of RESOURCE Q column chromatography eluates obtained from 105,000 g supernatants and particulate fractions of epidermal cells was performed using anti-PKC zeta specific antibody. Anti-PKC zeta antibody recognised proteins in low salt range corresponding to 25-125 mM NaCl (low salt-eluted PKC zeta; 1-PKC zeta) as well as high salt range corresponding to 175-300 mM NaCl (high salt-eluted PKC zeta; h-PKC zeta) in both subcellular fractions. 1-PKC zeta and h-PKC zeta were detected as a doublet protein of 79,000 and 85,000 M(r) in 105,000 g supernatants, but as a 79,000 M(r) protein in particulate fractions. Immunoprecipitated 1-PKC zeta and h-PKC zeta with anti-PKC zeta specific antibody possessed phosphatidylserine (PS)-dependent protein kinase activity, but neither 1-PKC zeta nor h-PKC zeta were further activated by 40 nM phorbol 12-myristate 13-acetate (PMA) in the presence of PS. Furthermore, 1-PKC zeta and h-PKC zeta can be autophosphorylated, indicating that both 1-PKC zeta and h-PKC zeta are PKC zeta. Treatment of intact epidermal cells with PMA or other PKC activators caused the apparent shift of 79,000 M(r) 1-PKC zeta to the 85,000 M(r) from in particulate fractions. Prolonged treatment of the cells with PMA induced the downregulation of both forms of 1-PKC zeta in particulate fractions. Under the same condition, 1-PKC zeta in 105,000 g supernatants and h-PKC zeta in both fractions did not respond to PMA. This apparent shift was reversible and the content ratio of 85,000 to 75,000 M(r) 1-PKC zeta was decreased by acid phosphatase treatment, indicating that the apparent shift results at least in part from phosphorylation of 79,000 M(r) 1-PKC zeta. Total activity of 1-PKC zeta was increased in association with the apparent shift from the 79,000 to 85,000 M(r) form in response to PMA treatment of intact epidermal cells. All of these results indicate that PKC zeta is present as multiple forms in mouse epidermal cells, and that especially 1-PKC zeta in particulate fractions play a significant role(s) in PMA-induced signal transduction in mouse epidermal cells.

Amino Acid Sequence↗
PubMed1994

Phosphorylation of calponin by PKC is blocked by F-actin in vitro.

Polyclonal antibody against phosphorylated calponin was raised in rabbits by application of the peptide corresponding to residues 183-195 of calponin phosphorylated by protein kinase C. When calponin was incubated with protein kinase C, only free calponin was recognized by this antibody and calponin of native thin filament or that binding to F-actin did not. In experiments done using [gamma-32P] ATP, no radioactivity was detected except for free calponin. Calponin phosphorylation was suppressed in an actin dose-dependent manner and the phosphorylation of calponin was completely blocked when the actin molar ratio to calponin exceeded 10. These data suggest that phosphorylation of calponin by protein kinase C was apparently blocked by F-actin.

Actins↗
PubMed1994

KP-10, a novel protein kinase C substrate in intact mouse epidermal cells, is phosphorylated by novel protein kinase C eta and/or zeta.

Recently this group found an endogenous substrate protein for Ca(2+)-independent novel protein kinase C (nPKC), i.e. KP-10 (pI 4.7/25,500 M(r)), in primary cultured mouse epidermal cells [Nishikawa, K. et al. (1992) Cell. Signal. 4, 757-776]. In the present study, the nPKC isozymes which phosphorylate KP-10 in these cells were determined. Western blot analysis revealed that PKC alpha, eta and zeta were present in epidermal cell 105,000 g supernatants and that the content of PKC zeta was much higher than those of PKC alpha and eta. Neither PKC beta, delta nor epsilon was detected in the 105,000 g supernatants. Phosphatidylserine and phorbol 12-myristate 13-acetate (PMA)-dependent KP-10 phosphorylating activity was immunoprecipitated by anti-PKC eta and zeta antibodies, but not by antiPKC alpha antibody. These results suggest that PKC eta and/or zeta phosphorylate KP-10 and play pivotal roles in intracellular signal pathways in intact epidermal cells.

Amino Acid Sequence↗
PubMed1993

Suppressive effect of transforming growth factor-beta on the phosphorylation of endogenous substrates by conventional and novel protein kinase C in primary cultured mouse epidermal cells.

The effect of transforming growth factor-beta (TGF-beta) on the endogenous protein phosphorylation caused by phorbol 12-myristate 13-acetate (PMA), a potent activator of protein kinase C (PKC), was examined in primary cultured mouse epidermal cells. PMA markedly stimulates phosphorylation of endogenous proteins, i.e. KP-1 and KP-2, through Ca(2+)-dependent conventional PKC (cPKC), and KP-10 through Ca(2+)-independent novel PKC (nPKC) in intact epidermal cells. TGF-beta strongly suppressed the PMA-stimulated phosphorylation of these three proteins. Rate of dephosphorylation of these phosphorylated proteins was not affected by TGF-beta. Treatment of epidermal cells with TGF-beta decreased cPKC activity both in cytosolic and particulate fractions, but not nPKC activity. These results indicate that TGF-beta suppresses cPKC- and nPKC-mediated endogenous protein phosphorylation in intact epidermal cells, but the mechanisms of suppression are different.

Animals↗
PubMed1991

Establishment of a new Epstein-Barr virus nuclear antigen-positive B-cell line, BALL-2, with t(8;14) (q24;q32) chromosome abnormality from B-cell acute lymphoblastic leukemia, L2.

A new Epstein-Barr virus nuclear antigen (EBNA)-positive B-cell line, designated BALL-2, was spontaneously established from the peripheral blood of a 14-year-old boy with an EBNA-negative B-cell acute lymphoblastic leukemia (B-ALL), L2 in the French-American-British classification. The BALL-2 cell line grew in suspension with or without forming clumps of cells. The cultured cells exhibited lymphoid morphology with indented or lobulated nuclei, prominent nucleoli, and relatively abundant cytoplasm. Immunologic and cytogenetic studies showed that the BALL-2 cell line expressed the B-cell phenotype, CpIg+, SmIg+, CD19+, CD20+, CD38-, Ia+, and had chromosome translocation, t(8;14) (q24;q32). The same phenotypic and chromosome markers were present in original leukemia cells. These results indicated that the cell line was derived from the patient's leukemia cells. Unexpectedly, however, BALL-2 cells were positive for EBNA and EB virus DNA. Gene analysis of the BALL-2 cell line showed biallelic rearrangements in the JH locus. One of the JH rearrangement comigrated with a rearranged c-myc gene, indicating the translocation had occurred between JH and c-myc loci. The t(8;14) abnormality is a known chromosome marker of Burkitt lymphoma and L3 type ALL. Our studies revealed that this translocation and myc gene rearrangement can also be found in L2 type B-ALL.

Adolescent↗
PubMed1990

[A case of a patient with the non-confluent main pulmonary artery with the left pulmonary artery after a left Blalock-Taussig shunt for tetralogy of Fallot, which underwent a successful two staged radical repair].

We report on a 14-year-old girl with tetralogy of Fallot and the non-confluent main pulmonary artery with the left pulmonary artery after a left Blalock-Taussig shunt. She underwent a left-sided classic Blalock-Taussig shunt at the age of one. However, she showed repeated dyspnea and increasing cyanosis, and cardioangiography showed the non-confluent main pulmonary artery with the left pulmonary artery. Corrective surgery of tetralogy of Fallot was done by a two-staged operation. In the first stage, a EPTFE prosthesis was grafted between the main pulmonary artery and the left pulmonary artery, and in the second stage, intracardiac operation was performed. The late postoperative status and hemodynamic results were satisfactory and we emphasize the rational for this approach.

Adolescent↗
PubMed1988

[Tissue distribution of CA-125 in female reproductive organs].

In order to elucidate the origin of elevated serum CA-125 values in patients with endometriosis, CA-125 content in the uterine endometrium, myometrium, leiomyoma, fallopian tube, ovary, adenomyotic tissue and endometriotic tissue, were measured by RIA. The CA-125 content in the normal endometrium was 334.7 +/- 39.1 U/mg-protein, and this was significantly (p less than 0.001) higher than that in the myometrium (66.1 +/- 8.6), cervical gland (131.7 +/- 24.2), fallopian tube (111.6 +/- 15.8) and ovary (64.6 +/- 15.6). Endometriotic tissue contained 217.5 +/- 23.1, and adenomyotic tissue contained 235.3 +/- 47.7. No significant difference was found between tissue from cervical and corporal malignancies of the uterus, but ovarian cancer tissue contained a high CA-125 level compared to normal ovarian tissue. The mean concentration of CA-125 in menstrual blood was 377.9 +/- 79.9 U/ml and was about 11 times as high as that seen in peripheral blood in the same donor. The fact that the endometrium contained the highest amount of CA-125 among normal tissues examined supports the hypothesis that externally developed endometrium is the primary source of elevated serum CA-125 in patients with endometriosis.

Adult↗