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Y Arita

Publications and source records attributed to Y Arita.

At least 19 recordsLinked to original sources
PubMed1992

Growth of human melanocyte cultures supported by 12-O-tetradecanoylphorbol-13-acetate is mediated through protein kinase C activation.

To investigate the role of protein kinase C (PKC) in the 12-O-tetradecanoylphorbol-13-acetate (TPA)-dependent growth of human melanocytes, we analyzed the effects of phorbol ester treatment on both PKC expression and growth control in these cells. We found that established cultures of normal melanocytes contain the PKC alpha, PKC beta, and PKC epsilon isoforms. The abilities of various phorbol ester compounds to stimulate DNA synthesis in these cultured melanocytes correlated with their known potencies for activation of PKC and tumor promotion. Dose-response studies revealed that the most effective TPA concentration for stimulation of DNA synthesis and growth of melanocytes (10 ng/ml TPA) also supported a relatively high level of PKC enzyme activity, increased membrane association of the PKC alpha and PKC epsilon isoforms, and led to a high level of phosphorylation of a major PKC substrate, the myristoylated alanine-rich C kinase substrate (MARCKS) protein. Melanocytes incubated for 48 h with TPA at a higher concentration (100 ng/ml TPA) exhibited suboptimal TPA-stimulated DNA synthesis (28% of maximal) and decreased phosphorylation of the MARCKS substrate protein (50% of maximal). Furthermore, treatment of melanocytes with 100 ng/ml TPA for 48 h resulted in a marked decrease in total PKC enzyme activity and the loss of expression of the PKC alpha and PKC epsilon isoforms in both the cytosol and membrane-bound fractions, when examined by immunoblot analysis. These results, taken together, suggest that continuous activation of PKC by TPA, rather than the loss of PKC due to TPA-induced down-regulation, is responsible for the growth-stimulatory effects of phorbol esters on normal human melanocytes. Additionally, the conditioned medium from TPA-treated human melanocytes stimulated DNA synthesis in quiescent melanocytes and human melanoma cells, thus suggesting that activation of the PKC signaling pathway in melanocytes leads to the production of an autocrine growth factor. These findings may be relevant to the autonomous growth of malignant melanomas.

Cell Division↗
PubMed1992

Phorbol ester attenuates inositol 1,4,5-trisphosphate-induced Ca2+ release in electropermeabilized rat pancreatic acini.

To investigate the mechanism of inositol trisphosphate (IP3)-induced Ca2+ release from the internal Ca2+ store, we examined the effects of heparin, phorbol ester and cyclic nucleotides on Ca2+ release induced by carbachol or inositol 1,4,5-trisphosphate (1,4,5-IP3). For monitoring changes of Ca2+ we used the fluorescent indicator, fura-2, in electropermeabilized rat pancreatic acini. An amount of 100 micrograms/ml heparin inhibited the Ca2+ release induced by 1 microM 1,4,5-IP3 in permeabilized acini. Pretreatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) for 10 min reduced the release of Ca2+ induced by 10 microM carbachol and 1 microM 1,4,5-IP3 in permeabilized acini. Staurosporine, a protein kinase C inhibitor, blocked the inhibitory effect of TPA. Cytosolic calcium concentration was restored by staurosporine in TPA-treated acini. Although cyclic AMP exaggerated the amylase release induced by carbachol, cyclic AMP and cyclic GMP had no effect on the carbachol-induced release of Ca2+ in permeabilized acini. These findings suggest that protein kinase C may act at the level of the IP3 receptors or the IP3-operated Ca2+ channels of the internal Ca2+ store and indicate that cyclic nucleotides do not affect the IP3-induced release of Ca2+ in rat pancreatic acini.

Animals↗
PubMed1992

Anorexia nervosa responding to zinc supplementation: a case report.

An emaciated 16-year-old female with anorexia nervosa was hospitalized for treatment of vomiting, epigastralgia and diarrhea. The finding of a taste disorder, low serum alkaline phosphatase activity and relatively low serum zinc level strongly suggested a zinc deficiency. Zinc was initially administered intravenously (40 mumol/day) for 7 days, then orally (15 mg elemental zinc/day) for about 60 days. Her digestive symptoms disappeared after the second day of intravenous treatment and she began to gain weight. She rapidly regained her normal weight after one month of receiving the oral zinc supplementation. Both exocrine pancreatic function and intestinal absorption were improved by the prolonged oral administration of zinc. In such cases zinc supplementation may be a therapeutic option in addition to psychologic and other approaches to management.

Adolescent↗
PubMed1992

Horseshoe anomaly of the pancreas.

A 72-year-old man with recurrent pancreatitis and a horseshoe-shaped anomaly of the pancreas is described. The diagnosis was made by endoscopic retrograde cholangiopancreatography (ERCP) and computed tomography scan; laparotomy was confirmatory. The abnormal duct branched to the lower left from an enlarged Santorini's duct; a thin Wirsung's duct was joined at its distal portion to the junction of the abnormal duct. The anomaly was associated with a cystic dilatation of the common bile duct with stone and cholecystolithiasis. This anomaly is considered to be a variation of the dominant dorsal duct syndrome.

Aged↗
PubMed1991

Structural studies on a binding site for Dolichos biflorus agglutinin in the small intestine of the mouse.

Glycoproteins which bound to Dolichos biflorus agglutinin (DBA) were isolated from the small intestine of 129/Sv mice. Among oligosaccharides released from the carbohydrate moieties of the glycoproteins by endo-beta-galactosidase, the major one with N-acetylgalactosamine at the non-reducing end was isolated by QAE-Sephadex A-25 column chromatography. The structure of the oligosaccharide was elucidated to be GalNAc beta 1----4(NeuAc alpha 2----3)Gal beta 1----4GlcNAc beta 1----3Gal by compositional analysis, methylation analysis before and after mild acid hydrolysis, sequential glycosidase digestion, secondary ion mass spectrometry (SIMS), and nuclear magnetic resonance spectroscopy. The SIMS signal of m/z 1,071 was consistent with the presence of the branched sequence, GalNAc(NeuAc)GalGlcNAc, and the signal was also detected in the high-molecular-weight fraction obtained after endo-beta-galactosidase digestion. The pentasaccharide identified here has the terminal structure of ganglioside GM2, and an apparently identical one has been identified as the epitope of blood group Sda and the DBA binding site in human T-H urinary glycoprotein. Thus, the present result has extended our knowledge of the biological meaning of the oligosaccharide structure and has established that GalNAc beta 1----4(NeuAc alpha 2----3)Gal beta 1----4GlcNAc is a DBA binding site in the small intestine of the mouse.

Animals↗
PubMed1991

Effects of H7 and staurosporine on cytosolic free calcium and amylase secretion in rat pancreatic acini.

Pretreatment of rat pancreatic acini with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) for 5 or 10 min reduced cytosolic free calcium and amylase secretion stimulated by submaximal concentration (10(-6) M) of carbachol in a dose-dependent manner. 10(-7) M TPA inhibited initial amylase secretion and had no effect on sustained secretion stimulated by 10(-6) M carbachol. 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7), a protein kinase C inhibitor, partially blocked these inhibitory effects of TPA. Cytosolic calcium concentration and initial amylase secretion were recovered with 10-100 microM H7 in TPA-treated acini. H7 was more effective than N-(2-guanidinoethyl)-5-isoquinoline-sulfonamide hydrochloride in increasing cytosolic free calcium in TPA-treated acini. TPA completely blocked an increase in cytosolic free calcium by 10 mM NaF. These findings indicated that TPA caused the inhibitory effects by means of activating protein kinase C, and suggested that protein kinase C might regulate enzyme secretion by inhibiting calcium mobilization, probably through a postreceptor-mediated mechanism.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Effects of calcium-channel blockers on cytosolic free calcium and amylase secretion in rat pancreatic acini.

We investigated the effects of verapamil and diltiazem on cytosolic free calcium and amylase secretion in rat pancreatic acini. Verapamil and diltiazem reduced a rise in cytosolic free calcium and amylase release stimulated by the maximal concentration (10(-5) M) of carbachol in a dose-dependent manner. High concentrations (500 microM) of verapamil and diltiazem inhibited both the initial and the sustained amylase secretion stimulated by 10(-5) M carbachol. However, at low concentration (1 microM), they showed no effect on amylase secretion by 10(-5) M carbachol. These calcium-channel blockers did not affect calcium mobilization and amylase secretion stimulated by either caerulein or neuromedin C. Binding of 3H-N-methylscopolamine to pancreatic acini was inhibited by verapamil and diltiazem in a dose-dependent manner. These findings suggested that verapamil and diltiazem reduced carbachol-induced amylase secretion probably not due to their calcium-channel blocking activities but due to their non-competitive effects on the level of muscarinic receptors.

Amylases↗
PubMed1990

Tumor necrosis factor enhances GD3 ganglioside expression in cultured human melanocytes.

Human skin melanocytes and melanocytes cultured in vitro express GM3 ganglioside almost exclusively, whereas malignant melanomas express high levels of both GM3 and GD3. We now show that treatment of cultured melanocytes with tumor necrosis factor-alpha, particularly in the presence of tetradecanoylphorbol-13-acetate, results in a change in morphology from spindle-shaped to epithelioid and greatly enhanced expression of GD3 ganglioside. This effect is specific and no other ganglioside is affected, except that GM3 expression (which is already high) is also increased. In contrast, these agents did not enhance the already high expression of GD3 on melanoma cells. This result provides an example of the plasticity of glycolipid expression in mammalian cells and their susceptibility to the influence of biological agents.

Antibodies, Monoclonal↗
PubMed1990

Frequent expression of myeloid antigen (CD13) on immature T cells in culture.

Leukemic cells from 12 patients with lymphoblastic lymphoma (LBL) and T cell acute lymphoblastic leukemia (T-ALL) were studied to determine the inducibility of myeloid antigens in culture in the presence and absence of 12-O-tetradecanoylphorbol-13-acetate (TPA) in association with discrete phenotypic and genotypic analyses on these cells. The investigation revealed that leukemic cells corresponding to common or mature thymocytes were never induced to express any myeloid antigens, and showed rearrangements of T cell antigen receptor (TcR) beta and gamma chain genes. Concomitant examination on leukemic cells from mature T cell malignancies, including adult T cell leukemia (ATL), T cell chronic lymphocytic leukemia (T-CLL) and T cell non-Hodgkin's lymphoma (T-NHL), also failed to express myeloid antigens in culture. By contrast, one of the panmyeloid antigens, CD13 (MCS-2) antigen was induced on leukemic cells corresponding to early thymocytes in 5 out of 7 cases in TPA-added culture and in 3 cases even in TPA-free culture. All of these CD13 antigen inducible cases exhibited the germ line configurations of TcR beta and gamma chain genes except for one case of T-ALL with sole TcR gamma chain gene rearrangement. These findings suggest that primitive T cells, still not undergoing TcR gene rearrangements, retain the characteristics of multipotent progenitor cells to possess different lineage markers and are able to express myeloid antigen not exceptionally. Both phenotypically and genotypically immature thymocytes are considered to be less restricted in the differentiation pathway of hematopoietic cells committed to T cell lineage.

Antigens, Differentiation, Myelomonocytic↗
PubMed1989

Acute transformation of chronic large granular lymphocyte leukemia associated with additional chromosome abnormality.

A patient with large granular lymphocyte (LGL) leukemia that transformed into an acute or aggressive form after 20 months of the chronic phase is reported. The patient's leukemic cells were mature, medium-sized lymphocytes with sparse azurophil granules and the surface phenotypes of the cells were CD2+, CD3-, CD11+, and CD16+. Molecular analysis showed a germ line configuration in both T-cell receptor beta-chain genes and T-cell receptor tau-chain genes. A clonal anomaly of chromosome (trisomy 8) was demonstrated in peripheral blood cells. LGL after acute transformation of the disease displayed large blastic morphology with prominent nucleoli, intense basophilic cytoplasm, and numerous granules. Karyotypic analysis demonstrated a mosaic of trisomy 8 and trisomy 8 with an additional marker chromosome. Thus, transformation of chronic LGL leukemia into an acute or aggressive form in this patient was associated with morphologic and karyotypic changes of the leukemic cells. Patients with a stable form of chronic LGL leukemia should be examined carefully for the possible acute crisis associated with a clonal evolution.

Adult↗
PubMed1989

Immunohistochemical analysis of peripheral T-cell lymphoma in Japanese patients.

The authors immunohistochemically analyzed the phenotype of 40 cases of peripheral T-cell lymphoma, including 12 adult T-cell leukemia/lymphoma (ATL) cases. Molecular genetic analysis of the T-cell receptor beta-chain and immunoglobulin heavy chain genes were also applied to cases of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD)-like lymphoma and so-called Lennert's lymphoma. Twenty non-ATL lymphomas expressed a helper/inducer phenotype, whereas only one extranodal case expressed a suppressor/cytotoxic phenotype. Three cases had a CD4-CD8- phenotype, and two cases a CD4+CD8+phenotype. No specific relationship between morphologic characteristics (LSG classification) and phenotype was found among non-ATL lymphomas. Six of eight AILD-like lymphomas had a helper/inducer phenotype. Monoclonality of neoplastic T-cells was demonstrated in six of the seven cases of AILD-like lymphoma by molecular genetic analysis. Two cases of Lennert's lymphoma also showed a helper/inducer phenotype and rearrangement of the T-cell receptor beta-chain gene. Serologically defined ATL cases had a helper/inducer phenotype except in one case that expressed both CD4 and CD8. None of the ATL cases had the CD7 antigen in this study using WT 1 as a CD7 antibody, which is in contrast with the non-ATL lymphomas in which 13 of 25 cases expressed CD7. CD25, strongly detectable in all ATL cases, was negative or weakly expressed in non-ATL lymphomas. These facts suggest that non-ATL and ATL are in the different biologic state, probably resulting from the integration of human T-cell leukemia virus type I (HTLV-I), although both are derived from helper/inducer T-cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

The relationship between free cytosolic calcium and amylase release in rat pancreatic acini.

We have studied the effects of various pancreatic secretagogues on free cytosolic calcium ([Ca2+]i) and amylase release in dispersed rat pancreatic acini, to determine the role of [Ca2+]i in stimulated enzyme secretion from the exocrine pancreas. Dispersed rat pancreatic acini were loaded with the new Ca2+-sensitive fluorescent indicator, fura-2. Resting [Ca2+]i was 110 +/- 2 nM (a mean +/- S.E.). Carbachol, caerulein, bombesin, and neuromedin B and C each caused a rapid increase in [Ca2+]i; maximal increases of 100 to 400-500 nM were reached within 20s following the secretagogue addition, and this was followed by a return to a lower sustained level within 2 min. When enzyme secretion from the acini was monitored as a function of time using a perifusion system, secretagogue-induced amylase release took a biphasic pattern consisting of an initial burst phase for a several minutes and a second sustained phase during stimulation. Although sustained amylase secretion occurred at near resting [Ca2+]i, the peak [Ca2+]i correlated with the amount of stimulated amylase release as well as with the initial release, during submaximal and maximal stimulation by these agents. At supramaximal concentrations of carbachol and caerulein, amylase release, but not the increase in [Ca2+]i, was attenuated. On the other hand, in response to supramaximal concentrations of bombesin, and neuromedin B and C, both the amount of amylase released and the peak [Ca2+]i were similar to those obtained in response to maximal concentrations. From a standpoint of time course analysis of enzyme secretion, both the first burst phase and the second sustained phase were inhibited during stimulation by 10(-3) M carbachol, compared with 10(-5) M carbachol, while supramaximal stimulation by neuromedin C caused a pattern of amylase release similar to that produced by maximal stimulation. These data suggest that in pancreatic acinar cells an increase in [Ca2+]i plays an important role in stimulus-secretion coupling; however, other factors may be indispensable in regulating enzyme secretion. Furthermore, it is suggested that there is a difference in the intracellular messenger system between carbachol and caerulein, and neurotransmitters belonging to the bombesin family, especially during supramaximal stimulations.

Amylases↗
PubMed1989

Cross-lineage gene rearrangements in human leukemic B-precursor cells occur frequently with V-DJ rearrangements of IgH genes.

Gene configurations of immunoglobulin (Ig), T-cell antigen receptor (TCR) beta chain, and T-cell rearranging gene gamma (TRG gamma) were studied in human B-precursor lymphoblastic leukemic cells. These cells were phenotypically classified into three developmental stages (stages II through IV) according to Nadler's criteria. All of them showed the Ig heavy chain (IgH) gene rearrangement, and 67% of the cells in stage IV had the rearranged TRG gamma, albeit seldom in other stages. We further analyzed IgH gene rearrangements in detail using upstream to DH (diversity region of IgH) region probe to distinguish DJ from V-DJ recombination. All dual genotyped cells in each stage except one case in stage II showed the V-DJ rearrangements. This suggests the cross-lineage involvement of the putative recombinase, particularly in the process of V-DJ rearrangements. We next examined the transcriptional status of Ig genes as an indirect reflection of the accessibility of these genes to the recombinase. Properly spliced IgH transcripts of normal size were observed in stage IV and surface Ig positive stage, but not in stage II nor III. However, IgH transcripts of aberrant sizes were seen in stage II, III, and also IV. Cross-lineage gene rearrangements were shown to occur frequently when normally spliced IgH gene begins to be transcribed or just before this. These findings may implicate that V-DJ or V-VDJ gene rearrangements forming functional IgH genes, induce frequently TCR or TRG gene rearrangements. We propose these dual genotypes are different in origin from those observed in stem cell leukemia.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1988

Fulminant clonal expansion of large granular lymphocytes. Characterization of their morphology, phenotype, genotype, and function.

A 39-year-old woman exhibited abrupt malignant transformation of the large granular lymphocytes (LGL) after a chronic course of T gamma-lymphoproliferative disease (T gamma-LPD). The T gamma-lymphocytes were CD2+, CD3-, CD8-, CD16+, Leu7-, and Leu19+ with morphologic characteristics of LGL. Newly appearing LGL were much larger and had more prominent azurophilic granules. Although fundamentally they had the same phenotype as the LGL in chronic stage, they showed increased Ia-like antigen and decreased CD16 antigen expressions. Immunoglobulin (Ig) G-kappa type monoclonal component was detected in the patient's serum. The LGL showed a germ-line configuration for T-cell receptor (TCR) beta and gamma chain genes, whereas the clonal chromosomal abnormalities indicated the neoplastic nature of the LGL. The LGL exhibited competent natural killer (NK), interleukin 2 (IL2) activated killer (AK), and antibody-dependent cell-mediated cytotoxicity (ADCC) activities. The LGL may have derived from NK cells at their mature stage with prethymic phenotype and may have influenced the homeostasis of the patient's humoral immune response.

Adult↗