Biomedical subjects

H Nishina

Publications and source records attributed to H Nishina.

At least 37 records · Page 2Linked to original sources

PubMed1998

Differential developmental process of respective behavioral states in human fetuses.

The presence of behavioral states has been recognized in human fetuses. However, developmental process of fetal behavioral states remains to be clarified. In thirty-one normal pregnant women between 20 and 41 weeks' gestation, fetal movements were examined by using multiple ultrasonic machines. The entire period was divided into eye movement (EM), no eye movement (NEM), and unclassified periods according to the mode of appearance of rapid eye movements. We investigated changes in the ratio of EM and NEM periods and the incidence of various fetal movements in these periods. The ratio of EM periods increased stepwise between 20 and 32 weeks. The difference in the incidence of "startle" and jaw movements between EM and NEM periods was found at 24-27 and 32-35 weeks, respectively. We found a significant decrease in the incidence of total body movements exclusively in NEM periods at 36-39 weeks and a significant increase in the incidence of "rolling" in EM periods at 40-41 weeks. Eye opening was ultrasonographically recognized, providing evidence for awake state in the human fetus. This study revealed the characteristic appearance of fetal movements as related to the presence or absence of EM during the second half of pregnancy, and thereby pointed to differential development process of behavioral states of human fetuses.

Adult↗

PubMed1998

Activation of c-Jun N-terminal kinase (JNK) by lysophosphatidic acid in Swiss 3T3 fibroblasts.

Lysophosphatidic acid (LPA) induced activation of c-Jun N-terminal kinase (JNK) in Swiss 3T3 fibroblasts. This activation reached the maximum at 20 min and required a high concentration of LPA with an EC50 value of approximately 3 microg/ml. LPA-induced activation of JNK was not suppressed by prior treatment of the cells with pertussis toxin, whereas it was completely blocked by suramin, a non-selective inhibitor of ligand-receptor interactions. The kinetics and concentration-dependency of LPA-induced JNK activation were in sharp contrast with those of LPA-induced extracellular signal-regulated kinase (ERK) activation, which reached the maximum within 3 min and occurred with an EC50 of 0.1 microg/ml. The ERK activation was susceptible to pertussis toxin, whereas it was not inhibited by suramin. These results indicate that the signal transduction pathways of LPA-induced JNK and ERK activations are distinct. Thus, this is the first report showing that LPA induces not only ERK activation but also JNK activation, which may be responsible for the induction of DNA synthesis in LPA-stimulated Swiss 3T3 fibroblasts.

3T3 Cells↗

PubMed1998

Upper cervical myelopathy associated with low CSF pressure: a complication of ventriculoperitoneal shunt.

A patient who had undergone ventriculoperitoneal shunting developed upper cervical myelopathy. His CSF pressure was markedly low, and deformation of the spinal cord and shrinkage of the subarachnoid space at the upper cervical level were found in radiologic examinations. Ligation of the shunt tube resulted in almost complete recovery. The effect of excessive drainage may have caused the abnormalities.

Cerebral Ventriculography↗

PubMed1997

Activation of stress-activated protein kinases/c-Jun N-terminal protein kinases (SAPKs/JNKs) by a novel mitogen-activated protein kinase kinase.

Mitogen-activated protein kinase (MAPK) kinases (MKKs) are dual-specificity protein kinases that phosphorylate and activate MAPK. We have isolated a cDNA encoding a novel protein kinase that has significant homology to MKKs. The novel kinase MKK7 has a nucleotide sequence that encodes an open reading frame of 347 amino acids with 11 kinase subdomains. MKK7 is ubiquitously expressed in all adult and embryonic organs but displays high expression in epithelial tissues at later stages of fetal development. When transiently expressed in 293 cells, MKK7 specifically activated stress-activated protein kinases (SAPKs)/c-Jun N-terminal protein kinases (JNKs) but not extracellular-regulated kinase or p38 kinase. A kinase-negative mutant of MKK7 inhibits interleukin-1beta, lipopolysaccharide, and MEKK1-induced SAPK/JNK activation. Thus, MKK7 is a new member of the MAPK kinase family that functions upstream of SAPK/JNK in the SAPK/JNK signaling pathway.

Amino Acid Sequence↗

PubMed1997

Impaired CD28-mediated interleukin 2 production and proliferation in stress kinase SAPK/ERK1 kinase (SEK1)/mitogen-activated protein kinase kinase 4 (MKK4)-deficient T lymphocytes.

The dual specific kinase SAPK/ERK1 kinase (SEK1; mitogen-activated protein kinase kinase 4/Jun NH2 terminal kinase [ JNK] kinase) is a direct activator of stress-activated protein kinases ([SAPKs]/JNKs) in response to CD28 costimulation, CD40 signaling, or activation of the germinal center kinase. Here we show that SEK1(-/-) recombination-activating gene (RAG)2(-/-) chimeric mice have a partial block in B cell maturation. However, peripheral B cells displayed normal responses to IL-4, IgM, and CD40 cross-linking. SEK1(-/-) peripheral T cells showed decreased proliferation and IL-2 production after CD28 costimulation and PMA/Ca2+ ionophore activation. Although CD28 expression was absolutely crucial to generate vesicular stomatitis virus (VSV)-specific germinal centers, SEK1(-/-)RAG2(-/-) chimeras mounted a protective antiviral B cell response, exhibited normal IgG class switching, and made germinal centers in response to VSV. Interestingly, PMA/Ca2+ ionophore stimulation, which mimics TCR-CD3 and CD28-mediated signal transduction, induced SAPK/JNK activation in peripheral T cells, but not in thymocytes, from SEK1(-/-) mice. These results show that signaling pathways for SAPK activation are developmentally regulated in T cells. Although SEK1(-/-) thymocytes failed to induce SAPK/JNK in response to PMA/Ca2+ ionophore, SEK1(-/-)RAG2(-/-) thymocytes proliferated and made IL-2 after PMA/Ca2+ ionophore and CD3/CD28 stimulation, albeit at significantly lower levels compared to SEK1(+/+)RAG2(-/-) thymocytes, implying that CD28 costimulation and PMA/Ca2+ ionophore-triggered signaling pathways exist that can mediate proliferation and IL-2 production independently of SAPK activation. Our data provide the first genetic evidence that SEK1 is an important effector molecule that relays CD28 signaling to IL-2 production and T cell proliferation.

Animals↗

PubMed1997

Brca2 is required for embryonic cellular proliferation in the mouse.

Mutations of the tumor suppressor gene BRCA2 are associated with predisposition to breast and other cancers. Homozygous mutant mice in which exons 10 and 11 of the Brca2 gene were deleted by gene targeting (Brca2(10-11)) die before day 9.5 of embryogenesis. Mutant phenotypes range from severely developmentally retarded embryos that do not gastrulate to embryos with reduced size that make mesoderm and survive until 8.5 days of development. Although apoptosis is normal, cellular proliferation is impaired in Brca2(10-11) mutants, both in vivo and in vitro. In addition, the expression of the cyclin-dependent kinase inhibitor p21 is increased. Thus, Brca2(10-11) mutants are similar in phenotype to Brca1(5-6) mutants but less severely affected. Expression of either of these two genes was unaffected in mutant embryos of the other. This study shows that Brca2, like Brca1, is required for cellular proliferation during embryogenesis. The similarity in phenotype between Brca1 and Brca2 mutants suggests that these genes may have cooperative roles or convergent functions during embryogenesis.

Animals↗

PubMed1997

Oscillation of ADP-ribosyl cyclase activity during the cell cycle and function of cyclic ADP-ribose in a unicellular organism, Euglena gracilis.

In Euglena gracilis, the activity of ADP-ribosyl cyclase, which produces cyclic ADP-ribose, oscillated during the cell cycle in a synchronous culture induced by a light-dark cycle, and a marked increase in the activity was observed in the G2 phase. Similarly, the ADP-ribosyl cyclase activity rose extremely immediately before cell division started, when synchronous cell division was induced by adding cobalamin (which is an essential growth factor and participates in DNA synthesis in this organism) to its deficient culture. Further, cADPR in these cells showed a maximum level immediately before cell division started. A dose-dependent Ca2+ release was observed when microsomes were incubated with cADPR.

ADP-ribosyl Cyclase↗

PubMed1997

Stress-signalling kinase Sek1 protects thymocytes from apoptosis mediated by CD95 and CD3.

Distinct and evolutionarily conserved signal transduction cascades mediate survival or death in response to developmental and environmental cues. The stress-activated protein kinases, or Jun N-terminal kinases (SAPKs/JNKs), are activated in response to a variety of cellular stresses such as changes in osmolarity and metabolism, DNA damage, heat shock, ischaemia, or inflammatory cytokines. Sek1 (JNKK/MKK4) is a direct activator of SAPKs/JNKs in response to environmental stresses or mitogenic factors. Here we investigate the role of Sek1 in development and apoptosis by deleting sek1 in embryonic stem (ES) cells by homologous recombination. We provide genetic evidence that different stresses utilize distinct signalling pathways for SAPK/JNK activation. sek1(-/-) rag2(-/-) chimaeric mice have normal numbers of mature T cells but fewer immature CD4+CD8+ thymocytes. The sek1 mutation did not affect the induction of apoptosis in response to environmental stresses in ES and T cells: instead, sek1 protected thymocytes from CD95 (Fas)- and CD3-mediated apoptosis. These data indicate that SEK1 mediates survival signals in T-cell development.

Animals↗

PubMed1997

Signal transduction via the CD38/NAD+ glycohydrolase.

The human cell surface CD38 molecule is a 46-kDa type-II transmembrane glycoprotein with a short N-terminal cytoplasmic domain and a long Cys-rich C-terminal extracellular one. We previously demonstrated that an ecto-form NAD+ glycohydrolase (NADase) activity induced by all-trans retinoic acid in HL-60 cells is due to the extracellular domain of CD38. In the present study, we investigated a possible signal transduction mediated through CD38 in the retinoic acid-differentiated HL-60 cells with anti-CD38 monoclonal antibodies (mAbs). The addition of selected anti-CD38 mAbs to the cells induced rapid tyrosine phosphorylation of the cellular proteins with the molecular weights of 120,000, 87,000 and 77,000; the phosphorylated 120-kDa protein was identified as the c-cbl proto-oncogene product, p120c-cbl. Furthermore, the phosphorylated p 120c-cbl associated with the 85-kDa subunit of phosphatidylinositol 3-kinase. To determine the relationship between the amino acid sequence responsible for the NADase activity and epitopes recognized by the stimulatory mAbs, we produced its carboxy-terminal deletion mutants in COS-7 cells. The mutants with less than 15 amino acids deleted from the carboxyl terminus of the 300-amino acid wild-type molecule still maintained NADase activity, but those with more than 27 amino acids deleted did not. Introduction of site-directed mutation of a cysteine residue (Cys275), located in the 273-285 sequence, completely abolished the NADase activity. These CD38 mutants were also used for an epitope mapping of anti-CD38 mAbs. All the epitopes recognized by the mAbs inducing the tyrosine phosphorylation were mapped on the same Cys275-containing sequence of 273-285. Thus, the discrete carboxy-terminal sequence not only plays a key role in its ecto-NADase activity, but also contains the epitopes of the agonistic anti-CD38 mAbs for the transmembrane signaling. We also found that the agonistic mAbs markedly potentiate superoxide generation induced by the stimulation of G protein-coupled chemotactic receptors. Our results suggested that the stimulation of CD38 might generate an accessory signal(s) to enhance the G protein-mediated signaling, probably though the protein-tyrosine phosphorylation.

ADP-ribosyl Cyclase↗

PubMed1997

Developmental sequence of human fetal body movements in the second half of pregnancy.

To describe fetal body movements precisely and to clarify their developmental sequence in the second half of pregnancy, fetal body movements were observed in 31 normal fetuses between 20 and 41 weeks of pregnancy by using multiple ultrasonic machines. All movements of the whole trunk were able to be classified into six fundamental movements: flexion, stretch, rolling, startle, stepping, and writhing. Startle was always observed as a single movement, but others were more frequently observed as a part of combination rather than as a single movements. The incidence of flexion and stretch peaked at 28-31 weeks, whereas the incidence of startle and stepping lowered at the period. The incidence of rolling and upper half trunk movements increased at 40-41 weeks. Limb movements were frequent and did not exhibit characteristic change in the incidence. In conclusion, we classified fetal body movements into several fundamental movements instead of using the expression of "general movements" by focusing principally on movements of the trunk. In particular, some of the fundamental movements seem to appear in characteristic ways as related to gestational age. In view of that fetal behaviors are closely related to the neural activity, the present findings may contribute to an understanding of the developmental process of the central nervous system.

Abdomen↗

PubMed1997

Differential clinical courses of pregnancies complicated by diabetes insipidus which does, or does not, pre-date the pregnancy.

We present six cases of diabetes insipidus (DI) complicating pregnancy. In three cases, DI was manifested during pregnancy and required the administration of desmopressin acetate (1-desamino-8-D-arginine vasopressin, DDAVP). All these cases exhibited abnormal laboratory data such as an elevation of liver enzymes or a decrease in serum antithrombin III. The remaining three cases had suffered from DI before pregnancy which was well controlled on DDAVP. The clinical courses of these pregnancies were all uneventful subsequent to therapy. If DI is first recognized during pregnancy, attention should be paid to the possibility of abnormal liver function and eclampsia.

Adult↗

PubMed1997

An evaluation of the system to control blood flow in maintaining goat fetuses on arterio-venous extracorporeal membrane oxygenation: a novel approach to the development of an artificial placenta.

We compared various methods to control blood flow for extrauterine incubation of goat fetuses without lung respiration using arterio-venous extracorporeal membrane oxygenation via umbilical vessels to develop a suitable system for a long-term life support system for premature neonates. In twenty-seven consecutive preparations of goat fetuses, 4 designs (System 1, manual flow control without a reservoir; System 2, manual flow control with an arterial open-top reservoir; System 3, semiautomatic flow control with an arterial open top reservoir; and System 4, semiautomatic flow control with a tube occluder and an arterial open top reservoir) were tested in terms of the duration of incubation periods during which fetuses were kept under stable conditions. The incubation periods became prolonged with the advancement of the system (System 1, 5.4 h; System 2, 11.6 h; System 3, 64.8 h; and System 4, 159.8 h medians of the incubation periods). The incubation periods with System 4 were significantly longer compared to those with System 1 and System 2. These results suggest that, for extrauterine incubation of goat fetuses using arterio-venous extracorporeal membrane oxygenation via umbilical vessels, the method to control blood flow is of utmost importance for long-term maintenance, and thus a control system with the fixed vascular resistance of the extracorporeal circuit is applicable to long-term maintenance of premature goat fetuses.

Animals↗

PubMed1997

Evidence for an elevation in serum interleukin-2 and tumor necrosis factor-alpha levels before the clinical manifestations of preeclampsia.

PROBLEM: The purpose of this study is to clarify whether the disruption of immune regulation occurs in early pregnancy before the clinical manifestations of preeclampsia. METHOD OF STUDY: The serum concentrations of interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) were determined by using enzyme-linked immunoadsorbent assay (ELISA) in the first trimester of pregnancy in women who had preeclampsia develop after 28 weeks of pregnancy (preeclamptic group) and in women who completed pregnancy uneventfully (control group). RESULTS: Serum concentrations of both IL-2 and TNF-alpha in the first trimester of the preeclamptic group were significantly higher than those of the control group. CONCLUSIONS: That the perturbation of feto-maternal immune regulation may precede the clinical manifestations of preeclampsia, which may be of relevance in the development of preeclampsia, is suggested.

Adult↗

PubMed1996

Stimulation of ADP-ribosyl cyclase activity of the cell surface antigen CD38 by zinc ions resulting from inhibition of its NAD+ glycohydrolase activity.

The lymphocyte cell surface antigen, CD38, which has an amino acid sequence similar to Aplysia ADP-ribosyl cyclase, catalyzes not only the hydrolysis of NAD+ and 1-(5-phospho-beta-D-ribosyl) adenosine 5'-phosphate cyclic anhydride (cyclic ADP-ribose) but also the formation of cyclic ADP-ribose from NAD+. To characterize the bifunctional enzyme properties, we produced the recombinant CD38 fused with a maltose-binding protein (MBP-CD38). Zinc ions stimulated the ADP-ribosyl cyclase activity of MBP-CD38, but inversely inhibited its NAD+ glycohydrolase activity which was approximately 100-fold dominant to the cyclase activity in the absence of Zn2+. Such dual effects of Zn2+ were also observed in the native membrane-bound CD38 of HL-60 cells which had been caused to differentiate by retinoic acid. Zinc ions inhibited the NAD+ glycohydrolase reaction catalyzed by MBP-CD38 in an uncompetitive manner, whereas they enhanced the ADP-ribosyl cyclase reaction without affecting the Km value for NAD+. There was an increase in the fluorescence intensity of a hydrophobic fluorescent probe, 8-anilino-1-naphthalenesulfonate, in the presence of MBP-CD38. The fluorescence increase was further enhanced by the addition of Zn2+ with a shift in the maximum emission wavelength from 484 nm to 470 nm, suggesting that Zn2+ caused conformational changes of MBP-CD38. These results indicate that Zn2+ directly interacts with CD38 to stimulate its ADP-ribosyl cyclase with inhibition of its NAD+ glycohydrolase, probably due to prevention of the access of water molecule to an intermediate of the enzymesubstrate complex.

ADP-ribosyl Cyclase↗

PubMed1996

Inhibition of NAD+ glycohydrolase and ADP-ribosyl cyclase activities of leukocyte cell surface antigen CD38 by gangliosides.

We have recently reported that gangliosides act as inhibitors of ADP-ribosyltransferases and NAD+ glycohydrolases (NADase) of pertussis toxin and the C3 exoenzyme from Clostridium botulinum (Hara-Yokoyama, M., Hirabayashi, Y., Irie, F., Syuto, B., Moriishi, K., Sugiya, H., and Furuyama, S. (1995) J. Biol. Chem. 270, 8115-8121). Here, we investigated the effect of gangliosides on the enzymatic activity of leukocyte cell surface antigen CD38, which is identified as an ecto-NADase (Kontani, K., Nishina, H., Ohoka, Y., Takahashi, K., and Katada, T. (1993) J. Biol. Chem. 268, 16895-16898). Gangliosides GM1a and GQ1balpha inhibited the NADase activity in the immunoprecipitate of anti-CD38 antibody from the membrane extract of retinoic acid-treated human leukemic HL-60 cells. Gangliosides also inhibited the NADase activity of the extracellular domain of CD38 antigen that was deprived of the transmembrane domain and was expressed in Escherichia coli as a fusion protein with maltose-binding protein (MBP-CD38). The order of the inhibitory effect of purified ganglioside species on the NADase activity on MBP-CD38 was as follows: GQ1balpha > GT1b, GQ1b > GD1a, GD1b, GM1a, GM1b, GD3, GM3. GQ1balpha inhibited the NADase of MBP-CD38 in a noncompetitive manner versus NAD+ with a Ki value of about 0.3 microM. Neither ceramide nor the oligosaccharide moiety of GQ1balpha had an effect on the NADase activity. GQ1balpha, GT1b, and GQ1b also efficiently inhibited the ADP-ribosyl cyclase activity of MBP-CD38. At present, gangliosides are the only endogenous species that can block the enzymatic activity of CD38 antigen. The present results suggest a potential role of gangliosides as inhibitors of the ecto-NADases.

ADP-ribosyl Cyclase↗

PubMed1996

Tyrosine phosphorylation of the c-cbl proto-oncogene product mediated by cell surface antigen CD38 in HL-60 cells.

The human cell surface antigen CD38 is a 46-kDa type II transmembrane glycoprotein with a short N-terminal cytoplasmic domain and a long Cys-rich C-terminal extracellular one. We demonstrated previously that the extracellular domain of CD38 has NAD+ glycohydrolase (NADase) activity and that the ecto-form NADase activity induced in HL-60 cells during cell differentiation by retinoic acid is due to CD38. In the present study, we investigated the intracellular signaling mediated by CD38 in retinoic acid-differentiated HL-60 cells with an anti-CD38 monoclonal antibody. The addition of anti-CD38 monoclonal antibody to the cells induced rapid tyrosine phosphorylation of the cellular proteins with molecular weights of 120,000, 87,000, and 77,000. An increase in tyrosine kinase activity in the anti-phosphotyrosine immunoprecipitates of the cells was also observed after the addition of anti-CD38 monoclonal antibody. Moreover, one of the prominent tyrosine-phosphorylated proteins stimulated by the anti-CD38 monoclonal antibody was identified as the c-cbl proto-oncogene product, p120c-cbl. These results indicated that tyrosine phosphorylation of cellular proteins, including p120c-cbl, is possibly involved in transmembrane signaling mediated by CD38.

ADP-ribosyl Cyclase↗

PubMed1996

Characteristic changes in sleep patterns during pregnancy in rats.

The purpose of this study was to evaluate changes in sleep patterns during pregnancy to better understand sleep regulation during pregnancy. We uninterruptedly recorded electroencephalogram (EEG), electromyogram (EMG), and brain temperature (Tbr) throughout pregnancy in rats. The duration of non-rapid eye movement (non-REM) sleep decreased after day 5 of pregnancy associated with an inverse increase in the number of non-REM sleep episodes. Thus, the amount of total non-REM sleep time remained constant throughout pregnancy. The amount of total REM sleep time decreased on day 17 of pregnancy after which the reduced state was sustained. That was mainly due to a decrease in the number of REM sleep episodes. Brain temperature (Tbr) gradually decreased as pregnancy advanced, reaching its lowest value 3 days before delivery. These observations provide a better understanding of the sleep patterns during pregnancy, and useful information for investigation of mechanisms of sleep regulation during pregnancy.

Animals↗

PubMed1995

Neuronal localization of CD38 antigen in the human brain.

CD38 is a lymphocyte differentiation antigen which is involved in the cyclic ADP-ribose-mediated second messenger system. We provide immunochemical and immunohistochemical evidence for the expression of CD38 in the adult human brain. We used six polyclonal antibodies against synthetic CD38 polypeptides, in addition to four monoclonal antibodies already available. Brain CD38 was detectable by Western blotting after immunoaffinity purification of the brain extracts. Immunoperoxidase staining localized CD38 immunoreactivity to the perikarya and dendrites of many neurons, such as the cerebellar Purkinje cells, implying that CD38 is involved in the signal transduction within the central nervous system neurons.

ADP-ribosyl Cyclase↗