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Biomedical subjects

N Yoshida

Publications and source records attributed to N Yoshida.

At least 271 records · Page 15Linked to original sources
PubMed1996

Molecular cloning and characterization of a murine pre-B-cell growth-stimulating factor/stromal cell-derived factor 1 receptor, a murine homolog of the human immunodeficiency virus 1 entry coreceptor fusin.

Pre-B-cell growth-stimulating factor/ stromal cell-derived factor 1 (PBSF/SDF-1) is a member of the CXC group of chemokines that is initially identified as a bone marrow stromal cell-derived factor and as a pre-B-cell stimulatory factor. Although most chemokines are thought to be inducible inflammatory mediators, PBSF/SDF-1 is essential for perinatal viability,. B lymphopoiesis, bone marrow myelopoiesis, and cardiac ventricular septal formation, and it has chemotactic activities on resting lymphocytes and monocytes. In this paper, we have isolated a cDNA that encodes a seven transmembrane-spanning-domain receptor, designated pre-B-cell-derived chemokine receptor (PB-CKR) from a murine pre-B-cell clone, DW34. The deduced amino acid sequence has 90% identity with that of a HUMSTSR/fusin, a human immunodeficiency virus 1 (HIV-1) entry coreceptor. However, the second extracellular region has lower identity (67%) compared with HUMSTSR/fusin. PB-CKR is expressed during embryo genesis and in many organs and T cells of adult mice. Murine PBSF/SDF-1 induced an increase in intracellular free Ca2+ in DW34 cells and PB-CKR-transfected Chinese hamster ovary (CHO) cells, suggesting that PB-CKR is a functional receptor for murine PBSF/SDF-1. Murine PBSF/ SDF-1 also induced Ca2+ influx in fusin-transfected CHO cells. On the other hand, considering previous results that HIV-1 does not enter murine T cells that expressed human CD4, PB-CKR may not support HIV-1 infection. Thus, PB-CKR will be an important tool for functional mapping of HIV-1 entry coreceptor fusin and for understanding the function of PBSF/SDF-1 further.

Adult↗
PubMed1996

Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1.

The chemokines are a large family of small, structurally related cytokines. The physiological importance of most members of this family has yet to be elucidated, although some are inducible inflammatory mediators that determine leukocyte chemotaxis. Pre-B-cell growth-stimulating factor/stromal cell-derived factor-1 (PBSF/SDF-1) is a member of the CXC group of chemokines PBSF/SDF-1 stimulates proliferation of B-cell progenitors in vitro and is constitutively expressed in bone-marrow-derived stromal cells. Here we investigate the physiological roles of PBSF/SDF-1 by generating mutant mice with a targeted disruption of the gene encoding PBSF/SDF-1. We found that mice lacking PBSF/SDF-1 died perinatally and that although the numbers of B-cell progenitors in mutant embryos were severely reduced in fetal liver and bone marrow, myeloid progenitors were reduced only in the bone marrow but not in the fetal liver, indicating that PBSF/SDF-1 is responsible for B-cell lymphopoiesis and bone-marrow myelopoiesis. In addition, the mutants had a cardiac ventricular septal defect. Hence, we have shown that the chemokine PBSF/SDF-1 has several essential functions in development.

Animals↗
PubMed1996

Involvement of dopamine D3 receptors in the area postrema in R(+)-7-OH-DPAT-induced emesis in the ferret.

We investigated the possible involvement of dopamine D3 receptors in R(+)-7-hydroxy-2-(N,N-di-n-propylamino)tetraline (R(+)-7-OH-DPAT)-induced emesis in the ferret. The R(+)enantiomer of 7-OH-DPAT (0.03-1 mg/kg, s.c.) caused emesis in a dose-dependent manner, whereas the S(-)enantiomer, even at 1 mg/kg s.c. failed to induce emesis. Quinpirole (0.1-1.0 mg/kg) and apomorphine (0.3 mg/kg, s.c. only) also elicited an emetic response. S(-)-Eticlopride, which has a high affinity for the dopamine D3 receptor, antagonized R(+)-7-OH-DPAT (0.3 mg/kg, s.c.)-induced emesis (ID50 1.4 micrograms/kg, s.c.). R(+)-7-OH-DPAT (0.1-1.0 microgram) administered into the 4th cerebral ventricle dose dependently induced emesis within 1 min of dosing in ferrets. Intracerebroventricularly administered S(-)-eticlopride (0.01-1 microgram) also inhibited the emesis induced by s.c. administration of R(+)-7-OH-DPAT. The emetic effect of R(+)-7-OH-DPAT was unaffected by abdominal vagotomy but was markedly reduced by ablation of the area postrema. These results suggest that dopamine D3 receptors in the area postrema play an important role in R(+)-7-OH-DPAT-induced emesis in the ferret.

Animals↗
PubMed1996

Essential role of Stat6 in IL-4 signalling.

Interleukin-4 (IL-4) is a pleiotropic lymphokine which plays an important role in the immune system. IL-4 activates two distinct signalling pathways through tyrosine phosphorylation of Stat6, a signal transducer and activator of transcription, and of a 170K protein called 4PS. To investigate the functional role of Stat6 in IL-4 signalling, we generated mice deficient in Stat6 by gene targeting. We report here that in the mutant mice, expression of CD23 and major histocompatibility complex (MHC) class II in resting B cells was not enhanced in response to IL-4. IL-4 induced B-cell proliferation costimulated by anti-IgM antibody was abolished. The T-cell proliferative response was also notably reduced. Furthermore, production of Th2 cytokines from T cells as well as IgE and IgG1 responses after nematode infection were profoundly reduced. These findings agreed with those obtained in IL-4 deficient mice or using antibodies to IL-4 and the IL-4 receptor. We conclude that Stat6 plays a central role in exerting IL-4 mediated biological responses.

Animals↗
PubMed1996

Sharp Increase in the Incidence of Mammary Carcinoma in Kagoshima Prefecture, Japan.

Between 1986 and 1990, among a female population of about 0.95 million, 1184 women living in Kagoshima Prefecture were diagnosed pathologically as having mammary carcinoma. The number of patients with mammary carcinoma, the crude incidence rate per 100000 women and age-standardized mammary carcinoma incidence rates were 205, 21.29 and 19.42 in 1986, 212, 22.04 and 19.48 in 1987, 238, 24.74 and 21.8 in 1988, 245, 25.47 and 22.33 in 1989 and 284, 29.57 and 25.69 in 1990, respectively. The number of patients with this disease increased annually. The increase in the age-specific incidence rate of this type of cancer between 1986 and 1990 was 1.38-fold in women between 40 and 49 years of age, 1.46-fold in women between 50 and 59, 1.37-fold in the 60-69 age group, 1.48-fold in the 70-79 age group and 1.91-fold in women over 80. In both the urban and rural areas, the incidence increased annually during the course of this study. In 1990, the age-standardized mammary carcinoma incidence rate in urban area was 1.17 times that in rural area.

Journal Article↗
PubMed1996

Enhanced and accelerated lymphoproliferation in Fas-null mice.

Fas is a 45-kDa membrane protein that transduces an apoptotic signal. The mouse lymphoproliferation (lpr) mutation is a leaky mutation of Fas. In this study, we examined lymphocyte development in Fas-null mice generated by gene targeting. The Fas-/- mice progressively accumulated abnormal T cells (Thy1+, B220+, CD4-, and CD8-) and developed lymphadenopathy and splenomegaly, which were much more accelerated and pronounced than those in lpr mice. In addition, the Fas-null mice showed lymphocytosis, accompanied by lymphocytic infiltration in the lungs and liver. The number of apparently normal B cells also increased, and large amounts of immunoglobulins, including anti-DNA antibodies, were produced. Thymic clonal deletion, assessed by deletion of T cells reactive to mouse endogenous superantigens, was apparently normal in the Fas-/- mice, whereas the peripheral clonal deletion of mature T cells against a bacterial superantigen was impaired. These results suggested that Fas plays a decisive role in peripheral clonal deletion but not in negative selection in the thymus.

Animals↗
PubMed1996

Targeted disruption of gp130, a common signal transducer for the interleukin 6 family of cytokines, leads to myocardial and hematological disorders.

gp130 is a ubiquitously expressed signal-transducing receptor component shared by interleukin 6, interleukin 11, leukemia inhibitory factor, oncostatin M, ciliary neurotrophic factor, and cardiotrophin 1. To investigate physiological roles of gp130 and to examine pathological consequences of a lack of gp130, mice deficient for gp130 have been prepared. Embryos homozygous for the gp130 mutation progressively die between 12.5 days postcoitum and term. On 16.5 days postcoitum and later, they show hypoplastic ventricular myocardium without septal and trabecular defect. The subcellular ultrastructures in gp130-/- cardiomyocytes appear normal. The mutant embryos have greatly reduced numbers of pluripotential and committed hematopoietic progenitors in the liver and differentiated lineages such as T cells in the thymus. Some gp130-/- embryos show anemia due to impaired development of erythroid lineage cells. These results indicate that gp130 plays a crucial role in myocardial development and hematopoiesis during embryogenesis.

Animals↗
PubMed1996

Treatment of high-risk acute lymphoblastic leukemia in children using the AL851 and ALHR88 protocols: a report from the Kyushu-Yamaguchi Children's Cancer Study Group in Japan.

A total of 125 children, who were diagnosed as having high-risk acute lymphoblastic leukemia (ALL), were treated with two consecutive protocols designated as AL851 (1985-1988) and ALHR88 (1988-1990). All patients received induction therapy consisting of vincristine (VCR), prednisolone (PSL), daunorubicin (DNR), and I-asparaginase (I-Asp). In the ALHR88 protocol, the patients whose blasts in the bone marrow (BM) were > or = 25% on day 14 of induction therapy and who were classified into T-cell type received additional cytosine arabinoside (AraC). After consolidation with intermediate-dose methotrexate (MTX), reinduction therapy including VCR, dexamethasone, and adriamycin followed by high-dose AraC was done for all patients. Intrathecal MTX and 24Gy of cranial irradiation were used to prevent central nervous system leukemia. A maintenance therapy consisting of 6-mercaptopurine, cyclophosphamide, MTX, DNR, VCR, and AraC was administered for 3 years after achieving a complete remission (CR). CR was achieved in 51/55 (92.7%) for AL851 and 68/70 (97.1%) for ALHR88. The 5-year event-free survival rates were 49.1 +/- 6.7% in AL851 and 62.5 +/- 6.1% in ALHR88. The factors related to a poor prognosis were a high initial leukocyte count of greater than 50 x 10(9)/L (P < 0.001), an L2 morphology of leukemic cells by FAB classification (P = 0.009), the chromosomal abnormality (P = 0.004) and high residual leukemic cells in BM (> or = 25%) on day 14 of induction therapy (P < 0.001). Taking these factors into consideration, more intensive protocols were started in 1990 for the patients with high-risk ALL.

Adolescent↗
PubMed1996

Rebamipide protects against activation of neutrophils by Helicobacter pylori.

Our objectives were to determine whether rebamipide, a unique antiulcer agent, would inhibit adhesive reactions between neutrophils and endothelial cells as well as the production of active oxygen species from neutrophils elicited by an extract of H. pylori. A water extract of H. pylori that was prepared from biopsy materials obtained from a patient with gastric ulcer increased the surface expression of CD18 on human neutrophils isolated from peripheral blood, the adhesion of neutrophil-endothelial cells, and the production of active oxygen species by neutrophils. Rebamipide, at concentrations of 10(-5) and 10(-6) M, reduced the adherence of neutrophils to endothelial cells as well as the CD18 expression on neutrophils induced by this bacterial extract. Rebamipide also inhibited the production of active oxygen species from neutrophils stimulated by H. pylori extract. These results suggest that rebamipide protects against the gastric mucosal inflammation associated with H. pylori by inhibiting neutrophil function.

Alanine↗
PubMed1996

A novel synthesis method for cyclodextrins from maltose in water-organic solvent systems.

A novel enzymatic synthesis method of cyclodextrin (CD) from low-mol-wt maltose using cyclomaltodextrin glucanotransferase (CGTase) from Bacillus macerans has been developed in various water-organic solvent systems. A beta-CD was synthesized in a two-phase system consisting of water and cyclohexane. However, no CDs could be synthesized in an aqueous buffer solution. A maximal yield of beta-CD has been obtained at a cyclohexane content volume of 44%. This synthesis has been obtained only at low temperatures, i.e., 7 degrees C, and did not take place at 50 degrees C. In addition, various organic solvents have been used for the enzymatic synthesis of CD from maltose. Consequently, beta-CD could be synthesized in various water-organic solvent systems, e.g., cyclohexane, benzene, xylene, and chloroform, but no enzymatic reaction occurred using aliphatic n-hydrocarbon solvents such as hexane, dodecane, and hexadecane. Furthermore, alpha- and beta-CD could be synthesized in water mixture solutions using organic solvents having an alcoholic group (e.g., ethanol, propanol, butanol, and pentanol) in a wide range of the reaction temperatures, typically 7-50 degrees C. In this temperature range, alpha- and beta-CD were also formed and the maximal yield from maltose to beta-CD of approx 13% was reached in 60 h.

Chromatography, High Pressure Liquid↗
PubMed1996

Intrathecally administered NMDA receptor antagonists reduce the MAC of isoflurane in rats.

PURPOSE: We studied the effects of intrathecal administration of an N-methyl-D-aspartate (NMDA) receptor antagonist and an antagonist of the glycine site of the NMDA receptor on the minimum alveolar anaesthetic concentration (MAC) of isoflurane in rats, and on locomotor activity in conscious rats. METHODS: In Wistar rats fitted with indwelling intrathecal catheters, we determined the MAC of isoflurane after the administration of saline (control group); the competitive NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosponic acid(CPP) at 0.01, 0.1, and 1.0 nM; and the selective antagonist of the glycine site on the NMDA receptor complex 7-chlorokynurenic acid (7CKA) at 0.1, 1.0, and 10 nM. After measurement of MAC following administration of the antagonist, the equipotent reversal dose of NMDA or D-serine was administered. The rats were examined for the presence of locomotor dysfunction by intrathecal administration of NMDA receptor antagonists, NMDA and D-serine in conscious rats. All of the experiments were performed using randomization and masking of drugs. RESULTS: CPP at 0.1 and 1.0 nM decreased the MAC of isoflurane by 9.9-17.6% (P < 0.05). 7CKA at 1.0 and 10 nM reduced MAC from 10.5-15.5% (P < 0.05). Intrathecal administration of NMDA or D-serine reversed the decreases in MAC to control values. Locomotor activity was not changed. CONCLUSIONS: We believe that NMDA receptor plays an important role in determining the MAC of isoflurane in the spinal cord.

Anesthetics, Inhalation↗
PubMed1996

A mutant trypsin-like enzyme from Streptomyces fradiae, created by site-directed mutagenesis, improves affinity chromatography for protein trypsin inhibitors.

The Ser-170 residue of a trypsin-like enzyme from Streptomyces fradiae (SFT), which is considered to be the active-site serine, was replaced with alanine by site-directed mutagenesis to improve the affinity chromatography step for a Kazal-type trypsin inhibitor pancreatic secretory trypsin inhibitor (PSTI). The resulting mutant SFT, designated as [S170A]SFT, was expressed in Streptomyces lividans and purified to homogeneity. [S170A]SFT was catalytically inactive, but still had the ability to bind tightly to PSTI and to soybean trypsin inhibitor with dissociation constants of 3.1 x 10(-7) M and 1.9 x 10(-8) M respectively. We further demonstrated that recombinant human PSTI secreted into Saccharomyces cerevisiae culture broth could be purified to homogeneity with a one-step [S170A]SFT-affinity column. The purified PSTI contained no molecules intramolecularly cleaved by active trypsin, which are found when trypsin-affinity chromatography is used for the purification. This eliminated the need for further separation of intact PSTI from intramolecularly cleaved PSTI by high-performance liquid chromatography, thus simplifying and improving its purification process.

Chromatography, Affinity↗
PubMed1996

Identification of a domain of Trypanosoma cruzi metacyclic trypomastigote surface molecule gp82 required for attachment and invasion of mammalian cells.

Recombinant proteins and synthetic peptides representing various sequences of gp82, a surface glycoprotein of Trypanosoma cruzi metacyclic trypomastigotes implicated in mammalian cell invasion, were used in this study aiming at the identification of the domain(s) of this molecule required for interaction with target cells. Invasion of cultured HeLa cells by metacyclic trypomastigotes was inhibited by about 80% in the presence of native gp82 or the corresponding recombinant construct J18. Inhibition by recombinant proteins J18a and J18b, containing respectively the N-terminal and the C-terminal portions of gp82, was on the order of 30% and 65%. As compared to J18b (amino acids 224-516), the truncated gp82 fragments J18b1 (amino acids 303-516) and J18b2 (amino acids 357-516) displayed lower inhibitory effect (approximately 40% and approximately 15%, respectively). Compatible with these observations, we found that the recombinant protein J18b, but not J18a or J18b2, binds to HeLa cells in a dose-dependent and saturable fashion. Experiments with ten overlapping synthetic peptides, representing the gp82 portion spanning amino acids 224-333, showed that peptides 4 (amino acids 254-273) and 8 (amino acids 294-313) have significant inhibitory activity on HeLa cell invasion by metacyclic forms. All these results indicate that the portion of gp82 required for mammalian cell attachment and invasion is located in the central domain of the molecule.

Amino Acid Sequence↗
PubMed1996

The effects of hyperinsulinaemia on myocardial mass, blood pressure regulation and central haemodynamics in rats.

Left ventricular hypertrophy is a condition with high mortality. An association with insulin resistance and hyperinsulinaemia has recently been suggested. The aim of this study was to examine the effects of isolated hyperinsulinaemia on cardiac weight and haemodynamic regulation. Rats were exposed to hyperinsulinaemia for 7 weeks after adrenalectomy with corticosterone substitution and continuous infusion of propranolol to control counter-regulatory mechanism (n = 15) (AIP group). Hypoglycaemia was prevented by glucose in the drinking water. Hyperinsulinaemic (AIP) rats were heavier and had increased relative masses of the myocardium (left ventricle 17% and right ventricle 20%), kidneys and adipose tissues in comparison with normoinsulinaemic adrenalectomized, corticosterone- and propranolol-treated controls (AP) (n = 10). Blood pressure in the insulin-exposed animals, measured weekly by the tail-cuff method in conscious rats, was not different from (AP) controls over 5 weeks, but increased in the sixth week. At the end of the seventh experimental week, blood pressure measured intra-arterially was also found to be elevated. Heart rate was not changed but total peripheral resistance was about twice that of controls (P < 0.001). Cardiac output and stroke volume was 30-40% lower in the AIP rats (P < 0.05). It is concluded that exposure to elevated insulin levels with control of counter-regulating mechanisms from beta-adrenergic mechanisms and adrenals is not immediately followed by blood pressure elevation. It is, therefore, suggested that early onset of blood pressure elevation after insulin exposure might be caused by insulin counter-regulatory events, causing both insulin resistance and blood pressure elevation. The long-term adaptations may involve a direct influence by insulin as a 'trophic factor' on myocardial and on peripheral resistance levels, followed by increased blood pressure, decreased cardiac and stroke volume.

Animals↗
PubMed1996

Simultaneous assessment of regional adrenergic activity and perfusion with 123I-MIBG and 201Tl in congestive heart failure.

Simultaneous assessment of regional adrenergic activity and perfusion with 123I-meta-iodobenzylguanidine (123I-MIBG) and 201Tl in various organs was performed in 13 patients with congestive heart failure (CHF) and 13 subjects without heart failure. In order to reduce the crosstalk of 201Tl to the 123I energy window to less than 5%, a dose of 123I-MIBG more than five times greater than that of 201Tl was administered following 201Tl scintigraphy. Regional uptake of 201Tl (%dose) was significantly increased in the heart (left ventricle) and lung (both P < 0.01) in the patients with CHF. The increased global cardiac uptake could have been related to the enlarged left ventricle. The patterns of regional uptake of 123I-MIBG (% dose) at 15 min were similar to those of 201Tl, suggesting that early 123I-MIBG uptake could in part depend on regional perfusion in both groups. At 3 h, regional uptake of 123I-MIBG was significantly increased in the heart, lung and kidney (all P < 0.01) in the patients with CHF. The delayed 123I-MIBG uptake indicates the degree of neuronal accumulation of the tracer, and therefore reflects adrenergic activity. Interestingly, the cardiac 123I-MIBG (adrenergic activity) to 201Tl (unit of perfusion) ratio decreased significantly in the heart (P < 0.01) but increased significantly in the kidney (P < 0.01) in the patients with CHF compared with the control group. Cardiac 123I-MIBG washout was also significantly increased in the CHF patients. Moreover, the cardiac 123I-MIBG:201Tl ratio was negatively correlated with plasma norepinephrine concentration (r = -0.74, P < 0.01), but positively correlated with LVEF (r = 0.60, P < 0.01). These data suggest that there may be impairment of both the neuronal uptake function and the vesicular storage function in the failing heart, and an increment in neuronal uptake function in the kidneys in patients with CHF. We suggest that dual-tracer scintigraphy is a useful non-invasive method for the simultaneous assessment of adrenergic activity and perfusion in various organs in patients with heart failure.

3-Iodobenzylguanidine↗