Search PubMed⌕ Search

Biomedical subjects

Y Hashimoto

Publications and source records attributed to Y Hashimoto.

At least 595 records · Page 33Linked to original sources
PubMed1996

Only sphingolipid activator protein B (SAP-B or saposin B) stimulates the degradation of globotriaosylceramide by recombinant human lysosomal alpha-galactosidase in a detergent-free liposomal system.

The degradation of globotriaosylceramide (GbO-se3Cer) by insect-cell derived recombinant human alpha-galactosidase (EC 3.2.1.22) was carried out in a detergent-free liposomal system in order to mimic intralysosomal conditions. GbOse3Cer incorporated into unilamellar liposomes was used as the substrate, and naturally occurring sphingolipid activator proteins, rather than detergents, were used to stimulate the enzyme reaction. The degradation of GbOse3Cer was dependent on the presence of both alpha-galactosidase and sphingolipid activator protein B (SAP-B or saposin B). It proceeded optimally at pH 4.6, and was enhanced by increasing amounts of both alpha-galactosidase (0.24-24 mU/50 microliters assay) and SAP-B (0-5 micrograms/50 microliters assay). The enzyme reaction was not affected by SAP-A, SAP-C, or SAP-D. Therefore, our results indicate that only SAP-B is essential for the degradation of GbOse3Cer by alpha-galactosidase.

Animals↗
PubMed1996

Inducer-specific bidirectional regulation by thalidomide and phenylphthalimides of tumor necrosis factor-alpha production.

Regulation by thalidomide [N(alpha)-phthalimidoglutarimide] of tumor necrosis factor (TNF)-alpha production was found to be inducer-specific. Thalidomide enhances TNF-alpha production by human leukemia HL-60 cells induced with 12-O-tetradecanoylphorbol 13-acetate (TPA), while it inhibits TNF-alpha production induced with okadaic acid (OA) in the same cell line. Some phthalimide analogs, included PP-33 [2-(2,6-diisopropylphenyl)-1H-isoindole-1,3-dione] and its 4,5,6,7-tetrafluora derivative FPP-33), also showed such an inducer-specific bidirectional TNF-alpha production-regulating activity. The structure-activity relationships of the compounds tested are similar, but not identical, in the TPA-stimulated HL-60 and OA-stimulated HL-60 assay systems.

Carcinogens↗
PubMed1996

K252a inhibits the phosphorylation of pRb without changing the levels of G1 cyclins and Cdk2 protein in human hepatoma cells.

A protein kinase inhibitor K252a suppressed the growth of HuH7 hepatoma cells and the hyperphosphorylation of retinoblastoma protein (pRb) at late G1 phase of cell cycle. However, K252a treatment did not alter the levels of cyclin D1, cyclin E, cyclin A and Cdk2 protein bound to cyclin E or cyclin A. Therefore, the K252a inhibition of pRb phosphorylation is considered to be brought about probably by inhibiting the action of Cdk-cyclin complex rather than by changing its cellular level. These results also suggest that K252a is a useful tool for investigating the mechanism of phosphorylation of pRb mediated by Cdk-cyclin.

CDC2-CDC28 Kinases↗
PubMed1996

Il-7 supports D-J but not V-DJ rearrangement of TCR-beta gene in fetal liver progenitor cells.

The rearrangement of TCR-beta gene, one of the earliest events in T cell development, consists of two consecutive steps: D-J rearrangement and V-DJ rearrangement. The present study examined the signals supporting D-J beta and V-DJ beta rearrangements during early T cell development from progenitor cells that reside in fetal liver. We have found that there is an interval of 1 to 2 days between D-J beta and V-DJ beta rearrangements during the early T cell development from fetal liver progenitor cells in deoxyguanosine-treated thymus lobes. We have also found that IL-7, a cytokine expressed in the subcapsular area of the thymus, can promote D-J beta rearrangement of fetal liver progenitor cells, and that anti-IL-7 and anti-IL-7R Abs inhibit the D-J beta rearrangement and further T cell development of fetal liver progenitor cells in the thymus environment. Interestingly, unlike the thymus environment, IL-7 alone was not capable of supporting V-DJ beta rearrangement in the fetal liver cell cultures. These results indicate that D-J beta rearrangement during fetal liver-derived early T cell development is supported in the thymus by IL-7. Furthermore, the present results demonstrate that IL-7, supporting D-J beta rearrangement, does not promote V-DJ beta rearrangement of fetal liver progenitor cells, suggesting that intrathymic molecules promoting V-DJ beta rearrangement are distinct from IL-7 that supports the D-J beta rearrangement.

Animals↗
PubMed1996

Clinicopathological, immunological and genetic studies of CD30+ anaplastic large cell lymphoma of B-cell type; association with Epstein-Barr virus in a Japanese population.

The clinicopathological features, the immunophenotype, and the presence of Epstein-Barr virus (EBV)-associated genomes and gene products were examined in 17 cases of CD30+ anaplastic large cell lymphoma (ALCL) of B-cell type. Microscopically, the 17 cases were divided into ten cases of the monomorphic type and seven cases of the pleomorphic type. EBV was detected in 6 of 17 cases (38 per cent) by RNA in situ hybridization (ISH) with EBV-encoded RNA (EBER1). EBER1+ cases consisted of two cases (20 per cent) of the monomorphic type and four cases (57 per cent) of the pleomorphic type. The five EBER1+ cases showed clonality of the EBV genome by Southern blotting, consistent with the presence of EBV in a monoclonal proliferation. The EBV-encoded latent membrane protein 1 (LMP1) was found in all six EBER1+ cases and EBV-encoded nuclear antigen 2 (EBNA2) was present in two cases by immunohistochemistry. No expression of LMP1 or EBNA2 was observed in the EBER1-cases. The EBER1+ cases had a tendency for a more favourable prognosis than the EBER1-cases. It is concluded that EBV has an association with CD30+ ALCL of B-cell type in the Japanese population studied, and especially with the large pleomorphic type. EBV infection may play a pathoaetiological role and may influence clinical behaviour.

Adult↗
PubMed1996

Positive and negative regulation of cell proliferation through prostaglandin receptors in NIH-3T3 cells.

Among major eicosanoids and their analogs, prostaglandin (PG) F2 alpha > PGD2 > PGE1 > or = PGE2 > iloprost, a stable agonist of PGI2, dose-dependently stimulated DNA synthesis in quiescent NIH-3T3 cells. PGF2 alpha, PGD2, and PGE2, in that order, formed inositol phosphates and elevated intracellular Ca2+ ([Ca2+]i) but did not form cAMP nor inhibit forskolin-induced cAMP formation. Iloprost, PGI2, and PGE1 induced cAMP formation dose dependently with an ED50 of around 10(-7) M, and PGE2 at more than 10(-6) M did it. [3H]PGF2 alpha and [3H]PGD2 bindings membranes from NIH-3T3 cells were displaced in the order of PGF2 alpha > PGD2 > or = PGE2, while [3H]PGE2 binding was displaced by PGE2 > PGD2 > or = PGF2 alpha. Expression of mRNA encoding EP1 and EP4 (EP2) subtypes could be detected by reverse transcription- polymerase chain reaction using primers specific for EP1 and EP4 (EP2) cDNAs, but not that of EP3 subtype mRNA. The dose dependence of cAMP formation on iloprost and PGI2 and that of [Ca2+]i elevation on PGF2 alpha, D2, and E2 were similar to that of [3H]thymidine incorporation on the corresponding agonists. Fluprostenol (1 microM), a PGF2 alpha receptor agonist > 17-phenyl-trinor-PGE2 (1 microM), an EP1 receptor agonist stimulated [3H]thymidine incorporation, but an EP3 receptor agonist, ONO-AP-324 nor an EP4 (EP2) receptor agonist, 11-deoxy-PGE1 (1 microM) did not. Iloprost, dibutyryl cAMP, forskolin, or cholera toxin, when applied alone, enhanced [3H]thymidine incorporation, while they inhibited [3H]thymidine incorporation induced by submaximal concentrations of PGF2 alpha or epidermal growth factor (EGF), when applied within 12 hr after agonist stimulation. These results suggest that the proliferation of NIH-3T3 cells is stimulated by PGs via the PGF2 alpha receptor, EP1 subtype of PGE receptor, and the PGI2/PGE1 receptor through [Ca2+]i- and cAMP-dependent pathways, and that cAMP pathway negatively cross-talks with [Ca2+]i-or receptor tyrosine kinase-mediated DNA synthesis in a cell cycle-dependent manner.

3T3 Cells↗
PubMed1996

Human serum dipeptidyl peptidase IV (DPPIV) and its unique properties.

Dipeptidyl peptidase IV (DPPIV, EC 3.4.14.5) has been purified 18,000-fold in a yield of 2.2% from human serum. Serum DPPIV, a serine enzyme with an apparent mass of 250 kDa, consists of two identical subunits with an apparent mass of 100 kDa and is inhibited by DPPIV-specific inhibitor Diprotin A and also by p-chloromercuribenzoate (p-CMB), 2-mercaptoethanol, HgCl2, CdCl2, SrCl2, and ZnCl2. One of the remarkable properties of DPPIV is that its activity is greatly enhanced by Gly-X (X: especially, Gly, Gln, Glu and Ser) dipeptides. Gly-X dipeptides increase not only an apparent Km of serum DPPIV for glycyl-L-proline 3,5-dibromo-4-hydroxyanilide nearly 10-fold, but also an apparent kcat nearly 4-fold. This mechanism is unclear, but one possibility is that Gly-Pro from substrate might bind amino acids or dipeptides instead of water molecules as DPPIV transpeptidyl activity reported previously. Another remarkable property of DPPIV is the ability to bind adenosine deaminase-I and -II, as is the case with recombinant soluble CD26 (rsCD26). This probably indicates that DPPIV purified from human serum by our method originates from T-lymphocytes.

Adenosine Deaminase↗
PubMed1996

Cortisol and catecholamine kinetics during continuous hemodiafiltration in patients with multiple organ dysfunction syndrome.

OBJECTIVE: To assess the influence of continuous hemodiafiltration (CHDF) on cortisol and catecholamine kinetics in multiple organ dysfunction syndrome. DESIGN: Consecutive clinical study. SETTING: General intensive care unit of a university hospital. PATIENTS: Ten adult patients with multiple organ dysfunction syndrome requiring CHDF. MEASUREMENTS AND RESULTS: A total of 40 samples were collected during CHDF for cortisol and catecholamine assays. The clearances for cortisol, epinephrine, norepinephrine and dopamine were 2.5 +/- 1.7 ml/min, 26.3 +/- 2.7 ml/min, 16.7 +/- 4.2 ml/min and 26.3 +/- 2.6 ml/min (Mean +/_ SE), and their daily extractions were 1.8 +/- 0.2 mg/day, 11.4 +/- 4.8 micrograms/day, 1.0 +/- 0.1 micrograms and 2.3 +/- 0.3 micrograms/day, respectively. There were no significant changes in blood cortisol and catecholamine levels during CHDF conducted for 48 h. CONCLUSIONS: The cortisol and catecholamine losses during CHDF were small and unlikely to lead to hemodynamic disturbances.

Blood Glucose↗
PubMed1996

Effects of FK506 and cyclosporin A on proliferation, histamine release and phenotype of murine mast cells.

Using mouse peritoneal cavity mast cells, we investigated the effects of FK506 and cyclosporin A (CsA) on cell proliferation and histamine release induced by anti-IgE antibody, calcium ionophore (A23 187), or neuropeptide (substance P). Both FK506 and CsA inhibited cytokine-dependent mast cell proliferation in a dose-dependent manner. The inhibitory effects of these compounds on mast cell proliferation was reversible; the removal of the chemicals from the incubation medium resulted in the reinitiation of mast cell proliferation. Flow cytometric analysis suggested that the inhibitory effect of FK506 and CsA was mostly due to G1/S boundary block, although a significant number of G2-arrested cells were also observed following FK506 treatment. Both FK506- and CsA-treated mast cells showed a similar inhibition of histamine release induced by A23187. However, CsA at higher concentrations inhibited the histamine release induced by anti-IgE antibody or substance P more markedly than FK506. Cellular histamine content was decreased by CsA treatment while FK506 had no effect. The staining properties of peritoneal mast cells changed from connective tissue-type mast cell-like to mucosal mast cell-like during CsA treatment but not during FK506 treatment. Thus FK506 and CsA have different effects on mast cell proliferation as well as histamine release, that might be associated with a phenotypic change of the cells during culture.

Animals↗
PubMed1996

Inhibitory effect of 1 alpha,25-dihydroxyvitamin D3 on mast cell proliferation and A23187-induced histamine release, also accompanied by a decreased c-kit receptor.

Using mouse peritoneal mast cells, we investigated the effects of 1 alpha,25-dihydroxyvitamin D3 (calcitriol) on mast cell proliferation and histamine release. Calcitriol did not affect IL-3/IL-4-dependent mast cell proliferation, but it selectively inhibited stem cell factor-dependent mast cell proliferation and colony formation. Immunohistochemical and immunoblot analyses revealed that calcitriol treatment reduced expression of purified peritoneal mast cell c-kit protein. Using a mast cell line, MC/9, both c-kit protein and c-kit mRNA transcript were seen to be reduced following calcitriol treatment. Calcitriol also reduced histamine release induced by calcium ionophore A23187. In contrast, anti-IgE antibody-dependent histamine release was not affected by calcitriol. Our results indicate that calcitriol inhibits mast cell proliferation and A23187-induced histamine release that might be associated with a decreased expression of c-kit receptor.

Animals↗
PubMed1996

Myocardial defect detected by 123I-BMIPP scintigraphy and left ventricular dysfunction in patients with idiopathic dilated cardiomyopathy.

The present study examined the role of myocardial fatty acid in patients with idiopathic cardiomyopathy (DCM) by means of 123I-beta-methyl-p-iodophenyl pentadecanoic acid (123I-BMIPP) scintigraphy. Thirteen patients underwent 123I-BMIPP imaging, 201Tl imaging and echocardiography. All patients showed defective myocardial uptake of 123I-BMIPP and 201Tl. The left ventricular end-diastolic dimension (64.1 +/- 7.3 mm vs. 55.6 +/- 1.5 mm, p < 0.05) and end-systolic dimension (52.4 +/- 8.0 mm vs. 40.6 +/- 2.1 mm, p < 0.01) were significantly large in the defect group (123I-BMIPP defect score (DS) > 8) than the small defect group (DS < 7). The % fractional shortening (%FS) was also significantly smaller (18.6 +/- 3.8% vs. 27.0 +/- 3.3%, p < 0.01) in the large defect group. The 123I-BMIPP DS correlated statistically with %FS (r = 0.75, p < 0.01), while the 201Tl DS did not (r = 0.41, ns). We conclude that the patients with DCM revealed a 123I-BMIPP uptake defect and the defect reflected the degree of left ventricular dysfunction.

Adult↗
PubMed1996

On-line column preconcentration for the determination of cobalt in sea water by flow-injection chemiluminescence detection.

A flow-injection method for the determination of dissolved cobalt(II) in sea water has been studied based on a combination of column preconcentration using 8-quinolinol immobilized on silica gel, fluoride containing metal alkoxide glass (8HQ-MAF) and chemiluminescence detection with a gallic acid-hydrogen peroxide system. Co(II) is selectively recovered from an acidified sample with 8-quinolinol immobilized on silica gel. After elution with dilute hydrochloric acid the resultant eluent is mixed with the reagent solutions, heated to 60 ( degrees )C and then introduced into the CL cell. The analysis time including the 2-min sample load was 8 min per sea water sample with a corresponding detection limit of 0.62 ng l(-1) (3sigma). The average standard deviation calculated for 10 replicate measurements of artificial sea water samples with a concentration of 10 ng l(-1) cobalt was +/-2.1%. The method has been tested with the standard reference sea waters NASS and CASS.

Journal Article↗
PubMed1996

Development of T-lymphocyte subpopulations in the postnatal chicken oviduct.

Postnatal development of t-cell subpopulations in the oviduct was investigated in the Dekalb strain of the White Leghorn chicken by using an immunohistochemical method. T-lymphocytes first infiltrated the oviduct at 5 weeks. The number of T cells peaked at 15 weeks in the magnum, isthmus and uterus, and at 19 weeks in the infundibulum and vagina. The epithelium of the oviduct contained both granular and agranular lymphocytes. TcR1+ cells were predominant in the epithelium, whereas TcR2+ cells were more numerous than TcR1+ cells in the lamina propria. TcR3+ cells were absent from the epithelium and were not numerous in the lamina propria. CT8+ cells, equivalent to CD8+ cells in mammals, were located both in the epithelium and in the lamina propria. The relative frequency of T-cell subpopulations was found to be higher in the vaginal part than in the other parts of the oviduct. These results suggest that the postnatal developmental changes of T-cell subpopulations depend on different anatomical regions of the oviduct and on the age of the chicken.

Animals↗
PubMed1996

Chemistry of biologically active benzoxazinoids.

2,4-Dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (DIMBOA) and its desmethoxy derivative (DIBOA) are major allelochemicals produced by corn, wheat, rye and related monocotyledons. These benzoxazinone derivatives have a wide variety of biological actions, including antifungal and mutagenic activities. Structure-activity relationships of these compounds and their derivatives (benzoxazinoids), the reactivity of benzoxazinoids with nucleophiles, and the substituent effects of the 7-methoxy and 2-hydroxy groups are discussed in relation to the molecular mechanisms of the biological activities.

Oxazines↗
PubMed1996

Lymphocyte subpopulations in the mammary gland of the goat.

Mammary glands of pregnant, lactating and resting goats were studied by immunohistochemistry for lymphocyte subpopulations using a panel of monoclonal antibodies. All T lymphocyte subpopulations that may have a role in the immune response, CD2+, CD4+, CD8+ and gamma delta T cells and subsets, were present in the mammary gland and were noted to increase in number progressively during pregnancy, decrease significantly during lactation, and then moderately increase during the resting period. CD4+ cells, the predominant cell type in the mammary gland, were located mainly in the connective tissue, whereas CD2+, CD8+ and TcR1-N24+ cells were predominant in the intraepithelial areas. TcR1-N6+ cells were detected almost exclusively during pregnancy, being localized mainly in the connective tissue. Their proportion decreased markedly following parturition. Very few WC1-N3+ and -N4+ cells were detected in the mammary gland. It is suggested that the majority of gamma delta T lymphocytes in the mammary gland of the goat are CD2+ CD8+ WCl-, a distinctive subset from that of the WCl+ subset in peripheral blood.

Animals↗
PubMed1996

Four years follow-up study in patients with Takayasu arteritis and severe aortic regurgitation; assessment by echocardiography.

We prospectively performed the follow-up study in 11 female patients with Takayasu arteritis and severe aortic regurgitation by echocardiography. A mean follow-up period was 4 years. The inflammatory state was controlled in all patients. Antihypertensive agents including beta-blocker were administered in nine patients. Heart failure did not progress in all patients except one. No candidate for cardiac surgery appeared during the follow-up period. Aortic root diameter, left atrial, left ventricular end-diastolic and end-systolic dimensions, wall thickness, left ventricular mass, and percent fractional shortening of the left ventricle showed no significant change in echocardiography. These data indicate that left ventricular disturbance might be slowly progressive in patients with Takayasu arteritis and severe aortic regurgitation. Systemic hypertension and the inflammatory state should be well controlled in managing the patients. beta-blocker might be useful in some patients with Takayasu arteritis and severe aortic regurgitation. Further follow-up is necessary for the decision of the cardiac surgical indication.

Adrenergic beta-Antagonists↗
PubMed1996

Effects of unilateral vagotomy on nitric oxide synthase and histamine H3 receptors in the rat dorsal vagal complex.

Nitric oxide synthase (NOS) and histamine H3 receptors are both markedly increased by neuronal injuries. To examine whether peripheral axotomy produced differential changes in NOS and H3 receptors, both NOS and H3 receptors were measured in the dorsal vagal complex after unilateral vagotomy. The presence of NOS-positive neurons was examined using both NADPH-diaphorase histochemistry and neuronal NOS-immunohistochemistry in rats vagotomized at the mid-cervical level. NADPH-diaphorase activity and NOS-immunoreactivity were markedly enhanced on the dorsal motor nucleus of the vagus (DMX) and in the ambiguous nucleus at the denervated side. Intraperitoneal injection of NOS inhibitors, N omega-nitro-L-arginine (10 mg/kg) or dexamethasone (0.5 mg/kg) attenuated the increase in NADPH-diaphorase activity. Glial fibrillary acidic protein (GFAP) was similarly induced 2 weeks after vagotomy in the vagal complex and surrounding area. Histamine H3 receptors in the vagal complex were visualized with [3H]N alpha-methylhistamine. The ligand-labeled H3 receptors were mainly located at the nucleus of the solitary tract (NST). The densities of H3 receptors did not change in the NST after unilateral vagotomy. These results suggest that peripheral axotomy such as mid-cervical vagotomy preferentially induces NOS in damaged neurons without affecting the level of H3 receptors.

Animals↗