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Biomedical subjects

Y Hashimoto

Publications and source records attributed to Y Hashimoto.

At least 937 records · Page 52Linked to original sources
PubMed1992

Specific inhibition of NGF receptor tyrosine kinase activity by K-252a.

An involvement of protein tyrosine kinase in the transduction of the signals initiated by nerve growth factor (NGF) was investigated. A tyrosine kinase inhibitor, herbimycin, inhibited neurite outgrowth of rat pheochromocytoma PC12 cells induced by NGF but not that by dibutyryl-cAMP. Herbimycin and genistein blocked NGF-dependent activation of ras p21 whose essential function in neuronal differentiation has been reported. These observations suggested that tyrosine kinase activity is involved in the signaling pathways. K-252a, by contrast, inhibited NGF-induced but not EGF-dependent activation of ras p21. Tyrosine kinase activity of gp140trk, a constituent of NGF receptor, is activated by NGF for much a longer period compared to the activation of EGF receptor autokinase activity by EGF. We further demonstrated that autophosphorylation of gp140trk is selectively inhibited by K-252a.

Adrenal Gland Neoplasms↗
PubMed1992

Reduction of NGF protein level in rat dorsal hippocampus following administration of kainic acid.

Intraperitoneal administration of kainic acid (KA) into adult rats caused a profound increase in nerve growth factor (NGF) mRNA and a significant reduction of NGF protein level in the hippocampus. Diazepam pretreatment suppressed both. The reduction of NGF level was apparent in the dorsal hippocampus at 2 h after KA administration, but a marked elevation of NGF protein was observed in the ventral hippocampus at 4 h. These results suggest that non-N-methyl-D-aspartate (NMDA) receptor agonists negatively influence NGF synthesis or stimulate NGF protein degradation in the dorsal hippocampus involving the CA1 sector.

Animals↗
PubMed1992

Significance of nerve growth factor content levels after transient forebrain ischemia in gerbils.

Involvement of nerve growth factor (NGF) in the pathogenesis of delayed neuronal death (DND) of CA1 neurons in the hippocampus has been suggested. We measured regional changes in the content of tissue NGF of the hippocampus in the Mongolian gerbil after 5 min forebrain ischemia. The NGF content was found to decrease significantly in the CA3 and dentate regions by 32% two days after ischemia. By contrast in the CA1 region, the level of NGF became significantly elevated by 50% two weeks after ischemia or later. The early reduction of NGF content in the afferent area projecting to the CA1 sector might be primarily linked to the pathogenesis of DND, whereas the delayed increase within the CA1 sector might be a secondary local response mainly of reactive astroglia.

Animals↗
PubMed1992

Human c-erbB-2 proto-oncogene product as a target for bispecific-antibody-directed adoptive tumor immunotherapy.

To develop an efficient strategy for the targeting of anti-tumor effector cells, we prepared bispecific antibody (BsAb) containing anti-CD3 and an anti-c-erbB-2 proto-oncogene product. The prepared BsAb specifically reacts with both c-erbB-2-positive tumor cells and CD3+ CTL. Human CD4+ helper/killer T cells, induced from peripheral-blood mononuclear cells by activation with immobilized anti-CD3 monoclonal antibody (MAb) plus IL-2, showed no significant cytotoxicity against tumor cells. However, treatment of human CD4+ helper/killer cells with the BsAb caused the induction of specific cytotoxicity against c-erbB-2-positive tumor cells. CD4+ helper/killer cells also produced significant amounts of IL-2 during co-culture with c-erbB-2-positive tumor cells in the presence of the BsAb. Moreover, by combination with the BsAb, CD4+ helper/killer cells showed a strong in vivo anti-tumor effect against c-erbB-2 transfectant or human colon-cancer cells implanted in nude mice. Our results strongly suggest that the c-erbB-2 proto-oncogene product on human tumor cells may be a good target for BsAb-directed adoptive tumor immunotherapy.

Antibodies, Monoclonal↗
PubMed1992

Enhanced flow velocity increase through the left ventricular inflow tract of patients with isolated aortic regurgitation.

Twenty-five patients with chronic aortic regurgitation (AR), and 12 control subjects were studied using Doppler echocardiography to investigate the effects of AR on transmitral flow. Peak early filling velocities at the levels of the mitral valve tips (E1) and annulus (E2) were measured, and the transmitral flow restriction index (delta E = (E1-E2)/E2) was obtained. Patients with AR were classified into 2 groups according to the ratio of the cross-sectional area of the regurgitant jet to that of the left ventricular outflow tract. Group I had the ratio less than 0.20, and group II had greater than or equal to 0.20. E2 in group II was lower than in control subjects, whereas E1 was not significantly different in any groups. delta E in group II was higher than in group I or in control subjects (p less than 0.05 and 0.01, respectively). delta E showed a significant correlation with the cross-sectional area ratio in all patients with AR (r = 0.70, p less than 0.01) and in group II (r = 0.82; p less than 0.01). Our data suggest that AR restricts early transmitral filling, and that delta E may indicate the increased driving pressure caused by flow restriction and is a useful hemodynamic index of AR.

Adult↗
PubMed1992

Base-catalyzed isomerization of retinoic acid. Synthesis and differentiation-inducing activities of 14-alkylated all-trans-, 13-cis-, and 20,14-retro-retinoic acids.

Retinoic acid (1) is isomerized regioselectively by excess amounts of lithium diisopropylamide (LDA) to give 20,14-retro-retinoic acid (3). Alkylation of the intermediate dianion of retinoic acid gave 14-alkylated derivatives of 3. By isomerization of the alkylated retro isomers under basic conditions, several 14-alkyl-all-trans- and -13-cis-retinoic acids were synthesized. The retinoidal activities of these derivatives were examined, based on the ability to induce differentiation of human promyelocytic leukemia cell line HL-60. 20,14-retro-Retinoic acid (3) is 1/50 as active as retinoic acid (1). Although 14-methyl-20,14-retro-retinoic acid (4) is as active as 3, the introduction of a 14-methyl group into all-trans- and 13-cis-retinoic acid resulted in decreased activity. Introduction of bulkier alkyl groups at the C-14 position caused the disappearance of the activity.

Alkylation↗
PubMed1992

Interaction of phomopsin A with porcine brain tubulin. Inhibition of tubulin polymerization and binding at a rhizoxin binding site.

Phomopsin A is an antimitotic cyclic peptide containing a 13-member ring including an ether linkage. It was isolated from the fungus Phomopsis leptostromiformis as the causal agent of lupinosis. Phomopsin A strongly inhibited microtubule assembly (IC50: 2.4 microM). Our study using radiolabeled phomopsin A, prepared biosynthetically by feeding L-[U-14C]isoleucine to the culture of P. leptostromiformis, indicated that at least two binding sites of phomopsin A exist on tubulin on the basis of a Scatchard analysis; i.e. the dissociation constants of a high affinity site (Kd1) and a low affinity site (Kd2) at 37 degrees were determined to be 1 x 10(-8) and 3 x 10(-7) M, respectively. Phomopsin A inhibited the binding of radiolabeled rhizoxin to tubulin with an inhibition constant (Ki) of 0.8 x 10(-8) M. This showed that the high affinity site of phomopsin A is identical to the rhizoxin binding site. The binding of the radiolabeled phomopsin A was also inhibited by rhizoxin and ansamitocin P-3, with an inhibition constant of 10(-7) M, and to a lesser extent by vinblastine. Phomopsin A had no inhibitory effect on colchicine binding to tubulin.

Animals↗
PubMed1992

Morphological and northern blot analysis of juxtaglomerular cells in experimental hydronephrotic mice.

The purpose of this study is to demonstrate the developmental changes of the experimental hydronephrotic kidney using immunohistochemical, histoplanimetrical, and Northern blot techniques. At 1 month after ligation of the ureter, a large number of renin-positive cells were detected immunohistochemically even at a dilution of 1:10,000 in this hydronephrotic kidney; however, there were few renin-positive cells in the non-ligated side. At 6 months after ligation, no difference in reactivity for renin between ligated and non-ligated kidneys was demonstrated. In the morphometrical analysis of the renin-positive region, the numerical value of the ligated side was already increased at 2 weeks, reached the highest value at 1 month, and then decreased gradually to almost the same value as the control kidney by the end of the experiment. On the other hand, the value of the non-ligated side decreased immediately after the unilateral ligation, increased later, and finally reached almost the same value as the control kidney. In the Northern blot analysis, the activity of renin mRNA in the ligated side at 1 month after ligation was markedly higher than that in the non-ligated side. However, the difference between the ligated and the non-ligated sides was not demonstrated at 6 months and the value came to be almost the same as in the non-operated kidney.

Animals↗
PubMed1992

Spectral characteristics of rapid off-response in congenital deuteranomaly in one of monozygotic female twins.

The spectral sensitivity of the rapid off-response in the electroretinogram was studied in monozygotic female twins. One case was diagnosed as congenital deuteranomaly, and the other was normal. The log ratio of the sensitivity at 480 nm to the sensitivity at 620 nm (log S480/S620) was within the deutan range in the first case and within the normal range in the second. The two case were determined to be different at the retinal receptor level by study of the rapid off-response. This result of the rapid off-response was consistent with the results of the psychophysical examinations.

Adult↗
PubMed1992

Duplicated origin of right vertebral artery with rudimentary and accessory left vertebral arteries.

We observed a rare cerebrovascular anomaly in a patient with brain-stem infarction. Two right vertebral arteries arose from the subclavian artery and communicated directly with each other under the transverse foramen of the fourth cervical vertebra. The left vertebral artery consisted of a rudimentary artery that arose from the left subclavian artery, ran through the transverse foramen of the sixth cervical vertebra and then tapered down to disappear at the fourth/fifth cervical vertebrae, plus a second, accessory artery that arose from a branch of the left thyrocervical trunk, ran through the transverse foramen of the fifth cervical vertebra and tapered off to disappear at the first/second cervical vertebrae.

Adult↗
PubMed1992

Cytokine regulation of hemostatic property and IL-6 production of human endothelial cells.

The effects of four inflammatory cytokines, IL-1, TNF, IFN-gamma, and IL-6, were assessed on the following functions of human vascular endothelial cells (EC) in culture: expression of procoagulant activity (PCA), endothelial cell-associated thrombomodulin (TM), and IL-6 production. Both IL-1 and TNF induced PCA, reduced TM, and induced IL-6 production in a dose-dependent manner. IFN-gamma had a weak but significant reducing effect on TM and an inducing effect on IL-6 production, while it had no effect on PCA expression. IFN-gamma, however, when added in combination with either IL-1 or TNF, modulated the effects of these cytokines; INF-gamma inhibited the PCA expression and enhanced the reduction of TM and the production of IL-6, which were induced by either IL-1 or TNF. In contrast, IL-6 had no significant effect on the EC functions studied. These results suggest that both IL-1 and TNF are the major cytokines affecting the EC functions that determine the association between the coagulation and the inflammatory response, and that IFN-gamma affects this phenomenon predominantly through the modification of the effects of these cytokines.

Blood Coagulation Tests↗
PubMed1992

Aortic regurgitation in patients with Takayasu arteritis: assessment by color Doppler echocardiography.

To characterize aortic regurgitation in patients with Takayasu arteritis, we studied 48 females with arteritis (mean age 47 +/- 12 years) by means of color Doppler echocardiography. Aortic regurgitation was confirmed in 32 out of 48 patients (67%) by color-flow mapping. Twenty-four patients had mild or no aortic regurgitation (group A), 9 had moderate (group B), and 15 had severe (group C) aortic regurgitation. We compared the echocardiographic data obtained from patients with Takayasu arteritis with those of 14 normal controls and 9 patients with severe aortic regurgitation of valvular origins (group V). The aortic root diameter (AOD) in group B (23 +/- 4 mm/M2) and group C (22 +/- 3 mm/M2) revealed a statistically significant large value as compared with that in group A (18 +/- 2 mm/M2) and normal controls (17 +/- 3 mm/M2). However, the differences, between groups B and C and groups C and V, were not significant. The AOD was not obviously dilated in a considerable number of group C patients. Aortic valve involvement was seen in several group C patients and moderate concentric left ventricular hypertrophy was present in all group C patients. Group C patients therefore, have concentric left ventricular hypertrophy but may or may not have dilatation of the aortic root which can be detected on echocardiography. We conclude that aortic valve involvement may cause aortic regurgitation in some patients with Takayasu arteritis and that aortic regurgitation is more common than previously believed.

Adult↗
PubMed1992

Left ventricular dysfunction and HLA Bw52 antigen in Takayasu arteritis.

Heart disease is the main cause of death in patients with Takayasu arteritis. It has been reported that this disease is closely related to the presence of HLA Bw52 antigen. To assess the correlation between this antigen and left ventricular involvement, we studied 40 patients with Takayasu arteritis, 21 with and 19 without Bw52, using Tl-201 stress myocardial scintigraphy and echocardiography. Those with Bw52 had a significantly higher incidence of abnormal electrocardiographic findings (67% vs 26%; P < 0.05) and of aortic regurgitation (52% vs 11%; P < 0.05). The echocardiographically determined interventricular septal wall thickness plus left ventricular posterior wall thickness (25 +/- 8 vs 17 +/- 3 mm; P < 0.01) and the left ventricular mass (257 +/- 132 vs 142 +/- 51 g; P < 0.01) were significantly increased in the patients with Bw52. Scintigraphically determined perfusion abnormalities were significantly more frequent in those with Bw52 (76% vs 32%; P < 0.05). These observations indicate that patients with Takayasu arteritis and Bw52 antigen have a more severe left ventricular involvement than the patients without that antigen. The left ventricular impairment may account for the poor prognosis of Takayasu patients with Bw52.

Adult↗
PubMed1992

Preventative effect of PGE1 for postoperative liver damage.

The efficacy of a low dose of PGE(1)-use on the postoperative liver damage was evaluated. PGE(1) was infused in with the mean rate of 0.026 microg.kg(-1).min(-1) during surgical procedure to 93 patients under GO-enflurane anesthesia (the PG). Serum GOT, GPT and total bilirubin (TBIL) values measured before, at the end of (End) and 3 days (3d) after the operation were compared to those obtained from 43 patients without PGE(1) administration (the control). This dose of PGE(1) did not change blood pressure and heart rate, but slightly decreased Pa(O)(2). In patients with preoperative normal values of GOT, GPT and TBIL, increases in GOT, GPT and TBIL observed at End in the PG were significantly lower than those in the control (31.9 vs 72.2 IU, 25.9 vs 61.9 IU, 0.68 vs 0.83 mg.dl(-1), respectively). GOT, GPT and TBIL at 3d significantly increased in both groups, and these levels were identical between the two groups. In patients with preoperative abnormal values, only GOT at End increased in both groups, while no significant difference between the PG and the control group was noted. GOT at 3d and GPT at End and 3d did not significantly changed in either group. These results suggest that the low dose of PGE(1) administered during an operation prevents the development of postoperative liver damage, but does not treat the damaged hepatic cells.

Journal Article↗
PubMed1992

Selective inhibition of T-cell-dependent immune responses by bisbenzylisoquinoline alkaloids in vivo.

The bisbenzylisoquinoline (BBI) alkaloids, chondocurine, tetrandrine, isotetrandrine and cepharanthine, were tested for immunosuppressive activity in mice. A plaque-forming cell (PFC) response to a T-cell-dependent antigen, sheep red blood cell, was significantly suppressed by a 7 day treatment of chondocurine or tetrandrine at 1 mg/kg/day and of isotetrandrine at 50 mg/kg/day, but not suppressed by cepharanthine treatment. The suppressive effect of chondocurine was greater when it was given after immunization rather than before or concurrently. However, it did not affect the PFC response to a T-cell-independent antigen, lipopolysaccharide. A delayed-type hypersensitivity was also suppressed by chondocurine treatment. There was no significant change in lymphocyte number and proportion of T-cell subsets in the BBI alkaloid-treated mice. These data suggest that there is selective inhibition by chondocurine and tetrandrine of the T-cell-dependent immune reactions.

Alkaloids↗
PubMed1992

Differences in DNA damage induced by mutagenic and nonmutagenic 4-aminoazobenzene derivatives in Escherichia coli.

DNA lesions produced in Escherichia coli AB2500 (uvrA) exposed to the carcinogen N-hydroxy-3-methoxy-4-aminoazobenzene (N-OH-3-MeO-AAB) or the noncarcinogen N-hydroxy-2-methoxy-4-aminoazobenzene (N-OH-2-MeO-AAB) were investigated by alkaline sucrose gradient sedimentation and 32P-postlabeling analysis. Alkali-labile sites appeared to be formed equally in cells treated with both aminoazobenzene derivatives. 32P-Postlabeling analysis revealed that the 3-MeO-AAB-DNA adduct level was 25-fold higher than that for 2-MeO-AAB-DNA adducts. In addition to major adducts, 4 minor spots were detected in N-OH-3-MeO-AAB-treated cells, while only one major adduct was found in N-OH-2-MeO-AAB-treated cells. The mutagenicities and cytotoxicities were also determined with E. coli with different repair capacities; we found that repair of 3-MeO-AAB damages is strongly dependent on the UVR repair system. Moreover, N-OH-3-MeO-AAB, but not N-OH-2-MeO-AAB, could induce recA and umuC gene expression, which was higher in uvrA strains than in the wild type.

Bacterial Proteins↗
PubMed1992

Identification of an equivalent to murine Thy-1+ dendritic epidermal cells in the rat epidermis.

In the murine epidermis, there exist Thy-1+ dendritic epidermal cells (Thy-1+DEC). These cells are Thy-1+, CD45+, CD3+ and asialo GM1+ but CD5-, CD4-, CD8-, or Ia-1-, and express T cell receptor (TCR) gamma delta. Recently, most of these TCR gamma delta of Thy-1 DEC are shown to consist of a V gamma 3-V delta 1 combination. There has been no evidence that the same type of cell population exists in other species except mice. In this study, we investigated the existence of a Thy-1+DEC equivalent in the rat epidermis. The epidermal sheets obtained from rats were stained with various monoclonal antibodies to rat lymphocytes. We developed a monoclonal antibody (1F4) to rat CD3 complex. 1F4 stained thymocytes and peripheral T cells and also immunoprecipitated T cell receptor with CD3 complex. Using 1F4 and a recently developed monoclonal antibody to rat TCR alpha beta, we could identify dendritic CD4-, CD8-, CD5-, CD3+, TCR alpha beta- cells in the rat epidermis. These CD3+, TCR alpha beta- cells are strong candidates as an equivalent to TCR gamma delta + murine Thy-1+ DEC.

Animals↗