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Biomedical subjects

S Shibata

Publications and source records attributed to S Shibata.

At least 253 records · Page 14Linked to original sources
PubMed1997

Effect of CD34+ selection and various schedules of stem cell reinfusion and granulocyte colony-stimulating factor priming on hematopoietic recovery after high-dose chemotherapy for breast cancer.

We evaluated the effects of various schedules of peripheral blood stem cell (PBSC) reinfusion, granulocyte colony-stimulating factor (G-CSF) priming, and CD34+ enrichment on hematopoietic recovery in 88 patients with advanced breast cancer treated with high-dose chemotherapy, consisting of cisplatin 250 mg/m2, etoposide 60 mg/kg, and cyclophosphamide 100 mg/kg. PBSC (> or = 7.5 x 10(8) nucleated cells/kg) were collected following priming with G-CSF and were either immediately cryopreserved (48 patients; cohorts A and B) or were first processed for CD34+ enrichment (40 patients; cohorts C and D). Patients in cohorts A and C received PBSC on day 0; patients in cohorts B and D received 25% of their nucleated cells on day -2 and 75% on day 0 (split reinfusion). Patients in cohorts A, B, and C were primed with G-CSF 10 micrograms/kg, subcutaneously (SC), once a day; patients in cohort D were primed with 5 micrograms/kg G-CSF, SC, twice daily (bid). Bid administration of G-CSF yielded 2.3 to 4.7 x higher numbers of CD34+ cells in the PBSC product than the same total dose given once a day (P = .002). Reinfusion of 25% of unselected PBSC on day -2 (median, 2.26 x 10(8)/kg nucleated cells [range, 1.7 to 3.3 x 10(8)/kg]) with the remaining cells reinfused on day 0 resulted in earlier granulocyte recovery to > or = 500/microL when compared with reinfusion of all stem cells on day 0 (group B, median of 8 days [range, 7 to 11] v group A, 10 days [range, 8 to 11], P = .0003); no schedule-dependent difference was noted in reaching platelet independence (group B, 11.5 days [range, 5 to 21]; group A, 12 days [range, 8 to 24], P = not significant). Split schedule reinfusion of CD34(+)-selected PBSC did not accelerate granulocyte recovery. In groups D and C, the median number of days to granulocyte recovery was 12 (range, 8 to 22) and 11.5 (range, 9 to 13); patients became platelet independent by day 15 (range, 6 to 22) and 14 (range, 12 to 23), respectively. CD34(+)-selected PBSC rescue decreased the incidence of postreinfusion nausea, emesis, and oxygen desaturation in comparison to unselected PBSC reinfusion (P < or = .005 for each). Hematopoietic recovery may be accelerated by earlier reinfusion of approximately 2.26 x 10(8)/kg unselected nucleated cells. Earlier recovery may be triggered by components other than the progenitors included in the CD34+ cell population. Sustained hematopoietic recovery can also be achieved with CD34(+)-selected PBSC alone. Dosing of G-CSF on a bid schedule generates higher CD34+ cell yield in the leukapheresis product. Whether even earlier "sacrificial" reinfusion of approximately 2 x 10(8)/kg unselected nucleated cells concomitant with the administration of high-dose chemotherapy would reduce the duration of absolute granulocytopenia further while initiating sustained long-term hematopoietic recovery will require further investigation.

Adult↗
PubMed1997

Endothelium- and cytochrome P-450-dependent relaxation induced by isoproterenol in rat aortic rings.

In rat aortic rings, the mechanism of endothelium-dependent relaxation induced by isoproterenol is examined. Pretreatment with (+/-)-1-[2,3]-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methyleth yl)amino] -2-butanol (ICI-118,551), a beta 2-adrenoceptor antagonist, or atenolol, a beta 1-adrenoceptor antagonist, partly inhibited the relaxing response to isoproterenol. The relaxing response to isoproterenol in the presence of ICI-118,551 or atenolol was markedly inhibited by removal of endothelium. In the aorta pretreated with ICI-118,551 or atenolol, residual relaxing response to isoproterenol was also inhibited by 2-methyl-1,2-di-3-pyridyl-1-propanone (metyrapone), alpha-naphthoflavone or 8-methoxypsoralen, cytochrome P-450 monoxygenase inhibitors, and methylene blue, but not by indomethacin, a cyclooxygenase inhibitor, 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1, 4-benzoquinone (AA861), a 5-lipoxygenase inhibitor, NG-nitro-L-arginine (NOARG), a nitric oxide synthase inhibitor, Zn protoporphyrin IX, a heme oxygenase inhibitor, or yohimbine, a alpha 2-adrenoceptor antagonist. In the aorta denuded of endothelium, metyrapone did not affect the residual relaxing response to isoproterenol in the presence of atenolol. These results suggest that the cytochrome P-450 system may be involved in the endothelium-dependent relaxation induced by isoproterenol through beta 1- and beta 2-adrenoceptor activation.

Adrenergic beta-Agonists↗
PubMed1997

Involvement of annexin V in antiproliferative effects of gonadotropin-releasing hormone agonists on human endometrial cancer cell line.

We studied the involvement of annexin V in the antiproliferative effects of gonadotropin-releasing hormone (GnRH) agonists on human endometrial cancer cell line HHUA. HHUA cell line expressed mRNA for GnRH receptors as assessed by reverse transcriptase-PCR with oligonucleotide primers. In the presence of buserelin, the proliferation of this cell line was significantly (P < 0.01) reduced to 60% of control after 72 hr. Peak intracellular concentrations of annexin V, equivalent to about twice the control value, were obtained after 48 hr exposure to buserelin. Intracellular annexin V concentration was increased not only by buserelin, but also by protein kinase C (PKC) activator. However, there was no increase in intracellular annexin V concentration when cells were incubated with PKC inhibitor before the addition of buserelin. The results suggest that GnRH agonists inhibit cell proliferation by increasing intracellular concentrations of annexin V, an effect mediated by the activation of PKC.

Annexin A5↗
PubMed1997

Cell death caused by the acute effects of aminoglycoside and zinc in the ampullary cristae of guinea pigs.

We reported that apoptosis occurred in the guinea pig vestibular hair cells after chronic aminoglycoside treatments. In the present study, we used in situ nick-end labeling to determine whether apoptosis was also induced by the acute effects of aminoglycosides in guinea pig ampullar cristae. In addition, we evaluated the effect of zinc supplements upon these ototoxic treatments. After a local application of streptomycin directly to the round window, we found labeled bodies in the vestibular hair cells. The zinc supplement increased the number of labeled bodies resulting in severe hair cell loss. These findings indicate that the acute effects of aminoglycosides also induce apoptosis of the vestibular hair cells, and that zinc enhances aminoglycoside ototoxicity. Consequently, we propose that an interaction with ion channels may play a key mechanism in the processes of apoptosis affecting the vestibular hair cells.

Administration, Topical↗
PubMed1997

Gentamicin ototoxicity induced apoptosis of the vestibular hair cells of guinea pigs.

To clarify mechanisms of inner ear cell death induced by aminoglycosides, we used an in situ nick-end labelling method to examine guinea pig vestibular epithelia after chronic systemic treatments with gentamicin to produce apoptosis. Such changes occurred in damaged hair cells, suggesting that this process may be crucial for subsequent repair and cell regeneration.

Animals↗
PubMed1997

Pharmacokinetics and toxicity of 120-hour continuous-infusion hydroxyurea in patients with advanced solid tumors.

A group of 18 patients with advanced cancer were entered on a phase I study of a 120-h continuous intravenous infusion of hydroxyurea. The dose of hydroxyurea was escalated in cohorts of patients from 1 to 2 to 3.2 g/ m2 per day. The primary dose-limiting toxicity was neutropenia, often accompanied by leukopenia, thrombocytopenia and generalized skin rash. Prophylactic treatment of patients with dexamethasone and diphenhydramine hydrochloride prevented the skin rash, but not the hematopoietic toxicities. The pharmacokinetics of hydroxyurea were studied in all patients. The steady-state concentrations of hydroxyurea were linearly correlated with the dose (R2 = 0.71, n = 18, P < 0.0001). The mean +/- SE concentrations were 93 +/- 16, 230 +/- 6 and 302 +/- 27 microM at 1, 2 and 3.2 g/m2 per day, respectively. The mean +/- SE renal and nonrenal clearances of hydroxyurea were 2.14 +/- 0.18 and 3.39 +/- 0.28 l/h per m2 (n = 16), neither of which correlated with the dose. The concentration of hydroxyurea in plasma decayed monoexponentially with a mean +/- SE half-life of 3.25 +/- 0.18 h (n = 17). The steady-state concentration of hydroxyurea was > 200 microM in all nine patients treated at 2 g/m2 per day, a dose which was well tolerated for 5 days. We recommend this dose for phase II trials in combination with other antineoplastic agents.

Adult↗
PubMed1997

Determination of the optimal walking speed for neural relaxation in healthy elderly women using electromyogram and electroencephalogram analyses.

The purpose of this study was to determine the walking speed which has the greatest influence on neural relaxation in healthy elderly women as determined by electromyogram (EMG) and electroencephalogram (EEG) analyses. Seven elderly female volunteers [mean age 68.5 (SD 3.95) years] served as subjects for this study. The EMG signals were recorded from the gastrocnemius (MG), soleus (SL) and tibialis anterior (TA) muscles while walking on a treadmill, starting at 40 m.min-1 and increasing 6 m.min-1 incrementally for 10 min. The turning point of muscle activities (by integrated EMG. iEMGtp) was determined as the walking speed at the point at which the mean rate of change of iEMG (MG + SL + TA) abruptly increased. After the determination of iEMGtp. the treadmill was set at three constant speeds, one corresponding to the speed for the iEMGtp and two others 20% higher or lower than that for the iEMGtp. The subjects then walked for 20 min at each of these speeds on 3 separate days and their EEG power spectrum data were obtained for frequencies from the 8 to 13 Hz (z-wave component, AWC). The mean of iEMGtp for our subjects was at a mean walking speed of 64.7 (SD 7.9) m.min-1. Considering the subjects' age and height, iEMGtp was somewhat faster than their expected self-paced normal walking speed. There were no differences between the mean AWC values of the subjects prior to exercising at each of the three speeds. The mean AWC values after exercise were significantly (P < 0.01) greater than before. The extent of the increase in AWC at iEMGtp was greater than those at slower speeds. Our data would suggest that walking exercise at the speed which corresponds with EMG evidence of iEMGtp may induce the most significant relaxing effects in elderly women.

Aged↗
PubMed1997

Correlation between shrinkage of uterine leiomyoma treated with buserelin acetate and histopathologic findings of biopsy specimen before treatment.

OBJECTIVE: To analyze histopathologic features related to myoma volume reduction after treatment with a GnRH agonist, buserelin acetate, in needle biopsy specimens obtained before treatment. DESIGN: Prospective clinical study. SETTING: University teaching hospital. PATIENT(S): Twenty women with normal menstrual cycles and symptomatic uterine myomas. INTERVENTION(S): Buserelin acetate was administered intranasally (900 micrograms/d) for at least 16 weeks; transcervical needle biopsy of the uterine myoma was done before this treatment. MAIN OUTCOME MEASURE(S): The relation between histopathologic features (degree of cellularity, hyaline change, and collagen content) and the percent decrease in the volume of the largest myoma at 16 weeks measured by magnetic resonance imaging. RESULT(S): The correlation between the degree of hyaline change and the percent decrease in the myoma volume was significant, as was that with the proportion of collagenous tissue in the specimens. CONCLUSION(S): We predicted myoma volume reduction after treatment with a GnRH agonist by histologic analysis of the uterine leiomyoma before treatment.

Administration, Intranasal↗
PubMed1997

Z-321, a prolyl endopeptidase inhibitor, augments the potentiation of synaptic transmission in rat hippocampal slices.

The present study investigated the effects of arginine-vasopressin (AVP) and (1-[3-(2-indanylacetyl)-L-thioprolyl] pyrrolidine (Z-321), an inhibitor of prolyl endopeptidase (PEP; (EC 3.4.21.26)) which degrades AVP in vitro, on the short-lasting potentiation of the field excitatory postsynaptic potentials (EPSP) coupled with a weak tetanus. The EPSP, after the electrical stimulation of the Schaffer collateral/commissural pathway, were recorded in the CA1 region of rat hippocampal slices. AVP at 10(-8) M and Z-321 at 10(-4) M augmented the potentiation induced by the weak tetanus; the magnitude of the post-tetanic potentiation of the EPSP was enhanced and the potentiation lasted for 60 min. In contrast, the racemic D-thioprolyl compound of Z-321, which virtually lacks any inhibitory effects on PEP, failed to affect the potentiation at 10(-4) M. The facilitatory effect of Z-321 was reversed by the application of [d(CH2)5,Tyr(Me)2]AVP (10(-8) M), an antagonist of the AVP V1 receptors, indicating that the effect of Z-321 was mediated through the V1 receptors. These findings suggest that Z-321 augmented the potentiation due to its inhibitory influence on the AVP degradation by PEP.

Animals↗
PubMed1997

The involvement of KCa, KATP and KV channels in vasorelaxing responses to acetylcholine in rat aortic rings.

1. In rat aortic rings contracted by phenylephrine, acetylcholine relaxation was partly inhibited by: iberiotoxin, a Ca(2+)-activated K(KCa) channel inhibitor; glyburide, an ATP-dependent K(KATP) channel inhibitor; and 4-aminopyridine, a voltage-dependent K(KV) channel inhibitor, and was almost abolished by the removal of endothelium. 2. NG-nitro-L-arginine (NOARG), a NO synthase inhibitor, markedly reduced acetylcholine relaxation and abolished the inhibitory effects of iberiotoxin and glyburide on the acetylcholine relaxation. The inhibitory effect of 4-aminopyridine on acetylcholine relaxation was partly reduced by NOARG. 3. Methylene blue, a guanylate cyclase inhibitor, markedly inhibited acetylcholine relaxation and also abolished the inhibitory effects of iberiotoxin and glyburide and partly inhibited that of 4-amino-pyridine on acetylcholine relaxation. 4. Metyrapone, a cytochrome P-450-dependent monooxygenase inhibitor, and AA861, a 5-lipoxygenase inhibitor, but not indomethacin, a cyclooxygenase inhibitor, partly inhibited acetylcholine relaxation and reduced the inhibitory effect of 4-aminopyridine on acetylcholine relaxation. 5. These results indicate that, in rat aortic rings, acetylcholine relaxation may be dependent on the activation of KCa, KATP and KV channels. The activations of KCa and KATP channels may also be dependent on NO synthesis and subsequent formation of cGMP. The activation of KV channels may also be dependent on NO synthesis and subsequent activation of guanylate cyclase. In addition, the activation of KV channels may be dependent on the metabolism of arachidonic acid through 5-lipoxygenase and cytochrome P-450-dependent on the monooxygenase pathways.

4-Aminopyridine↗
PubMed1997

Potentiation of the relaxing action of isoproterenol by forskolin in rabbit aortic rings: the involvement of beta 2-adrenoceptors.

1. Forskolin, an activator of adenylate cyclase, potentiated the relaxing response to isoproterenol in rabbit aortic rings precontracted by phenylephrine (PE). 2. The potentiating effect of forskolin was inhibited by propranolol, a beta-adrenoceptor inhibitor, but not by methylene blue, a guanylate cyclase inhibitor. 3. The relaxing response to terbutaline, a beta 2-adrenoceptor agonist, but not lower concentrations of dobutamine, a beta 1-adrenoceptor agonist, also was potentiated by forskolin. Forskolin, however, potentiated the relaxing response to high concentrations of dobutamine, which activates both beta 1- and beta 2-adrenoceptors. 4. Yohimbine, an alpha 2-adrenoceptor inhibitor, glyburide, an ATP-sensitive K+ channel inhibitor, iberiotoxin, a Ca(2+)-activated K+ channel inhibitor, or endothelium-removal failed to affect the potentiating effect of forskolin. 5. Dibutyryl cyclic AMP (cAmp) also potentiated the relaxing response to terbutaline. 6. These results suggest that in rabbit aortic rings forskolin causes the apparent potentiation of isoproterenol-induced relaxation by mainly affecting the relaxing response due to the activation of beta 2-adrenoceptors by the forskolin-induced increase in the level of cAMP.

Adenylyl Cyclases↗
PubMed1997

Nitric oxide synthase and contractile protein in the rat cochlear lateral wall: possible role of nitric oxide in regulation of strial blood flow.

The present study demonstrated by histochemical and immunohistochemical methods that NADPH diaphorase reactivity, endothelial nitric oxide synthase (eNOS)-like immunoreactivity, and tropomyosin-like immunoreactivity, were located within the rat cochlear lateral wall. Both NADPH diaphorase reactivity and eNOS-like immunoreactivity were found mainly in the endothelium of the strial capillaries (ESC) and that of the vessels of the spiral ligament (ESL). These reaction products appeared to be somewhat more common in the ESC than in the ESL. On the other hand, tropomyosin-like immunoreactivity was localized in tissues outside the endothelium and its intensity was greater in the ESL than in the ESC. These findings suggest that nitric oxide (NO) produced by eNOS may play a role in regulating the blood flow of the cochlear lateral wall. In addition, NADPH diaphorase reactivity, eNOS-like immunoreactivity, and tropomyosin-like immunoreactivity showed different patterns of distribution between ESC and ESL. This suggests that in these two sites blood circulation is controlled by NO through two different mechanisms that are suitable for regulating strial blood flow.

Animals↗
PubMed1997

Triggers of hair cell regeneration in the avian inner ear.

We performed an in vitro study in order to determine possible triggers of hair cell regeneration in the chick basilar papilla following degeneration. We compared the response of sensory epithelium damaged by collagenase treatment with that damaged by acoustic trauma. The former exhibited no proliferative activity, but the latter did. The basilar papillae damaged by acoustic trauma could have proliferating activity in medium containing fetal bovine serum (FBS) or epidermal growth factor (EGF) but not in the medium without FBS or EGF. These findings indicate that regeneration of basilar papillae depends on the manner of cell death and that FBS or EGF is required for regeneration.

Animals↗
PubMed1997

Interleukin-10 inhibits the autocrine growth of leukemic blast cells from patients with acute myeloblastic leukemia.

The effect of interleukin-10 (IL-10) on the growth of leukemic blast cells from patients with acute myeloblastic leukemia (AML) is in need of clarification. We therefore examined the effect of IL-10 on AML cells obtained from 10 patients. Although granulocyte colony-stimulating factor (G-CSF) and/or granulocyte/macrophage colony-stimulating factor (GM-CSF) was able to stimulate the growth of AML progenitor cells to form leukemic blast colonies, IL-10 itself demonstrated no leukemic blast colony-forming activity and no synergistic stimulating activity with other cytokines. However, leukemic blast colonies were formed without the addition of exogenous cytokines in four cases and IL-10 suppressed these spontaneous colony formations in two of the four cases. Since the production of G-CSF and GM-CSF was observed in these two cases, the presence of an autocrine growth mechanism mediated by these cytokines was suggested. When serial concentrations of IL-10 were added, the production of G-CSF and GM-CSF was dramatically inhibited in a dose-dependent manner. These findings suggested that IL-10 could suppress the autocrine growth of AML cells by inhibiting their production of G-CSF and/or GM-CSF. In addition, the administration of IL-10 may be harmless to normal hematopoiesis because IL-10 did not suppress the growth of normal hematopoietic progenitor cells. Our study provides experimental support for the clinical application of IL-10 in patients with AML.

Autocrine Communication↗
PubMed1997

The endothelin ETA receptor exists in the caudal solitary tract nucleus of the rat brain.

1. The receptor autoradiographic method done on the rat lower brain stem and cerebellum plus 125I-endothelin-1, BQ-123, an antagonist for the endothelin ETA receptor, and sarafotoxin S6c, an agonist for the ETB receptor, revealed minute amounts of the ETA receptor coexisting with the ETB receptor in the caudal solitary tract nucleus of the rat lower brain stem. 2. The ETB receptor is present predominantly in other parts of the lower brain stem. 3. Knowledge of the heterogeneous distribution of the central endothelin receptor subtypes aids in understanding the neurophysiology of endothelins.

Amino Acid Sequence↗
PubMed1997

Endothelin receptors in rat pituitary gland.

1. We used the quantitative receptor autoradiographic method plus 125I-endothelin-1 (125I-ET-1), BQ-123, a specific antagonist for the endothelin ETA receptor, and sarafotoxin S6c, a selective agonist for the ETB receptor to investigate the ET receptor in the rat pituitary gland. 2. The method revealed that the BQ-123-sensitive ETA receptor was present predominantly in the anterior lobe and Rathke's pouch. 3. The posterior lobe contained BQ-123-sensitive ETA and sarafotoxin S6c-sensitive ETB receptors, in almost the same proportion. There was no significant 125I-ET-1 binding to the intermediate lobe. 4. Knowledge of the heterogeneous distribution of ET receptor subtypes in the pituitary gland supplies information that will be pertinent to physiological investigations of the gland.

Animals↗
PubMed1997

TCR beta-independent development of CD4+ CD8+ thymocytes observed in a strain of scid mice.

Mice homozygous for severe combined immunodeficiency (scid) mutation usually halt their thymocyte development at the CD4-CD8- double negative (DN) stage due to their inability of TCR gene rearrangement. In this study, we report that SCID-bg mice, which were originally generated by mating CB-17-scid mice with KSN-bg mice, spontaneously develop dominant CD4+ CD8+ double positive (DP) thymocytes. Their thymi were mainly composed of DN, CD4-CD8+ and DP cells, and the majority of them did not present CD3. Similarly, they lacked TCR beta expression both on cell surface and in cytoplasm, which suggests that the thymocyte development to the DP stage observed in SCID-bg mice, was independent of CD3 and TCR beta expression. In spite of significant DP thymocytes in SCID-bg mice, the histology of their thymi was not so different from those of CB-17-scid mice. Analysis of bone marrow cells in SCID-bg mice showed that the development of B lineage cells was not altered when compared with CB-17-scid mice. These findings point out the fact that thymocytes in SCID-bg mice have a peculiar characteristic compared to CB-17-scid mice, and provide evidence of TCR beta-independent development of thymocytes to the DP stage.

Animals↗