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Biomedical subjects

T Shibuya

Publications and source records attributed to T Shibuya.

At least 127 records · Page 7Linked to original sources

Involvement of nitric oxide in intracerebroventricular beta-endorphin-induced neuronal release of methionine-enkephalin.

Previous work has suggested that the antinociceptive effect of nitrous oxide (N2O) in rats is mediated, at least in part, by beta-endorphin (beta-EP) and that centrally administered beta-EP stimulates release of methionine-enkephalin (ME) in the rat spinal cord. Since inhibition of central nitric oxide (NO) production has been found to suppress N2O antinociception, we examined the possible involvement of NO in the release of spinal cord ME by i.c.v. beta-EP. Urethane-anesthetized, male Sprague-Dawley rats were intrathecally (i.t.) perfused with artificial cerebrospinal fluid (aCSF) and fractions of perfusate were assayed for immunoreactive (i.r.) ME. The beta-EP-induced increase in ME concentration in the i.t. perfusate was significantly suppressed by perfusing the animal with aCSF containing 100 microM L-NG-nitro arginine (L-NOARG), an inhibitor of NO synthase (NOS). The further addition of 50 microM L-arginine (L-ARG), but not D-arginine (D-ARG), to the aCSF reversed the suppression of the ME change by L-NOARG. However, the potency of L-ARG decreased with increasing concentrations of L-ARG. On the other hand, increasing the concentration of L-NOARG in the aCSF to 250 microM failed to produce a greater suppression of the beta-EP-induced increase in ME. These findings suggest that NO may mediate the beta-EP-induced release of ME in the spinal cord and that interference with this mechanism might be an explanation for the antagonism of N2O antinociception in rats by NOS inhibitors.

Animals↗

Bioactive bone cement: the effect of amounts of glass powder and histologic changes with time.

A study was conducted to examine the influence of the amount of glass powder added to a bioactive bone cement of our formula on its mechanical and biologic properties. Serial changes in the cement with time were also examined. The bioactive bone cement consisted of CaO-SiO2-P2O5-CaF2 glass powder and bisphenol-a-glycidyl methacrylate resin. Glass powder was added to the cement in 30, 50, 70, and 80% weight ratios. The compressive strengths of the resulting cements (171-239 MPa) were more than double that of polymethylmethacrylate cement (68 MPa). Histologic examination of rat tibiae bearing artificial defects packed with each bioactive cement showed direct bone contact 4 weeks after surgery. The cement with a higher percentage of glass powder showed better direct formation of bone around its periphery with a thicker reactive layer. Under scanning electron microscopic observation, the reactive layer showed increased levels of calcium and phosphorus. Examination of histologic changes up to 26 weeks showed progressive bone formation around the cement and no sign of biodegradation.

Animals↗

Suppression of pseudointimal hyperplasia by a novel prostacyclin analogue: beraprost.

The aim of this study was to evaluate the effect of a novel prostaglandin I2 analogue, beraprost (BPT), on the pseudointimal hyperplasia (PIH) of polytetrafluoroethylene (PTFE) prostheses. A total of 12 rabbits were equally divided into three groups. The control group was given a placebo daily, group 1 was given BPT orally 2 mg/kg per day, and group 2 was given BPT orally 4 mg/kg b.i.d. Exactly 1 cm of the inferior vena cava was resected and replaced by a 3-cm PTFE tube graft. All the grafts were patent when harvested 4 weeks after implantation, but the lumens were narrowed to various extents by PIH. PIH, determined by the dry weight of the intraluminal tissue deposit, was significantly (P < 0.01) suppressed in groups 1 and 2 compared with the control group. High-magnification light microscopy with various staining methods revealed the PIH to be composed mainly of smooth muscle cells (SMCs) and collagen fibrils in all three groups. Transmission electron microscopy revealed that the majority of SMCs in groups 1 and 2 were contractile in form, in contrast with the synthetic form seen in the control group. In conclusion, BPT attenuated the PIH of PTFE grafts by inhibiting the phenotype change in the SMCs.

Animals↗

Clinicopathological study of clear-cell tumors of the thyroid: an evaluation of 22 cases.

Twenty-two cases of partial or wholly composed clear-cell thyroid tumors were reviewed to differentiate between a primary nodule and metastatic clear-cell renal carcinoma in the thyroid. Pathological reevaluation of HE-stained specimens, immunohistochemical observation using anti-thyroglobulin (TG) antibody, and periodic acid-Schiff (PAS) staining were performed. The pathological characteristics in metastases from the kidney have a greater tendency to demonstrate a strikingly clear cytoplasm with small nuclei, rich vascularization, and a trabecular arrangement of tumor cells than do primary thyroid cases. The immunohistochemical TG staining in conjunction with PAS staining for the recognition of follicular colloid could provide much more reliable information of primary cases compared to that using TG staining alone. Clinically, in primary cases, the female:male ratio is substantially higher while the mean age is lower than in metastatic cases reflecting differentiated thyroid carcinoma. In conclusion, immunohistochemical staining for TG with PAS staining for the recognition of follicular colloid proved to be the most sensitive method for identifying primary clear cell thyroid tumors. In addition, a careful assessment of past and/or present kidney disorders to rule out metastatic renal cell carcinoma is advisable. Age, gender, and physiological findings are also informative when differentiating between them.

Adenocarcinoma, Clear Cell↗

Scanning electron microscopy-electron probe microanalysis study of the interface between apatite and wollastonite-containing glass-ceramic and rabbit tibia under load-bearing conditions after long-term implantation.

Glass-ceramic implants containing oxy- and fluoroapatite [Ca10(PO4)6(O, F2)] and beta-wollastonite (CaSiO3) were studied under load-bearing conditions in a segmental replacement model in the tibia of the rabbit. A 16-mm segment of the middle of the tibial shaft was resected at a point distal to the junction of the tibia and the fibula. The defect was replaced by a 15 mm-long hollow, cylindrical implant that was fixed by intramedullary nailing using Kirschner wire. The implants were 9 mm in diameter and 15 mm long bearing a central hole 3.05 mm in dianeter. The rabbits used were killed 6 months, 1 year, 18 months, and 2 years after implantation. The interface between the bone and the glass-ceramic was investigated by scanning electron microscopy-electron-probe microanalysis (SEM-EPMA). None of the glass-ceramic implants broke, and the glass-ceramic had bonded directly to the bone tissue without any intervening soft tissue. A calcium-phosphorus layer (Ca-P layer) was observed at the glass-ceramic/bone interface. This layer was 30-100 microns thick at 6 months after implantation, 60-110 microns thick at 1 year after implantation, 80-200 microns thick at 18 months, and 120-350 microns thick at 2 years. At the lateral surface of the glass-ceramic uncovered by the bone, the calcium-phosphorus layer was 50-80 microns thick at 6 months after implantation, 250-450 microns thick at 1 year, 300 approximately 400 microns thick at 18 months, and 300 microns thick at 2 years. The thickness of the calcium-phosphorus layer increased moderately after long-term implantation. However, it was difficult to estimate the rate of increase in the thickness of calcium-phosphorus layer.

Animals↗

Adenomyoma of the common hepatic duct.

A very rare case of adenomyoma of the common hepatic duct is described. A 54-year-old woman was admitted with impending obstructive jaundice secondary to adenomyoma of the common hepatic duct. Our impression, formulated from her clinical presentation, endoscopic investigations, and biochemical and radiological findings, was a cancer of the proximal common hepatic duct. The patient was treated successfully by combination surgical resection and hepaticojejunostomy. Despite our obtaining an intraoperative frozen section, final histological examination was required to confirm the diagnosis. The patient remains well 16 months postoperatively. A survey of the world literature revealed that this is the second report of adenomyoma occurring in the common hepatic duct.

Adenomyoma↗

Angioscopic identification of coronary thrombus in patients with postinfarction angina.

OBJECTIVES: The purpose of this study was to determine the prevalence of intracoronary thrombus and associated anatomic abnormalities in patients with postinfarction angina using coronary angioscopy and angiography. BACKGROUND: Postinfarction angina, previously studied by angiographic methods only, identifies patients at high risk for sudden death, recurrent angina and refractory angina. The recent development of coronary angioscopy, which permits direct observation of a thrombus or atheroma and is especially used for the detection of intraluminal changes, encourages a reexamination of the pathogenesis of postinfarction angina. METHODS: Fifty-one consecutive patients with a diagnosis of acute myocardial infarction underwent cardiac catheterization. Coronary angiography followed immediately by coronary angioscopy was performed in 17 patients with and 34 without postinfarction angina during the same period of time (10.2 +/- 3.7 or 15.7 +/- 5.5 days [mean +/- SD]) after the onset of acute myocardial infarction. RESULTS: The frequency of thrombus, as observed by angioscopy, was significantly higher in patients with than without postinfarction angina (17 of 17 vs. 5 of 34, respectively, p < 0.01). There were no significant differences between groups with respect to degree of stenosis in the infarct-related artery, number of vessels with significant stenosis, presence of collateral flow, type of therapy and risk factors. CONCLUSIONS: Infarct-related artery thrombus is universally present in postinfarction angina and may be the primary pathogenic factor. Angioscopy is much more sensitive than coronary angiography for the detection of coronary thrombus.

Aged↗

An infection-resistant PTFE vascular graft; spiral coiling of the graft with ofloxacin-bonded PTFE thread.

OBJECTIVE: To develop an infection-resistant polytetrafluoroethylene (PTFE) vascular graft for potential clinical use in grafting in sites of bacterial contamination and in replacement of the infected grafts. SETTING: Experimental study in rabbits. MATERIALS AND METHODS: An antibiotic ofloxacin (OFLX) was bonded to a sheet of PTFE by impregnation, which was cut and twisted into fine threads. The in-vitro antibacterial activity of OFLX-PTFE thread was determined by measuring the zone of growth inhibition against Escherichia coli. The thread was spirally coiled around a ridged outerwall PTFE to make the OFLX-PTFE graft. OFLX-PTFE graft or control graft was interposed in the inferior vena cava (IVC) of rabbits and the entire graft was covered with fibrin containing a fixed number of E. coli. Three or 7 days after the grafting, the grafts with perigraft tissue were harvested and subjected to bacteriological studies. RESULTS: In spite of early phase rapid elution of OFLX, a significant antibacterial activity was retained for more than 2 weeks. The antibacterial activity of OFLX-PTFE threads implanted in the subcutaneous space of rabbits decreased to 48% after 24 h and to approximately 1% after a week. The swab culture of all the control grafts was positive, while only one of 13 PTFE-OFLX grafts was positive. The number of viable bacteria in the perigraft tissue of OFLX-PTFE grafts was remarkably low in comparison with that of control grafts. Thus, the OFLX-PTFE grafts exhibited a marked in-vivo antibacterial activity. CONCLUSION: By a unique method, it was possible to furnish PTFE graft with an excellent infection-resistant property, without affecting the original biological behaviour.

Animals↗

Characterization of blasts from a patient with eosinophilic blast crisis of chronic myelogenous leukaemia.

We investigated the biological characteristics of 'eosinophilic' leukaemic blasts from a patient with eosinophilic blast crisis of chronic myelogenous leukaemia (CML). Southern blot analysis of the bcr gene demonstrated the identical single rearranged band in both the leukaemic blasts and mature eosinophils. IL-3, IL-5 and GM-CSF significantly enhanced proliferation and differentiation of these leukaemic blasts, and only eosinophils were generated from in vitro cultures. Those eosinophils expressed the B3A2 chimaeric messenger RNA seen in the leukaemic blasts. These observations indicate that eosinophil progenitors may be involved in the development of eosinophilic blast crisis of CML and that IL-3, IL-5 and GM-CSF act on the leukaemic eosinophil progenitors.

Blast Crisis↗

Healing of polytetrafluoroethylene vascular grafts analyzed by anti-smooth muscle myosin heavy chain isoforms.

The purpose of this study was to characterize the cellular contributions to the formation of the pseudointima (PI) using immuno-histochemistry with antibodies to specific smooth muscle myosin isoforms, SM1, SM2, SMemb, and to alpha-smooth muscle actin. The outer wall of polytetrafluoroethylene tube grafts were coated with a 10-microns silicon film except for 5 mm of the midportion and the grafts were implanted into the inferior vena cava of rabbits. The PI in the anastomotic area was mainly formed by dedifferentiation and redifferentiation of medial smooth muscle cells of the host vessel, while PI in the midgraft was formed by differentiation of myofibroblasts into smooth muscle cells in the internodal space.

Animals↗

[Effect of fluvoxamine, a new antidepressant drug, on monoamine dynamics in the rat cerebral limbic system and its pharmacological characteristic].

The effect of fluvoxamine (FLU) on the amine dynamics in serotonergic, noradrenergic or dopaminergic nervous systems in the rat cerebral limbic system was investigated, with reference to the pharmacological characteristics of FLU. Following single oral administration of 30 and/or 60 mg/kg FLU, significant decreases in the 5-hydroxyindole-3-acetic acid (5-HIAA)/serotonin (5-HT) ratios in the amygdala and hippocampus and the 4-hydroxy-3-methoxyphenylglycol (MHPG)/norepinephrine (NE) ratio in the amygdala were produced. FLU at 15 mg/kg, p.o. also caused a significant increase in MHPG/NE ratio in the hippocampus. On the other hand, imipramine (IMI) at 30 mg/kg, p.o. induced significant decreases in 5-HIAA/5-HT ratio in the hippocampus, MHPG/NE ratios in the amygdala and hippocampus, and 3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine (DA) ratios in the amygdala, hippocampus and septum. The 5-HIAA/5-HT ratios in the amygdala and hippocampus and the MHPG/NE ratio in the septum were significantly decreased after repeated oral administration of 30 mg/kg FLU twice daily for 14 days, but the MHPG/NE ratio in the amygdala was increased. In the septum, DOPAC/DA ratio was significantly decreased following repeated administration of IMI at 30 mg/kg, p.o. These findings suggest that FLU inhibits 5-HT turnover in the amygdala and hippocampus as a result of the interference with the neuronal re-uptake mechanism for 5-HT. Also, FLU has an effect on NE turnover in the cerebral limbic system, and the effect may appear in connection with a change in the interaction of nervous systems.

Administration, Oral↗

Potentiation of excito-toxicity by glutamate uptake inhibitor rather than glutamine synthetase inhibitor.

The neuroprotective functions of glia cells in the presence of excessive amounts of extracellular glutamate (Glu) were examined using glia-rich and glia-poor cultured cerebellar granule cells that contained the same number of neurons. In order to focus on the metabolic enzyme glutamine synthetase (GS) and the uptake system in glia cells, selective inhibitors such as L-methionine sulfoximine (MSO) and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) were used as pharmacological tools. The increased amount of lactate dehydrogenase (LDH) leakage induced by 50 microM Glu and SITS was equivalent to that of 1 mM Glu. However, the simultaneous treatment with 50 microM Glu and 5 microM MSO did not increase the LDH leakage. The larger quantities of extracellular Glu were sustained in both glia-rich and glia-poor cultures. After the administration of Glu and MSO, however, the larger quantities of Glu were not sustained. Taking these results into consideration, the Glu uptake system in glia cells seems to be more important than the Glu metabolic enzyme system in the regulation of neuronal protection from Glu toxicity.

Animals↗

Structural elucidation of aculeximycin. III. Planar structure of aculeximycin, belonging to a new class of macrolide antibiotics.

The planar structure of aculeximycin (1) produced by Streptosporangium albidum has been determined by spectral methods and chemical degradations such as 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU)-methanol reaction, ozonolysis, and periodative oxidation. The antibiotic consists of a 30-membered polyhydroxy lactone ring, an alpha, beta-unsaturated ester group, an intramolecular hemiketal, an oligosaccharide (aculexitriose), a neutral sugar and an amino sugar. The structure of aculeximycin is closely related to those of sporaviridins produced by Streptosporangium viridogriseum. We consider that aculeximycin and sporaviridins belong to a new class of macrolide antibiotics, which is different from the polyol macrolides produced by Streptomyces.

Acetylation↗

Structural elucidation of aculeximycin. IV. Absolute structure of aculeximycin, belonging to a new class of macrolide antibiotics.

Aculeximycin (1) produced by Streptosporangium albidum possesses a 30-membered polyhydroxy macrocyclic lactone and five sugars including aculexitriose. We have described the determination of the planar structure of N-diacetylated aculeximycin (2) using degradation products, which were obtained by DBU-methanol treatment, ozonolysis and periodative oxidation. In order to determine the relative and absolute configurations of aculeximycin, first, the relative and absolute configurations of the degradation products 10, 11, 12 and 13 were determined. Rychnovsky's method was very useful to determine the relative configurations of these degradation products, and CD exciton chirality and the modified Mosher's methods were applied to determine their absolute configurations. From these results, fourteen out of the twenty asymmetric centers in aculeximycin were determined to be 5S, 17R, 20S, 21R, 23R, 24R, 29S, 30R, 31S, 34R, 35S, 36S and 37R. The absolute configurations at C-14 and C-15 on the hemiketal ring were confirmed using 12 obtained by the partial glycol bond cleavage of 9. Absolute configurations of the remaining asymmetric centers were determined by spectral analysis of 15 and NOE experiment on 1. From these results, the absolute configuration of 1 was determined to be 5S, 7R, 10S, 11R, 14R, 15S, 17R, 19R, 20S, 21R, 23R, 24R, 25S, 29S, 30R, 31S, 34R, 35S, 36S and 37R.

Anti-Bacterial Agents↗

Relationship of infused CFU-GM and CFU-Mk mobilized by chemotherapy with or without G-CSF to platelet recovery after autologous blood stem cell transplantation.

Although hematologic reconstitution is usually rapid after autologous blood stem cell transplantation (ABSCT), there is an occasional delay in platelet recovery. We studied the hematologic recovery of 27 adult patients with hematologic malignancies who received marrow-ablative chemotherapy and ABSCT to determine whether or not the numbers of infused mononuclear cells (MNC), colony-forming units granulocyte/macrophage (CFU-GM), and colony-forming units megakaryocyte (CFU-Mk) were related to the speed of platelet recovery after ABSCT. Peripheral blood stem cells were collected using chemotherapy-induced mobilization with or without cytokine therapy. While the number of MNC infused did not show a significant correlation with time to platelet recovery as well as granulocyte and reticulocyte recovery, the logarithmic number of CFU-GM-infused did (p < 0.01). We also found a significant correlation between the logarithmic number of CFU-Mk-infused and the time to platelet recovery (p < 0.01). These findings suggest that the number of CFU-GM-infused is a reliable indicator of hematopoietic recovery and that the number of CFU-Mk-infused is no more reliable than CFU-GM for predicting platelet recovery after ABSCT.

Adolescent↗

Relation between age-related changes in hyper-emotionality and serotonergic neuronal activities in the rat limbic system.

To examine the relationship between higher concentrations of 5-HT and 5-HIAA in the aged rat brain and their hyper-emotionality, behavioral and neurochemical studies were performed. In the behavioral studies, under novel circumstances, the aged rats showed an significant increase in defecation. Furthermore, their locomotor activity was much less than that of young rats, and the numbers of head-dips of aged rats were significantly decreased compared to those of young rats. In the neurochemical studies, the concentrations of 5-HT and 5-HIAA in the limbic system (e.g., hippocampus, amygdala and septal area) of aged rats were much higher than those of young rats (P < 0.001) under normal conditions. The possibility that the hyper-emotionality of aged rats might be related to the hyper-activities of serotonergic neurons in their limbic system were taken into consideration when the results were analyzed.

Aging↗

Inhibitory effects of newly synthesized Ser-contained GABA-peptides administered into either caudate putamen or amygdala on methamphetamine-induced hyperactivity.

The locomotor activities induced by methamphetamine (MAP: 1 mg/kg) following the microinjection of either GABA or three synthesized GABA-peptides (PLG, PSLG, PDSLG) into the rat caudate putamen or the amygdala were measured by using behavioral analysis. The ip administration of MAP induced hyperactivities in a time-dependent manner, and the maximum activity was measured 30 min after MAP administration. This hyperactivity was observed for more than 2 hrs. By the microinjection of GABA-peptides (0.054-540 nmol) into each brain region, the MAP-induced hyperactivity was significantly reduced in a dose-dependent manner, although the single administration of examined dosages of these peptides did not influence the locomotor activity. In the case of microinjection of GABA into either one of the brain regions, only the larger dosage (27,000 nmol) significantly reduced the MAP-induced hyperactivity, whereas this inhibition was less than that seen at the dose of 540 nmol of GABA-peptides. Furthermore, the microinjection of newly synthesized GABA-peptides, PSLG and PDSLG, into the caudate putamen was more effective than those obtained by injection into the amygdala. However, either microinjection of PLG or GABA into both regions showed similar inhibition. These results suggest that the pharmacological properties of newly synthesized GABA-peptides are different compared to those of PLG and GABA, and that these differences might be due to the primary inhibitory effects of the serine-contained GABA-peptides on dopaminergic neuronal activity, but not on GABA neurons.

Amygdala↗