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Biomedical subjects

T Hashizume

Publications and source records attributed to T Hashizume.

At least 91 records · Page 5Linked to original sources
PubMed1996

Sphingosine enhances phosphatidylinositol 4-kinase activity in rabbit platelets.

The modulating effect of sphingosine on the metabolism of inositol phospholipids was investigated using rabbit platelets. When [3H]arachidonic acid- or [3H]inositol-labeled platelets were incubated at 37 degrees C with sphingosine, the radioactivity of the phosphatidylinositol (PI) fraction obtained on TLC decreased time-dependently up to 5 min, and phosphatidylinositol monophosphate (PIP) and phosphatidylinositol bisphosphate (PIP2) increased concomitantly, though neither arachidonic acid nor 1,2-diacylglycerol was formed. The effect of sphingosine was dose-dependent, the maximum effect being observed at 20 microM. Treatment with a sphingosine derivative, sphingosine-1-phosphate (Sph-1-P) or N-hexanoyl-sphingosine (C6-ceramide), did not result in an increase in PIP. The increased radioactivity of PIP with sphingosine was attributable to an increase in phosphatidylinositol 4-phosphate, but not phosphatidylinositol 3-phosphate. Furthermore, wortmannin, an inhibitor of PI 3-kinase, did not affect the modulating effect of sphingosine at 100 nM, at which the enzyme is known to be completely inhibited. The activity of PI 4-kinase in the platelet lysate was increased by sphingosine but not by Sph-1-P. These results suggest that sphingosine enhances the activity of PI 4-kinase and thereby contributes to the regulation of inositol phospholipid metabolism.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1996

Immunohistochemical detection of basic fibroblast growth factor as a prognostic indicator in pulmonary adenocarcinoma.

The expression of basic fibroblast growth factor (bFGF) was studied immunohistochemically in tissue specimens from 157 patients with pulmonary adenocarcinoma. Tumor cells that expressed bFGF were found in 89 patients (74%). The expression of bFGF was correlated with T and M in the TNM classification, disease stage and curability. The 5-year survival rate was 24% in bFGF-positive patients but 66% in bFGF-negative patients, the difference being significant (P<0.01). The 5-year survival rate of patients with stage I disease was 73% in those who were bFGF-positive but 88% in those who were bFGF-negative, the difference being significant (P<0.05). Multivariate analysis showed that the expression of bFGF was significantly related to prognosis. These findings suggest that bFGF plays an important role in tumor progression and that its expression may be a useful prognostic indicator for pulmonary adenocarcinoma.

Adenocarcinoma↗
PubMed1996

Studies on internal structure of tablets. VI. stress dispersion in tablets by excipients.

The aim of this study was to reduce the stress concentration of a medicine by dispersing the stress in tablets at tableting by addition of excipients. The mechanism of the stress dispersion was elucidated. Phenacetin (PHE) was used as a model of crystalline medicine with a high brittleness, and the degree of stress dispersion was evaluated by the change in the exposed surface area of PHE. To learn the mechanical strength of tablets, the crushing strength and friability were measured, their internal structure was analyzed by the porosity and pore size distribution, and stress relaxation experiments were performed. The results were as follows. Calcium silicate (Florite RE, FLR) showed a high stress dispersion effect, adding a high formability and mechanical strength to tablets. It was thought that the high stress dispersion resulted from the rapid stress relaxation caused by the plastic deformation and brittleness fracture of pores in FLR under a low compression pressure. Thus the stress caused locally on PHE particles may disperse.

Drug Compounding↗
PubMed1996

The effects of xylazine on plasma concentrations of growth hormone, insulin-like growth factor-I, glucose and insulin in calves.

The purpose of the present study was to examine the responses of plasma growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels to intravenous injection of xylazine in female dairy calves. Xylazine (0.05, 0.15 and 0.30 mg/kg body wt., i.v.) injections induced a significant dose-dependent increase in plasma GH level within 30 min. After plasma GH levels reached peaks, GH concentrations began to decrease immediately and they returned to control levels 1 h after xylazine injection. Plasma IGF-I concentration tended to be suppressed by xylazine treatment. Xylazine induced a significant dose-dependent increase in plasma glucose for 3.5 to 5.5 h after the treatments. Xylazine also induced a significant decrease in plasma insulin level within 30 min after treatments. The present data suggested that xylazine stimulates GH release in cattle.

Analgesics↗
PubMed1996

Effects of atipamezole, an alpha 2-adrenergic antagonist, and somatostatin on xylazine-induced growth hormone release in calves.

In order to clarify the mechanism of xylazine-induced GH release, we investigated the effects of atipamezole, a selective alpha 2-adrenergic antagonist, and somatostatin (SRIF) on xylazine-stimulated GH release in calves. Xylazine injection (0.30 mg/kg BW, iv) induced a rapid increase in the GH concentration. When atipamezole was used in combination with xylazine, it blunted the increase in the plasma GH concentration induced by the xylazine injection. The GH levels at 15-50 min after the simultaneous injection of xylazine and atipamezole were significantly (P < 0.05) lower than the corresponding values in the animals given xylazine alone. The area under the GH response curve for 120 min after the simultaneous injection of xylazine and atipamezole was significantly (P < 0.05) smaller than that for the xylazine alone. A series of five intravenous injections of 1 mg of SRIF at 10-min intervals also blunted xylazine-stimulated GH release. Atipamezole partially suppressed xylazine-induced hyperglycemia, but SRIF completely suppressed the hyperglycemia for the first 60 min after the xylazine injection and the suppression by SRIF was stronger than that by atipamezole. On the other hand, both atipamezole and SRIF failed to blunt xylazine-induced hypoinsulinemia. The present results suggest that xylazine stimulates GH release via the alpha 2-adrenergic pathway in cattle, but the mechanism of xylazine-induced hyperglycemia remains to be determined.

Adrenergic alpha-Antagonists↗
PubMed1996

[Eosinophilic pneumonia presenting as a mass shadow].

A 35-year-old man underwent routine chest roentgenography and a mass shadow was seen in the left lung field. Examination of a transbronchial lung biopsy specimen revealed that many eosinophils had infiltrated under the bronchial mucosa and into the alveolar septum. The total serum IgE concentration was high, and skin tests with Aspergillus antigen and serum precipitating antibodies against Aspergillus were positive. The mass lesion disappeared without any therapy, and a cystic lesion remained. Mediators released from eosinophils were thought to have damaged the lung tissue. We should have administrated corticosteroids as soon as possible.

Adult↗
PubMed1995

Bilirubin is oxidized in rats treated with endotoxin and acts as a physiological antioxidant synergistically with ascorbic acid in vivo.

We examined the possibility that bilirubin physiologically acts as an antioxidant by using scurvy-prone ODS-od/od rats treated with endotoxin (lipopolysaccharide: LPS). Recently, bilirubin oxidative metabolites were isolated from human urine and named biotripyrrin-a and biotripyrrin-b. The LPS injection markedly increased bilirubin oxidative metabolites in urine of rats fed an ascorbic acid-free diet. This increase was supressed by feeding an adequate amount of ascorbic acid, a physiological antioxidant. the concentrations of biotripyrrin-a and -b in urine collected 6.5-10 h after the LPS injection were lower in rats fed an ascorbic acid-supplemented diet than in rats fed an ascorbic acid-free diet. Moreover, feeding with ascorbic acid suppressed the elevation of hepatic mRNA level of heme oxygenase-1, the rate-limiting enzyme of bilirubin biosynthesis, in rats injected with LPS. These findings suggest that bilirubin is oxidized in rats treated with LPS and acts as a physiological antioxidant synergistically with ascorbic acid in vivo.

Animals↗
PubMed1995

Microdialysis measurement of intracerebral somatostatin in the goat.

A microdialysis sampling technique for the intracerebral measurement of somatostatin (SS) in extracellular fluid was examined in the goat. The microdialysis probe (70-mm shaft, 0.5 mm outer diameter) contained at its tip a 4-mm length of copolymer dialysis membrane (20 kDa cut-off). Artificial cerebrospinal fluid (artificial CSF) was pumped through the probe tip at a rate of 4 microliters/min with a batter-driven syringe pump, and effluent fractions of dialysate (120 microliters) were collected every 30 min. An in vitro recovery test showed that changes in the SS concentration in dialysate were highly correlated (r = 0.95, P < 0.01) with those in the external medium, and the relative recovery averaged 2.0%. As a validation for in vivo microdialysis, trails were conducted with conscious behaving goats wherein the inflow dialysate was changed transiently from artificial CSF with low potassium (2.5 mM) to a solution of 300 mM KCl. Potassium-induced depolarization around the probe tip located in the preoptic area and in the hypothalamus induced an increase in SS concentrations in dialysate at each location. In the most remarkable response, the concentrations of SS were increased 6-fold and 11-fold in the first and second 30-min fractions, respectively, compared with prepotassium concentrations. These results suggest that intracerebral SS levels in extracellular fluid could be estimated from conscious behaving goats by the use of our intracerebral microdialysis system.

Animals↗
PubMed1995

Stimulation of platelet-activating factor synthesis in polymorphonuclear leukocytes from streptozotocin-induced diabetic rats.

The platelet-activating factor (PAF)-synthesizing capacity was investigated and compared in peritoneal polymorphonuclear leukocytes (PMN) from streptozotocin-induced diabetic and normal rats. PAF synthesis was significantly enhanced in the PMN from diabetic rats compared with that from normal rats stimulated with fMLP. This was manifested as the increased incorporation of [3H]acetate into PAF. Selected ion monitoring/GC/MS analysis revealed that the molecular species of PAF synthesized were mostly of the 1-hexadecyl type, and the amount synthesized in fMLP-stimulated diabetic rat PMN was 1.5 times higher than that in normal rat PMN. The fMLP-induced arachidonic acid liberation resulting from phospholipase A2 activation, was facilitated with a concomitant increase in the cytosolic Ca2+ concentration in diabetic rat PMN. The CoA-independent transacylase activity was similar in both PMN lysates, whereas acetyl-CoA:lyso-PAF acetyltransferase activity was accelerated in the diabetic rat PMN lysate. These results revealed that diabetic rat PMN has more ability to synthesize PAF, presumably due to the large increase in activated phospholipase A2 and acetyltransferase, as well as the increased cytosolic Ca2+ concentration.

Acetates↗
PubMed1995

Mechanism of enhanced antipseudomonal activity of BO-2727, a new injectable 1-beta-methyl carbapenem.

The mechanism of the enhanced activity of BO-2727 against imipenem-resistant Pseudomonas aeruginosa was studied by using a set of four isogenic strains derived from beta-lactamase-deficient P. aeruginosa PAO4089 (blaJ blaP). Complementation of the blaJ and blaP mutations conferred greater resistance to biapenem, panipenem, and imipenem than to BO-2727 and meropenem, most notably in the outer membrane protein D2-deficient strain. The higher levels of resistance to biapenem, panipenem, and imipenem can be explained by the slow but significant hydrolysis by beta-lactamase, whereas the reduced levels of resistance to BO-2727 and meropenem would be attributable to their stability in the presence of high levels of beta-lactamase and the fact that they cause only low induction of beta-lactamase. It is also noted that the activity of BO-2727 against the beta-lactamase-deficient strain was less affected by the loss of the D2 porin than was that of meropenem, indicating that BO-2727 in comparison with meropenem can overcome an intrinsic resistance caused by the loss of D2. Moreover, comparative in vitro resistance studies have shown that BO-2727 and meropenem selected fewer resistant cells than other carbapenems. In conclusion, BO-2727 exhibited improved activity against imipenem-resistant P. aeruginosa, probably because of its ability to overcome loss of the D2 porin and beta-lactamase hydrolysis.

Anti-Bacterial Agents↗
PubMed1995

The interactive effects of VIP, PHI, GHRH, and SRIF on the release of growth hormone from cultured adenohypophysial cells in cattle.

The effects of hypothalamic peptides [vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI), growth hormone (GH)-releasing hormone (GHRH) and somatostatin (SRIF) on GH release from cultured bovine adenohypophysial cells were studied. The cells were incubated for 2 h with the peptides after preincubation for 3.5 days. At doses from 10(-9) to 10(-7)M VIP, the amount of GH released was significantly greater than in the controls (P < 0.05 to P < 0.001). PHI (10(-10 to 10(-7)M did not alter the bovine GH concentration in the media. Incubation with the media containing 10(-7)M GHRH, 10(-7)M VIP, and combined treatment with the VIP plus GHRH increased GH by 186, 40 and 182%, respectively (P < 0.001). Furthermore, although VIP-induced GH release was significantly decreased by SRIF compared with the treatment with VIP alone (P<0.001), the VIP significantly blunted the inhibitory effect of the SRIF on GH release by 24% when compared with that of the SRIF plus GHRH without the VIP (P < 0.05). GH release in combined treatments with VIP, GHRH and SRIF was significantly less than that of the VIP plus GHRH (P < 0.001), but it was significant 29% increase compared with the SRIF plus GHRH (P < 0.05). The combined effects of the VIP (10(-7)M) with GHRH (10(-7), 10(-8) and 10(-10)M significantly induced GH release compared with the controls (P < 0.001), but no additive effect was not observed when compared with the GHRH alone. The results indicate that VIP, but not PHI, acts directly on cultured adenohypophysial cells to induce GH release in cattle.

Animals↗
PubMed1995

Primary pulmonary lymphoma: relationship between clinical features and pathologic findings in 24 cases. The Japan National Chest Hospital Study Group for Lung Cancer.

To elucidate the relationship between the clinical features and pathologic findings of primary pulmonary lymphoma, we reviewed 24 patients with this disease. The pulmonary lymphomas were divided into four groups: (1) B-cell lymphoma composed of small to medium-sized lymphoid cells (19 cases); (2) B-cell lymphoma composed of large lymphoid cells (three cases); (3) T-cell lymphoma (one case); (4) malignant lymphoma of lymphomatoid granulomatosis (LYG) type (one case). Radiographs of the first group revealed a predominance of infiltration associated with ill-defined tumor margins upon gross pathology, corresponding histologically to lymphangitic spread. Air bronchogram and pleural tail or abutment were additional radiographic features. Characteristics of the second group were a nodule or mass evident on radiographs and well-circumscribed tumor margins upon gross pathology. Lack of air bronchogram was an another radiographic feature in this group. Seventeen patients in these two groups underwent complete resection of the tumors and survived without recurrence, whereas four received chemotherapy after biopsy and survived with disease. These results indicate that primary pulmonary B-cell lymphoma is a low-grade malignancy and that complete resection is the only therapy which leads to cure. In a single patient with T-cell lymphoma, the radiographic and pathologic features of the tumor were indistinguishable from those in the first group, but the patient had an unfavorable prognosis. We consider that, from a prognostic viewpoint, it is important to determine the T- or B-immunophenotype of the tumor cells for diagnosis of primary pulmonary lymphoma. The only patient in this series with pulmonary lymphoma of LYG type showed distinctive clinicopathologic findings. We consider that this uncommon disease should be separated from other types of primary pulmonary lymphoma.

Adolescent↗