Wrong site for Japanese labs.
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Biotechnology↗
Biomedical subjects
S Shibata
Publications and source records attributed to S Shibata.
A neuroprotective effect of histamine H1 receptor antagonist on ischemia-induced decrease in 2-deoxyglucose uptake in rat hippocampal slices.
The effects of histamine (HA) receptor antagonists on hypoxia + hypoglycemia (ischemia)-induced impairment of 2-deoxyglucose (2-DG) uptake by rat hippocampal slices was evaluated. Hippocampal slices were exposed to 20-min ischemia and then returned to oxygenated and glucose-containing Krebs-Ringer solution for 6 h. Ischemia reduced 2-DG uptake in the hippocampal slices. The ischemia-induced reduction in 2-DG uptake was attenuated by pretreatment with H1 receptor antagonist but not with H2 receptor antagonist. Treatment with HA exacerbated the ischemia-induced decrease. The H1 receptor antagonist-induced neuroprotective effect was blocked by co-treatment with HA. The present study suggests that the blockade of H1 receptor-mediated function has a protective role in ischemia-induced decreases in glucose metabolism in hippocampal slices.
Animals↗
Improving effect of acetylcholine receptor agonists on a deficit of 2-deoxyglucose uptake in cerebral cortical and hippocampal slices in aged and AF64A-treated rats.
The aim of the present study was to determine whether the facilitation of 2-deoxyglucose (2-DG) uptake in the cerebral and hippocampal slices by nicotinic and muscarinic receptor agonists is compromised in the aged rat brain. For this, the effects of the nicotinic receptor agonist nicotine, the muscarinic receptor agonists oxotremorine and McN-A-343, and the ACh esterase inhibitors physostigmine and NK247 on 2-DG uptake in the brain slices of young (2-month-old) and aged (24-26-month-old) rats were tested. The decrements of 2-DG uptake in the cortical slices of aged rats were significantly attenuated by treatment with oxotremorine, nicotine and amiridine. In contrast, the metabolic responsivity of hippocampal slices to these drugs was reduced. To assess whether age-related changes in 2-DG uptake may be due to deficits in cholinergic function, we tested these drugs on the decrements of 2-DG uptake in ethylcholine aziridinium (a neurotoxic analog of choline) injected rats. The reductions of 2-DG uptake by injection of ethylcholine aziridinium was attenuated by oxotremorine but not by physostigmine. The present results reveal that metabolic decrements in the cerebral cortex from aged or ethylcholine aziridinium-injected rats were attenuated by muscarinic and nicotinic receptor agonists, suggesting that the muscarinic and nicotinic receptor mechanism in the cerebral cortex may be involved in cholinergic drug-induced functional recovery in aged rats.
Acetylcholine↗
Facilitation of 2-deoxyglucose uptake in rat cortex and hippocampus slices by somatostatin is independent of cholinergic activity.
2-Deoxyglucose (2-DG) uptake is an index of regional glucose utilization which reflects predominantly activity in the axonal terminal of neuronal pathways. The present experiments showed that somatostatin elevated 2-DG uptake in rat cortex and hippocampus slices. Treatment with somatostatin-14 and somatostatin-28 markedly enhanced 2-DG uptake, whereas the amino-terminal fragment of somatostatin-28 did so only slightly. This effect appeared to be mediated by an interaction with somatostatin receptors because cyclo-somatostatin, a somatostatin antagonist, abolished the effect of somatostatin-14. The increase in 2-DG uptake caused by somatostatin-14 was blocked by the calcium channel antagonist, nifedipine, but not by tetrodotoxin, suggesting that the action of somatostatin does not require the initiation of impulse activity, somatostatin enhanced the KCl-induced release of acetylcholine, suggesting that a cholinergic mechanism is involved in the somatostatin-induced cellular responses. We therefore examined whether acetylcholine receptor antagonists block the somatostatin-induced increase in 2-DG uptake. Neither muscarinic nor nicotinic receptor antagonists affected the somatostatin-14-induced response. The present results suggest that somatostatin has a stimulatory effect on energy metabolism and that this effect is independent of acetylcholine receptor mechanism.
Animals↗
Monoclonal antibodies to heparan sulfate inhibit the formation of thrombin-antithrombin III complexes.
As components of the cell surface and extracellular matrix, heparan sulfate proteoglycans play an important role in the function of most organs, including the vasculature. Autoimmunity to heparan sulfate (HS) glycosaminoglycan epitopes may play a role in tissue injury. Tight skin (TSK) mice suffer a disease resembling scleroderma, an autoimmune disease associated with alterations in the extracellular matrix of the skin and other organs, as well as vascular injury. Studies of autoimmunity to HS were performed in TSK mice employing a solid-phase radioimmunoassay for the detection of anti-HS antibody. An increase in the clonal frequency of hybridomas secreting anti-HS antibody was noted in TSK mice compared to that in control mice. Liquid-phase competitive inhibition specificity studies of IgM and IgG anti-HS monoclonal antibodies demonstrated little cross-reactivity with other glycosaminoglycans. Some cross-reactivity, albeit at lower affinity, with phosphorylated antigens including DNA, cardiolipin, and RNA polymerase were noted. Negatively charged sulfate groups and carboxyl groups played a role in the immunodominant site. Monoclonal antibodies to HS inhibited the binding of HS to antithrombin III and the formation of thrombin-antithrombin III complexes. These results demonstrate autoimmunity to HS in TSK mice. The results also indicate that HS is a high-affinity antigen of pathological significance for anti-DNA and anti-phospholipid antibodies. Thrombosis induced by polyclonal anti-phospholipid antibodies may be mediated by a subset of these antibodies with high affinity for HS. Anti-HS antibodies may promote a procoagulant state by the blockade of HS binding to antithrombin III, inhibiting the accelerated formation of thrombin-antithrombin III complexes.
Animals↗
Induction of skin fibrosis and autoantibodies by infusion of immunocompetent cells from tight skin mice into C57BL/6 Pa/Pa mice.
Tight skin (TSK/+) mice develop a cutaneous hyperplasia associated with the occurrence of autoantibodies characteristic for scleroderma. In order to study the role of autoimmunity in the production of skin fibrosis, we conducted adoptive transfer experiments in which bone marrow cells of TSK/pa mice were infused into pa/pa mice littermates. (C57BL/6 pa/pa mice are used to produce heterozygous TSK/pa mice). Our results showed that after a prodromal period of several months, the transfer of bone marrow cells led to skin fibrosis, the presence of autoantibodies, and increased transcription of (alpha 1) collagen I and TGF beta genes. Infusion of enriched B or T cells alone did not cause skin fibrosis but of B cells alone increased autoantibody production. By contrast, transfer of T and B lymphocytes led to earlier mild fibrosis, cellular infiltration and autoantibody production as well as increased transcription of the (alpha 1) collagen gene. Our results strongly demonstrate, for the first time, that immunocompetent cells can play a role in the activation of collagen synthesis leading to skin fibrosis.
Animals↗
Experimental and clinical studies on the intraperitoneal administration of cis-diamminedichloroplatinum (II) for peritoneal carcinomatosis caused by gastric cancers.
The effectiveness of the intraperitoneal administration of cis-diamminedichloroplatinum (II) (DDP) on peritoneal carcinomatosis caused by gastric cancers was evaluated. Seventeen patients were treated with one of three protocols, consisting of the intraperitoneal injection (ip) of DDP at doses of 70 and 110 mg/m2, with or without sodium thiosulfate (STS) rescue. The area under the curve (AUC) of DDP for sufficient anticancer activities against cultured human cell lines in vitro was estimated at 240 micrograms h/ml, which was equivalent to the AUC gained by 110 mg/m2 ip DDP in the clinical studies. The cytotoxic activity of DDP was reduced by approximately 50% with 100-fold STS in the AUC in the experimental studies. However, this was achieved only in urine, and not in either the peritoneal cavity or in plasma in the clinical studies. Three cases of a partial response against peritoneal carcinomatosis were seen from a total of four evaluable cases treated with 110 mg/m2 DDP, and no renal toxicities were observed in those treated with the STS rescue. The results of this study led us to conclude that high-dose ip DDP treatment combined with the STS rescue would be useful chemotherapy against peritoneal carcinomatosis caused by gastric cancers.
Adult↗
Biphasic effects of suramin on 125I-epidermal growth factor binding to human meningiomas.
1. We studied the effects of suramin, a nonspecific growth factor antagonist, on epidermal growth factor (EGF) binding to cell surface receptors in surgically excised human meningiomas, using quantitative receptor autoradiographic methods with radioluminography. 2. High concentrations (10(-4) - 10(-2) M) of suramin inhibited 125I-EGF binding to meningioma sections with IC50's of 3.2 +/- 0.4 x 10(-4) M, whereas lower concentrations (10(-5) - 10(-4) M) of the drug significantly enhanced EGF binding to the tumor. Scatchard analysis of EGF binding profile revealed significant increases in binding affinity following incubation in the presence of 5 x 10(-5) M suramin, without significant alterations in maximal binding capacity. 3. The addition of 10(-3) M suramin to the incubation buffer rapidly dissociated 125I-EGF previously bound to meningioma tissues as a function of time (dissociation half-life, T1/2 = 12.4 min). 4. Preincubation in the presence of 5 x 10(-5) M suramin resulted in significant increases in the subsequent binding of 125I-EGF to meningiomas, compared to findings in the control. 5. Our data indicate that (a) suramin exerts biphasic effects on EGF binding to the tissue sections of meningiomas in vitro, depending on the concentration of the drug; and (b) low concentrations of suramin enhance the affinity of the EGF receptor in the tumor sections, probably by interacting with the EGF receptor molecule rather than with the EGF peptide. 6. The functional role of increased EGF receptor affinity in meningioma sections in the presence of lower concentrations of suramin remains to be determined.
Aged↗
Report of colon cancer detection in mass surveys using immunological occult blood test (Latex method).
Occult blood test for the screening of colon cancer has been made by immunological method using latex agglutination for 4 years since 1988. A total of 35,139 persons have received the screening test and out of 1886 persons, that is, 5.4% showed positive. Five hundred seventy of the positive result subjects (30.2%) underwent barium enema examination. Three hundred fifty nine subjects (62.8%) showed some abnormal findings. They underwent colonoscopic examination and 45 of them (7.9%) had colon cancer. Twenty six of these were of early stage type and 19 persons were of advanced stage.
Adenocarcinoma↗
Esophageal cancer associated with multiple cancerous lesions: clinicopathologic comparisons between multiple primary and intramural metastatic lesions.
Detailed histopathological examination of serial blocks and subserial sections of the entire resected esophagus in 111 patients who underwent esophagectomy for esophageal squamous cell carcinoma revealed 38 associated cancerous lesions apart from the main tumors, in 33 patients (29.7%). These associated lesions were divided into multiple primary lesions (MPLs; 27 lesions in 23 patients) and intramural metastatic lesions (IMLs; 11 lesions in 10 patients). Thirteen and fourteen MPLs were distributed on the proximal and distal sides, respectively, of the main tumor with the same mean distance of 2.6 cm. Three and 8 IMLs were located on the proximal and distal sides, respectively, with mean distances of 3.4 cm and 4.6 cm. With respect to the histological depth of cancer invasion, MPLs were all confined within the submucosal layer (superficial cancer) while IMLs varied from the submucosa to the adventitia. Histological findings indicate that MPLs may be associated with a possible increased multicentric carcinogenic potential in the non-cancerous epithelium of the esophagus of patients who have had an antecedent esophageal cancer, and that IMLs are developed by intramural lymphatic spread from the primary esophageal cancer. These results emphasize the need for careful attention to the choice of margins during the surgical resection of the esophagus.
Aged↗
Characterization of a system of mineralized-tissue formation by rat dental pulp cells in culture.
Pulp tissue was obtained from maxillary incisors of young adult male Wistar rats, minced and digested with 0.5% trypsin and 0.02% EGTA at 37 degrees C for 30 min. Dissociated cells were cultured with or without 10 nM dexamethasone using Eagle's minimal essential medium supplemented with 10% fetal bovine serum and 50 micrograms/ml ascorbic acid. Confluent cells were subcultured at 7 days and the medium further supplemented with beta-glycerophosphate (beta-GP). Dexamethasone in primary culture and/or secondary culture enhanced the formation of mineralized tissue while > 5 mM beta-GP was necessary for mineralization to occur. Biochemical analysis of the radiolabelled medium revealed that these cells produced type I, type I trimer and type III collagens. Analysis of [32PO4]-labelled medium, using DEAE-Sephacel ion-exchange chromatography and sodium dodecylsulphate-polyacrylamide gel electrophoresis, showed that these cells produced phosphophoryn-like protein. These results indicate that some of the rat dental pulp cells in culture express an odontoblast-like phenotype.
Animals↗
A comparative ultrastructural study of the mitotic chondrogenic cells in the mandibular condyle and tibial growth plate of the rat.
Mitotic cells in the rat mandibular condyle (proliferative mandibular cells) were compared with mitotic cells in the rat tibial growth plate (proliferative tibial cells). In the tibial proliferative cells, the rough endoplasmic reticulum mostly became vacuolated during the latter stage of mitosis, whereas the rough endoplasmic reticulum of the proliferative mandibular cells rarely underwent disorganization. Further, a wide area remained outside of the mitotic spindle in the proliferative tibial cells at the metaphase, while only a narrow area remained in the proliferative mandibular cells. This finding might account for the difference of disorganization of the rough endoplasmic reticulum.
Animals↗
An ultrastructural study of the mitotic preosteoblasts in the primary spongiosa of the rat mandibular condyle.
In this study, we observed mitotic preosteoblasts that have the structural features of osteoblasts in the primary spongiosa of the rat mandibular condyle. The rough endoplasmic reticulum and the Golgi apparatus showed remarkable disorganization during mitosis. The Golgi saccules were replaced by groups of large vacuoles and small vesicles. The cisternae of the rough endoplasmic reticulum also were vacuolized. Since this disorganization occurred in conjunction with the formation of the mitotic spindle, it is probably related to the changes of the microtubular cytoskeleton. Further, secretory granules were arrayed along the mitotic spindle microtubules at the metaphase, and concentrated around the midbody at the telophase. These findings indicate a close relationship exists between secretory granules and microtubules.
Animals↗
An ultrastructural study of mitotic chondrocytes in the proliferative zone of the rat tibial growth plate.
Mitotic chondrocytes containing fairly prominent cell organelles were observed in the proliferative zone of the rat tibial growth plate by electron microscopy. During the later stage of mitosis, the endoplasmic reticulum was mostly vacuolated, and the Golgi stacks were replaced by spherical and cylindrical vacuoles and small vesicles. The cytoplasmic division began at early telophase. However, the cytoplasmic cleavage furrow was so narrow that dividing chondrocytes looked as if they were partitioned by a slit. This is probably one reason for the appearance of the binuclear cells that are occasionally observed in the tibial growth plate.
Animals↗
Hemodynamic mechanisms of the antianginal action of a novel vasodilator FK409 in dynamic exercise-induced angina.
FK409 is a novel vasodilator with a unique chemical structure. We wished to elucidate the mechanisms of antianginal action of FK409 in dynamic exercise-induced angina. Twelve patients with stable effort angina pectoris were studied before and after a single 40-mg oral dose of FK409. Chest pain was induced in all of 12 patients during the control multistage bicycle ergometer exercise. After FK409 administration, the same workload did not induce chest pain in 6 patients. The ST segment at peak exercise showed less severe depression from 0.15 +/- 0.02 to 0.05 +/- 0.01 mV (p < 0.001). Left ventricular (LV) filling estimated by the Doppler method was reduced, and pulmonary artery wedge pressure decreased significantly (p < 0.001) throughout exercise testing after FK409. Myocardial oxygen uptake and coronary sinus flow throughout exercise testing decreased significantly (p < 0.05) after FK409 administration. The results of the present study demonstrate that decrease in myocardial oxygen demand may be caused by pre- and afterload reduction and that it could be a major mechanism of the antianginal action of FK409. However, other mechanisms such as redistribution of coronary blood flow to the subendocardium, direct dilatation of the stenotic parts of the epicardial arteries, and an increase in collateral blood flow should be considered additional possible mechanisms of the antianginal action of FK409.
Aged↗
Pharmacologic properties of KT2-962 (6-isopropyl-3-[4-(p- chlorobenzenesulfonylamino)-butyl]-azulene-1-sulfonic acid sodium salt); a new TXA2/prostaglandin endoperoxide receptor antagonist.
Pharmacologic properties of KT2-962 (6-isopropyl-3-[4-(p-chlorobenzenesulfonylamino)butyl]-azulene+ ++-1-sulfonic acid sodium salt, KT) were studied in isolated rat aorta, rat tail artery, rabbit aorta, rabbit renal artery, and pig coronary artery. KT competitively inhibited the contractions induced by thromboxane A2 (TXA2) mimetic, U46619 (pA2 values 9.95, 8.85, 7.87, 8.49, and 9.12, respectively). KT also inhibited the contraction of rabbit aorta induced by prostaglandin2 alpha (PGF2 alpha, pA2 value 7.85) and the contraction of guinea pig ileum induced by LTD4 (pA2 value 5.48) but did not alter the contractions induced by norepinephrine (NE), Ca2+, serotonin, and histamine. KT did not alter the contractions of guinea pig ileum, which did not contract with U46619, induced by PGE2 and PGF2 alpha. KT inhibited the aggregations of rabbit platelets induced by U46619, arachidonic acid, and collagen (IC50 values 7.9, 140, and 16 microM, respectively) but not those induced by ADP. It also inhibited the specific binding of TXA2/PGH2 receptor antagonist, [3H]SQ29,548, to rabbit gel-filtered platelets with an IC50 value of 1.5 x 10(-8) M. In in vivo experiments with mice, oral administration of KT protected the U46619-induced sudden death with the minimum effective dose of 0.3 mg/kg and provided such protection for > 8 h at 1.0 mg/kg. These results indicate that KT is a new nonprostanoid type TXA2/PGH2 receptor antagonist that is orally effective and long acting.
Animals↗
Measurements of 10Be and 26Al production cross sections with 12 GeV protons by accelerator mass spectrometry.
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Journal Article↗
Age-associated increase of CD5+ B cells in the liver of autoimmune (NZB x NZW) F1 mice.
The liver has been demonstrated to be a major site for extrathymic differentiation of T cells. In this study, an identification of CD5+ B cells, which are responsible for the onset of autoimmune disease by virtue of autoantibody production, was performed in autoimmune (NZB x NZW) F1 mice. An age-associated increase of CD5+ B cells was demonstrated in the liver of these mice. Although CD5+ B cells (i.e., CD5+IgM+ and CD5+B220+) constituted a minor population of hepatic mononuclear cells (MNC) (< 5%) when mice were young (8 weeks), a large population of CD5+ B cells (10 to 30% of whole MNC) was identified in the liver of mice aged 25 to 30 weeks after the onset of disease. Such age-dependent increase of CD5+ B cells was not observed in any other strains including NZB, NZW, C3H/He and BALB/c mice. The phenotype of hepatic CD5+ B cells was the same as that of CD5+ B cells in the peritoneal cavity and spleen, showing dull-CD5, bright-IgM and dull-B220. High levels of CD5+ B cells were observed in the peritoneal cavity and liver, but not in the spleen nor in any other lymphoid organs in mice aged 30 weeks. Radioimmunoassay of autoantibodies in the 5-day culture supernatants demonstrated that hepatic MNC were unable to produce any amounts of IgM- and IgG-autoantibodies against double-stranded DNA and single-stranded DNA, despite the increased proportion of CD5+ B cells. On the other hand, peritoneal exudate cells produced only IgM-, but not IgG-, autoantibodies, whereas splenic cells were able to produce both IgM- and IgG-autoantibodies.(ABSTRACT TRUNCATED AT 250 WORDS)
Aging↗