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Biomedical subjects

J Tanaka

Publications and source records attributed to J Tanaka.

At least 343 records · Page 19Linked to original sources

Detection of protein kinase activity specifically activated at metaphase-anaphase transition.

We have previously reported that Ser13 and Ser34 on glial fibrillary acidic protein (GFAP) in the cleavage furrow of glioma cells are phosphorylated during late mitotic phase (Matsuoka, Y., K. Nishizawa, T. Yano, M. Shibata, S. Ando, T. Takahashi, and M. Inagaki. 1992, EMBO (Eur. Mol. Biol. Organ.) J. 11:2895-2902). This observation implies a possibility that there is a protein kinase specifically activated at metaphase-anaphase transition. To further analyze the cell cycle-dependent GFAP phosphorylation, we prepared monoclonal antibodies KT13 and KT34 which recognize the phosphorylation of GFAP at Ser13 and Ser34, respectively. Immunocytochemical studies with KT13 and KT34 revealed that the GFAP phosphorylation in the cleavage furrow during late mitotic phase occurred not only in glioma cells but also in human SW-13 and mouse Ltk- cells in which GFAP was ectopically expressed, thus the phosphorylation can be monitored in a wide range of cell types. Furthermore, we detected kinase activity which phosphorylates GFAP at Ser13 and Ser34 in the lysates of late mitotic cells but not in those of interphase cells or early mitotic cells. These results suggest that there exists a protein kinase which is specifically activated at the transition of metaphase to anaphase not only in GFAP-expressing cells but also in cells without GFAP.

Anaphase↗

Erythrocyte flow and elasticity of microvessels evaluated by marginal cell-free layer and flow resistance.

Flow dynamics of human erythrocytes was compared in elastic (E) and hardened (H) microvessels with inner diameters of 10-40 microns. The thickness of the marginal cell-free layer and the overall flow resistance were measured with a vascular bed isolated from rabbit mesentery (E vascular bed) as well as with a 4% paraformaldehyde-fixed bed (H vascular bed). 1) In both E and H microvessels, the thickness of the cell-free layer increased with increasing inner diameter of the microvessels and with decreasing hematocrit accompanied by an overall decrease in the flow resistance. The hematocrit-dependent change of the cell-free layer thickness was greater in the E microvessels than in the H microvessels. The flow resistance was always greater in the H vascular beds than in the E vascular beds. 2) With decreasing erythrocyte deformability induced by treatment with 2 mM diazenedicar-boxylic acid bis(N,N-dimethylamide), the thickness of the cell-free layer decreased at a low hematocrit in the E microvessels and at a high hematocrit in the H microvessels, although the flow resistance was increased in both vascular beds. 3) Dextran of 70,400 average molecular weight accelerated the formation of the cell-free layer by inducing erythrocyte aggregation. A drastic increase in the cell-free layer thickness at 2-4 g/dl of dextran in the E microvessels and at 1-2 g/dl of dextran in the H microvessels was accompanied by a significantly lower increase in the flow resistance. This study concludes that the elasticity of microvessels may play an important role for reducing the overall flow resistance of a vascular bed, which is modulated by the marginal cell-free layer, itself a function of the rheological properties of the erythrocytes.

Animals↗

Involvement of pituitary adenylate cyclase-activating polypeptide in growth hormone secretion induced by serotoninergic mechanisms in the rat.

Pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) stimulated GH secretion in superfused rat anterior pituitary cell in vitro and in conscious male rats in vivo. PACAP-38-induced GH secretion was inhibited by PACAP-(6-38), an N-terminal-deleted analog, at 100-fold concentrations of PACAP-38 both in vitro and in vivo. In contrast, a GH-releasing hormone antagonist did not affect the action of PACAP-38 to stimulate GH release in vitro. Plasma GH increase induced by i.v. injection of 5-hydroxy-L-tryptophan (1 mg/100 g BW), a precursor of serotonin, was blunted by PACAP-(6-38) (1 nmol/100 g BW, i.v.), whereas spontaneous pulsatile GH secretion in conscious male rats, which is governed by hypothalamic GH-releasing hormone and somatostatin, was not affected by repeated i.v. injection of PACAP-(6-36). These findings suggest that PACAP-(6-38) is a potent antagonist of PACAP-38 to stimulate GH secretion both in vivo and in vitro. Taken together with the facts that PACAP-38 is highly concentrated in the hypothalamus and that is released into the hypophysial portal blood, our present findings suggest that PACAP-38 might play a stimulatory role on GH secretion induced by serotoninergic mechanisms in the rat.

5-Hydroxytryptophan↗

Inhibitory effect of acetylshikonin on the activation of NADPH oxidase in polymorphonuclear leukocytes in both whole cell and cell-free systems.

The effects of acetylshikonin (AS) on the activation of NADPH oxidase (EC 1.6.99.6) in guinea pig polymorphonuclear leukocytes (PMNs) in both whole cell and cell-free activation systems were investigated. When PMNs were treated with AS before exposure to phorbol myristate acetate (PMA), superoxide (O2-) generation in these cells was significantly reduced, but after exposure of PMNs to PMA, inhibition of O2- generation by AS did not occur. Thiol compounds completely abolished the inhibitory effect of AS on the O2- generating activity of PMNs. In the cell-free system, AS inhibited the activation of NADPH oxidase induced by myristate in a combination of cytosol and membrane fractions obtained from intact PMNs, but did not inhibit the activity of NADPH oxidase already induced. These results suggest that AS inhibits the generation of NADPH oxidase complex in the activation of respiratory burst of PMNs, but does not directly inhibit the activity of NADPH oxidase already generated.

Animals↗

Lipid peroxidation in gastric mucosal lesions induced by indomethacin in rat.

The peroxidation of lipids and changes in the activities of related enzymes in the gastric mucosa were studied in a rat model of gastric mucosal injury induced by the nonsteroidal anti-inflammatory drug indomethacin. The area of gastric erosion and the amount of thiobarbituric acid reactive substances (TBARS) in gastric mucosa were significantly increased beginning 4h after administration of indomethacin. Xanthine oxidase (XOD) activity in the gastric mucosa also increased immediately after administration of the drug. Although XOD activity was significantly suppressed by allopurinol treatment, the induction of gastric mucosal injury and the increase of TBARS in the gastric mucosa were not. Myeloperoxidase (MPO), a marker enzyme of leukocytes, was unaffected by indomethacin administration. But the depletion of polymorphonuclear leukocyte (PMN) counts induced by an injection of anti-rat PMN antibody inhibited both the injury and the increase in TBARS. Indomethacin activated PMN in peripheral blood at 30mg/kg per as and enhanced release of oxygen radicals from PMN in peripheral blood. As compared with the XOD system, the generation of oxygen free radicals may derived mainly from activated PMN. On the other hand, superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) were reduced by the administration of indomethacin. Decreases in SOD and GSH-px activity in gastric mucosa may aggravate mucosal injury by free radicals and lipid peroxidation.

Allopurinol↗

Cellular distribution of the P2X4 ATP receptor mRNA in the brain and non-neuronal organs of rats.

RNA blot analysis has shown that an ionotropic ATP receptor P2X4 is widely distributed, as compared with other P2X subtypes. Cellular distribution of the P2X4 ATP receptor mRNA was investigated by in situ hybridization technique in the brain and non-neuronal organs. In the brain, transcripts of the P2X4 were widely distributed in various regions, with the highest signals in the cerebellar Purkinje cells and granule cells. In other organs, intense and selective expression was detected in seminiferous tubules of the testis and intestinal crypts of the colon, suggesting an involvement of ATP in spermatogenesis and intestinal secretion. A low but significant level of the P2X4 mRNA was detected in the adenohypophysis and the cortex of the adrenal gland. The tissue- or cell-specific expression of the P2X4 mRNA is of importance to understand the functional roles of the purinergic transmission system.

Adrenal Glands↗

Very low incidence rates of community-acquired hepatitis C virus infection in company employees, long-term inpatients, and blood donors in Japan.

To assess the contemporary rate of hepatitis C virus (HCV) propagation in Japanese community, we conducted a sentinel study on three groups of people: company employees, long-term inpatients, and blood donors. A total of 3079 company employees negative for anti-HCV were followed thereafter, and seroconversion to anti-HCV was found in 5 per 5786 person-years. None of them was positive for HCV RNA. In the group of 703 long-term inpatients (25 of whom were initially positive for anti-HCV) none showed seroconversion to anti-HCV per 2712 person-years. As for 114,266 repeated blood donors who were initially antibody-negative, 227 became anti-HCV positive later. Of these seroconverted donors, 83 were found to have anti-HCV with titers of 2(6) or greater. HCV RNA was positive in only 3 of them. Thus, the incidence rates of acquired HCV viremia in these three groups were 0 for both company employees and long-term inpatients, and 1.78 (95% C.I.: 0.37-5.19) per 100,000 person-years in blood donors. These results suggest that community-acquired HCV infection is now rare in Japan, and that even if it occurred it hardly leads to persistent viremia.

Adolescent↗

Antitumor effect in cyclosporine A- or FK506-treated mice after syngeneic bone marrow transplantation.

We investigated the possibility for induction of graft-versus-tumor (GVT) effects in cyclosporine A (CsA)- or FK506 (FK)-treated DBA/2 mice after syngeneic bone marrow transplantation (BMT). For in vitro assays of spleen cells, the CsA-treated mice had more enhanced cytotoxic activity against YAC1 and P388, while the FK-treated animals had more against P815, YAC1, and P388. IL-4 mRNA expression was detected in spleen cells of the FK-treated mice and IL-6 mRNA expression was clearly detected in both the treated groups. Concerning GVT effects, FK had more pronounced immunostimulatory potential than CsA in this experimental setting using DBA/2 mice. In tumor-loading in vivo experiments, we could not show any antitumor effect on survival. However, this immunostimulation could be expected to eradicate the minimal residual disease after autologous BMT and autologous peripheral blood stem cell transplantation.

Actins↗

Graft-versus-leukemia effect and its clinical implications.

Graft-versus-leukemia (GVL) effect is an immunologically important phenomenon which decreases the relapse rate of leukemia after allogeneic bone marrow transplantation. GVL effect is sometimes associated with the occurrence of graft-versus-host disease (GVHD). Analyses of GVL effect and GVHD showed that these two phenomena were separable in some conditions. Although we cannot yet completely control the development of the GVL effect without inducing GVHD in humans, basic analyses using animal models show potential benefits of the GVL effect for clinical applications. Autologous GVHD is another important phenomenon which can help to eradicate minimal residual disease. Interleukin 2 and/or cyclosporin A are extensively used in animal models and in humans to induce autologous GVHD, showing beneficial effects. In the future, cytokine usage and allogeneic stem cell transplantation or leukocyte infusion appear to be promising in the control of minimal residual disease. Further studies on the mechanisms of GVL effects and GVHD may well open a new era for cell transplantation.

Animals↗

[A case of familial cardiac myxoma].

We experienced a case of familial cardiac myxoma observed in a mother and her daughter. A 58-year-old woman was addmited to our hospital because of repeated cerebral embolism. Echocardiography showed a left atrial myxoma to be considered as the cause of cerebral embolism. At the operation, 3 myxomas were found in the left atrium, and were removed successfully. No recurrence has been observed for 14 years after the operation. Three years after that, her 3rd child, 31-year-old-women, suffered from cerebral embolism and was also diagnosed as a left atrial myxoma. A friable myxoma was removed with the interatrial septum. She had no recurrence for 11 years after the operation. In patients with cardiac myxoma who have unusual biologic behavior, including familial myxoma, "complex" type myxoma must be suspected. We suggest that it is important to distinguish patients with "complex" type myxoma, because the recurrence rate is much higher in those than in patients with "sporadic" type myxoma.

Adult↗

[A case report of aortic root replacement with fresh aortic homograft for valve detachment due infective endocarditis].

A 28-year-old male received a redo aortic valve replacement (AVR) with a 19 mm St. Jude Medical mechanical valve 3 months after the initial AVR because of recurrent valve detachment. We re-operated on this patient by aortic root replacement using a fresh aortic homograft. The donor of the homograft was a 59-year-old female who died of a traffic accident. The aortic root and valve was harvested aseptically and stored in a nutrient medium including antibiotics at 4 degrees C for 4 days. At the 3rd operation, aortico-ventricular discontinuity and an annular-abcess-like cavity were found. After debridement, the cavity was closed with a homograft aortic wall and then aortic root replacement was performed using a fresh aortic homograft. At first, prosthetic valve detachment seemed to be caused by infective endocarditis on the basis of his clinical history. However, causative organisms had never been recovered from the blood or the specimens obtained at the time of operation and reoperation. Post-operative HLA examination revealed No. 51 on HLA-B locus and thus we suspected that valve detachment might have been due to inflammation of the aortic wall caused by a subtype of Behçet disease. The early post-operative course was uneventful with a low dose of predonine. Post-operative aortography showed no aortic regurgitation and normal coronary anastomosis. Unfortunately however, he died suddenly 8 months after the operation. Autopsy demonstrated the presence of aortic wall necrosis with massive infiltration of macrophages and leucocytes resulting in dehiscence of the coronary anastomotic site. The cause of homograft detachment could not be determined for sure but might be recurrent infective endocarditis, although causative organisms were never identified, or infective endocarditis in combination with Behçet vasculopathy.

Adult↗

[Sport-anemia: studies on hematological status in high school boy athletes].

High prevalence of anemia and iron deficiency state are found among athletes. To determine the influence of sports activities on the hematological state, we have performed hematological tests and examined the iron metabolism, in addition to some serum enzyme activities and some characters of red blood cells before and after exercise in high school boy athletes. The red blood cell count, hemoglobin level, and hematocrit value were significantly lower than those in the non-athletes boy students. The serum ferritin level in the athletes was significantly lower than that in the control group and healthy adults. Iron deficiency anemia was found in 12% of the athletes. The serum haptoglobin level in the athletes was significantly lower than that in the control group and the level before exercise, suggesting intravascular hemolysis, but the serum hemopexin level showed no difference before and after exercise, suggesting that the hemolysis was not so severe. The serum CPK and myoglobin levels showed a significant increase after exercise, but those levels were quite lower than that of muscle diseases. These findings suggest that daily exercise is closely associated with the increased risk of iron deficiency state, particularly in the high school boy athletes. The mechanism of hemolysis in athletes may partly depend on the increased fragility of iron deficiency red blood cells on mechanical strength.

Adolescent↗

Analysis of 1,000 consecutive cases of acute poisoning in the suburb of Tokyo leading to hospitalization.

We have analyzed retrospectively 1,000 consecutive admissions due to acute poisonings over 13 years. Total mortality was 27%. Acute poisonings due to pesticides, therapeutic drugs and other substances were 518, 332 and 150 cases with mortalities of 51, 1 and 5%, respectively. The most frequent cause of acute poisoning was paraquat/diquat products, whose mortality reached 76% (220 deaths/291 cases). The second most frequent cause was organophosphate/carbamate products with a mortality of 24% (37/155). When these 2 pesticides are excluded, the mortality was only 3% (15/554). To reduce instances of paraquat/diquat poisoning, dilution of the available product or formulation in other than liquid form would be desirable, because no effective treatment is currently available. In cases of organophosphate/carbamate poisoning, early hospitalization and stabilization is crucial.

Accidents↗

In vitro expansion of murine hematopoietic progenitor cells by leukemia inhibitory factor, stem cell factor, and interleukin-1 beta.

Murine hematopoietic progenitor cells were markedly expanded in the presence of leukemia inhibitory factor (LIF), interleukin (IL)-1 beta and/or stem cell factor (SCF), although SCF+IL-1 beta +IL-3, LIF+SCF+IL-3, and SCF+IL-1 beta showed an appreciable effect on the in vitro expansion of hematopoietic progenitor cells as well. In the presence of LIF+SCF+IL-1 beta, highly proliferative potential colony-forming units (CFU-HPP) and colony forming units of mixed lineages (CFU-Mix) were more efficiently expanded than colony forming units granulocytes/macrophage (CFU-GM) and burst-forming units of erythroid lineage (BFU-E) compared with the colony formations of freshly obtained bone marrow cells. The cell yield on day 5 in the presence of LIF+SCF+IL-1 beta was comparable to that in SCF+IL-1 beta and SCF+IL-1 beta +IL-3. Nevertheless, colony formations were marked in LIF+SCF+IL-1 beta, thus suggesting that this combination can generate hematopoietic progenitor cells that possess greater potential for CFU-HPP, CFU-Mix, CFU-GM, and BFU-E colony formations. Hematopoietic cells expanded in the presence of LIF+SCF+IL-1 beta showed increased mRNA expressions of IL-1 beta, IL-3, IL-6, granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage (GM)-CSF, interferon gamma (IFN-gamma), and LIF compared with those of nontreated hematopoietic cells. Furthermore, LIF+SCF+IL-1 beta induced increased IL-3 and GM-CSF mRNA expression in hematopoietic cells but induced decreased macrophage inflammatory protein 1 alpha (MIP1 alpha) mRNA expression as compared with SCF+IL-1 beta +IL-3. These results suggest that the balance between stimulatory and inhibitory cytokines plays an important role in in vitro expansion of hematopoietic progenitor cells.

Animals↗

Renal Salmonella enteritidis abscess in a patient with severe aplastic anemia after allogeneic stem cell transplantation.

We describe an unusual case of a renal abscess by Salmonella enteritidis in a 32-year-old man with severe aplastic anemia undergoing allogeneic stem cell transplantation. He was receiving immunosuppressive therapy with CsA and corticosteroids for chronic GVHD. He was not neutropenic and had no history of enterocolitis or cholelithiasis before the onset. Four months after the transplantation, he developed an abscess in the upper pole of his right kidney from which Salmonella enteritidis was isolated in culture. He was successfully treated with a combination of percutaneous drainage and washing the cyst through the catheter using piperacillin sodium-containing solution. The possibility of salmonellosis should be considered in the differential diagnosis of such patients.

Abscess↗