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Biomedical subjects

M Takata

Publications and source records attributed to M Takata.

At least 163 records · Page 9Linked to original sources

Signal transduction by IgG receptors induces calcium mobilization, but not histamine release, in the human basophilic cell line KU812F.

Human blood basophils selectively express Fc gamma RII (CDw32) among IgG receptor subtypes, but its functional role in allergic reactions remains unknown. Using the human basophilic leukemia cell line KU812F as a model system, we investigated cellular signaling events mediated through IgG receptor stimulation. KU812F cells express Fc gamma RII on their surface. mRNAs for both Fc gamma RIIA and IIB subtypes were detected by reverse transcriptase-PCR analysis. In this cell line, Fc gamma RII stimulation induced mobilization of free intracellular calcium and actin polymerization. Yet, no significant histamine release was observed, nor did blood basophils stimulated by anti-Fc gamma RII monoclonal antibody IV.3 and by a secondary antibody release histamine. These data indicate that Fc gamma RII stimulation induces cellular signaling events such as calcium mobilization in human basophils. However, these events do not lead to histamine release.

Actins↗

Successful treatment of livedo vasculitis with beraprost sodium: a possible mechanism of thrombomodulin upregulation.

BACKGROUND: Livedo vasculitis is thought to be a thrombogenic disorder. We demonstrated that thrombomodulin (TM) expression on the endothelial cells in livedo vasculitis was markedly reduced, while blood tests of coagulation and fibrinolytic activities were within the normal range. OBJECTIVE: Since prostacyclin (PGI2) upregulates the TM expression of endothelial cells, we tried a PGI2 analogue for the treatment of livedo vasculitis. METHOD: Four patients with livedo vasculitis were started on a regimen of beraprost sodium (120 micrograms daily). Additional intake of low-dose aspirin was combinated with a maintenance dose of beraprost sodium (60 micrograms daily). RESULT: All 4 patients experienced a clinical improvement with a combination therapy with beraprost sodium and low-dose aspirin. CONCLUSION: We propose that PGI2 analogue therapy is useful for the treatment of livedo vasculitis, since the drug upregulates TM expression in this disorder.

Adolescent↗

Longitudinal distribution of pulmonary vascular compliance in dogs.

The longitudinal distribution of pulmonary vascular compliance was evaluated in isolated canine lung lobes using arterial-(AO), venous-(VO), and double-occlusion (DO) techniques. Total vascular compliance (Ctau) was separated into pulmonary arterial (Ca) and venous compliance (Cv) in lumped model of pulmonary circulation. Under constant pulmonary venous pressure (Pv) at 5 mmHg, blood inflow to the lobe (Q) was gradually increased by changing pulmonary arterial pressure (Pa) from 10 to 22 mmHg at 4 mmHg ranges. Changes in vascular blood volume (deltaV) with each increment in Q were determined by decreased reservoir blood volume of perfusion system. DO was performed at each level of Q and allowing all vascular pressures to equilibrate at the same static pressure (Ps), which was equal to the compliance-weighted average pressure in the circulation. Ctau was obtained from the slope of the relationship between Ps and deltaV. When Pa and Pv were 14 and 5 mmHg, AO, VO, and DO were performed to measure pressures at Ca (Pca) and Cv (Pcv) and Ps. The arterial-to-venous compliance ratio (Ca/Cv) was evaluated using Pca, Pcv, and Ps measurements. Ctau was 0.113 +/- 0.012 ml/kg/mmHg. Ca/Cv was 0.30. Ca and Cv were 0.026 +/- 0.013 and 0.087 +/- 0.007 ml/kg/mmHg, respectively. These data demonstrated the usefulness of AO, VO, and DO techniques in evaluating the longitudinal distribution of compliance in canine pulmonary vasculature.

Animals↗

[Dual biochemical modulation therapy using 5-FU, leucovorin and cisplatin on human rectal carcinoma xenografts in nude mouse].

This study examined a combined treatment for colorectal carcinoma, the dual biochemical modulation therapy, consisting of 5-FU, Leucovorin (LV) and Cisplatin (CDDP). We compared its anti-tumor effects with other treatments: 5-FU alone, CDDP alone and 5-FU with LV. Primary diffuse infiltrated colorectal carcinoma is well known for its biological malignancy and its lack of response to chemotherapy. We used SRM cells from a cell line of carcinoma of the rectum, and subcutaneously injected them into nude mice. The anti-tumor effects were estimated from the growth rate, inhibition rate and thymidylate synthetase inhibition rates in the tumor tissue. Results indicated that even if the concentration of 5-FU and LV were reduced by half, these combined with CDDP were more effective than other therapies. Dual biochemical modulation therapy is particularly promising because the reduction of the dosages would reduce the side effects while still serving as an excellent anti-tumor therapy.

Animals↗

[8;21 translocation acute myelocytic leukemia developing in the second trimester of pregnancy with successful delivery].

A 28 year-old woman in the 26th week of pregnancy was admitted to our hospital on February 6, 1993, because of anemia and thrombocytopenia. On admission, her hemoglobin was 8.2 g/dl, platelet count 6.3 x 10(4)/microliter, and WBC 6,300/microliter with 43% blasts. The bone marrow examination showed hyperplastic bone marrow with 38.8% blasts. She was diagnosed as having 8;21 translocation acute myelocytic leukemia (M2). In the 30th week of pregnancy, she gave birth to a 1449 g male infant by induction delivery. After DCMP therapy, complete remission was obtained. She has been in complete remission for 32 months and her child is growing healthy after overcoming an underweight condition due to premature birth, respiratory distress syndrome, circulation insufficiency and hyperbilirubinemia. This case suggests that in the event of second trimester pregnant patients with acute leukemia, we should wait for the proper time at which successful delivery can be expected, and then intensified remission induction chemotherapy should be carried out after the delivery.

Adult↗

Exposure of B-lineage lymphoid cells to low energy electromagnetic fields stimulates Lyn kinase.

Here, we present evidence that exposure of B-lineage lymphoid cells to low energy electromagnetic fields (EMF) stimulates the protein tyrosine kinases Lyn and Syk, results in tyrosine phosphorylation of multiple electrophoretically distinct substrates, and leads to downstream activation of protein kinase C (PKC). EMF exposure enhances protein tyrosine phosphorylation in Syk deficient but not in Lyn-deficient B-lineage lymphoid cells and stimulates Lyn kinase activity in wild-type as well as Syk-deficient B-lineage lymphoid cells. These results indicate that activation of Lyn kinase is sufficient and mandatory for EMF-induced tyrosine phosphorylation in B-lineage lymphoid cells. The PKC activity increases later than the Lyn activity and pretreatment with the PTK inhibitors genistein or herbimycin A abrogates the EMF-induced PKC signal. Thus, stimulation of Lyn is a proximal and mandatory step in EMF-induced activation of PKC in B-lineage lymphoid cells. Our observations prompt the hypothesis that a delicate growth regulatory balance might be altered in B-lineage lymphoid cells by EMF-induced activation of Lyn.

Amino Acid Sequence↗

The catalytic activity of Src-family tyrosine kinase is required for B cell antigen receptor signaling.

The Src family protein-tyrosine kinases (PTKs) are known to be important for B cell antigen receptor (BCR) signaling. To study the mechanism of action of Src-PTK in BCR signaling, kinase deficient- and Src homology 2 (SH2)-mutants of Src-PTK were transfected into Lyn-deficient B cells and analyzed. Kinase activity of Src-PTK was essential for tyrosine phosphorylation of Syk and calcium mobilization upon receptor ligation, whereas these events were not affected by the mutation of SH2 domain. Receptor-mediated tyrosine phosphorylation of Lyn was still observed in Syk-deficient B cells. These results demonstrate that the BCR-induced phosphorylation of Src-PTK is independent of Syk and that the kinase activity of Src-PTK is critical for BCR signaling.

Amino Acid Sequence↗

Requirement of phospholipase C-gamma 2 activation in surface immunoglobulin M-induced B cell apoptosis.

Surface IgM (sIgM) stimulation induces the tyrosine phosphorylation of multiple cellular substrates, including phospholipase C (PLC)-gamma 2, which is involved in the activation of phosphatidylinositol pathway. DT40 B cells underwent apoptotic cell death when activated through sIgM, a phenomenon that is related to elimination of self-reactive B cells. To examine the roles of PLC-gamma 2 in sIgM signaling, we have generated DT40 cells deficient in PLC-gamma 2 Cross-linking of sIgM on PLC-gamma 2-deficient cells evoked neither inositol 1,4,5-trisphosphate nor calcium mobilization. In PLC-gamma 2- or Syk-deficient DT40 cells, the induction of apoptosis was blocked, but was still observed in Lyn-deficient cells. Src homology 2 domains of PLC-gamma 2 were essential for both its activation and sIgM-induced apoptosis. Since tyrosine phosphorylation of PLC-gamma 2 is mediated by Syk, these results indicate that activation of PLC-gamma 2 through Syk is required for sIgM-induced apoptosis.

Animals↗

Experimental evidence for the existence of non-nuclear maxima in the electron-density distribution of metallic beryllium. A comparative study of the maximum entropy method and the multipole refinement method.

The electron-density distribution (EDD) of metallic beryllium has been derived from the structure factors of Larsen & Hansen [(1984). Acta Cryst. B40, 169-179] using the maximum entropy method (MEM). Subsequent topological analysis reveals non-nuclear maxima (NNM) in the EDD. Plots of the gradient field of the electron density illustrates this finding. A possible critical-point network for the hexagonal close-packed (h.c.p.) structure of beryllium is suggested. It is thus demonstrated that it is possible to obtain detailed topological information about the electron density in metallic beryllium without the use of a structural model. In order to test the findings of the MEM, the same set of structure factors were analysed using the multipole refinement method (MRM). Use of the MRM also reveals NNM. The results of the two different approaches to electron-density analysis are contrasted and discussed. Expressed within the framework of the theory of atoms in molecules, our results suggest that the h.c.p. structure of beryllium has no Be atoms directly bonded to other Be atoms. The structure is held together through a three-dimensional network of bonds between the NNM and Be atoms as well as between different NNM. The topological analysis thus reveals that the beryllium structure has important interactions connecting Be atoms of different basal plane layers. The breaking of these interactions when forming a surface may explain the abnormally large expansion of the inter-layer distance in the beryllium surface structure.

Beryllium↗

Long Horizontal Parallel Slits with 0.03 degrees Angular Resolution for Powder Diffraction Using Synchrotron Radiation.

Long horizontal parallel slits with angular apertures of 0.032 and 0.065 degrees were constructed for powder diffraction experiments with synchrotron radiation. They have been tested at the BL-4B experimental station at the Photon Factory by using a monochromated beam with a wavelength of 1.528 A. The horizontal parallel slits with the smaller aperture gave a full-width at half-maximum of 0.030 (1) degrees for the (200) reflection from CeO(2) and an intensity about one order of magnitude higher than that obtained with a receiving slit in the same angular resolution, demonstrating the finest horizontal parallel slits developed so far. The misalignment of the horizontal parallel slits does not affect the intensity whilst it shifts the Bragg-peak positions systematically.

Journal Article↗

Stimulative effects of lead on bone resorption in organ culture.

To clarify whether hypercalcemia after injection of Pb to rats is due to biological bone resorption or physicochemical mineral dissolution, the effect of lead (Pb) on release of previously incorporated 45Ca in organ culture was investigated. Pb at 50 microM and above stimulated the release of 45Ca and hydroxyproline (Hyp). Pb did not stimulate 45Ca release from the bones inactivated by freezing and thawing. Eel calcitonin (ECT), bafilomycin A1 and scopadulcic acid B (SDB) inhibited Pb-stimulated 45Ca release. These results indicate that Pb-induced 45Ca release is due to osteoclastic bone resorption. Pb-stimulated bone resorption was inhibited by indomethacin and flurbiprofen. Pb stimulated the release of prostaglandin E2 (PGE2) from the bones into the media. There was significantly high correlation between 45Ca and PGE2 release. Pb-induced bone resorption was inferred to be mediated by PGE2. From these results, it was suggested that hypercalcemia after Pb injection might be caused by biological bone resorption.

Animals↗

Tyrosine phosphorylation of Shc is mediated through Lyn and Syk in B cell receptor signaling.

Shc protein is tyrosine phosphorylated upon B cell receptor (BCR) activation and after its phosphorylation interacts with the adaptor protein Grb2. In turn, Grb2 interacts with the guanine nucleotide exchange factor for Ras, mSOS. Several protein-tyrosine kinases (PTKs) participate in BCR signaling. However, it is not clear which PTK is involved in the phosphorylation of Shc, resulting in coupling to the Ras pathway. Tyrosine phosphorylation of Shc and its association with Grb2 were profoundly reduced in both Lyn- and Syk-deficient B cells upon BCR stimulation. Furthermore, kinase activity of these PTKs was required for phosphorylation of Shc. Shc interacted with Syk in B cells. This interaction and the requirement of Syk kinase activity for phosphorylation of Shc were also demonstrated by cotransfection in COS cells. Because Lyn is required for activation of Syk upon receptor stimulation, our results suggest that the Lyn-activated Syk phosphorylates Shc during BCR signaling.

Adaptor Proteins, Signal Transducing↗

Intratracheal administration of phosphodiesterase III inhibitor attenuates bronchoconstriction in cats: a preliminary report.

The effects of intratracheal administration of MKS 492, a selective phosphodiesterase (PDE) III inhibitor, were studied in five anesthetized bronchoconstricted cats. The animals were challenged by four repeated doses of intratracheal methacholine (67 micrograms/kg), and the degree of bronchoconstriction was assessed from increases in respiratory system resistance (Rrs). All animals demonstrated good bronchoconstrictive responses (i.e., 86-99% increases in Rrs) to methacholine without tachyphylaxis. On a separate day, the cats received the same four doses of methacholine after being pretreated with either intratracheal saline or three different doses of MKS 492 (0.17, 1.7, and 17 micrograms/kg). The increases in Rrs with 1.7 micrograms/kg [52.6 +/- 8.4% (SE)] and 17 micrograms/kg of MKS 492 (44.4 +/- 10.1%) were smaller than those with saline pretreatment (88.1 +/- 16.8%) (P < 0.05). There were no treatment-associated changes in mean arterial pressure or heart rate during administration of MKS 492. We conclude that intratracheal MKS 492 effectively reduced methacholine-induced bronchoconstriction in a dose-dependent fashion without substantial systemic effects. These preliminary results suggest that inhalation of isozyme-selective PDE inhibitors may deserve consideration for clinical trials provided that more extensive preclinical investigations justify such trials.

3',5'-Cyclic-AMP Phosphodiesterases↗

Distinct behavior of portal venous and arterial vascular waterfalls in porcine liver.

PURPOSE: Hepatic dysfunction is associated with morbidity and mortality in critically ill patients. Understanding liver hemodynamics in pathological states requires characterization of the normal portal venous and hepatic arterial circulations. Using pressure flow analysis, we tested the hypothesis that vascular waterfalls determine blood flows in the normal liver. METHODS: In 14 vascularly isolated porcine livers, steady-state pressure-flow relationships, which defined a slope (incremental resistance) and a zero flow pressure intercept (Po), were generated for each vessel over a range of hepatic venous pressures (Phv). RESULTS: Critical closing pressures occurred in the portal venous circulation (Po = 3.8 +/- 0.4 mm Hg) with classical waterfall physiology observed as Phv was raised. The hepatic arterial critical closing pressure (Po = 8.3 +/- 1 mm Hg) showed a constant positive pressure difference of mm Hg versus Phv as the latter was increased from 0 to 28 mm Hg (P < .05). Portal venous resistance decreased when Phv was greater than Po (P < .05), but no effect on hepatic arterial resistance was seen as Phv was increased. CONCLUSION: Both critical closing pressures and incremental resistances showed markedly different responses to increased outflow pressures in the portal venous and hepatic arterial circulations. The results provide the physiological basis to analyze hemodynamic changes in the liver under normal and pathological conditions.

Animals↗

Immunohistochemical identification of perforin-positive cytotoxic lymphocytes in graft-versus-host disease.

To study the role of functionally active cytotoxic lymphocytes in human graft-versus-host disease (GVHD), perforin expression in infiltrating mononuclear cells was immunohistochemically investigated in skin biopsy specimens. Perforin is a component of intracytoplasmic granules of cytotoxic lymphocytes and serves as a specific marker of functionally active cytotoxic lymphocytes. The study included two cases of transfusion-associated GVHD, seven cases of acute GVHD and five cases of lichenoid chronic GVHD after allogeneic bone marrow transplantation. All specimens obtained from transfusion-associated GVHD and one case of acute GVHD with extracutaneous involvement contained a significant number of perforin-positive lymphocytes. In contrast, perforin-positive lymphocytes were few or absent in the other six cases of acute GVHD and in all five cases of lichenoid chronic GVHD after bone marrow transplantation. These findings suggest that perforin-mediated cytolysis by cytotoxic lymphocytes may be a major effector mechanism in transfusion-associated GVHD and at least in some cases of acute GVHD after bone marrow transplantation.

Adolescent↗

Syk and Lyn are involved in radiation-induced signaling, but inactivation of Syk or Lyn alone is not sufficient to prevent radiation-induced apoptosis.

Radiation-induced biochemical events that mediate the intracellular signal transduction leading to cell apoptosis are largely unknown. Limited evidence suggests the possible involvement of one or more protein-tyrosine kinases (PTKs) in radiation-induced cellular responses, including apoptosis. However, so far, a PTK(s) responsible for the radiation-induced tyrosine phosphorylation of cellular substrates has not been identified and the role of the PTK(s) in the radiation-induced apoptosis remains unclear. To examine the roles of Syk and Lyn in radiation-induced signal transduction and radiation-induced apoptosis, we analyzed Syk-deficient or Lyn-deficient DT40 B cells along with wild-type cells following radiation. When DT40 B cells were exposed to radiation, the activity of Syk kinase dramatically increased and reached a maximum with 0.25 Grays (Gy) (15 s), and then decreased, whereas Lyn kinase activity increased and reached a maximum with a dose of 1.00 Gy (1 min). However, an apparent difference was not observed in radiation-induced apoptosis among wild-type, Syk-deficient, and Lyn-deficient DT40 B cells. These results indicate that Syk and Lyn kinases are involved in radiation-induced signal transduction, with different kinetics. In addition, our results revealed that functional inactivation of Syk or Lyn alone is not sufficient to prevent radiation-induced apoptosis. Thus, it is suggested that the activation of Syk or Lyn kinase alone may be sufficient to mediate the radiation-induced apoptosis in DT40 B cells, or both kinases may not be required for this biological process.

Animals↗

Confirmation of endotracheal intubation over a jet stylet: in vitro studies.

An accepted method of tracheal reintubation is to pass an endotracheal tube (ETT) over a jet stylet (JS). It is desirable to confirm tracheal reintubation prior to removing the JS from its known intratracheal location. The purpose of this study was to determine the functional size equivalent of the annular space between the JS and ETT for all combinations of variously sized ETTs and JSs and to determine whether this annular space will permit detection of exhaled carbon dioxide (CO2). Our experiment consisted of two parts. One model measured the airflow resistance of variously sized test catheters (14- to 18-gauge intravenous catheters and ETT sizes 2.5-9.0 mm inside diameter (ID)) and all of the possible combinations of small, medium, and large Sheridan JSs within 4.9-9.0-mm ID ETTs (ETT/JS) by determining pressure versus annular space flow curves. The other model measured the times to first detection of CO2, to 70% maximum (max) [CO2] detection, and from first detection to 70% max [CO2] through empty 4.0- to 9.0-mm ID ETTs and through the annular space between all possible ETT/JS combinations at lung driving pressures of 5-10 mm Hg. The resistance of the catheters and ETT/JS combinations increased as the flow rate increased and/or the net conducting area of the conduit decreased. Some ETT/JS had an annular space < a 4.0 mm ID ETT. All three CO2 detection times increased with decreasing size of the net conducting area and with decreasing driving pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗