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Biomedical subjects

M Uda

Publications and source records attributed to M Uda.

At least 37 records · Page 2Linked to original sources

[Evaluation of thermal damage after hyperthermia on murine experimental tumor by 31P-NMR spectroscopy--correlation between ATP and growth curve].

The possibility of using 31P-NMR spectroscopy (31P-MRS) to estimate the effect of hyperthermic treatment on mouse FM3A tumor was investigated. 1 x 10(6) cells, suspended in saline, were subcutaneously inoculated to the right thigh of C3H mice. For hyperthermic treatment, the tumor-bearing leg was heated by immersing it in a water bath at 44 degrees C for 10, 20 or 30 min. The signal intensities of ATP and Pi of the tumor were measured utilizing the 31P-MRS technique to calculate the ATP/Pi ratio. Immediately after heating, the ATP/Pi ratio decreased markedly. Eighteen hours after hyperthermic treatment, the ratio recovered but was still smaller than the control value, then became almost constant by 24 hours after heating. The ATP/Pi ratio at 24 hours after heating decreased with increased length of heating and was inversely related to tumor regrowth after hyperthermic treatment. We concluded that non-invasive monitoring with 31P-MRS might provide a good indication of the effect of hyperthermic treatment.

Adenosine Triphosphate↗

Analysis of suppressor T cells induced by donor-specific transfusion (DST): establishment of a human T cell hybridoma producing an antigen-nonspecific suppressor factor.

Formation of suppressor T cells (Ts) induced by donor-specific transfusion (DST) is one of the most commonly suggested mechanisms for the beneficial effect of DST. In this study, we established a human T cell hybridoma derived from the peripheral blood lymphocytes (PBL) of a DST-treated patient, which produced an antigen-nonspecific suppressor factor. Post-DST PBL were fused with an azaguanine-resistant mutant of a human T cell leukemia cell line, CCRF-CEM(AG). After selection and cloning, we established one clone producing the mixed lymphocyte reaction (MLR) inhibitory factor (C524: 18%-43% suppression). Suppressive activity of the supernatant obtained from C524 after activation by PHA was highly augmented (64%-88% MLR suppression). This factor inhibited MLR dose-dependently in an antigen-nonspecific and HLA non-restricted manner. These results indicated that Ts clones could be generated in patients receiving DST and that the immunoregulatory factors produced by activated clones may play a role in the prolongation of renal allograft survival.

Antibody Specificity↗

Effects of interleukin 2 receptor b chain (P75)-specific monoclonal antibody on the generation of cytotoxic T lymphocytes and suppressor T cells in mixed lymphocyte culture.

The interaction of interleukin 2 (IL-2) with its receptor (IL-2R) plays an essential role in the proliferation and differentiation of T cells. The IL-2R beta-chain is considered to function directly in the intracellular signal transduction. In this study, we investigated using a newly established IL-2R beta-chain-specific monoclonal antibody (MAb) (TU-25) and an IL-2R alpha-chain-specific MAb (H-31). The IL-2-induced proliferation of concanavalin blasts and the mixed lymphocyte reaction (MLR) were suppressed by TU-25 in combination with H-31. This combination had a greater suppressive effect than each of them alone. The generation of cytotoxic T lymphocytes (CTL) using a cell-mediated lympholysis (CML) assay, was not inhibited by TU-25 alone. TU-25 in combination with H-31 suppressed the generation of CTL completely in this assay even if recombinant IL-2 (rIL-2) was added. Although the CTL generation was inhibited, cells that suppressed a fresh MLR were preserved. Our study suggests that the combination of TU-25 with H-31 completely blocks the functional high-affinity binding site of IL-2 but does not inhibit the generation of suppressor cells. This may lead to immunosuppressive therapy using an IL-2R beta-chain-specific MAb in combination with an IL-2R alpha-chain-specific MAb in clinical organ transplantation.

Antibodies, Monoclonal↗

Renal transplantation from HLA-haploidentical living-related donors: the effects of donor-specific blood transfusions and different immunosuppressive regimens.

One-hundred-nine HLA-haploidentical living related renal transplants have been retrospectively analysed to compare the effect of donor-specific blood transfusion (DST) and different immunosuppressive regimens on graft survival and acute rejection. The recipients were divided into four groups according to the immunosuppressive therapy. Group 1 (n = 44): conventional therapy with posttransplant azathioprine (AZP) + methylprednisolone (MP). Group 2 (n = 25): pretransplant DST + posttransplant AZP + MP. Group 3 (n = 12): triple-drug therapy with posttransplant AZP + MP + cyclosporine (CS). Group 4 (n = 25): pretransplant DST + posttransplant AZP + MP + CS. The five-year actuarial survival rates for groups 1, 2, 3 and 4 were 48%, 73%, 79%, and 89%, respectively. The graft survival rate in group 3 was significantly (p less than 0.01) better than that in group 1. The transfusion effect was reduced, and appears as a 10% improvement in the graft survival in the cyclosporin era compared with a 25% improvement at pre-cyclosporin era. Furthermore, the incidence of the first rejection episode was decreased in recipients that received DST. The present study revealed that DST, as pretransplant conditioning has a definite impact on rejection-free long-term graft survival in HLA-haploidentical living-related kidney recipients and the most favorable outcome in such patients could be achieved by DST pretreatment in conjunction with posttransplant triple-drug therapy including cyclosporine.

Blood Transfusion↗

The impact of triple drug immunosuppression on clinical results of cadaveric kidney transplantation: a comparison of conventional immunosuppression.

A retrospective study was carried out in 110 cadaveric kidney transplant recipients to compare the effects of low doses of cyclosporine (CsA), azathioprine (AZP) and steroids (triple-drug therapy) with those of higher doses of steroids plus AZP (conventional immunosuppression). Graft survival rate in the triple-drug therapy was 77%, 69%, and 69% at 1, 3, and 5 years, respectively. This was significantly better than 48%, 34%, and 29% in conventional immunosuppression. The incidence of acute rejection episodes was significantly lower in the triple-drug therapy than in conventional immunosuppression (25% vs 58%). In conclusion, our study shows that triple-drug therapy using low-dose cyclosporine is the safest of the immunosuppressive regimens and provides a beneficial effect on the long-term survival of cadaveric kidney transplants.

Adult↗

Expression of the interleukin 2 receptor beta chain (p75) in renal transplantation--applicability of anti-interleukin-2 receptor beta chain monoclonal antibody.

The interaction of interleukin 2 with specific cellular receptors plays an essential role in the allostimulated proliferation and differentiation of T cells. Recent chemical linking studies have demonstrated that the human high-affinity IL-2 receptor is a membrane complex composed of at least two distinct subunits, which are the p55 (alpha-chain) and p75 (beta-chain) subunits. The IL-2R beta chain is supposed to play a role in the signal transduction of IL-2, but the exact mechanism is still unknown. In this study, we investigated the effects of a newly established anti-IL-2R beta chain monoclonal antibody (MoAb, TU-27) on the induction of cytotoxic T lymphocytes (CTLs) using the cell-mediated lympholysis (CML) assay. TU-27 in combination with H-31, a MoAb directed against the IL-2R alpha chain, produced inhibition of cytotoxicity, while TU-27 alone could not inhibit cytotoxicity, while TU-27 alone could not inhibit cytotoxicity at any concentration. TU-27 plus H-31 prevented the expansion of CD4+ cells and CD8++ cells in mixed lymphocyte culture (MLC). Furthermore, we examined the serial changes in the expression of the IL-2R beta chain on peripheral blood lymphocytes from renal transplant recipients using two-color immunofluorescence flow cytometry, so as to investigate correlations between IL-2R beta chain expression and the occurrence of allograft rejection. Here, we report that the IL-2R beta chain is expressed on CD4-positive (CD4+) cells and strongly CD8-positive (CD8(+)+) cells in association with acute rejection, indicating that IL-2R beta chain expression appears to increase on alloreactive T cells.

Antibodies, Monoclonal↗

[A family of von Hippel-Lindau disease with renal cell carcinoma--case report and review of the literature].

We report a 63-year-old woman with renal cell carcinoma associated with von Hippel-Lindau disease. The patient was referred to the department of neurosurgery at our hospital, complaining of gait disturbance. There was a history of retinal hemangioma. After further examination, von Hippel-Lindau disease was the conclusion with evidence of cerebellar hemangioblastoma. An abdominal CT-scan and arteriography revealed multiple hypervascular tumors in the right kidney, but not in the left. She underwent a right radical nephrectomy and lymphadenectomy 2 months after resection of a brain tumor. Von Hippel-Lindau disease is generally recognized as an autosomal-dominant inherited disorder. The patient had a positive family history, seen in both her younger brother and son. Both were diagnosed with renal cell carcinoma with central nervous system involvement before any sign of disease was found in the patient. Twenty one cases of von Hippel-Lindau disease associated with renal tumors have been reported in the Japanese literature. The clinical findings of these cases are discussed.

Adult↗

Pathophysiological changes after local heating of rat liver.

Changes in blood flow in rat liver by local heating of the left lateral lobe were studied. A small portion of the left lateral lobe was heated by capacitive application of 8 MHz RF with a 2 cm diameter electrode on the ventral surface and a 7 cm diameter electrode on the dorsal surface of upper body of rats. A circular area with diameter of about 1 cm in the left lateral lobe could be heated to relatively homogeneous temperatures. The temperature in the remaining part of the left lateral lobe as well as in the rest of liver tissue also increased to varying degrees during the local heating of the left lateral lobe. When heated at 39 degrees or 41 degrees C for 45 min, the arterial blood flow, as measured with the radioactive microsphere method, in the heated area, and that in the rest of the left lateral lobe as well as in the whole liver initially increased during the first 30 min and then started to decline. During a 45 min heating at 43 degrees C, the arterial blood flow in the heated area slightly increased for 15 min and then significantly decreased thereafter. The arterial blood flow in the rest of the liver tissue also increased during the first 15 min of a 43 degrees C heating and began to decline. Histological examination of liver heated at 43 degrees C for 30 min showed wedge-shaped infarctions early on, which appeared to be organized into scar tissue by 7 days after heating. The concentrations of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and lactate dehydrogenase (LDH) in the serum significantly increased 2 hr after heating the small portion of the left lateral lobe at 43 degrees C for 30 min and began to decrease thereafter although the serum level of GOT and GPT was still greater than the control value 24 hr after heating.

Alanine Transaminase↗

[Arterial blood flow changes after hyperthermia on normal liver, normal brain, and normal small intestine].

Arterial blood flow changes are studied after hyperthermia on normal liver, normal brain, and normal small intestine. A small part in left lateral lobe of rat liver was heated by RF capacity heating. Arterial blood flow in heated area of liver decreased to 69.2 +/- 8.1 and 51.3 +/- 6.6 ml/min/100 g dry weight respectively after heating at 43 degrees C for 30 min and 45 min, from 83.1 +/- 2.6 ml/min/100 g dry weight at 37 degrees C. To heat a small part in left hemisphere of rat cerebral tissue, RF interstitial heating device was utilized. Arterial blood flow in heated area increased to 289.1 +/- 41.5 ml/min/100 g dry weight after heating at 42 degrees C for 30 min from 223.6 +/- 18.8 ml/min/100 g dry weight at 37 degrees C. For small intestine heating, water bath was used. Arterial blood flow increased to 6.60 +/- 1.36, 7.44 +/- 1.16, and 11.6 +/- 2.2 ml/min/g dry weight respectively after heating at 39 degrees C, 41 degrees C, and 43 degrees C for 30 min, from 5.04 +/- 0.85 ml/min/g dry weight at 37 degrees C. These data suggest that blood flow changes after hyperthermia differ from tissue to tissue, and require further investigation on the effect of hyperthermia on blood flow changes in liver, brain, small intestine, and other normal tissues.

Animals↗

Mechanism of membrane damage induced by the amphipathic peptides gramicidin S and melittin.

The action of gramicidin S and melittin on human erythrocytes, Staphylococcus aureus and Escherichia coli was studied as an extension of the previous study (Katsu, T., Ninomiya, C., Kuroko, M., Kobayashi, H., Hirota, T. and Fujita, Y. (1988) Biochim. Biophys. Acta 939, 57-63). These amphipathic peptides stimulated the release of membrane phospholipids outside cells in a concentration range causing permeability change. The shape change of erythrocytes from normal discoid to spiculate form was observed just prior to the release of membrane components. We have proposed the following action mechanism of gramicidin S and melittin. The peptide molecules were predominantly accumulated in the outer half of the bilayer, deforming the erythrocyte cell into crenature. A large accumulation made the membrane structure unstable, resulting in the release of membrane fragments and the simultaneous enhancement of permeability. The action mechanism of these peptides was compared with that of simple surfactants.

Bee Venoms↗

[Measurement of DNA content and analysis of chromosome using flow cytometry].

This include review of recent paper about sensitivity and effective of radiation therapy using flow cytometry. This paper discuss the prediction of tumor response. As predictor of response in cancer. It is DNA aneuploidy, growth fraction (% S fraction), chromosome changes, and monoclonal antibody by oncogene product protein. It is possible that the protocol of cancer treatment will be determined based on prediction data from an individual cancer. Flow cytometry would be a useful tool to get a predictor of radiation, drugs response on each cancer.

Aneuploidy↗