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Biomedical subjects

N Murase

Publications and source records attributed to N Murase.

At least 91 records · Page 5Linked to original sources
PubMed1997

[Combination hepatic intra-arterial 5-fluorouracil and CDDP administration with oral regimen in patients with colorectal cancer metastasis to the liver].

We investigated therapeutic effectiveness and side effects of a combination weekly high-dose 5-FU plus one shot CDDP HAI (WHF + CDDP method) with oral regimen in patients with colorectal cancer metastasis to the liver. All 24 patients enrolled in this study showed 54% efficacy whereas patients combined HAI with oral regimen over one week obtained 83% efficacy for multiple liver metastasis. They showed good quality of the life during combination chemotherapy without any symptoms of metastatic lesions. The WHF + CDDP method combined with oral regimen is a promising treatment for colorectal cancer metastasis to the liver as well as extrahepatic distant organs, and this protocol may be satisfactorily accepted by most colorectal cancer laden patients because of negligible side effects.

Administration, Oral↗
PubMed1996

Effect of anticomplement agent K76 COOH on hamster-to-rat and guinea pig-to-rat heart xenotransplantation.

In normal rats, the xenobiotic K76 inhibited the C5 and probably the C2 and C3 steps of complement and effectively depressed classical complement pathway activity, alternative complement pathway activity, and the C3 complement component during and well beyond the drug's 3-hr half-life. It was tested alone and with intramuscular tacrolimus (TAC) and/or intragastric cyclophosphamide (CP) in rat recipients of heterotopic hearts from guinea pig (discordant) and hamster (concordant) donors. Single prevascularization doses of 100 and 200 mg/kg increased the median survival time of guinea pig hearts from 0.17 hr in untreated controls to 1.7 hr and 10.2 hr, respectively; with repeated injections of the 200-mg dose every 9-12 hr, graft survival time was increased to 18.1 hr. Pretreatment of guinea pig heart recipients for 10 days with TAC and CP, with or without perioperative splenectomy or infusion of donor bone marrow, further increased median graft survival time to 24 hr. Among the guinea pig recipients, the majority of treated animals died with a beating heart from respiratory failure that was ascribed to anaphylatoxins. Hamster heart survival also was increased with monotherapy using 200 mg/kg b.i.d. i.v. K76 (limited by protocol to 6 days), but only from 3 to 4 days. Survival was prolonged to 7 days with the addition of K76 of intragastric CP at 5 mg/kg per day begun 1 day before operation (to a limit of 9 days); it was prolonged to 4.5 days with the addition of intramuscular TAC at 2 mg/kg per day beginning on the day of transplantation and continued indefinitely. In contrast to the limited efficacy of the single drugs, or any two drugs in combination, the three drugs together (K76, CP, and TAC) in the same dose schedules increased median graft survival time to 61 days. Antihamster antibodies rapidly increased during the first 5 days after transplantation, and plateaued at an abnormal level in animals with long graft survival times without immediate humoral rejection. However, rejection could not be reliably prevented, and was present even in most of the xenografts recovered from most of the animals dying (usually from infection) with a beating heart. Thus, although effective complement inhibition with K76 was achieved in both guinea pig- and hamster-to-rat heart transplant models, the results suggest that effective interruption of the complement cascade will have a limited role, if any, in the induction of xenograft acceptance.

Animals↗
PubMed1996

Allogeneic hematolymphoid microchimerism and prevention of autoimmune disease in the rat. A relationship between allo- and autoimmunity.

Conventional allogeneic bone marrow transplantation after myeloablation can prevent experimental autoimmunity and has been proposed as treatment for humans. However, trace populations of donor hematolymphoid cells persisting in solid organ allograft recipients have been associated in some circumstances with therapeutic effects similar to replacement of the entire bone marrow. We therefore examined whether inducing hematolymphoid microchimerism without myeloablation could confer the ability to resist mercuric chloride (HgCl2)-induced autoimmunity. Brown-Norway (BN) rats were pretreated with a syngeneic or allogeneic bone marrow infusion under transient FK506 immunosuppression before receiving HgCl2. They were compared with BN rats receiving either no pretreatment (naive) or FK506 alone. Administration of HgCl2 to naive BN rats induced marked autoantibody production, systemic vasculitis and lymphocytic infiltration of the kidneys, liver and skin in all of the animals and a 47% mortality. In contrast, BN rats pretreated with HgCl2-resistant allogeneic Lewis bone marrow and transient FK506 showed less clinical disease and were completely protected from mortality. More specifically, IgG anti-laminin autoantibody production was decreased by 40% (P < 0.05), and there was less histopathological tissue injury (P < 0.005), less in vitro autoreactivity (P < 0.05), less of an increase in class II MHC expression on B cells (P < 0.01), and 22% less weight loss (P < 0.01), compared with controls. Protection from the experimental autoimmunity was associated with signs of low grade activation of the BN immune system, which included: increased numbers of circulating B and activated T cells before administration of HgCl2, and less autoreactivity and spontaneous proliferation in vitro after HgCl2.

Animals↗
PubMed1996

In vitro characterization of rat bone marrow-derived dendritic cells and their precursors.

Although the rat is commonly used for basic immunology and transplantation research, phenotypic and functional characterization of rat dendritic cells (DCs) lags behind similar studies in the human and mouse. Therefore, these features were examined using DCs propagated from cultures of rat bone marrow maintained in a medium supplemented with granulocyte-monocyte colony-stimulating factor. Analysis of cytospin preparations of cultured cells showd that DCs arise from OX7+ myelomonocytic precursors. Typical mature rat DCs were morphologically similar to their mouse and human counterparts and expressed major histocompatibility complex (MHC) class II (common part determinant of Ia), OX62 (integrin molecule), OX7 (CD90), ICAM-1 (CD54), and CTLA4 counterreceptor, but were negative for OX8 (CD8), OX19 (CD5), W3/25 (CD4), and ED2, a rat macrophage marker. Functional analysis of OX62+ sorted DCs showed that they could effectively present the soluble antigen ovalbumin to naive T cells in vitro. A combination of anti-MHC class II monoclonal antibody and CTLA4-immunoglobulin inhibited allostimulatory ability more effectively than either reagent alone. Implications for studying the role of DCs in immune responses in the rat are discussed.

Abatacept↗
PubMed1996

NMR studies on water and polymer diffusion in dextran gels. Influence of potassium ions on microstructure formation and gelation mechanism.

At room temperature aqueous solutions of dextrans with concentrations > 25% (w/w) exhibit a sol-gel transition in the presence of > 1.0 M potassium chloride. In dextrans the gelation was unexpected due to missing anionic groups that usually provide the binding sites for cations. The quantitative investigation of the gel formation is based on changes of the diffusibility of water and dextran chains. The apparent diffusion coefficients of bulk water (in the order of 10(-6) cm2/s) and of water trapped in the junction zones as well as of polymer chains (in the order of 10(-7) to 10(-8) cm2/s) are determined by employing pulsed field gradient stimulated echo (PFGSTE) NMR. The restricted diffusion of bulk water in viscous sols and in soft and rigid gels has been quantitatively analyzed providing data for interbarrier distances (pore size), permeabilities of the diffusion barriers (density of junction zones) and interbarrier diffusion coefficients of water. Based on already published x-ray structure data and in accordance with the diffusion data presented in this paper "potassium-bonding" is assumed to be the most important interaction for the formation of a microstructure and for the stabilization of cross-links. The ionic radius of the potassium ion perfectly fits to the cage established by six oxygen atoms of glucose units of three polymer chains. Other cations, such as Li+, Na+, Rb+ and Cs+, according to their nonfitting ionic radii, do not provoke dextran gelation under these conditions. The mechanism of the transitions from sol to soft gel and further to rigid gel is discussed on the basis of restricted diffusion and x-ray structure data.

Dextrans↗
PubMed1996

The two-way paradigm of transplantation immunology.

The events following organ transplantation require a reciprocal cell interaction which includes both the conventional host-versus-graft reaction and a graft-versus-host component. With all successful transplantation, both graft and recipient become genetic composites. Where donors were available, chimerism has been confirmed in 30-year kidney-recipient survivors, as well as in several liver and lung recipients. A majority of liver recipients have been able to acquire an immunosuppressant-free state after 10-year survival. Animal models suggest that donor-derived cells may exert a tolerogenic effect.

Animals↗
PubMed1996

Noninvasive measures of oxidative metabolism on working human muscles by near-infrared spectroscopy.

The purpose of this study was to determine whether the initial rate of hemoglobin and myoglobin deoxygenation during immediate postexercise ischemia, a reflection of muscle O2 consumption (VO2mus), can be a quantitative measure of muscle oxidative metabolism. The finger flexor muscles of five healthy men (aged 25-31 yr) were monitored by 31P-magnetic resonance spectroscopy for changes in phosphocreatine (PCr), Pi, and pH. Tests were conducted during 15 min of cuff ischemia and during 5 min of submaximal isotonic grip exercise at 10, 20, 30, and 40% of maximal voluntary contraction, one contraction every 4 s. The VO2mus changes were also monitored by near-infrared spectroscopy with continuous wave. The VO2mus during exercise was expressed relative to the resting value. The resting metabolic rate, calculated from the PCr breakdown rate after complete O2 depletion, was 0.0010 (SD) mM ATP/s. During submaximal exercise (pH > 6.9), the VO2mus increased with a rise in intensity (0.036 +/- 0.011, 0.054 +/- 0.016, 0.062 +/- 0.012, and 0.067 +/- 0.020 mM ATP/s during 10, 20, 30, and 40% maximal voluntary contraction, respectively) and showed significant correlation with changes in both calculated ADP and PCr values (r2 = 0.98 and r2 = 0.99, respectively). In conclusion, because of the significant correlation with regulatory metabolites (ADP and PCr) of oxidative phosphorylation, O2 decline rate in immediate postexercise ischemia determined by near-infrared spectroscopy with continuous wave can be utilized for the quantitative evaluation of localized muscle oxidative metabolism.

Adult↗
PubMed1996

[Familial Binswanger-type encephalopathy with Sneddon syndrome].

We reported a family with early onset cerebrovascular disease. Patient 1 (a 36-year-old man) demonstrated a combination of livedo reticularis and cerebral infarction as previously described as Sneddon syndrome. He also showed transient focal neurologic symptoms and mild dementia. Patient 2 (an elder sister of Patient 1) was suffering from migraine. Their father and paternal uncle died of cerebral infarction, which had developed in their thirties or forties. Patients 1 and 2 showed MRI findings compatible with encephalopathy with Binswanger-type. Contrary to the previous reports on Binswanger-type encephalopathy, both of these patients demonstrated decreased levels of fibrinogen as well as those of factor V, together with negative antiphospholipid antibody. Thus, juvenile onset, autosomal dominant inheritance, the diversity of clinical findings and the coagulopathy in this family were characteristic features. The level of thrombin-antithrombin III complex (TAT) was markedly increased in Patient 1. Treatment with antithrombin (argatroban 20mg i.v. everyday for 28 days) not only reduced the level of TAT but also improved the livedo reticularis and neurological findings. Although gene analysis has not been performed yet on this family, this condition is similar to cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL), which involve juvenile cerebral infarction and dementia as well as migraine.

Adult↗