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S Ohtake

Publications and source records attributed to S Ohtake.

212 records · Page 12Linked to original sources
PubMedDate not supplied

A recombinant human interleukin-1 beta protects adriamycin-induced toxicity. Adriamycin cardiotoxicity and interleukin-1.

Pretreatment with recombinant human interleukin-1 beta (IL-1) protected normal BALB/c mice from the lethal effect adriamycin (ADM) of related to dose and frequency of administration. Posttreatment with IL-1 failed to protect. Neutrophil and platelet counts after the administration of ADM (16 mg/kg) did not differ between the group with and that without IL-1 pretreatment, whereas lipid peroxide levels in the heart were reduced in the group pretreated with IL-1. It appears that the chemoprotection mechanism of IL-1 lies in the prevention of cardiotoxicity due to ADM-induced free radicals.

Animals↗
PubMedDate not supplied

Evaluation of the biocompatibility of a new method for heparin coating of a cardiopulmonary bypass circuit.

The biocompatibility of the Terumo (Terumo Corporation, Tokyo, Japan) covalent heparin coating method in a cardiopulmonary bypass (CPB) circuit was evaluated in ex vivo and in vivo experiments. In the ex vivo experiment, fresh human heparinized blood primed both a miniature heparin coated circuit (HCC) and the identical noncoated circuit (NCC), and was circulated simultaneously for 2 hr (n = 6). In the in vivo experiment, 10 rabbits underwent 2 hr of CPB under systemic heparinization (ACT > 400 sec) with HCC (n = 5) and with NCC (n = 5). In the ex vivo study, thrombin/anti-thrombin III complex, thromboglobulin, platelet factor IV, granulocyte elastase, and C3a were significantly lower in the HCC than in the NCC at 60 and 120 min of circulation (p < 0.05). In the in vivo study, platelet counts (percent of value at 10 min of CPB) were significantly higher in the HCC than NCC (HCC:NCC 87 +/- 10:71 +/- 12 at 60 min, 81 +/- 17:56 +/- 16 at 120 min). Scanning electron microscopic examination of the circuits showed less significant adhesion and pseudopod formation of platelets in the HCC than NCC in both ex vivo and in vivo situations. These results demonstrate that this heparin coated CPB circuit provides superior biocompatibility compared with a noncoated circuit by reducing the activation of the coagulation cascade, platelets, leukocytes, and complement.

Animals↗
PubMedDate not supplied

Nitric oxide gas infusion to the oxygenator enhances the biocompatibility of heparin coated extracorporeal bypass circuits.

Heparin coated bypass circuits have been reported to improve the biocompatibility of extracorporeal circulation, although it is still insufficient and improvable. Nitric oxide (NO) is known to inhibit platelet activation and inflammatory reactions. In this study, the authors evaluated exogenous NO infusion in enhancing the effect of a heparin coated bypass circuit on the biocompatibility of an extracorporeal circuit, especially in view of the attenuation of the inflammatory response. A miniature closed bypass circuit, including an oxygenator (BioActive surface; Carmeda, Stockholm, Sweden) was primed with fresh human heparinized blood and perfused with a centrifugal pump. Either pure N2 gas (control group: n = 7) or NO gas (NO group [100 ppm in N2]: n = 7) was infused to the oxygenator. NO metabolites (nitrite and nitrate), platelet count, thrombin-antithrombin III complex (TAT), alpha2-plasmin-plasminogen inhibitor complex (PIC), beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), serotonin, complement 3 activation products (C3a), granulocyte elastase, and bradykinin were measured at 0, 30, 60, 120, and 180 min after starting perfusion. At every sampling point, platelet counts were significantly higher, and TAT, beta-TG, and bradykinin were lower in the NO group than in the control group. PF4, C3a, and granulocyte elastase were significantly lower in the NO group at 60, 120, and 180 min. These results suggest that NO gas infusion to the oxygenator enhances the biocompatibility of heparin coated extracorporeal circuits.

Biocompatible Materials↗
PubMedDate not supplied

Endovascular stent graft placement for patients with aortic aneurysm and end-organ dysfunction.

Endovascular stent grafts (ESGs) for the treatment of aortic aneurysm is becoming popular because it is less invasiveness for the patient. This new modality seems to be especially useful for treating high risk patients, such as those with end-organ dysfunction. In this study we retrospectively analyzed the results of ESG placement for patients with renal or hepatic dysfunction. From January 1996 to December 1997, six patients with end-organ dysfunction (two with descending thoracic aneurysm and four with abdominal aneurysm) underwent ESG placement. Five of these patients had renal dysfunction, with serum creatinine levels of 2.0 mg/dl or greater, and the remaining patient had hepatic dysfunction with a prothrombin time less than 60%. One of the patients also had severe atherosclerotic disease with a history of multiple brain infarctions. All the patients received custom made endovascular spiral Z stents covered with a woven Dacron (DuPont Co., Wilmington, DE) graft, which was delivered via a femoral artery under local anesthesia. None of the patients showed significant changes in renal or hepatic function after the procedure. None of the five patients with renal dysfunction needed hemodialysis after ESG placement, although the mean preoperative level of serum creatinine and blood urea nitrogen was 3.4 mg/dl and 42.0 mg/ dl, respectively. All the patients left the recovery room on postoperative day 1. These results indicated that endovascular stent graft placement is extremely useful in the treatment of aortic aneurysm patients with end-organ dysfunction.

Aged↗
PubMedDate not supplied

P-selectin monoclonal antibody may attenuate the whole body inflammatory response induced by cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) is known to induce an inflammatory response in association with neutrophil mediated lung injury. P-Selectin has been reported to be involved in the initiation of this inflammatory response by promoting the adhesion of neutrophils to endothelial cells in postcapillary venules. However, the role of P-selectin in the inflammatory response induced by CPB has never been clarified. To elucidate its role, we evaluated the effect of an anti-rat specific P-selectin monoclonal antibody (ARP2-4; Sumitomo Pharmaceutical) on the response of inflammatory cytokines and lung injury in a rat-CPB model. Twenty Sprague-Dawley rats underwent CPB for 30 minutes (80 ml/kg per minute, 34 degrees C) under one of two conditions. In group P, ARP2-4 (3 mg/kg) was added to the priming solution of the bypass circuit (n = 10). Saline alone was given to group C (n = 10). Inflammatory cytokines (tumor necrosis factor-alpha [TNF-alpha], interleukin[IL]-1beta, IL-6, and IL-8) and respiratory index (RI) as a marker of pulmonary gas-exchange ability were measured 1) before the initiation of CPB, 2) at the termination of CPB, and 3) 2 hours after the termination of CPB. Neither TNF-alpha nor IL-1beta was detected during the experimental period in either group. The plasma levels of IL-6 and IL-8 increased after CPB in both groups, but they were significantly lower in group P than in group C. The RI value increased in a pattern similar to that of the inflammatory cytokines and was significantly lower in group P. These data demonstrate that the addition of an anti-rat specific monoclonal antibody inhibits the abnormal release of inflammatory cytokines and attenuates CPB induced lung injury in rats. Thus, P-selectin may play a role in the augmentation of CPB induced inflammatory response, and the use of its inhibitory monoclonal antibody seems to be a promising strategy for the treatment of CPB induced lung injury.

Animals↗
PubMedDate not supplied

Anti-Fas IgM monoclonal antibody enhances apoptosis induced by low-dose cytosine arabinoside.

BACKGROUND: Although low-dose cytosine arabinoside (LD-Ara-C) therapy has been accepted as an effective treatment for patients with acute non-lymphocytic leukemia (ANLL) transformed from myelodysplastic syndromes or elderly patients with ANLL, the anti-leukemic mechanism remains to be resolved. Recently, the potential role of the Fas/Fas ligand system in chemotherapeutic drug-induced apoptosis has been studied. In the present study the relationship between the anti-leukemic effect of LD-Ara-C and the Fas/Fas ligand system was examined. MATERIALS AND METHODS: The human myeloid leukemia cell line HL60 was treated with LD-Ara-C in combination with anti-Fas IgM MoAb, and apoptosis in the treated cells was estimated by morphological observation, DNA electrophoresis and flow cytometry. Simultaneously, changes in Fas antigen expression on cells treated with LD-Ara-C were investigated. RESULTS: Only limited apoptosis was observed following treatment with LD-Ara-C alone or anti-Fas MoAb alone; however, a synergistic increase in apoptosis was observed by treatment with the MoAb in combination with pretreatment with LD-Ara-C. LD-Ara-C induced a slight but consistent increase in the expression of Fas antigen on the treated cells. Moreover, the expression of Fas antigen was enhanced by repeated administration of LD-Ara-C. CONCLUSIONS: These findings suggest the possible involvement of the Fas/Fas ligand system in the anti-leukemic effect of LD-Ara-C therapy.

Antibodies, Monoclonal↗
PubMedDate not supplied

Hepatectomy for metastases from breast cancer offers the survival benefit similar to that in hepatic metastases from colorectal cancer.

BACKGROUND/AIMS: There have been no reports comparing surgical results of hepatectomy for metastases between breast cancer origin and colorectal cancer origin. The aim of the present study was to compare the both and to clarify the survival benefit brought by hepatectomy for metastases from breast cancer. METHODOLOGY: Between 1990 and 1999, 6 patients with hepatic metastases from breast cancer and 94 patients with those from colorectal cancer underwent hepatectomy with curative intent. All patients in the breast-cancer-origin group received adjuvant chemotherapy following hepatectomy, however, fewer patients (55% of the 94 patients) did in the colorectal-cancer-origin group (P = 0.034). RESULTS: Morbidity and mortality rates after hepatectomy in patients with hepatic metastases from breast cancer were 0% and 0%, respectively, and those in patients with metastases from colorectal cancer were 12% and 1%, respectively. Postoperative survival curves in the both groups were similar. Three- and five-year survival rates in the breast-cancer-origin group were 60% and 40%, respectively, and those in the colorectal-cancer-origin group were 54% and 42%, respectively. CONCLUSIONS: When appropriate adjuvant chemotherapy is performed, hepatectomy for metastases from breast cancer offers the survival benefit similar to that in hepatic metastases from colorectal cancer.

Adult↗
PubMedDate not supplied

The relation of argyrophilic proteins of nucleolar organizer regions (AgNORs) to the proportions of Ki-67 or DNA polymerase alpha-reacting cells in non-Hodgkin's lymphomas.

In order to examine the relationship between argyrophilic proteins of nucleolar organizer regions (AgNORs) and the proliferation activity of cells, we investigated lymph nodes obtained from 25 untreated non-Hodgkin's lymphoma (NHL) patients. Two monoclonal antibodies (MoAb) (Ki-67 antibody and anti-DNA polymerase alpha antibody) were used for evaluating cell proliferation activity. A linear relation between the mean number of agNORs per nucleus and the proportion of NHL cells reacting with Ki-67 MoAb was observed (r = 0.48, P less than 0.05). A similar relation between AgNORs and DNA polymerase alpha MoAb was also observed (r = 0.51, P less than 0.01). From these data, it was confirmed that AgNORs reflect the proliferation activity of NHL cells. We conclude that the AgNOR staining procedure is one of the simplest and most reliable methods for analyzing cell proliferation potential.

Antibodies, Monoclonal↗
PubMedDate not supplied

Induction of apoptosis in HL60 leukemic cells by anticancer drugs in combination with anti-Fas monoclonal antibody.

Some anticancer drugs kill tumor cells through the mechanism of apoptosis. Fas antigen has been generally noticed as an apoptosis-signalling receptor molecule on the surface of different cells. Recently, it has become clear that some tumor cells express Fas antigen on their surface, and apoptosis is induced in those cells by IgM-anti-Fas monoclonal antibody (IgM-anti-Fas MoAb). If it is possible to induce apoptosis in tumor cells effectively by anticancer drugs in combination with IgM-anti-Fas MoAb, then we may be able to develop a new strategy for cancer chemotherapy. HL60 human leukemic cell line was incubated with anticancer drugs adriamycin (ADM) or cytosine arabinoside (Ara-C) at different doses alone and in combination with IgM-anti-Fas MoAb. We then observed the morphologic changes of tumor cells, the DNA fragmentation by agarose gel electrophoresis, and the changes in the amount of Fas antigen expression in their cell surface by using flow cytometry. In ADM- or Ara-C-treated tumor cells, apoptotic cells increased in number time- and dose-dependently. By the combination of ADM or Ara-C with IgM-anti-Fas MoAb, the induction of apoptosis in HL60 cells was enhanced significantly. The DNA electrophoresis supported those results. The amount of Fas antigen expression was slightly increased only in cells treated with a low dose of Ara-C, not in others. Our results suggest that apoptosis is a major process of leukemic cell death induced by anticancer drugs. Furthermore, it has become clear that the combination of anticancer drugs with IgM-anti-Fas MoAb enhances leukemic cell death through apoptosis in vitro, though the mechanism remains to be resolved.

Antibodies, Monoclonal↗
PubMedDate not supplied

Hemodynamic effect of inhaled nitric oxide in dilated cardiomyopathy patients on LVAD support.

Recently it has been shown that inhaled nitric oxide (NO), which has been proven to contribute to improvement in critical pulmonary hypertension, may provide a favorable effect early after left ventricular assist device (LVAD) support. To improve right ventricular function, inhalation of NO was added to treatment with conventional catecholamines for four consecutive dilated cardiomyopathy (DCM) patients following institution of LVAD. In two patients 1 hr after inhalation of NO, central venous pressure (CVP), mean pulmonary arterial pressure (PAm), and pulmonary vascular resistance (PVR) were improved. These results led to better LVAD output and resulted in an adequate cardiac index. On the other hand, a right VAD (RVAD) was implemented in one patient whose high CVP, PAm, and PVR continued; he was weaned after 8 days of RVAD support. Another patient who had a high CVP but normal PAm and PVR before and after inhalation of NO had no improvement in his hemodynamic state. These data suggest that inhaled NO may improve systemic circulation by reducing right ventricular afterload and may become a promising and convenient therapy before placing RVAD in DCM patients under LVAD support. RVAD should be conducted in patients with right ventricular failure or when pulmonary hypertension is associated with impaired right ventricular reserve, even after inhalation of NO.

Administration, Inhalation↗
PubMedDate not supplied

Portable cardiopulmonary support system as a bridge to left ventricular assist system implantation. A new strategy for the treatment of end stage cardiac disease.

The key to the successful implantation of a left ventricular assist system (LVAS) for patients with end stage cardiac disease is whether the functions of other vital organs are irreversibly damaged or not. The portable cardiopulmonary support system (PCPS) is not only as convenient as, but is more powerful than, the intra-aortic balloon pump (IABP) in resuscitating impaired end organ function. To investigate the efficacy of PCPS in end stage cardiac disease, end organ function before and after the application of PCPS was retrospectively analyzed for end stage cardiac disease. From 1992 to 1996, five cardiomyopathy patients with deterioration in end organ function, despite application of IABP, underwent PCPS support before implantation of LVAS. Urine volume and levels of liver enzymes (sAST and sALT) and serum creatinine were determined before and after institution of PCPS. After the start of PCPS, the urine output increased significantly (1,840 +/- 450-4,340 +/- 470 ml/day, p < 0.01), and levels of sAST, sALT, and serum creatinine decreased significantly (630 +/- 220-150 +/- 50 IU/L, 630 +/- 260-260 +/- 130 IU/L, and 2.9 +/- 0.5-1.2 +/- 0.1 mg/dl, respectively; p < 0.05). All five patients were successfully bridged to LVAS implantation, and none died of multiple organ failure caused by pre-existing cardiac failure. These results indicate that PCPS before LVAS implantation is useful in resuscitating impaired end organ function and improving the survival rate with LVAS implantation for end stage cardiac disease.

Adult↗
PubMedDate not supplied

Hepatic sinusoid endothelial dysfunction plays a role in hyperbilirubinemia in patients following implantation of an LVAD.

To clarify the mechanism of hyperbilirubinemia in the setting of a left ventricular assist device (LVAD), the change in hepatocellular function, hepatic sinusoid endothelial microcirculation, and inflammatory response before and after LVAD implantation were evaluated. Eight consecutive patients underwent the placement of an LVAD, and serum levels of total bilirubin (TB), transaminases [alanine transaminase (ALT), aspartate transaminase (AST)], interleukin (IL-6, IL-8), and hyaluronic acid (HA), an indicator of hepatic sinusoidal circulation, were measured before and after LVAD implantation. The TB of all patients increased significantly in the first post operative week (p < 0.05 vs. pre-operatively). In five patients, the elevated TB (4.6 +/- 4.1 mg/dl) returned to pre-operative levels (2.7 +/- 2.0 mg/dl) by the 14th post operative day (Group R), but in the other three patients who died of multiple organ failure, the level of TB increased to 39.9 +/- 16.4 mg/dl (Group A). Levels of HA and IL-8 had good correlation with the level of TB (HA: r = 0.60, p < 0.05; IL-8: r = 0.55, p < 0.05). However, AST, ALT, and IL-6 were not related to changes in TB. These results suggest that hepatic sinusoid endothelial dysfunction and inflammatory reaction may play a significant role in hepatic failure in patients following implantation of an LVAD.

Adult↗