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Biomedical subjects

Shigeru Saito

Publications and source records attributed to Shigeru Saito.

156 records · Page 9Linked to original sources
PubMed2002

Increasing mean arterial blood pressure has no effect on jugular venous oxygen saturation in insulin-dependent patients during tepid cardiopulmonary bypass.

UNLABELLED: Preexisting diabetes mellitus is one of the major factors related to adverse postoperative neurological disorders after cardiac surgery. In previous reports, we found that diabetic patients more often experienced cerebral desaturation than nondiabetic patients during normothermic cardiopulmonary bypass (CPB). The purpose of this study was to examine the effects of increasing mean arterial blood pressure (MAP) by the administration of phenylephrine on internal jugular venous oxygen hemoglobin saturation (SjvO2) during tepid CPB in diabetic patients. We studied 20 diabetic patients scheduled for elective coronary artery bypass graft surgery and, as a control, 20 age-matched nondiabetic patients. After the induction of anesthesia, a fiberoptic oximetry catheter was inserted into the right jugular bulb to monitor SjvO2. After measuring the baseline partial pressure of the arterial and jugular venous blood gases and cardiovascular hemodynamic values, MAP was increased by the repeated administration of a 10-microg bolus of phenylephrine until it reached 100% of baseline values. There was a significant difference in SjvO2 value between the Diabetic and CONTROL GROUPs after the administration of phenylephrine (Diabetic group, 56% +/- 6%; CONTROL GROUP: 60% +/- 4%) (P < 0.05). There was a significant difference in the arterial-jugular oxygen content difference value between the Diabetic and CONTROL GROUPs after the administration of phenylephrine (diabetic group, 4.9% +/- 0.6%; CONTROL GROUP, 4.5% +/- 0.4%) (P < 0.05). We subdivided the Diabetic group into three groups (Diet Therapy group [n = 4], Glibenclamide group [n = 10], and Insulin-Dependent group [n = 6]). There was a significant difference in the mean slopes of SjvO2 versus cerebral perfusion pressure for increasing cerebral perfusion pressure between the Insulin-Dependent group and the other groups (Dunnett test: P = 0.04). Increasing MAP had no effects on the SjvO2 value in insulin-dependent patients during tepid CPB. IMPLICATIONS: We examined the effects of increasing mean arterial blood pressure (MAP) by the administration of phenylephrine on internal jugular venous oxygen saturation (SjvO2) during tepid cardiopulmonary bypass in diabetic patients and found that increasing MAP had no effect on the SjvO2 value in insulin-dependent patients.

Adrenergic alpha-Agonists↗
PubMed2002

Impairment of hepatosplanchnic oxygenation and increase of serum hyaluronate during normothermic and mild hypothermic cardiopulmonary bypass.

UNLABELLED: Hepatic sinusoidal endothelial cells (SECs) are more vulnerable to hypoxia or hypothermia than hepatocytes. To test the hypothesis that hepatic venous desaturation during cardiopulmonary bypass (CPB) leads to impairment of SEC function, we studied the plasma kinetics of endogenous hyaluronate (HA), a sensitive indicator of SEC function, and hepatosplanchnic oxygenation during and after CPB. Twenty-five consecutive patients scheduled for elective coronary artery bypass graft surgery, who underwent normothermic (>35 degrees C; n = 15) or mild hypothermic (32 degrees C; n = 10) CPB participated in this study. A hepatic venous catheter was inserted into each patient to monitor hepatosplanchnic oxygenation and serum levels of HA concentration. Hepatic venous oxygen saturation decreased essentially to a similar degree during normothermic and mild hypothermic CPB. Hepatosplanchnic oxygen consumption and extraction increased during normothermic (P < 0.05), but not mild hypothermic, CPB. Both arterial and hepatic venous HA concentrations showed threefold increases during and after CPB in both groups. A positive correlation was found between hepatosplanchnic oxygen consumption and arterial HA concentrations during CPB, suggesting a role of changes in hepatosplanchnic oxygen metabolism in the mechanisms of increases in serum HA concentrations. The failure of the liver to increase HA extraction to a great degree suggests that a functional impairment of the SEC may contribute to the observed increase of serum HA. IMPLICATIONS: Hepatic sinusoidal endothelial cells (SECs) are pivotal in the regulation of sinusoidal blood flow. This study showed that SEC function might be impaired during and after cardiopulmonary bypass, irrespective of the temperature management.

Aged↗
PubMed2002

Growth cone collapsing effect of lidocaine on DRG neurons is partially reversed by several neurotrophic factors.

BACKGROUND: Local anesthetics were suggested to have a potential for neurotoxicity in both clinical reports and laboratory experiments. Growing neurons have been shown to be susceptible to the toxic effects of local anesthetics in culture. These findings have generated the interest in factors that would rescue the neurons affected by the neurotoxicity of local anesthetics. METHODS: Primary cultured dorsal root ganglia were isolated from age-matched chick embryos and exposed to lidocaine. After 60 min of exposure, the culture media were replaced to wash out the lidocaine. Neurotrophic factors (NTFs)-brain-derived neurotrophic factor, glial-derived neurotrophic factor, or neurotrophin 3-were added to the replacement media to examine the capacity of these NTFs to support the reversibility of the lidocaine-induced growth cone collapse. The growth cone collapse assay was applied a quantitative method of assessment. RESULTS: When any of the three NTFs was added to the replacement media at a minimum concentration of 10 ng/ml, significantly high reversibility of the lidocaine-induced growth cone collapse was observed, especially at 48 h after washout (P < 0.05). At that time point, there was no significant difference between the values of growth cone collapse percentage in the cells that were exposed to lidocaine and supported by the NTFs after the washout, and the control cells (not exposed to lidocaine) (P > 0.05). CONCLUSION: The NTFs-brain-derived neurotrophic factor, glial-derived neurotrophic factor, and neurotrophin 3-were demonstrated to support the reversibility of lidocaine-induced growth cone collapse in primary cultured sensory neurons, an effect that was concentration- and time-dependent. Because similar effects were observed after tetracaine washout, the supporting effects of NTFs may not be specific to lidocaine.

Anesthetics, Local↗
PubMed2002

HER2 is frequently over-expressed in ovarian clear cell adenocarcinoma: possible novel treatment modality using recombinant monoclonal antibody against HER2, trastuzumab.

Ovarian clear cell adenocarcinoma (CCA) is generally chemo-resistant. Recently the poor prognosis and resistance to chemotherapeutic agents of HER2/neu over-expressing tumors have become clear. Thus, we investigated the expression level of HER2 in surgically resected CCA and ovarian serous adenocarcinoma, endometrioid adenocarcinoma, and mucinous adenocarcinoma specimens, as well as CCA cell lines, by an immunohistochemical method. HER2 was over-expressed in 42.9% of CCA (P=0.026, vs. ovarian serous adenocarcinoma), 20.8% of ovarian serous adenocarcinoma, 23.1% of ovarian endometrioid adenocarcinoma, and 30.0% of mucinous adenocarcinoma specimens. Three CCA cell lines, RMG-1, HAC-II and KK were also positively stained for HER2. A flow-cytometric study of HER2 revealed 7.2-, 6.4- and 4.5-fold greater expression of HER2 than that of normal mammary gland, respectively. Trastuzumab, a humanized recombinant monoclonal antibody against HER2 significantly and dose-dependently reduced the growth of CCA cell lines in vitro. The extent of the inhibitory effect of trastuzumab was dependent on the expression level of HER2. Trastuzumab also dose-dependently inhibited the growth of xenografted RMG-1 tumor. The survival period of trastuzumab-treated mice was longer than that of the control group. From these findings, trastuzumab appears to be a candidate as a treatment modality for HER2 over-expressing ovarian CCA.

Adenocarcinoma, Clear Cell↗
PubMed2002

Macrophage colony-stimulating factor (M-CSF) prevents infectious death induced by chemotherapy in mice, while granulocyte-CSF does not.

To clarify the effect of granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF/CSF-1) on chemotherapy-induced infection, we estimated the effect of those CSFs on a mouse model under severe myelosuppression. First, we established an animal model in which 48.9% (22/45) of C3H/Hej mice died of sepsis related to severe myelosuppression after intraperitoneal administration of a single dose (9 mg/kg) of mitomycin C (MMC). G-CSF or M-CSF was administered to this model on various administration schedules after chemotherapy, and the effect of those CSFs on survival rates, peripheral blood granulocyte counts, expression of adhesion molecules (CD11a, CD11b, CD18) on granulocytes and granulocyte function (phagocytosis and superoxide anion production) were examined. In all G-CSF administration groups, peripheral blood granulocyte counts were increased, but improvements in expression of adhesion molecules such as CD11a and CD18, and granulocyte function were less marked and survival rates were not improved. Meanwhile, when M-CSF was administered from 1 to 7 days after chemotherapy, granulocyte and platelet counts were increased, and moreover, expression of adhesion molecules and granulocyte function were markedly improved. Furthermore, the survival rate was significantly improved to 77.8% (28/36) compared with the MMC group (P < 0.05). Positive rate of blood culture examination at 7 days after chemotherapy in the M group was 0%, and was significantly lower than that in the G group (40%) and the MMC group (40%) (P < 0.05). These results demonstrated that it is important not only to increase the granulocyte counts, but also to improve granulocyte functions for preventing infection under myelosuppression after chemotherapy.

Animals↗
PubMed2002

Vascular access.

Explore the source record for details and available documents.

Catheterization↗
PubMed2002

Localization of the induced metallothionein and DNA damage in rat kidney after gold injection.

To clarify the relationships between DNA damage and Cu-MT and between DNA damage and Cu in kidneys of rats injected with Au, we examined the histochemical localization of DNA damage, metallothionein (MT), and the accumulated Cu in the kidneys of rats injected with Au, Cu, or Cu-MT. The immunoreactivity of MT was observed predominantly in the outer stripe of the outer medulla and the inner cortex of the Au-injected rat, and the signals of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) were observed in the cortex. Cu detected by Timm's method was mainly distributed in the cortex of the Au-injected rat. These results indicated that DNA damage could be caused by free Cu in the cortex but not by the Cu bound to MT in the outer stripe of the outer medulla. This consideration was supported by the data from rats injected with Cu and Cu-MT. Furthermore, we determined the Cu contents in three fractions (cytosol, organelle, and precipitate-containing nuclei) of the kidneys. Interestingly, most of the Cu content in the kidney of the rat injected with Au or Cu-MT was detected in the cytosol, whereas most of the Cu content in the kidney of the rat injected with Cu was detected in the nuclei-containing precipitate. These findings suggest that the DNA damage in the kidneys of rats injected with Au may be associated with Cu-binding proteins but not with Cu-MT.

Animals↗
PubMed2002

[Apoptosis as a measure of chemosensitivity to anti-cancer drugs in gynecological cancer].

OBJECTIVE: To examine apoptosis as a measure of chemosensitivity to anti-cancer drugs in gynecological cancer xenografted into nude mice. METHODS: The TUNEL method was used to investigate the induction of apoptosis after exposure to anti-cancer drugs in thirteen gynecological cancers xenografted into nude mice. Moreover, in vivo sensitivities of gynecologic cancer to anti-cancer drugs were determined according to the protocol developed by Battle Laboratories, Columbus, Ohio USA. Both methods were examined for correlation. RESULTS: The apoptosis index by the TUNEL method showed a correlation with the findings using the protocol developed by Battle Laboratories, Columbus, Ohio USA. CONCLUSIONS: Our findings indicate the ability to determine the measure of chemosensitivity by the apoptosis index.

Animals↗
PubMed2002

Selective inhibition of the epidermal growth factor receptor by ZD1839 decreases the growth and invasion of ovarian clear cell adenocarcinoma cells.

The mechanism that regulates the growth of ovarian clearcell adenocarcinoma (CCA) are not well understood. We investigated the role of several growth factors that bind to membrane tyrosine kinase receptors and added them to the ovarian CCA cell lines KK, RMG-1, and HAC-II to evaluate their effect on growth and cellular invasion. Epidermal growth factor and transforming growth factor-alpha significantly stimulated the growth and invasion of CCA cell lines in vitro. ZD1839, an epidermal growth factor receptor-tyrosine kinase inhibitor, decreased the growth and invasion of CCA cell lines in vitro and in vivo inhibited the growth of xenografts of the CCA cell line RMG-1. Severe combined immunodeficient mice bearing RMG-1 xenografts treated with ZD1839 survived for longer than the untreated control group. From these findings, we conclude that ZD1839 may offer a new and effective treatment for ovarian CCA.

Adenocarcinoma, Clear Cell↗
PubMedDate not supplied

Freeze-thawing procedures have no influence on the phenotypic and functional development of dendritic cells generated from peripheral blood CD14+ monocytes.

Little is known about the potential influence of cryopreservation on the biologic activities of dendritic cells (DCs). In this study, we examined the effects of freeze-thawing on the phenotypic and functional development of human DCs obtained from granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood CD14+ cells. CD14+ cells were cultured, immediately or after freeze-thawing, with granulocyte-macrophage CSF and interleukin-4 for 9 days, and then with added tumor necrosis factor-alpha for another 3 days. For both fresh and freeze-thawed monocytes, immature DCs harvested on day 6 and mature DCs harvested on day 9 of culture were examined under the same conditions. Cells were compared with regard to their 1) capacities for antigen endocytosis and chemotactic migration (immature DCs), and 2) allogeneic mixed lymphocyte reaction and antigen-specific cytotoxic T lymphocyte responses (mature DCs). Freeze-thawing did not affect the viability or subsequent maturation of DCs at any stage of development. Furthermore, essentially no difference was observed in phenotype or function between cells generated from fresh or cryopreserved/thawed cells. Although this study design was limited with the use of fetal bovine serum, the observation still suggests that freeze-thawing does not affect viability, phenotype, subsequent maturation, or functions of DCs at any stage of maturation.

Cells, Cultured↗
PubMedDate not supplied

Expansion of alpha-galactosylceramide-stimulated Valpha24+ NKT cells cultured in the absence of animal materials.

Valpha24+ NKT is an innate lymphocyte with potential antitumor activity. Clinical applications of Valpha24+ natural killer (NK) T cells, which are innate lymphocytes with potential antitumor activity, require their in vitro expansion. To avoid the potential dangers posed to patients by fetal bovine serum (FBS), the authors evaluated non-FBS culture conditions for the selective and efficient expansion of human Valpha24+ NKT cells. Mononuclear cells (MNCs) and plasma from the peripheral blood of normal healthy donors were used before and after G-CSF mobilization. MNCs and plasma separated from apheresis products were also used. MNCs were cultured for 12 days in AIM-V medium containing alpha-galactosylceramide (alpha-GalCer) (100 ng/mL) and IL-2 (100 U/mL) supplemented with FBS, autologous plasma, or autologous serum. The cultured cells were collected and their surface markers, intracellular cytokines, and cytotoxicity were evaluated. The highest expansion ratio for Valpha24+ NKT cells was obtained from G-CSF-mobilized MNCs cultured in medium containing 5% autologous plasma. Cultures containing MNCs and autologous plasma obtained before and after G-CSF mobilization had approximately 350-fold and 2,000-fold expansion ratios, respectively. These results suggest that G-CSF mobilization conferred a proliferative advantage to Valpha24+ NKT cells by modifying the biology of cells and plasma factors. Expanded Valpha24+ NKT cells retained their surface antigen expression and production of IFN-gamma and exhibited CD1d-independent cytotoxicity against tumor cells. Valpha24+ NKT cells can be efficiently expanded from G-CSF-mobilized peripheral blood MNCs in non-FBS culture conditions with alpha-GalCer and IL-2.

Blood Component Removal↗