Protecting Ohmeda 7900 Ventilator flow sensor.
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Biomedical subjects
Publications and source records attributed to K Mizutani.
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OBJECTIVE: To study the alteration in the biomechanical properties of the thoracic aorta and its composition in young normotensive Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR), and stroke-prone SHR (SHRSP). METHODS: The in-vitro biomechanical properties of the aorta in 4- and 12-week-old SHRSP were determined by means of a tensile testing machine and compared with those of the SHR and WKY rats; in addition, a biochemical analysis of collagen, elastin and advanced glycation endproducts was performed. RESULTS: The aortic biomechanical properties were altered in the 4- and 12-week-old SHRSP, compared with age-matched WKY rats and SHR. The maximum stress in the 12-week-old SHRSP was reduced by 27% compared with the normotensive WKY rats, and by 26% compared with the SHR. The maximum strain values in the 4- and 12-week-old SHRSP were lower than those in the age-matched WKY rats, by 12 and 9% respectively, whereas this value in the 12-week-old SHR was significantly increased (by 26%) compared with the age-matched WKY rats. No differences were observed in the aortic contents of collagen and elastin between the SHRSP and SHR. However, the extractability of collagen by pepsin digestion in the 12-week-old SHRSP was lower than that in the age-matched SHR and WKY rats, and a significantly larger accumulation of advanced glycation endproducts was observed in the 12-week-old SHRSP than in the age-matched SHR and WKY rats, suggesting a greater formation of collagen-derived cross-links in SHRSP. CONCLUSIONS: From these results, we conclude that decreased aortic distensibility and mechanical strength values are partly related to the greater formation of collagen-derived cross-links in 12-week-old SHRSP, and that the mechanical properties in SHRSP may be the result not only of the larger formation of collagen-derived cross-links but also of primary defects, since the aortic mechanical strength value was decreased even in 4-week-old SHRSP.
We studied the effect of the extract of wine phenolics (EWP) on blood pressure, vasorelaxing activity and aortic biomechanical properties in stroke-prone hypertensive rats (SHRSP). Thirty-six 4-week-old male SHRSP/Izm rats were divided into 6 equal groups fed one of the following 6 diets: A control diet (plain laboratory diet), the control diet substituted with 0.5 or 1.0% polyphenolic compounds derived from the extract of apple phenolics (EAP), the control diet substituted with 0.5 or 1.0% polyphenolic compounds derived from the extract of tea phenolics (ETP), or the control diet along with drinking water containing 1.0% polyphenolic compounds derived from EWP. Systolic blood pressure (SBP) and body weight (BW) were checked once a week. At the end of the 8th week of feeding, all of the rats were sacrificed and the heart weight and aortic biomechanical properties were measured. The relaxation effect of the addition of EWP on endothelium-intact aortic rings precontracted with prostaglandin (PG) F2 alpha was also measured. Only EWP, not EAP or ETP, significantly lowered the SBP values a compared with the control group at the 4th, 7th and 8th weeks of feeding (p < 0.05). The heart weight and ventricular weight, expressed as the percentage of BW, were significantly lower in the EWP group than in the control group (p < 0.05). The aortic maximum stress was significantly increased (p < 0.05), and the aortic incremental elastic modulus was significantly reduced (meaning higher elasticity) (p < 0.001) in the EWP group as compared with the control group. The aortic rings showed concentration-dependent relaxation induced by EWP, and the relaxation was significantly greater than that induced by a commercial red wine preparation. In conclusion, EWP attenuated the elevation of blood pressure in SHRSP possibly by increasing the vasorelaxation activity. The aortic fragility and elasticity were also improved in EWP-fed SHRSP.
We performed retroperitoneal lymph node dissection (RPLND) on 14 patients (IIA: 1, IIB: 4, IIIA: 3, IIIB2: 2, IIIC: 4) with testicular and one with retroperitoneal germ cell tumor at the Nagoya University Hospital between 1986 and 1997. According to the international germ cell consensus classification, 4 patients were classified as "good-prognosis", three as "intermediate-prognosis" and eight as "poor-prognosis". RPLND was performed on 12 patients with the tumor marker levels normalized preoperatively and on three without the marker normalization. The mean surgical time was 510 (195-1, 125) minutes and the mean bleeding volume was 3,806 (100-12,598) g. The surgical time and bleeding volume were correlated with the size of the tumor in the body axis. Intraoperative complications occurred in 5 (33%) out of 15 patients: injury of renal artery (2), renal vein (1), ureter (1) and common iliac artery (2). Postoperative complications occurred in 2 patients: ileus (2) and lower extremity edema resulting from resection of the inferior vena cava (1) and would dehiscence (1). Of the 8 patients whose completely resected retroperitoneal tumors were necrosis/fibrosis or teratoma (psCR), 6 achieved survival with no evidence of disease (NED). Among 4 patients, whose tumor was not completely resected but pathologically diagnosed as necrosis/fibrosis or teratoma (pCR), NED without recurrence was achieved in 2 and also in one with resection of relapsed teratoma 2.5 years after RPLND. All three patients with cancer tissues pathologically retained in the resected tumors (sCR or psIR), consequently died of the disease. In six patients with relapse, the initial sign was elevation of the tumor marker levels, which was noted more than 30 days postoperatively in 2 patients with psCR and 7 to 15 days in 4 patients without psCR. We believe that RPLND is needed to examine the pathology and to predict the prognosis of the poor-risk patients with NSGCT. Careful dissection of vessels is needed to reduce vascular complications.
The purpose of this study was to look for evidence of changes in angiotensin converting enzyme activity in the renal vascular bed of streptozotocin (STZ)-induced diabetic rats. To assess the activity of the enzyme, we examined angiotensin I- and angiotensin II-induced vasoconstriction in perfused kidneys from controls and diabetic rats. Angiotensin I (3x10(-9) to 3x10(-6) M) induced a dose-dependent vasoconstriction in control kidneys; this response was completely inhibited by losartan (10(-5) M) and markedly inhibited by both captopril (10(-4) M) and indomethacin (10(-5) M). Angiotensin II (10(-10) to 3x10(-7) M) also caused a dose-dependent vasoconstriction in control kidneys; this response was markedly enhanced by 10(-4) M L-NNA, and significantly inhibited by losartan (10(-5) M). Angiotensin I-induced vasoconstriction was slightly greater in STZ-induced diabetic rats than in controls, but the maximal response was unaffected. These results suggest that angiotensin I is rapidly converted to angiotensin II in the renal vascular bed, and that converting enzyme activity in the renal vascular bed may be decreased in STZ-induced diabetic rats.
Between January 1997 and December 1998, six patients with germ cell tumor were treated with high-dose CEC: carboplatin (1,500 mg/m2), etoposide (1,200 mg/m2) and cyclophosphamide (100 mg/kg), followed by peripheral blood stem cell transplantation (PBSCT) at Nagoya University Hospital. Four patients received one cycle of high-dose CEC and two received two cycles. The reasons why the high-dose CEC was administered included: 1) refractory to the induction chemotherapy (AFP/beta-HCG elevated during the induction chemotherapy or prolonged half-life of each marker) in three patients, 2) relapse in two patients, and 3) consolidation in one with unresectable mediastinal residual tumor. There were no treatment-related deaths and grade 1 hepatotoxicity occurred in one (17%) patient. The median duration (range) from PBSCT until a granulocyte count of 500/microL and a platelet count of 50,000/microL was 8.5 (8-11) and 11 (9-16) days, respectively. Of the six patients studied, 5 responded to the treatment; two achieved a complete response (CR) and three achieved a partial response (PR). One patient achieving a CR and two achieving a PR remained in complete remission after 23 to 24 months of follow-up, while the remaining patients with a CR, a PR and an incomplete response died of the disease. High-dose CEC could be administered without serious toxicity but the effectiveness of high-dose CEC for the poor-risk patients with germ cell tumor needs to be further investigated.
This study was undertaken to determine whether preoperative epidural morphine using double-catheter technique would improve postoperative analgesia in patients undergoing esophagectomy with or without continuous intraoperative epidural lidocaine in a randomized double-blind and controlled manner. Thirty patients undergoing esophagectomy for esophageal cancer received preoperative epidural morphine 2 mg at T 6-7 and 2 mg at L 3-4 through the catheters, respectively. Thereafter, continuous thoracic epidural infusion of either 1% lidocaine (lidocaine group, n = 15) or normal saline solution (control group, n = 15) at 6 ml/h was initiated. After surgery, mean verbal rating scale of pain (0 to 10) at rest was maintained below 4 and pain on deep breathing was maintained mild in all patients in both groups. There was no significant difference in these values between the groups. In conclusion, preoperative epidural morphine using double-catheter technique provided adequate analgesia following esophagectomy. The addition of intraoperative continuous epidural lidocaine did not improve analgesia.
Nutritional and pharmacological factors are needed to prevent bone loss that occurs with increasing age. The chemical compounds that act on bone metabolism as nutrients in food, however, are poorly understood. The effect of resveratrol, a natural phytoestrogen, on the proliferation and differentiation of osteoblastic MC3T3-E1 cells was studied. Resveratrol dose-dependently increased DNA synthesis (10(-9)-10(-7) M) of MC3T3-E1 cells. In addition, resveratrol increased alkaline phosphatase (ALP) activity and prolyl hydroxylase activity of MC3T3-E1 cells (10(-6)-10(-5) M). Moreover, the antiestrogen tamoxifen eliminated the stimulation of MC3T3-E1 cells on the proliferation and ALP activity by resveratrol. On the other hand, resveratrol inhibited prostaglandin E2 production in MC3T3-E1 cells (10(-8)-10(-6) M). Our present study is the first to demonstrate that resveratrol directly stimulates cell proliferation and differentiation of osteoblasts.
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Immunocytochemical expression of tumor necrosis factor-alpha (TNF-alpha) was examined in nerve biopsy samples of patients with various disorders, focusing on nerve injury. TNF-alpha was mainly associated with phagocytosing macrophages in acute axonal injury, but the staining was more frequently seen in sections from patients with vasculitis than with metabolic neuropathy. Ramifield macrophages outside nerve fibers were also positive for TNF-alpha in the acute stage of vasculitis. In active demyelinating lesions from patients with chronic inflammatory demyelinating neuropathy (CIDP), macrophages outside nerve fibers showed weak staining with TNF-alpha, but the cells adhering to myelinated nerve fibers showed definite staining. This may be due, in part, to the smouldering course of CIDP, and expression may be up-regulated transiently during the demyelinating process. These results indicate that macrophages, as the effector cells for both axonal injury and active demyelination, express TNF-alpha, buth their activation mechanisms may vary among vasculitis, metabolic axonopathy and inflammatory demyelination.
Licochalcone A-D and echinatin, retrochalcones isolated from the roots of Glycyrrhiza inflata, showed antimicrobial activity. Among them, licochalcone A and C had potent activity against some Gram-positive bacteria. These retrochalcones inhibited oxygen consumption in susceptible bacterial cells. The oxidation of NADH in bacterial membrane preparations was also inhibited by them. NADH-cytochrome c reductase was inhibited by licochalcones, while cytochrome c oxidase was not. NADH-CoQ reductase and NADH-FMN oxidoreductase were not inhibited. The site of respiratory inhibition of licochalcones was thought to be between CoQ and cytochrome c in the bacterial respiratory electron transport chain.
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Licochalcone A, B, C, D and echinatin, retrochalcones isolated from the roots of Glycyrrhiza inflata (licorice), along with an ordinary chalcone isoliquiritigenin, were assessed for their inhibitory activities on lipid peroxidation in various systems and radical scavenging activity. Among those tested, licochalcones B and D strongly inhibited superoxide anion production in the xanthine/xanthine oxidase system. These two compounds also showed potent scavenging activity on DPPH radical. Microsomal lipid peroxidation induced by Fe(III)-ADP/NAPDH was inhibited almost completely by 3 micrograms/ml of licochalcones B and D. Mitochondrial lipid peroxidation induced by Fe(III)-ADP/NADH was more sensitive to these retrochalcones; almost complete inhibition was observed at 10 micrograms/ml of all retrochalcones tested. Licochalcones B and D scavenged superoxide anion in microsome. Furthermore, these retrochalcones protected red cells against oxidative hemolysis. These phenolic compounds were shown to be effective to protect biological systems against various oxidative stresses.
Astilbin, a dihydroflavonol rhamnoside isolated from the leaves of Engelhardtia chrysolepis, enhanced the vanadate-stimulated release of lipoprotein lipase (LPL) activity from rat isolated fat pads. N-[2-(Methyl-amino)ethyl]-5-isoquinolinesulfonamide (H-8), a potent inhibitor of cAMP-dependent protein kinase (PKA), markedly inhibited the enhancement by astilbin. Lipolysis in the fat pads was stimulated by astilbin alone in a dose-dependent manner and this stimulation was suppressed in the presence of vanadate, probably due to its antilipolytic action. A significant enhancement by astilbin was observed with increasing effects of vanadate on cAMP content in the fat pads and on cAMP phosphodiesterase (PDE) activity in the particulate fraction although astilbin alone showed only a slight increase in the cellular cAMP content and PDE activity. Astilbin may enhance the vanadate-stimulated release of LPL activity through a synergistic effect on an increase in the cellular cAMP content produced by vanadate accompanied by more potent activation of PKA.
In Bacillus sp. YUF-4, acetylacetoin synthase was induced by acetoin, while glucose inhibited the induction. The enzyme was purified 111-fold by 6 purification steps, and a further purification followed, by HPLC using a TSK gel, Phenyl-5PW RP. The resulting enzyme gave a single band with a molecular mass of 62 kDa by SDS-PAGE and 220 kDa by gel filtration. Some enzymic characteristics were studied.
We conducted a preliminary controlled study in order to evaluate 5'-DFUR dose dependency in efficacy and safety in combination therapy of radiotherapy, 5'-DFUR and SPG for patients with uterine cervical cancer, which was regarded as suitable for cases of radiotherapy. The patients were randomly allocated into group A (5'-DFUR 600 mg/body/day) and group B (5'-DFUR 800 mg/body/day), who underwent radiotherapy with simultaneous administration of 5'-DFUR and SPG (20 mg twice/week or 40 mg/ week). Those enrolled were 33 patients in stage II, III or IV a with histologically diagnosed primary squamous cell carcinoma of uterine cervix. CR was shown in 19, PR in 7, NC in 1, and PD in 2 out of 29 efficacy-evaluable cases, so the overall response rate was 89.7% (26/29, 95% CI 72.7%-97.8%). Regarding safety, some side effects were observed in 26 out of 33 safety-evaluable cases (81.3%, 95%, CI 63.6%-92.8%), but no serious cases. No significant difference in efficacy and safety was observed between the two treatment groups. These results suggested that the combination therapy of radiotherapy, 5'-DFUR and SPG might be one of the therapies whose effectiveness must be confirmed for advanced squamous cell carcinoma of uterine cervix. To confirm dose dependency of 5'-DFUR, it seems further consideration with more patients is needed.
Between 1988 and 1996, we treated 11 poor-risk patients with non-seminomatous germ cell tumors (NSGCT) at Nagoya University Hospital. "Poor-risk" was defined as i) advanced disease equal to or greater than class 7 of the Indiana University Classification (7 patients), ii) primary mediastinal extragonadal NSGCT (2), iii) tumor markers not normalized by the induction chemotherapy (1) or iv) primary retroperitoneal NSGCT with multiple lung metastases (1). Two patients with mediastinal tumors died during the chemotherapy. The minimal volume of fluid must be administered to patients with giant mediastinal tumors. The tumor marker normalized during the induction chemotherapy in only three patients. Three patients, whose tumor markers elevated during or one month after the induction chemotherapy, eventually died of cancer. The tumor markers in five of the seven patients which had not normalized during the induction chemotherapy, had decreased to the normal range during the salvage chemotherapy and two of the five subsequently achieved the status of "no evidence of disease" (NED). Six patients with and two without normalized tumor markers underwent retroperitoneal lymph nodes dissection and/or resection of residual tumors. Pathological examination of the resected tumors showed necrosis/fibrosis in five patients and two had elevated tumor markers immediately after the surgery and eventually died of the disease. Overall, eight (73%) of 11 poor-risk patients achieved a complete response but only five (45%) eventually achieved a NED status that was maintained (6.6 +/- 3.0 years). Our results were not satisfactory, and we believe that new strategies, such as early high-dose chemotherapy, are required for poor-risk patients, who are not likely to respond well to the induction chemotherapy.