[Protective effect of nicardipine hydrochloride on the perfused ischemic canine myocardium].
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Biomedical subjects
Publications and source records attributed to T Okamura.
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The promoting effect of sodium L-ascorbate on two-stage urinary bladder carcinogenesis in F344 rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine at levels of 0.01 and 0.05% in drinking water was studied. Administration of 5.0% but not of 1.0% sodium L-ascorbate in the diet significantly increased the incidence and number of preneoplastic lesions, papillary or nodular hyperplasia, papilloma, and cancer of the urinary bladder. In groups given 5.0% sodium L-ascorbate, the urine was characterized by an apparent elevation of pH, a decrease of osmolality, and an increase of MgNH4PO4 crystalline. Addition of sodium L-ascorbate to the diet also resulted in increase in the content of ascorbic acid and its metabolite, dehydroascorbic acid, in the urine. These results show that an extremely high dose of sodium L-ascorbate (5.0%) promotes urinary bladder carcinogenesis under the present experimental conditions, while a high dose (1.0%) does not.
Among colorectal cancer patients operated at the 2nd Department of Surgery, Kyushu University Hospital between 1974 to 1980. 6 developed this cancer after partial or total gastrectomy for gastric cancer or ulcer. The interval between the gastric operation and colorectal surgery ranged from 15 months to 17 years. The colorectal cancers arose in the transverse colon (1) the sigmoid colon (2), there were 3 rectal cancers. Therefore, not only the occurrence of recurrent or primary cancer in the remnant stomach, but also the occurrence of colorectal cancer should be monitored carefully after partial or total gastrectomy for gastric cancer or ulcer.
Cloned neuroblastoma cells (Neuro-2a) in culture were found to contain a renin inhibitory substance. The inhibitor in the extract of cloned neuroblastoma cells was separated from renin activity by anti-renin IgG-Sepharose and selectively concentrated by adsorption to renin-agarose gel. The present study demonstrated the coexistence of renin and its inhibitor in the same cell and suggested a possible regulatory mechanism of intracellular renin activity by an endogenous renin inhibitor in neuronal cells.
The tissue activator was extracted with 2 M ammonium thiocyanate and purified by L-arginine methyl ester, concanavalin A and ion-exchange chromatographies, and Sephacryl S-200 gel filtration in buffers containing Triton X-100 and/or ammonium thiocyanate. The final preparations had specific activities of 25 000-40 000 IU/mg protein and were shown to be a single band with an apparent molecular weight of 54 00 by SDS-polyacrylamide gel electrophoresis with or without reducing agent. When subjected to isoelectric focusing, its major component had an isoelectric point of approx. 8.2 with minor components. (7.8-8.6). The purified tissue activator was a serine protease, dissimilar to urokinase in some respects including antigenicity, strong affinity to insoluble fibrin monomer and hydrolytic activities for synthetic substrates. The crude extract contained another plasminogen activator with antigen identity to urokinase, which constituted approx. 15% of the total activity in crude extract. These findings indicated that human kidney would produce at least two plasminogen activators, namely, the tissue activator as a major plasminogen activator and urokinase.
The purpose of this study is to evaluate benign and/or malignant thyroid tumors with 201TI thyroid scan. We studied 76 cases of histologically verified thyroid tumors, all seen as cold nodules on the 123I thyroid scan. 201TI thyroid scan was performed 5-15 minutes (early scan) and 3-5 hours (delayed scan) after intravenous administration of 1.5-2.0 mCi of 201TI. In 35 (94.6%) of 36 malignant tumors (anaplastic carcinoma, six; papillary carcinoma 23; follicular carcinoma, five; epidermoid carcinoma, one; malignant lymphoma, 1) 201TI accumulated in the cold nodule of the 123I thyroid scan on both early and delayed scans. On the other hand, the delayed 201TI scan was negative in 35 out of 39 (89.7%) benign tumors. Employing early and delayed 201TI scans, we were able to differentiate most malignant thyroid tumors from those which were benign. False-negative and -positive cases are discussed.
Nineteen male Wistar rats received N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in drinking water (83 mg/L) to initiate glandular adenocarcinoma of the stomach; eight control rats received tap water. After 12 weeks a pyloroplasty was performed on nine rats receiving MNNG and three control rats. Ten MNNG-treated rats and five control rats had no operation. All were observed for 38 weeks before being killed. No difference in the incidence of antral adenocarcinomas was found between the MNNG-treated groups; however, those without operation showed in situ changes in the duodenum and those treated with pyloroplasty showed five invasive adenocarcinomas. In this model pyloroplasty alone did not increase the risk of gastric cancer but increased the risk of duodenal tumors. Pyloroplasty apparently accelerated the gastric evacuation rate, resulting in greater insult to the duodenal mucosa. Such a condition may require a higher proliferative rate in the duodenum and may increase subsequent formation of malignant tumors.
Glutathion (GSH) plays an important role in maintenance of the redox state of the myocardium and acts as the membrane stabilizer. Seventeen patients who underwent cardiac surgery were subjected to cardiopulmonary bypass (CPB) and ischemic cardioplegia. The effect of GSH on ischemic myocardium was evaluated by serum lysosomal enzymes (acid phosphatase, beta-glucuronidase), isoenzymes of creatine phosphokinase (MB-CPK) and aspartate aminotransferase (m-GOT). standard CPB was instituted and systemic hypothermia was employed. GSH was administered to 8 patients in a dose of 200 mg/kg i.v. prior to institution of CPB. Mixed venous blood was sampled before administration of GSH, 10 min after institution of CPB and 0, 1, 6, 24 and 48 hr of reperfusion period following cardioplegia. Activity of acid phosphatase and beta-glucuronidase were significantly suppressed in the GSH-treated group compared to the non-treated group at 24 hours of reperfusion and immediately after aortic unclamping, respectively. Serum MB-CPK levels remained stable during reperfusion, but in the non-treated group, the level increased significantly at 6 hours of reperfusion. Increment of serum m-GOT levels was significantly suppressed at 1, 6 and 24 hours of reperfusion, compared to the non-treated group. These data suggest that pretreatment of GSH can protect the myocardium subjected to CPB from ischemic insult.
Myocardial protective effect of lidocaine hydrochloride on the ischemic myocardium was evaluated by serum (MB-CK) and cardiac function in 48 patients; 24 patients in control (C) and 24 patients in lidocaine-treated group (L), who underwent aorto-coronary bypass surgery. Lidocaine hydrochloride, 1 mg/min was administered by continuous drip infusion from initiation of anesthesia, and throughout the operation and postoperative period for 24 hours. There were no significant differences between two groups with regard to duration of cardioplegia and cardiopulmonary bypass, hypothermic level and the number of grafts implanted. Serum MB-CK at 18-24 hours following cardioplegia was 39.5 +/- 15.2 I.U. (C) and 14.2 +/- 4.0 I.U. (L), (p less than 0.05). Cardiac index and stroke volume index were significantly increased in the lidocaine-treated group at 24 hours following aorto-coronary bypass surgery, as compared to the control group. Lidocaine thus appears to be beneficial in aorto-coronary bypass surgery to prevent ischemic changes in the myocardium.
Effectiveness of prophylactic extensive lymph node dissection (PELD) plus postoperative long term combination chemotherapy (PLCC) for patients with curatively resected gastric carcinoma was assessed in terms of the degree of serosal invasion and lymph node metastasis. Either the Group 1 and Group 2 lymph nodes were eradicated by PELD. PLCC included intermittent intravenous administration of mitomycin C (0.4 mg/kg intraoperatively followed by 0.2 mg/kg every 3 months) and oral administration of Tegafur (600-800 mg/day) and PSK (3.0 g/day), an immunostimulator, for as long a period as possible. PELD alone resulted in a cure when the malignancy was confined to the mucosal and muscular layers of the stomach as well as to the Group 1 lymph nodes. In cases when the carcinoma involved the serosa and/or the Group 2 lymph nodes, the 5 year survival rate was about 55 per cent the PELD and PLCC groups, such being significantly higher than about 27 per cent in the PELD alone group. Therefore, PELD plus PLCC is highly effective for advanced gastric carcinoma, under a condition of curative resection.
The effect of 2 hours of hypothermic Mg-lidocaine cardioplegia upon left ventricular function, myocardial high-energy stores, edema, and ultrastructure was studied as compared to glucose-insulin-potassium (GIK) cardioplegia in 12 mongrel dogs. The myocardial temperature recorded in the ventricular septum was kept at 20 degrees C during the cardioplegia. The heart was re-warmed up to 37 degrees C by the support of cardiopulmonary bypass, then, observations were made during a 60 minutes reperfusion. Left ventricular function was preserved at a more physiological level in cases of Mg-lidocaine cardioplegia. Myocardial ATP as preserved at significantly higher levels following Mg-lidocaine cardioplegia than in cases of GIK cardioplegia (p < 0.05). However, content of myocardial creatine phosphate was higher in the GIK cardioplegia group than that in Mg-lidocaine group in the subendocardium and the ventricular septum. Myocardial edema was significantly suppressed following Mg-lidocaine cardioplegia, and such was significantly lower than in cases of GIK cardioplegia (p < 0.05). The myocardial ultrastructure was protected from ischemic insult in the Mg-lidocaine cardioplegia group. These data suggest that Mg-lidocaine-1-aspartate solution is superior to GIK solution as a cardioplegic solution, and that such will feasibly provide myocardial protection for 2 hours of hypothermic cardiac arrest, in an experimental reperfused model.
In attempts to predict the recurrence of gastric cancer, postoperative changes in serum carcinoembryonic antigen (CEA) levels are monitored in our clinic by radioimmunoassay (Dainabot, Japan). Recurrences are suspected when serum CEA levels are 4 ng/ml, in the postoperative period. Out of 34 patients in whom there were increases in serum CEA, 18 were confirmed to have a recurrence and 15 of these 18 patients were assessed accurately by serial postoperative levels of CEA, two patients died of a recurrence after elevation of serum CEA levels. Thus, recurrence was predicted in 17 out of 34 patients (50 per cent) and in 12 out of 17 patients there was a metastasis to the liver. In 14 out of 34 patients there are no signs of recurrence 9 to 25 months after serum CEA elevations.
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A monolayer cell culture of juxtaglomerular cells (JGC) was derived from the renal cortex of neonatal rats. The JGC had the characteristics of those within the kidney, including peripheral dense bodies and myofibrils indicating a smooth muscle origin; rough ER containing fluffy material consistent with protein synthesis; a prominent Golgi apparatus for packaging granules, and granules having the characteristics of secretory granules and lysosomes. Transplants of the cultured cells into syngeneic recipients survived for 2 weeks or longer and retained the features of JGC. The JGC granules fluoresced when treated with a rabbit antibody against pure rat renin, followed by fluorescein isothyocyanate conjugated F(ab')2 fragment of goat antirabbit IgG (Fc fragment) heavy chain specific. The latter indicated the presence of renin. The JGC were lysed in the presence of DFP, captopril, leupeptin, and EDTA, and were extracted in the presence of pepstatin. The lysate contained renin activity that was inhibited by a specific renin antibody. Nonspecific proteases were excluded by the antibody and its pH optimum. Angiotensin I-converting enzyme was detected in the lysate prepared without the use of EDTA and captopril. Angiotensins I and II/III were derived from the extract by additional extractions, TLC, and RIA, using highly specific antibodies. The angiotensins were confirmed by chromatography monitored by authentic angiotensins. We concluded that the cultured JGC contained renin, angiotensin I-converting enzyme, and angiotensin I and II/III.
This experiment was designed to determine the optimal flow rate during early reperfusion after ischemic arrest for one hour at 28 degrees C of myocardial temperature, assessed by cardiac function, biochemistry and fine structure of the left ventricle. Under cardiopulmonary bypass (CPB) at a flow rate of 80 ml/kg/min, the ascending aorta was clamped for one hour at 28 degrees C of myocardial temperature in 19 mongrel dogs. After the aorta was declamped, the perfusion pressure was maintained at 50 mmHg and dogs were divided into 3 groups by flow rate of 50 (Group A), 80 (Group B) and 150 ml/kg/min (Group C) for 15 min of reperfusion. The left ventricular function was measured and calculated before the institution of CPB and 30 and 60 min after the declamping of the aorta. Myocardial isoenzymes (m-GOT, MB-CPK) in the coronary sinus venous blood were measured. Myocardial adenosine triphosphate (ATP), creatine phosphate (CP) and water content were measured by the samples of the epicardial and endocardial layers of the left ventricle and the ventricular septum at the end of experiment. The subendocardium of the left ventricle was examined by electron microscopy. Mortality rates were 1/6 (16.7%) in Group A, 2/7 (28.6%) in Group B and 4/6 (66.7%) in Group C. The myocardial water content was the lowest, and ATP was significantly higher in Group A compared to others. Left ventricular endodiastolic pressure was the lowest and the ultrastructure was well maintained in Group A. These data suggest that a high flow rate is detrimental to myocardial recovery during early reperfusion, and the optimal flow rate during early reperfusion after ischemic arrest (60 min, 28 degrees C) appears to be 50 ml/kg/min.
Twenty-nine anesthetized mongrel dogs were subjected to characterize the effect of lidocaine in ischemic reperfused myocardium. The left anterior descending coronary artery was ligated for 40 min and reperfused for 15 min. Two mg/kg of lidocaine was administered intravenously prior to the ligation and 2 mg/min (= 0.12 mg/kg/min) was infused continuously throughout the periods of coronary artery ligation and the reperfusion. Hemodynamic indices of left ventricular function were measured before ligation, 40 min after ligation and after 15 min of reperfusion, respectively. Transmural myocardial samples obtained from both the ischemic and the non-ischemic regions after 15 min of reperfusion were divided into the subendocardial and subepicardial layers and used for measurements of adenosine triphosphate (ATP), creatine phosphate (CP) and water content. ATP in ischemic endocardium was 1.73 +/- 0.69 mumole/g in the lidocaine-treated group and 1.36 +/- 0.41 in the non-treated group (p less than 0.05), and CP was 2.38 +/- 0.90 mumole/g and 1.59 +/- 0.95, respectively (p less than 0.01). Thus, high energy phosphate was at a significantly higher level in the lidocaine-treated group. Water content was significantly decreased in the lidocaine-treated group as compared with the non-treated group. Coronary blood flow and left ventricular functions were not significantly different between the two groups. These data suggest that lidocaine has a protective effect on ischemic reperfused myocardium and does not depress the left ventricular function in the commonly used doses.
Although the brain contains cathepsins at high concentrations which exhibit a non-specific renin-like activity at acidic pH, the presence of specific renin in the brain has been demonstrated by characterizing its specific properties. Renin was separated from cathepsin by affinity chromatography on casein-Sepharose. Brain renin showed neutral pH optima for the reaction to generate angiotensin I. The presence of inactive prorenin was also found. The isoelectric points of brain renin were significantly lower differences from that of renal or plasma renin. Immunohistochemical studies demonstrated a wide-spread localization of renin in many different regions. Angiotensin II, the final product of the prohormone-to-hormone conversion reaction mediated by renin and angiotensin converting enzyme, was found to exist in the same cell as renin by immunohistochemical studies of brain sections and with cloned and cultured neuroblastoma cells. This is the first demonstration of the mechanism of peptide hormone formation in neuronal cells. Similar intracellular formation was demonstrated in gonadotrophs of adenohypophysis. Coexistence of renin and angiotensin II was demonstrated in some cells. Electrophysiological studies have shown that angiotensin II functions to disinhibit the inhibition of neuronal response to electrical stimuli in the hippocampus.