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Biomedical subjects

M Ueno

Publications and source records attributed to M Ueno.

At least 469 records · Page 26Linked to original sources

Pathophysiology in malignant hypertension: with special reference to the renin-angiotensin system.

Pathophysiology of malignant hypertension, of which underlying disease was essential hypertension (EHT) in 33 cases and chronic glomerulonephritis (CGN) in 26 cases, was studied with reference to the renin-angiotensin system. Plasma renin activity (PRA) was significantly higher in the EHT than in the CGN group, and angiotensin II antagonist [Sar1, Ile8]angiotensin II (AIIA) induced a significant lowering of blood pressure only in the former group. PRA was linearly correlated with both pretreatment mean blood pressure (MBP, r = 0.474, n = 29, p less than 0.01) and serum creatinine (r = 0.540, n = 29, p less than 0.01) in the EHT group but not in CGN patients, although there was an inverse correlation between PRA and serum sodium in both groups. Multiple regression analysis revealed that PRA was independently related to MBP, serum creatinine, and serum sodium in the EHT group, but not in the CGN group. These results suggest that the renin-angiotensin system plays a significant role in elevating blood pressure and deteriorating renal function in malignant hypertension derived from EHT, but it is less important in CGN related hypertension.

1-Sarcosine-8-Isoleucine Angiotensin II↗

Inhibitory effects of tetradecanoylphorbol acetate and diacylglycerol on erythropoietin production in human renal carcinoma cell cultures.

A human renal carcinoma from a patient with an erythrocytosis, serially transplanted into athymic nude mice, was grown in primary monolayer cell cultures. After reaching confluency the cultured cells formed multicellular hemicysts (domes) which became more abundant as the cultures approached saturation density. Erythropoietin (Ep) production by this renal carcinoma in culture was only slightly increased at the time of semiconfluency but showed a marked increase in Ep levels in the culture medium after the cultures reached confluency, in parallel with an increase in dome formation. The phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) showed a significant dose-related inhibitory effect on Ep production and dome formation in the renal carcinoma cell cultures, suggesting an important role of protein kinase C, the only known receptor for TPA, in inhibiting the expression of differentiated phenotypes in the renal carcinoma cells. TPA also suppressed Ep secretion over a period of 96 h, indicating a time course of suppression of this differentiated function of the renal carcinoma cells in culture. This hypothesis was further supported by the observation that diacylglycerol, the endogenous activator of protein kinase C, likewise inhibited Ep production and dome formation in the renal carcinoma cell cultures. These studies suggest a role of the inositol-lipid second messenger path and protein kinase C in the regulation of Ep production.

Carcinoma, Renal Cell↗

Augmentation of cell-mediated cytotoxicity against renal carcinoma cells by recombinant interleukin 2.

The effects of recombinant interleukin 2 (IL-2) on natural killer (NK) cell activity against established renal carcinoma cell lines CaKi 1, KU-2, and freshly prepared renal carcinoma cells were studied. Augmentation of NK cell activity by IL-2 was dose- and time-dependent. The results indicate that the optimal dose of IL-2 was 100 to 500 U/mL, and that cytotoxicity increased significantly even at a low concentration such as 4 U/mL. IL-2 induced significantly higher levels of cytotoxicity against renal carcinoma cells than did gamma-interferon. The influence of IL-2 on lymphocyte subpopulations was then examined using flow cytometry with monoclonal antibodies OKT3, OKT4, OKT8, Leu 7, and Leu 11. The results showed that IL-2 increased the number of cells positive to Leu 11, the so-called active NK cells. We concluded that IL-2 has an important role in the treatment of renal carcinoma.

Carcinoma, Renal Cell↗

Effects of low calcium levels on erythropoietin production by human renal carcinoma cells in culture.

Recent investigations have shown that calcium entry blockers enhance the effects of hypoxia on erythropoietin (Ep) production in vivo. To determine whether deprivation of calcium increases Ep production and/or release, studies were carried out to determine the effects of low levels of extracellular calcium on Ep (radioimmunoassay) secretion in human renal carcinoma cells in culture. Low extracellular calcium levels (0.3 mM) in culture medium significantly (P less than 0.01) enhanced Ep secretion (64-145% increase per day) by renal carcinoma cells in culture when compared with a concentration of 1.9 mM calcium in the control culture medium (23-68% increase per day) incubated for 24 h or more. A 53% increase per day in Ep secretion was also produced by the calmodulin inhibitor trifluoperazine. To determine whether the effects of low calcium levels on Ep production could be due to nonspecific leakage of large intracellular molecules caused by a permeabilization of the cell membrane, the effect of low calcium levels in the cultures of the renal carcinoma cells on lactate dehydrogenase release into the culture medium was studied. Low calcium concentrations failed to significantly enhance lactate dehydrogenase secretion by the renal carcinoma cells. In conclusion, our results indicate a possible involvement of the calcium ion and calmodulin in the biosynthetic pathway for Ep and that calcium may exert a suppressive effect on Ep production.

Calcium↗

Age-dependent changes in phenytoin tissue distribution in rats.

Age-dependent changes of phenytoin disposition in rats were studied following intravenous administration of 5,5-[4-14C]-diphenylhydantoin to 1-d, 1-, 3- and 8-week-old rats. The distribution volumes changed similarly to those of warfarin in the growth process of rats. The lower clearances in infant and young rats were considered to be caused by the undeveloped liver function to metabolize phenytoin. The changes of distribution volumes in the growth process of rats were assumed to be based upon not only the changes in blood free fractions but also other factors. In any aged rats, the muscle largely contributed to the distribution of phenytoin in the body and the Kp values in the muscle decreased in the growth process of rats. This change of phenytoin transfer to the muscle affected the decrease of distribution volumes of phenytoin in 8-week-old rats and the distribution volumes of brain, lung and liver in infants and young rats were greater than those in adult rats. The Kp value in the lung in 8-week-old rats was smaller than the values in 1-d, 1- and 3-week-old rats and there was no significant difference in the Kp values in the liver among the 4 ages. These results were different from those in warfarin reported previously and suggested that warfarin and phenytoin bind different macromolecules in the liver and the lung.

Aging↗

Age-dependent change in warfarin distribution volume in rats: effect of change in extracellular water volume.

The pharmacokinetics of insulin was studied following intravenous administration of 14C-inulin to 1-d, 1-, 3- and 8-week-old rats. The distribution volume of inulin varied 2-fold, from 689 ml/kg in 1-d-old rats to 340 ml/kg in 8-week-old rats in the growth process of rats. This result was similar to that of warfarin and there was a statistically significant correlation between the distribution volume of warfarin and inulin (r = 0.984, p less than 0.02). In the growth process of rats, the Kp values of warfarin in muscle, which play an important role in the distribution kinetics of warfarin changed in parallel with those of inulin. These results and pharmacokinetic considerations indicated that in warfarin, which is highly bound to serum protein and shows a small distribution volume, the change in the distribution volume in the growth process of rats following administration of a pharmacologically realistic dose (1 mg/kg) is led by the change in the extracellular volume of tissues and that the change in serum protein binding of warfarin might play a minor role in the change in the distribution volume in the growth process.

Aging↗

Age-dependent changes in phenytoin tissue bindings in rats: comparison between in vivo and in vitro tissue-to-blood partition coefficients (Kp values) of phenytoin.

Age-dependent changes in phenytoin tissue bindings in rats were investigated by equilibrium dialysis using serum and 10% tissue (brain, lung, liver, kidney and muscle) homogenates. All percentages of phenytoin bound to serum and tissue homogenates were independent of the initial phenytoin concentration (2 to 25 micrograms/ml) in 1-d, 1-, 3- and 8-week-old rats. The percentages bound to serum, brain, liver, kidney and muscle in newborn rats (1-d-old rats) were lower than those in 8-week-old rats and the percentages bound increased gradually in the growth process. However, those in lungs were constant in all ages of rats. It was assumed that the age-dependent changes in phenytoin tissue binding were caused by the changes in the quantities of tissue constituents to which phenytoin bound in the growth process. Tissue-to-blood partition coefficients (Kp values) were calculated from in vitro tissue binding data and the pH-difference across the cell membrane. These Kp values were in good agreement with the in vivo Kp values reported previously. It was concluded that the age-dependent changes in phenytoin tissue distribution were caused by the age-dependent changes in phenytoin binding to blood constituents and tissues but that the change of phenytoin blood binding contributed to the age-dependent changes in Kp values of phenytoin more than to phenytoin tissue binding and consequently the Kp values of phenytoin decreased as rats grew.

Aging↗

Comparative study of subjective fatigue between automatic transmission bus drivers and manual transmission bus drivers.

The difference in the physiological condition of drivers of manual transmission buses (MTB) and automatic transmission buses (ATB) was examined from the viewpoint of occupational health. This study was based on a self-administered questionnaire which involved items concerning subjective fatigue complaints. No differences in the mental fatigue and stress between MTB drivers and ATB drivers were observed. Although ATB drivers tended to feel less physical fatigue than MTB drivers, the difference was not statistically significant. From these results, it was suggested that there was little difference in the subjective fatigue between ATB drivers and MTB drivers.

Adult↗

Single oral administration of captopril may not bring an improvement in screening of primary aldosteronism.

Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured in 19 cases with primary aldosteronism (PA) and 72 with essential hypertension (EHT) to differentiate the two disorders in the following conditions: after overnight recumbency (basal state) and after oral administration of captopril. Screening criteria were determined in order to pick up all of PA patients as positive. After the captopril administration, the specificity of a criterion based on the combination of PAC and PAC/PRA ratio was 93% and positive predictive value 79%. This criterion was superior to other conventional screening methods. However, higher specificity (97%) and positive predictive value (90%) were obtained from a combination criterion based on the basal PAC and PAC/PRA ratio. The single oral administration of captopril may not bring an improvement in the screening of PA.

Aldosterone↗

OF4949, new inhibitors of aminopeptidase B. V. Effect on the murine immune system.

OF4949-I inhibited the growth of the solid form of IMC carcinoma and protected against pulmonary metastases of Lewis lung carcinoma. It also augmented the cytostatic activity of mouse peritoneal macrophages, the natural killer activity, and the antibody-dependent cell-mediated cytotoxicity of mouse spleen cells. This substance was not cytotoxic to cultured tumor or normal cells even at high concentrations. These results suggest that a cell-mediated immune response stimulated by this compound might account for its antitumor activity.

Aminopeptidases↗

[Clinicopathological study of AFP producing gastric cancer--significance of AFP in gastric cancer].

We experienced fifteen cases (3.9%) out of 387 with gastric cancer showing elevation of alphafetoprotein (AFP) in serum. In these cases AFP producing cells in primary lesion demonstrated positive for anti-AFP by means of immunohistochemical study. In this report, clinicopathological feature and clinical significance as a tumor marker of gastric cancer were discussed. Gross type showed Borrmann II and III which were located in atrophic area in the stomach. Histological type revealed papillary, moderately differentiated and poorly differentiated adenocarcinoma, all of which showed medullary growth in stroma. In clinical field, liver metastasis was observed in 12(80%) of 15 cases. In these cases, elevation of serum AFP was already observed before the detection of liver metastases by CT or Echo. Immunohistochemical study showed no difference between primary tumor and metastases, and no AFP positive cells were seen in 68 early gastric cancers without elevation of serum AFP.

Aged↗

[The analysis of prognostic factors on postsurgical pyuria of benign prostatic hypertrophy].

The outcome of postsurgical pyuria in benign prostatic hypertrophy was studied in 87 patients, and the factors that might affect the outcome were determined. No significant differences were found between operation method and duration until normalization of pyuria, which was 75.5 +/- 46.0 days for transurethral resection of the prostate, 72.7 +/- 30.6 days for suprapubic prostatectomy and 69.3 +/- 32.7 days for retropubic prostatectomy. Prognostic factors were statistically analyzed preoperatively, at operation, and postoperatively. The definite prognostic factors were preoperative diabetes mellitus, preoperative pyuria, preoperative bacteriuria, and postoperative hypoproteinemia. The probable prognostic factors were old-age, preoperative indwelling catheters, heavy prostate tissue, postoperative bacteriuria, postoperative anemia and postoperative complications.

Aged↗

[Comparative study of the activating effects of recombinant human interleukin 2 and interferon-gamma on cell-mediated cytotoxicity against renal cell carcinoma in vitro].

The effects of recombinant interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) on lymphocyte-mediated cytotoxicity against established human renal carcinoma cell lines KU-2 and Caki 1, and freshly prepared human renal carcinoma cells were compared in vitro. After incubation of peripheral blood lymphocytes from normal adult volunteers with IL-2 and IFN-gamma over a range of concentrations, cytotoxicity was determined by 4-h 51Cr-release assay. Augmentation of cytotoxicity by IL-2 and IFN-gamma was dose-and time-dependent. IL-2 induced significantly greater cytotoxicity against renal carcinoma cells than did IFN-gamma. The optimal dose of IL-2 was 100 to 500 units/ml, and cytotoxicity was increased even at concentrations as low as 4 units/ml. The results indicated that the systemic administration of IL-2 to patients will be effective for treatment of renal cell carcinoma which is resistant to interferon therapy. A continuous infusion or multiple repeated bolus doses over a period of one day, however, should be considered in order to maintain high levels of IL-2 in the serum.

Adult↗

[A case of multiple urothelial tumors with chronic renal failure].

We report a case of multiple urothelial tumors (left renal pelvis, ureter and bladder) with chronic renal failure in a 72-year-old man. The patient was admitted because of gross hematuria with increasing volume and intervals on September 14, 1985. Admission evaluation including excretory urography, retrograde pyelography, computed tomography and cystoscopy revealed multiple urothelial tumors in the left renal pelvis, ureter and bladder. Radical surgery, however, was postponed because of pneumothorax induced by an inadvertent insertion of the CVP catheter at operation. Subsequent respiratory disturbance persisted so that he was observed at the outpatient clinic following right ureterocutaneostomy. Gradual increase in anemia and decrease in renal function, however, prompted another admission. Gross hematuria necessitating frequent blood replacement could not be controlled by transurethral resection of bladder tumors. Therefore left nephroureterectomy with resection of bladder cuff was performed after internal arteriovenous shunt had been established, because favorable results regarding tumor resection were obtained from preoperative evaluations. He showed satisfactory recovery and was spared hemodialysis despite eventful postoperative course with transient decrease in renal function. The patient was discharged on 130th postoperative day and is now being followed up at the outpatient clinic. The relevant literature is also reviewed briefly.

Aged↗

[Clinical study of urinary tract infections in transurethral surgery].

Effect of prophylactic administration of antimicrobials on postoperative urinary tract infection was studied in 40 patients who had undergone transurethral surgery. Two gm of cefoperazone (CPZ) per day was administered intravenously starting on the day of surgery for 5 days consecutively. In group I, 1 g of CPZ was administered 1 hour before surgery and another 1 g after surgery, while in group II 2 g of CPZ was administered after surgery only. Thereafter, in either group, 1 g of CPZ was administered intravenously 2 times a day. Urinary tract infection (UTI) was diagnosed when urine specimens yielded 1 X 10(4)/ml or more cells. In group I, 8 patients (40%) had UTI before surgery. Of 8 patients, 3 had bacteria resistant to CPZ. Of the remaining 5 patients with bacteria sensitive to CPZ 4 patients were cleared of bacteria after surgery. All these patients had bacteria sensitive to CPZ and therefore all were cleared of bacteria after surgery. In either group of patients all without bacteriuria at the time of preoperative evaluation were free from bacteriuria after surgery. All bacteria yielded after surgery were weak pathogens. All patients except 1 had no postoperative infectious complication such as septicemia, epididymitis and UTI. One patient showed UTI with fever after surgery. Urine culture yielded S. faecalis. This study showed that the prophylactic administration of antimicrobials for patients undergoing transurethral surgery was valuable, but the both methods of administration were similarly effective.

Adult↗