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Biomedical subjects

K Uchida

Publications and source records attributed to K Uchida.

At least 1,297 records · Page 72Linked to original sources

Direct effects of heparin on basal and stimulated aldosterone production in rat adrenal glomerulosa cells.

Direct effects of heparin (0.1-10 IU/ml) on basal and stimulated aldosterone production have been studied using intact rat adrenal glomerulosa cells. Heparin at any dose did not affect basal aldosterone production when added to the incubation medium. Heparin at a 0.01 IU/ml dose had no effect on aldosterone production maximally stimulated by angiotensin II (AII, 4.8 X 10(-8) M), ACTH (4.3 X 10(-9) M) or potassium (8.0 mM). However, heparin at 0.1 and 0.3 IU/ml doses selectively blocked aldosterone production maximally stimulated by AII but not by ACTH or potassium, while the compound at 1 and 10 IU/ml doses inhibited aldosterone production maximally stimulated by these three stimuli. In addition, the inhibitory effect of 0.3 IU/ml heparin occurred as early as 30 min after incubation with heparin. These data suggest that heparin at 0.1 and 0.3 IU/ml doses acts directly on adrenal zona glomerulosa to selectively block the stimulatory action of AII, while the compound at 1 and 10 IU/ml doses inhibits all the stimulatory actions of AII, ACTH and potassium.

Adrenal Cortex↗

Immunohistochemical study on the distribution and significance of mononuclear cells in human breast carcinoma.

Lymphocyte subsets in the tumor nests of breast carcinoma were immunohistochemically investigated and a quantitative analysis was added. The majority of cases showed predominance of T cell and suppressor T cell (T8). A decrease in number of lymphocyte subsets and the helper T (T4)/T8 ratio in the stroma of tumor nests correlated well with the progression of clinical stage and the presence of metastasis. This correlation could not be found in the peripheral region of the tumor nests. Macrophages and NK cells were infrequently observed only in the peripheral region of ductal carcinoma. T cell infiltration was prominent in medullary carcinoma with lymphocyte infiltration (MC), and macrophages, NK cells, and T zone histiocytes were frequently encountered. For the purpose of knowing the activity of T cells, IL-2 receptor (Tac) and transferrin receptor were examined immunohistochemically. The fact that a few activated T cells were found only in the peripheral region of tumor nest suggested the local immune response in ductal carcinoma not to be so active as to reject the tumor cells. Since numerous activated T cells were recognized in the tumor nests of MC, this type of breast carcinoma was thought to have a higher immune reactivity. There was little evidence indicating NK cells to play a role for natural cytotoxicity in breast carcinoma.

Adenocarcinoma, Mucinous↗

Ileal atresia and absence of appendix.

A case of ileal atresia with absence of vermiform appendix in a female newborn is reported. At the region about 105 cm from the Treitz's arch, intestinal atresia was observed with an associated V-shaped deformity of the mesentery. Polyp-like protuberance was observed in the area a few centimeters from the blind end of the distal intestine. Histologically, keratinizing squamous cells, bile pigments, lanugo hair, and alcian-blue stained materials and cells were observed in the serosal layer of the tip of the proximal blind segment and mesenterium connecting to this portion. Thrombi were not observed in the mesenterium connecting to the proximal blind segment, gap segment, and distal blind segment. Squamous cells and lanugo hair were found in the green meconium taken from the large intestine. Polyp-like protuberance was surfaced by normal intestinal mucosa, and in its inside there were two layers consisting of folded muscular tissue. In this report, we describe the detailed pathology of ileal atresia and discuss its possible cause.

Abnormalities, Multiple↗

Effect of moxalactam on human fecal microflora.

Five healthy male adults received 2 g of moxalactam every 12 h for 7 days. The alterations of fecal microflora were investigated before, during, and after treatment with moxalactam. On day 7 of treatment, the number of total bacteria was decreased in all subjects. There was marked suppression of the obligate anaerobic bacteria and enterobacteria to undetectable levels, but the counts of Streptococcus spp. and Lactobacillus spp. increased. On day 7, two subjects had Clostridium innocuum and Clostridium ramosum in their feces but not Clostridium difficile. On day 7 after treatment, the counts of Streptococcus spp., enterobacteria, Lactobacillus spp., and Clostridium spp. in all subjects were still not normal.

Adult↗

In vitro activity of ME1401, a new antifungal agent.

The in vitro antifungal activity of ME1401, a potential topical antifungal agent, was compared with that of haloprogin, clotrimazole, miconazole, tolnaftate, and ciclopirox olamine by using an agar dilution procedure. ME1401 showed a broad antifungal spectrum and inhibited all of the 428 strains of 52 species of pathogenic yeasts and filamentous fungi tested at concentrations ranging from 0.01 to 12.5 micrograms/ml. In general, the activity of ME1401 was comparable or superior to that of clotrimazole and was greater than that of haloprogin and the other reference drugs under the conditions used. Only tolnaftate was superior to ME1401 in its activity against clinical isolates of Trichophyton rubrum. ME1401 showed no cross-resistance with any of the reference drugs and exhibited potent fungicidal activity.

Antifungal Agents↗

Possible model of liver carcinogenesis using inhibitors of NAD+ ADP ribosyl transferase in rats.

The response of cellular NAD+ metabolism to DEN and/or ABA and the carcinogenesis of the liver initiated by DEN and ABA were studied in rats. The liver NAD+ level was depleted by an ip injection of 20 mg or 200 mg/kg body weight of DEN. ABA, administered ip at a dose of 600 mg/kg simultaneously with or 4 hours after DEN, prevented the depletion of NAD+ by DEN. These biochemical findings correlated with the changes of conspicuous intranuclear immunofluorescence of poly(ADP-ribose), which were studied by immunohistochemistry. When initiated by 20 mg/kg body weight DEN and 600 mg/kg ABA and then processed to selection pressure, the liver was found to be capable of developing hepatocellular carcinomas with or without PB promotion. These results suggest that the inhibition of poly(ADP-ribosylation) might lead to irreversible initiation of liver carcinogenesis by DEN in rats.

Animals↗

Effects of angiotensin II, adrenocorticotropin, and potassium on aldosterone production in adrenal zona glomerulosa cells from streptozotocin-induced diabetic rats.

Hyporeninemic hypoaldosteronism has been shown to occur in streptozotocin-induced chronic diabetic rats with normokalemia. To test the nature of the aldosterone deficiency, we investigated the responses of aldosterone production to angiotensin II (AII), ACTH, and potassium in adrenal zona glomerulosa cells from diabetic rats at 6 weeks after an injection of streptozotocin compared with those in the cells from control rats. In diabetic rats, plasma glucose was high and plasma immunoreactive insulin was low. Diabetic rats also had low levels of PRA and plasma AII, low levels of plasma aldosterone, and normal levels of plasma corticosterone and plasma potassium. The zona glomerulosa width was narrower in diabetic rats than in control rats. Basal aldosterone production, when corrected to an uniform number of cells per group, was similar in the cells from control and diabetic rats. Cells from diabetic rats showed a less sensitive and lower response of aldosterone production to AII, increases in the threshold and the ED50, and a decrease in the maximal AII-stimulated aldosterone level. ACTH, however, caused a similar effect on aldosterone production in the cells from control and diabetic rats. Cells from diabetic rats exhibited a less sensitive response of aldosterone production to potassium and a tendency to be low in the maximal potassium-stimulated aldosterone level, presumably attributable to the impairment of adrenal zona glomerulosa cells to AII. We conclude that the hypoaldosteronism observed in our diabetic rats may be secondary to the deficiency of AII.

Adrenal Glands↗

Effects of castration and testosterone administration on serum lipoproteins and their apoproteins in male spontaneously hypertensive rat.

Serum triglyceride and very low density lipoprotein (VLDL) concentrations were higher in male spontaneously hypertensive rat than in male control Wistar Kyoto rat, whereas serum cholesterol, phospholipids, and high density lipoprotein (HDL) concentrations were lower. Castration of hypertensive rats induced an increase in serum cholesterol, phospholipids, and HDL, and a decrease in serum triglyceride and VLDL. The cholesterol content of HDL increased, whereas the triglycerides decreased after gonadectomy of hypertensive rats. These changes in serum lipids and lipoproteins could be reversed by the administration of testosterone. Apolipoprotein E contents in VLDL and HDL of hypertensive rats were low when compared with control rats but rose after castration and could be reduced by testosterone administration. Hypertensive rats accumulated triglycerides and cholesterol in the liver, which resulted in an increase of liver weight. Castration reduced the hepatic lipids as well as liver weight. The effects of castration and testosterone treatment on lipids and lipoproteins were more prominent in spontaneously hypertensive rats than in control rats. These results suggest that testosterone reduces VLDL catabolism which is related to changes of apolipoprotein composition, and that hypertensive rats are more sensitive to testosterone than control rats.

Animals↗

Responsiveness of hypophyseal-adrenocortical axis to repetitive administration of synthetic ovine corticotropin-releasing hormone in patients with isolated adrenocorticotropin deficiency.

The primary lesion site in isolated ACTH deficiency was studied in three patients by examining the responses of immunoreactive ACTH to insulin-induced hypoglycemia, lysine vasopressin, and synthetic ovine corticotropin-releasing hormone (CRH). In all patients, no significant changes in immunoreactive ACTH followed insulin-induced hypoglycemia or lysine vasopressin. Fifty micrograms (greater than or equal to 1 microgram/kg BW) of CRH administered as an iv bolus dose daily for 6 consecutive days elicited no significant increase in plasma immunoreactive ACTH, beta-lipotropin, or cortisol levels in all patients. Eight iv bolus injections of 0.63 microgram/kg BW CRH at 4-h intervals also failed to induce a significant response of immunoreactive ACTH to an iv bolus dose of 1 microgram/kg CRH at 36 h in one patient. In contrast, a single bolus dose of 50 micrograms CRH induced a response of plasma immunoreactive ACTH in a patient with Cushing's disease and a patient with Addison's disease. The present results suggest that the primary lesion of isolated ACTH deficiency is not the hypothalamus, but, rather, is located in pituitary ACTH-secreting cells.

Addison Disease↗

Effects of vitamin K-deficient diets and fasting on blood coagulation factors in conventional and germ-free rats.

Feeding of vitamin K-deficient diets or fasting produced vitamin K deficient syndromes in both conventional and germ-free male rats in 3 days, increasing prothrombin time (PT), activated partial thromboplastin time (APTT), plasma and liver descarboxyprothrombin (PIVKA) levels and liver gamma-glutamylcarboxylase activities, but decreasing plasma clotting factor VII and prothrombin levels. These changes were not found when daily 30 micrograms/rat of vitamin K1 was injected during this period. The changes caused by fasting were comparable with those caused by a diet containing 20-30 ng/g of vitamin K1, while a diet containing less than 5 ng/g caused greater changes in both conventional and germ-free rats. Germ-free rats on a diet containing sufficient amounts of vitamin K1 showed PT and APTT values similar to those in conventional rats, but lower plasma clotting factor levels and higher PIVKA and microsomal gamma-glutamylcarboxylase activities. The values for PT, APTT, factor VII, prothrombin and PIVKA in the fasted germ-free rats were almost the same as those in the fasted conventional rats. These findings suggest that menaquinones synthesized in the large intestine are not utilized sufficiently to prevent vitamin K deficiency in rats.

Animals↗

Effects of antibiotics on fibrinolytic activity.

Latamoxef, cefamandole, carbenicillin and cefotaxime were examined for their effects on fibrinolytic activity in vitro by means of the fibrin plate method, fibrin clot lysis time and euglobulin lysis time with human, rabbit and rat plasma. These antibiotics showed no fibrinolytic but weak antifibrinolytic activity at 1000 or 3000 micrograms/ml in some assay systems.

Animals↗

Effect of angiotensin II on aldosterone and its precursor steroid production in adrenal zona glomerulosa cells from heparin-treated rats.

To assess the nature of the heparin-induced aldosterone deficiency, we investigated the stimulatory effect of angiotensin II (AII) on aldosterone and its precursor steroids in adrenal zona glomerulosa cells from heparin-treated rats compared with those in the cells from vehicle-treated rats. Heparin-treated rats had low plasma aldosterone levels, high plasma renin activity and plasma AII levels, and normal plasma corticosterone level 6 weeks after the treatment (1500 IU/kg, twice daily). Basal aldosterone production, when corrected to a uniform number of cells per group, was similar in the cells from heparin- and vehicle-treated rats. The cells from heparin-treated rats had a less sensitive and lower response of aldosterone production to AII; an increase by 4 orders of magnitude in the threshold dose for AII and a decrease in the maximum AII-stimulated level. The maximum AII-stimulated levels, but not the basal levels, of pregnenolone, corticosterone and 18-OHB production were low in the cells from heparin-treated rats. ACTH caused a similar stimulatory effect on aldosterone production in the cells from heparin- and vehicle-treated rats. The cells from heparin-treated rats had a less sensitive and lower response of aldosterone production to potassium; an increase by one order of magnitude in the threshold dose for potassium and a decrease in the maximum potassium-stimulated level, presumably because of the glomerulosa hyporesponsiveness to AII. These results suggest that our heparin-treated rats have selective impairment of adrenal zona glomerulosa cells, involving the specific receptors and the aldosterone biosynthesis, to AII.

18-Hydroxycorticosterone↗

Aclarubicin in the treatment of elderly patients with acute nonlymphocytic leukemia.

Thirteen previously untreated patients aged 70 and above with acute nonlymphocytic leukemia were treated with aclarubicin (ACR) alone. Among 10 cases (3, acute myelocytic leukemia; 4, acute myelomonocytic leukemia; 2, acute monocytic leukemia; and one, acute erythroleukemia) in which an evaluation was possible, 5 cases (3, acute myelomonocytic leukemia; and 2, acute monocytic leukemia) obtained complete remission (CR). The CR rate was 83% in 6 patients with acute myelomonocytic leukemia or acute monocytic leukemia. The median CR duration and survival was 7.5 and 10 + months, respectively. Although side effects of the drug on digestive system such as nausea, vomiting and anorexia were observed in all patients, they were controllable by conventional treatments. The results suggest that ACR is effective for the clinical management of elderly patients with acute nonlymphocytic leukemia, especially those with acute myelomonocytic leukemia or acute monocytic leukemia.

Aclarubicin↗

Simultaneous measurement of cardiac output and pulmonary diffusing capacity for CO by a rebreathing method.

A rebreathing method was developed to obtain the pulmonary diffusing capacity for CO, DL(CO) and the cardiac output, Q, simultaneously at rest and during exercise. From DL(CO) and Q, contact time of the red blood cell (RBC) through the lung capillary, tc, was estimated by referring to a reaction rate factor of CO with RBC, Fc(CO). The DL(CO) and Q were calculated from the changes in CO, O2, and CO2 concentrations in rebreathing air. The Fc(CO) was evaluated so as to attain a proportional relation between the DL(CO) and Fc(CO) by varying a transfer coefficient for CO across the RBC boundary including the capillary wall. The PO2 dependence of Q was also taken into account in the above analyses. The tc was determined by dividing the DL(CO) by Fc(CO), Q, and fractional hematocrit. The DL(CO) and Q measured in five normal subjects in a sitting position were 26.6 +/- 2.9 ml X min-1 X Torr-1 and 5.9 +/- 0.6 l X min-1 (mean +/- S.D.), respectively, which increased during moderate exercise up to 34.6 +/- 3.9 ml X min-1 X Torr-1 and 13.0 +/- 1.2 l X min-1. The tc was 0.70 +/- 0.06 s at rest and 0.40 +/- 0.05 s during exercise. The rebreathing method for measuring DL(CO) was more advantageous than the single breath method, because the tc could be obtained as well as the Q and the influence of the dead space and ventilation-perfusion uneveness on DL(CO) was reduced.

Carbon Monoxide↗

Change in O2 uptake during rebreathing in hyperoxia in man.

In pertaining to PO2 dependency of the pulmonary CO diffusing capacity during rebreathing, the O2 uptake (VO2) and cardiac output (Q) were measured at three different PO2 levels between 100 and 500 Torr. Since the VO2 measured by an O2 injection method is strongly influenced in hyperoxia by a gas exchange ratio (R), a simulation method using a R-PCO2 relation during rebreathing was developed. Gas volume in the lung-bag-system needed in the computation was measured from the difference in O2 concentration between before and after injecting a known amount of O2 into the rebreathing circuit. The accuracy of the volume was checked by comparing it with the volume measured successively with a body box. The VO2 was determined by comparing the simulated O2 and CO2 concentrations in rebreathing gas with the measured ones. The VO2 significantly increased by rebreathing in hyperoxia. To analyze the VO2 increase, the Q was computed by dividing the VO2 by the arteriovenous O2 content difference, which in turn was obtained by dividing the slope of the CO2 dissociation curve by that of the R-PCO2 line. The Q was almost linearly related to the VO2. Since there was no difference in VO2 in steady state breathing between normoxia and hyperoxia, the increase in VO2 and Q seemed to occur transiently. This finding is very important in evaluating the PO2 dependency of the pulmonary diffusing capacity for CO.

Adult↗