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Biomedical subjects

Y S Do

Publications and source records attributed to Y S Do.

At least 73 records · Page 4Linked to original sources
PubMed1988

Mechanisms of hyperkalemia in systemic lupus erythematosus.

We found that nearly 10% of 142 patients with systemic lupus erythematosus (SLE) had persistent, unexplained hyperkalemia. Renal mineralocorticoid resistance has been suggested to account for the hyperkalemia in SLE. We studied the renin-aldosterone response to intravenous furosemide (60 mg) and upright posture and the renin response to converting enzyme inhibition (captopril, 50 mg) and upright posture in five patients with SLE and hyperkalemia (group 1) and five normokalemic patients with SLE (group 2). Renal function was comparable. Plasma chloride level was higher and bicarbonate level slightly lower in group 1 than in group 2. Plasma cortisol level was normal in all patients. None of the patients was receiving nonsteroidal anti-inflammatory drugs or corticosteroids at the time of study. Basal plasma renin concentration and plasma aldosterone level were not significantly different between the two groups, although both tended to be higher in group 2. However, four of the five patients in group 1 had significantly blunted renin response to captopril compared with group 2. The same four patients also had blunted renin and aldosterone responses to furosemide. Thus, the majority of hyperkalemic patients with SLE had an impaired renin and aldosterone response to stimulation. We conclude that hyporeninemic hypoaldosteronism plays a key role in the pathogenesis of hyperkalemia in SLE.

Adult↗
PubMed1987

Characterization of pure human renal renin. Evidence for a subunit structure.

Renin was completely purified from human kidney cortex employing a rapid three-step procedure which included homogenization and ammonium sulfate precipitation, aminohexyl-pepstatin affinity chromatography, and affinity chromatography using a synthetic octapeptide renin inhibitor (H-77) with a reduced peptide bond (-CH2-NH- instead of -CO-NH-) between Leu5-Leu6, Three kg of cortex dissected from 10 kg of human cadaver kidney yielded 1.7 +/- 0.5 mg of protein (mean +/- S.E. for five procedures) with a specific activity of 1094 +/- 166 Goldblatt units/mg of protein and an overall recovery of 52 +/- 2%. Both gel filtration high performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed a molecular weight of 44,000, although Mr = 22,000 and 18,000 bands were also identified by SDS-PAGE. The pH optima with sheep angiotensinogen were 5.5 and 7.8 and the Km was 0.31 microM. With pure human substrate the pH optimum was 6.0 and the Km was 1.15 microM. Enzyme activity was inhibited by two different anti-human renal renin antibodies. Amino-terminal sequencing demonstrated a leucine residue at the 1-position. Sequencing of 15 additional amino acids agreed with that predicted from the gene sequence and indicated that prorenin is converted to renin following cleavage at the carboxyl end of two basic residues, Lys-2 Arg-1. As with SDS-PAGE analysis, high performance liquid chromatography in the presence of 6 M urea demonstrated Mr = 44,000, 22,000, and 18,000 bands. Immunoblot studies revealed that all of these bands cross-reacted with antihuman renin antibody. Amino-terminal sequencing indicated the Mm = 22,000 band is the amino terminus and the Mr = 18,000 band the carboxyl terminus of Mr = 44,000 renin. In the aqueous phase, these subunits bound to H-77 suggesting that they represent components of the active enzyme complex. Unlike mouse renin, there was no evidence of disulfide bonds. These results raise the question of whether human renin circulates as a subunit aggregation as well as a single chain protein. This may serve as a possible mechanism to regulate renin activity in plasma and tissues.

Amino Acid Sequence↗
PubMed1987

Increased fetoplacental active renin production in pregnancy-induced hypertension.

Since pregnancy-induced hypertension is associated with impaired uteroplacental blood flow, we studied fetoplacental and maternal renin production in controls and subjects with pregnancy-induced hypertension. We measured total, active, and inactive (pro-) renin in maternal serum, fetal arterial and venous blood, and chorion homogenate in eight normotensive term patients and 18 patients with pregnancy-induced hypertension. No differences in active or prorenin were found in maternal blood from normal women or patients with pregnancy-induced hypertension. In contrast, fetal artery and vein, as well as chorionic tissue, contained significantly higher active renin in pregnancy-induced hypertension compared with normal subjects. No difference in fetal or chorionic prorenin was seen in the two groups. Thus active to total renin ratio was higher in the fetus and chorion of subjects with pregnancy-induced hypertension, which suggests enhanced active renin production. These results suggest that pregnancy-induced hypertension is associated with increased activity of the renin-angiotensin system in the fetoplacental unit, which is not reflected in the maternal circulation. This may be an attempt by the fetus and chorionic membranes to maintain vascular homeostasis in the face of altered uteroplacental blood flow.

Enzyme Precursors↗
PubMed1986

Complete purification of human renal renin and sequence of the amino terminus.

Renin was completely purified from human kidney cortex using a rapid 3-step procedure which included homogenization and ammonium sulfate precipitation, aminohexyl pepstatin affinity chromatography, and affinity chromatography using a synthetic octapeptide renin inhibitor (H-77) with a reduced peptide bond between Leu5 - Leu6. Three kg of cortex dissected from 10 kg of human cadaver kidney yielded 0.7 mg protein with a specific activity of 1123 GU/mg protein and an overall recovery of 52%. Both gel filtration high pressure liquid chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) revealed a molecular weight of 44,000, although 22,000 and 18,000 molecular weight bands were also identified by SDS PAGE. Amino terminal sequencing demonstrated a leucine residue at the 1 position indicating that prorenin is converted to renin following cleavage at the carboxyl end of two dibasic residues, Lys-2-Arg-1. Sequencing of the first 19 amino acids was in agreement with the sequence deduced from human renin cDNA sequence.

Amino Acid Sequence↗
PubMed1986

Uteroplacental unit as a source of elevated circulating prorenin levels in normal pregnancy.

Circulating levels of inactive renin, that is, prorenin, are increased in normal pregnant women. To determine whether the uteroplacental unit secretes prorenin into the maternal circulation, we measured enzymatically active and inactive renin in plasma simultaneously obtained from the radial artery and uterine vein of 12 normotensive, nonlaboring patients undergoing elective cesarean section at term. We also measured these forms of renin in the umbilical arterial and venous blood of these patients. Our data reveal that the levels of inactive renin in both arterial and uterine venous blood of normal pregnant women are significantly higher than in peripheral venous blood of nonpregnant, normotensive control subjects; normotensive term patients have a ratio of plasma inactive to active renin of 9:1 in contrast to the 1:1 ratio in normotensive nonpregnant subjects; there is a significant uterine arteriovenous difference of prorenin (66.2 +/- 24.4 ng/ml/hr, p less than 0.05) but not of active renin (1.8 +/- 1.5 ng/ml/hr, not significant). These results suggest that the uteroplacental unit contributes to the elevated prorenin levels at term pregnancy.

Cesarean Section↗
PubMed1986

Biochemical similarity of expressed human prorenin and native inactive renin.

Prorenin is secreted by mammalian cells transfected with a human preprorenin expression construct. The purpose of this investigation was to compare the physicochemical properties of expressed prorenin in culture medium with the known characteristics of human inactive renin, which accounts for nearly half the renin in plasma and kidney. We found that expressed human prorenin strongly resembles human renal and plasma inactive renin. The expressed prorenin was inactive and could be equally activated by acid (dialysis to pH 3.3) or trypsin. Acid activation was completely reversible; reexposure to acid could reactivate the expressed inactive renin. Exposure to cold (-5 degrees C for 3 days) could also activate expressed renin. The Michaelis-Menten constant of acid-activated expressed renin with sheep substrate was 0.29 microM, and the pH optimum was 7.8. Expressed inactive renin bound to a cibacron-blue affinity column and could be eluted with 0.5M NaCl. All the above characteristics resemble those of human renal and plasma inactive renin. In addition, the molecular weight of expressed prorenin and human chorionic renin was 47,000, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and 46,000, as measured by high-performance liquid chromatography. These data, taken together with the published observation that native human inactive renin cross-reacts with antibodies generated against amino acid sequences in the prosegment of renin, provide strong support for the hypothesis that human inactive renin is prorenin.

Cold Temperature↗
PubMed1984

Saccharomyces cerevisiae produces a yeast substance that exhibits estrogenic activity in mammalian systems.

Partially purified lipid extracts of Saccharomyces cerevisiae contain a substance that displaces tritiated estradiol from rat uterine cytosol estrogen receptors. The yeast product induces estrogenic bioresponses in mammalian systems as measured by induction of progesterone receptors in cultured MCF-7 human breast cancer cells and by a uterotrophic response and progesterone receptor induction after administration to ovariectomized mice. The findings raise the possibility that bakers' yeast may be a source of environmental estrogens.

Animals↗
PubMed1980

Demonstration of glucocorticoid receptors in the adrenal cortex: evidence for a direct dexamethasone suppressive effect on the rat adrenal gland.

The adrenal cortex was evaluated for the presence of glucocorticoid receptors and functions. Substantial binding of [3H]dexamethasone was observed in aminoglutethimide-treated, hypophysectomized, and intact rats. Further studies demonstrated binding in cultured bovine adrenocortical cells and in Y-1 cells, a cloned murine cell line of adrenal cortical origin. Scatchard analysis of specific binding data in cytosol from hypophysectomized rats revealed an apparent Kd of approximately 15 nM and a receptor content (Nmax) of 123 fmol/mg cytosol protein. Analysis of Y-1 cell cytosol showed a Kd of approximately 17 nM and Nmax of 190 fmol/mg protein. The binding site in hypophysectomized rats had the following steroid specificities: high affinity for dexamethasone, corticosterone, and progesterone; moderate affinity for 11 beta-cortisol, and low affinity for testosterone, estradiol, pregnenolone, and 11 alpha-cortisol. Sedimentation in sucrose density gradients revealed 8S binding peaks in cytosols prepared from intact rat adrenal glands, Y-1 cells, and cultured bovine adrenocortical cells. Time- and temperature-dependent nuclear uptake of [3H]dexamethasone in Y-1 cells was demonstrated. In vivo treatment of hypophysectomized rats with dexamethasone significantly enhanced the rate of adrenal atrophy. ACTH stimulation tests in hypophysectomized rats showed a decreased corticosterone response in dexamethasone-treated rats compared to that in control animals. However, in vitro, there was no evidence for an effect of dexamethasone on ACTH-stimulated corticosterone production. The data indicate that the adrenal cortex possesses a high affinity binding site that fulfills the criteria for a glucocorticoid receptor. Glucocorticoid administration enhances adrenal atrophy and impairs adrenal function. We speculate that this action contributes to the suppressive effect of glucocorticoids on the pituitary-adrenal axis.

Adrenal Cortex↗
PubMed1979

Synthesis and secretion of corticosteroid-binding globulin by rat liver. A source of heterogeneity of hepatic corticosteroid-binders.

Classical glucocorticoid receptors (type II) have a high affinity for synthetic and natural glucocorticoids. We have previously demonstrated an additional binding site in kidney cytosol (type III) which has a high affinity for corticosterone but a low affinity for dexamethasone. In many ways, this binder resembles plasma corticosteroid-binding globulin (CBG). The first goal of this study was to determine the organ distribution of the type III binding sites. Cytosol was prepared from isolated cells to avoid plasma contamination. Of the tissues examined, type III sites were found only in liver and kidney; sites were absent from thymocytes, IM-9 lymphocytes, adipocytes, and bone cells. The second goal of this study was to ascertain whether CBG is synthesized in liver and kidney. Liver and kidney slices were incubated in vitro and the concentration of type III sites was seen to rise in hepatic cytosol and incubating medium but not kidney. To verify the impression that liver was synthesizing and secreting CBG, the following experiments were performed: (a) To demonstrate that type III sites were CBG, steroid-binding profiles and migration on polyacrylamide gel electrophoresis were shown to be identical for hepatic type III sites and serum. (b) To indicate that the rise in type III sites was dependent on protein synthesis, it was shown that cycloheximide blocked the appearance of new type III sites. (c) To establish that the type III sites were being secreted, in situ liver perfusion experiments showed time-dependent release of new sites into the perfusate. In conclusion, liver synthesizes and secretes type III sites, a finding previously suspected but never proved. The presence of type III sites in kidney remains to be explained.

Animals↗
PubMedDate not supplied

Radiological prediction of the depth of invasion and histologic type in early gastric cancer.

In cases of early gastric cancer (EGC), the depth of tumor invasion and histologic type are important factors in its prognosis. To predict the depth of invasion and histologic type by a double-contrast barium study of the stomach, 304 consecutive patients with EGC were analyzed, comparing barium study with pathologic findings. We predicted the depth of invasion and histologic type according to the lesion size, surface pattern, and surrounding mucosal pattern. The depth of tumor invasion was correctly diagnosed in 65.3% (66 of 101) of cancers limited to the mucosal layer (m), and in 59.1% (110 of 186) of cancers which have invaded to the submucosal layer (sm). The histologic type was correctly predicted in 78.9% (56 of 71) of a differentiated adenocarcinoma, and 73.1% (57 of 78) of an undifferentiated adenocarcinoma. Prediction of the depth of tumor invasion and histologic type was promising and showed good correlation to the pathologic findings.

Adenocarcinoma↗
PubMedDate not supplied

Obstructive jaundice in gastric carcinoma: cause, site, and relationship to the primary lesion.

OBJECTIVE: Obstructive jaundice is frequently present in patients with advanced gastric carcinoma. The purpose of this study was to assess the cause and preferential site of bile duct obstruction in patients with gastric carcinoma and to evaluate correlativity of biliary obstruction with the nature of the primary gastric lesion. METHODS: Cholangiographic findings of 54 patients with metastatic gastric carcinoma presenting with obstructive jaundice were reviewed retrospectively. The level of the bile duct obstruction was divided into four segments: segment 1, from an individual intrahepatic duct to the biliary hilum; segment 2, common hepatic duct (CHD) involvement from the biliary hilum to the level of the cystic duct; segment 3, the proximal half of the common bile duct (CBD); segment 4, the distal half of the CBD. To evaluate the characteristics of the primary gastric lesion, operative records and pathologic findings were reviewed. RESULTS: Obstruction sites were segment 1 in eight patients (15%), segment 2 in 25 (46%), segment 3 in 17 (32%), and segment 4 in four (7%). The causes of obstruction were metastatic lymphadenopathy in the hepatoduodenal ligament (50 of 54) and direct invasion of the primary or recurrent tumor (four of 54). The location of the primary gastric lesions was the antrum, antrum and body, and body in 36 (67%), 17 (31%), and 1 (2%), respectively. Borrmann type 3 lesions were present in 72% of cases, and type 2 lesions in the remaining 24%. Histologic type was undifferentiated adenocarcinoma in 91% of patients, and differentiated adenocarcinoma in the remaining. Serosal invasion was shown in 96% of the patients. CONCLUSION: Our results show that the cause of bile duct obstruction in advanced gastric carcinoma is predominantly metastatic lymphadenopathy in the hepatoduodenal ligament, and its preferential site is around the level of the cystic duct. Obstructing lesions showed characteristic cholangiographic findings.

Adenocarcinoma↗
PubMedDate not supplied

Transjugular liver biopsy: modified Ross transseptal needle versus quick-core biopsy needle.

BACKGROUND: We evaluated the differences in sample adequacy and safety between a transseptal needle and Quick-core biopsy needle for transjugular liver biopsy. METHODS: Eighteen consecutive patients who had a bleeding diatheses and/or ascites underwent transjugular liver biopsy using a transseptal needle (11 patients) and Quick-core biopsy needle (seven patients). The length of the specimens was measured before fixation. A pathologist reviewed histologic slides for sample adequacy and pathologic diagnoses. Clinical records were reviewed for complication. RESULTS: In all patients, liver biopsy was successful. A total of 45 specimens were obtained, with an average of 2.5 passes per patient. The length of specimen was significantly longer with the Quick-core biopsy needle than with the transseptal needle (p<0.05). Biopsied tissue was fragmented in 17 of 25 specimens with the transseptal needle but not fragmented in any specimen with the Quick-core biopsy needle. All specimens were determined to be adequate except one with the transseptal needle. There was no early or delayed complication in any patient. CONCLUSION: Transjugular liver biopsy is a safe and effective procedure without any significant difference in complication and adequacy when using a transseptal needle or Quick-core biopsy needle. Larger specimens can be obtained without tissue fragmentation with the Quick-core biopsy needle.

Adolescent↗
PubMedDate not supplied

New self-expandable spiral metallic stent: preliminary clinical evaluation in malignant biliary obstruction.

PURPOSE: To describe a new self-expandable spiral-shaped metallic stent and to evaluate its clinical efficacy in malignant biliary obstructions. PATIENTS AND METHODS: The stent was made of a 0.01-inch (0.25-mm) stainless steel wire bent in a zigzag pattern and was formed into a spiral configuration by differing the length of legs on each bend. One revolution was composed of 10 bends, and the stent was longitudinally connected by hanging each bending point of abutting bends, without use of suture or silver solder. Twenty-six stents were placed to relieve malignant biliary obstruction in 18 patients. Follow-up of 5-11 months (mean, 7 months) was obtained. RESULTS: All stents were placed in the desired location, and no procedural complications were encountered. Within 1 week after placement, all stents regained 90% or more of their original diameters. Five patients died (range, 5-36 weeks), and 13 patients are still alive (range, 20-45 weeks). Two patients experienced recurrent jaundice and underwent further treatment. The stent was easily inserted, expanded well, was flexible, could be repositioned, and did not shorten. CONCLUSION: Favorable clinical results were obtained with this spiral stent in malignant biliary obstruction, and further clinical testing is warranted.

Adult↗