Biomedical subjects

Y S Do

Publications and source records attributed to Y S Do.

At least 55 records · Page 3Linked to original sources

PubMed1994

Stage IIb cervical carcinoma: MR evaluation of effect of intraarterial chemotherapy.

PURPOSE: To evaluate magnetic resonance (MR) imaging in assessment of tumor response after intraarterial chemotherapy (IAC) in cervical carcinoma. MATERIALS AND METHODS: MR images of 19 patients who underwent IAC because of stage IIb cervical carcinoma were prospectively analyzed and compared with pathologic findings. Three courses of IAC were administered, and MR images were obtained before and after treatment. Extent of reduction of tumor volume determined eligibility for surgery. MR images of 17 patients who were candidates for surgery were correlated with pathologic specimens. RESULTS: Average reduction in tumor volume was 88.5%. Response to IAC was complete in seven patients, partial in 11, and minor in one. MR imaging findings after IAC correlated well with pathologic findings. CONCLUSION: MR imaging is useful in assessment of tumor response to IAC and provides criteria for decision making with regard to further radiation or surgical therapy.

Adult↗

PubMed1994

Covered, expandable esophageal metallic stent tubes: experiences in 119 patients.

PURPOSE: To study fluoroscopic placement of covered expandable stent tubes in patients with esophagogastric strictures. MATERIALS AND METHODS: Under fluoroscopic guidance, 132 stent tubes were placed in 116 patients with malignant neoplasm; four, in three patients with benign lesions. All patients had aphagia or dysphagia to soft food or liquid. RESULTS: After placement (successful in 100% of cases), 93 (78%) of the patients could ingest solid food; 24 (20%), soft food. Complications in the 119 patients included blockage in 13, stent tube migration in 12, gastroesophageal reflux in nine, severe pain in nine, and delayed massive bleeding in four. Most major complications were managed by means of a balloon catheter, a second stent tube, or analgesics. One hundred four patients died 2-80 weeks after stent placement. CONCLUSION: Treatment with placement of a covered expandable stent tube is effective in most patients with dysphagia due to malignant esophogastric strictures and is less effective in patients with benign strictures.

Catheterization↗

PubMed1993

Plasma cyclic guanosine monophosphate in chronic heart failure: hemodynamic and neurohormonal correlations and response to nitrate therapy.

This study evaluated the relation between plasma cyclic guanosine monophosphate (cGMP) and hemodynamic and neurohormonal parameters in patients with chronic congestive heart failure and assessed the effect of organic nitrate on plasma cGMP levels. Plasma cGMP was fourfold higher in 18 patients with congestive heart failure compared with 15 control subjects (16.7 +/- 9.7 versus 4.0 +/- 1.0 pmol/ml; p < 0.0001) but did not correlate with plasma levels of catecholamines, renin, atrial natriuretic peptide, or with baseline hemodynamic values. The administration of a hemodynamically effective dose of oral isosorbide dinitrate (40 mg) resulted in a transient reduction in plasma cGMP from 16.7 +/- 9.7 pmol/ml at baseline to 13.0 +/- 6.6 pmol/ml at 1 hour (p < 0.05). This change was associated with small and statistically insignificant changes in neurohormonal values and had no relation to any of the hemodynamic changes. We concluded that (1) elevated plasma cGMP in congestive heart failure does not correlate with other neurohormonal or hemodynamic parameters and may be an independent parameter of heart failure, (2) in contrast to previously documented nitrate-mediated increases in intracellular cGMP, nitrate therapy results in a reduction in plasma cGMP, and (3) changes in plasma cGMP cannot serve as a surrogate measurement of changes in intracellular cGMP.

Administration, Oral↗

PubMed1993

Esophagorespiratory fistula associated with esophageal cancer: treatment with a Gianturco stent tube.

A self-expanding silicone-covered tube constructed of Gianturco stents was used for palliative treatment of esophagorespiratory fistula related to esophageal carcinoma in eight patients. All eight were unable to swallow food or water before treatment. The tubes were inserted under fluoroscopic guidance, without technical failure or complication. Clinical improvement was determined by grading food intake capacity on a five-point scale: none, liquid, soft food, most food, or all food. After the procedure, all fistulas were occluded. Four patients could swallow most foods, two could swallow soft food, one could swallow all foods, and one (who died of preexisting pneumonia 10 days after the procedure) could manage only liquids. Three patients were surviving without symptoms of aspiration for 4-24 weeks. Four patients died 6-16 weeks after placement of the stent tubes. Insertion of a silicone-covered stent tube was an effective palliative treatment for esophagorespiratory fistulas caused by esophageal cancer.

Bronchial Fistula↗

PubMed1993

Angiotensin II causes mesangial cell hypertrophy.

Angiotensin II, a potent vasoconstrictor and known growth factor for vascular smooth muscle cells, has been implicated in the development of glomerulosclerosis. Because mesangial cell growth plays a critical role in the glomerulosclerotic process, the objective of this study was to determine the direct effect of long-term (48-hour) angiotensin II treatment on the growth of cultured murine mesangial cells. Subconfluent, quiescent adult murine mesangial cells were treated for 48 hours with media containing angiotensin II with and without its specific inhibitor losartan. In comparison to cells treated with serum-free medium, cells treated with serum plus insulin demonstrated a significant increase in cell number (1.93 +/- 0.1 times control, p < 0.05), [3H]thymidine incorporation per 10(5) cells (2.29 +/- 0.12 times control, p < 0.05), [3H]leucine incorporation per 10(5) cells (1.81 +/- 0.18 times control, p < 0.05), and total protein content per 10(5) cells (1.65 +/- 0.07 times control, p < 0.05). In contrast, cells treated with angiotensin II (10(-6) M) had no significant increase in cell number (0.84 +/- 0.01 times control) or [3H]thymidine incorporation per 10(5) cells (1.23 +/- 0.12 times control) but demonstrated a significant increase in [3H]leucine incorporation per 10(5) cells (1.61 +/- 0.09 times control) and total protein content per 10(5) cells (1.38 +/- 0.04 times control). Pretreatment with losartan blocked 56% of the angiotensin II-induced increase in [3H]leucine incorporation and 84% of the angiotensin II-induced increase in total protein content.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1992

Purification and characterization of human truncated prorenin.

Posttranslational processing of enzymatically inactive prorenin to an active form participates in the control of the activity of a key system involved in blood pressure regulation, growth, and other important functions. The issue is complicated because renin can be produced by a number of tissues throughout the body, in addition to the kidney, but the mechanism by which they process prorenin to renin is unknown and difficult to determine because of the small amounts of renin present. In the juxtaglomerular cell of the kidney, a 43 amino acid prosegment is cleaved from the amino terminus of prorenin to generate renin of molecular weight 44,000 [Do, Y. S., Shinagawa, T., Tam, H., Inagami, T., & Hsueh, W. A. (1987) J. Biol. Chem. 262, 1037-1043]. Using human uterine lining or a recombinant human prorenin system, we employed the same approach as that used in kidney, ammonium sulfate precipitation at pH 3.1 followed by pepstatin and H-77 affinity chromatography or gel filtration, to purify to homogeneity a 45,500-MW totally active renin. The specific activity of the active truncated prorenin was 850 Goldblatt units (GU)/mg of protein for chorion-decidua renin and 946 GU/mg of protein for recombinant renin, both similar to that reported for pure human renal renin. Both forms of renin cross-reacted with an antibody generated against 44,00-MW pure human renal renin and with an antibody generated against a peptide identical to the carboxy-terminal one-third of the prosegment.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1992

Secretion of prorenin by a virilizing ovarian tumor.

A 53-year-old normotensive, normokalemic female presented with a 6-month history of virilization. Estradiol, LH, FSH, urinary-free cortisol, and DHEA-S levels were normal. Pelvic ultrasound and computerized tomography were also within normal limits. Her serum testosterone (551 ng/dl; nl, 20-70) and plasma prorenin (124 ng AI/ml/hr; nl, less than 50) levels were elevated. At surgery, a lipoid/steroid cell tumor of the right ovary was removed. Postoperative testosterone and prorenin levels were normal. Ovarian tumor cells, in culture, produced large amounts of prorenin. Immunohistochemistry localized prorenin and/or renin to tumor cells. Determining plasma prorenin levels may be a useful adjunct in diagnosing or following patients with nonepithelial ovarian tumors. A larger clinical study of prorenin levels in patients with such tumors is needed.

Adenoma↗

PubMed1991

Identification of renal cathepsin B as a human prorenin-processing enzyme.

Prorenin, the inactive biosynthetic precursor of renin, is proteolytically cleaved in the renal juxtaglomerular cells to renin. The activity of renin is rate-limiting for generation of angiotensin II in the circulation. We identified a renal thiol protease which activates and accurately cleaves the 43-amino acid prosegment of human recombinant prorenin. In the current studies, 6.5 mg of this protease was purified from human renal cortex using a three-step procedure dependent upon Leu-Leu-arginyl affinity chromatography. This represented an overall 766-fold purification and resulted in three protein bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis of molecular weights 30,000, 25,000, and 24,000. All three bands cross-reacted with an anti-human liver cathepsin B antibody upon immunoblot analysis; electrolution of each band and amino-terminal sequence analysis confirmed that the Mr 30,000 protein was mature cathepsin B and the Mr 25,000 and 24,000 bands were cathepsin B subunits. The pH optimum for the hydrolysis of pure human recombinant prorenin by pure renal cathepsin B was 6, and the Michaelis-Menten constant, Km, of the reaction was 1.4 x 10(-9) M. Immunostaining of human kidney using a sheep anti-human cathepsin B antibody demonstrated the presence of cathepsin B in the juxtaglomerular areas of the kidney, as well as in the renal proximal tubules. Electron microscopic immunohistochemistry using the same antibody demonstrated cathepsin B in dense secretory granules of the juxtaglomerular cells. Renin was also shown to be present in these granules. This study provides both biochemical and morphological evidence that renal cathepsin B is a human prorenin-processing enzyme.

Amino Acid Sequence↗

PubMed1991

Observations on the renal processing and sorting of prorenin.

Human prorenin is the biosynthetic precursor of renin. In general, prorenin is enzymatically inactive until it is converted to renin. The kidney is the major source of renin in the circulation, and is also an important source of circulating prorenin. The mechanisms of prorenin sorting and processing to renin in the juxtaglomerular cell may be a determinant of renal renin production. Therefore, our studies have focused on renal enzymes involved in "limited proteolysis" of prorenin to renin and on the morphology of prorenin sorting in the human juxtaglomerular cell.

Enzyme Precursors↗

PubMed1990

Effects of renin inhibition in systemic hypertension.

The effect of the direct renin inhibitor enalkiren (Abbott Laboratories) was examined in 8 healthy patients with essential hypertension. With an unrestricted sodium diet, plasma renin concentration was inhibited within 10 minutes by intravenous enalkiren and remained essentially undetectable for greater than or equal to 6 hours (11.9 +/- 4 to 1.0 +/- 0.6 ng angiotensin I/ml/hour, p less than 0.05). Mean arterial blood pressure declined gradually (108 +/- 5 to 84 +/- 4 mm Hg, p = 0.02), as did plasma aldosterone concentration (14.4 +/- 3.8 to 4.4 +/- 0.8 ng/dl, p = 0.03), whereas plasma immunoreactive active renin concentration increased progressively (35 +/- 14 to 160 +/- 60 pg/ml, p greater than 0.05). Urinary excretion of the stable metabolite of prostacyclin (6-keto-prostaglandin F1 alpha) decreased slightly, but not significantly (42 +/- 10 to 33 +/- 11 ng/g creatinine, p = 0.13). The addition of a diuretic decreased baseline blood pressure and increased baseline plasma renin and aldosterone values. Blood pressure responses to enalkiren were slightly (though not significantly) greater than those observed before diuretic administration. We conclude that enalkiren is effective in decreasing blood pressure and in inhibiting the renin system, without significantly altering urinary prostacyclin excretion, in patients with essential hypertension. These results suggest that the renin system contributes to the maintenance of elevated blood pressure in some patients with essential hypertension.

Adult↗

PubMed1990

Identification of an enzyme in human kidney that correctly processes prorenin.

Using pure recombinant human prorenin as a substrate, we have identified an enzyme in human kidney that accurately processes prorenin to active renin (EC 3.4.23.15). In the crude homogenate, the predominant activity of this potential renin-processing enzyme (RPE) converted the Mr 47,000 inactive prorenin to Mr 44,000 active renin and had a pH optimum of approximately 6. The activity was blocked by cysteine protease inhibitors, but not by pepstatin, EDTA, or serine protease inhibitors. This RPE activity was not detected in a similarly prepared homogenate of human chorion decidua tissue, which produces primarily prorenin, or in human plasma. The activity was purified 100-fold by ammonium sulfate precipitation, p-chloromercuribenzoate affinity chromatography, and chromatofocusing. The partially purified enzyme has a Mr of approximately 27,000 and an isoelectric point in the pH 4.8-5.6 range. The activity in the purified RPE preparation had the same pH optimum as that in crude homogenate, cleaved the prosegment at the same site used by the kidney in vivo based on amino-terminal sequencing of the processed renin, and did not degrade prorenin or renin. These data suggest that the cysteine protease we have isolated is a candidate for authentic renal RPE.

Amino Acid Sequence↗

PubMed1990

Carbon monoxide dehydrogenase inhibitor in cell extracts of Pseudomonas carboxydovorans.

Extracts of heterotrophically grown cells of Pseudomonas carboxydovorans were found to contain an inhibitor of carbon monoxide dehydrogenase (CO-DH). The inhibitor activity was not detected in CO-autotrophically grown cells. The inhibitor was extremely stable to heat treatment based on the extent of inhibition of CO-DH activity. The extent of inhibition was proportional to the amount of cell extract added to the reaction mixture. The inhibition was independent of a prior incubation period of the extracts with CO-DH. The inhibitor was precipitable with ammonium sulfate, phenol, and trichloroacetic acid. It was passed through benzoylated dialysis tubing and Amicon ultrafiltration membrane YM2. Denaturing and nondenturing polyacrylamide gel electrophoresis of CO-DH inactivated by inhibitor revealed that the mobilities of native enzyme and subunits were identical to those of active CO-DH. The inhibitor-treated CO-DH retained its original antigenic sites and exhibited enzyme activity upon activity staining. The CO-DH inhibitor of P. carboxydovorans was also active on CO-DHs from Pseudomonas carboxydohydrogena, Acinetobacter sp. strain JC1, and Pseudomonas carboxydoflava.

Aldehyde Oxidoreductases↗

PubMed1989

Ovarian renin production in vitro and in vivo: characterization and clinical correlation.

The purpose of this study was to examine the in vitro production of prorenin and active renin by human theca cells and to examine the clinical significance of this production by correlating prorenin and active renin levels with oocyte maturity in follicular fluid samples. Human theca cell cultures were established and were found to produce both prorenin as well as active renin. Androstenedione levels (126 +/- 28 pg/500,000 cells/24-hr incubation) correlated with prorenin levels (8.5 +/- 1.1 ng angiotensin I per milliliter per hour (AI/ml/hr) in culture supernatant (r = 0.61, P less than 0.05). Active renin levels in follicular fluid were higher in stimulated versus spontaneous cycles (359 +/- 67 versus 126 +/- 37 ng AI/ml/hr, P less than 0.05). Renin substrate levels were similar in follicular fluid and in the peripheral serum (1,610 +/- 216 versus 2,160 +/- 490 ng/ml) in spontaneous cycles. Follicular fluid prorenin and active renin did not correlate with oocyte maturity or with steroid levels. The authors conclude that ovarian theca cells produce renin in vitro. However, renin production does not correlate with oocyte maturity or follicular fluid steroids in vivo.

Androstenedione↗

PubMed1989

Extrarenal renin-secreting tumors: insights into hypertension and ovarian renin production.

Although renin-secreting tumors are rare, they must be considered in the differential diagnosis of hypertension associated with hypokalemia, which occurs commonly in the hypertensive population. The finding of an ovarian renin-secreting tumor emphasizes the potential importance of the ovary as an extrarenal source of renin; the local ovarian renin-angiotensin system may play a key role in reproductive function by regulating vascular reactivity, local blood flow, steroidogenesis and other physiologic effects. In the illustrative case presented, a renin-secreting ovarian leiomyosarcoma was obtained from a women who presented with hypertension and hypokalemia. Plasma prorenin levels were markedly elevated. Tumor excision was quickly followed by a fall in prorenin levels and tumor recurrence was accompanied by an increase in prorenin levels. Active renin concentration in the tumor homogenates was similar to that found in kidney homogenates while the tissue prorenin concentration was approximately 20 times that found in kidney tissue. When cultured for up to 4 weeks, ovarian tumor cells secreted greater than 95% prorenin. Immunoblot analysis demonstrated that tumor renin had a molecular weight of 47,000, similar to that of human recombinant prorenin. Immunohistochemical staining of tumor tissue with antibodies against human renal renin at the electron microscopic level demonstrated the presence of renin primarily in membrane-bound vesicles and rarely in dense-core secretory granules. These findings suggest that prorenin in this ovarian tumor was secreted by the constitutive pathway, which is mediated by these amorphous vesicles.

Aged↗

PubMed1989

Human decidua is a major source of renin.

Plasma prorenin levels are elevated in normal pregnant women. Current evidence suggests renin production by tissues of the uteroplacental unit contribute to this elevation. The purpose of this investigation was to define the source of renin biosynthesis within the human uteroplacental unit and to characterize the renin produced. RNA extraction and Northern blot analysis consistently demonstrated renin mRNA expression in uterine lining both in the pregnant (decidua) and nonpregnant states (endometrium) and in fetal chorion laeve, which is inseparable from the decidua. In contrast, renin mRNA expression was not detected in basal plate and intertwin chorion (which is separate from decidua), amnion, myometrium, or placental villi. The total renin content in decidual homogenates was two- to threefold greater than in endometrial homogenates, and cultured human decidual cells produced significantly more total renin than cultured human endometrial cells, suggesting that pregnancy enhanced renin production by the cells lining the uterus. Immunoblot analysis and [3H]leucine incorporation identified 47,000-mol wt prorenin as the major form of renin produced by cultured human decidual cells. These studies indicate that maternal decidua is the major source of prorenin in the uteroplacental unit.

Adult↗

PubMed1989

CT findings of clonorchiasis.

Clonorchiasis is a snail-transmitted trematodiasis caused by Chinese liver fluke, Clonorchis sinensis. Forty-two patients with the disease were examined with CT. Seventeen patients had clonorchiasis alone, and 25 patients had clonorchiasis with hepatobiliary malignancies (20 cholangiocarcinomas, four hepatocellular carcinomas, one carcinoma of the ampulla of Vater). In three of the 17 patients with clonorchiasis alone, the CT scans were normal. In 14 patients (82%), CT showed diffuse, minimal, or mild dilatation of the intrahepatic bile ducts. None of the patients had marked dilatation. The extrahepatic biliary tree was normal in all 17 patients. All 25 patients with clonorchiasis and hepatobiliary malignancies had diffuse dilatation of the intrahepatic bile ducts on CT, including 18 patients with minimal or mild dilatation and seven patients with marked dilatation. All seven patients with marked dilatation had extrahepatic biliary malignancies. Clonorchis sinensis per se or thickening of the bile duct wall could not be recognized on CT scans. Additional abnormalities evident on CT included pyogenic liver abscesses in two patients and gallstones in five patients. The diagnosis of clonorchiasis can be suspected when CT shows diffuse, uniform, and minimal or mild dilatation of the intrahepatic bile ducts, particularly in the periphery of the liver, without evidence of extrahepatic biliary dilatation.

Adenoma, Bile Duct↗

PubMed1988

Gradients of prorenin and active renin in ovarian venous and peripheral venous blood samples obtained simultaneously.

Previous studies have demonstrated the presence of prorenin, active renin, and angiotensin II in human follicular fluid. The purpose of this study was to analyze prorenin, active renin, and ovarian steroids in ovarian venous blood and peripheral venous blood samples obtained simultaneously. We studied 10 premenopausal patients undergoing oophorectomy in various phases of the menstrual cycle. Prorenin levels in the ovarian venous effluent were more than twofold higher than levels in peripheral blood, 136.8 +/- 34.1 versus 35.6 +/- 8.3 ng angiotensin 1 per milliliter per hour (p less than 0.01). Active renin levels were also higher in ovarian venous blood than in peripheral venous blood, 12.9 +/- 2.5 versus 8.9 +/- 2.7 ng angiotensin 1 per milliliter per hour, but this difference did not achieve statistical significance (p = 0.07). Prorenin levels correlated with those of active renin in ovarian venous blood (r = 0.76, p less than 0.05), suggesting that prorenin is locally activated. In the peripheral circulation, estradiol levels correlated negatively with prorenin levels (r = -0.73, p less than 0.05), although prorenin levels did not correlate with steroid levels in ovarian venous blood. We conclude that prorenin is produced by the ovary throughout the menstrual cycle and may be locally activated.

Blood Specimen Collection↗

PubMed1988

Human ovarian theca cells are a source of renin.

Human ovarian follicular fluid contains renin-like activity. In normal women, circulating levels of prorenin, the biosynthetic precursor of renin (EC 3.4.23.15), change in parallel with changes in progesterone during the menstrual cycle. Therefore, the ovary has been implicated as a source of plasma prorenin. In the present studies, we report the finding of high concentrations of prorenin in human ovarian follicular fluid (3000 ng.ml-1.hr-1 vs. 10-40 ng.ml-1.hr-1 in normal human plasma) obtained from follicles of women prepared for in vitro fertilization. The inactive renin-like enzyme was identified as prorenin by its activation characteristics, its molecular weight of 47,000, which is the same as that for recombinant prorenin, and its cross-reactivity with human renal renin antibodies. Culture of isolated human theca cells and isolated granulosa cells indicated that prorenin is secreted by theca cells but not by granulosa cells. Prorenin production by theca cells peaked during the first 10 days of culture and gradually decreased by 17 days. Active renin levels were 10% or less of the prorenin levels. Prorenin was barely detectable in medium from granulosa cells cultured for 24 days. Immunohistochemical staining of human ovaries (n = 5) with anti-human renin antibody demonstrated the presence of renin primarily in theca cells. These studies suggest that the theca cell is the source of the large quantities of prorenin in human ovarian follicular fluid.

Enzyme Precursors↗