Is dehydroepiandrosterone sulfate a natriuretic digitalis-like factor in human serum?
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Biomedical subjects
Publications and source records attributed to A Goto.
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The effects of adrenalectomy or nephrectomy, carried out one hour previously, on the levels of endogenous digitalis-like factors were determined in rat plasma. Factors were assayed by digoxin-like immunoreactivity and direct Na+,K(+)-ATPase inhibitory activity. Digoxin-like immunoreactivity significantly decreased one hour after bilateral ablation of adrenals, while Na+,K(+)-ATPase inhibitory activity remained unaltered. There were no changes in either activity one hour after bilateral nephrectomy. These results suggest that digoxin-like immunoreactivity may be derived from the adrenal gland or under adrenal control and the major substances detected by digoxin-like immunoreactivity and direct Na+,K(+)-ATPase inhibitory activity may be different.
Effects of human urine-derived endogenous digitalis-like factor (EDLF) and ouabain on endothelin (ET) secretion were examined in cultured endothelial cells. ET was secreted in a linear fashion over 5 hours from bovine pulmonary artery endothelium into serum-free medium. EDLF stimulated ET secretion in a dose-dependent manner. In contrast, ouabain did not affect ET secretion at the concentration of 10(-9)-10(-5) M. These results indicate that human urine-derived EDLF is distinct from plant-derived ouabain and act as a stimulator of ET secretion by endothelial cells.
We report a case of early congenital syphilis in which the placenta showed diffuse proliferative villitis and Treponema pallidum was identified by indirect immunoperoxidase stain in formalin-fixed paraffin-embedded placental tissue. This is the first report demonstrating T. pallidum in placental tissue using an immunohistochemical method.
PURPOSE: On the assumption that renal tubular cells are more important as the target cells for a natriuretic factor than blood cells, we used a well-characterized cultured renal tubular cell line, Madin-Darby canine kidney (MDCK), cells to monitor the circulating digitalis-like factor in human plasma and examine its role in the regulation of blood pressure and sodium balance. SUBJECTS AND METHODS: We investigated the effects of plasma on binding of radioactive ouabain to monolayered MDCK cells in order to determine the level of a circulating digitalis-like factor. First, we measured specific 3H-ouabain binding to MDCK cells in the presence of plasma from 71 outpatients (34 normotensive subjects and 37 hypertensive patients) after incubation for 4 hours. Second, we measured specific 3H-ouabain binding after incubation of cells with plasma from 16 hospitalized subjects (eight normotensive subjects and eight hypertensive patients) receiving low and high sodium diets. RESULTS: In Study 1, ouabain binding was lower by 30% with plasma from hypertensive patients than with plasma from normotensive subjects (p less than 0.01). There was a significant negative correlation between individual subject's systolic or mean blood pressure and ouabain binding (r = -0.34, p less than 0.01 or r = -0.29, p less than 0.01). In Study 2, ouabain binding was also significantly reduced by 25% in the presence of plasma from hypertensive subjects as compared with plasma from normotensive subjects irrespective of sodium intake (p less than 0.01). A significant negative correlation was also found for all subjects between either systolic, diastolic, or mean blood pressure and ouabain binding (r = -0.58, p less than 0.01, r = -0.51, p less than 0.01, or r = -0.55, p less than 0.01, respectively). With the changes from low to high sodium intake, there was a corresponding decrease in ouabain binding (p less than 0.01) and an increase in sodium excretion (p less than 0.01). A significant negative correlation was observed between these two parameters (r = -0.47, p less than 0.05). CONCLUSIONS: These findings suggest that a circulating digitalis-like factor, which may act on renal tubular cells as the ouabain-displacing compound, is increased in patients with essential hypertension and also demonstrate that plasma levels may be influenced by changes in dietary sodium intake.
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Isolates from various clinical materials in 13 hospitals in Akita prefecture and their drug susceptibility were investigated by the Chemotherapy Research Committee of Akita Prefecture during the period from Dec., 1987 to Feb., 1988. The results were as follows: 1. The total number of isolates was 8,387, including Staphylococcus aureus (18.9%), Pseudomonas aeruginosa (10.9%), Staphylococcus epidermidis (7.3%) and Enterococcus faecalis (6.6%). S, aureus and P. aeruginosa were detected more frequently in the larger hospitals. 2. The detection frequency of S. aureus from the sputum, throat swab and pus exudate was also very high. There was a diversity in isolates from the urine and the frequency of Escherichia coli was low. More than half of the isolates from the blood were S. epidermidis and S. aureus. Many kinds of bacteria were detected from pleural fluid and ascites, but the isolate showed no particular tendency. 3. The susceptibility of S. aureus to oxacillin were variable in hospitals, and the susceptibility to cefazolin were even lower. Low susceptibility were also seen with norfloxacin. S. aureus showed the highest susceptibility to minocycline. The susceptibility was lower for inpatients than for outpatients. P. aeruginosa showed low susceptibility to cefsulodin. The number of ampicillin-resistant Haemophilus influenzae isolates tended to decrease. Enterobacter cloacae showed a low susceptibility for cephems. Serratia marcescens showed low susceptibility to many drugs. Based on the above results, we concluded that attention should be paid to S. aureus, P. aeruginosa and Enterobacter in clinical practice.
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A 33-year-old previously healthy woman was seen at this hospital after a week of fever and nonproductive cough. A roentgenogram of the chest showed consolidation in the left upper and middle lung fields. Transbronchial lung biopsy from left S1 + 2 revealed an increase of mononuclear leukocytes within the interstitial spaces and slight cell infiltration with in the alveoli. Bronchoalveolar lavage cellular constituents showed 47% alveolar macrophage, 38% lymphocytes and 15% neutrophils. She had kept a parakeet, which died just after her illness. We could isolated organisms from the liver, spleen, kidney, lung, heart and bowel of her pet bird revealing C. psittaci by Giemsa stain, three days after it was buried in the ground. She was given three hundred mg of ofloxacin per day orally for fourteen days and the clinical effect was good. The in vitro activity of ofloxacin was 0.75 microgram/ml.
General pharmacological properties of BMY-28100, a new semisynthetic oral cephalosporin, were studied in experimental animals. The obtained results are summarized as follows: 1. BMY-28100 had no effect on gross behavior and the central nervous system in mice and rats nor on EEG activities in rabbits. 2. BMY-28100 did not affect the smooth muscle isolated from rats, guinea pigs or rabbits nor did it influence ganglionic transmission in cats. 3. Effects of BMY-28100 on the atrium and heart isolated from guinea pigs were not obvious. Several parameters of the cardiovascular system were examined and found unchanged by administration of BMY-28100 to rabbits. 4. In the digestive system, BMY-28100 had no effect on charcoal meal transport in the small intestine of mice. In rats, however, gastric secretion was reduced at a dose level of 125 mg/kg or higher and bile secretion was enhanced at a dose level of 500 mg/kg. 5. BMY-28100 had no effect on neuromuscular transmission in rabbits and showed no local anesthetic activity in guinea pigs. 6. BMY-28100 decreased urine volume and urinary excretion of electrolytes in dose-dependent manners in rats. Sulfobromophthalein excretion in rats was inhibited only at the highest dose tested. BMY-28100 had no effect on blood coagulation and red blood cell resistance in rats or rabbits. BMY-28100 revealed no antiinflammatory activity in rats. 7. BMY-28167, a trans-isomer of BMY-28100, had no or weak effects on some of above test systems when compared with BMY-28100. These results suggest that BMY-28100 has hardly any pharmacological properties leading to severe adverse reactions in clinical use.
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We were able to partially purify a polar digitalis-like factor from rat and bovine hypothalami based on the capacity to inhibit [3H]ouabain binding to intact human erythrocytes. This factor was characterized in reference to the digitalis-like factor that we have isolated and reported on. Hypothalamic factor shared digitalis-like activities and physicochemical properties with the one derived from human urine and mammalian plasma. These findings strongly suggest that a polar digitalis-like factor identical to the circulatory factor does exist in mammalian hypothalamus.
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We report a case of an extragonadal germ cell tumor from the retrovesical region associated with Klinefelter's syndrome. The patient presented with symptoms of macroscopic hematuria and micturition pain. An x-ray and digital examination were suspicious for prostatic carcinoma. However, needle biopsy of the tumor revealed embryonal cell carcinoma. Serum alpha-fetoprotein was 10,700 ng. per ml. Preoperatively, combined cytotoxic chemotherapy was administered and the antineoplastic effect was excellent. Serum alpha-fetoprotein rapidly returned to the normal range and the tumor volume decreased. Although the preoperative diagnosis was extragonadal germ cell tumor of the prostate, surgery revealed that the tumor originated from the retrovesical region. Orchiectomy and resection were performed. The resected tissue was mostly necrotic with a few viable cells of embryonal cell carcinoma, no metastatic lesions were detected in the lymph nodes and no masses were noted in the testes. Postoperatively, the patient was treated with cytotoxic chemotherapy. His condition has remained good with no clinical evidence of recurrence of the disease.
A fetus at 20 weeks' gestation was shown by ultrasonography to have ascites and intrahepatic calcifications. We aspirated the fetal ascites at 29 and 30 weeks' gestation to decompress the fetal lungs due to the progression of the ascites and the concomitant compression in the fetal lungs. The newborn had neither hypoplasia of the lungs nor any respiratory complication, though congenital cytomegalovirus infection was present. This is the first report of such congenital cytomegalovirus infection associated with fetal ascites and intrahepatic calcifications. Careful monitoring and early intervention is necessary for a good prognosis.
We were able to purify two distinct sodium pump inhibitors to homogeneity from human urine based on [3H]ouabain-displacing activity from intact human erythrocytes. The polar and less polar compounds were eluted off the C18 reverse-phase column with 18% and 31% acetonitrile, respectively. The polar compound cross-reacted very weakly with specific antidigoxin antibody and lacked a characteristic ultraviolet absorption peak between 190 and 300 nm. The less polar compound showed a prominent digoxinlike immunoreactivity and had an ultraviolet spectrum similar to that of digoxin. We examined the effects of these compounds on cytosolic free calcium concentration in cultured rat vascular smooth muscle cells (A10 cells) using the fluorescent calcium chelator fura-2. Only the polar ouabain-displacing compound caused a significant increase, from 108 +/- 7 to 162 +/- 8 nM (n = 6, p less than 0.01), in cytosolic free calcium concentration in A10 cells. The rise in cytosolic free calcium concentration induced by the polar ouabain-displacing compound tended to be slower in onset and more sustained than that induced by arginine vasopressin. In contrast, ouabain and bufalin had no appreciable effects on cytosolic free calcium concentration in A10 cells. These results suggest that the polar ouabain-displacing compound we isolated from human urine may possess a vasoactive property and may play an important role in the modulation of vascular tone.
Combination chemotherapy with methotrexate, vinblastine, adriamycin and cisplatin (M-VAC regimen) was administered to 12 patients with advanced epithelial cancer of the urinary tract in a clinical trial undertaken to assess clinical efficacy of this multiagent therapy. This series comprised 11 males and 1 female ranging in age from 46 to 76 years (mean age: 63), with performance status (PS) being rated 0 in 2, 1 in 5, 2 in 2, 3 in 2 and 4 in 1 of these 12 patients. The site of primary lesion was bladder in 8, renal pelvis in 3 and ureter in 1. Histologically, these tumors were all identified as transitional cell carcinoma (grade 3) with the exception of 1 mixed type (transitional cell carcinoma plus squamous carcinoma). Nine of the patients had already their primary tumor resected surgically while the remaining 3 had undergone only biopsy. The site of metastasis was lung in 7, bone in 4 and lymph nodes in 3. In consideration of the patients' general condition, the dosages of the chemotherapeutic agents were set at 80% of those recommended by Sternberg. Of the 9 patients with primary tumor resected, 1 died of chemotherapy; of the remaining 9 patients, the M-VAC regimen brought about CR in 1 and PR in 4, hence with a response rate of 62.5%. The 4 patients showing PR underwent surgical resection of residual tumor and 2 of them achieved CR and have been free of a recurrence during a 33- or 29-month period of the chemotherapeutic regimen.(ABSTRACT TRUNCATED AT 250 WORDS)
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