Hazards of phenothiazines in chronic renal failure.
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Biomedical subjects
Publications and source records attributed to A White.
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Binding of cortisol and corticosterone by serum proteins is well established, but discrepancies exist regarding aldosterone. We have observed that approximately 1% of 3H-aldosterone incubated with rat serum was bound in a time-dependent process, although it was not competed by a large excess of non-radioactive aldosterone, assessed by Florisil separation or gel filtration on Sephadex G-50 columns. After electrophoresis on cellulose acetate of rat serum incubated with 3H-aldosterone, specific or non-specific binding to protein fractions was not obtained. Further, a 10 000-fold molar excess of aldosterone (10 microM) displaced only 34% of the bound 3H-aldosterone to rat serum, preventing the calculation of the IC50 value. Increasing concentrations of aldosterone (3-83 nM) did not displace 3H-corticosterone bound in rat serum to presumably corticosterone binding globulin (CBG). In contrast, inhibition of this binding by 3-83 nM corticosterone was concentration dependent, showing an IC50 value of 10(-8) M. In normal human serum, binding of 3H-aldosterone demonstrated competition by a 100 and 1 000-fold excess of aldosterone. Displacement curves of 3H corticosterone bound to human serum by 1.7-75 nM corticosterone or 0.05-8.8 microM aldosterone yielded IC50 values in the range of 10(-8) M for corticosterone and 10(-6) M for aldosterone. With horse serum, aldosterone's binding affinity was three orders of magnitude lower than that of corticosterone. These studies suggest that in the rat aldosterone was loosely and weakly bound to a high capacity binder, possibly albumin. In agreement with the work of others, in humans aldosterone may be bound to both CBG and albumin. The current data do not substantiate for the presence of specific aldosterone binding proteins in serum.
An enzyme linked immunosorbent assay was developed to detect urinary antigen excreted by patients with Legionnaires' disease. Of 47 patients tested, antigen was detected in 39. Antigen was not detected in any of 178 urine specimens from patients with other pulmonary, bacteremic, or urinary tract infections after performance of a quick and simple confirmatory test. The assay required more time to perform than a previously described radioimmunoassay but was of equivalent sensitivity and specificity and did not require expensive equipment of contact with radioactive reagents. We conclude that enzyme linked immunosorbent assay is a rapid, sensitive, and specific means for rapidly diagnosing Legionnaires' disease which can be performed in clinical laboratories unwilling or unable to use radioisotopes.
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Further evidence is presented for the existence in teleost fish of proteins homologous with mammalian C-reactive protein. The amino acid composition is given for a C-reactive protein isolated from the eggs of a marine teleost, Cyclopterus lumpus, by extraction with lecithin in the presence of Ca2+, followed by electrofocusing. A molecular weight of 150,000 was calculated from gel filtration and electrophoresis at different polyacrylamide gel concentrations, while the s20,w was 7.4 S. The 1.5-S subunit had an apparent Mr of 20,000 by SDS-polyacrylamide gel electrophoresis and 21,000 by computer analysis based on amino acid composition. Comparison is made with the physicochemical properties of mammalian C-reactive protein.
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Of patients with staphylococcal infections, high levels of IgM antibodies of staphylococci measured by radioimmunoassay were present in 13 of 17 patients with endocarditis, nine of 23 with complicated bacteremia, one of 20 with uncomplicated bacteremia, and two of 21 with nonbacteremic infections. Of control subjects, high levels of IgM antibodies were present in seven of 26 individuals with gram-positive infections, two of 16 with gram-negative infections, two of 20 with rheumatoid arthritis, and two of 50 uninfected persons. Concomitant elevation of IgG and IgM antibody levels occurred in 20 of 40 patients with endocarditis or complicated bacteremia compared with two of 41 patients with other types of staphylococcal infections and three of 112 control subjects. IgM antibodies only were present early in the infection in six of 13 patients with staphylococcal endocarditis or complicated bacteremia. IgG or IgM antibody levels remained elevated at least four weeks after initiation of treatment.
The changes in labelling index of neuroglial cells of the rat cervical cord following 20 Gy X rays are compared with the timing and pattern of the repair of radiation damage in the spinal cord. The start of time-dependent repair coincides with the release of the proliferative neuroglia from a block at the G1/S border. The evidence suggests that the time-dependent repair reflects the normal unstimulated proliferation of the surviving neuroglial cells and that homeostatically stimulated recruitment to the proliferative neuroglia does not occur until the period just before the development of paralysis. A normal cell-cycle time of about one month for the spinal cord neuroglia is indicated from the observed pattern of labelling.
Urine from nine patients with serogroup 1 Legionnaires' disease, 100 with infected or contaminated urine, 50 with bacteremic infections, 26 with infectious or infiltrative pulmonary diseases, and 65 with miscellaneous infectious or noninfectious illnesses, was examined by radioimmunoassay for the presence of Legionella pneumophila antigen(s). Urine of all nine Legionnaires' disease patients was clearly differentiated from that of the 241 control subjects by the assay. The antigen was detected from 2 to at least 10 days after the initiation of erythromycin therapy. A probable false-positive results occurred in a patient with necrotizing nosocomial pneumonia who died before definitive serologic evaluation for Legionnaires' disease could be completed. The antigen was stable at 100 degrees C for 30 minutes and was not degraded by trypsin. Its elution behavior suggested that its molecular weight is approximately 10 000. The radioimmunoassay appears to be a useful method for rapidly diagnosing serogroup 1 Legionnaires' disease.
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1. The ability of phlorrhizin to inhibit the galactosylation of glucose was re-examined with Golgi membrane vesicles purified from rat mammary gland, and extended to the galactosylation of several glucose analogues and N-acylglucosamines. 2. The inhibition is ascribed, contrary to previous conclusions, to a general annealing of leaky membranes comprising a minority of the vesicles. 3. Three thiol reagents were able to inhibit the galactosylation of N-acylglucosamines with less, or no, inhibition of galactosylation of glucose. This demonstrates the existence of a Golgi membrane carrier that distinguishes between glucose and N-acylglucosamines.
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Rat kidney contains membrane-bound renin (EC 3.4.99.19) and kallikrein (EC 3.4.21.8). Kallikrein activity was measured by a spectrophotometric assay and renin by radioimmunoassay. Plasma membrane-bound kallikrein was activated by lysolecithin and by melittin, which was a more potent activator., This activation by mellitin was independent of calcium concentration. Mellitin was, however, a more potent activator of membrane-bound renin in the presence of calcium. Administration of aldosterone to rats for 6 days increased kallikrein activity in the renal homogenate and in the membrane-enriched fractions, whereas renin activity was not affected. It was proposed that kallikrein may also be located on the basal membrane of tubular epithelial cells, where aldosterone can enhance its activity.