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Biomedical subjects

K Nelson

Publications and source records attributed to K Nelson.

At least 217 records · Page 12Linked to original sources

The effects of piretanide on catecholamine metabolism, plasma renin activity and plasma aldosterone: a double-blind study versus furosemide in healthy volunteers.

In a double-blind, crossover study, 8 male volunteers (mean age: 25.9 years) received successively 6 different regimens of two diuretics, piretanide and furosemide, with a 1-week wash-out period between each drug regimen. Piretanide (6 mg) or furosemide (40 mg) were given either once daily at 08.00 hours or twice daily at 08.00 and 12.00 hours or at 08.00 and 20.00 hours. Each of these phases lasted for 1 week. Serial measurements were performed on plasma renin activity, plasma aldosterone, plasma adrenaline, plasma noradrenaline, plasma dopamine, cumulative urinary excretion of aldosterone, urine volume and urine osmolality. Plasma catecholamines showed no clinically relevant changes during all three regimens of piretanide or furosemide dosage. Piretanide and furosemide both induced a short-term increase in plasma renin activity with a maximum about 4 hours after dosing which returned to initial levels after approximately 12 hours regardless of whether a single or twice daily dose had been given. After 1 week of piretanide given once daily, lower plasma renin activity was found than after furosemide. Furosemide given once daily caused higher plasma aldosterone concentrations than did piretanide. The lowest plasma aldosterone concentrations were found during the twice-daily piretanide regimen at 08.00 and 20.00 hours. Aldosterone excretion in urine was also higher during furosemide than during piretanide administration. Piretanide given twice daily at both 08.00 and 12.00 hours or 08.00 and 20.00 hours caused the most insignificant changes in aldosterone excretion. It is suggested that piretanide, in comparison to furosemide, activates the counter-regulatory mechanisms, which may diminish the antihypertensive effect of the diuretic, to a much lesser extent.

Adult↗

Steroid receptor analysis by size-exclusion liquid chromatography: considerations for the clinical laboratory.

Steroid receptor activity can be more quickly estimated by size-exclusion chromatography than by conventional analysis on sucrose gradients, and profiles of receptor activity are better resolved. Here we discuss several factors affecting this form of analysis in clinical laboratories. The composition of the elution buffer influences steroid receptor elution and recovery: high ionic strength, neutral pH, and the presence of dimethylformamide are important. Of the TSK-SW (Beckman) size-exclusion chromatographic columns we considered, the TSK-G2000SW column appeared to be the most appropriate. "Reference" elution profiles are presented for several marker proteins and estrogen receptor forms generated under different sample-treatment conditions. In examining the sensitivity of receptor analyses by this method, we used fresh rodent preparations, a commercial receptor reference (Estrocept), and human tumor material obtained by needle biopsy. We also compared frozen and lyophilized receptor preparations with fresh ones.

Animals↗

Clinical evaluation of muzolimine and indapamide during treatment for essential hypertension.

Muzolimine, a new saliuretic, has been shown to combine high ceiling and long-acting effects in animal experiments. This study was designed to examine whether this desirable combination of effects, which up until the present time has not been incorporated into any substance also occurs during patient treatment. Fifty-three patients with mild essential hypertension (WHO groups I and II) in three medical centers were treated with either muzolimine or indapamide, which served as the reference preparation, in a randomised, double-blind study. After a two week run-in phase during which the patients received placebo, half of the patients received 20 mg muzolimine and the other half 2.5 mg indapamide once daily. Eight weeks of therapy were followed by a 2 week follow-up phase, during which placebo was dispensed. During the trial period a weekly clinical examination was performed including the measurement of blood pressure, pulse, hematocrit, electrolytes, uric acid, glucose, creatinine and lipid status. An electrocardiogram and Schellongtest were conducted every two weeks. Patients were instructed to keep a diary in which they were to note drug related complaints. Statistical analysis was carried out using the Pratt-Wilcoxon Pair Test. Differences were judged significant at the 5% level. Both muzolimine and indapamide were tolerated well with minimal side effects, which however, did not make it necessary to discontinue treatment. Both preparations induced mild blood pressure reductions of approximately 10 and 5 mmHg for the systolic and diastolic blood pressure, respectively. Two weeks after cessation of muzolimine treatment neither systolic nor diastolic blood pressure showed any significant difference to values achieved during the treatment phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Estrogenicity of coumestrol in the mouse: fluorescence detection of interaction with estrogen receptors.

The estrogenicity of coumestrol, a fluorescent phytoestrogen, has been examined in murine uteri. Coumestrol competed with 17 beta-[3H]estradiol for binding to cytoplasmic estrogen receptors, caused cytoplasmic estrogen receptors to associate with chromatin in the nucleus, and induced progesterone receptors. By use of size-exclusion high-performance liquid chromatography (SEHPLC), the interaction of coumestrol with estrogen receptors was examined directly by monitoring the fluorescence associated with macromolecules having properties characteristic of estrogen receptors. These analyses were made possible by the addition of dimethylformamide to the elution buffer, at a concentration (7.5%) which improved recoveries but did not interfere with estrogen receptor binding. It was possible to detect fluorescent coumestrol at approximately 0.5 nM. All determinations were performed with preparations in which estrogen receptor activity was 3-10 nM. Exposure of these preparations to coumestrol (50 nM) resulted in the elution of increased fluorescent activity in the regions where estrogen receptors eluted during SEHPLC. This fluorescent activity was reduced when diethylstilbestrol, 17 beta-estradiol, hexestrol, or tamoxifen was present as a competitor (2 microM) but was unaffected by testosterone or progesterone. Diethylstilbestrol reduced fluorescence below endogenous base lines and thereby displayed a fluorescence quench property which was not observed with other ligands. When hepatic and renal estrogen receptor preparations were used, the injected receptor activity was observed to be the major limiting factor in detecting the interaction of coumestrol with estrogen receptors. These observations are relevant to attempts to visualize estrogen receptors in tumor cells and demonstrate that accepted biochemical criteria for ligand-receptor interaction can be satisfied when fluorescent ligands are examined.

Animals↗

VisiCalc and VisiPlot software routines and the analysis of data routinely encountered in steroid biochemistry.

The use of VisiCalc and VisiPlot software routines for performing calculations and graphing of data commonly encountered in steroid biochemistry is described. These software routines have utility and are relatively easy to use, requiring little or no programming experience. Use of these routines is demonstrated in terms of data processing associated with chromatography of receptor preparations and equilibrium binding analyses. The execution of these software routines is rapid and can result in a considerable savings of time and personnel. These and other generically similar software routines should have the greatest utility in laboratories where the experimental design is subject to on-going change.

Animals↗

Interleukin 1 production by peripheral blood mononuclear cells from leprosy patients.

Quantitation of interleukin 1 production by adherent mononuclear cells from peripheral blood was performed in patients with tuberculoid and lepromatous forms of leprosy. Cells from patients with tuberculoid leprosy either secreted interleukin 1 spontaneously or produced amounts within the normal range in response to lipopolysaccharide stimulation. Conversely, stimulated cells from lepromatous patients failed to produce interleukin 1 in 5 of 13 (38.5%) cases.

Adult↗

Acquisition of an unfamiliar script in story form by young children.

Preschool, first, and third graders heard similar versions of an unfamiliar scriptlike story followed by a novel story, and were tested for immediate and delayed recall. Children more often confused parts of the similar stories with each other than with the novel story, indicating that the similar versions were perceived as belonging to a separate category or script. "Very specific" story items were recalled better in immediate recall, whereas "very general" items were recalled better in delayed recall, suggesting a transition from reproductive to reconstructive recall. Preschoolers showed less evidence of constructive processing than older children, and their performance was more affected by the degree to which story items were schematically organized.

Child↗

Murine arylsulfatase C: evidence for two isozymes.

SWR/J mice possess high arylsulfatase C, estrone sulfatase, and dehydroepiandrosterone sulfatase activities in liver, spleen, and kidney compared to A/J mice. This interstrain activity variation appears to be determined by at least 1 autosomal gene. Murine arylsulfatase C activity occurs in both hydrophobic and hydrophilic forms which differ with respect to certain biochemical properties and exhibit different subcellular distributions. The hydrophilic isozyme is a major component in kidney and brain extracts and a minor isozyme in liver and spleen extracts. The hydrophobic arylsulfatase C isozyme appears to be identical to steroid sulfatase. The hydrophilic arylsulfatase C isozyme does not possess steroid sulfatase activity; however, hydrophilic and hydrophobic arylsulfatase C share certain properties, suggesting that they may be structurally related. The autosomal gene(s) affects both arylsulfatase isozymes.

Animals↗

Simultaneous three color and electronic cell volume analysis with a single UV excitation source.

We have adapted an Ortho ICP-22 flow cytometer (Ortho Instruments, Westwood MA) for the simultaneous measurement of three independent fluorochromes and cell volume. This has been accomplished by the addition of a third photomultiplier tube and the development of a new electronic cell volume (ECV) flow cell. Cells are first analyzed as they pass through the 100 U ECV aperture and are then excited approximately 15 musec later by the 365 nm mercury are beam reflected by a 400 nm dicroic mirror. Independent blue, green and red signals can be associated by a delay circuit to the ECV signal from the same cell. We have developed this system as an aid in the analysis of tumor cell and macrophage heterogeneity and differentiation. The choice of stain combinations to be used is extremely flexible and permits the analysis of a wide range of enzyme activities in conjunction with DNA/RNA and phagocytic probes. Data presented indicates the value of this approach in identifying the presence of plasminogen activator-like activity in both tumor and inflammatory cells within a malignant effusion as well as the quantitative expression of a number of markers of macrophage differentiation. Although the described techniques have been developed on a mercury arc instrument, they can be used equally well with cell sorters.

Color↗

Genetic analysis of murine arylsulfatase C and steroid sulfatase.

SWR/J mice possess two- to threefold higher 4-methylumbelliferyl sulfate (4MUS), dehydroepiandrosterone sulfate (DHEAS) and estrone sulfate (E1S) sulfatase activities in liver and kidney extracts than do A/J mice. These interstrain activity differences are maintained throughout the 6- to 45-day postnatal period. Characteristics of the hepatic activities of SWR/J mice suggest that all three activities reside in the same enzyme. Biochemical properties of the SWR/J and A/J enzyme were not significantly different. Expression of hepatic enzyme activity is subject to regulation by an autosomal locus possessing two alleles with additive effects. Postnuclear E1S- and DHEAS-sulfatase activities are primarily microsomal. Although postnuclear hepatic 4MUS-sulfatase activity is predominantly microsomal, renal activity is primarily nonmicrosomal. Only that portion of 4MUS-sulfatase occurring in cell membranes appears capable of hydrolyzing E1S and DHEAS. The hepatic- and renal-specific subcellular distributions of 4MUS-sulfatase activity may reflect tissue differences in enzyme processing. Renal 4MUS-sulfatase activity is also controlled by an autosomal gene with two alleles having additive effects. Positive correlation between hepatic and renal 4MUS-sulfatase activities indicates that both activities are most likely influenced by the same gene.

Alleles↗