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Biomedical subjects

S C Brown

Publications and source records attributed to S C Brown.

At least 19 recordsLinked to original sources
PubMed1992

Flow cytometric analysis of opposite effects of a monokine on proliferation and differentiation of murine B lymphocytes.

A 35,000 mw factor able to replace macrophages (FRM) in the induction of the in vitro antibody response to sheep erythrocytes has been isolated from the supernatant of murine resident peritoneal macrophage cultures. Purified FRM, when added at the outset of cultures, induced B cells to generate an antigen-specific antibody response. The signals provided by FRM in the process of B cell activation were analyzed using a polyclonal model. Cell cycle analysis by multiparameter flow cytometry after acridine orange staining showed that FRM, on its own, did not trigger the transition of B cells from the G0 to the G1 stage of the cell cycle. In addition, FRM affected neither the basal intracellular free calcium level ([Ca2+]i) nor the rapid increase in [Ca2+]i induced by crosslinking of membrane immunoglobulin (mIgM) with anti-mu antibodies. In parallel with its positive effect on B cell differentiation, FRM markedly reduced both proliferation and cell cycle progression of B cells stimulated with anti-mu plus interleukin 4 (IL-4). Indeed, the addition of FRM to such cultures led to a preferential accumulation of cells in the early G1 compartment of the cell cycle and to a decreased frequency of cells in all other phases including G1B, S and G2/M.

Animals↗
PubMed1992

The estimate of glomerular filtration rate during urography. Acceptability of a nonionic contrast medium as a marker of renal function.

RATIONALE AND OBJECTIVES: An estimate of glomerular filtration rate (GFR) may be obtained at the same time as urography by measuring the plasma clearance of the radiographic contrast medium using an x-ray fluorescence technique. It must be established whether the function measured or one modified by an effect of the contrast medium itself represents a true value. METHODS: Technetium 99m-DTPA (99mTc-DTPA) plasma clearance was measured in 21 patients using a single-injection technique, before, during, and after an intravenous injection of 50 mL of 350 mg I/mL iohexol. Iohexol clearance also was determined using an alternative single-injection, two-sample technique. RESULTS: The mean 99mTc-DTPA clearances before, during, and after contrast were 71.2, 71.5, and 70.7 mL/minute, respectively. The within-patient standard deviation in clearance values was 3.84 mL/minute. One factor repeat measures analysis of variance indicated no significant difference between the three measurements (F ratio = 0.24). Contrast and 99mTc-DTPA clearances performed simultaneously agreed closely (r = .976; ClDTPA = 1.02ClCon - 1.35). CONCLUSION: The authors conclude that no change in function is observed during or 48 hours after contrast injection. Imaging doses of iohexol can be used for GFR measurement during urography.

Aged↗
PubMed1992

The importance of renal function in the interpretation of diuresis renography.

Interpretation of the diuresis renogram is dependent on a full understanding of the factors that contribute to the washout curve, a major determinant being the urinary flow rate induced by the diuretic. Frusemide-induced flow rates were measured in 86 patients over a 30-min period and related to creatinine clearance in 39, 99mTc-DTPA clearance (glomerular filtration rate (GFR)) in 27, and 123I-Hippuran clearance (effective renal plasma flow) in 20. The flow rates 3 to 6 min and 15 to 18 min after administration of the diuretic received specific attention because of their importance to F + 20 and F - 15 diuresis renography respectively. The mean urinary flow rate 15 to 18 min after frusemide was 3.5 ml/min greater than at 3 to 6 min (P less than 0.001), explaining the value of the F - 15 renogram in further evaluating equivocal F + 20 curves. Linear relationships were observed between each parameter of function and the 3 to 6 min and 15 to 18 min periods as follows: creatinine clearance r = 0.66, r = 0.77; 99mTc-DTPA clearance r = 0.66, r = 0.77; 123I-Hippuran clearance r = 0.59, r = 0.71. From regression analysis of the data presented it is possible, with knowledge of total and split function, to predict single-kidney flow rates. It is demonstrated that these may commonly exceed flow rates used for perfusion studies if function is normal, but a single-kidney flow rate of 10 ml/min is unlikely to be attained if the single-kidney GFR is less than 15 ml/min.

Adult↗
PubMed1992

Delay in presentation and misdiagnosis of strangulated hernia: prospective study.

The purpose of this study was to examine the presentation and management of strangulated hernia. The clinical course of 54 patients was recorded. Twenty-one patients (39%) presented after 48 h from the onset of symptoms. Fifteen (28%) had a bowel resection and two (4%) died. Twenty (37%) patients had previously consulted their general practitioner about the hernia, but only seven had been referred for surgery. Five (25%) had been warned of the risk of strangulation. In the 32 (59%) patients previously aware of a hernia, delayed presentation was related to ignorance of the risk of strangulation (P less than 0.01). The strangulated hernia was misdiagnosed by the general practitioner in 17 (33%) patients (necessitating a second visit) and by the hospital registrar in eight (15%). We conclude that strangulated hernia is too often misdiagnosed and all patients who present with a hernia must be referred to a surgeon and warned about strangulation.

Adult↗
PubMed1991

Amphibian prolactins: activity in the eft skin transepithelial potential bioassay.

The effects of purified prolactins isolated from frogs (fPRL; Rana catesbeiana) and newts (nPRL; Cynops pyrrhogaster) were compared with those of ovine prolactin (oPRL) and thyrotropin releasing hormone (TRH) in the eft (Notophthalmus viridescens) skin transepithelial potential (TEP) bioassay. At total doses as low as 0.4 micrograms/animal, both fPRL and nPRL were as effective as oPRL in reducing eft skin TEP. By contrast, TRH at total doses as high as 400 micrograms/animal was ineffective in altering eft skin TEP. These data provide the first direct evidence that amphibian PRLs can exert significant physiological control over salamandrid integumental sodium transport.

Animals↗
PubMed1991

Iohexol clearance for the determination of glomerular filtration rate in clinical practice: evidence for a new gold standard.

X-ray fluorescence analysis provides a simple method of measuring glomerular filtration rate from the clearance of ordinary unlabeled radiographic contrast media. To measure the accuracy of iohexol clearance using a clinically simple 2-sample single injection technique, a comparison was made in 30 patients with classical continuous infusion techniques for plasma (y = 1.03x - 0.015, r = 0.981) and renal (y = 0.950x + 7.26, r = 0.964) iohexol clearance. A comparison was made with classical inulin clearance. The renal clearance of iohexol and inulin was virtually identical (y = 0.998x + 2.31, r = 0.986). Single injection iohexol clearance agreed closely with the renal inulin clearance (y = 0.947x + 4.92, r = 0.983) as did clearance based on a single 3-hour sample (y = 0.875x + 12.63, r = 0.962). Iohexol clearance using x-ray fluorescence is a simple, rapid and accurate alternative to inulin clearance for clinical and research purposes.

Adult↗
PubMed1991

Compartmental analysis and glomerular filtration in chick embryos.

We have developed microtechniques that allow the determination of compartmental fluid distribution and glomerular filtration rate in chick embryos during three significant developmental periods: phase 1, the developmental period when the mesonephros alone is functioning; phase 2, periods of simultaneous meso/metanephric kidney function; and phase 3, the period during late development when the metanephros completely replaces the degenerated mesonephros. Water content of tissues is greater in younger embryos (89.4 +/- 0.2%, day 10) compared with older animals (78.3 +/- 0.5%, day 18). Although all major tissue components show an absolute increase in mass during this period, the embryo proper increases at five times the rate of the extraembryonic tissues. Glomerular filtration rate increases during development from 0.61 +/- 0.08 ml/h at day 10 to 2.31 +/- 0.11 ml/h at day 18. Glomerular filtration rate scales to body mass with an allometric exponent identical to adult birds only if total tissue mass (embryo + membranes) is considered. Our data suggest that significant errors in allometry will be encountered when scaling measurements are made on embryonic or fetal amniotes without taking into consideration the extraembryonic tissues.

Animals↗
PubMed1991

Risk factors and operative mortality in surgery for colorectal cancer.

The operative mortality rate after surgery for colorectal carcinoma remains significant. A series of 578 patients has been studied prospectively. The features which most significantly affect operative mortality are the age of the patient, a history of loss of weight, limited preoperative patient mobility and the presence of intestinal obstruction with perforation of the bowel. By identifying high-risk groups of patients, attention may be focused on particular patients at risk, in order to reduce operative mortality.

Activities of Daily Living↗
PubMed1990

Analysis of the membrane potential of rat- and mouse-liver mitochondria by flow cytometry and possible applications.

Washed and purified rat- or mouse-liver mitochondria exhibiting high membrane integrity and metabolic activity were studied by flow cytometry. The electrophoretic accumulation/redistribution of cationic lipophilic probes, rhodamine 123, safranine O and a cyanine derivative, 3,3'-dihexyloxadicarbocyanine iodide, during the energization process was studied and was consistent with the generation of a negative internal membrane potential. An exception to this was nonylacridine orange which spontaneously bound to the mitochondrial membrane by hydrophobic interactions via its hydrocarbon chain. Energized purified mitochondria stained with potentiometric dyes exhibited both higher fluorescence and population homogeneity than the non-energized or deenergized (nigericin plus valinomycin) mitochondria. By contrast, under non-energized or deenergized conditions, the mitochondrial population exhibited fluorescence intensity heterogeneity related to the residual membrane potential; two subpopulations were evident, one of low fluorescence which may be related to the autofluorescence of the mitochondria (plus non-specific dye binding) and a second population which exhibited high fluorescence. Flow cytometry of the unpurified, simply washed, rat-liver mitochondria stained with rhodamine 123, a classically used dye, provided evidence of their heterogeneity in terms of light-scattering properties and membrane-potential-related fluorescence. One third of the washed mitochondria were found to be non-functional by such assays. The fluorescence of purified rat-liver mitochondria due to the membrane potential built up by endogenous substrates indicates heterogeneity of the mitochondrial population with respect to levels of endogenous substrates. The low-angle light scattering increases upon energization and provides some original information about the shape and modification of the inner mitochondrial conformation accompanying the energization. The heterogeneity of the rat liver mitochondrial population, from a structural, metabolic (existence of endogenous substrates) and functional (active and non-active mitochondrial population dispersion) point of view could thus be demonstrated by flow-cytometry analysis. Two animal models were examined with regard to the alteration of the mitochondrial membrane potential under the effects of drugs (rat-liver mitochondria), and the effects of ammonium toxicity (mouse-liver mitochondria). These results are promising and open new perspectives in the study of mitochondriopathies.

Ammonia↗
PubMed1990

Solution structures of human transforming growth factor alpha derived from 1H NMR data.

The 600-MHz 1H NMR spectrum of the des-Val-Val mutant of human transforming growth factor alpha (TGF-alpha) was reassigned at pH = 6.3. The conformation space of des-Val-Val TGF-alpha was explored by distance geometry embedding followed by restrained molecular dynamics refinement using NOE distance constraints and some torsion angle constraints derived from J-couplings. Over 80 long-range NOE constraints were found by completely assigning all resolved cross-peaks in the NOESY spectra. Low NOE constraint violations were observed in structures obtained with the following three different refinement procedures: interactive annealing in DSPACE, AMBER 3.0 restrained molecular dynamics, and dynamic simulated annealing in XPLOR. The segment from Phe15 to Asp47 was found to be conformationally well-defined. Back-calculations of NOESY spectra were used to evaluate the quality of the structures. Our calculated structures resemble the ribbon diagram presentations that were recently reported by other groups. Several side-chain conformations appear to be well-defined as does the relative orientation of the C loop to the N-terminal half of the protein.

Computer Simulation↗
PubMed1990

Visual stool examination--a screening test for infants with prolonged neonatal cholestasis.

Visual inspection of stools for the presence or absence of bile pigment was evaluated prospectively to determine its value in differentiating between biliary atresia and hepatitis. In a group of 23 infants with prolonged neonatal cholestasis the presence of stool pigment excluded extrahepatic biliary atresia, while its absence was suggestive of extrahepatic biliary atresia. This simple test was found to be more reliable than more sophisticated diagnostic techniques.

Bile Pigments↗
PubMed1990

Selective alteration of mitochondrial function by Ditercalinium (NSC 335153), a DNA bisintercalating agent.

The bifunctional intercalator Ditercalinium (NSC 335153) demonstrates an anti-tumoral cytotoxicity markedly different from other intercalating agents. A delayed toxicity is observed in eucaryotic cells, both in vitro and in vivo, at drug concentrations far below those required to observe immediate toxic effects. Fluorescence microscopy demonstrates that Ditercalinium and the mitochondrial-staining fluorophore DiOC2(5) are concentrated in the same cellular organelles of L1210 cells. Electron microscopy of Ditercalinium-treated cells reveals extensive and progressive swelling of mitochondria, with no other ultrastructural changes observed. Ditercalinium uptake and toxicity are in part related to mitochondrial membrane potential. However, drug accumulation itself does not immediately alter the mitochondrial membrane potential. Cellular ATP pool levels and the rate of respiration fall progressively after drug treatment. Nucleotide pools in DC3F cells, measured between drug treatment and death, show marked drops in pyrimidine levels while purine nucleotide levels decline more slowly. Addition of uridine or cytidine partially rescues Ditercalinium-treated cells, while toxicity is increased in the presence of 2-deoxyglucose. The combined evidence indicates that the toxicity of Ditercalinium to murine leukemia cells (L1210) and Chinese Hamster lung cells (DC3F) is due to disruption of mitochondrial function.

Adenosine Triphosphate↗
PubMed1990

Action of 1,25-dihydroxyvitamin D3 and parathyroid hormone on 45calcium uptake by the yolk sac membrane of chick embryos.

During development, the chick embryo mobilizes the calcium it needs from two extraembryonic sources, initially from the yolk and later from the eggshell. Calcium may be hormonally regulated during avian embryogenesis, but details of this regulation are lacking. We investigated the effects of 1,25-dihydroxycholecalciferol [1,25(OH)2D3], bovine parathyroid hormone [bPTH], and vehicle [ethanol or saline] on blood calcium values and incorporation of 45Ca into the yolk sac membrane of 9, 12, and 15 day chick embryos. Control data were also collected from uninjected 6 day embryos. Solutions were injected directly into the yolk sac compartment 48 and 24 hours prior to the experiment. Exogenous 1,25(OH)2D3 induced hypercalcemia in all age groups examined, while exogenous PTH induced hypercalcemia in day 12 and 15 embryos. Small disks of yolk sac membrane were incubated in medium to which 45Ca was added and assayed for 45Ca content at various intervals after start of incubation. In control yolk sac tissue, the uptake of 45Ca was greatest in younger embryos with decreasing uptake at developmentally more advanced ages; 1,25(OH)2D3 treatment significantly enhanced the uptake of 45Ca into yolk sac tissue in all groups (9, 12, and 15 day embryos). PTH treatment caused a significant elevation in 45Ca uptake in the day 12 and 15 embryos.

Aging↗
PubMed1990

The relationships among ecto- and endoparasite levels, class I antigens of the bovine major histocompatibility system, immunoglobulin E levels and weight gain.

Natural infestations of the cattle tick Boophilus microplus, levels of the buffalo fly Haematobia irritants exigua and faecal nematode egg concentrations (Bunostomum phlebotomum, Cooperia spp., Haemonchus placei, Oesophagostomum radiatum and Trichostrongylus axei) were assessed in 221 Belmont Red calves during the post-weaning period, when the animals were between 9 and 18 months of age. In addition, the 98 males of this group were challenged with B. microplus larvae on two separate occasions. There were strong positive correlations among replicate assessments of the same parasite. Field tick counts and tick counts following deliberate challenge were strongly correlated, and both showed negative correlations with post-weaning weight gain. There was a weak positive correlation between buffalo fly counts and post-weaning weight gain. There was a negative correlation between total worm egg count and weight gain. Among worm species, only the effect of O. radiatum on weight gain was significant. Cattle with bovine major histocompatibility (BoLA) antigens W6.1 and W7 had significantly fewer ticks than cattle lacking these antigens. Cattle with BoLA antigens W7 and CA36 had lower concentrations of nematode eggs in their faeces than cattle lacking these BoLA antigens.

Analysis of Variance↗
PubMed1990

Monensin does not consistently inhibit the spreading of normal or Duchenne fibroblasts on glass.

The spreading on glass of monensin-treated normal and Duchenne fibroblasts has been investigated with the intention of extending this approach to a study of the comparative spreading of these cells on differing substrata. Untreated normal and Duchenne fibroblasts varied considerably in their ability to spread on glass. The spreading properties of normal and DMD fibroblasts treated in four different ways were compared: (1) pre-incubated and plated without monensin; (2) pre-incubated with, but plated without monensin; (3) pre-incubated without, but plated with monensin; (4) pre-incubated and plated with monensin. The response to plating with monensin (and pre-incubation/plating with monensin) also varied from patient to patient, but no statistically significant differences in the degree of spreading between the four treatment groups were observed in pooled data for either normal or dystrophic fibroblasts. Our data thus do not substantiate the previous finding of Pizzey et al. (1984) that Duchenne fibroblasts spread less well than normal fibroblasts after pre-incubation or plating with monensin, and possible explanations for this are discussed. The observations made are, however, consistent with the recent report that dystrophin is effectively not expressed in fibroblasts, and with the idea that the abnormal behaviour of endomysial fibroblasts in Duchenne dystrophy is a secondary consequence of their proximity to degenerating muscle.

Cell Adhesion↗