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Biomedical subjects

S C Brown

Publications and source records attributed to S C Brown.

At least 91 records · Page 5Linked to original sources

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↗

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↗

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↗

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↗

Flow Cytometric Fluorescence Anisotropy of Lipophilic Probes in Epidermal and Mesophyll Protoplasts from Water-Stressed Lupinus albus L.

The blue emission anisotropy, r, of two lipophilic probes, diphenylhexatriene (DPH) and its trimethyl-ammonium derivative (TMA-DPH), has been measured in foliar Lupinus albus L. protoplasts for the first time by flow cytometry. Distinctive values have been obtained for protoplasts of epidermal and mesophyll origin, identified by their intensities of chlorophyll fluorescence. Fluorescence microscopy confirmed that TMA-DPH remained in the plasma membrane while DPH penetrated into intracellular lipid domains. Typical emission anisotropy values at 22 degrees C for mesophyll and epidermal protoplasts, respectively, were 0.225 and 0.312 with TMA-DPH, and 0.083 and 0.104 with DPH. This indicates that epidermal cells-and notably their plasma membranes (TMA-DPH)-have higher lipid microviscosity and/or more ordered lipid structure. Two lupin genotypes characterized as resistant or susceptible to drought were analyzed with or without 9 days of water stress shown to increase ion leakage from foliar discs. Water stress greatly increased the apparent fluidity, and more so in the susceptible genotype; the effect was more pronounced in the chlorophyll-containing mesophyll cells than in the epidermal cells.

Journal Article↗

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↗

Improving a hospital pharmacy externship program.

The revision and implementation of a pharmacy student externship program at a cancer treatment and research facility are described. The Department of Pharmacy Academic Programs evaluated the student externship program of the Division of Pharmacy at The University of Texas M. D. Anderson Cancer Center and identified a variety of weaknesses. These included scheduling conflicts, insufficient supervision and feedback, excessive task orientation, lack of defined roles and responsibilities of program participants, and generally poor organization. As a result, the program was revised by establishing specific goals, defining program participants and their roles, setting specific responsibilities for externs and encouraging self-initiated learning, developing standardized evaluation forms and documentation requirements, and educating the pharmacy staff about the program. Since the revised program was implemented in June 1988, 21 students have completed externship rotations. Their evaluations of the program suggest greater satisfaction with this important educational experience than was realized before the revision was undertaken. A more organized approach to the externship program gave pharmacy students a better opportunity to experience the range of professional activities and challenges that occur in the institutional practice setting.

Cancer Care Facilities↗

1H NMR assignment and secondary structural elements of human transforming growth factor alpha.

The 1H NMR spectrum of human transforming growth factor alpha (hTGF-alpha) has been completely assigned, and secondary structural elements have been identified as a preliminary step in determining the structure of this protein by distance geometry methods. Many of these structural elements closely correspond to those previously found in a truncated human EGF [Cooke et al. (1987) Nature (London) 327, 339-341] and murine EGF [Montelione et al. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 5226-5230]. These include the presence of an antiparallel beta-sheet between residues G19 and C34 with a type I beta-turn at V25-D28, a type II beta-turn at H35-Y38, and another short beta-sheet between residues Y38-V39 and H45-A46.

Amino Acid Sequence↗

Effects of prolactin on water balance and kidney function in bullfrog tadpoles.

In four experiments of similar design, stage III-XII bullfrog tadpoles were treated for 5-13 days with either 10 micrograms/day ovine prolactin (PRL) or 10 microliters/day saline (0.7% NaCl). In all cases, saline-treated tadpoles lost ca. 10% of their body weight, whereas PRL-treated animals either maintained their weight or gained slightly. Compared with controls, PRL-treated tadpoles showed a significantly higher water content and a 10-20% increase in inulin space (= extracellular volume). PRL treatment also significantly decreased plasma [Na+] (but not total extracellular [Na+]), and the rates of renal inulin clearance (= glomerular filtration rate) and urine production. PRL-treated tadpoles showed significant retention of the water taken up in response to a salt load. These data suggest that the PRL-induced weight gain observed in bullfrog tadpoles is accompanied by major changes in renal function and the size, water content, and sodium concentration of the extracellular fluid compartment.

Animals↗

Class I antigens of the bovine major histocompatibility system and resistance to the cattle tick (Boophilus microplus) assessed in three different seasons.

Two consecutive calf crops consisting of 141 three-quarters Brahman/one-quarter Shorthorn cattle were assessed for resistance to the Australian cattle tick Boophilus microplus in May, July and October 1983. Although the level of expressed resistance to artificial infestation varied considerably between seasons, the animals maintained very similar rankings for resistance in all three seasons, and the repeatability of tick resistance ranged from 0.59 to 0.82. The cattle were typed for 30 bovine class I lymphocyte antigens. Antigens W6 and CA31 were associated with susceptibility to artificial tick infestation but none of the other lymphocyte antigens showed strong associations with resistance or susceptibility.

Animals↗

Talc deposition and effects after 20 days of repeated inhalation exposure of rats and mice to talc.

The relationship between the inhalation exposure concentration of talc and the resulting lung burdens and histologic lesions was studied using groups of 20 F344/Crl rats and 20 B6C3F mice (10 male and 10 female) exposed to one of three concentrations of asbestos-free talc for 6 hr/day, 5 days/week for 4 weeks. Controls were exposed to filtered air using the same schedule. The pulmonary retention of talc and the development of pulmonary pathology were evaluated. The mass median aerodynamic diameter (MMAD) of the talc aerosol was 3.0 microns with a geometric standard deviation (sigma g) of 1.9. The mean exposure concentrations for rats were 0, 2.3, 4.3, and 17 mg talc/m3. Lung burdens in rats averaged 0, 0.07, 0.17, and 0.72 mg talc/g lung after the 20-day inhalation exposure; thus, the amount retained in the lung per unit of exposure concentration increased with increasing concentration. Mean exposure concentrations for the mice were 0, 2.2, 5.7, and 20.4 mg of talc/m3, which resulted in lung burdens of 0, 0.10, 0.29, and 1.0 mg talc/g lung; thus, the relationship between exposure concentration and the amount retained in the lung was approximately constant. Lung burdens from this study were used to project lung burdens that would result from longer exposures of rodents and man. No clinical signs were observed in the rats or mice prior to sacrifice 24 hr after the last exposure day. Histologic alterations in lung tissue consisted of only a modest, diffuse increase of talc-containing, free macrophages within alveolar spaces in both rat and mouse groups exposed to the highest level of talc for 20 days. A model simulating chronic talc inhalation exposure of rats and mice predicted lung burdens of 2-3 mg talc/g lung (wet wt) if animals were exposed to 17 mg talc/m3 for 2 years, and deposition and clearance of talc were unchanged by continued exposure. A potential limitation in this modeling is that if clearance of talc is delayed by continued exposure, the accumulated talc lung burdens would be higher than those projected by the simulation model. Humans exposed to aerosols of respirable talc are projected to accumulate much higher lung burdens than would occur in rodents exposed to the same aerosol, because humans have a higher estimated deposition fraction and slower estimated clearance of the deposited talc dust. Equilibrium lung burdens of greater than or equal to 2 mg talc/g lung were predicted for human exposures at or near the TLV for talc.

Aerosols↗

Presbycusis.

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Aged↗

Results of excision of a cervical rib in patients with the thoracic outlet syndrome.

Excision of a cervical rib in patients with the thoracic outlet syndrome has been the subject of debate. One surgeon's experience of 23 cervical rib excisions is presented. Ten operations produced a complete cure, eleven improvement, and two no change in the patient's condition. Of 15 cases with neurological symptoms alone, 9 were cured, 5 improved and 1 was not helped; in contrast, of 8 patients with vascular symptoms, 1 was cured, 6 were improved and 1 was not helped. We conclude that cervical rib resection is the correct treatment for patients whose symptoms are predominantly neurological. Rib resection alone may not be sufficient in patients with vascular symptoms. The management of a cervical rib with vascular involvement is discussed.

Adult↗

Operative mortality rate and surgery for colorectal cancer.

Different authors use different definitions of operative mortality rate when reporting results of their operations. Four definitions used in current literature were applied to our own series of 578 patients with colorectal carcinoma. The operative mortality rate was found to vary from 7.3 per cent to 12.2 per cent, depending on the definition used. 'Death within 30 days of the last operation' was the definition which best reflected true operative deaths. We urge that this definition of operative mortality rate be adopted as a standard for all operations.

Cause of Death↗

Nuclear RNA quantification in protoplast cell-cycle phases.

Using acridine orange staining and flow cytometry the DNA and RNA levels (arbitrary units) of individual cells may be established. Here, this method has been applied to nuclei isolated from plant protoplasts during culture. The specificity of the technique has been validated for such plant material; ribonuclease markedly reduced nuclear staining without modifying the DNA histogram; ribonuclease inhibitor prevented the action of released cell nucleases; and protoplasts cultivated with actinomycin D did not synthesize RNA. First RNA synthesis was evident 18 h after Petunia hybrida protoplasts had been put into culture. An increase of RNA above a critical level was required for cells to be able to initiate DNA replication from G1, termed G1B. G2 nuclei had an RNA:DNA ratio similar to that of G1 nuclei.

Acridine Orange↗