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Biomedical subjects

S C Brown

Publications and source records attributed to S C Brown.

At least 127 records · Page 7Linked to original sources

Method for determining the lung burden of talc in rats and mice after inhalation exposure to talc aerosols.

A method has been developed to quantitate talc lung burdens in rats and mice after inhalation exposure to talc aerosols. The method is based on acid-insoluble magnesium (Mg) determination by flame atomic absorption. Precipitating protein from homogenates of lungs of unexposed rodents with 5% perchloric acid and washing with 5% trichloroacetic acid removed the soluble and naturally occurring Mg. This resulted in residual Mg content averaging 0.43 micrograms Mg per g lung in rats and less than 0.1 microgram Mg per g lung in mice for young rodents less than 12 weeks old. Rodents 12-18 months old had residual mean (+/- SD) Mg contents of 3.4 +/- 2.0 micrograms Mg per g rat lung (n = 17) and 6.5 +/- 2.9 micrograms Mg per g mouse lung (n = 12). Thus, the background residual acid-insoluble Mg content in rodent lungs appears to increase with age. Negligible quantities of Mg were extracted directly from the talc treated by these procedures. Adding 50-2000 micrograms talc to lungs from unexposed rodents, followed by the sample treatment, gave mean (+/- SD) Mg recoveries of 89 +/- 12% (n = 19) for rat lungs and 96 +/- 26% (n = 15) for mouse lungs. The lung burden of talc in rodents exposed to talc aerosols for 6 h per day, 5 days per week for 4 weeks was determined. Mean lung burdens in rats were 77, 187, and 806 micrograms talc per g lung (n = 10) for exposures at 2.3, 4.3, and 17 mg talc m-3, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗

Thyroid function in adult rough-skinned newts (Taricha granulosa): effects of hypophysectomy and hormone replacement.

This study examines the regulation of thyroid activity in adult rough-skinned newts, Taricha granulosa. Aquatic, breeding-condition newts were hypophysectomized and were injected for 23 days with the mammalian adenohypophysial hormones: ACTH, PRL, and GH. During a fourth week of treatment, these newts also received TSH. Plasma T4 concentrations were lower in hypophysectomized newts than in sham-hypophysectomized newts 23 days after surgery. Both ACTH and PRL increased T4 titers above these in saline-injected control newts; GH alone had no effect. TSH effectively increased the plasma T4 concentrations in newts from all five groups. GH, and possibly PRL, depressed the response to TSH. Plasma T4 concentration was positively correlated with body fluid loss, suggesting that hormone concentration/dilution effects may occur generally in animals such as these that undergo substantial seasonal changes in degree of hydration.

Adrenocorticotropic Hormone↗

Sensitivity and specificity of salamandrid integumental transepithelial potential to prolactin.

The effects of ovine prolactin (oPRL), bovine growth hormone (bGH) and human placental lactogen (hPL) on in vivo integumental transepithelial potential (TEP) were examined in two salamandrid urodeles, adult terrestrial-phase Taricha granulosa and the juvenile red-eft stage of Notophthalmus viridescens. TEP in efts treated with 1.0 microgram oPRL/2 days fell from 73.3 +/- 6.1 to 15.2 +/- 5.5 mV by Day 7 (P less than 0.001), whereas the TEP of efts treated with either 1.0 or 10 micrograms bGH/2 days remained at control levels for as long as 24 days. TEP in efts treated with a single dose of 10 micrograms oPRL dropped from 65.74 +/- 4.1 to 23.0 +/- 3.4 mV (P less than 0.01) in 3 days. Efts treated with various doses of oPRL showed a linear log total dose response over the range of 0.05 to 10.0 micrograms oPRL/animal, with a minimum detectable total dose of 0.4 micrograms/g (0.01 IU/g). In the same experiments, tail height increased by Day 7 in efts treated every other day with 10.0 micrograms oPRL, but not 1.0 microgram oPRL or either 1.0 or 10.0 micrograms bGH/2 days. In Oregon newts injected every other day with 10 micrograms oPRL, TEP decreased by 33% in 8 days (P less than 0.05), whereas in animals treated with 10 micrograms bGH/2 days, TEP did not change from control values even after 23 days. TEP in Oregon newts receiving a single dose of 100 micrograms oPRL dropped to 68% of initial values within 2 days (P less than 0.05), but subsequently recovered to control values 3 weeks after the last injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A comparison of bovine lymphocyte antigens.

In Canberra, 31 antigens have been described on the surface of bovine lymphocytes. Seven antigens are subgroups of other antigens. Eleven antigens are similar to the eleven antigens which have been described in Melbourne. Fourteen antigens are similar to twelve international-workshop antigens and two European-workshop antigens.

Animals↗

Binding of ethidium and bis(methidium)spermine to Z DNA by intercalation.

The interaction of ethidium bromide, a DNA intercalating drug, and bis( methidium )spermine, a DNA bis-intercalating compound, with the left-handed Z form of poly(dG-dC) has been studied in 4.4 M NaCl. Spectrophotometric analysis using absorption, fluorescence and circular dichroism indicates that the complex formed between ethidium and Z DNA resembles very closely that formed with B DNA. This suggests that ethidium binds to Z DNA by intercalation. 31P NMR spectra are presented showing both the conversion of the Z form to the B form with increasing amounts of drug and the typical Z form spectrum at low binding densities. Data are also presented which show that the bifunctional intercalator bis( methidium )spermine binds to Z DNA in a manner similar to its binding to B DNA, i.e., by bis-intercalation. These results are important for our understanding the behavior of Z DNA and its biological significance.

Animals↗

Aqueous solution structure of an intercalated actinomycin D-dATGCAT complex by two-dimensional and one-dimensional proton NMR.

Two-dimensional NOESY and COSY 1H NMR techniques have been employed to determine the conformation of the complex formed by actinomycin D and the hexanucleoside pentaphosphate dATGCAT. One-dimensional NOE experiments in H2O confirmed the intact nature of the oligonucleotide double helix within the complex. The drug chromophore was intercalated between the GC base pairs, with the pentapeptide lactones nestled in the minor groove. No significant conformational change of the pentapeptide lactones between bound and free drug was observed.

Dactinomycin↗

Osmoregulatory changes during the aquatic-to-terrestrial transition in the rough-skinned newt, Taricha granulosa: the roles of temperature and ACTH.

Aquatic breeding-condition newts kept at 5, 11, or 18 degrees showed temperature-dependent changes in body weight (BW), tail height, plasma [Na+], hematocrit, integumental osmotic permeability, urine production, and transepithelial potential. Net urine production could account for the change in weight observed in animals kept at 11 and 18 degrees, suggesting that initial weight change results from a reduction in extracellular volume. Weight loss was correlated with increased hematocrit and plasma [Na+]. In another experiment, newts were sham-hypophysectomized (sham-HX) or hypophysectomized (HX) and injected with saline, ovine prolactin (PRL), ovine growth hormone (GH), or porcine adrenocorticotropic hormone (ACTH) and maintained at 5 degrees for 13 days. All animals lost 3-7% of their initial BW. Plasma [Na+] was reduced in animals injected with hormone compared with both sham-operated and saline-injected controls. Following an increase in water temperature to 11 degrees for 13 days, weight loss in sham-operated and ACTH-injected newts increased to 16% of BW compared with a total of 4-8% in newts injected with PRL, GH, or saline. In this experiment also, loss of body weight was correlated with increased plasma [Na+]. Although measurements of plasma Na+ concentrations indicated that ACTH caused "sodium retention," estimates of changes in total extracellular Na+ revealed that both sham-operated and ACTH-injected newts experienced a net sodium loss. In Taricha granulosa, warm temperatures and ACTH (presumably acting via interrenal hormones) appear necessary for the fluid and electrolyte loss which accompanies the transition from the aquatic to the terrestrial condition.

Adrenocorticotropic Hormone↗

Tick resistance and the major histocompatibility system.

199 3/4 Brahman 1/4 Shorthorn cattle, whose resistance to the cattle tick Boophilus microplus had been determined by clinical trial, were tested for 19 bovine lymphocyte antigens. Of eleven antigens detected at a frequency greater than 5%, two were found to be associated with tick resistance and a third was associated with susceptibility to ticks. However, none of these antigens accounts for more than 2.1% of the variance, indicating that these associations are not strong.

Animals↗

Breeding condition, temperature, and the regulation of salt and water by pituitary hormones in the red-spotted newt, Notophthalmus viridescens.

In vivo integumental transepithelial potential (TEP) in the Eastern red-spotted newt (Notophthalmus viridescens) increases linearly with external [Na+] from 0.1 to 10 mM and is anion independent. Both integumental TEP and osmotic permeability are higher in laboratory-conditioned (LC, terrestrial) than in breeding-condition (BC, aquatic) newts at temperatures of 5-25 degrees. Prolactin (PRL) treatment of LC newts decreased both TEP and rate of water uptake. Arginine vasotocin (AVT) treatment resulted in a substantial increase in water uptake in LC newts, while little or no AVT response was seen in PRL-treated or BC newts. Hypophysectomy (HX) or ergocryptine treatment increased TEP in BC newts, whereas HX + PRL maintained TEP at control levels. Although ergocryptine and HX were without effect on water uptake in BC newts kept at 5 degrees for 9 days, HX + ACTH increased water uptake. HX produced a substantial fall in serum [Na+] in BC newts, while either PRL or ACTH replacement elevated serum [Na+]. Combined ACTH and PRL treatment returned serum [Na+] to control levels. These data suggest that high endogenous prolactin plays a significant role in maintaining serum [Na+] and integumental permeability and transport characteristics in breeding-condition N. viridescens. Although PRL and ACTH are both sodium retaining in the aquatic breeding stage, these two hormones promote opposite effects on the integument; PRL decreases both water uptake and integumental TEP, whereas ACTH (presumably acting through the adrenals) increases water uptake and possibly TEP.

Adrenocorticotropic Hormone↗

Biosynthesis and characterization of [15N]actinomycin D and conformational analysis by nitrogen-15 nuclear magnetic resonance.

We describe the production and characterization of actinomycin D labeled with 15N at all twelve nitrogen positions. Cultures of Streptomyces parvulus were incubated in the presence of racemic [15N]glutamic acid and, following an initial delay, labeled antibiotic was produced. Evidence is presented that the D enantiomorph of glutamic acid was ultimately used for actinomycin biosynthesis. The 15N NMR spectrum at 10.14 and 20.47 MHz of the labeled drug in CDCl3 is presented. All nitrogens except the phenoxazone chromophore nitrogen are inverted when spectra are obtained under broad-band proton irradiation conditions. All 15N resonances have been assigned, and the proton-nitrogen one-bond coupling constants were determined in CDCl3 to be 92.5 +/- 0.3 Hz for the valine and threonine amide protons by both 1H and 15N NMR. 15N NMR spectra were also obtained in dimethyl sulfoxide, methanol, and water in order to probe solvent interactions with the peptide nitrogens and carbonyl groups. Large downfield shifts (greater than 5 ppm) were seen for the Pro, sarcosine, and methylvaline resonances when the solvent was changed from dimethyl sulfoxide to water. Smaller downfield shifts were observed for the Val and Thr peaks. These results are discussed in terms of a model for the solution conformation of the actinomycin pentapeptide rings based on different hydrogen-bonding interactions in the monomer in organic solvents and the dimer which is formed in water.

Dactinomycin↗

A conformational analysis of daunomycin considering D-ring repucker.

We present a complete molecule mechanics optimization of daunomycin. Two different D-ring puckers are found to be of comparable energy, consistent with NMR data, although only one of these low-energy structures has been observed by X-ray crystallography. Our results are more consistent with the previous conformational analysis of daunomycin by Neidle and Taylor (Neidle, S. and Taylor, G.L. (1979) FEBS Lett. 107, 348-354) than that of Nakata and Hopfinger (Nakata, Y. and Hopfinger, A.J. (1980) FEBS Lett. 117, 259-264).

Calorimetry↗

Hydromineral balance in the chick embryo: effects of hypophysectomy.

The developing chick embryo exhibits a regular pattern of accumulation and reabsorption of fluid in its extraembryonic compartments. Fluid volume (measured by dye dilution) peaks at Day 14 in both the allantois (12.4 ml) and the amnion (5.1 ml). The standard experimental procedure of removing 2 ml of albumen at 33-36 hr of incubation does not alter this pattern, but leads to a maximum decrease in fluid volume of ca. 1 ml in both amniotic and allantoic compartments. Although [Na] and [Cl] remain essentially constant in the serum, they steadily decrease in the allantois (remaining substantially below serum levels). In the amnion, [Cl] is maintained above that of serum, whereas [Na] falls below serum [Na] by Day 14. In the Day 12 (stage 38) embryo, hypophysectomy (HX) causes a substantial increase in the allantoic fluid volume and [Na] and [Cl], thus resulting in a 166% increase in total Na and Cl over that of sham-operated embryos. By contrast, HX did not alter amniotic fluid volume, although it did decrease [Na] and to a lesser degree, [Cl]. Serum [Na], but no [Cl], was reduced by HX. HX abolished the normally steep ionic gradients maintained between the allantois and both serum and amnion. Thus, the most dramatic effects of HX at Day 12 are on the allantois, which accumulates both Na and Cl at the expense of the amnion and serum. This suggests that pituitary hormones may normally act by Day 12 to reduce urinary volume and electrolyte excretion and/or to increase fluid and electrolyte reabsorption from the allantois.

Allantoin↗

Water balance in the California newt, Taricha torosa.

Both dehydration to 87% of original body weight (Wo) and arginine vasotocin (AVT: 20 mU/g) elicited rapid weight gains (ca. 9% of Wo in the 1st h) when terrestrial-phase T. torosa were given access to water. In each case, net weight gain resulted from increased integumental osmosis and antidiuresis. Mesotocin (0.001 -- 0.1 micrograms/g) elicited modest but significant weight gains (ca. 1%/h) caused solely by increased integumental osmosis. Integumental water uptake from wet moss was 66% that of totally immersed animals. Water movement from ventral to dorsal body surface occurred along channels on the skin. Urinary bladder storage capacities in excess of 50% of Wo were observed. Following AVT administration, bladder water resorption increased significantly, while glomerular filtration rate dropped to 16% of control values. The structural and physiological adaptations for water balance in T. torosa are comparable to those found in some terrestrial anurans.

Animals↗

Recognition of differentiation antigens of spermatogenesis in the mouse by using antibodies from spleen cell-myeloma hybrids after syngeneic immunization.

Two differentiation antigens of spermatogenesis in the mouse are defined by monoclonal antibodies from hybridomas produced between the myeloma P3-X63Ag8 and spleen lymphocytes immunized with syngeneic testis cells. These antigens are on testis cells, and not liver, kidney, brain, spleen, or whole ovary. They are species but not strain specific and trypsin sensitive but collagenase insensitive. On the basis of their appearance during the onset of spermatogenesis they appear to be differentiation antigens expressed during different but overlapping time windows during spermatogenesis.

Animals↗