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Biomedical subjects

S C Brown

Publications and source records attributed to S C Brown.

At least 109 records · Page 6Linked to original sources
PubMed1988

Electrophysiology of newt skin: effects of prolactin.

Integumental transepithelial potential (TEP) was measured by both in vivo and in vitro (Ussing chamber) techniques in the same adult terrestrial-phase California newts (Taricha torosa). In both types of preparation, TEP showed a logarithmic relation to external sodium (as Na2SO4) concentrations between 0.1 and 10 meq/liter, with in vivo values exceeding in vitro values at all points. KM was ca. 1 and 5 meq/liter for the in vivo and in vitro preparations, respectively. When terrestrial-phase newts were treated with prolactin (PRL; 50 mIU/g/day), in vivo TEP declined significantly within 3 days. In vivo TEP versus [Na+]ext curves of recently collected aquatic-phase newts were found to be not significantly different from those of PRL-treated terrestrial-phase animals. Current/voltage (I/V) plots likewise showed that skin from aquatic-phase and PRL-treated terrestrial-phase newts was electrophysiologically alike. Estimates and calculations based on the I/V relationship suggest that PRL acts primarily to increase the epithelial electrical resistance in the transcellular pathway, with no effect on the electromotive force of the sodium pump.

Animals↗
PubMed1988

Electrophysiology of newt skin: responses to salt-depletion, aldosterone, arginine vasotocin and epinephrine.

1. Newts (Taricha granulosa), salt-depleted by 3 weeks' immersion in distilled water, showed significantly higher in vitro integumental short-circuit current (SCC) than control newts immersed in dilute saline. 2. Isolated, in vitro preparations of newt skin responded to aldosterone (10(-6) M), arginine vasotocin (10(-9)-10(-8) M), and epinephrine (10(-7)-10(-5) M) by increasing SCC. 3. The hormonal response of the skin of this salamandrid urodele, as judged from in vitro (Ussing chamber) measurements, is similar to that seen in classical anuran ("frog skin") preparations.

Aldosterone↗
PubMed1988

Class I antigens of the bovine major histocompatibility system are weakly associated with variation in faecal worm egg counts in naturally infected cattle.

Three bulls selected for high faecal worm egg counts and three bulls selected for low faecal worm egg counts were mated to Africander-Hereford cross cows. Faecal worm egg counts were taken on four occasions from the 132 offspring. Also, each animal was typed for 32 class I antigens of the bovine major histocompatibility system (BoLA). Least squares analysis of variance showed that line, sex and some of the antigens were associated with differences in worm egg output in the faeces. After adjusting for the effects of line and sex, cattle with antigen W9 had about twice as many worm eggs in their faeces as cattle without W9; cattle with antigen CA45 had about half the concentration of faecal worm eggs as cattle without CA45. However, the antigen associations were of borderline significance at the 5% level and more work in additional populations is necessary to confirm these associations.

Animals↗
PubMed1987

Sequential 1H NMR assignments and secondary structure identification of human ubiquitin.

1H NMR assignments of human ubiquitin (76 amino acids, Mr 8565) have been made by a combination of DQF-COSY, DQF-RELAY, NOESY, DQ, and isotropic mixing experiments. Complete NH, C alpha H, and C beta H assignments were obtained; resonances not yet assigned are the side-chain amides of Q-40, Q-41, Q-49, N-60, and Q-62 and the peripheral protons (C gamma H and outward) of M-1 and K-27. A total of 558 out of 579 (96%) potentially observable protons were assigned. Particular attention was directed toward obtaining complete assignments of the aliphatic residues (seven Ile, nine Leu, four Val) since these residues form an extensive hydrophobic core and NOEs from these residues are invaluable for structure calculations. The secondary structure elements were also identified from the sequential NOE data and differ slightly in description from the published 2.8 A resolution crystal structure [Vijay-Kumar, S., Bugg, C. E., Wilkinson, K. D., & Cook, W. J. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 3582-3585]; the NMR data suggest that residues 48-50 form a short fifth strand in the beta-sheet and that residues 56-61 form a helical turn. The sequential assignment results presented here are in agreement with the main chain directed assignments presented in the preceding paper [Di Stephano, D., & Wand, A. J. (1987) Biochemistry (preceding paper in this issue)].

Amino Acid Sequence↗
PubMed1987

NMR studies of the interaction of chromomycin A3 with small DNA duplexes I.

1H and 31P NMR spectral analysis of a chromomycin/d(ATGCAT)2 complex provides strong evidence for a nonintercalative mode of drug binding. Investigation of the imino proton region of the duplex suggests a protection of one of the two guanine imino protons from fast exchange with the bulk water up to at least 45 degrees C by the drug. Subsequent one-dimensional nuclear Overhauser enhancement experiments place the exchangeable chromomycin chromophoric hydroxyl proton less than 0.45 nm from this guanine imino proton and the chromophore 7-methyl less than 0.45 from the internal thymine 6-proton and/or the guanine 8-proton. 1H two-dimensional NMR reveals that the duplex retains a right-handed B conformation but there are distortions at the TGC region of one chain and large deviations in the chemical shift of protons relative to the uncomplexed duplex in the other chain in the same TGC region. The data suggest that the chromomycin chromophore is oriented such that the hydrophilic side of the ring system is proximal to the helix center in the major groove near the TG region while the aromatic side of the ring is oriented away from the helix but is partially protected from the solvent by the aliphatic chain, which bends back over the two aromatic protons. Changes in the 31P spectrum of the duplex on binding of the drug are different from the effect of either actinomycin or netropsin on nucleic acid fragments.

Base Composition↗
PubMed1987

Kinetic studies of actinomycin D binding to mono-, oligo-, and polynucleotides.

The kinetics of association of actinomycin D with poly(dG-dC) and the oligonucleotides d-(CGCGCGCG), d(GCGCGC), d(ATGCAT), d(CGCG), and d(GC), as well as with several mononucleotides, have been investigated. In all cases, the association interaction was characterized by several slow, unimolecular processes with qualitatively similar rate constants. The activation enthalpies and entropies for the association of actinomycin with deoxyguanosine 5'-monophosphate resemble closely those typical for calf thymus DNA. This observation of little or no sequence or length dependence in the binding kinetics suggests that the slow phases arise from properties of the drug alone. These results are discussed in terms of both the shuffling model of Fox and Waring [Fox, K.R., & Waring, M.J. (1984) Eur. J. Biochem. 145, 579] and the model of Muller and Crothers [Muller, W., & Crothers, D.M. (1968) J. Mol. Biol. 35, 251] involving both rapidly forming and slowly forming complexes, with the rapidly forming species being the predominant one.

Base Sequence↗
PubMed1987

Moyamoya disease--a review of clinical experience and anaesthetic management.

Moyamoya disease is a rare neurovascular condition that affects both children and adults. Increasingly these patients present for surgical management to improve the cerebral circulation since medical therapy is essentially ineffective. Because of the precarious cerebral circulation, these patients represent an anaesthetic challenge. In this report we review the pathophysiology of moyamoya disease, summarize our experience with seven patients and discuss the anaesthetic management.

Adult↗
PubMed1987

The effect of high-dose mannitol on serum and urine electrolytes and osmolality in neurosurgical patients.

The effect of mannitol on serum and urine electrolytes and osmolality was investigated intraoperatively in neurosurgical patients. Patients in Group A (n = 7) received 1 gm . kg-1 of 20 per cent mannitol ("low"-dose) and in Group B, (n = 7) 2 gm . kg-1 ("high"-dose). There was a significant decrease in serum sodium and bicarbonate, and a significant increase in serum osmolality in both groups after mannitol administration. The decrease in serum sodium and the increase in serum osmolality were significantly greater in patients receiving the larger dose of mannitol. The infusion of low-dose mannitol resulted in a slight decrease in serum potassium. In contrast, after high-dose mannitol there was a significant rise in serum potassium reaching a maximum mean increase of 1.5 mmol . l-1. Urine electrolyte concentration and osmolality showed a similar decrease in both groups. The significant changes that occurred with the administration of mannitol were of short duration in these patients with normal cardiac and renal function. The clinically most important change is the increase in serum potassium with high-dose mannitol. The exact mechanism of this increase remains unclear.

Adult↗
PubMed1987

Breed differences in the frequency of bovine lymphocyte antigens.

Lymphocytes from 1,564 cattle of 18 breeds and cross-bred groups in Australia were tested for major histocompatibility system class 1 antigens. Gene frequencies were calculated for the Angus, Belmont Red, Brahman, Hereford and Holstein-Friesian breeds. There were substantial differences among these breeds in antigen and gene frequency. There were striking differences among all 18 breeds in the presence or absence of certain antigens. Two antigens, CA13 and CA36, were strongly associated in Hereford cattle but occurred independently of each other in the other breeds.

Animals↗
PubMed1986

Computer modeling of actinomycin D interactions with double-helical DNA.

We have performed molecular mechanical calculations on intercalation complexes of actinomycin D with a series of base-paired hexanucleoside pentaphosphates; d(GCGCGC)2, d(GCCGGC)2, d(GCATGC)2, d(GCTAGC)2 and d(ATGCAT)2. Our results are in good agreement with previous experimental work on sequence selectivity. The results provide a rationalization for the strong preference of actinomycin D to intercalate on the 3' side of guanine residues, consistent with previously proposed models. Finally, the computed structures for d(ATGCAT)2-actinomycin D complexes have been compared with two-dimensional nuclear magnetic resonance nuclear Overhauser effect experimental results. To our knowledge, this is the first extensive comparison of molecular mechanical model structures for a drug-DNA complex with experimental solution phase data. We find generally good agreement between our computational models and the experimental solution phase structures.

Computers↗
PubMed1986

Surgical treatment of perineal hidradenitis suppurativa with special reference to recognition of the perianal form.

Severe cases of hidradenitis suppurativa affecting the perineum and gluteal regions may be treated successfully by 'deroofing' the sinus and fistulae tracts. These lie in the dermis and are partly epithelialized by cells from involved hair follicles and disrupted sweat glands. Careful preservation of the floor of the tracts leads to re-epithelialization with disease-free skin. More radical surgery is unnecessary and the problems of covering widely excised areas in this heavily contaminated region are avoided. By spreading the treatment over several operating sessions and hospital admissions, postoperative discomfort and in-patient nursing requirements are minimized. The technique of deroofing is described and the treatment of three severe cases is discussed. One patient illustrated the recognized complication of malignant change occurring in long-standing untreated disease. A fourth case illustrates the difficulties in diagnosing perianal hidradenitis suppurativa and literature cited suggests it to be a more common condition than once thought and a diagnosis frequently missed.

Adult↗
PubMed1986

Changes in body water and plasma constituents during bullfrog development: effects of temperature and hormones.

The osmoregulatory responses to warmer temperatures and hormone treatment in cold-adapted (5 degrees C) Rana catesbeiana tadpoles and newly metamorphosed frogs were examined. Tadpoles transferred to 11 degrees C and 18 degrees C and left for 5 days lost 7% and 10% of their body weight. Plasma [Na+] was elevated 28% and 21%, respectively. Control (5 degrees C) animals maintained their body weight and plasma [Na+] constant. Daily treatment with either ovine prolactin (oPRL) or ovine growth hormone (oGH) prevented the weight loss and the increase in extracellular [Na+] that occurred when tadpoles were transferred to 18 degrees C. Neither propylthiouracil (PTU) nor arginine vasotocin (AVT) were effective in countering temperature-induced weight loss in tadpoles. Newly metamorphosed frogs transferred to 18 degrees C also lost weight; this was not prevented by daily treatment with saline, oPRL, oGH or PTU. However, in frogs treated daily with AVT, initial BW was regained by day 6. When warm-adapted (18 degrees C) tadpoles were treated daily for 18 days with saline, bPRL, bGH, thyroxine (T4), ergocornine, cortisol, or cortisol + T4, bPRL was most effective in retarding weight loss and maintaining body water content, whereas T4 + cortisol caused the greatest loss of weight and body water. By day 20, the correlations between weight loss and both body water content and hematocrit were highly significant. These data suggest that reported increases in plasma solute concentrations in larval amphibians may actually reflect decreases in extracellular fluid volume, rather than increased amounts of solutes, per se.

Animals↗
PubMed1986

Osmoregulatory effects of prolactin and growth hormone in embryonic chicks.

Intact White Leghorn chick embryos were treated daily (on Days 6-13) with bovine prolactin (PRL) or ovine growth hormone (GH) at doses of 4-10 micrograms/g embryo wet wt. A control group received an equal volume of avian saline. [Na+] and [Cl-] were determined in allantoic fluid samples taken on Days 10, 12, and 14, and in amniotic fluid and blood plasma on Day 14. Allantoic fluid, amniotic fluid, and plasma osmolarities, embryo wet weight, hematocrit, and allantoic fluid volume were also determined on Day 14. PRL-treated embryos showed significantly lower allantoic [Na+] and [Cl-] compared to controls at Days 10, 12, and 14. Allantoic fluid osmolarity was reduced, and plasma osmolarity increased, at Day 14 in PRL-treated embryos. By contrast, PRL had no effect on allantoic volume, amniotic fluid [Na+], [Cl-], or osmolarity, plasma [Na+] or [Cl-], hematocrit, or embryo wet weight. GH-treated embryos showed significantly reduced allantoic [Na+] at both Days 10 and 14, but no other treatment effect. Calculations show that the decrease in total allantoic Na+ seen in PRL-treated embryos is equivalent in magnitude to 10% of the total egg Na+. Results from studies on embryonic amphibians and mammals suggest that this sodium is likely to be sequestered in an expanded extracellular volume.

Allantois↗
PubMed1986

Embryonic chick allantois: functional isolation and development of sodium transport.

By removing the shell membranes from the chorioallantoic membrane, the chorion is damaged, as visualized by electron microscopy, and rendered permeable, as evidenced by penetration of horseradish peroxidase and increased inhibition of the allantoic Na+-K+ pump by ouabain applied on the chorionic side. The short-circuit current (SCC) of this functionally isolated allantoic epithelium is augmented by nystatin, a channel-forming ionophore, when applied to the mucosal surface. Electrical parameters were determined for three age groups between 12 and 19 days of incubation. The SCC approximately doubled from the youngest (12-13 days) to the oldest (18-19 days) groups, whereas the transepithelial resistance (Re) of 700-900 omega X cm2 remained the same. Amiloride, an inhibitor of apical Na+ uptake, inhibited 98-100% of the SCC at 10(-4) M in both 15-16 and 18-19 day epithelia. In the 12- to 13-day preparation 20-25% of the SCC was insensitive to 10(-3) M amiloride. The Ki's for amiloride were similar in all preparations, at about 5 X 10(-7) M. Determination of the Hill coefficients for inhibition revealed a lower value (0.75 +/- 0.03) for the 12-13 day preparation compared with the two older preparations with coefficients not significantly different from unity. Replacing Na+ in the bathing solutions abolished the SCC of 18-19 day epithelia, whereas about 15% of the SCC remained at 12-13 days. Thus, during development, the SCC of the allantoic epithelium increases in magnitude and becomes increasingly (to 100%) amiloride-sensitive and Na+-dependent.

Allantois↗
PubMed1986

Auditory backward recognition masking with well-practiced listeners.

Five adult listeners who had extensive previous practice on a pitch discrimination task participated in an auditory backward recognition masking (ABRM) experiment. S identified the relative pitch "higher"-"lower" of a test tone. A standard tone of 20 msec duration at 800 c/s was followed after 500 msec by a similar 20-msec test tone at 800 +/- delta f. delta f varied from 3.3-11.4 c/s across Ss, adjusted for each S to yield approximately 75%-correct performance. The test tone was followed, after a silent interval of 20-250 msec, by a 100-msec mask, either a tone of 800 c/s or white noise. All stimuli were approximately equal to 77 dbA. All Ss exhibited substantial ABRM when the backward mask was a tone but substantially less when it was white noise. Evidently it is not necessary to use relatively naive listeners to demonstrate ABRM. The performance of most Ss was reduced by the tone masker (i.e., ABRM was in evidence) to chance or nearly chance levels (i.e., little or no ABRM) until the ISI exceeded 80 msec, and for 3 of the Ss ABRM with the tone masker was still evident after 250 msec. It was concluded that a backward mask interferes with test-tone information held in a multichannel preperceptual store and that such interference depends, in part, on the degree to which the properties of the test tone and mask overlap.

Acoustic Stimulation↗
PubMed1985

NMR studies of chromomycin A3 interaction with DNA.

The binding of chromomycin A3 to calf thymus DNA and poly(dG-dC) has been studied by 13C and 1H NMR with emphasis on the mode of binding, the role of Mg2+, and pH effects. The most prominent changes in the DNA base pair 13C NMR resonances upon complexation with chromomycin were observed for G and C bases, consistent with the G-C preference exhibited by this compound. Comparison of the 13C spectrum of DNA-bound chromomycin A3 with that of DNA-bound actinomycin D, a known intercalator, showed many similarities in the base pair resonances. This suggested the possibility that chromomycin A3 binds via an intercalative mechanism. 1H NMR studies in the imino proton, low-field region of the spectrum provided additional evidence in support of this binding mode. In the low-field spectrum of chromomycin A3 bound to calf thymus DNA, a small shoulder was observed on the upfield side of the G-C imino proton peak. Similarly, in the chromomycin A3 complex with poly(dG-dC), a well-resolved peak was found upfield from the G-C imino proton peak. These results are expected for ligands that bind by intercalation. Furthermore, in both the calf thymus and poly(dG-dC) drug complexes (in the presence of Mg2+) a broad peak was also present downfield (approximately 16 ppm from TSP) from the DNA imino protons. This was attributed to the C-9 phenolic hydroxyl proton on the chromomycin chromophore. Visible absorbance spectra at different pH values showed that the role of Mg2+ in the binding of chromomycin A3 to DNA is more than simple neutralization of the drug's anionic change.

Animals↗