Conformational studies of myelin basic protein (MBP) in solution generally have used protein purified in organic solvents and acid. The use of such conditions raises the possibility that the secondary structure reported for the basic protein represents a denatured state. Therefore we have purified this protein by using a procedure that avoids denaturants. Bovine myelin was extracted with 0.2 M-CaCl2 and the protein was purified from the supernatant by chromatography on Sephadex G-75. The conformation of the basic protein was characterized by using c.d. and 1H-n.m.r. spectroscopy. In solution, it appeared to be predominantly randomly coiled, with only small segments of persistent structure. However, in the presence of myristoyl lysophosphatidylcholine the secondary structure of MBP became more ordered, and sedimentation-velocity experiments showed that MBP aggregated. Comparison of our results with published data indicates that Ca2+-extracted basic protein behaves similarly to the protein purified by traditional methods with respect to its ordered conformation in solution in the absence and in the presence of lipid and with respect to its self-association. Thus its thermodynamically stable structure in aqueous solution appears to be a highly flexible coil.

Animals↗

PubMed1989

Models of spinal trabecular bone loss as determined by quantitative computed tomography.

Noninvasive bone densitometry techniques have significantly improved our understanding of the pattern and magnitude of bone loss over the life span. Quantitative computed tomography (QCT) is capable of selectively measuring highly labile trabecular bone in the central portion of the vertebrae. Trabecular bone mineral density (mg/ml) was determined in 538 healthy women ranging in age from 20 to 80 using GE CT/T scanners at 80 kVp. Various statistical regressions were performed for the entire population to describe the general pattern of bone loss from the spine; a cubic model (r = -0.69, SEE = 26.0 mg/ml) was found to be statistically superior (p less than 0.01) to linear, quadratic, or exponential models. An average bone loss was approximated from these regression analyses with a yearly absolute rate of -2.02 +/- 0.097 mg/ml per year (p less than 0.0001). The average rate of change for premenopausal women was -0.45 mg/ml per year (p less than 0.05), for perimenopausal women was -4.39 mg/ml per year (p less than 0.0001) and for postmenopausal women was -1.99 mg/ml per year (p less than 0.0001). QCT values were also stratified into 5 and 10 year age groups and analyzed separately for pre- and postmenopausal women. The 5 and 10 year interval stratification revealed no identifiable bone density decrements prior to midlife using analysis of variance statistical methods; significant losses of bone mineral density were noted to correspond with the usual time of menopause and to continue into old age. Various two-phase regressions were employed using age and menstrual status to improve the description of age- and menopause-related bone loss.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Mineralocorticoid specificity of renal type I receptors: binding and metabolism of corticosterone.

In cytosol preparations renal mineralocorticoid receptors have equivalent affinity for aldosterone and corticosterone; in vivo, such receptors are clearly aldosterone-selective. To explore this difference, we have compared the binding of both steroids in kidney slices, high speed supernatants and true cytosols in vitro, in the presence of RU28362 to exclude steroids from Type II glucocorticoid receptors, and/or in the presence of cortisol 17 beta-COOH to exclude corticosterone from transcortin. In addition, we have explored the effect of tissue preparation and cortisol 17 beta-COOH on the level of activity of the renal enzyme 11 beta-OH steroid dehydrogenase. The results of the present studies support the hypothesis that the predominant aldosterone specific-conferring mechanism for renal Type I receptors in vivo in the enzyme 11 beta-OH steroid dehydrogenase, and underline the potential difficulties in interpreting studies which include multiple potential ligands to multiple potential binding sites.

Aldosterone↗

PubMed1989

The action of hypothalamic and placental corticotropin releasing factor on the corticotrope.

Explore the source record for details and available documents.

Adrenocorticotropic Hormone↗

PubMed1989

Preventing osteoporosis with exercise: a review with emphasis on methodology.

Exercise is thought to have considerable potential as a preventive for osteoporosis. We critically examined 27 studies that address the prophylactic role of exercise in osteoporosis. The results from both cross-sectional and longitudinal studies showed that differences in bone mass were more pronounced in the axial skeleton as opposed to the peripheral compact skeleton. The 17 cross-sectional studies demonstrated greater bone mass among highly trained athletes compared with sedentary subjects, while results among recreational athletes were inconsistent. The 10 prospective investigations examining the effect of exercise on bone mass yielded conflicting results; only one study of six found an overall positive response in compact bone mass at the radial site, and only one study examining the spine showed a significant gain among the exercisers. Additionally, all the prospective investigations included serious methodologic flaws; most failed to employ a randomized design, appropriate estimates of sample size were lacking, none provided information on blind outcome assessment, and most studies were of short duration. Current evidence suggests that exercise may have only limited value in affecting bone mass in the short term and widespread recommendations for the prophylactic use of exercise should await further validation using better methodological rigor.

Bone and Bones↗

PubMed1989

Iododeoxyuridine (IdUrd) incorporation into DNA of human hematopoietic cells, normal liver and hepatic metastases in man: as a radiosensitizer and as a marker for cell kinetic studies.

Iododeoxyuridine (IdUrd) was administered as a continuous infusion for 14 days to patients with glioblastoma and sarcoma, and for 3 days to patients with metastatic colorectal carcinoma. In the first group, the maximum incorporation of IdUrd into DNA was determined, taking granulocytes as parameter. In the second group, selective incorporation into DNA of normal liver and hepatic metastases of colorectal cancer was investigated. The highest dose of 675 mg/sq.m./day for 14 days produced IdUrd plasma concentrations of 1.8 +/- 0.3 microM, and a substitution of dThd by IdUrd in the range of 7.1-11.7%. Coadministration of fluorodeoxyuridine did not show significant enhancement of IdUrd-incorporation in granulocytes. Three-day intravenous infusions of IdUrd 1000 mg/sq.m./day produced 1.7-4.5% IdUrd-incorporation in hepatic metastases. Three-day intraarterial infusions (hepatic artery) produced 3.8-10.5% dThd-replacement, whereas, in 9/10 patients this was less than 1% in normal liver. In tumor tissue there was a trend towards FdUrd-modulated enhancement of IdUrd-incorporation, although there was considerable scatter. Cell kinetic studies revealed that IdUrd-incorporation in monocytes and granulocytes was very similar. In lymphocytes, a much lower fraction incorporated IdUrd. Liver tumor contained a considerably higher fraction of IdUrd-labeled cells, compared with normal liver. Potential doubling times for the tumors were estimated to be 10 days.

Cell Cycle↗

PubMed1989

Importance of balloon size in coronary angioplasty.

The effect of balloon size on the success of coronary angioplasty was studied to develop quantitative criteria for optimal selection of balloon size. Coronary dimensions of 165 stenotic lesions were measured by computer-assisted cinevideodensitometry in 120 patients who had undergone angioplasty with a balloon selected by visual estimates. Cross-sectional areas and diameters of normal and stenotic arterial segments were measured before and after angioplasty by a previously validated cinevideodensitometric technique. The diameter of the inflated balloon compared with that of the normal arterial segment was expressed as a ratio for sizing balloons. Oversized balloons with a ratio greater than 1.3 (n = 35) caused a high (37%) incidence of dissection, with three severely compromised arterial lumens. Undersized balloons with a ratio less than 0.9 (n = 29) often resulted in significant (greater than 50% diameter stenosis) residual stenotic lesions (21%) and a significantly (p less than 0.05) higher rate of repeat angioplasty for restenosis. Selection of balloon sizes with ratios in the 0.9 to 1.3 range (n = 101) resulted in a low (4%) incidence of dissection with few patients (3%) having significant residual stenosis. Mean residual stenosis (percent diameter reduction) was most severe for undersized (35.0 +/- 18%) or oversized (23.1 +/- 19%) balloons and least severe for balloons with a ratio of 0.9 to 1.3 (18.7 +/- 14%) (p less than 0.001). Repeat angioplasty for restenosis was more frequently required (p less than 0.05) for lesions dilated with undersized balloons. Thus, selection of angioplasty balloons that approximate or slightly exceed the diameter of the normal arterial diameter yields optimal angiographic results with minimal dissections and minimal residual stenotic lesions.

Angioplasty, Balloon↗

PubMed1989

Determination of the structure of a membrane-incorporated ion channel. Solid-state nuclear magnetic resonance studies of gramicidin A.

Solid-state nuclear magnetic resonance (NMR) measurements on 13C-labeled analogues of the ion channel-forming peptide, gramicidin A, have been used to directly determine the structure of this peptide in lipid membranes. Seven gramicidin analogues, each labeled in a single carbonyl group of gly2, L-ala3, D-leu4, L-val7, D-leu10, D-leu12, or D-leu14 were synthesized by the solid-phase method. These gramicidin analogues were incorporated into aligned multilayers of dimyristoylphosphatidylcholine, or diether lipid bearing 14- or 16-carbon chains, at a 1:15 peptide:lipid mole ratio. Proton-enhanced, 13C, solid-state spectra were obtained at several temperatures and over a range of sample orientations with respect to the spectrometer magnetic field to permit accurate measurement of the chemical shift anisotropies. The observed anisotropies indicate that all of the labeled carbonyl bonds are oriented almost parallel to the molecular long axis and perpendicular to the lipid bilayer plane. These orientations are consistent with gramicidin forming a beta 6.3 single-strand helix that is oriented parallel to the methylene chains of the lipid molecules. Comparison of the linewidths from labeled residues that are in the innermost turn of the helix (gly2, ala3, and D-leu4), in the center of the molecule (val7), and in the turn nearest the lipid bilayer surface (D-leu10, D-leu12, and D-leu14) suggests that although the peptide behaves largely as a rigid barrel, segments of the peptide close to the membrane surface possess greater motional freedom. At temperatures above the gel-to-liquid crystalline transition temperature (Tc) the gramicidin molecules rotate, with a less than millisecond correlation time, about the bilayer normal: several degrees below Tc they become immobile on the NMR timescale, without change in the channel conformation. In the L beta' phase the linewidths of the D-leu10, D-leu'2, and D-leu" resonances become equal to those of the other labeled sites, indicating reduced but equivalent motion for all of the peptide carbonyl groups.

Amino Acid Sequence↗

PubMed1989

Expertise, procedure and the possibility of a comparative history of forensic psychiatry in the nineteenth century.

The comparative history of forensic psychiatry may help unravel relations between legal and administrative procedure, medical knowledge and expertise, and social interests, as they determine judgements about the criminal responsibility of the mentally disordered. But little has been done to compare the past or the present under different jurisdictions. This paper, therefore, suggests some points which would encourage such comparisons, and particularly a comparison between France and England in the nineteenth century, for both of which countries there is now a valuable historical literature. It also illustrates the complex interaction of procedure and medical expertise by reference to the case of George Victor Townley (1863).

Cross-Cultural Comparison↗

PubMed1989

Relation between plasma beta-endorphin and the ventilatory response to hypercapnia in humans.

1. Endogenous opioids have been implicated in the control of breathing in neonates, but their role in ventilatory control in adults remains unclear. 2. We studied the relationship between circulating immunoreactive beta-endorphin and the ventilatory and mouth occlusion pressure responses to hypercapnia in 12 healthy male subjects. In addition, we examined the effect of repetitive hypercapnia on plasma beta-endorphin and cortisol levels. 3. A weak but significant negative relationship between the ventilatory response to hypercapnia and basal plasma beta-endorphin levels was observed (r = -0.35, P less than 0.01). A similar negative relationship was noted between mouth occlusion pressure response to hypercapnia and basal plasma beta-endorphin levels (r = -0.36, P less than 0.01). 4. Repetitive hypercapnia prevented the fall in plasma cortisol that occurred under control conditions (P less than 0.02) but had no effect on plasma beta-endorphin. 5. We conclude that plasma beta-endorphin may play a role in the central chemical control of breathing in man.

Adult↗