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Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 1,117 records · Page 62Linked to original sources

Equilibrium binding of myristoyllysophosphatidylcholine to bovine myelin basic protein: an example of ligand-mediated acceptor association.

The interaction of myristoyllysophosphatidylcholine with bovine myelin basic protein at pH 7.4 and 4.5, I = 0.48, has been investigated by a recycling partition equilibrium technique with Bio-Gel P-2 as the gel phase. Important points to emerge from this direct binding study are that it is a monomeric (not micellar) amphiphile that binds to myelin basic protein, that the amphiphile binds preferentially to the monomeric form of myelin basic protein, that this binding to monomer is highly cooperative, that the similarity of binding behavior in the two environments tested is consistent with the dominance of a hydrophobic contribution to the protein-amphiphile interaction, and that the self-association of myelin basic protein in the presence of phospholipid [Smith, R. (1982) Biochemistry 21, 2697-2701] must reflect the aggregation of a protein-amphiphile complex(es) coupled with concomitant release of some lipid. These findings are then related to earlier nuclear magnetic resonance and circular dichroism studies in which the results were interpreted on the basis that myelin basic protein bound preferentially to micellar phospholipid.

Animals↗

Maternally transmitted antigens are codominantly expressed by mouse cells containing two kinds of mitochondrial DNA.

Mtf, a cytoplasmic, probably mitochondrial factor, controls Mta polymorphism. We tested for dominance between two forms of Mtf to determine whether Mta is controlled by positive or negative genetic mechanisms. We fused Mtf-disparate cells containing distinct mtDNA markers and selected for hybrids containing both. Such mtDNA heteroplasmons codominantly and stably express alternative Mta antigens. Stable codominance excludes negative genetic mechanisms as well as a model of induced nuclear compensation, and implies Mtf controls Mta expression through a positive genetic mechanism.

Animals↗

The enzymatic degradation of polymers in vitro.

Specimens of 14C-labeled poly(ethylene terephthalate), nylon 66, and poly(methyl methacrylate) have been synthesized and exposed, in vitro, to a number of enzyme solutions. Poly(ethylene terephthalate) was found to be affected by esterase and papain, although in different ways, but not by trypsin or chymotrypsin. Nylon 66 was unaffected by esterase but degraded by the other three. Poly(methyl methacrylate) was not affected by any of these enzymes. This indicates that some nominally stable polymers are susceptible to degradation by enzymes under some circumstances. The amount of degradation is small, but could have significant sequelae should it be reproduced in vivo.

Chymotrypsin↗

"Pyruvate recycling" and its influence on the estimation of the pentose pathway in intact liver and Morris hepatoma 5123TC cells.

The phenomenon of "pyruvate recycling" is demonstrated in perfused rat liver, rabbit liver in situ and in Morris Hepatoma 5123TC cells and quantitatively measured using [2-14C]pyruvate and the method of Friedmann et al. (1971). Various metabolites, viz. lactate, DHAP, glucose, glucose 6-P and fructose 6-P were isolated and degraded following the metabolism of [2-14C]pyruvate and [2-14C]glycerol in order to assess the 14C-distributions imparted by "pyruvate recycling" reactions. The labelling of DHAP, lactate, glucose and glucose 6-P showed 14C randomizations consistent with the operation and the quantitative extent of "pyruvate recycling". These findings support the proposal that the actions of "pyruvate recycling" may account for the failure to find significant levels of 14C isotope at C-1 of glucose 6-P following the metabolism of [4,5,6-14C]- or [6-14C]glucose by L-type pentose pathway metabolism in aerobic intact tissues. "Pyruvate recycling" diminishes the measured value of the L-type pentose cycle in intact tissues and qualifies one of the mechanistic predictions of the L-type pentose pathway which was unravelled by tracing its reactions with labelled ribose 5-P and liver enzymes (Horecker et al., 1954; Williams et al., 1978a,b) in vitro. The demonstration of an association of L-type pentose pathway reactions with "pyruvate recycling" by way of the common reactions of their triose-P intermediates qualifies the superficial acceptance of the predictions of the L-type pathway in vitro for the distribution of isotopic labels by aerobic tissues in vivo.

Animals↗

Differences between the F10, BL6 and F1 sublines of the B16 melanoma in the enhancement of plasminogen activator and plasminogen activator inhibitor secretion by phorbol myristate acetate.

Analysis of conditioned medium from three sublines of the B16 melanoma [F1 (parental), BL6 (invasive), F10 (metastatic)] by SDS-PAGE and zymography revealed the presence of plasminogen activator activity at 60,000 daltons. The relative activity was F10 greater than F1 greater than or equal to BL6. Treatment of the cells with the tumor promoter, phorbol myristate acetate (PMA) led to increased secretion of PA by F10 cells and a lesser increase in secretion by F1 cells and BL6 cells. In addition, a second plasminogen activator activity at 45,000 daltons was detected in conditioned medium from PMA treated F10 cells. Conditioned medium from F10 and F1 cells was also shown to contain a 33,000 dalton plasminogen activator binding protein. Upon PMA treatment the concentration of the binding protein increased in medium from F10 cells but not in similarly treated F1 cells. The binding protein, very likely a plasminogen activator inhibitor, was nearly undetectable in conditioned medium from control and PMA-treated BL6 cells. Therefore, the three sublines, which differ in in vivo phenotypic characteristics, also differ in their in vitro regulation of proteinase and proteinase inhibitor synthesis.

Animals↗

In vivo effects of beta-endorphin on lymphocyte proliferation and interleukin 2 production.

Experiments were undertaken in rats to investigate the effects of in vivo infusion of beta-endorphin (BEP) on subsequent Con A-induced proliferation and interleukin 2 (IL-2) production by spleen cells in vitro. BEP administration induced a dose-dependent enhancement of the proliferative response to Con A. Infusion of the opiate antagonist naloxone (NAL) inhibited the Con A response and infusion of NAL prior to BEP resulted in even further inhibition. None of these treatments resulted in detectable alterations in IL-2 production after 48 h in culture. To demonstrate a direct interaction between BEP and lymphocytes, spleen cells were incubated in vitro with varying concentrations of BEP and/or NAL. Enhanced Con A-induced proliferation was observed following incubation with BEP in the range 10(-12) to 10(-9) M (levels comparable to the effective in vivo doses) and this effect was abrogated by NAL pretreatment (10(-6) M). These data indicate a role for BEP in enhancing lymphocyte reactivity which is to some extent dependent on opiate receptors on the cell surface. This report extends the evidence obtained from in vitro experiments implicating endogenous opioids in modulation of host immunity by demonstrating that these effects can be obtained in vivo.

Animals↗

Quantitative computed tomography in assessment of osteoporosis.

Computed tomography (CT) has been widely investigated and applied in recent years as a means for noninvasive quantitative bone mineral determination. The usefulness of computed tomography for measurement of bone mineral lies in its ability to provide a quantitative image and, thereby, measure trabecular, cortical, or integral bone, centrally or peripherally. For measuring the spine, the potential advantages of quantitative computed tomography (QCT) over dual-photon absorptiometry (DPA) are its capability for precise three-dimensional anatomic localization providing a direct density measurement, and its capability for spatial separation of highly responsive cancellous bone from less responsive compact bone. Currently, QCT vertebral mineral determination has been implemented at over 800 sites encompassing a wide geographic distribution and a wide array of commercial scanners. With a world-wide distribution of approximately 8,000 advanced CT body scanners, the capability now exists for widespread application of vertebral bone mineral determination by quantitative computed tomography. These QCT techniques for vertebral mineral determination have been used to study skeletal changes in osteoporosis and other metabolic bone diseases. Longitudinal and cross-sectional bone mass measurements have been obtained at the University of California at San Francisco (UCSF) in over 3,000 patients seen clinically or on research protocols. The results presented here illustrate the use of QCT spinal mineral measurement in the delineation of normal age-related bone loss, in the evaluation of estrogen effects on bone, in the assessment of fracture threshold and risk, and in the study of the effects of various exercise regimens on bone mineral and the determination of relationships to other techniques of bone mineral measurement. The laboratory and clinical results presented herein indicate that QCT provides a reliable means to evaluate and monitor the many forms of osteoporosis and the various interventions aimed at ameliorating this condition. The greatest advantages of spinal QCT for noninvasive bone mineral measurement lie in the high precision of the technique, the high sensitivity of the vertebral trabecular measurement site, and the potential for widespread application.

Aging↗

Opioid peptides in blood and cerebrospinal fluid during acute stress.

The opioid peptides beta-endorphin and [met]enkephalin are present in the peripheral circulation. Plasma beta-endorphin originates from the pituitary gland and its cosecretion with ACTH is stimulated by a variety of noxious stimuli. Although the adrenal medulla contains high concentrations of [met]enkephalin-containing polypeptides which are costored with catecholamines, and although the adrenal gland appears to secrete [met]enkephalin into the adrenal vein, the relative adrenal contribution to plasma [met]enkephalin appears to be negligible. Plasma concentrations of immunoreactive [met]enkephalin may be increased by insulin and by endotoxic shock, but they are not significantly altered by acute haemorrhagic stress nor by surgical stress. Thus blood plasma concentrations of beta-endorphin, but not of [met]enkephalin, are generally increased during acute stress. The physiological significance of endogenous opioids in the circulation is not known. It is unlikely that transient increases in the concentrations of opioid peptides in peripherally circulating blood modulate nociception, since the peptides do not enter ventricular cerebrospinal fluid in detectable amounts under these conditions. Recent evidence has raised the possibility that circulating opioids may be involved in regulating blood glucose and in activating the immune system. It is also possible that circulating beta-endorphin and related polypeptides have non-opioid actions on a variety of peripheral tissues.

Acute Disease↗

The nonsuppressibility of plasma cortisol persists after pregnancy.

To determine if normal balance is restored to the hypothalamic-pituitary-adrenal axis after pregnancy, we compared the dexamethasone suppressibility of plasma cortisol in women four days after delivery of their infant, with that of nonpregnant women. Plasma concentrations of cortisol before dexamethasone administration were similar in the post-partum women and in women taking oestrogen contraceptives, but both were higher than in normally cycling women. After dexamethasone, plasma cortisol in the post-partum women was significantly higher than in both oestrogen-taking and normally cycling nonpregnant women. The reduced dexamethasone-suppressibility of plasma cortisol, which is characteristic of pregnancy, extends into the post-partum period.

Contraceptives, Oral↗

Parapoxvirus infections in New Zealand farmed red deer (Cervus elaphus).

Outbreaks of infection due to a parapoxvirus were reported on eight New Zealand deer farms. Scabby lesions were seen variably on the muzzle, lips, face, ears and neck of red deer (Cervus elaphus) with morbidity rates reaching 100%. On three farms multifocal lesions were also present on the velvet. Deaths were reported on two properties where the lesions were extensive and secondary bacterial infections had occurred. On one of these farms multifactorial disease was suspected. Poxvirus particles were seen by negative contrast electron microscopy in scab material from all eight properties. Morphologically the deer virus resembled a parapoxvirus, but restriction endonuclease analysis showed its DNA fragment patterns were distinct from those of orf (contagious ecthyma) virus.

Journal Article↗

Joint mobility with particular reference to racial variation and inherited connective tissue disorders.

Joint mobility scores were compared in 248 normal English Caucasian males and females between the ages of 8 and 70 years. The results were contrasted with those in a group of normal Asian Indians and patients suffering from a variety of inherited disorders including Type II Ehlers-Danlos syndrome (EDS), Type I osteogenesis imperfecta (OI), Marfan syndrome, generalized osteoarthritis (GOA), achondroplasia and pseudoachondroplasia. The first-degree relatives of ten subjects with severe or lethal OI were also examined. Asian Indians were significantly more mobile than English Caucasians. Males and females with EDS were hypermobile but only the females with OI and the female relatives of those with severe or lethal OI showed excess joint laxity. Patients with pseudoachondroplasia exhibited a grosser type of joint laxity than other subjects while those with GOA represented a relatively stiff group. No evidence was found to support the view that hypermobility is associated with particular length variants at the Type II collagen structural gene locus (COL2A1).

Achondroplasia↗