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Biomedical subjects

M Cox

Publications and source records attributed to M Cox.

At least 127 records · Page 7Linked to original sources

Occupational arthropathy: evidence from the past.

The relation between osteoarthritis and occupation was examined in a group of skeletons from the crypt of Christ Church, Spitalfields, in east London used for burial between 1729 and 1869. Of the total of 968 discrete skeletons excavated, 367 had legible coffin plates giving details of name, age, sex, and date of death. Various sources were used to find the occupations of the group for which these details were known. As many of those buried in the crypt were Huguenots interest centred on the relation between weaving and osteoarthritis of the hands but none was found using a case-control study. Further analyses failed to show a relation between occupation and osteoarthritis of the shoulder or osteoarthritis at any site. There was a statistically significant association between non-manual occupations and osteoarthritis of the spine, the reasons for which are not yet clear.

Bone and Bones↗

Aldosterone-induced proteins: purification and localization of GP65,70.

Aldosterone stimulates sodium transport in responsive epithelia by inducing "effector" proteins that control or modulate transcellular sodium flux. We have previously identified a group of electrophoretically microheterogeneous (pI 5.8-6.2) and polymorphic (Mr 65 and 70) glycoproteins that are specifically induced by aldosterone in toad urinary bladders (TUBs) and cultured toad kidney cells (A6 cell line). We raised a series of monoclonal antibodies (MAb) to these proteins and, using light and electron immunohistochemistry, localized the higher Mr glycoproteins (GP70) to the apical plasma membrane and subapical granules of the sodium-transporting cell of the TUB epithelium, the granular cell. GP70 appears to be discharged into the bladder lumen; this process is increased by phorbol myristate acetate, an agent known to induce granule exocytosis. These findings are consistent with the possibility that GP70 represent components or modulators of the "high-resistance" renal epithelial sodium channel. MAbs reactive against GP65 did not identify these glycoproteins within TUB epithelial cells; these lower Mr aldosterone-induced proteins may be incompletely processed forms of GP70.

Aldosterone↗

Insulin and IGF I receptor-mediated Na+ transport in toad urinary bladders.

We compared the concentration dependence of insulin- and insulin-like growth factor I (IGF I)-stimulated Na+ transport with ligand-receptor affinities in the urinary bladder of the toad Bufo marinus. Threshold, half-maximal, and maximal natriferic concentrations of both peptides were approximately 0.1, 1, and 10 nM, respectively. Amiloride, but not ethyl isopropyl amiloride, (10(-5) M), abolished Na+ transport. Maximal responses to either peptide rendered the tissue insensitive to challenge with the other. Separate insulin and IGF I receptors were identified by equilibrium binding and polyacrylamide gel electrophoresis of cross-linked ligand-receptor complexes. For both peptides, half-maximal binding occurred at 3-10 nM; crossover binding to the other receptor occurred with 10- and 100-fold lower affinity. Thus, in this model "high-resistance" renal epithelium, 1) ligand binding to specific insulin and IGF I receptors stimulates transcellular Na+ flux, 2) the natriferic effects of insulin and IGF I apparently depend on activation of apical Na+ channels rather than Na+-H+ antiporters, and 3) the natriferic pathways activated by insulin and IGF I appear to converge subsequent to ligand-receptor binding but before the final transport ("effector") step(s).

Amiloride↗

Sport fish consumption advisories and projected cancer risks in the Great Lakes basin.

Because Great Lakes sport fish are contaminated with several toxicants, the Great Lakes states individually issue advisories, principally based on Food and Drug Administration (FDA) action levels, that suggest limiting or eliminating consumption of contaminated fish. We describe the procedures the states use to determine when to issue consumption advisories and we evaluate the associated cancer risks using EPA-IARC-OSTP risk assessment procedures. Projected cancer risks are high for consumers of small quantities of sport fish contaminated with DDT or dieldrin at their respective action levels. Projected risks at concentrations that are common but below the action levels are also substantial. We propose that sport fish with tissue concentrations of DDT or dieldrin one-fifth and one-third of the action levels should be covered by consumption advisories to warn consumers of the potential adverse health impacts.

Animals↗

Evaluation of dressing protocols that reduce peritoneal dialysis catheter exit site infections.

Exit site infections (ESIs) remain a major complication of peritoneal dialysis (PD). This study was designed to evaluate various catheter care techniques that would decrease ESIs during the 3 months following catheter implantation. Factors that affect wound healing were studied by evaluating preoperative and postoperative variables, skin cleansing agents, and three types of dressings. A 40% reduction in ESIs occurred following implementation of a new protocol that was developed from the knowledge acquired after studying the catheter care protocols.

Bandages↗

Aldosterone-induced glycoproteins: electrophysiological-biochemical correlation.

Aldosterone induces the synthesis of a group of glycoproteins (GP65,70) in toad urinary bladders which are potential effectors of the natriferic action of this hormone. In the present study we have confirmed that aldosterone produces a two-phase electrophysiological response. During the early phase (less than 3 h) short-circuit current and transepithelial conductance increase in parallel, while during the late phase (greater than 3 h) short-circuit current continues to increase without any further change in conductance. By biosynthetically labeling aldosterone-treated toad bladders with [35S]methionine either during the early (h 0-2 or 1-3) or the late (h 4-6 or 7-9) phases of the natriferic response, we have demonstrated that GP65,70 is synthesized as a late effect of aldosterone. Since synthesis of GP65,70 occurs at a time when the electromotive force of the Na+ pump is increasing, and since GP65,70 biochemically resembles the beta subunit of Na+/K+-ATPase, studies were undertaken to examine whether GP65,70 is the beta subunit. Purified amphibian renal beta subunit was analyzed by two-dimensional polyacrylamide gel electrophoresis and was found to have an isoelectric point and Mr value similar to those of GP65,70. However, when nitrocellulose blots containing wheat germ agglutinin-purified proteins from aldosterone-treated bladders were stained with monospecific polyclonal antibodies developed against the beta subunit, GP65,70 was not recognized, whereas a group of slightly more acidic proteins of similar Mr were recognized. Thus, GP65,70 is not the beta subunit of Na+/Ka+-ATPase. Further studies are needed to determine the cellular function of GP65,70.

Aldosterone↗

Retinoschisis associated with optic nerve pits.

Stereoscopic transparencies studied with magnification and projection suggest that the retinal elevation that communicates with optic pits is frequently a schisislike separation of the internal layers of retina. Thirteen of 15 eyes with optic pits and maculopathy fit the schisis pattern. Separation of the outer layers of the retina is a secondary phenomenon that starts in the macula.

Adult↗

The role of operator position in SV40 T-antigen-mediated repression.

We have manipulated positional relationships between the SV40 early operator and promoter to study the repression of transcription by T antigen. Single or multiple insertions of T-antigen-binding region I resulted in only weak repression even when the operator was placed immediately adjacent to known promoter elements. The low levels of repression appear to reflect the intrinsic strength of the T-antigen-operator interaction.

Antigens, Polyomavirus Transforming↗

Insulin-like growth factor 1 stimulates renal epithelial Na+ transport.

Insulin-like growth factor 1 (IGF1) stimulates vectorial Na+ transport in a classical model of the mammalian distal nephron, the toad urinary bladder. Net mucosal to serosal Na+ flux is stimulated by concentrations of IGF1 as low as 0.1 nM, and the response is maximal at 10 nM. Na+ transport increases within minutes of the serosal addition of IGF1, reaches a maximum in 2-3 h, and is sustained for at least 5 h. Neither the initial nor the sustained response to IGF1 is dependent on a new protein synthesis. The IGF1 response is inhibited by a concentration of amiloride (10(-5) M) that is known to specifically block the conductive apical Na+ channel but that has little effect on the Na+-H+ antiporter. Further studies will be necessary to establish a role for this growth factor in normal renal epithelial function, but it is possible that the natriferic and growth-stimulatory effects of IGF1 are intimately related.

Animals↗

Increased resting energy expenditure in cystic fibrosis.

To explore the hypothesis that there is an increased metabolic rate in cystic fibrosis, resting energy expenditure was measured by indirect calorimetry in 23 subjects with cystic fibrosis in a stable clinical state and in 42 normal control subjects. Resting energy expenditure was found to be elevated by an average of 0.45 MJ/24 h [95% confidence interval (CI) = 0.26-0.64, t = 4.91, P less than 0.001] (108 kcal/24 h), or 9.2% above expected values derived from the regression relating resting energy expenditure to whole body weight and sex in control subjects. When related to lean body mass, values were still elevated by 0.36 MJ/24 h (95% CI = 0.18-0.53, t = 4.15, P less than 0.001) (86 kcal/24 h), or 7.2%. The increased values were found to be independent of age, sex, or body size. There were significant correlations between increased values and poor pulmonary function as measured by the ratio of the forced expiratory volume in 1 s to forced vital capacity (r = -0.44, P less than 0.05) and subclinical infection as indicated by the blood leukocyte count (r = 0.40, P less than 0.05). However, the correlations were low, suggesting that other factors may contribute to the increased resting energy expenditure, possibly including the putative metabolic defect in cystic fibrosis.

Adolescent↗

Lithium-induced renal disease: a prospective study.

Considerable controversy exists as to whether lithium maintenance therapy is associated with the development of renal insufficiency. In 1980 we initiated a prospective study of renal function in manic-depressive patients beginning lithium therapy. None of the patients had evidence of pre-existing renal disease. Sixty-five patients were entered, and 51 and 18 patients completed 1 and 3 years of follow-up, respectively. Lithium doses were titrated to the lowest level consistent with control of psychiatric symptoms; there were no episodes of overt lithium intoxication. Serum creatinine levels in all patients, and endogenous creatinine clearance in women, remained stable over the course of the study. In contrast, creatinine clearances (mean +/- SEM, ml/min/1.73 m2) in men significantly decreased over both 1 year (110 +/- 4 to 95 +/- 5, n = 21, p = 0.0126) and 3 years (107 +/- 4 to 80 +/- 11, n = 8, p = 0.0385) of evaluation. Although all patients demonstrated a mild reduction in renal concentrating ability after initiation of lithium, the decrease was not progressive over the course of the study. Quantitative urinary protein excretion did not change, and repeated urinalyses did not reveal any evidence of renal disease. Thus, lithium therapy appears to result in modestly reduced rates of glomerular filtration, as measured by endogenous creatinine clearance, in men receiving lithium maintenance therapy for manic-depressive illness. Whether this reduction is progressive and leads to clinically significant renal insufficiency requires further investigation.

Adult↗