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Biomedical subjects

M J Field

Publications and source records attributed to M J Field.

152 records · Page 9Linked to original sources

Characterization of a structural glycoprotein from bovine ligamentum nuchae exhibiting dual amine oxidase activity.

A structural glycoprotein has been extracted from bovine ligamentum nuchae by using 5 M guanidine hydrochloride containing a disulfide bond reducing agent and purified by preparative gel electrophoresis. The isolated material appeared to be monodisperse, with a molecular weight of approximately 34000, as shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by analytical ultracentrifugation. It contains 10% carbohydrate comprising mannose, N-acetylglucosamine, galactose, and sialic acid in a 6:5:3:3 molar ratio. The glycoprotein has been assayed for peptidyl-lysine oxidase activity by using [3H]lysine-aortic elastin, prepared from 15- to 17-day-old chick embryos, as a substrate. In the absence of free lysine, the specific activity of the preparation over a 2-h incubation was approximately 60 X 10(4) dpm/mg of purified protein. Addition of 10 mM lysine resulted in an approximately 50% decrease in the specific activity. Free lysine was shown to act as a substrate for the glycoprotein preparation as indicated by control experiments using [3H]lysine in place of the aortic substrate. These results demonstrate that the glycoprotein exhibits a dual amine oxidase activity. In the presence of 0.27 mM beta-aminopropionitrile fumarate, a concentration which completely inhibits peptidyl-lysine oxidase activity in other lysyl oxidases, the glycoprotein preparation was inhibited by approximately 14%. In the absence of 5 M guanidine hydrochloride and reducing agent, the glycoprotein undergoes aggregation which in the presences of copper ions results in the formation of cylindrical tactoids, the diameter of which (11 nm) corresponds closely to that of the fibrils which in the majority of connective tissue matrices constitute the microfibrillar component mainly associated with elastic fibers.

Amino Acid Oxidoreductases↗

The impact of Hill-Burton: an analysis of hospital bed and physician distribution in the United States, 1950-1970.

The Hospital Survey and Construction Act of 1946, commonly known as the Hill-Burton Act, was intended to improve the supply, distribution and quality of general hospital beds across the United States. Some also saw the program as a means of affecting the supply and distribution of physicians. The strategy used here for evaluating the Hill-Burton program derives in part from the assumptions about health resources supplies on which Hill-Burton policy was found and in part from a model of socioeconomic convergence developed in public policy research on the American states. Major conclusions include 1) Hill-Burton had a major redistributive impact on state bed supplies; 2) physician redistribution lagged far behind progress in bed redistribution; and 3) interstate distribution of physicians appears to have been unaffected by Hill-Burton-associated bed redistribution, a finding contrary to other work in this area.

Beds↗

Direct comparison of cognitive facilitation by physostigmine and tetrahydroaminoacridine in two primate models.

Cognitive facilitation by physostigmine and tetrahydroaminoacridine (THA) was compared in two primate models. Disruption of spatial delayed response performance by scopolamine (0.03 mg/kg) was fully reversed by coadministration of 5 doses of physostigmine in the range 0.03-0.08 mg/kg, but by only one dose (4.0 mg/kg) of THA; partial reversal of some effects of scopolamine was observed at 1 and 3 mg/kg of THA. Visual recognition memory was enhanced following treatment with 4 doses of physostigmine in the range 0.001-0.03 mg/kg. The effect of THA across the group of animals was not significant but performance tended to improve using a dose of 0.8 mg/kg. Our findings indicate that THA does not have a superior profile to physostigmine as a cognitive enhancer in primates.

Animals↗

Fibrogenic effects of cyclosporin A on the tubulointerstitium: role of cytokines and growth factors.

The clinical utility of cyclosporin A (CyA) as an immunosuppressive agent has been significantly limited by the frequent occurrence of chronic nephrotoxicity, characterised by tubular atrophy, interstitial fibrosis and progressive renal impairment. The pathogenesis of this condition remains poorly understood, but has been postulated to be due to either direct cytotoxicity or indirect injury secondary to chronic renal vasoconstriction. Using primary cultures of human proximal tubule cells (PTCs) and renal cortical fibroblasts (CFs) as an in vitro model of the tubulointerstitium, we have been able to demonstrate that clinically relevant concentrations of CyA are directly toxic to these cells and promote fibrogenesis by a combination of suppressed matrix metalloproteinase activity and augmented fibroblast collagen synthesis. The latter effect occurs secondary to the ability of CyA to stimulate autocrine secretion of insulin-like growth factor-I by CFs and paracrine secretion of transforming growth factor-beta(1) by PTCs. Many of these pro-fibrotic mechanisms are completely reversed by concurrent administration of the angiotensin-converting enzyme inhibitor, enalaprilat, which has proven efficacy in preventing chronic CyA nephropathy in vivo. These studies highlight the unique potential that human renal cell cultures offer for studying the role of local cytokine networks in tubulointerstitial disease and for developing more effective treatment strategies which specifically target fibrogenic growth factor activity following nephrotoxic injuries.

Animals↗

Thin-membrane nephropathy--a common cause of glomerular haematuria.

Thin-membrane nephropathy recently has been described as a cause of glomerular haematuria. The prognosis of the condition is unclear but it generally is considered to be benign. In a series of 92 patients with glomerular haematuria, thin-membrane nephropathy was found to be a common cause, occurring in 26 (28%) patients. Sixteen patients were women. The mean age was 42 years. Four patients had a family history of renal disease or haematuria and no patient was deaf. Haematuria had been present from six days to 30 years. Loin pain occurred in 31% of patients. Hypertension was not a feature and mild renal impairment was present in one case only, while a further three cases showed proteinuria at a level of greater than 500 mg of protein per day. Glomerular basement membranes in patients with thin-membrane nephropathy gave a mean (+/- standard deviation) width of 319 + 37 nm which was significantly (P less than 0.002) less than the control value of 394 +/- 61 nm. On the basis of clinical features and serological parameters, thin-membrane nephropathy could not be separated from other renal causes of haematuria but required careful electronmicroscopic examination of renal biopsy material to establish the diagnosis. Limited follow-up has confirmed the good prognosis of the condition.

Adult↗