Primary care for patients at genetic risk.
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European Union↗
Biomedical subjects
H J Harris
Publications and source records attributed to H J Harris.
Cystic fibrosis carrier screening at first diagnosis of pregnancy in general practice.
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Carrier State↗
Endothelial cells metabolize NG-monomethyl-L-arginine to L-citrulline and subsequently to L-arginine.
NG-monomethyl-L-arginine (MeArg) inhibits the release of endothelium-derived relaxing factor (EDRF) from endothelial cells (EC) and the formation of nitric oxide (NO) from L-arginine (Arg) in EC and activated macrophages. We have compared the inhibitory potency of MeArg to that of N omega-nitro-L-arginine (NO2Arg), a more potent inhibitor of EDRF synthesis in vitro. NO2Arg (100 microM) was significantly more potent than MeArg in inhibiting the endothelium-dependent relaxation of rabbit aorta induced by acetylcholine. MeArg and NO2Arg (10 and 30 microM) also inhibited the release of EDRF from bovine aortic cultured EC. In the anaesthetized rat in vivo, the pressor effect of NO2Arg (3 and 10 mg kg-1) was significantly larger and longer lasting than that of MeArg. These differences in potency could be due to the extensive metabolism of MeArg but not NO2Arg to L-citrulline (Cit) and subsequently to Arg by EC. The enzyme responsible for the conversion of MeArg to Cit had the characteristics of a novel deiminase, NG,NG-dimethylarginine dimethylaminohydrolase, recently isolated from rat kidney.
Acetylcholine↗
The metabolism of L-arginine and its significance for the biosynthesis of endothelium-derived relaxing factor: cultured endothelial cells recycle L-citrulline to L-arginine.
We have investigated the mechanism by which cultured endothelial cells generate L-arginine (L-Arg), the substrate for the biosynthesis of endothelium-derived relaxing factor. When Arg-depleted endothelial cells were incubated in Krebs' solution for 60 min, L-Arg levels were significantly (9.7-fold) elevated. The generation of L-Arg coincided with a substantial decrease (90%) in intracellular L-glutamine (L-Gln), whereas all other amino acids were virtually unaffected. Changes in calcium, pH, or oxygen tension had no effect on L-Arg generation, which was, however, prevented when the cells were incubated in culture medium containing L-Gln. L-Arg generated by endothelial cells labeled with L-[14C]Arg was derived from an unlabeled intracellular source, for the specific activity of the intracellular L-Arg pool decreased substantially (8.8-fold) over 60 min. Arg-depleted endothelial cells did not form urea or metabolize L-ornithine but converted L-citrulline (L-Cit) to L-Arg possibly via formation of L-argininosuccinic acid. Nondepleted cells stimulated with the calcium ionophore A23187 showed only a transient accumulation of L-Cit, indicating that L-Cit is recycled to L-Arg during the biosynthesis of endothelium-derived relaxing factor. The generation of L-Arg by Arg-depleted endothelial cells was partially (45%) blocked by protease inhibitors, and various Arg-containing dipeptides were rapidly cleaved to yield L-Arg. Thus, cultured endothelial cells recycle L-Cit to L-Arg and possibly liberate peptidyl L-Arg. The Arg-Cit cycle appears to be the equivalent in the endothelial cell to the formation of urea by the liver. The biosynthesis of endothelium-derived relaxing factor may, therefore, not only produce a powerful vasodilator but also relieve the endothelial cell of excess nitrogen.
Animals↗
Microcontaminants and reproductive impairment of the Forster's tern on Green Bay, Lake Michigan--1983.
For the 1983 nesting season, Forster's tern (Sterna forsteri) reproductive success was significantly impaired on organochlorine contaminated Green Bay, Lake Michigan compared to a relatively uncontaminated inland location at Lake Poygan, Wisconsin. Compared with tern eggs from Lake Poygan, eggs from Green Bay had significantly higher median concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), other polychlorinated dibenzo-p-dioxins (PCDDs), total polychlorinated biphenyls (PCBs), total (three congeners) non-ortho, ortho' PCBs, five individual PCB congeners known to induce aryl hydrocarbon hydroxylase (AHH) and several other organochlorine contaminants. Conversions of analytical concentrations of TCDD and PCB congeners based on relative AHH induction potencies allowed for estimation of total 2,3,7,8-TCDD equivalents. Two PCB congeners, 2,3,3',4,4'- and 3,3',4,4',5-pentachlorobiphenyl (PeCB) accounted for more than 90% of the median estimated TCDD equivalents at both Green Bay and Lake Poygan. The median estimated TCDD equivalents were almost 11-fold higher in tern eggs from Green Bay than in eggs from Lake Poygan (2175 and 201 pg/g). The hatching success of Green Bay sibling eggs from nests where eggs were collected for contaminant analyses was 75% lower at Green Bay than at Lake Poygan. Hatchability of eggs taken from other nests and artificially incubated was about 50% lower for Green Bay than for Lake Poygan. Among hatchlings from laboratory incubation, those from Green Bay weighed approximately 20% less and had a mean liver weight to body weight ratio 26% greater than those from Lake Poygan. In both field and laboratory, mean minimum incubation periods were significantly longer for eggs from Green Bay compared to Lake Poygan (8.25 and 4.58 days, respectively). Mean minimum incubation time for Green Bay eggs in the field was 4.37 days longer than in the laboratory. Hatchability was greatly improved when Green Bay eggs were incubated by Lake Poygan adults in an egg-exchange experiment, but was sharply decreased in Lake Poygan eggs incubated in Green Bay nests. Nest abandonment and egg disappearance were substantial at Green Bay but nil at Lake Poygan. Thus, not only factors intrinsic to the egg, but also extrinsic factors (parental attentiveness), impaired reproductive outcome at Green Bay. The epidemiological evidence from this study strongly suggested that contaminants were a causal factor. AHH-active PCB congeners (intrinsic effects) and PCBs in general (extrinsic effects) appeared to be the only contaminants at the concentrations measured in eggs, capable of producing the effects that were observed at Green Bay.
Animals↗
Reaction to attitudinal deviance: impact of deviate's direction and distance of movement.
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Attitude↗
Lepromatous leprosy presenting with polyarthritis, myositis, and immune-complex glomerulonephritis.
A Pakistani man aged 19 years was admitted to a rheumatological unit in the United Kingdom with acute widespread polyarthritis accompanied by night sweats and fever. Preliminary examination suggested Reiter's disease, but further investigation showed acute glomerulonephritis with uraemia. The possibility of periarteritis nodosa, and the prominence of muscle tenderness in the legs, led to biopsies of striated muscle and skin, in both of which were changes typical of lepromatous leprosy, with many Mycobacterium leprae on Ziehl-Neelsen staining. Serum showed IgG-IgM cryoglobulinaemia without antiglobulin activity, and in the recovery phase renal biopsy showed a resolving proliferative glomerulonephritis with linear IgG and IgM immunofluorescence and granular deposits of C3. Clinical signs subsided rapidly under steroid treatment and subsequent progress on anti-leprosy drugs was uneventful. The term erythema nodosum leprosum is inadequate and misleading as a title for a common and important immune-complex reaction of lepromatous leprosy, in which numerous body systems may be involved.
Adult↗