The one-appointment indirect ceromer restoration.
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Biomedical subjects
Publications and source records attributed to J Woolf.
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Members of the epidermal growth factor family of receptors have long been implicated in the pathogenesis of various tumors, and more recently, apparent roles in the developing heart and nervous system have been described. Numerous ligands that activate these receptors have been isolated. We report here on the cloning and initial characterization of a second ligand for the erbB family of receptors. This factor, which we have termed Don-1 (divergent of neuregulin 1), has structural similarity with the neuregulins. We have isolated four splice variants, two each from human and mouse, and have shown that they are capable of inducing tyrosine phosphorylation of erbB3, erbB4, and erbB2. In contrast to those of neuregulin, high levels of expression of Don-1 are restricted to the cerebellum and dentate gyrus in the adult brain and to fetal tissues.
Deficient myocardial cyclic AMP concentrations contribute to abnormal Ca2+ handling and systolic and diastolic dysfunction in chronic heart failure (CHF). We tested the hypothesis that decreased cyclic AMP in skeletal muscle of animals with failure may contribute to the weakness and easy fatiguability also common in patients with CHF. We compared intracellular Ca2+ signaling and contractility in skeletal muscle preparations from rats 6 weeks after myocardial infarction-induced CHF versus sham-operated controls. Bundles of 100 to 200 cells were dissected from the extensor digitorum longus (EDL) muscle of control and CHF rats. Muscles from CHF rats exhibited depressed tension development compared with control muscles during twitches. Treatment with 2mM dibutyryl cyclic AMP returned tension and Ca2+ towards normal levels. There was no evidence of cellular atrophy in the CHF rats. In conclusion, EDL skeletal muscle from rats with CHF had intrinsic abnormalities in excitation-contraction coupling that could be reversed with cyclic AMP supplementation as previously reported for the heart. This suggests that deficient cyclic AMP levels may contribute to both cardiac and skeletal muscle dysfunction in CHF.
The plasma of patients with overt variegate porphyria contains porphyrin with a fluorescence emission maximum at about 626 nm, which is diagnostic for the condition. We have evaluated qualitative fluorescence emission scanning of saline-diluted plasma as a method for the identification of asymptomatic carriers of the gene for variegate porphyria. Plasma from 36 unrelated patients with variegate porphyria, 136 of their asymptomatic first- and second-degree relatives aged 15 years or over, and 322 normal subjects was scanned. An emission maximum between 621 and 627 nm was observed in the 36 patients with variegate porphyria and 54 of their relatives, but not in any normal subject, nor in 56 patients with other types of porphyria. For the detection of asymptomatic adult carriers of the gene for variegate porphyria, fluorescence emission scanning of plasma appears to be 100% specific, with a sensitivity of 86% (95% confidence interval 71-98%). In contrast, the sensitivity of faecal porphyrin analysis as a test for adult gene carriers was 36%. These results suggest that fluorescence emission scanning of plasma should replace faecal porphyrin analysis as the test of first choice for this purpose.
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