Localisation and dynamics of receptor-insulin contacts by NMR studies on the human insulin receptor ectodomain.
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Biomedical subjects
Publications and source records attributed to L E Ellis.
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Increased intestinal permeability to lactulose has been reported in patients with cystic fibrosis (CF). To determine whether this finding is unique to CF or whether it is related to accompanying exocrine pancreatic dysfunction, we evaluated 31 patients with CF and 10 with Shwachman syndrome who had variable degrees of pancreatic dysfunction, together with 17 healthy control subjects. There was no significant difference in the mean urinary lactulose excretion, expressed as the percentage of dose recovered, between CF and non-CF patients with pancreatic insufficiency (2.1% +/- 1.2% and 1.9% +/- 0.8, respectively) or between CF and non-CF patients with pancreatic sufficiency (0.6% +/- 0.5% and 0.6% +/- 0.3%, respectively). However, there was a significant difference in mean lactulose excretion between the pancreatic-insufficient and the pancreatic-sufficient patients (both CF and non-CF groups; p less than 0.001 and p less than 0.013, respectively). We further analyzed the results from 26 of the 41 patients (16 patients with CF and 10 non-CF patients) with pancreatic dysfunction who had previously undergone quantitative pancreatic function testing. A nonlinear, inverse relationship was found between urinary lactulose excretion and exocrine pancreatic function determined by duodenal trypsin output. These data confirm a direct relationship between intestinal lactulose permeability and the degree of exocrine pancreatic dysfunction, unrelated to the cause of the pancreatic disease.
The records of all children with peptic ulcer disease at the Hospital for Sick Children were retrospectively evaluated, excluding neonates, throughout a 5-year period. Only cases with a definite ulcer crater identified either at endoscopy or at surgery were included. There were 36 patients, 20 boys and 16 girls. Duodenal ulcers were more common than gastric ulcers (2.8:1). Ages ranged from 3 months to 17 years, with a mean age of 10 years. Patients were reviewed with respect to etiology of peptic ulcer disease, age when first examined, initial symptoms, and clinical course. Patients were divided into two groups, those with primary (n = 19) and those with secondary (n = 17) peptic ulcer disease. All peptic ulcers in patients younger than 10 years of age were secondary in nature. Secondary ulcers occurred generally in association with a severe underlying illness (11/17), and many ulcers necessitated emergency surgery because of perforation and/or severe hemorrhage (8/17). None of these patients had chronic or recurrent symptoms. In contrast, in children with primary peptic ulcer disease, initial symptoms were more benign. Most patients had abdominal pain and only one required emergency surgery. Children with primary duodenal ulcer disease had a high incidence of recurrent symptoms (67%), however, with surgery for intractable disease necessitated in 40%. Single-contrast barium meals were found to be unreliable in establishing a diagnosis of peptic ulcer disease, particularly cases of gastric ulcer disease.
Breeding mink for a fine dark fur has coselected male infertility, which may be manifest at the onset of breeding (primary infertility) or after one or more fertile breeding seasons (secondary infertility). Mink with primary infertility have low LH and testosterone levels. However, they respond to exogenous GnRH with increases in LH production and in the number and size of LH and FSH positive gonadotropes in the anterior pituitary. Exogenous human CG also induces testosterone secretion. Thus, mink with primary infertility are probably defective in GnRH secretion, which is due either to abnormal hypothalamic function or its control mechanisms. Autoimmune orchitis with testicular immune complexes are frequent in mink with secondary infertility, suggesting an autoimmune etiology. In contrast, fertile dark mink and fertile mink with the opaline and pastel fur have normal serum LH and testosterone levels; their testes are also normal. In mink with secondary infertility, the frequency and degree of orchitis and testicular immune complexes increased from March (peak sexual activity) to April (onset of testicular regression). Thus, testicular autoimmunity most likely develops during testicular regression. Antisperm antibodies also increased in frequency during testicular regression in the fertile dark mink and in dark mink with primary and secondary infertility. Thus, antisperm antibody per se is insufficient to induce autoimmune orchitis. It is concluded that the infertile mink is a useful model of human male infertility, involving both endocrinological and immunological mechanisms.
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The chemical and enzymatic oxidations of 6-, 7- and 10-methylbenzo[a]-pyrenes, 6,10- and 7,10-dimethylbenzo[a]pyrenes and benzo[a]pyrene (BP) itself have been investigated to study the effects of alkyl substitution on the pathways of oxidation. The chemical oxidizing systems employed were Fenton's reagent (FeSO4/H2O2); trifluoroacetic acid-hydrogen peroxide (TFA/H2O2); thallium tristrifluoracetate in trifluoroacetic acid (TTFA/TFA) and H2SO4. The enzymatic systems were horseradish peroxidase (HRP/H2O2) and rat liver microsomes. The oxidations were investigated by electron paramagnetic resonance (EPR) spectroscopy to detect radical intermediates and by high performance liquid chromatography (HPLC) to separate the products. All the compounds studied produced radicals, identified as cationic species, in both H2SO4 and TTFA/TFA. In addition the 7-methyl-, 10-methyl- and 7,10-dimethyl-BP's produced 6-oxy radicals in some or all of the remaining oxidizing systems. Both chemically and enzymatically these same three compounds were observed to produce quinones as stable products. Microsomal oxidations gave the broadest range of products exhibiting HPLC peaks in the diol, quinone and phenol regions of the chromatograms, however, there were considerable differences between products from the individual derivatives and those from the parent molecule. 6-Methyl and 6,10-dimethyl-BP's showed no evidence of oxy radical intermediates or quinones under any set of conditions, the 6-substituent effectively blocking this oxidation pathway. The observations are consistent with the expected effects of alkyl substituents at particular positions and indicate that studies such as this one are potentially useful in better understanding oxidation and possible activation pathways of polycyclic aromatic hydrocarbons.
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Lichen striatus is an uncommon, self-limited eruption of unknown etiology. What role genetic or environmental influences play in its pathogenesis is unclear. We report two nonrelated, adopted children living in the same household who simultaneously developed lichen striatus.