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Biomedical subjects

E Brun

Publications and source records attributed to E Brun.

At least 37 records · Page 2Linked to original sources
PubMed1996

Insulin infusion amplifies 17 alpha-hydroxycorticosteroid intermediates response to adrenocorticotropin in hyperandrogenic women: apparent relative impairment of 17,20-lyase activity.

Recent data suggest that insulin is a modulator of ovarian and adrenal steroidogenesis and that, in the ovary of hyperandrogenic women, hyperinsulinemia might cause dysregulation of cytochrome P450c17 alpha activity. To further assess in vivo the effects of insulin on adrenal steroidogenesis, ACTH stimulation was carried out in 21 hyperandrogenic women during a 3-h hyperinsulinemic (80 mU/m2-min) euglycemic clamp. In all of these women the procedure was repeated during saline infusion as n control. In nonamenorrheic patients, the tests were performed in the early follicular phase of two different menstrual cycles. Serum cortisol, progesterone, 17-hydroxypregnenolone (17-OHJPREG). 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA), and androstenedione (A) were measured after 2 h of insulin or saline infusion (zero time) and, subsequently, 30 and 60 min after an iv bolus of 0.25 mg ACTH-(1-24). At zero time, no difference was found in the serum steroid concentrations between the two protocols. ACTH-stimulated serum 17-OHPREG and, to a lesser extent, 17-OHP were significantly higher during insulin than during saline infusion (peaks, 60.6 +/- 9.0 vs. 40.7 +/- 7.9 and 7.7 +/- 7.7 vs. 6.6 +/- 0.6 nmol/L; P < 0.005 and P < 0.01, respectively). Serum DHEA was also slightly higher during hyperinsulinemia, although only after 30 min (54.5 +/- 3.0 vs. 48.2 +/- 4.2 nmol/L; P < 0.05). No statistically significant difference in the cortisol, progesterone, or androstenedione response to ACTH was found between the two protocols. ACTH-stimulated 17-OHPREG/DHEA and 17-OHP/A molar ratios, indexes of apparent 17,20-lyase activity, were significantly higher during the clamp studies than during saline infusion (by ANOVA, F = 12.8; P < 0.001 and F = 6.7; P < 0.005, respectively), suggesting an impaired enzyme activity. These in vivo data support the hypothesis that insulin potentiates ACTH-stimulated steroidogenesis. This effect of insulin seems to be associated with a relative impairment of 17,20-lyase activity.

17-Hydroxycorticosteroids↗
PubMed1996

The insulin resistance in women with hyperandrogenism is partially reversed by antiandrogen treatment: evidence that androgens impair insulin action in women.

To assess whether androgen excess per se might impair insulin action, insulin sensitivity was measured by a two-step (20 and 80 mU/m2.min) hyperinsulinemic euglycemic clamp combined with indirect calorimetry and tracer glucose infusion in 43 women (13 obese and 30 nonobese) with normal glucose tolerance and clinical evidence of increased androgen action (hirsutism and/or polycystic ovary syndrome) as well as 12 age- and body mass index-matched healthy controls. Hyperandrogenic women were studied basally and after 3-4 months of antiandrogen treatment with 3 different drugs: spironolactone (n = 23), flutamide (n = 10), or the GnRH agonist buserelin (n = 10). Six women given spironolactone were also reexamined after 1 yr of therapy. At baseline, insulin-mediated glucose uptake was lower in hyperandrogenic women than in controls (by ANOVA, F = 14.3; P < 0.001). Insulin resistance was observed in both ovarian and nonovarian hyperandrogenism, as distinguished by acute GnRH agonist testing. After antiandrogen therapy, insulin action on glucose metabolism significantly increased for both the patients as a whole (F = 7.4; P < 0.01) and each treatment group separately. However, insulin action remained lower than in controls and showed no further improvement in patients reevaluated after I yr of treatment. Increases in both oxidative and nonoxidative glucose metabolism accounted for the improvement in substrate disposal induced by antiandrogen drugs. The increase in the effectiveness of insulin was greater in the lean subjects, whereas the change was small and not statistically significant in the obese women. Response to treatment was more pronounced in women with nonovarian hyperandrogenism, particularly at the low insulin infusion rate. Endogenous glucose production in hyperandrogenic patients was similar to that in healthy women and was unaffected by therapy. In conclusion, antiandrogen treatment partially reversed the peripheral insulin resistance associated with hyperandrogenism regardless of which antiandrogen was used. These data strongly suggest that in women, androgen excess per se contributes to impairment of insulin action.

Adult↗
PubMed1995

Overproduction, purification and characterization of the cellulose-binding domain of the Erwinia chrysanthemi secreted endoglucanase EGZ.

EGZ is the major endoglucanase secreted by Erwinia chrysanthemi. Functional characterization indicates that it is made of a catalytic N-terminal domain linked to a C-terminal cellulose-binding domain (CBD) by a Ser/Thr-rich linker. A chimeric plasmid, in which the CBD-encoding region was fused downstream of the ompA signal sequence, was constructed and introduced into Escherichia coli. This allowed for the production of processed and disulfide-bonded CBD, mostly recovered from the culture supernatant of E. coli. One-dimensional NMR analysis of the purified CBD reveals that it folds into a well-structured domain. Moreover, comparison with the one-dimensional NMR analysis of full-length EGZ strongly suggests that the CBD folds autonomously, providing experimental support for the existence of domains of EGZ.

Binding Sites↗
PubMed1995

A phase I/II evaluation of metoclopramide as a radiosensitiser in patients with inoperable squamous cell carcinoma of the lung.

The feasibility of administering metoclopramide (MCA) as a radiosensitizer has been evaluated in 23 patients with a pathological or cytological diagnosis of a squamous cell carcinoma of the lung, clinically evaluated as inoperable. All patients received 40-60 Gy radiotherapy fractionated into 1.8 Gy fractions 5 times per week (Monday-Friday). Two MCA treatment regimens were used: (i) MCA at 2 mg/kg administered by intravenous-infusion 1-2 h prior to radiotherapy 3 times per week (Monday, Wednesday, Friday); and (ii) MCA at 1 mg/kg administered by intravenous infusion 1-2 h prior to radiotherapy 5 times per week (Monday-Friday). 11 of the 23 patients treated with radiotherapy and MCA had none to mild pneumonitis or fibrosis and another 8 of the 23 had moderate levels. No patient had their therapy interrupted due to radiation-related side-effects. The MCA-related side-effects were as expected, i.e. 78% of the patients experienced sedation/tiredness and 48% expressed restlessness/anxiety symptoms. Both the total dose and serum levels of MCA were significantly associated to the MCA side-effect profile. Tumour response, duration of tumour response and survival were significantly positively correlated to the total and weekly doses of MCA administered to the patients during their radiotherapy treatment. These favourable phase II data have justified the initiation of a phase II/III randomised multicentred trial being carried out in Europe to evaluate MCA as a radiosensitiser.

Aged↗
PubMed1995

A large pedigree with early-onset Alzheimer's disease: clinical, neuropathologic, and genetic characterization.

We present clinical, neuropsychological, and neuropathologic data on a large pedigree including 34 subjects with early-onset progressive dementia. The mean (+/- SD) age at onset was 46 +/- 3.5 years and the mean age at death 52.6 +/- 5.7 years. Twelve patients were clinically diagnosed as having probable Alzheimer's disease (AD) according to the NINCDS-ADRDA criteria. Neuropsychological evaluation, performed at a moderate stage of the disease, was available in six subjects and showed a classic pattern of cognitive deficit. Myoclonus and extrapyramidal signs were common, and seizures were present in all affected subjects. There were neuropathologic changes typical of AD in two brains. A significant lod score of 5.48 was observed at a recombination fraction of theta = 0.0 with the genetic marker D14S43, thereby establishing that the responsible gene was located on chromosome 14q24.3. These results suggest that epilepsy could represent a particular feature in AD families linked to chromosome 14q.

Age of Onset↗
PubMed1994

Periplasmic disulphide bond formation is essential for cellulase secretion by the plant pathogen Erwinia chrysanthemi.

Secretion to the cell exterior of cellulase EGZ and of at least six pectinases enables the Gram-negative Erwinia chrysanthemi to cause severe plant disease. The C-terminal cellulose-binding domain (CBD) of EGZ was found to contain a disulphide bond which forms, in the periplasm, between residues Cys-325 and Cys-382. Dithiothreitol (DTT)-treatment of native EGZ showed that the disulphide bond was dispensable, both for catalysis and cellulose binding. Adding DTT to E. chrysanthemi cultures led to immediate arrest of secretion of EGZ which accumulated in the periplasm where the CBD was eventually proteolysed. Site-directed mutagenesis that affected Cys residues involved in disulphide bond formation resulted in molecules that were catalytically active and able to bind to cellulose but were no longer secreted. Instead they accumulated in the periplasm. Interestingly, the region around EGZ Cys-325 is conserved in two pectinases secreted by the same pathway as EGZ. We conclude that the conserved Cys, and possibly adjacent residues, bear essential information for EGZ to be secreted and that periplasmic disulphide bond formation is an obligatory step which provides a pre-folded functional form of EGZ with secretion competence.

Amino Acid Sequence↗
PubMed1993

Endocarditis caused by Rochalimaea henselae.

A case of community-acquired, culture-negative, infective endocarditis was diagnosed in a 57-year-old construction worker. Small, pleomorphic gram-negative rods were seen in Brown-Hopps tissue gram stains and Warthin-Starry silver stains. The organism was identified as Rochalimaea henselae by polymerase chain reaction amplification and sequencing of the 16S rDNA gene sequence. This is the first report of infective endocarditis caused by R henselae.

Community-Acquired Infections↗
PubMed1992

Primary gastric non-Hodgkin's lymphoma. A retrospective clinico-pathological study.

Prognostic factors and treatment results were analysed in 72 consecutive patients with primary gastric lymphoma treated between 1970 and 1985. There were 37 patients in stage IE, 17 in IIE, 3 in IIES and 15 in stage IV. Histopathological re-evaluation and classification according to the TNM system were performed. We found that disseminated disease (stage IV), serosal penetration (T3), involvement of adjacent organs (T4) and extensive abdominal lymph node involvement (N3) were poor prognostic factors. Neither histological malignancy grading, nor the appearance of lympho-epithelial lesions were significantly associated with relapse-free survival. Forty-six patients with 'limited localized' disease (stage IE, IIE, N3 excluded) received potentially curative treatment (surgery, radiotherapy, chemotherapy or combinations thereof), of whom 85% remained relapse-free. Thirty-four patients did only get local treatment (surgery and/or radiotherapy) with curative potential, the relapse-free survival rate was 85%. We conclude that primary gastric lymphoma stage IE and IIE (N3 excluded) is often a truly localized disease that can be cured with local therapy.

Adolescent↗
PubMed1991

On the mode of evolution of alpha satellite DNA in human populations.

The hypothesis that highly reiterated satellite DNAs in present-day populations evolve by molecular mechanisms that create, by saltatory amplification steps, new long arrays of satellite DNA, and that such long arrays are used for homogenization purposes, has been tested both in mouse and in humans. In mouse, the data obtained are consistent with this hypothesis. This was tested in more detail on chromosomes 13 and 21 of the human genome. A Centre d'Etudes du Polymorphisme Humain family, which in some individuals exhibits strong supplementary DNA bands following TaqI restriction endonuclease digestion and conventional gel electrophoresis, was analyzed by pulse field gel electrophoresis following restriction by BamHI. The supplementary bands on chromosome 13 (18 times the basic alpha satellite DNA repeat) and on chromosome 21 (a 9.5-mer) segregated with centromeric alpha satellite DNA blocks of 5 and 5.3 megabases, respectively. These are by far the largest alpha satellite block lengths seen in all chromosome 13 and chromosome 21 centromeric sequences so far analyzed in this manner. The possibility that these supplementary alpha satellite sequences were created in single individuals by saltatory amplification steps is discussed in light of our own data and that published by others. It is proposed that deletion events and unequal cross-overs, which both occur in large satellite DNA arrays, contribute to the homogenization of size and sequence of the alpha satellite DNA on most chromosomes of humans.

Animals↗
PubMed1989

Turbidimetric measurement of immunoglobulin G in serum using an automatic centrifugal analyser.

Turbidimetry and radial immunodiffusion techniques are compared for measuring the average amounts of IgG in serum from healthy sheep, swine and chickens using different rabbit antisera. The correlation coefficients (r) between the IgG values measured by the two techniques, were high; r greater than 0.97. Turbidimetric measurement was found to be a reliable, rapid and simple method for IgG determination in serum.

Animals↗