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Biomedical subjects

S Gerber

Publications and source records attributed to S Gerber.

105 records · Page 6Linked to original sources
PubMed1992

A gene for Usher syndrome type I (USH1A) maps to chromosome 14q.

Usher syndrome (US) is an autosomal recessive disease characterized by congenital hearing impairment and retinitis pigmentosa. It is the most frequent cause of deaf-blindness in adults and accounts for 3 to 6% of deaf children. Here, we report the genetic mapping of a gene for US type I (USH1A), the most severe form of the disease, to the long arm of chromosome 14, by linkage to probe MLJ14 at the D14S13 locus in 10 families of Western France ancestry (Z = 4.13 at theta = 0). Among them, 8 families originated from a small area of the Poitou-Charentes region (Z = 3.78 at theta = 0), suggesting that a founder effect could be involved. However, since not all US type I families were found to be linked to this locus, the present study provides evidence for genetic heterogeneity of this condition (heterogeneity versus homogeneity test HOMOG, P < 0.05; heterogeneity versus no linkage, P < 0.01).

Chromosome Mapping↗
PubMed1989

[The diagnostic importance of different imaging technics in temporomandibular joint dysfunction].

Various imaging techniques enable to explore the Temporo-mandibular joints (T.M.J.). The physicians prescribing them, must be perfectly aware of the informations they provide as well as their costs, for a judicious formulation of their indications. Conventional radiography is absolutely necessary and, most of the time, sufficient, since it simply permits to evaluate the bony structures. An orthopantomogram and modified Schüller views of each T.M.J., "open mouth" and "closed mouth" will be performed. Conventional tomograms are no longer indicated. They will be abandoned for Computed Tomograms. This examination permits, at a relatively low cost, to analyse a bony abnormality and explore the muscular soft tissues. It may also be possible to assess the meniscus, its position and displacement when the mouth is opened. In fact, if a meniscal or articular pathology is considered, which could result in surgical or endoscopic procedure, it is absolutely necessary to perform: -either an arthro-tomography, with contrast material, -or a magnetic resonance examination. The latter provides perfect anatomical and pathological informations of the joint and meniscus, in an atraumatic fashion for the patient. Its only contraindication is in the cost of the examination. It will be possible to look for a dislocation, a malformation or a structural alteration of the meniscus which could result in a perforation, a rupture of the posterior frenulum, adhesions or joint extravasation. A necrosis or early osteochondritis of the condyle will be ruled out.

Humans↗
PubMed1988

[Effect of an antacid on duodenal pH in severe excretory pancreatic insufficiency].

pH was measured continuously in the lower duodenum before and 90 min after a standard meal in 15 controls and 13 patient with severe pancreatic insufficiency (PI); gastric acid secretion was unimpaired in all of them. 7 out of the 13 pat. with PI received additionally 30 ml of an A-Mg-silicate preparation (MegalacR) 45 min after the meal. Mean pH dropped after the meal from 6.9 to 6.2 in the controls and from 7.1 to 4.9 in the pat. with PI. The overall time of pH-values below 5 amounted to 0.5% of the measuring period in the controls, in PI-pat. to 35%. In pat. with PI there were additionally pH-values below 4 during 11% of the postcibal period. Antacid administration increased duodenal pH significantly but only over 15 min; this transient effect had, however, no significant influence on the overall time of the pH-values below 5 and 4. Al-Mg-silicate has obviously no relevant effect on the postcibal duodenal pH in pat. with PI and can therefore not be regarded as a means to prevent inactivation of pancreatic enzymes in the duodenum.

Aluminum Compounds↗
PubMed1988

[The pH dependence of lipase and trypsin activity].

We investigated in-vitro the relation of the lipase and trypsin activity, containing in native duodenale juice, to pH-values, similar to them registered in the duodenum of patients with severe exocrine insufficiency. Therefore week alcaline duodenal juice was acidified by native gastric juice or hydrochloric acid to pH-value 7, 6, 5 und 4. The remaining activity was estimated after 5, 10, 15 and 20 minutes. We determined a fast inactivation of lipase at pH 5.0 or below (incubation of 5 minutes only decreased the activity to 35% of origin), and of trypsin at pH 4.0 or below (incubation of 5 minutes at this pH-value decreased the activity to 26% of origin). According to the denaturating effect on the enzymes, there was no difference between gastric juice and hypochloric acid. It is concluded, that the activity of decreased secreted pancreatic enzymes in severe exocrine pancreatic insufficiency and also of the oral substituted enzymes is additionally reduced by acidic duodenal circumstances, so that a gastric acid neutralizing or inhibiting therapy proves as necessary.

Duodenum↗
PubMed1987

[Interdigestive and postprandial duodenal pH in healthy probands, in patients with ulcer and in chronic pancreatitis].

In patients with chronic pancreatitis (48), gastric ulcer (6), duodenal ulcer (6) and controls (12) duodenal pH was measured continuously by a glass electrode before and 90 minutes after a standard meal. The capacity of the stomach to secrete acid was known in all test persons, the degree of exocrine pancreatic insufficiency was determined according to the results of the S-CCK-test: 6 had no, 29 moderate and 13 severe pancreatic insufficiency. There were no significant differences between the mean interdigestive duodenal pH of the groups. After a meal, however, even patients with a normal pancreatic function but with hyperchlorhydria had a significantly lower pH (mean pH 5.5) than those with normo-chlorhydria (mean pH 6.1) and hypochlorhydria (mean pH 6.5). In patients with severe pancreatic insufficiency and normo-/hyperchlorhydria duodenal pH was much lower (mean pH 4.2) in some cases to pH 3.5, thus well below a level known as inactivating pancreatic enzymes. The total duration of the pH being less than 4.5 amounted to 12% of the postprandial measuring time (11 of 90 min). If, however, severe pancreatic insufficiency was combined with a-/hypochlorhydria duodenal pH did not differ from controls. Thus, reduced acid secretion of the stomach exerts beneficial effect on duodenal pH in patients with severe pancreatic insufficiency.

Acid-Base Equilibrium↗
PubMed1980

Regulation of iron absorption and storage iron turnover.

The regulation of iron supply to plasma was studied in male rate. Repeated exchange transfusions were first carried out with plasma from iron-deficient or iron-loaded animals. There was no recognizable effect on the amount of iron entering the plasma as evidenced by plasma iron concentration or iron absorption by recipient animals. In other studies, iron compounds having different tissue distribution were injected. Subsequent iron release was greater from reticuloendothelial cells than from other iron-loaded tissues. When requirements for transferrin iron were increased by exchange transfusion with high reticulocyte blood, within minutes there was a doubling of the rate of tissue iron donation. It was concluded from these studies that (1) iron turnover in the plasma is primarily determined by the number of tissue receptors for iron, particularly those of the erythron, (2) that the amount of iron supplied by each donor tissue is dependent on the output of other donor tissues, and (3) that a humoral mechanism regulating iron exchange is unlikely in view of the speed of response and magnitude of changes in plasma iron turnover. It is proposed that there is some direct mechanism that determines the movement of iron from donor tissues to unsaturated transferrin binding sites.

Absorption↗
PubMedDate not supplied

Modulation of murine in vitro immune response by verapamil (V).

Functionally distinct lymphocyte subsets differ with regard to necessary activation signals. In selected circumstances lymphocyte activation has been shown to be critically dependent upon transcellular calcium influx. Whether calcium plays a central role in the activation of all lymphocytes remains to be determined. The effect of the calcium channel blocker verapamil on the induction of murine cytotoxic T lymphocytes (CTL), suppressor cells, T helper cells, and B cells was investigated. Verapamil (V) was found to inhibit the induction of cytotoxic effector cells. V acted primarily on the afferent limb of this immune response, was synergistic with cyclosporin A (CsA), and its effects could be largely reversed by the addition of exogenous helper factors. V also inhibited B cell proliferation in response to anti-mouse IgM in the presence of 2-mercaptoethanol, but in the absence of cognate or non-cognate T cell help. In contrast to this, V did not inhibit the activation of cells capable of inducing B cell proliferation nor did it inhibit the induction of suppressor cells. The selective suppression of V is discussed in terms of activation requirements of CTL, suppressor cells and helper cell subsets.

Animals↗
PubMedDate not supplied

Spectrum of ABCR gene mutations in autosomal recessive macular dystrophies.

Stargardt disease (STGD) and late-onset fundus flavimaculatus (FFM) are autosomal recessive conditions leading to macular degenerations in childhood and adulthood, respectively. Recently, mutations of the photoreceptor cell-specific ATP binding transporter gene (ABCR) have been reported in Stargardt disease. Here, we report on the screening of the whole coding sequence of the ABCR gene in 40 unrelated STGD and 15 FFM families and we show that mutations truncating the ABCR protein consistently led to STGD. Conversely, all mutations identified in FFM were missense mutations affecting uncharged amino acids. These results provide the first genotype-phenotype correlations in ABCR gene mutations.

ATP-Binding Cassette Transporters↗
PubMedDate not supplied

Blood pressure and prolactin: effects of guanfacine. Three-year follow-up study.

Serum prolactin was measured in 76 patients with essential hypertension: 47.4% had elevated serum prolactin, and those with organ damage had presented higher prolactin than those with Phase I (WHO) hypertension. The effect of prolonged treatment (3 years) with guanfacine, an alpha-adrenoceptor stimulant drug, on blood pressure levels, heart rate, and prolactin was evaluated in 15 patients with moderate essential hypertension (WHO: Phase II) and hyperprolactinemia. Treatment produced a marked reduction in blood pressure levels and heart rate. Guanfacine decreased serum prolactin significantly (p less than 0.001), and the inhibition persisted during the 3-year follow-up. The daily dosage of guanfacine did not have to be changed during the 3 years of treatment. Side effects of guanfacine were only observed during the first 3-4 months of therapy. The hypotensive effect of guanfacine was increased by the administration of a diuretic, a vasodilator, or a beta-adrenergic blocking drug. The results indicate that guanfacine administered alone or in combination is an effective drug for treatment of patients with essential hypertension. The inhibitory effect of guanfacine on prolactin suggests that hypothalamic or extrahypothalamic adrenergic pathways may participate in the regulation of prolactin secretion.

Adult↗
PubMedDate not supplied

Two novel missense mutations in the peripherin/RDS gene in two unrelated French patients with autosomal dominant retinitis pigmentosa.

PURPOSE: To report the identification of two novel RDS mutations in the peripherin/RDS gene of two unrelated French patients affected by autosomal dominant retinitis pigmentosa (ADRP). METHODS: Fifty-eight unrelated patients affected by ADRP were analyzed. Our diagnostic for RP were bilateral fundus involvement, concentric depression of the visual field and severe involvement on electroretinogram. Transmission of the trait was unambiguous. Our strategy was to analyze the coding sequence of the gene using a combination of single-strand conformation polymorphism (SSCP) and direct sequence analysis of the exons of the gene. Exons that displayed conformational polymorphisms were sequenced on an automated DNA sequencer. RESULTS: The sequence analyses revealed two previously unreported missense mutations: Cys165Tyr and Phe211Leu in exons 1 and 2, respectively. None of the 70 controls analyzed carried these base changes. Cosegregation of the base substitution with the disease could be tested in both families presenting the Cys165Tyr and Phe211Leu mutations. CONCLUSIONS: Several lines of evidence support the idea that these base substitutions are disease-causing mutations. To the best of our knowledge, no peripherin/RDS gene analysis has been previously reported in ADRP in France.

Amino Acid Sequence↗
PubMedDate not supplied

Integrated homology modelling and X-ray study of herpes simplex virus I thymidine kinase: a case study.

Knowledge-based homology modelling together with site-directed mutagenesis, epitope and conformational mapping is an approach to predict the structures of proteins and for the rational design of new drugs. In this study we present how this procedure has been applied to model the structure of herpes simplex virus type 1 thymidine kinase (HSV1 TK, HSV1 ATP-thymidine-5'-phosphotransferase, EC 2.7.1.21). We have used, and evaluated, several secondary structure prediction methods, such as the classical one based on Chou and Fastman algorithm, neural networks using the Kabsch and Sander classification, and the PRISM method. We have validated the algorithms by applying them to the porcine adenylate kinase (ADK), whose three-dimensional structure is known and that has been used for the alignment of the TKs as well. The resulting first model of HSV1-TK consisted of the first beta-strand connected to the phosphate binding loop and its subsequent alpha-helix, the fourth beta-strand connected to the conserved FDRH sequence and two alpha-helix with basic amino acids. The 3D structure was built using the X-ray structure of ADK as template and following the general procedure for homology modelling. We extended the model by means of COMPOSER, an automatic process for protein modelling. Site-directed mutagenesis was used to experimentally verify the predicted active-site model of HSV1-TK. The data measured in our lab and by others support the suggestion that the FDRH motif is part of the active site and plays an important role in the phosphorylation of substrates. The structure of HSV1 TK, recently solved in collaboration with Prof. G. Schulz at 2.7 A resolution, includes 284 of 343 residues of the N-terminal truncated TK. The secondary structures could be clearly assigned and fitted to the density. The comparison between crystallographically determined structure and the model shows that nearly 70% of the HSV1 TK structure has been correctly modelled by the described integrated approach to knowledge based ligand protein complex structure prediction. This indicate that computer assisted methods, combined with "manual" correction both for alignment and 3D construction are useful and can be successful.

Crystallography, X-Ray↗