Search PubMed⌕ Search

Biomedical subjects

E Engel

Publications and source records attributed to E Engel.

At least 37 records · Page 2Linked to original sources
PubMed1995

Bicarbonate diffusion through mucus.

The mucus layer overlying duodenal epithelium maintains a pH gradient against high luminal acid concentrations. Despite these adverse conditions, epithelial surface pH remains close to neutrality. The exact nature of the gradient-forming barrier remains unknown. The barrier consists of mucus into which HCO3- is secreted. Quantification of the ability of HCO3- to establish and maintain the gradient depends on accurate measurement of this ion's diffusion coefficient through mucus. We describe new experimental and mathematical methods for diffusion measurement and report diffusion coefficients for HCO3- diffusion through saline, 5% mucin solutions, and rat duodenal mucus. The diffusion coefficients were 20.2 +/- 0.10, 3.02 +/- 0.31, and 1.81 +/- 0.12 x 10(-6) cm2/s, respectively. Modeling of the mucobicarbonate layer with this latter value suggests that for conditions of high luminal acid strength the neutralization of acid by HCO3- occurs just above the epithelial surface. Under these conditions the model predicts that fluid convection toward the lumen could be important in maintaining the pH gradient. In support of this hypothesis we were able to demonstrate a net luminal fluid flux of 5 microliters.min-1.cm-2 after perfusion of 0.15 N HCl in the rat duodenum.

Animals↗
PubMed1995

Barrier function of the gastric mucus gel.

The gastric epithelium is covered by a continuous layer of secreted mucus and bicarbonate. The function of this mucobicarbonate layer in terms of protecting the epithelial cells from luminal acid is controversial. Several studies conducted in vitro have shown that gastric mucus can slow proton diffusion and can enable the formation of a pH gradient across the mucobicarbonate layer. In our laboratory, simultaneous measurements of intracellular pH and the thickness of the mucus gel overlying gastric surface cells in vivo indicated that surface cell acidification rates and mucus gel thickness were inversely related. This suggests that the gastric mucobicarbonate layer delays proton permeation into gastric surface cells, enabling secreted bicarbonate to neutralize luminal acid. Several theoretical models, including the effects of mucus and bicarbonate secretion, convection, stirring, and lipids are offered as a possible explanation for the experimental observations. Lipid content and additional unstirred layers outside of the mucus gel are offered as possible explanations for the experimental observations. On the basis of the available data and theoretical considerations, we can conclude that all of these factors probably interact in an integrated manner to protect the gastric epithelial cells from damage due to luminal acid.

Animals↗
PubMed1995

[Uniparental disomy: a review of causes and clinical sequelae].

1) Uniparental disomy (UPD) results from the exceptional derivation of a pair of the offspring chromosome from one parent only and has been documented thus far for chromosomes 2, 4, 5, 6, 7, 11, 13, 14, 15, 20, 21, 22 both X's and the XY pair. Its consequences on the phenotype may result from three potentially harmful effects, namely isodisomy, interference with genomic imprinting and, occasionally the vestigial aneuploidy from which UPD may have originated. 2) In isodisomy, the uniparental pair is partially or entirely homozygous, through the duplication of a same chromosomal DNA template, thus bringing about an increased risk of recessive disorders. As a result, conditions such as cystic fibrosis, a type of osteogenesis imperfecta, thalassemia alpha or beta, retinoblastoma, rod monochromacy, etc., have now been reported. 3) Duplication of both homologues of a parental pair in a diploid genome is called heterodisomy. Both iso- and heterodisomy may also cause disruption of the genomic imprints normally modifying the differential expression of some maternal and paternal genes or gene sequences needed for eugenic growth and development, in the course of normal biparental inheritance. Such a disturbance can be one of the causes of congenital clinical entities as well defined as Angelman, Prader-Willi or Beckwith-Wiedemann syndromes and some new syndromes, for instance for UPD 7 mat, UPD 14 mat and, probably also 14 pat. 4) All in all, UPD can cause morbidity or lethality by altering imprinting processes, mimicking certain deletions or duplications, generating recessive disorders or prompting malignant tumor development. 5) In the clinical field, UPD occasionally upsets some mendelian tenets of traditional inheritance, and raises, the question of the evolutional role plaid by genomic imprinting (GI). An hypothetical opinion is that one of GI potential side effects is a biased intergenerational preferential display or skip of parental features. This could be so because some of the inherited genes or gene domains only gain maternal or paternal expression in the offspring, as a function of their parental imprint.

Chromosome Aberrations↗
PubMed1995

Modeling of the gastric gel mucus layer: application to the measured pH gradient.

The gastric gel mucus layer plays an important role in the defense against acid-induced injury. Previous investigations have modeled the interaction between the mucus, bicarbonate, acid moving towards the epithelial surface, and water carrying ions away from the epithelium. We measured the diffusion coefficient of protons through gastric mucus and applied this parameter to the model. Using the measured diffusion coefficient, we applied the model to previously published gastric mucus gel pH gradients to assess the relative contribution of bicarbonate or water fluxes in maintaining the gradient in the face of luminal acid. Mucus was harvested from the stomachs of anesthetized rats, mixed with bromphenol blue, and placed in capillary tubes. The tubes were submerged in 0.15 N HCl at 37 degrees C. The color change from blue to yellow was measured with time as the HCl migrated through the tube. From the distance and time data, the diffusion coefficient could be calculated. Controls of bromphenol blue in water were studied. The diffusion coefficient for water was 30.2 +/- 0.8 x 10(-6) cm2 s-1, almost identical to the standard value reported in the literature. The HCl diffusion coefficient through saline was 67.8 +/- 0.7 x 10(-6) cm2 s-1. For gastric mucus it was 5.4 +/- 1.3 x 10(-6) cm2 s-1. Application of this diffusion coefficient to the model and subsequently to observed pH gradients suggested that the most potent defense mechanism against concentrations of luminal acid is the bulk movement of water away from the epithelial surface through the mucus gel layer.

Animals↗
PubMed1994

Angelman syndrome due to paternal uniparental disomy of chromosome 15: a milder phenotype?

The Angelman syndrome (AS) is a neurological disorder characterized by severe mental retardation, absent speech, seizures, gait disturbances, and a typical age-dependent facial phenotype. Most cases are due to an interstitial deletion on the maternally inherited chromosome 15, in the critical region q11-q13. Rare cases also result from paternal uniparental disomy of chromosome 15. In a group of 14 patients with sporadic AS diagnosed in Switzerland, we found 2 unrelated females with paternal isodisomy for the entire chromosome 15. Their phenotypes were milder than usually seen in this syndrome: one girl did not show the typical AS facial changes; both patients had late-onset mild seizures; as they grew older, they had largely undisturbed gross motor functions, in particular no severe ataxia. Both girls were born to older fathers (45 and 43 years old, respectively). The apparent association of a relatively milder phenotype in AS with paternal uniparental disomy will have to be confirmed by detailed clinical descriptions of further patients.

Adult↗
PubMed1993

Uniparental disomy revisited: the first twelve years.

Uniparental disomy (UPD), the exceptional derivation of a pair of the offspring chromosomes from one parent only, may be compatible with normal or abnormal development and can result from gamete complementation, chromosome loss in trisomy, or duplication in monosomy (with or without residual mosaicism) and somatic recombination. In isodisomy, the uniparental pair is a duplicate of a same chromosome DNA template and causes an increased risk of recessive disorder by reduction to homozygosity. In heterodisomy, the pair remains heterozygous, made up of 2 non-recombinant homologous segments. But both iso- and heterodisomy may also cause disruption of the genomic imprints needed for differential expression of some maternal and paternal genes crucial to growth and development. Pure UPD preserves euploidy and, when harmful, is best regarded as a genomic qualitative imbalance by symmetrical excess and loss of parental homologous contribution affecting zygosity and imprint content. Instances of UPD reported till the spring 1992 are reviewed and their deleterious effects are described as they carried out lethality or morbidity by altering imprinting processes, mimicking deletions, generating recessive disorders, or prompting malignant cellular growth.

Chromosome Aberrations↗
PubMed1993

Effect of Toremifene in patients with metastatic melanoma: a phase II study of the EORTC Melanoma Cooperative Group.

The EORTC Melanoma Cooperative Group conducted a phase II trial (study number 18891) to study the effect of Toremifene in 45 patients with advanced, metastatic melanoma. Male and female patients, median age 61 (range 23-88) years received a mean total dose of 11 g (4.3-62.6) orally for at least 6 weeks. No objective remissions were seen. Four patients (3 women and 1 man; 9%) experienced 3-6 months' disease stabilization. The toxicity of the drug, given at a dose of 240 mg daily, was negligible. Because of the minimal side-effects, Toremifene may be recommended for patients who have only a small number of slowly growing metastases, in particular to soft tissue and lung.

Adult↗
PubMed1992

Mechanisms of ring chromosome formation in 11 cases of human ring chromosome 21.

We studied the mechanism of ring chromosome 21 (r(21)) formation in 13 patients (11 unique r(21)s), consisting of 7 from five families with familial r(21) and 6 with de novo r(21). The copy number of chromosome 21 sequences in the rings of these patients was determined by quantitative dosage analyses for 13 loci on 21q. Nine of 11 r(21)s, including the 5 familial r(21)s, showed no evidence for duplication of 21q sequences but did show molecular evidence of partial deletion of 21q. These data were consistent with the breakage and reunion of short- and long-arm regions to form the r(21), resulting in deletion of varying amounts of 21q22.1 to 21qter. The data from one individual who had a Down syndrome phenotype were consistent with asymmetric breakage and reunion of 21q sequences from an intermediate isochromosome or Robertsonian translocation chromosome as reported by Wong et al. Another patient, who also exhibited Down syndrome, showed evidence of a third mechanism of ring formation. The likely initial event was breakage and reunion of the short and long arms, resulting in a small r(21), followed by a sister-chromatid exchange resulting in a double-sized and symmetrically dicentric r(21). The phenotype of patients correlated well with the extent of deletion or duplication of chromosome 21 sequences. These data demonstrate three mechanisms of r(21) formation and show that the phenotype of r(21) patients varies with the extent of chromosome 21 monosomy or trisomy.

Alleles↗