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E Engel

Publications and source records attributed to E Engel.

At least 19 recordsLinked to original sources
PubMed1997

Imprinting is also a mechanism for immediate or delayed hemizygous expression of several uniparental haplotypes selected from the genome of each sex.

A peculiar and interesting aspect of monoallelic or hemizygous expression, resulting from genomic imprinting, should be a likeness or resemblance for some phenotypic traits between relatives inheriting identical active genes or domains. Although the word "likon," a neologism, is reminiscent of the above implication, it is here proposed for use in a broader sense, namely, to designate a haplotype or part of a haplotype of an imprinted domain. As learned from earlier studies of imprinting and uniparental disomies, haplotypes at loci of such domains may be expressed (E) or unexpressed (U) in somatic cells; they may also be transmitted to be expressed or not in the next generation by germ cells "acting" (A) or marked to be "resting" (R) for such loci. Thus the soma/germinal status of "likons" might for each genitor be abbreviated as EA, UA, ER, and UR. In an evolutionary sense the assumption is that the same monoallelically expressed loci and domains when carried by two or more relatives should be the source of identical transcripts contributing to a closely similar phenotype. If so, the overall phenotype would be distinct if arising from some 10 to 20 imprinted genes or domains potentially gaining expression from the germ cells of either one or the other sex in humans. The result may have evolutionary implications by narrowing the scope of random individual variation and by strengthening assortative and associative values (physical, behavioral, and instinctual) in one's own lineage and species.

Chromosome Aberrations↗
PubMed1997

In vivo color stability of resin-veneered telescopic dentures: a double blind pilot study.

STATEMENT OF PROBLEM: Discoloration is a major disadvantage of resin veneers on telescopic dentures. In vitro color measurements with large and flat samples of resin veneer composites have been published, but no in vivo data are available. PURPOSE: This study describes the discoloration of resin veneers in vivo by use of spectrophotometry and the L*a*b* system of the Commission Internationale de L'Eclairage (CIE). METHODS: In a clinical evaluation of this technique, two composite veneer materials were compared in 18 patients. RESULTS: Both brands discolored significantly after 1 year. While L* and a* were not changed significantly, b* and the total color difference delta E increased by approximately 2 units each year. No statistically significant differences were found between the materials.

Color↗
PubMed1997

Human spasmolytic polypeptide decreases proton permeation through gastric mucus in vivo and in vitro.

Exogenously administered trefoil peptides are gastroprotective in rat injury models. We hypothesized that trefoil-associated gastroprotection occurred by decreasing the rate of proton permeation through mucus. Gastric surface cell intracellular pH and mucus gel thickness were measured by in vivo microscopy. Gastric mucosal blood flow was measured by laser-Doppler flowmetry. The effect of human spasmolytic peptide (hSP) on H+ diffusion through 5% purified porcine mucin was measured using an Ussing chamber. Buffering action of mucin was measured by titration. In vivo, gastric mucosal blood flow and mucus gel thickness were not affected by any of the treatments. Topical hSP, but not intravenous hSP, decreased initial acidification rate and elevated the intracellular pH of gastric surface cells during luminal acid challenge. In in vitro studies, hSP dose dependently decreased the diffusion coefficient of H+ through 5% porcine mucin solution. hSP had no significant effect on the buffering action of mucin solutions. These data support our hypothesis that hSP interacts with gastric mucin in a manner that inhibits proton permeation through the mucus gel layer.

Animals↗
PubMed1997

Uniparental disomy (UPD). Genomic imprinting and a case for new genetics (prenatal and clinical implications: the "Likon" concept).

Uniparental disomy (UPD) is often the result of an aneuploid event masquerading under the features of diploidy. As such, it may never be recognized, being at 2 opposite phenotypic poles, harmless to the bearer, or, if harmful, eventually responsible for uncharacteristic although perhaps serious conditions. UPD can also be associated with problems such as recessiveness or mosaicism. This article considers the chances of unmasking UPD, in the course of CVS or AC prenatal diagnosis, by reviewing the main cytogenetic signals and major familial or personal antecedents raising its suspicion. Once suspected, the lead toward UPD may or may not be followed through appropriate molecular studies. UPD for either maternal or paternal chromosomes 13, 21 and 22 may not have consistent, common deleterious effects, while other identified UPD's are too rare to call. Unconditionally, main, consistent or near consistent damages to the phenotype have been traced to specific chromosome pairs such as 15 mat (Prader-Willi syndrome), 15 pat (Angelman syndrome), 11 pat (Wiedemann-Beck with syndrome), 14 mat and pat (multiple cogenital and developmental anomalies [MCDA]-several rather constant) and 7 mat (Russel-Silver [RS] and Growth-failure [GF]). The above problems all stem from an alteration of the normal, developmentally important genomic imprinting processes and most of them may recognize several etiopathogenic paths, other than UPD, none of which abides by straight Mendelian rules. In this very area, therefore, a new, non-traditional type of inheritance is confronting genetic counselling. In this paper, for want of appropriate semantic language, the neologism "likon" (or "laïkon") is coined to make reference to the hemizygously expressed sequences of the genomic parts imprinted in the somatic tissues. Broadening the definition, the word is then applied to the 4 possible epigenotypes of imprinted domains, which depend on the parental sex-of-origin: germinally "resting" (R), or "acting" (A), to be made somatically silent, that is to say "unexpressed" (U), or transcribed and "expressed" (E), thus abbreviated as EA, ER, UA and UR. Entire pedigrees may then be analyzed accordingly in health and in disease. Examples are presented herewith.

Aneuploidy↗
PubMed1996

Chronic recurrent multifocal osteomyelitis: an evolving clinical and radiological spectrum.

OBJECTIVE: To describe unusual clinical and radiological features in patients with chronic recurrent multifocal osteomyelitis (CRMO). DESIGN AND SUBJECTS: Based on radiographic and microscopic findings, three patients were prospectively diagnosed as having chronic recurrent multifocal osteomyelitis (CRMO). They form the basis of this report because of either the unusualness of the clinical presentation, hitherto undescribed associated diseases or the unusual age of presentation and sites of lesions. RESULTS: One patient developed pyoderma gangrenosum at the site of one of the skeletal lesions and then went on to develop ulcerative proctitis. A second patient presented with a soft tissue mass, which on MRI mimicked a sarcoma. The final patient presented with lesions in the wrist and phalanges of the toes at the unusual age of 38. None of the patients was treated with steroids or antibiotics for the skeletal lesions. Steroids were administered to one patient for treatment of pyoderma gangrenosum. CONCLUSIONS: The pattern and distribution of skeletal lesions in CRMO are well recognized in the pediatric age group. The unusual clinical and/or radiological features discussed herein suggests that this is a disease that continues to evolve with a broader spectrum of features than recognized.

Adult↗
PubMed1995

Isoforms of Bet v 1, the major birch pollen allergen, analyzed by liquid chromatography, mass spectrometry, and cDNA cloning.

Bet v 1, the major allergen of birch pollen, displays a considerable degree of heterogeneity. Several charge variants have been detected by two-dimensional IgE immunoblots and isoelectric focusing techniques. This heterogeneity has been attributed to glycosylation (or other post-translational modifications) or to isogenes coding for Bet v 1 isoforms and/or allelic variants. However, until now, only limited structural data for Bet v 1 have been published. Recently, we described the expression, purification, and immunological properties of recombinant Bet v 1 (rBet v 1) produced in Escherichia coli as a non-fusion protein (Ferreira, F. D., Hoffmann-Sommergruber, K., Breiteneder, H., Pettenburger, K., Ebner, C., Sommergruber, W., Steiner, R., Bohle, B., Sperr, W. R., Valent, P., Kungl, A. J., Breitenbach, M., Kraft, D., and Scheiner, O. (1993) J. Biol. Chem. 268, 19574-19580). Here, we present a more detailed structural characterization of Bet v 1 by both cDNA cloning and mass spectrometry. Thirteen different cDNA clones coding for Bet v 1 isoforms were obtained by polymerase chain reaction amplification of birch pollen cDNA with a sequence-specific 5'-terminal primer and a nonspecific 3'-terminal primer or by immunological screening of a birch pollen cDNA library. These isoforms are referred to as Bet v 1b to Bet v 1n, whereas the previously isolated Bet v 1 cDNA (Breiteneder, H., Pettenburger, K., Bito, A., Valenta, R., Kraft, D., Rumpold, H., Scheiner, O., and Breitenbach, M. (1989) EMBO J. 8, 1935-1938) is now referred to as Bet v 1a. High performance liquid chromatography and plasma desorption mass spectrometry of proteolytic fragments of purified natural Bet v 1 (nBet v 1) and rBet v 1a were used to (i) confirm the primary structure of all Bet v 1 isoforms and (ii) to investigate any possible postsynthetic modifications on rBet v 1a or on the natural mixture of isoallergens obtained from birch pollen. Except for the cleavage of initiating methionine, no postsynthetic modifications were found in either nBet v 1 or rBet v 1a.

Allergens↗
PubMed1995

Uniparental disomy in humans: development of an imprinting map and its implications for prenatal diagnosis.

Uniparental disomy (UPD) in humans is caused primarily by meiotic nondisjunction events, followed by trisomy or monosomy 'rescue'. The majority of cases appear to be associated with advanced maternal age, and may be initially detected as mosaic trisomies during routine prenatal diagnosis by chorionic villus sampling or amniocentesis. In addition, structural abnormalities including Robertsonian translocations, reciprocal translocations and supernumerary marker chromosomes appear to be associated with an increased risk of UPD. Predicting the phenotypic effects of UPD is complex, as three independent factors are involved: (i) effects of trisomy on the placenta or the fetus; (ii) autosomal recessive disease due to reduction to homozygosity; and (iii) imprinted gene effects for some chromosomes. To date, UPD in humans has been reported for 25 of the 47 possible uniparental types. Imprinting effects have been established with certainty for four human chromosomes that have homology to mouse chromosomes which have been shown to have significant phenotypic effects in uniparental animals. A normal phenotype has been reported for 14 other UPD types. Thus, collection of data on UPD cases in humans is providing an imprinting map analogous to the experimentally derived imprinting map in mouse. This human imprinting map has important clinical implications, particularly in the area of prenatal diagnosis.

Animals↗
PubMed1995

Palliative therapy of melanoma patients with fotemustine. Inverse relationship between tumour load and treatment effectiveness. A multicentre phase II trial of the EORTC-Melanoma Cooperative Group (MCG).

Fotemustine (FM) is a new chloronitrosurea (CNU), chemically characterized by the graft of an aminophosphonic acid on the CNU radical, which makes it highly lipophilic. Following single-institution phase I and II studies with remarkably high response rates of some 40%, including brain metastases of 25% and more, the EORTC-MCG started a multicentre phase II trial to confirm these results according to EORTC guidelines. Treatment consisted of an induction cycle of FM (100 mg/m2 on days 1 + 8 + 15), followed by maintenance courses (q3w). Fifty-four patients were entered by 11 institutions. General interest in this promising new agent, however, led clinicians of six additional institutions to join the EORTC trial and 90 more patients were included in only 4 months. This rapidly rising accrual rate became inversely related to the physicians' adherence to the eligibility criteria: palliation of symptoms rather than clinical research was the dominant reason to start treatment. Clinical characteristics and results in the eligible vs non-eligible patient group (in parentheses) were as follows: male/female 29/26 (68/65), mean age 54 years (53), ECOG-PS 0-1 (0-4), CR 2 (0), PR 10 (2), NC 17 (5) and for brain metastases: PR 4 (1), NC 2 (1), for an ORR of 12% (5%). Median duration of response was 6 months (range 4-16). The clinically relevant toxicity was limited to the haematopoiesis with delayed platelet nadirs (30% grade III+IV), granulocyte (25% grade III + IV) and the gastrointestinal tract: nausea and vomiting (26% grade II, 18% III, 1% IV). This study confirms that FM is active in melanoma including brain metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
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↗