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Biomedical subjects

E Engel

Publications and source records attributed to E Engel.

At least 37 records · Page 2Linked to original sources

Sensory pathways and cyclooxygenase regulate mucus gel thickness in rat duodenum.

We previously showed that the duodenal hyperemic response to acid occurs through activation of capsaicin-sensitive afferent nerves with subsequent release of vasodilatory substances such as calcitonin gene-related peptide (CGRP) and nitric oxide. We then tested the hypothesis that similar factors regulate duodenal mucus gel thickness. Gel thickness was optically measured using in vivo microscopy in anesthetized rats. Duodenal mucosae were superfused with pH 7.0 buffer with vanilloid receptor agonist capsaicin, bradykinin, or PGE(2) injection or were challenged with pH 2.2 solution, with or without the vanilloid antagonist capsazepine, human CGRP-(8-37), N(G)-nitro-L-arginine methyl ester, and indomethacin. Other rats underwent sensory ablation with high-dose capsaicin pretreatment. Acid, bradykinin, capsaicin, and PGE(2) all quickly thickened the gel. Antagonism of vanilloid and CGRP receptors, inhibition of nitric oxide synthase, and sensory deafferentation delayed gel thickening, suggesting that the capsaicin pathway mediated the initial burst of mucus secretion that thickened the gel. Indomethacin abolished gel thickening due to acid, bradykinin, and capsaicin. Inhibition of gel thickening by indomethacin in response to multiple agonists suggests that cyclooxygenase activity is essential for duodenal gel thickness regulation. Duodenal afferent neural pathways play an important role in the modulation of cyclooxygenase-mediated physiological control of gel thickness.

Animals↗

Acute adaptive cellular base uptake in rat duodenal epithelium.

We studied the role of duodenal cellular ion transport in epithelial defense mechanisms in response to rapid shifts of luminal pH. We used in vivo microscopy to measure duodenal epithelial cell intracellular pH (pH(i)), mucus gel thickness, blood flow, and HCO secretion in anesthetized rats with or without the Na(+)/H(+) exchange inhibitor 5-(N,N-dimethyl)-amiloride (DMA) or the anion transport inhibitor DIDS. During acid perfusion pH(i) decreased, whereas mucus gel thickness and blood flow increased, with pH(i) increasing to over baseline (overshoot) and blood flow and gel thickness returning to basal levels during subsequent neutral solution perfusion. During a second brief acid challenge, pH(i) decrease was lessened (adaptation). These are best explained by augmented cellular HCO uptake in response to perfused acid. DIDS, but not DMA, abolished the overshoot and pH(i) adaptation and decreased acid-enhanced HCO secretion. In perfused duodenum, effluent total CO(2) output was not increased by acid perfusion, despite a massive increase of titratable alkalinity, consistent with substantial acid back diffusion and modest CO(2) back diffusion during acid perfusions. Rapid shifts of luminal pH increased duodenal epithelial buffering power, which protected the cells from perfused acid, presumably by activation of Na(+)-HCO cotransport. This adaptation may be a novel, important, and early duodenal protective mechanism against rapid physiological shifts of luminal acidity.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Cellular bicarbonate protects rat duodenal mucosa from acid-induced injury.

Secretion of bicarbonate from epithelial cells is considered to be the primary mechanism by which the duodenal mucosa is protected from acid-related injury. Against this view is the finding that patients with cystic fibrosis, who have impaired duodenal bicarbonate secretion, are paradoxically protected from developing duodenal ulcers. Therefore, we hypothesized that epithelial cell intracellular pH regulation, rather than secreted extracellular bicarbonate, was the principal means by which duodenal epithelial cells are protected from acidification and injury. Using a novel in vivo microscopic method, we have measured bicarbonate secretion and epithelial cell intracellular pH (pH(i)), and we have followed cell injury in the presence of the anion transport inhibitor DIDS and the Cl(-) channel inhibitor, 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB). DIDS and NPPB abolished the increase of duodenal bicarbonate secretion following luminal acid perfusion. DIDS decreased basal pH(i), whereas NPPB increased pH(i); DIDS further decreased pH(i) during acid challenge and abolished the pH(i) overshoot over baseline observed after acid challenge, whereas NPPB attenuated the fall of pH(i) and exaggerated the overshoot. Finally, acid-induced epithelial injury was enhanced by DIDS and decreased by NPPB. The results support the role of intracellular bicarbonate in the protection of duodenal epithelial cells from luminal gastric acid.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

[A comparative morphometrical study on development of anterior septonasal accessory organs in the cleft palate mice].

OBJECTIVE: The aim of this study was to investigate whether cleft palate is associated with the mal-development of the vomer, Jacobson's organ and para-septal cartilage. METHODS: Sixty craniomaxillary complexes, which came from 30 pairs of trisomy 18 with cleft palate (Ts + CP) and euploid mouse fetuses were precisely orientated in the coronal plane, and serially sectioned at 7 microns thickness. With the aid of computer imaging analysis system the vomer in coronal and sagittal direction, Jacobson's organ and para-septal cartilage in the boundary plane of the primary and secondary palate were measured and compared quantitatively. RESULTS: The hard tissues (including the vomer and para-septal cartilage) of the anterior nasal septum in Ts + CP foetuses show serious developmental hypoplasia, however, the Jacobson's organ had no significant different between the cleft and non-cleft samples. CONCLUSION: Development hypoplasia of these hard tissues may be more closely related with the autosomal trisomic condition more than the cleft palate.

Animals↗

Murine Bv8 gene maps near a synteny breakpoint of mouse chromosome 6 and human 3p21.

The genomic structure of the murine Bv8 gene was determined in 129/SvJ mouse, and the chromosomal localization was identified. Bv8 has first been characterized from skin secretion of the yellow-bellied toad, Bombina variegata. When injected into rat brain, this polypetide causes hyperalgesia. The murine Bv8 gene was shown to consist of four exons and was localized on chromosome 6 between the microsatellite markers D6Mit66 and D6Mit36 near the gene mem1, whereas the human counterpart was assigned to the non-syntenic region 3p21.1. Furthermore, the primary Bv8 transcript appeared to be alternatively spliced. The first variant contained all four exons yielding a product with a stretch highly enriched in basic amino acids in its central part. This domain is absent in the peptides from frog as well as in a splice variant expressed in mouse testis. A third variant gives rise to a truncated polypeptide.

Alternative Splicing↗

Taste active compounds in a goat cheese water-soluble extract. 1. Development and sensory validation of a model water-soluble extract.

The aim of this study was to evaluate the impact of the components of a goat cheese water-soluble extract (WSE) on its flavor by both physicochemical and sensory techniques with special emphasis on taste. After characterization of the organoleptic properties of the cheese, the WSE was extracted with pure water and submitted to successive tangential ultrafiltrations and nanofiltration. The physicochemical assessment of these fractions led to the constitution of a model mixture (MWSE) compared by sensory evaluation to the crude WSE, using a panel of 16 trained members. The results of both sensory profile and triangular tests indicate no significant difference, therefore proving that the reconstitution of the WSE was correct, thereby showing the sensory neutrality of lipids and peptides smaller than 500 Da, which had not been included in the MWSE. Moreover, the cheese gustatory characteristics are comparable to those of the WSE despite weaker levels of sharpness and astringency in the extract, the respective origins of which are discussed.

Animals↗

Taste active compounds in a goat cheese water-soluble extract. 2. Determination of the relative impact of water-soluble extract components on its taste using omission tests.

The aim of this work was to determine the relative impact of water-soluble compounds on the gustatory properties of a goat cheese water-soluble extract (WSE). Using a semisynthetic model mixture (MWSE) previously elaborated in physicochemical and gustatory accordance with the cheese WSE (see part 1, Engel et al. J. Agric. Food Chem. 2000, 48, 4252-4259), omission tests were performed. Among the main taste characteristics of the WSE (salty, sour, and bitter), saltiness was explained by an additive contribution of sodium, potassium, calcium, and magnesium cations, whereas sourness was mainly due to a synergistic effect involving sodium chloride, phosphates, and lactic acid and bitterness was found to result from calcium and magnesium chlorides, the impact of which was partially masked by sodium chloride. In contrast, amino acids, lactose, and peptides did not have any significant impact on WSE taste properties. To quantify the contribution of the taste active compounds to bitterness and saltiness, stepwise multiple linear regressions were performed. Those contributions were expressed as a percentage of the considered taste characteristic intensity in the WSE. The model obtained allowed up to 97.4% of the perceived saltiness to be described and approximately 85% of the bitterness.

Animals↗

Dynamic regulation of mucus gel thickness in rat duodenum.

We examined the dynamic regulation of mucus gel thickness (MGT) in vivo in rat duodenum in response to luminal acid, cyclooxygenase (COX) inhibition, and exogenous PGE(2). An in vivo microscopic technique was used to measure MGT with fluorescent microspheres in urethan-anesthetized rats. Duodenal mucosa was topically superfused with pH 7.0 or pH 2.2 solutions with or without PGE(2) and indomethacin treatments. Glycoprotein concentration of duodenal loop perfusates was measured with periodic acid/Schiff (PAS) or Alcian blue (AB) staining. MGT and perfusate glycoprotein concentration were stable during a 35-min perfusion with pH 7.0 solution. Acid exposure increased MGT and PAS- and AB-positive perfusate glycoprotein concentrations. Indomethacin pretreatment increased both PAS- and AB-positive perfusate glycoprotein at baseline; subsequent acid superfusion decreased perfusate glycoproteins and gel thickness. PGE(2) (1 mg/kg iv) simultaneously increased MGT and PAS-positive perfusate glycoprotein concentrations followed by a transient increase in AB-positive glycoprotein concentration, suggesting contributions from goblet cells and Brunner's glands. Parallel changes in MGT and perfusate glycoprotein concentration in response to luminal acid and PGE(2) suggest that rapid MGT variations reflect alterations in the balance between mucus secretion and exudation, which in turn are regulated by a COX-related pathway. Luminal acid and PGE(2) augment mucus secretion from goblet cells and Brunner's glands.

Acids↗

An experimental study on the developmental malformations of the trisomy 18 NMRI mice.

OBJECTIVE: To study the incidence of trisomy 18 in NMRI mice and its developmental malformations. METHODS: Sixty female NMRI mice and 11 male mice with the Rb(2.18) 6 Rma and Rb (1 +/-18) 10 Rma chromosomes were used. On the gestational days 16 and 17, the pregnant mice were randomly killed by cervical dislocation. A total of 823 implants were gained from 60 litters; they comprised 569 living foetuses, and chromosomal examination was performed in the generated living foetuses. Gross morphological study was performed in all living fotuses. RESULTS: Ninety-five foetuses were identified as trisomic foetuses in all of 569 living foetuses. Among them, there were 68 trisomy 18 NMRI mice with cleft palate. Gross morphological study showed that trisomy 18 foetuses had significant body flexion. Some cases of trisomy 18 showed shortened limbs, oedematous body or exencephaly as additional symptoms. CONCLUSION: Developmental malformations in trisomy 18 NMRI mice showed a seried of abnormalities; they had not only the underdeveloped body weight, but also the highter incidence of congenital cleft palate.

Animals↗

[Morphometrical study on the development of the trisomy-18 with cleft palate and euploid mice].

OBJECTIVE: To quantitatively compare the whole body, the lateral maxillofacial profile in Ts18 foetuses with cleft palate (Ts + CP) and euploid foetuses in order to answer the question whether this animal model is associated with maldevelopment or hypoplasia of the craniomaxillofacial region. METHODS: Sixty female Hanmice and 11 male mice with the Rb(2.18) 6Rma and Rb(1.18) 10Rma chromosomes were used to generate 569 living foetuses. Of these, 52 pairs Ts + CP and euploid foetuses were selected according to about equal body weight, and used in gross morphometric study. RESULTS: Ts + 18 foetuses had greater body flexion, a significant maxillary and mandibular retrusion, also mandible in Ts + CP foetuses were smaller than in euploids without cleft. CONCLUSIONS: This animal model of congenital cleft palate developed hypoplasia of the maxilla and mandible.

Animals↗

[Comparative histomorphological study on the craniomaxillary development of the trisomy-18 with cleft palate and euploid mice].

OBJECTIVE: The aim of this study is to compare histological morphology of craniomaxillary complex of Trisomy 18 with cleft palate (Ts + CP) and euploid mouse foetuses to understand whether cleft palate is associated with maldevelopment of the craniomaxillary complex or with hypoplasia of the adjacent tissues. METHODS: Thirty pairs of Ts + CP and euploid mouse foetuses with about equal body weight were selected, and sixty craniomaxillary complex were precisely orientated in the coronal plane, then serially sectioned with 7 microns thickness through the primary palate, the whole hard palate and the soft palate. Finally six sections were selected for comparative histomorphological study based on anatomical landmarks. RESULTS: The trisomy with cleft palate mouse foetuses had significantly developmental hypoplasia in the primary palatal shelves. The palatal shelves, vomer, palatal bone and nasal septal cartilage in cleft samples showed significantly developmental hypoplasia with a relatively wider nasal septum, nasal capsule and a bigger nasal airway volume, nasopharyngeal cavity. CONCLUSION: The hard tissues of the craniomaxillary complex in Ts + CP mouse foetuses, including bone and cartilage show serious maldevelopment or developmental hypoplasia, and these may be closely related to the autosomal trisomic condition.

Animals↗

The mammalian homologues of frog Bv8 are mainly expressed in spermatocytes.

Bv8, a protein from skin secretions of Bombina variegata, reacts with receptors present in mammalian brain and intestine (Mollay et al. (1999) Eur. J. Pharmacol. 374, 189-196). As deduced from cloned cDNAs, the murine and human Bv8 homologues have identical amino-terminal sequences and also contain 10 cysteines. From mouse testes, two forms of Bv8 mRNA have been characterized, of which one contains an additional exon which codes for 21 mostly basic amino acids. The mouse Bv8 gene is most active in mid-late pachytene spermatocytes. In mouse testes, Bv8 mRNA can first be detected at the end of the second week post partum.

Amino Acid Sequence↗

Acid-sensing pathways of rat duodenum.

We tested the hypothesis that the duodenal hyperemic response to acid occurs through activation of capsaicin-sensitive afferent nerves with subsequent release of vasodilatory substances such as calcitonin gene-related peptide (CGRP) and nitric oxide (NO). Laser-Doppler flowmetry was used to measure duodenal blood flow in urethan-anesthetized rats. Duodenal mucosa was superfused with pH 7. 0 buffer with capsaicin or bradykinin or was acid challenged with pH 2.2 solution, with or without vanilloid receptor antagonists, a CGRP receptor antagonist, an NO synthase (NOS) inhibitor, or a cyclooxygenase inhibitor. The selective vanilloid receptor antagonist capsazepine (CPZ) dose dependently inhibited the hyperemic response to acid and capsaicin but did not affect bradykinin-induced hyperemia. Ruthenium red was less inhibitory than capsazepine. Selective ablation of capsaicin-sensitive nerves, CGRP-(8-37), and N(G)-nitro-L-arginine methyl ester inhibited acid-induced hyperemia, but indomethacin did not. We conclude that luminal acid, but not bradykinin, stimulates CPZ-sensitive receptors on capsaicin-sensitive afferent nerves of rat duodenum. Activation of these receptors produces vasodilation via the CGRP-NO pathway but not via the cyclooxygenase pathway. Acid appears to be the endogenous ligand for duodenal vanilloid receptors.

Acids↗

Retention of prefabricated attachments for implant stabilized overdentures in the edentulous mandible: an in vitro study.

STATEMENT OF PROBLEM: Bar and stud attachments are widely used to stabilize overdentures on implants in the mandible. There is strong evidence that retention of the attachment is an important factor for a patient's satisfaction. PURPOSE: This study describes retentive forces and wear of commercially available attachments of 4 implant systems (31, IMZ, Nobel Biocare, ITI Straumann) and 2 magnets (Steco). METHODS: Forces while removing the keyway portion of an attachment in its path of insertion were measured with a platform load cell. A total of 15,000 removals were performed to simulate fatigue. RESULTS: Retentive forces ranged between 3 and 85 N. The fatigue test revealed an initial increase of forces with some attachments. After 15,000 cycles, most of the attachments showed little loss of retention compared with the initial retentive forces. It is suggested that conventional fatigue tests with application of axial loads do no simulate clinical fatigue adequately.

Dental Abutments↗

Immunological and biological properties of Bet v 4, a novel birch pollen allergen with two EF-hand calcium-binding domains.

We have isolated a cDNA clone coding for a birch pollen allergen, Bet v 4. The deduced amino acid sequence of Bet v 4 contained two typical EF-hand calcium-binding domains. Sequence similarities of Bet v 4 to calmodulin are primarily confined to the calcium-binding domains. However, significant sequence similarities extending outside the Ca2+-binding sites were found with a recently described group of pollen-specific allergens of Brassica and Bermuda grass. Both EF-hand domains of Bet v 4 are able to bind Ca2+, as demonstrated by 45Ca2+ blot overlay of wild type and calcium-binding deficient mutants of Bet v 4. Among pollen-allergic patients, protein-bound Ca2+ was not an absolute requirement for IgE recognition of Bet v 4. However, disruption of the carboxyl-terminal Ca2+-binding domain indicated that most IgE antibodies from allergic patients are directed against this site. IgE inhibition experiments suggested that Bet v 4 represents a highly cross-reactive pollen allergen. Pre-absorption of allergic sera with Bet v 4 drastically reduced IgE binding to proteins of similar molecular weight in pollen extracts from distantly related plant species (e.g. timothy grass, mugwort, lily) but not in extracts from plant-derived foodstuff. To test for a possible biological role in pollen germination and tube growth, we introduced recombinant Bet v 4 protein into growing lily pollen tubes by iontophoresis. As a result, cytoplasmic streaming stopped in the vicinity of the electrode tip, and a slight depolarization of the membrane voltage was measured. These effects were not observed with Ca2+-binding deficient mutants of Bet v 4. Thus, Bet v 4 and homologous proteins represent a new class of pollen-specific Ca2+-binding allergens that may have a physiological role as inhibitors of cytoplasmic streaming in outgrowing pollen tubes.

Allergens↗

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↗