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Role for retinoid signaling in left-right asymmetric digestive organ morphogenesis.

The looping events that establish left-right asymmetries in the vertebrate gut tube are poorly understood. Retinoic acid signaling is known to impact left-right development in multiple embryonic contexts, although its role in asymmetric digestive organ morphogenesis is unknown. Here, we show that the genes for retinaldehyde dehydrogenase (RALDH2) and a retinoic acid hydroxylase (CYP26A1) are expressed in complementary patterns in the Xenopus gut during looping. A late-stage chemical genetic assessment reveals that agonists and antagonists of retinoid signaling generate abnormal gut looping topologies, digestive organ heterotaxias, and intestinal malrotations. Accessory organ deformities commonly associated with intestinal malrotation in humans, such as annular pancreas, pancreas divisum, and extrahepatic biliary tree malformations, are also induced by distinct retinoid receptor agonists. Thus, late-stage retinoic acid signaling is likely to play a critical role in asymmetric gut tube morphogenesis and may underlie the etiology of several clinically relevant defects in the digestive system.

Aldehyde Dehydrogenase 1 Family↗

Immunolocalization of an FGF-binding protein reveals a widespread expression pattern during different stages of mouse embryo development.

Fibroblast growth factors (FGFs) play important roles during fetal and embryonic development. FGF-2 (basic FGF, bFGF) is widely expressed in the embryo and has been linked to tissue growth and remodeling. However, it is tightly bound to heparin sulfate proteoglycans of the extracellular matrix which quenches its biological activity. We showed previously that a secreted FGF-binding protein (FGF-BP) can mobilize and activate FGF-2 from the extracellular matrix. While considerable data exist on the expression and pivotal role of FGF-BP in tumor growth, less is known about FGF-BP during embryonic development. In this immunohistochemical study in mice, we show FGF-BP protein expression in a broad spectrum of tissues at various stages between day 8 and day 16 of embryonal development, and compare FGF-BP and FGF-2 immunolocalization. FGF-BP is detected in the digestive system, thymus, skin, hair follicles, dental germ, respiratory tract, various glandular tissues, kidney, liver, and certain areas of the CNS, with immunoreactivity being mainly confined to cells of primitive epithelia. The putative significance of these findings with regard to mobilization of FGF-2 or other molecules is discussed. From the locally confined, time-dependent, and apparently tightly regulated FGF-BP expression we propose that FGF-BP may play an important role in embryonic development.

Adrenal Glands↗

Influence of molting and starvation on the synthesis of proteolytic enzymes in the midgut gland of the white shrimp Penaeus vannamei.

We investigated the effect of starvation as a stimulant of the digestive system on digestive proteinase activities in the white shrimp Penaeus vannamei. The starved organisms were sampled periodically according to the molting stage and compared with a continuously fed group. Molting stage was included as an independent variable. Most analyzed variables, except for trypsin, were more affected by starvation than by molting, indicating that starvation is a stimulant that masks the effect of molting and showing that food or alimentary stress is more conspicuous than physiological ones. We found that starvation is a stimulant that surpasses the effect of molting, and because it affects the activity of digestive proteinases, studies of starving organisms in combination with tools of molecular biology, can be a helpful working model in the understanding of mechanisms of regulation of digestive enzyme activity. In the starved organisms, trypsin and chymotrypsin activities were similar, suggesting dependence of one to the other. Changes in proteolytic activities and the number of protein bands in electrophoresis showed evidence of synthesis regulation in the midgut gland of white shrimp.

Chymotrypsin↗

Immunohistochemical distribution of cytochrome P4501A in larvae and fingerlings of the Siberian sturgeon, Acipenser baeri.

In this paper we investigate by means of immunohistochemistry, the tissue distribution of constitutive cytochrome P4501A (CYPIA), from hatching until 30 days posthatching in developing Siberian sturgeon, Acipenser baeri. For this purpose, a polyclonal (BN-1) antiserum developed against a conservative sequence of piscine CYP1A and a monoclonal (C10-7) antiserum directed against cod CYP1A were used on paraffin-embedded samples. From hatching onwards, distinct CYP1A immunoreactivity was distinctly observed in the following tissues and cells: envelope of oil droplets, matrix and syncytium of the yolk-sac, sinusoids, biliary epithelial cells and hepatocytes. In the digestive tract, buccopharyngeal, oesophageal, gastric and intestinal epithelia, as well as the cytoplasm and brush border of enterocytes were CYP1A-positive. Interestingly, gastric glands and melanin-plug present within lumen of the digestive system were strongly immunoreactive. Kidney (epithelia of renal tubules), gills (pillar and endothelial cells), skin (epithelial cells), muscle fibres of heart and eye (retina) were positive. In brain, we observed a strong CYP1A staining in the developing telencephalon and especially in olfactory system, as well as in those nerve fibres running ventrally toward the posterior brain. A strong CYP1A staining was observed in vascular endothelia of all organs/tissues, especially in the liver. In general, the intensity of CYP1A immunostaining increased during larval development, suggesting besides its known metabolic function (endogenous and/or exogenous), a possible participation of this heme-protein in control of cell division, regulation of growth and differentiation.

Animals↗

[Distribution of the enterochromaffin ("EC") cells and those of the "APUD" series in the gastrointestinal tract of ruminants].

The research was carried out on the vorestomachs, abomasum and on the various tracts of gut of adult Cattle, Sheep and Goat, because Ruminants, not previously studied with respect to this problem, have, as is well known, particular morpho-functional characteristics of the digestive system. The results can be synthetized as follows: 1) either "EC" (5-HT-producing) or "APUD" cells (peptide hormones-producing) are not demonstrable in the vorestomachs. 2) "EC" cells are present in the various areas of abomasum (particularly numerous in the fundus glands) and in the different tracts of the gut (predominantly in the duodenum and in the rectum). 3) In the "APUD" cells of the abomasum gastrin-producing "G" cells are certainly demonstrable. They are present only in the pyloric glands, where they prevail in the middle third. Only in the cattle, cells which have all the histochemical characteristics of "G" cells, but are quite morphologically different, are also present in the same area. An interesting peculiarity seems to be the reduced number of "APUD" cells, compared with that of Monogastrics: it was impossible, in fact, to demonstrate some cells ("A", "A-like","X", "D", "D1", "ECL") which are described by other Authors in the stomach of various Mammals. 4) In the small intestine, endocrine cells, probably heterogenous are present, resulting more numerous in the duodenum. 5) In the coecum, colon and rectum, cells comparable to enteroglucagon-producing "EG" cells, are present; they are particularly numerous in the rectum, where cells similar to "H" cells are also present.

Abomasum↗

[Sarcoidosis--an uncommon cause of pancreatic mass].

Sarcoidosis is a multi-system granulomatous disease that mainly affects the lungs and the lymphatic system. Involvement of the digestive system is rare, while the presentation of a mass in the pancreas as the first sign of sarcoidosis in the digestive system is yet rarer. Very few cases have been reported in the literature. The presentation of a mass in the pancreas is indicative of malignancy or inflammation and thus makes the diagnosis of sarcoidosis very difficult. Often it is discovered only after surgical intervention. We present a case study in which the involvement of the pancreas, bile ducts and mesentery lymph nodes led to a Whipple operation. However, on biopsy, non-caseating granulomas were found with no signs of malignancy. In view of the difficulties in diagnosing sarcoidosis of the digestive system and pancreas, we present a review of the literature on the diagnosis and management of this form of sarcoidosis.

Female↗

General pharmacological properties of the new vasodilator flosequinan.

Pharmacological effects of a new vasodilator, flosequinan (7-fluoro-1-methyl-3-(methylsulfinyl)-4(1H)-quinolone, BTS 49 465, CAS 76568-02-0) on the central nervous system, somatic nervous system, autonomic nervous system and smooth muscle, digestive system and miscellaneous organs were investigated. 1. The central nervous system: Flosequinan inhibited acetic acid-induced writhing at doses of more than 30 mg/kg p.o. and decreased body temperature and tended to decrease spontaneous movement slightly in mice at a dose of 100 mg/kg p.o. However, flosequinan had little effect on hexobarbital-induced hypnosis, reserpine-induced hypothermia and motor coordination and lacked anticonvulsant and analgesic activities in mice. Flosequinan had little effect on general behavior in rats and did not have any effect on spontaneous EEG and EEG arousal response in rabbits. 2. The somatic nervous system: Flosequinan did not cause muscle relaxation in mice and had little effect on neuromuscular transmission in cats. No local anesthetic activity was exhibited through inhibition of the corneal reflex in guinea pigs. 3. The autonomic nervous system and smooth muscle: Flosequinan produced a relaxation of the isolated trachea of guinea pigs at concentrations of more than 3 x 10(-5) mol/l, but its potency was very weak in comparison with that of isoproterenol (isoprenaline). Flosequinan inhibited spontaneous motility of the isolated uterus of pregnant rats at concentrations higher than 10(-4) mol/l and the motility of the uterus of non-pregnant rats in vivo was inhibited at 30 mg/kg i.v. Flosequinan does not seem to exert any on norepinephrine, serotonin, acetylcholine or histamine. This is supported by the fact that at concentrations of 10(-4)-3 x 10(-3) mol/l non-competitive inhibition was observed with regard of the contractions of the isolated aorta and vas deferens of rats induced by norepinephrine, the contraction of isolated rat stomach induced by serotonin, the contraction of isolated guinea-pig ileum induced by acetylcholine, histamine and barium chloride and the contraction of the isolated uterus of non-pregnant rats induced by oxytocin. However, flosequinan was more potent as a relaxant of vascular than of these other smooth muscles. The drug was slightly inhibitive at a high dose of 30 mg/kg i.v. with regard of the contraction of nictitating membrane induced by stimulation of preganglionic sympathetic nerve in cats. 4. The digestive system: Flosequinan at 100 mg/kg p.o. inhibited intestinal propulsion in mice and inhibited spontaneous motility of stomach and duodenum of rats at a dose of 30 mg/kg i.v.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Comparative studies on the distribution mode of orthomyxo-virus and paramyxo-virus receptor possessing cells in mice and birds.

Many experimental studies have shown that orthomyxo- and para-myxoviruses may be pneumotropic, but not enterotropic in mammals. On the other hand, these viruses are both pneumotropic and enterotropic in avian species. We have devised a new method for detecting virus receptor possessing cells (VRPC) in tissue sections. VRPC could be detected in the cells lining the airways of both mice and birds. The mode of distribution of VRPC in mouse digestive system differed remarkedly from that in avian digestive system. VRPC were not found in the epithelium of mouse digestive systems whereas the epithelium of bird digestive system were abundant in VRPC. When the large intestines from mice or duck undergoing laparotomy and inoculated directly into intestine with influenza virus were examined, viral antigen was detected in the epithelial cell of duck colon, but not in mouse intestines. From the study utilizing the new method, it could be concluded that the distribution mode of VRPC is one of the most important factors determining the virus tissue specificity.

Animals↗

Assessing workplace chemical exposures: the role of exposure monitoring.

Occupational exposure is the condition of being subjected through employment to a chemical, physical, or biological agent, or to a specific process, practice, behavior, or organization of work. Exposure to a chemical agent is typically the contact of that agent with the outer boundary of a subject, such as the respiratory system, skin, or digestive system. In occupational hygiene we are most concerned with exposure through the respiratory system, although, increasingly we are concerned with the results of dermal exposures, including those exposures to the skin that can be transferred to the mouth and digestive system. This presentation will detail methods available for assessing personal exposures to chemicals through monitoring. The results from monitoring can then be compared to established guidelines and regulations, although this is not the only rationale for making measurements. These monitoring methods are currently used around the world to establish the benchmark hazard from which risk to the worker can be predicted. The presentation will describe the general techniques for assessing exposures to the respiratory system from chemical gases and vapors, chemical dusts, and exposures to the skin from bulk chemicals or chemical contamination of surfaces. For respiratory exposures, direct-reading instruments are available for spot measurements, and for monitoring short-term fluctuations in concentration. However, most standards and regulations are based on time-integrated (time-weighted average) exposures, requiring longer-term integrative methods. Therefore, the specific focus of this review will be the methods available for full work-shift sampling. For gases and vapors this will include taking whole-air samples in canisters or polymer bags, or concentration of chemicals by absorption in liquids or adsorption on solid sorbents, with subsequent chemical analysis. Chemical concentration can take place by pumping air through the sorbing media, or by allowing molecules to diffuse to the sorbent surface. Transfer of the collected chemicals to the analytical instrumentation can be accomplished using solvent displacement and injection, or through the application of heat to bring the collected molecules back into the vapor phase. For particles, the particle size is important as this determines the site of deposition in the lungs, and so time-integrated sampling on filters using various types of size-selective samplers is preferred. Finally, some techniques that have been used to assess the potential for chemical contamination of the skin are presented. Biomonitoring is another tool that can be used to assess exposure, and the results are more relevant to dosimetric considerations than exposure. Biomonitoring is a complex subject worthy of a separate review, and will be considered only briefly here.

Air Pollutants, Occupational↗

[Abdominal and digestive manifestations in systemic vasculitides].

Digestive involvement is frequent during the course of systemic small and medium-sized vessel vasculitides. Clinical manifestations range from rapidly regressive abdominal pain to surgical manifestations associated with poor prognosis. These are usually associated with extra-abdominal signs, reflecting vasculitis activity. Isolated gastrointestinal involvement is observed in only 16% of these patients. The main clinical manifestations are common to all vasculitides (ischemia, bowel infarction and perforations, gastrointestinal hemorrhage due to mucosal ulcerations or aneurysmal ruptures), but some are more specific to one type (granulomatous ileo-colitis during Wegener's granulomatosis, eosinophilic colitis during Churg-Strauss syndrome). Gastrointestinal arteriography can be helpful for diagnosis, but has no prognostic value, likewise for the presence of ANCA. As there are no identified factors predictive of a surgical abdomen, therapy must be adapted individually, using steroids and immunosuppressive agents, generally cyclophosphamide. Prompt surgical and medical care of these seriously ill patients has lowered mortality from nearly 100% twenty years ago to approximately 23 to 56% currently.

Gastrointestinal Diseases↗

Unique and conserved aspects of gut development in zebrafish.

Although the development of the digestive system of humans and vertebrate model organisms has been well characterized, relatively little is known about how the zebrafish digestive system forms. We define developmental milestones during organogenesis of the zebrafish digestive tract, liver, and pancreas and identify important differences in the way the digestive endoderm of zebrafish and amniotes is organized. Such differences account for the finding that the zebrafish digestive system is assembled from individual organ anlagen, whereas the digestive anlagen of amniotes arise from a primitive gut tube. Despite differences of organ morphogenesis, conserved molecular programs regulate pharynx, esophagus, liver, and pancreas development in teleosts and mammals. Specifically, we show that zebrafish faust/gata-5 is a functional ortholog of gata-4, a gene that is essential for the formation of the mammalian and avian foregut. Further, extraembryonic gata activity is required for this function in zebrafish as has been shown in other vertebrates. We also show that a loss-of-function mutation that perturbs sonic hedgehog causes defects in the development of the esophagus that parallel those associated with targeted disruption of this gene in mammals. Perturbation of sonic hedgehog also affects zebrafish liver and pancreas development, and these effects occur in a reciprocal fashion, as has been described during mammalian liver and ventral pancreas development. Together, these data define aspects of digestive system development necessary for the characterization of zebrafish mutants. Given the similarities of teleost and mammalian digestive physiology and anatomy, these findings have implications for developmental and evolutionary studies as well as research of human diseases, such as diabetes, liver cirrhosis, and cancer.

Alleles↗

Screening for foetal malformations: performance of routine ultrasonography in the population of the Swiss Canton of Vaud.

OBJECTIVE: To determine the sensitivity of ultrasonography in screening for foetal malformations in the pregnant women of the Swiss Canton of Vaud. STUDY DESIGN: Retrospective study over a period of five years. METHOD: We focused our study on 512 major or minor clinically relevant malformations detectable by ultrasonography. We analysed the global sensitivity of the screening and compared the performance of the tertiary centre with that of practitioners working in private practice or regional hospitals. RESULTS: Among the 512 malformations, 181 (35%) involved the renal and urinary tract system, 137 (27%) the heart, 71 (14%) the central nervous system, 50 (10%) the digestive system, 42 (8%) the face and 31 (6%) the limbs. Global sensitivity was 54.5%. The lowest detection rate was observed for cardiac anomalies, with only 23% correct diagnoses. The tertiary centre achieved a 75% detection rate in its outpatient clinic and 83% in referred patients. Outside the referral centre, the diagnostic rate attained 47%. CONCLUSIONS: Routine foetal examination by ultrasonography in a low-risk population can detect foetal structural abnormalities. Apart from the diagnosis of cardiac abnormalities, the results in the Canton of Vaud are satisfactory and justify routine screening for malformations in a low-risk population. A prerequisite is continuing improvement in the skills of ultrasonographers through medical education.

Central Nervous System↗

[Advances in gastrointestinal peptides: somatostatin].

Twenty years after being identified as "somatotropin release inhibiting factor" (SRIF) and "growth-hormone release inhibiting hormone" (GH-RIH), under a new name, somatostatin (SMS) has reached an outstanding position in gastroenteropancreatic endocrinology. It is a powerful and universal inhibitor of the digestive functions: secretion, motility, absorption and splanchnic blood flow. Long-acting synthetic analogues have made possible its therapeutic trial in certain clinical problems. This review covers the advances in several areas of interest for gastroenterologists: (a) the role of SMS in the regulation of digestive physiology and its participation in neurohumoral and inmunoneuropeptidic interrelations; (b) in relation to gastric acid secretion, hypotheses on supposed links between duodenal ulcer and Helicobacter pylori infection; (c) theoretical and experimental bases for somatostatin analogues use in the treatment of bleeding esophageal varices; (d) current status of the management of other nonneoplastic gastroenteropancreatic diseases; and (d) strategy for the therapy of endocrine tumors of the digestive system.

Digestive System↗

Hospitalizations among employees in the Danish hotel and restaurant industry.

BACKGROUND: The aim of the present study was to provide a broad picture of the morbidity among employees in the Danish hotel and restaurant industry. METHODS: Cohorts of all 20-59-year-old employees in the Danish hotel and restaurant industry in the years 1981, 1986, 1991 and 1994 were formed to calculate age-standardized hospitalization ratios (SHR) and time trends (1981-1997) for many different diagnoses. RESULTS: Both for women and men, significantly higher SHRs were found for infectious and parasitic diseases, neoplasms, diseases in the nervous system and sense organs, diseases of the circulatory system, diseases of the respiratory system, diseases of the digestive system and diseases of the musculoskeletal system among employees in hotels and restaurants than in the digestive system and diseases of the musculoskeletal system among employees in hotels and restaurants than in the working population at large. Furthermore, among women a significantly elevated risk was found for injuries in the lower extremities, injuries in the upper extremities and head injuries, and among men a high risk was found for head injuries and a low risk for ruptures in ligaments and muscles. The trend assessments did not detect any significant changes in SHRs over time. CONCLUSION: Employment in the Danish hotel and restaurant industry is associated with an elevated hospitalization risk due to many diseases, which may be related to occupation and lifestyle. In line with the official policy of reducing inequality in health, focus should be placed on the health problems in this group.

Adult↗

[The development of the endoscopic treatment].

With development and improvement of the endoscope equipment, the role of the digestive system endoscope is developing to the application from the pickup of mere lesion to precise diagnosis and endoscopic treatment. The range of the digestive system endoscopic treatment tends to also expand year by year. From the viewpoint of the medicine side, the update of the digestive system endoscope is reported this time. Digestive system endoscopic treatment can be divided roughly into the digestive tract region and the bile pancreas region. There are foreign body extraction, hemostasis methods(peptic ulcer, esophageal varix), excision for the tumor, dilatation methods for the stenosis, etc. as endoscopic treatment in the digestive tract region. In the bile pancreas region, there are endoscopic sphincterotomy, calculus removal of bile duct and ductus pancreaticus, drainage, dilatation methods for the stenosis, etc. The endoscopic treatment develops more and more on both regions with development of together various equipment and improvement in the technique. The invasion to the patient is less than the surgery for the endoscopic treatment, and it is possible to position with the therapy that it retained the function of the organ and was excellent concerning the QOL. It is anticipated with that the effort with the aim of further low invasion will advance in future too.

Catheterization↗