Refeeding the malnourished patient.
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Editorial↗
Biomedical subjects
D H Alpers
Publications and source records attributed to D H Alpers.
Sulphydryl blocker-induced rat colitis is ameliorated by intravenous injection of antibody to colonic surfactant-like particle.
A rat model of experimental colitis and jejunitis induced by iodoacetamide (IA), a sulphydryl blocker is accompanied by increased leukotriene, prostaglandin E2 (PGE2) generation, and nitric oxide synthase (NOS) activity. Rat small intestinal and colonic surfactant-like particles (SLP) that accumulate on the apical surface of mucosal cells have been identified and specific antibodies to them have been produced. The aim of this study was to evaluate a possible role of SLP in IA-induced colitis and jejunitis. Inflammation was induced in Sprague-Dawley rats either by intracolonic administration of 3% IA (0.1 ml) or by intrajejunal administration of 2% IA (0.1 ml). Antisera raised against either colonic SLP, pulmonary SP-A (a major protein associated with colonic SLP), or small intestinal SLP were injected into the tail vein of rats 48 h before, simultaneous with, or 24 h after IA administration. Rats were killed 2 or 10 days after IA was given, their colon or small intestine was isolated and rinsed, and a segment of colon (10 cm) or small bowel (30 cm) was weighed and processed for microscopy, NOS and myeloperoxidase (MPO) activities, and PGE2 generation. Intracolonic or jejunal IA resulted after 48 h in extensive macroscopic and microscopic damage, accompanied by increased segmental weight, MPO and NOS activity, and PGE2 generation. Colonic SLP antibody administration, either 48 h before or at the time of damage induction, significantly decreased macroscopic as well as microscopic damage, segmental weight, MPO activity, and PGE2 generation, but had no effect on NOS activity. Neither control sera nor antisera against SP-A had any protective effect, nor did injection of anti-colonic SLP antisera given 24 h after IA. Small bowel SLP antibody offered no protection against IA jejunitis. IA-induced colitis but not jejunitis is ameliorated by intravenous injection of SLP antibody by a mechanism yet to be determined. These data provide further evidence of a physiologic role for gastrointestinal SLP.
Animals↗
Binding of pili from uropathogenic Escherichia coli to membranes secreted by human colonocytes and enterocytes.
PapG adhesins mediate the binding of uropathogenic Escherichia coli. Although receptors for these adhesins have not been demonstrated in intestinal epithelia, the colonic microflora includes strains of uropathogenic E. coli. We now report that surfactant-like particles secreted by the human intestine contain receptors for PapG adhesins and may provide an intestinal habitat for uropathogenic bacteria.
Adhesins, Escherichia coli↗
Fundamentals of neurogastroenterology.
Current concepts and basic principles of neurogastroenterology in relation to functional gastrointestinal disorders are reviewed. Neurogastroenterology is emphasized as a new and advancing subspecialty of clinical gastroenterology and digestive science. As such, it embraces the investigative sciences dealing with functions, malfunctions, and malformations in the brain and spinal cord, and the sympathetic, parasympathetic and enteric divisions of the autonomic innervation of the digestive tract. Somatomotor systems are included insofar as pharyngeal phases of swallowing and pelvic floor involvement in defecation, continence, and pelvic pain are concerned. Inclusion of basic physiology of smooth muscle, mucosal epithelium, and the enteric immune system in the neurogastroenterologic domain relates to requirements for compatibility with neural control mechanisms. Psychologic and psychiatric relations to functional gastrointestinal disorders are included because they are significant components of neurogastroenterology, especially in relation to projections of discomfort and pain to the digestive tract.
Colonic Diseases, Functional↗
Rat intestinal alpha1-antitrypsin secretion is regulated by triacylglycerol feeding.
alpha1-Antitrypsin (AAT) is secreted by the enterocyte, but its regulation of expression, intramucosal distribution, and functional status are unclear. After corn oil gavage (plus Pluronic L-81 to block chylomicron release), rat intestine was examined for mRNA encoding AAT, immunoreactivity by light and electron microscopy, and protein content by Western blot. Species-specific antisera used were raised against both AAT and surfactant-like particle (SLP), a membrane secreted by the enterocyte in response to fat feeding. Purified luminal SLP was fractionated by Bio-Gel P-200 chromatography to assess its interaction with AAT. Triacylglycerol feeding maximally increased mucosal mRNA-encoding AAT and AAT intracellular protein content by 3 and 5 h, respectively. Immunocytochemistry revealed predominance of AAT in basolateral spaces around enterocytes and Pluronic-blocked extracellular accumulation of AAT, patterns nearly identical to those of secreted SLP. About 10% of AAT was reversibly associated with SLP. Luminal AAT was smaller (51 kDa) than mature AAT (55 kDa) and did not form a complex with pancreatic elastase. When the common bile duct was tied, excluding pancreatic proteases from the lumen, mature AAT that was cleaved by pancreatic elastase was secreted. The luminal secretion of AAT and its reversible association with SLP suggest an intracellular association and a possible role for AAT during lipid digestion and absorption.
Administration, Oral↗
Use of macro- and micronutrients for nutrition support in inflammatory bowel disease.
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Anemia, Iron-Deficiency↗
Caco-2 cells express a combination of colonocyte and enterocyte phenotypes.
Caco-2 cells are derived from a human colonic adenocarcinoma, but differentiate into small intestinal-like cells after confluence. While this enterocytic differentiation has been well studied, the presumed parallel loss of colonocyte function has not been as thoroughly examined. To follow the phenotype for both tissues, Western blots were performed using antisera recognizing liver/bone/kidney alkaline phosphatase and surfactant-like particle proteins found in normal human colon, along with antisera against the small bowel representatives of the same proteins. Antisera against proteins enriched in either enterocytes (alpha1-antitrypsin) or colonocytes (surfactant protein A) were also evaluated. Alkaline phosphatase activity increased from 3 to 18 days post-confluence. Activity at 3 days post-confluence derived substantially from both isomers. Thereafter, the colonic (liver/bone/kidney) isomer declined to low levels as the content of the enterocytic isomer rose. A similar pattern was found with colonic (decreasing expression) and enterocytic (increasing expression) surfactant-like particle proteins. In particular, the content of larger enterocytic particle proteins (97 and 116 kDa) increased with time in culture. Expression of alpha1-antitrypsin increased early and remained high, whereas surfactant protein A generally declined after the third day post-confluency. In summary, undifferentiated Caco-2 cells express very low levels of proteins characteristic of either colonocytes or enterocytes. Immediately after confluence, they expressed proteins characteristic of both cell types. Thereafter, the content of colonocyte-specific proteins decreased, whereas those specific for the enterocyte increased. The timing and degree of this phenotypic switch have implications for the interpretation of experiments using Caco-2 cells as a model of small intestinal function.
Alkaline Phosphatase↗
Vitamin A up-regulates expression of bone-type alkaline phosphatase in rat small intestinal crypt cell line and fetal rat small intestine.
Vitamin A is a potent inducer for liver/bone/kidney alkaline phosphatase (L/B/K ALP) in a variety of tissues. However, the evidence for induction of L/B/K ALP by vitamin A in small intestine is limited. In this study, we investigated the influence of vitamin A on L/B/K ALP expression in rat small intestinal crypt IEC-6 cells and fetal rat small intestine. Treatment of IEC-6 cells with all-trans retinoic acid (RA) increased the levels of activity, protein and mRNA of L/B/K ALP, whereas enterocyte-specific proteins, including intestinal ALP, sucrase-isomaltase and glucose transporter-2, were not induced. The reverse transcription-polymerase chain reaction technique revealed that this L/B/K ALP transcript had the bone-type but not the liver-type leader exon. IEC-6 cells constitutively expressed mRNAs of all subtypes of retinoic acid receptor (RAR) and retinoid X receptor (RXR) at varied concentrations. Among these receptor mRNAs, RARbeta mRNA quickly responded to RA treatment, and the level was doubled within 4 h. Gel mobility shift assay showed that RA induced an RXRE-binding activity in IEC-6 cells. The L/B/K ALP transcript, expressed in fetal rat small intestine, also contained the bone-type leader exon. Intragastric administration of 10 mg retinyl acetate to pregnant rats from gestational d 7 to 15 increased the levels of this transcript and enzyme in 15-d fetal rat small intestine. Our results suggest that vitamin A may be an important regulator for L/B/K ALP expression in fetal rat small intestine as well as in IEC-6 cells.
Alkaline Phosphatase↗
Expression of intrinsic factor and pepsinogen in the rat stomach identifies a subset of parietal cells.
Morphological and functional heterogeneity of parietal cells has been thought to be due to different maturation positions within the gastric gland. Morphodynamic studies have shown that 2% of parietal cells in mice derive from a pre-neck (chief) cell precursor. Intrinsic factor (IF) and pepsinogen, markers of rat chief cells, were used to determine if these proteins identified a subset of parietal cells that might reflect origin from the pre-neck cell lineage. The zymogenic region of the rat stomach and gradient-isolated fractions enriched in parietal and chief cells were fixed in 10% buffered Formalin or in Bouin's solution. Immunostaining was performed using indirect immunoperoxidase histochemistry and double-labeled immunofluorescence with antibodies raised against human IF, pepsinogen II, and H(+)-K(+)-adenosinetriphosphatase (H(+)-K(+)-ATPase). In intact tissue, parietal (H(+)-K(+)-ATPase-positive) cells were found starting at the upper edge of the isthmus, but parietal cells positive for IF and pepsinogen were only found from just below the isthmus and neck region to the base of the gastric gland. Three to four percent of isolated parietal cells were positive for these ectopic markers. This subset of cells was also positive for H(+)-K(+)-ATPase. Thus products of rat chief cells are expressed in a subset of parietal cells. The percentage of positive cells is similar to that predicted to be derived from the pre-neck (chief) precursor lineage in the mouse. The distribution of these cells to the lower neck and base of the gland suggests that the expression of chief cell products is consistent with either predetermination by lineage or parietal cell maturation or with both processes.
Animals↗
ERK and p38 MAP kinase pathways are mediators of intestinal epithelial wound-induced signal transduction.
Repair of gastrointestinal epithelial injury involves cell migration, proliferation, and specific gene expression. The pathways responsible for epithelial wound signal transduction are poorly understood. Mechanical wounding of IEC-6 cell monolayers resulted in rapid activation of the extracellular signal-regulated kinase (ERK) and p38 MAP kinase pathways, while c-Jun amino-terminal protein kinases were not significantly activated. Two minutes after wounding cells at the wound edge strongly expressed cytoplasmic phospho-ERK. By five minutes, immunostaining was concentrated within the nucleus. Consistent with activated MAP kinase signaling cascades (which phosphorylate transcription factors implicated in immediate-early gene induction), monolayer wounding resulted in greater than 30- and 8-fold increases in c-Fos and early growth response-1 mRNA by Northern blot analysis, peaking at 20 minutes. Only slight increases in c-Jun mRNA were detected. Thus, intestinal epithelial wound signal transduction is, at least in part, mediated by activation of ERK and p38 MAP kinase signaling cascades. ERK and p38 pathways may regulate pathophysiologically relevant genes in wound repair by the induction of transcription factors.
Animals↗
A receptor binding site on intrinsic factor is located between amino acids 25-44 and interacts with other parts of the protein.
A receptor-binding region of intrinsic factor (IF) has been localized to amino acid residues 25-44 by in vitro transcription/translation studies. To further define sites within the region that are necessary for binding, the effects on binding activity of brush border membranes were tested when peptides corresponding with residues 1-44 were added to normal IF and when point mutations were made between residues 25 and 44. Both human IF and IF-cobalamin (cbl) complex bound equally to membranes. None of the peptides tested inhibited human IF or IF-cbl complex binding. Both control rat IF and rat IF that was mutated to be like human IF in residues 25-44 bound to guinea pig and rat membranes; the mutant with altered charge showed 50- to 100-fold decreased affinity. Thus, the putative receptor binding region is important, but cannot alone account for all the physiologic parameters of IF binding. Conformational changes in IF are additionally important.
Amino Acids↗
Expression of functional intrinsic factor using recombinant baculovirus.
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Animals↗
Rat intestinal alkaline phosphatase II messenger RNA is present in duodenal crypt and villus cells.
BACKGROUND & AIMS: Rats produce two messenger RNA (mRNA) isoforms encoding intestinal alkaline phosphatase that are regulated differentially by fat feeding but whose tissue distribution is not known. The aim of this study was to examine the distribution of these isoforms along the crypt/villus axis during fat feeding. METHODS: Nucleotide probes and polyclonal antibodies unique for each isoform were used for in situ hybridization and immunocytochemistry. RESULTS: mRNAs encoding isoforms I and II were distributed along the entire villus. The mRNA content of isoform II was more abundant. Quantitative grain counts showed that mRNA abundance of each isoform in the upper third of the villus was significantly (40%-65%) lower than in the remaining villus in the fasting duodenum. After fat feeding, the mRNA content of both isoforms increased over the villus. Five hours after feeding, the content of the mRNA encoding only isoform II was increased in the upper third of the villus relative to the rest of the villus. Only the mRNA encoding isoform II was found in the crypt cells. However, no immunoreactive enzyme was present in the crypt cells. CONCLUSIONS: The spatial expression of the two rat intestinal alkaline phosphatase isoforms is regulated differently in response to fat feeding.
Alkaline Phosphatase↗
The centennial year: the development of important ideas during the last 100 years. Nutrition and the gastroenterologist: the last 100 years.
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Animals↗
Apical expression of functional asialoglycoprotein receptor in the human intestinal cell line HT-29.
BACKGROUND & AIMS: The asialoglycoprotein receptor localizes to the basolateral membrane of hepatocytes and to the apical membrane of enterocytes. The aim of this study was to examine HT-29 cells as a polarized cell model for studying apically localized endogenous asialoglycoprotein receptor. METHODS: Subunits H1 and H2 (human) were detected by Western blot and immunoprecipitated using subunit-specific antisera against hepatic receptor peptides. Receptor function was assessed by uptake of iodinated asialo-orosomucoid, immunoglobulin (Ig) A1, and haptocorrin. Immunocytochemistry was analyzed by standard light and confocal microscopy. RESULTS: Receptor content of the minor subunit, H2, was predominant. HT-29 cells mediated specific uptake and degradation of 125I-asialo-orosomucoid. A high-affinity (0.6 x 10(-9) mmol/L) and a low-affinity binding site were present. The specific ligand binding capacity of the apical surface was approximately twice that of the basolateral surface. Immunocytochemistry revealed a predominant apical membrane location of the minor receptor subunit, with some intracellular receptor. The apical H2 subunit was preferentially labeled with amino acid precursors compared with basolaterally located subunit. Human IgA1 bound specifically to HT-29 cells with a molar ratio of 0.26 compared with asialo-orosomucoid; porcine haptocorrin bound with a molar ratio of 1.35. CONCLUSIONS: HT-29 cells produce a functional apically located asialoglycoprotein receptor and provide a model for receptor trafficking in the enterocyte.
Asialoglycoprotein Receptor↗
Isolation and characterization of surfactant-like particles in rat and human colon.
The source of a phospholipid-rich layer recovered from the surface of the mammalian colon has been obscure. This report describes the isolation of a low-density membrane from the surface of rat and human colons (d = 1.07-1.08 g/ml), with a low cholesterol-to-phospholipid ratio and phosphatidylcholine as its major phospholipid. Electron microscopy shows unilamellar and partially coiled membranes. Compared with microvillous membranes isolated from underlying mucosa, this extracellular membrane is enriched for tissue-unspecific alkaline phosphatase and surfactant protein A. It does not contain small intestinal marker proteins (intestinal alkaline phosphatase and sucrase-isomaltase). The human membrane contains only traces of the colonic microvillous membrane marker, carcinoembryonic antigen. Antiserum against the rat colonic membrane does not recognize colonic microvillous membrane or small intestinal surfactant-like particle proteins. Antiserum against human colonic membrane identifies one protein in the surfactant-like particle from the adjacent small intestine and two proteins in the colonic microvillous membrane. These data show that the colonocyte microvillous membrane is covered by another membrane with a different protein composition. Enrichment for surfactant protein A suggests that this colonic membrane is another example of a surfactant-like particle sharing proteins with pulmonary surfactant.
Alkaline Phosphatase↗
Gastrointestinal symptoms and psychiatric disorders in the general population. Findings from NIMH Epidemiologic Catchment Area Project.
High rates of psychiatric disorder have been documented in patients with functional bowel syndromes sampled from physicians' offices. Lifetime psychiatric disorder and/or current psychiatric symptoms are thought to be much more highly associated with current gastrointestinal bowel symptoms in clinical settings than in the community. The relationship of lifetime functional gastrointestinal symptoms to lifetime psychiatric disorders has not been examined systematically in randomly selected samples of general community populations. The current study reports findings from existing data on a large, randomly selected population sample that may help to clarify these associations. Epidemiologic Catchment Area (ECA) project data were analyzed to examine relationships of functional gastrointestinal symptoms and psychiatric diagnoses in the community. Individuals with two or more medically unexplained gastrointestinal symptoms had high rates of psychiatric disorders. This was also true for the subgroup in which abdominal pain was one of the two symptoms. The overwhelming majority of subjects reporting medically unexplained gastrointestinal symptoms said they had consulted physicians for those symptoms. General population ECA data indicate that women in the community report more functional gastrointestinal complaints than men, that individuals with lifetime gastrointestinal complaints have high rates of lifetime psychiatric disorders (not necessarily currently symptomatic), and most have contacted a physician regarding their gastrointestinal symptoms. These data complement studies showing that patients with current gastrointestinal symptoms often do not consult a physician, or when they do, such behavior is associated with active psychiatric symptoms. These present data are consistent with the hypothesis that patients with recurrent symptoms are those who routinely seek medical help and who have high rates of psychiatric disorders, whereas those with symptoms that resolve or are improved by a medical intervention do not maintain treatment-seeking behavior.
Catchment Area, Health↗
Centennial report to American Gastroenterological Association members.
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Gastroenterology↗