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D H Alpers

Publications and source records attributed to D H Alpers.

At least 55 records · Page 3Linked to original sources

Immunolocalization of alpha-integrin subunits and extracellular matrix components during human colonic organogenesis.

BACKGROUND & AIMS: The role of cell adhesion molecules in colonic organogenesis remains poorly understood. This study examined the expression of alpha-integrin subunits and extracellular matrix ligands during human colonic development. METHODS: Standard immunohistochemistry was used to characterize extracellular matrix and alpha-integrin subunit expression during development. RESULTS: At 9 weeks, type-IV collagen and laminin were present underlying epithelium, around vascular structures, and surrounding inner circular muscle layer fibers. Fibronectin was uniformly expressed in the mesenchyme. Tenascin distribution was restricted to the presumptive muscle layer and, later, to the villus core and muscularis mucosae. The 9-week epithelium expressed alpha 2, alpha 3, alpha 5, and alpha 8, and, by 11 weeks, alpha 9. alpha 3, alpha 6, and alpha 8 expression was accentuated at the basal membrane. During transition from pseudostratified to simple columnar epithelium, a vertical alpha 2 gradient formed. Mesenchymal cells expressed alpha 5 and alpha 8 by 9 weeks. The developing muscularis (propria and mucosae) showed accentuated alpha 5 expression. By 16 weeks, alpha 8 expression localized to the muscularis mucosae and villus core. Mesenchymal vascular elements stained strongly with anti-alpha 2 and alpha 6 by 9 weeks. CONCLUSIONS: These observations show the complexity and overlap of adhesive receptor expression and ligands during development and reveal early cell commitment to the formation of specific structures.

Collagen↗

Immunolocalization of alkaline phosphatase and surfactant-like particle proteins in rat duodenum during fat absorption.

BACKGROUND & AIMS: In response to triacylglycerol feeding, rat duodenum secretes into the lumen and lamina propria phospholipid-rich membranes (surfactant-like particles) that are enriched with intestinal alkaline phosphatase. The purpose of this study was to determine whether the enzyme and particle proteins were coordinate in tissue distribution and in time. METHODS: Immunocytochemistry using specific polyclonal antisera against alkaline phosphatase and against the complex of particle proteins and its 40-kilodalton component was performed. RESULTS: Triacylglycerol feeding produced a peak between 3 and 5 hours in stain intensity for both antigens, intracellularly as well as in the paracellular space and lamina propria. In fasting animals, the microvillous membrane stained strongly for alkaline phosphatase; surfactant-like particle proteins were mainly localized to the lamina propria. Feeding Pluronic L-81 (BASF Wyandotte, Wyandotte, MI), a detergent that decreases transcellular triacylglycerol movement and surfactant-like particle secretion, produced a decrease in reactivity of both antigens in the paracellular space, lamina propria, and lumen and redistributed intracellular alkaline phosphatase and surfactant-like particle proteins from Golgi or cytosol to intracellular membranes, corresponding to the circumference of lipid droplets. CONCLUSIONS: These data support the hypothesis that some intestinal alkaline phosphatase is secreted from the cell associated with the surfactant-like particle and are consistent with a role for this particle in transepithelial transport of triacylglycerols in the enterocyte.

Alkaline Phosphatase↗

Abundance of surfactant-like particles reflects mucosal integrity in patients with peptic ulcer disease.

BACKGROUND: Surfactant-like particles, normal products of the human enterocyte, are released into the lumen and secreted into blood. AIMS: To assess their role as markers for mucosal functional integrity, this study examined their content in biopsy specimens and serum of patients with duodenal ulcer disease, compared with non-diseased control subjects. PATIENTS: Endoscopic biopsy specimens were taken 1-2 cm from areas of active inflammation or ulcer (peptic ulcer patients) or just beyond the duodenal bulb (normals) in 35 consecutive subjects. METHODS: After staining for phospholipid, extracellular and intracellular particles were counted on transmission electron micrographs of coded specimens. Serum was obtained from 24 patients, and densitometry of the 59 kDa band detected on western blot by antiserum against human jejunal particle was measured. RESULTS: Normal duodenum (n = 15) contained more particles (44 (4.7)) particles/block, mean (SD) than active duodenal ulcer (n = 13, 17 (3.9)) or gastritis/duodenitis patients (n = 4, 9 (2.7)). Three patients examined after healing of duodenal ulcers showed abundant particles (n = 3, 67 (2.2)). Similarly, the 59 kDa band was decreased in serum of patients with active peptic ulcer disease (n = 11, 0.25 (0.04) absorbance units) compared with normal patients (n = 10, 0.40 (0.03)) or healed ulcers (n = 3, 0.62 (0.04)). There was good correlation between morphological mucosal particle abundance and particle protein content of serum assayed from the same patients (r = 0.831). These changes were independent of Helicobacter pylori status. CONCLUSION: The mucosal and serum content of surfactant-like particles may reflect general mucosal integrity of the enterocytes from which they are derived.

Adult↗

Human gastric intrinsic factor expression is not restricted to parietal cells.

Gastric parietal cells have been accepted as the only site of intrinsic factor production in the human stomach. In animals, however, intrinsic factor has been localised to various other cell types of foregut origin, including chief and enteroendocrine cells in gastric mucosa, and duct cells from salivary glands and pancreas. The availability of recombinant human intrinsic factor has led to production of high titre, monospecific antiserum which was used to reexamine the distribution and subcellular localisation of intrinsic factor in the human stomach. Immunolight microscopy revealed that most positively stained cells were gastric parietal cells, but at the margins of the anatomical regions (e.g. cardia/fundus, body/antrum) clusters of gastric chief cells and individual enteroendocrine cells were found to contain intrinsic factor. Immunoelectron microscopy demonstrated the highest antigen density on endocytic and apical membranes of parietal cells. Exocrine secretory granules of a subpopulation of chief cells, the secretory granules of some enteroendocrine cells, and the plasma membranes and smooth vesicles of endothelial cells of the lamina propria capillaries underlying enteroendocrine cells were also positive for the antigen. Labelling in all cells was specific, as it was abolished by preabsorption of the antisera with purified recombinant human intrinsic factor. These findings demonstrate a potential for cellular expression of human intrinsic factor in nonparietal cells. Because such expression occurs normally at the margins of anatomical gastric regions, it suggests that local factors may influence expression of intrinsic factor.

Adult↗

Two rat intestinal alkaline phosphatase isoforms with different carboxyl-terminal peptides are both membrane-bound by a glycan phosphatidylinositol linkage.

Two cDNAs encode rat intestinal alkaline phosphatases having completely different carboxyl-terminal peptides; one is hydrophobic and fulfills the consensus requirements for glycan phosphatidylinositol linkage, and the other is neither hydrophobic nor hydrophilic, but contains a small amino acid domain (-NSASS-) just distal to a region of 17 threonine residues. Constructs were created using 80% of the amino-terminal portion of one alkaline phosphatase and the carboxyl-terminal portions of each of the isoforms. Both of the carboxyl-terminal peptides supported glycan phosphatidylinositol linkage as demonstrated by the following criteria: 1) plasma membrane targeting in transfected COS-1 cells, 2) release of transfected alkaline phosphatase by phosphatidylinositol-specific phospholipase C, 3) appearance of the trypanosome variable glycoprotein cross-reacting determinant after phospholipase C treatment, 4) ethanolamine incorporation into newly synthesized enzyme, 5) loss of phospholipase C release after mutation of the omega and omega + 2 positions in the putative linkage site, -NSA-, and 6) evidence of surface membrane localization by immunofluorescence using antibody against rat intestinal alkaline phosphatase. These data demonstrate that a predicted hydrophobic carboxyl-terminal sequence is not essential for glycan phosphatidylinositol linkage. Moreover, because both isomers are membrane-bound, the origin of soluble enzyme in the serum is likely to arise from the action of serum phosphatidylinositol-specific phospholipase C.

Alkaline Phosphatase↗

Appearance of surfactant-like particles in apical medium of Caco-2 cells may occur via tight junctions.

Intestinal alkaline phosphatase (AP) is secreted by Caco-2 cells bound to surfactant-like particles (SLP), which can be localized by electron microscopy to the basolateral space and the intestinal lumen, especially over tight junctions. To investigate the hypothesis that SLP are secreted basolaterally and enter the lumen through the tight junction, Caco-2 cells were incubated with agents known to increase permeability at tight junctions. Cytochalasin D and phorbol 12-myristate 13-acetate increased Caco-2 cell monolayer permeability and the appearance of particles in apical medium two- to threefold, as monitored by mannitol movement and AP activity, respectively. Blocking the apical secretory pathway by nocodazole or colchicine had no effect on either parameter. Estimation of SLP content demonstrated an increase in apical media particles similar to that determined by AP activity. Quantitative image analysis established that apical SLP content increased 4-10 times, whereas total cell particle content remained unchanged. These data indicate that SLP may be secreted initially into the basolateral space and then transported to the intestinal lumen through the tight junctions.

Adenocarcinoma↗

Synthesis and parallel secretion of rat intestinal alkaline phosphatase and a surfactant-like particle protein.

Rat intestinal microvillous alkaline phosphatases are secreted bidirectionally from the enterocyte attached to a phospholipid-rich membrane (surfactant-like particle). To determine the intracellular pathways for newly synthesized alkaline phosphatases and for the extracellular enzyme-particle complex in the intestinal mucosa, pulse-chase experiments were performed. Synthesis of both isoforms of alkaline phosphatase in fasted rats peaked in the Golgi at 15-30 min and in the microvillous membrane at 60 min, without intermediate localization in the basolateral membranes. A second peak of incorporation was found at 15-30 min in scrapings obtained from the apical surface of the enterocytes. These results demonstrate a dominant direct Golgi-to-microvillous membrane transport for newly synthesized alkaline phosphatase. An additional precursor pool(s) appears responsible for the early appearance of enzyme in the lumen. Newly synthesized alkaline phosphatase isoforms and the 97-kDa protein of surfactant-like particles showed parallel patterns of appearance in enterocytes, luminal washings, and lamina propria after triacylglycerol feeding and were preferentially secreted into the lumen and lamina propria at times (5-7 h) when enterocyte content of these newly synthesized proteins had declined toward basal rates. Enhanced secretion of newly synthesized proteins for hours after fat feeding could explain the prolonged rise in serum and luminal washings of both the enzyme and the particle.

Alkaline Phosphatase↗

Cathepsin L mediates intracellular ileal digestion of gastric intrinsic factor.

Although acidic proteases of lysosomal origin are implicated in the degradation of intrinsic factor (IF) during cobalamin (cbl) transport across enterocytes and proximal renal tubule cell lines, the enzyme(s) involved in this process is not known. Recombinant (baculovirus-produced) rat 125I-labeled IF (125I-rIF), 43 kDa, added in vivo to the lumen of rat ileum was converted intracellularly to peptides of 33 and 26 kDa. In vitro rat 125I-rIF was degraded to peptides of 33 and 31 kDa by addition of cathepsin L; this conversion was fully inhibited by leupeptin. Western blot analysis using antiserum against denatured native rat IF identified additional cathepsin L degradation products in the 17- to 23-kDa range. In vitro the binding of cobalamin partially inhibited cathepsin L degradation of IF. Rat rIF produced from either insect (Sf9) or mammalian (CHO) cells and native rat IF were all degraded by cathepsin L, although the prominence of the various products differed in the recombinant preparations, being 33 and 36 kDa, respectively. Native rat IF was most sensitive to proteolysis, and no degradation products were identified. Rat 125I-rIF was taken up by LLC-PK1 cells, and 125I from degraded IF appeared abundantly on the basolateral side of cell monolayers by 1 h. The intracellular products of rat rIF in LLC-PK1 cells were the same size as those produced in vitro by the action of cathepsin L. Antiserum against a human kidney cDNA cathepsin L fusion protein easily demonstrated the protease in rat intestinal mucosa, as well as in all other tissues tested. These data suggest that cathepsin L is the protease responsible for the leupeptin-sensitive intracellular degradation of IF.

Animals↗

Complaints of constipation in obsessive-compulsive disorder.

Psychoanalytic observation has launched a long tradition in medical literature that links constipation with obsessive-compulsive traits. This association, however, has never been tested empirically. The current investigation sought to test this hypothesized association empirically using a large, randomly sampled population database. Data from the Epidemiologic Catchment Area project collected with the Diagnostic Interview Schedule were analyzed to determine the association, if any, of complaint of medically unexplained constipation (ascertained from the somatization disorder section of the interview) with a DIS diagnosis of obsessive compulsive disorder (OCD). Reported history of constipation was significantly associated with a lifetime diagnosis of OCD in women (not men), even when controlling for symptom-reporting biases using number of other positive somatoform symptoms. This association was specific to constipation and OCD and did not apply to other functional bowel symptoms including diarrhea, bloating (gas), and abdominal pain. Other psychiatric disorders commonly implicated with functional bowel complaints--major depression and panic disorder--were not significantly associated with constipation controlling for effects of other somatoform symptoms. The lack of association of constipation with OCD in men in a general population sample fails to support psychoanalytic concepts that historically have linked these two phenomena, but a special relationship of OCD with constipation was present in women.

Constipation↗

Development and hormonal modulation of postnatal expression of intestinal alkaline phosphatase mRNA species and their encoded isoenzymes.

In the rat, intestinal alkaline phosphatase (IAP) activity in the duodenum, but not jejunum, increases on day 22-24 after birth and exhibits higher activity hydrolysing phenyl phosphate (PhP) than beta-glycerophosphate (beta GP) [Moog and Yeh (1973) Comp. Biochem. Physiol. 44B, 657-666]. The mechanism underlying these developmental changes remains unknown. To define possible mechanisms, we have measured IAP activity and mRNA levels, and analysed IAP mRNA species and isoenzymes on postnatal days 12, 18, 24 and 32. Duodenal IAP activity and mRNA content were identical on postnatal days 12 and 18, but were 7-fold and 3-fold higher on day 24, respectively than on day 18. The increased IAP activity exhibited a high PhP/beta GP ratio and was accompanied by initial appearance of the 3.0 kb mRNA and 90 kDa isoenzyme. On day 32, duodenal IAP activity did not increase over the levels on day 24, whereas mRNA levels doubled. The lack of enzyme increase might be related in part to increased apical release, as luminal IAP activity increased from 2% of total mucosal IAP on days 12 and 18 to 7% and 14% on days 24 and 32 respectively. In the jejunum, IAP activity decreased postnatally, but mRNA content was unaltered; only the 2.7 kb mRNA and 65 kDa IAP isoenzyme were present. Administration of cortisone or cortisone+thyroxine induced simultaneous appearance of the duodenal 3.0 kb mRNA and 90 kDa isoenzyme with an increased PhP/beta GP ratio. Thus postnatal increase in duodenal IAP activity is related to the expression of a 90 kDa PhP-preferring isoenzyme encoded by the 3.0 kb mRNA. The low-PhP/beta GP-ratio 65 kDa isoenzyme is expressed in the duodenum and in the jejunum and is encoded by the 2.7 kb mRNA.

Alkaline Phosphatase↗

Expression of an endogenous asialoglycoprotein receptor in a human intestinal epithelial cell line, Caco-2.

We have previously shown that rat asialoglycoprotein receptor expressed in the intestine and liver differ in mRNA size, cell surface distribution, and ratio of compositional protein subunits. In this study, we examined a well characterized intestinal epithelial cell line, Caco-2, as a potential model for studying endogenous receptor in a polarized cell line. Both subunits H1 and H2 of human asialoglycoprotein receptor were detected in Caco-2 cells by Western blots using subunit-specific antisera raised against the hepatic receptor. Antigenic receptor level in fully differentiated Caco-2 cells was approx. 1/3 to 1/2 the level of hepatic HepG2 cells H1 was the dominant subunit in both cell lines. The apparent size of H1 and H2 in Caco-2 cells was not the same as that in HepG2 cells, due to differences in N-linked glycosylation. Consistent with this finding, Northern blot analysis showed that receptor mRNA in the two cell types was of identical size. In pulse-chase experiments H1 was first detected as a 'high-mannose' precursor (40 kDa) in Caco-2 cells that was converted to mature H1 (43 kDa) with a half-life of approx. 60 min. Antigenic levels of H1 and H2 in undifferentiated Caco-2 cells were low, but increased rapidly during cell differentiation, reaching a peak level at 7 days after confluence. Immunocytochemical staining and domain-selective cell surface biotinylation assays showed that the ASGP-R was predominantly localized in the basolateral domain. The receptor in Caco-2 cells was capable of mediating specific uptake and degradation of [125I]asialoorosomucoid. The ligand uptake capacity of the basolateral surface of was approx. 10-fold higher than the apical. These characteristics (H1 subunit and basolateral predominance) of the receptor in Caco-2 cells, resembles the hepatic receptor. We conclude that Caco-2 cells endogenously express in ectopic hepatic-type functional asialoglycoprotein receptor.

Asialoglycoprotein Receptor↗

Antidepressant therapy in 138 patients with irritable bowel syndrome: a five-year clinical experience.

BACKGROUND: Antidepressant agents may have a therapeutic role in functional gastroenterologic disorders, but controlled investigations in irritable bowel syndrome (IBS) have not provided satisfactory practice recommendations. To help with future study design, we reviewed a five-year clinical experience with antidepressant agents in out-patients with IBS. METHODS: Presenting features, treatment course, and clinical outcome were determined from a chart review of 138 patients attending a university-based gastroenterology practice. RESULTS: Patients were treated with up to five antidepressants in separate, consecutive trials if a satisfactory end-point had not been reached. Tricyclic antidepressants were utilized 130 times, newer antidepressants 39 times, and anxiolytic-antidepressants 47 times. Improvement and complete remission in bowel symptoms occurred in 89% and 61% of patients, respectively, during antidepressant therapy. Median dosages being prescribed when remission occurred were less than those conventionally used in clinical psychiatry (50 mg/day for several tricyclic antidepressants). Age, gender, symptom duration, and presence of psychological symptoms did not discriminate those who remitted from those who did not, whereas a pain predominant symptom pattern was more commonly associated with symptom remission (P < 0.05 comparing symptom patterns). Symptom remission was more likely during the first antidepressant treatment than with subsequent trials in the group with continued symptoms (P = 0.01), but nearly half of the patients with side effects or no benefit from the first agent who went on to subsequent trials remitted during treatment with an alternative antidepressant. CONCLUSIONS: The design of this retrospective review is not capable of determining the efficacy of antidepressants for IBS. Our observations in conjunction with other available data suggest that future trials should employ low daily dosages, carefully assess pain response, include patients with and without active psychiatric symptoms, and utilize a second agent for subjects intolerant or unresponsive to the first.

Adolescent↗

Clearance of surfactant-like particle proteins from circulation in rats.

Surfactant-like particles (SLP) have been isolated from the apical surface of rat enterocytes but appear to arise within the enterocyte and to be secreted into neighboring lymphatics (K. DeSchryver-Kecskemeti, R. Eliakim, S. Carroll, W. F. Stenson, M. A. Moxley, and D. H. Alpers. J. Clin. Invest. 84: 1355-1361, 1989). The present study was undertaken to analyze the clearance and distribution of these particle-associated proteins in vivo in the rat. Labeling of particles isolated from apical scrapings of rat enterocytes with 125I enabled identification of proteins of 116, 92, 68, 58, 48, 31, and 25 kDa. After the intravenous administration of 125I-SLP, the trichloroacetic acid-precipitable radioactivity in the plasma disappeared in a biphasic pattern. The average half-life of the early phase was 7.5 min and the second phase was 75 min. The half-life of a subset of the proteins (116, 92, and 48 kDa) was shorter, measuring 4.5 min for the first phase and ranging from 20 to 52 min for the second phase. The amounts of labeled particle distributed to the liver, kidney, and spleen were much greater than could be accounted for by distribution in the extracellular space alone. The liver accounted for removal of approximately 50% of label in the first phase, with the kidney and spleen contributing 10 and 1%, respectively. Only 0.5 and 2.5% of labeled protein appeared in the bile and urine, respectively. The majority of labeled protein remaining in the serum after the initial phase of tissue uptake migrated at a density of 1.07-1.08, characteristic of intact particles, but slowly shifted to higher densities over 24 h. The maximum binding capacity was 56 nmol/mg membrane protein (Michaelis constant = 51 pM) using hepatic basolateral membranes. The particle was taken up into hepatocytes, as demonstrated by autoradiography. These data demonstrate the importance of the liver in clearing SLP from the blood in rats. The slow clearance of a portion of the particle protein provides support for the continued presence of these proteins in the serum of rats.

Animals↗

Secretion and distribution of rat intestinal surfactant-like particles after fat feeding.

Triacylglycerol feeding increases serum intestinal alkaline phosphatase (IAP) activity and leads to the appearance of an alkaline phosphatase-containing particle in the luminal washings over the apical surface of the rat enterocyte and in the blood (J. Clin. Invest. 84: 1355-1361, 1989). To examine the coordinate appearance of these particles and the enzyme and to follow their distribution in vivo after feeding, an enzyme-linked immunoabsorbent assay (ELISA) was developed, using antisera raised against the purified intact surfactant-like particle. Tissue compartments that were examined for phosphatase activity and particle content included isolated enterocytes, lamina propria, intestinal luminal washings, and serum. Alkaline phosphatase activity peaked earliest in the lamina propria (3 h), followed by the enterocyte and the luminal washings (5 h) and serum (7 h). Surfactant-like particle content peaked in the enterocyte and lamina propria at 3 h, followed by the serum (3-5 h) and the luminal washings (5 h). The buoyant density of the particle in the enterocyte (d = 1.08-1.09) and serum (d = 1.07-1.08) after fat feeding was similar to that of the isolated particle (d = 1.07-1.08). The density of particle proteins detected by ELISA in fasted serum was more diffuse and > 1.10, consistent with partial degradation of the particle and/or its proteins. These data confirm that the particle and its bound IAP are secreted from the enterocyte after triacylglycerol feeding and that they appear in compartments adjacent to both the basolateral (serum) and apical (luminal wash) surfaces of the enterocyte.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗

A possible role for rat intestinal surfactant-like particles in transepithelial triacylglycerol transport.

To further examine whether surfactant-like particles (DeSchryver-Kecskemeti, K., R. Eliakim, S. Carroll, W. F. Stenson, M. A. Moxley, and D. H. Alpers. 1989. J. Clin. Invest. 84:1355-1361) were involved in the transepithelial transport of lipid, alkaline phosphatase activity and surfactant-like particle content were measured in apical mucosal scrapings, enterocytes, lamina propria, and serum after inhibition of chylomicron transport. Serum triacylglycerol levels were decreased 60-76% by Pluronic L-81, fenfluramine, and choline deficiency compared with fat-fed controls. 5 h after triacylglycerol feed, alkaline phosphatase activity in all three experimental groups was decreased compared with controls by 52-69% in mucosal scrapings and by 33-72% in serum. A parallel decline (60%) in alkaline phosphatase activity occurred in the lamina propria of Pluronic-treated animals. Total particle content (measured by an ELISA using antiserum against purified particle) after Pluronic treatment was decreased in mucosal scrapings, lamina propria, and serum by 16, 22, and 29% at 3 h and by 33, 40, and 8%, respectively, at 5 h after fat feeding. In contrast, particle content was increased in enterocytes by 29% 3 h and by 8% 5 h after fat feeding. By electron microscopy, enterocytes from Pluronic- and fenfluramine-treated animals exhibited a two- to threefold increase in large intracellular cytoplasmic lipid globules and the appearance of lamellae in apposition, with a marked decrease in the number of surfactant-like particles overlying the brush border. These changes, produced by inhibition of chylomicron transport, in the distribution of surfactant-like particles and particle-bound alkaline phosphatase are consistent with a role for these particles in transepithelial triacylglycerol transport across and out of the enterocyte.

Animals↗

Effects of 1,25-dihydroxyvitamin D3 on proliferation and differentiation of Caco-2 cells.

The effect of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], or calcitriol, on the proliferation and differentiation of Caco-2 cells was studied. Vitamin D receptor mRNA was detected in both pre- and postconfluent cells, and its abundance was unchanged with time and in response to calcitriol. 1,25-(OH)2D3-binding activity increased during differentiation, but there was no difference in binding between 1,25-(OH)2D3-treated and control cells. 1,25-(OH)2D3 caused a dose-dependent reduction in proliferation, as assessed by [3H]thymidine incorporation and DNA content. 1,25-(OH)2D3 significantly enhanced the normal rise in alkaline phosphatase activity during differentiation and increased alkaline phosphatase mRNA abundance. In contrast, 1,25-(OH)2D3 inhibited the normal rise in sucrase-isomaltase activity and the corresponding mRNA level, although the inhibition occurred after the initial period of cell differentiation (> 10 days postplating). Morphological analysis demonstrated that by day 12 postplating, 1,25-(OH)2D3 increased the mean dome diameter and microvillus length and density. Although 1,25-(OH)2D3 decreases the proliferation of Caco-2 cells and enhances certain parameters of differentiation, not all brush-border hydrolases respond in a similar fashion, making it necessary to interpret with caution their individual use as markers of differentiation.

Calcitriol↗

A review of studies of psychiatric factors in Crohn's disease: etiologic implications.

Researchers have recently challenged long-held concepts of psychological origins to inflammatory bowel disease, in particular with ulcerative colitis. The purpose of this paper is to review published studies on psychiatric factors in Crohn's disease to determine whether available evidence points to the absence or presence of a significant relationship between Crohn's disease and stressful life events or psychiatric symptoms or disorders. Twelve articles with > or = 10 subjects on which statistical data were reported from standardized instruments of measure were found. Most reported a significant association between Crohn's disease and psychiatric factors. Many of the investigative groups reporting such an association in Crohn's disease had also studied ulcerative colitis and failed to find a similar association in that disease. Published data indicate that Crohn's disease, unlike ulcerative colitis, may be statistically associated with lifetime psychiatric disorders. This association appears to be more modest than in irritable bowel syndrome, in which far higher rates of psychiatric disorders are reported than in Crohn's disease.

Anxiety Disorders↗