Biomedical subjects

A B West

Publications and source records attributed to A B West.

At least 37 records · Page 2Linked to original sources

PubMed1999

Corticosteroids reverse the inhibition of Na-glucose cotransport in the chronically inflamed rabbit ileum.

In a rabbit model of chronic ileal inflammation, we previously demonstrated inhibition of Na-glucose cotransport (SGLT-1). The mechanism of inhibition was secondary to a decrease in the number of cotransporters and not solely secondary to an inhibition of Na-K-ATPase or altered affinity for glucose. In this study, we determined the effect of methylprednisolone (MP) on SGLT-1 inhibition during chronic ileitis. Treatment with MP almost completely reversed the reduction in SGLT-1 in villus cells from the chronically inflamed ileum. MP also reversed the decrease in Na-K-ATPase activity in villus cells during chronic ileitis. However, MP treatment reversed the SGLT-1 inhibition in villus cell brush-border membrane vesicles from the inflamed ileum, which suggested an effect of MP at the level of the cotransporter itself. Kinetic studies demonstrated that the reversal of SGLT-1 inhibition by MP was secondary to an increase in the maximal velocity for glucose without a change in the affinity. Analysis of immunoreactive protein levels of the cotransporter demonstrated a restoration of the cotransporter numbers after MP treatment in the chronically inflamed ileum. Thus MP treatment alleviates SGLT-1 inhibition in the chronically inflamed ileum by increasing the number of cotransporters and not solely secondary to enhancing the activity of Na-K-ATPase or by altering the affinity for glucose.

Animals↗

PubMed1998

Epizootiology, pathology, and ultrastructure of the myxosporean associated with parasitic encephalitis of farmed Atlantic salmon Salmo salar in Ireland.

In 1995 at a sea-farm in Ireland, Atlantic salmon Salmo salar smolts were introduced in the spring and autumn into 2 marine rearing sites, one with and one without recent histories of neurologic disease and mass mortality believed to be due to parasitic encephalitis. In order to monitor disease, determine the onset and anatomic distribution of parasites and encephalitis, and determine the ultrastructure and identity of the parasite, randomly selected smolts were necropsied from both sites at intervals of 1 to 3 d for periods of 1 to 2 mo, and clinical signs and cumulative mortalities were monitored. The prevalences of parasites and encephalitis were assessed by light microscopy, and sections of brain were examined by transmission electron microscopy. No clinical signs of neurologic disease were observed, but parasites and encephalitis were detected in smolts from both sites, with prevalences of each that were significantly greater in smolts from the site with recent disease. Based on light microscopy, the parasite was first detected in smolts sampled at 26 d post-introduction. Parasites were detected with significantly greater frequency in the optic tectum of the mesencephalon than in the diencephalon, metencephalon, and myelencephalon, and were not detected in the telencephalon. Foci of non-suppurative encephalitis were detected with significantly greater frequency in the myelencephalon than in each of the other 4 anatomic subdivisions. In each anatomic subdivision the prevalence of encephalitis was significantly greater than that of parasitic infection. The ultrastructure of the parasite was consistent with that of a histozoic presporogonic multicellular developmental stage of a myxosporean, characterized by intercellular branching tubular structures containing generative cells arranged individually or in cell-in-cell doublets. Parasitic stages were located between bundles of axons, with compression of axons along segments of their plasmalemma. No mature spores were detected.

Animals↗

PubMed1998

An inverse relation between cagA+ strains of Helicobacter pylori infection and risk of esophageal and gastric cardia adenocarcinoma.

Gastric colonization with Helicobacter pylori, especially cagA+ strains, is a risk factor for noncardia gastric adenocarcinoma, but its relationship with gastric cardia adenocarcinoma is unclear. Although incidence rates for noncardia gastric adenocarcinoma have declined steadily, paralleling a decline in H. pylori prevalence, rates for adenocarcinomas of esophagus and gastric cardia have sharply increased in industrialized countries in recent decades. To clarify the role of H. pylori infection in these tumors with divergent incidence trends, we analyzed serum IgG antibodies to H. pylori and to a recombinant fragment of CagA by antigen-specific ELISA among 129 patients newly diagnosed with esophageal/gastric cardia adenocarcinoma, 67 patients with noncardia gastric adenocarcinoma, and 224 population controls. Cancer risks were estimated by odds ratios (OR) and 95% confidence intervals (CI) using logistic regression models. Infection with cagA+ strains was not significantly related to risk for noncardia gastric cancers (OR, 1.4; CI, 0.7-2.8) but was significantly associated with a reduced risk for esophageal/cardia cancers (OR, 0.4; CI, 0.2-0.8). However, there was little association with cagA- strains of H. pylori for either cancer site (OR, 1.0 and 1.1, respectively). These findings suggest that the effects of H. pylori strains on tumor development vary by anatomical site. Further studies are needed to confirm these results and to assess whether the decreasing prevalence of H. pylori, especially cagA+ strains, may be associated with the rising incidence of esophageal/gastric cardia adenocarcinomas in industrialized countries.

Adenocarcinoma↗

PubMed1998

Body mass index and risk of adenocarcinomas of the esophagus and gastric cardia.

BACKGROUND: Incidence rates have risen rapidly for esophageal adenocarcinoma and moderately for gastric cardia adenocarcinoma, while rates have remained stable for esophageal squamous cell carcinoma and have declined steadily for noncardia gastric adenocarcinoma. We examined anthropometric risk factors in a population-based case-control study of esophageal and gastric cancers in Connecticut, New Jersey, and western Washington. METHODS: Healthy control subjects (n = 695) and case patients with esophageal squamous cell carcinoma or noncardia gastric adenocarcinoma (n = 589) were frequency-matched to case patients with adenocarcinomas of esophagus or gastric cardia (n = 554) by 5-year age groups, sex, and race (New Jersey only). Classification of cases by tumor site of origin and histology was determined by review of pathology materials and hospital records. Data were collected using in-person structured interviews. Associations with obesity, measured by body mass index (BMI), were estimated by odds ratios (ORs). All ORs were adjusted for geographic location, age, sex, race, cigarette smoking, and proxy response status. RESULTS: The ORs for esophageal adenocarcinoma rose with increasing adult BMI. The magnitude of association with BMI was greater among the younger age groups and among nonsmokers. The ORs for gastric cardia adenocarcinoma rose moderately with increasing BMI. Adult BMI was not associated with risk of esophageal squamous cell carcinoma or noncardia gastric adenocarcinoma. CONCLUSIONS: Increasing prevalence of obesity in the United States population may have contributed to the upward trends in esophageal and gastric cardia adenocarcinomas.

Adenocarcinoma↗

PubMed1998

Immunohistochemical detection of Listeria antigens in the placenta in perinatal listeriosis.

Listeria monocytogenes, a worldwide pathogen, causes significant perinatal mortality and morbidity and has been implicated in spontaneous abortions, still-births, premature delivery, and neonatal sepsis, often with meningitis. Maternal symptoms are frequently minimal, and diagnosis is made only if the suspicion is high and diagnostic maternal blood or amniotic fluid cultures are performed. Because cultures are not routinely performed on spontaneously aborted fetuses, many authors feel that the true incidence of the disease may be underestimated. To date, the absence of a test to retrospectively diagnose Listeria infection has contributed to the lack of accurate estimates of the incidence of the disease. Seven cases in which immunohistochemical stains were used to confirm the diagnosis of placental listeriosis are described. All placentas showed the characteristic lesions with severe chorioamnionitis, numerous microabscesses, and focal necrotizing villitis. Immunohistochemical localization of Listeria antigen was made to the amnion (focally in areas with no inflammatory infiltrate), the abscesses, and the areas with villitis. In general, the antigen was extracellular and intracellular, predominantly within macrophages or the amnion epithelium. Listeria antigen was often found where definite identification of the organism was not possible on Brown-Hopps or Warthin-Starry stains. The immunohistochemical technique may therefore show an increase in sensitivity of detection of L monocytogenes compared with routine bacterial stains. Moreover, the ability to retrospectively evaluate placental specimens for evidence of this organism should permit the true incidence of perinatal listeriosis to be determined.

Adult↗

PubMed1998

Long-term symptom patterns, endoscopic findings, and gastric histology in Helicobacter pylori-infected and -uninfected patients.

There is a paucity of data on the long-term behavior of dyspepsia, endoscopic findings, and gastroduodenal histology in patients with or without Helicobacter pylori colonization. We evaluated these parameters during a period of 7 to 19 years (average, 12.3 years) by baseline and follow-up studies. In 36 patients studied, the pattern of gastroduodenal dyspepsia and esophagogastroduodenoscopy findings remained essentially unchanged in 67% and 56% respectively. Dyspepsia patterns did not correlate significantly with either endoscopic or histologic findings, including the severity or location of gastritis in the fundus or antrum, or the presence or absence of H. pylori gastritis. Of 36 patients with adequate biopsies of the fundus and antrum, H. pylori colonization with gastritis was present in 73% but not in 27%. Progression to various degrees of atrophic gastritis was noted in 100% with, and in none without, H. pylori gastritis. In the fundus, atrophy progressed from 14% to 56%, but intestinal metaplasia did not change. In the antrum, atrophy increased from 22% to 64% and intestinal metaplasia increased from 17% to 36%. No patient demonstrated dysplasia, but severe atrophy was seen in the fundus (6%) and antrum (11%). Only two patients (5%) had severe loss of glandular elements and very low pepsinogen I, and thus can be considered to have developed advanced gastric atrophy.

Adult↗

PubMed1998

Use of aspirin and other nonsteroidal anti-inflammatory drugs and risk of esophageal and gastric cancer.

Regular users of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are at reduced risk of colon cancer, but the evidence for protective effects of NSAIDs elsewhere in the digestive tract is scant. We investigated the association between the use of NSAIDs and risk of esophageal and gastric cancer, using data from a large population-based, case-control study. Cases were individuals, ages 30-79 years, diagnosed with esophageal adenocarcinoma (n = 293), esophageal squamous cell carcinoma (n = 221), gastric cardia adenocarcinoma (n = 261), or noncardia gastric adenocarcinoma (n = 368) in three areas with population-based tumor registries. Controls (n = 695) were selected by random digit dialing and through the rosters of the Health Care Financing Administration. After controlling for the major risk factors, we found that current users of aspirin were at decreased risk of esophageal adenocarcinoma [odds ratio (OR), 0.37; 95% confidence interval (CI), 0.24-0.58], esophageal squamous cell carcinoma (OR, 0.49; 95% CI, 0.28-0.87), and noncardia gastric adenocarcinoma (OR, 0.46; 95% CI, 0.31-0.68), but not of gastric cardia adenocarcinoma (OR, 0.80; 95% CI, 0.54-1.19), when compared to never users. Risk was similarly reduced among current users of nonaspirin NSAIDs. The associations with current NSAID use persisted when we excluded use within 2 or 5 years of reference date, which might have been affected by preclinical disease in cases, and when we restricted analyses to subjects reporting no history of chronic gastrointestinal symptoms. Our findings add to the growing evidence that the risk of cancers of the esophagus and stomach is reduced in users of NSAIDs, although whether the association is causal in nature is not clear.

Adenocarcinoma↗

PubMed1998

Risk of esophageal and gastric adenocarcinomas in relation to use of calcium channel blockers, asthma drugs, and other medications that promote gastroesophageal reflux.

Incidence of adenocarcinomas of the esophagus and gastric cardia has risen dramatically over the past 2 decades in the U. S., for reasons that are not yet clear. A number of common medications (e.g., calcium channel blockers, tricyclic antidepressants, and certain asthma medications) promote gastroesophageal reflux by relaxing the lower esophageal sphincter (LES). Reflux is thought to increase cancer risk by promoting cellular proliferation, and by exposing the esophageal epithelium to potentially genotoxic gastric and intestinal contents. Recent studies have suggested that calcium channel blockers may also increase cancer risk by inhibiting apoptosis. Using personal interview data from a multicenter, population-based case-control study conducted between 1993 and 1995 in three areas of the U. S., we evaluated whether the use of LES-relaxing drugs was associated with increased risk of adenocarcinomas of the esophagus and gastric cardia. Cases of esophageal adenocarcinoma (n = 293) and gastric cardia adenocarcinoma (n = 261) were compared with general population controls (n = 695). Information on additional case groups of esophageal squamous cell carcinoma (n = 221) and noncardia gastric cancer (n = 368) were also available for comparison. Overall, 27.4% of controls had used one or more of these drugs for at least 6 months, compared with 30.2% of esophageal adenocarcinoma and 23.8% of gastric cardia adenocarcinoma cases. The adjusted odds ratios (ORs) for ever use were 1.0 [95% confidence interval (CI) = 0.7-1.5] and 0.8 (95% CI = 0.5-1.1), respectively. There was little evidence of increasing risk with increasing duration of use of all LES-relaxing drugs together. We found an increased risk of esophageal adenocarcinoma among persons reporting use of asthma drugs containing theophylline (OR = 2.5; 95% CI = 1.1-5.6) or beta agonists (OR = 1.7; 95% CI = 0.8-3.8). Risks were higher among long-term users (>5 years) of these drugs (OR = 3.1; 95% CI = 0.9-10.3 and OR = 2.3; 95% CI = 0.8-7.0, respectively). In contrast, there was no evidence that the use of calcium channel blockers or other specific groups of drugs increased the risk of any of the cancers studied. These results provide reassuring evidence that the increases in incidence of adenocarcinomas of the esophagus and gastric cardia are not likely to be related to the use of LES-relaxing drugs as a group, or calcium channel blockers in particular, but they do suggest that persons treated for long-standing asthma may be at increased risk of esophageal adenocarcinoma.

Adenocarcinoma↗

PubMed1998

Differential diagnosis of bile duct injury and ductopenia.

Injury and loss of intrahepatic bile ducts are relatively common manifestations of liver disease in both adults and children. They occur in a wide variety of conditions ranging from developmental abnormalities and errors of metabolism to autoimmune disorders, infections, and iatrogenic states. Consequently the differential diagnosis is often complex. Moreover, although duct injury is generally easily detected in needle biopsy specimens, ductopenia is not infrequently both overlooked and overdiagnosed. This article reviews the differential diagnosis of duct injury and ductopenia in liver biopsy specimens and provides an algorithmic framework for narrowing down the differential diagnosis before correlation with the clinical findings.

Adult↗

PubMed1997

Tobacco, alcohol, and socioeconomic status and adenocarcinomas of the esophagus and gastric cardia.

BACKGROUND: Incidence rates for adenocarcinomas of the esophagus and gastric cardia have risen steeply over the last few decades. To determine risk factors for these tumors, we conducted a multicenter, population-based, case-control study. METHODS: The study included 554 subjects newly diagnosed with esophageal or gastric cardia adenocarcinomas, 589 subjects newly diagnosed with esophageal squamous cell carcinoma or other gastric adenocarcinomas, and 695 control subjects. Estimates of risk (odds ratios [ORs] and corresponding 95% confidence intervals [CIs]) were calculated for the four tumor types separately and for esophageal and gastric cardia adenocarcinomas combined. RESULTS: Risk of esophageal and gastric cardia adenocarcinomas combined was increased among current cigarette smokers (OR = 2.4; 95% = 1.7-3.4), with little reduction observed until 30 years after smoking cessation; this risk rose with increasing intensity and duration of smoking. Risk of these tumors was not related to beer (OR = 0.8; 95% CI = 0.6-1.1) or liquor (OR = 1.1; 95% CI = 0.8-1.4) consumption, but it was reduced for drinking wine (OR = 0.6; 95% CI = 0.5-0.8). Similar ORs were obtained for the development of noncardia gastric adenocarcinomas in relation to tobacco and alcohol use, but higher ORs were obtained for the development of esophageal squamous cell carcinomas. For all four tumor types, risks were higher among those with low income or education. CONCLUSIONS: Smoking is a major risk factor for esophageal and gastric cardia adenocarcinomas, accounting for approximately 40% of cases. IMPLICATIONS: Because of the long lag time before risk of these tumors is reduced among ex-smokers, smoking may affect early stage carcinogenesis. The increase in smoking prevalence during the first two thirds of this century may be reflected in the rising incidence of these tumors in the past few decades among older individuals. The recent decrease in smoking may not yet have had an impact.

Adenocarcinoma↗

PubMed1997

Diffuse pagetoid squamous cell carcinoma in situ of the esophagus: a case report.

BACKGROUND: In Western countries, esophageal squamous cell carcinoma is usually advanced at presentation and is rarely diagnosed in situ. The authors studied an in situ squamous cell carcinoma that occupied the entire mucosa of a 9 cm length of esophagus, causing dysphagia for solid food in a woman aged 68 years. METHODS: The esophagectomy specimen contained a circumferential region of depressed tan mucosa in the middle and lower thirds, bordered above and below by normal squamous mucosa, without ulcer, stricture, or mass. The entire lesion was submitted for histology and evaluated with immunostains for cytokeratins and markers of Paget's cells, p53 mutation, and proliferation. RESULTS: The lesion involved 45 cm2 of mucosa. Large, atypical cells with frequent mitoses occupied the basal layers of the squamous epithelium and were often separated from more superficial maturing cells by acantholysis. Pagetoid spread of tumor cells into nonneoplastic surface and gland duct epithelium was prominent. The tumor cells expressed cytokeratins of low molecular weight, p53 gene product, and proliferating cell nuclear antigen (PCNA), but lacked markers usually seen in Paget's cells in the breast or vulva. No invasion was evident. CONCLUSIONS: This extensive in situ squamous cell carcinoma of the esophagus resulted from pagetoid spread of tumor cells. These cells had a phenotype suggestive of origin from primitive epidermal stem cells and also had overexpressed p53 and PCNA, but they lacked the capacity to penetrate the basement membrane. Flat, erythematous areas of esophageal mucosa seen during endoscopy could represent early squamous cell carcinoma and should be biopsied.

Aged↗

PubMed1997

Partially purified soy hydrolysates retard proliferation and inhibit bacterial translocation in cultured C2BBe cells.

Hydrolyzed soybean isolates SP-A and SP-B (Abbott Laboratories, OH), developed for use in enteral nutritional products, were tested in cultures of C2BBe cells, a colonic adenocarcinoma cell line with enterocytic differentiation, to evaluate effects on cell growth, maturation and ability to resist infection by enteric bacteria. SP-A delayed formation of confluent monolayers by 10 d compared with cells cultured without SP-A. SP-A also caused a retardation in the development of intercellular tight junctions as measured by transmonolayer electrical resistance (TER). SP-B had no effect on cell proliferation or TER of intestinal cell cultures. SP-A and SP-B enhanced the development of the brush border enzymes alkaline phosphatase and isomaltase over a 28 d period. By these criteria, SP-A and SP-B appear to affect intestinal epithelial cell development in culture. When C2BBe monolayers were exposed to the enteric bacteria, Salmonella typhimurium or Salmonella typhi, an inhibition of the passage of S. typhi was seen in cultures with SP-A and SP-B. No effect on the passage of S. typhimurium was seen with either soy isolate. Partially purified soy isolates therefore impart resistance to selected enteroinvasive bacteria. Addition of soy hydrolysates to the media of cultured intestinal cells may serve as a rapid and economical screening mechanism for preclinical trials that would test the therapeutic benefits of soybean isolates.

Adenocarcinoma↗

PubMed1997

Cathepsin D in intestinal ganglion cells. A potential aid to diagnosis in suspected Hirschsprung's disease.

There is still a need for a better method of detecting immature ganglion cells in paraffin sections of colorectal luminal biopsies in cases suspected of Hirschsprung's disease. The lysosomal aspartic proteinase cathepsin D has been immunolocalized to various cell types, including ganglion cells. We investigated its expression in intestinal ganglion cells to determine whether it could be used as an aid in the detection of immature ganglion cells in rectal biopsies from children suspected of having Hirschsprung's disease. Routinely processed tissues of eight adult intestines resected for gunshot wounds and six ganglioneuromas (for mature ganglion cells), of six colons resected for neonatal necrotizing enterocolitis (for immature ganglion cells), and of 11 cases of suspected and three cases of known Hirschsprung's disease were immunostained with a polyclonal antibody to cathepsin D using the avidin-biotin-peroxidase method. In all cases, all ganglion cell bodies present showed intense granular cytoplasmic reactivity for cathepsin D. The granules crowded the cytoplasm and formed a collarette around the nucleus. In the submucosa, the only other immunoreactive cells were histiocytes, but they could be distinguished from ganglion cells by their characteristic nuclear features and their occurrence singly and unassociated with nerves. The three resection specimens with Hirschsprung's disease showed a clear transition between the ganglionic and the aganglionic segments. We conclude that cathepsin D is a promising marker of immature ganglion cells in cases suspected of Hirschsprung's disease.

Adult↗

PubMed1997

Mucosal inflammation in pediatric diversion colitis: a quantitative analysis.

BACKGROUND: Diversion colitis commonly occurs in bypassed segments of colorectum, and has been described qualitatively in Hirschsprung's disease patients with colostomies. The objective of this study was to characterize quantitatively the changes in the inflammatory cell population in the mucosa of children with diversion colitis. METHODS: Paraffin blocks of well-oriented, full-thickness colorectal tissues were obtained from 15 children with diversion colitis (all with Hirschsprung's disease), four pediatric controls and four adult controls. Sections were immunostained for B and T lymphocytes, macrophages, IgG, IgM, and IgA. Measurements were made referent to a standard length of muscularis mucosae. Lymphoid follicles were counted and the areas occupied by B and T cells were determined by image analysis. Cells in the interfollicular lamina propria were counted separately, but IgA-containing plasma cells were too abundant to enumerate. RESULTS: Pediatric diversion colitis was characterized by enlarged and more numerous lymphoid follicles with approximately four times as many B lymphocytes and twice as many T lymphocytes in the follicular compartment of the mucosa when compared to pediatric controls. The interfollicular mucosa was thickened (499 +/- 27 versus 380 +/- 56 microns) and contained approximately six times as many B cells and eight times as many T cells as controls. Macrophages and plasma cells containing IgG and IgM were not significantly increased. CONCLUSIONS: These findings extend the qualitative observations of increased follicular and lamina propria lymphoid tissue in bypassed segments of colon, and are consistent with the hypothesis of persistent antigenic stimulation of the mucosa-associated lymphoid tissue.

Adult↗

PubMed1997

Supernatant from cultured intestinal cells inhibits the growth of gram-negative bacteria.

Bacterial growth chambers of Transwell units bearing intestinal epithelial monolayers (C2BBe) was consistently observed to be stagnant during the course of transmigration studies with Salmonella typhi. This limitation could not be explained by varying the bacterial load in the inoculum. Conditioned media produced by cultured C2BBe cells would not support bacterial growth. Growth support of the media was restored by heating to 95 C for 10 min. C2BBe conditioned media had bacteriostatic activity for a large variety of gram-negative, enteropathogenic bacteria but had no effect on gram-positive bacteria.

Anti-Bacterial Agents↗

PubMed1997

Effects of insulin-like growth factor I on glucose metabolism in rats with liver cirrhosis.

To determine the effect of insulin-like growth factor I (IGF-I) on glucose metabolism in cirrhosis, a 2-h euglycemic clamp with IGF-I (0.65 nmol.kg-1.min-1) or insulin (12 pmol.kg-1.min-1) was performed in awake rats with carbon tetrachloride-induced liver cirrhosis. Rates of [3-3H]glucose-determined whole body glucose turnover were similar in the fasting state in cirrhotic and control rats (36.4 +/- 2.6 and 37.7 +/- 2.8 mumol.kg-1.min-1, respectively). In the control group, IGF-I and insulin had similar effects on turnover (81.6 +/- 27.0 and 76.1 +/- 9.9 mumol.kg-1.min-1), muscle glycogen synthesis (47.5 +/- 12.3 and 37.5 +/- 2.5 nmol.g muscle-1.min-1), and suppression of endogenous glucose production (EGP; -54 +/- 14 and -60 +/- 12%). Cirrhotic rats were markedly insulin resistant, reflected by a 43% reduction of turnover (43.8 +/- 9.4 mumol.g muscle-1.min-1; P = 0.03), a 73% reduction in muscle glycogen synthesis (10.2 +/- 3.4 nmol.g muscle-1.min-1; P < 0.0001), and a diminished suppression of EGP (-32 +/- 17% vs. control: -56 +/- 14%; P < 0.05). In contrast, during the IGF-I clamps, turnover increased threefold in the cirrhotic rats (P = 0.001), rates of muscle glycogen synthesis were 7.4 times higher than during the insulin stimulation (P < 0.0001), and EGP was suppressed by 80 +/- 12% (P < 0.05). In conclusion, insulin resistance in cirrhotic rats is mostly due to defects in insulin-stimulated muscle glycogen synthesis, and the ability of IGF-I to stimulate muscle glycogen synthesis as well as suppress EGP is maintained in cirrhotic rats. These findings suggest that alterations in both hepatic and peripheral glucose metabolism in patients with cirrhosis might be amenable to IGF-I therapy.

Animals↗

PubMed1997

Effect of chronic inflammation on electrolyte transport in rabbit ileal villus and crypt cells.

The effect of chronic inflammation on electrolyte transport in rabbit ileal villus and crypt cells was determined with the use of a rabbit model of chronic ileitis. In both cells, Na+/H+ exchange was monitored by following recovery from an acid load, and Cl-/HCO3- exchange was monitored by following recovery from an alkaline load. In villus cells, recovery from an acid load was not affected; however, recovery from an alkaline load was slowed. These data suggest that chronic inflammation inhibits Cl-/HCO3- exchange in villus cells. In contrast, in crypt cells, recovery from an alkaline load was unaffected, whereas recovery from an acid load was accelerated. These data suggest that chronic inflammation stimulates Na+/H+ exchange in crypt cells. Inhibition of Cl-/HCO3- exchange in villus cells would be expected to inhibit coupled NaCl absorption, which occurs by the coupling of brush-border membrane (BBM) Na+/H+ and Cl-/HCO3- exchange. Stimulation of Na+/H+ exchange in crypt cells, known to be present only on the basolateral membrane, alkalinizes the cell. This alkalinization may stimulate BBM Cl-/HCO3- exchange, resulting in HCO3- secretion. Thus these unique alterations in transporter activity suggest that different endogenous immune-inflammatory mediators may have differing effects on specific transporters in villus and crypt cells in the chronically inflamed ileum.

Animals↗

PubMed1997

Mechanism of inhibition of Na+-glucose cotransport in the chronically inflamed rabbit ileum.

In a rabbit model of chronic ileal inflammation, we previously demonstrated that coupled NaCl absorption was reduced because of an inhibition of Cl-/HCO3- but not Na+/H+ exchange on the brush-border membrane (BBM) of villus cells. In this study we determined the alterations in Na+-stimulated glucose [Na+-O-methyl-D-glucose (Na+-OMG)] absorption during chronic ileitis. Na+-OMG uptake was reduced in villus cells from the chronically inflamed ileum. Na+-K+-adenosinetriphosphatase (ATPase), which provides the favorable Na+ gradient for this cotransporter in intact cells, was found to be reduced also. However, in villus cell BBM vesicles from the inflamed ileum Na+-OMG uptake was reduced as well, suggesting an effect at the level of the cotransporter itself. Kinetic studies demonstrated that Na+-OMG uptake in the inflamed ileum was inhibited by a decrease in the maximal rate of uptake for OMG without a change in the affinity. Analysis of steady-state mRNA and immunoreactive protein levels of this cotransporter demonstrates reduced expression. Thus Na+-glucose cotransport was inhibited in the chronically inflamed ileum, and the inhibition was secondary to a decrease in the number of cotransporters and not solely secondary to an inhibition of Na+-K--ATPase or altered affinity for glucose.

Animals↗