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BACKGROUND AND AIMS: Animal studies have reported positive effects of glutamine on intestinal absorption and morphology; human studies have been less convincing. The aim of this study was to evaluate the effects of glutamine and diet on intestinal morphology, motility, and absorption. METHODS: A randomized, double blind, placebo-controlled crossover study in 8 patients with short-bowel on a high carbohydrate, low fat (HCLF) diet, was performed. Active treatment was oral glutamine (0.45 g kg(-1)day(-1)) for eight weeks. Intestinal morphology was evaluated by light microscopy. Gastrointestinal transit was measured by dual gamma camera scintigraphy. D-xylose and fecal fat collection was used to evaluate intestinal absorption. Results of active treatment versus placebo were compared by the signed-rank test. RESULTS: Morphology analysis, reported as median active treatment versus placebo, was villus height: 0.48 mm versus 0.50 mm, P=1.0, and crypt depth: 0.11 mm versus 0.10 mm, P=0.469. Percent D-xylose absorption, reported as median active treatment versus placebo, was 7% versus 10.5%, P=0.109. There was not a significant difference in wet weight or fat absorption compared to placebo, P>0.05. Likewise, gastrointestinal transit was not different compared to placebo. CONCLUSIONS: The results of this controlled study would support that 8 weeks of treatment with oral glutamine and a HCLF diet does not significantly improve intestinal morphology, gastrointestinal transit, D-xylose absorption and stool losses in short bowel patients.

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We report here a murine model for experimental chronic colitis where administration of trinitrobenzene sulfonic acid (TNBS) in 50% ethanol induced inflammation of large intestine in susceptible (C3H/HeJ and BALB/c) but not resistant (C57BL/6 and DBA/2) mouse strains. We queried whether mucosal trinitrophenyl (TNP)-specific B cell responses were induced in mice with TNBS-induced colitis, and if induction of tolerance to TNBS by oral administration of this hapten protected mice from development of colitis. Isotypes and subclasses of polyclonal and TNP-specific Ab-forming cells (AFC) were assessed in mucosal and peripheral lymphoid tissues of C3H/HeJ mice with TNBS-induced colitis. Increased numbers of IgA- and IgG-secreting cells were found in the inflamed colon lamina propria. Inflamed colonic tissue also contained high frequencies of IgG anti-TNP AFC (predominantly of IgG1, IgG2a, and IgG2b subclasses); however, anti-TNP responses in noninflamed mucosal tissues of mice with colitis exhibited dominant IgA and IgM with low IgG anti-TNP responses. CD4+ T cells stimulated with TNP-splenocytes produced more IFN-gamma and less IL-4, suggesting a Th1-type response. Oral administration of TNBS before induction of colitis markedly decreased mucosal anti-TNP responses and completely inhibited anti-TNP IgG2a and IgG2b responses. Control mice did not show inhibition of anti-TNP AFC responses or TNBS-induced colitis. Intracolonic sensitization of susceptible C3H/HeJ mice with TNBS induces a localized IgG anti-TNP B cell response in the inflamed tissue, whereas prior oral administration of TNBS results in unresponsiveness to this agent and protects mice from development of TNBS-induced colitis.

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The mechanisms of wound healing in the gut are poorly understood but are mediated by cytokines in other tissues. In this study we wanted to determine which cytokines were expressed after nonspecific colonic injury, the kinetics of that expression, and how cytokine expression correlated with tissue histology. At 0, 4, 8, 12, 24, 48, and 72 h after intrarectal administration of 3% acetic acid to C3H/HeJ mice, their colons were removed for histology, organ culture, and RNA extraction. Cytokine mRNA expression for various cytokines was assessed by reverse transcriptase-polymerase chain reaction with primers specific for each cytokine. Cytokine production in organ cultures was measured with bioassays. Shortly after colonic injury and during colonic regeneration, proinflammatory cytokines such as interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein (MIP), and transforming growth factor-beta (TGF-beta) were expressed. In contrast, expression of T cell-derived cytokines was not detected at any time point. Cytokines such as IL-1 beta, IL-6, IL-10, TNF-alpha, and MIP-1 are important mediators of tissue repair and restitution after nonspecific colonic injury and may subserve a similar role in human colitis.

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BACKGROUND/AIMS: Oral administration of dextran sulfate sodium (DSS) has been reported to induce colitis in mice. The purpose of this study was to determine whether the possible pathogenic mechanism involved the acquired immune system. METHODS: Normal BALB/c and related C.B17 severe combined immunodeficient mice were fed 5% DSS (40 kilodaltons) in their drinking water for 7 days; controls were fed only water. Colons were scored for histological activity at various times. Cytokine production by cultures of colon and of draining lymph node cell was measured. The effect of DSS on the proliferation of the MCA-38 colonic epithelial cell line was assessed. RESULTS: DSS feeding resulted in a very reproducible acute distal colitis in both BALB/c and C.B17 severe combined immunodeficient mice. The lesions of BALB/c mice had an increased production of macrophage-derived cytokines, such as interleukin (IL) 1 beta, IL-6, tumor necrosis factor, and granulocyte-macrophage colony-stimulating factor, but not the T-cell cytokines IL-3 or interferon gamma. Draining lymph node cells produced these cytokines plus interferon gamma and IL-3. DSS inhibited MCA-38 cells at doses that would be easily achieved in the distal colon. CONCLUSIONS: Acute DSS-induced colitis does not require the presence of T cells or B cells because it occurred in C.B17 severe combined immunodeficient mice that lack these cells. Its induction may result from a toxicity of DSS for colonic epithelial cells.

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Neurofibromatosis in cattle is typically a noncutaneous disease. A small group of cows in a Holstein dairy herd developed cutaneous neurofibromatosis. This unique condition was investigated and compared with neurofibromatosis type 1 (NF1) in humans. All cutaneous lesions but one were consistent with neurofibromas in noncutaneous sites in cattle and neurofibromas in patients with NF1. One bovine lesion was classified as a neurofibrosarcoma. Immunohistochemistry and electron microscopy supported Schwannian differentiation in benign and malignant lesions. Linkage analysis with a polymorphism in the bovine NF1 gene confirmed that two affected animals from the same sire inherited the same paternal NF1 allele. Bovine cutaneous neurofibromatosis is a naturally occurring disease in this group of animals, characterized by skin tumors morphologically identical to those of NF1. An informative polymorphism at the NF1 locus of two animals and their sire suggests this disorder may be caused by hereditary mutations at the bovine NF1 locus.

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We report an unusual presentation of gastroesophageal reflux disease in a 14-yr-old boy with cervical dysphagia and vomiting immediately after swallowing. Reflux disease was diagnosed by the combination of eosinophils on esophageal biopsies and abnormal 24-h pH results. The cervical site of dysphagia demonstrated acid-induced hypersensitivity to esophageal distension with water or air. The patient's symptoms resolved with marked acid suppression, which was made difficult because intact capsules of omeprazole initially could not be ingested.

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Patients with liver disease frequently have impaired blood coagulation. The optimal method for liver biopsy in this situation is not established. To investigate this issue we randomised 117 patients with impaired blood coagulation, in whom liver biopsy was required, to receive either transjugular or plugged-percutaneous biopsy. Seventeen patients were excluded prior to biopsy and a protocol biopsy was performed in 100 patients (44 transjugular, 56 plugged-percutaneous). Liver tissue was obtained in 97 (42 transjugular, 55 plugged-percutaneous). Plugged-percutaneous liver biopsy was quicker and easier than transjugular liver biopsy and the biopsies obtained were significantly larger (12 +/- 5 mm vs. 6 +/- 4 mm; p < 0.001). However, 2 of 56 (3.5%) patients who received plugged-percutaneous biopsy had haemorrhage which required transfusion, while none of the 44 patients who received transjugular biopsy had haemorrhage (not significant). Both methods of liver biopsy were associated with a high success rate and a low incidence of complications. Plugged-percutaneous liver biopsy provides larger biopsies but may be associated with an increased risk of haemorrhage.

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A DNA polymorphism in the coding region of coagulation factor IX--potentially valuable for carrier detection, prenatal diagnosis, and population studies--was described in 1985. It had been discovered with monoclonal antibodies that distinguish between threonine and alanine as the 148th residue of the peptide. Its use as a diagnostic tool has been limited because threonine-containing factor IX (Malmö A) is dominant to alanine-containing factor IX (Malmö B) in immunoassays of plasma; therefore, detection of Malmö heterozygotes is not possible in all instances. A DNA method for recognizing all heterozygotes has been developed, but it also has limitations. We report the development of another DNA procedure based on amplification of the relevant DNA with the polymerase chain reaction (PCR). This method is quick, avoids the use of isotopes and x-ray film, and specifically identifies all the Malmö genotypes: hemizygotes, homozygotes, and heterozygotes. The procedure can be performed satisfactorily on small samples of blood (less than 1 mL) as suggested by Kogan et al (N Engl J Med 317:985, 1987). The method described is applicable to any genetic polymorphism that overlaps a restriction enzyme recognition site.

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Multinucleate cells (MNC) form in a number of tumor cell lines treated with vincristine (VCR) and constitute the major difference between cell lines in which the affected cells survive VCR treatment and those in which the affected cells perish. We investigated the cell cycle traverse and proliferative potential of MNC which form among rat tracheal squamous carcinoma cells. Continuous-labeling curves for VCR-treated mononucleate and multinucleate cells were similar to those of untreated cells, and VCR-treated MNC survived for at least 7 days in culture. Observation of individual MNC, however, revealed no cytokinesis or continued proliferation. We conclude that although MNC arising after VCR treatment are capable of cell cycle traverse and prolonged survival in vitro, they are incapable of proliferation and, therefore, would not contribute to tumor regrowth.

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We investigated the effect of in vitro and in vivo environments on the growth behavior of two stable, related rat tracheal squamous cell carcinoma lines while controlling for cell selection. One line was transplanted as tumors in syngeneic hosts for 2 years of continuous passage, and the other was derived from an early tumor passage and maintained continuously in cell culture, The in vitro cell cycle kinetics and doubling time of cells from the transplanted tumor line were identical to those of the long-term-cultured cell line and, when implanted into syngeneic hosts, the cultured cell line gave rise to tumors with growth behavior that was the same as that of the transplanted tumors. The differences in the cell cycle kinetics and growth parameters of the cells in the solid tumors and of the same cells in culture can be explained on the basis of differences in their environments. Selection for different populations of cells when the cells are transferred between environments is unlikely. The comparability of the populations in each of the two environments supports the validity of tests on cells isolated from solid tumors, as long as the cells are simply transferred between the environments and are not allowed to undergo selection during passage in the new environment.

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