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Biomedical subjects

M H Ulshen

Publications and source records attributed to M H Ulshen.

12 recordsLinked to original sources

Rectal mucosal ornithine decarboxylase activity is not a useful marker of risk for colorectal neoplasia.

Rectal mucosal ornithine decarboxylase activity has been reported to distinguish patients with adenomas from normal controls. In order to further explore this association, we assayed biopsy samples from 119 unselected individuals undergoing routine colonoscopic examinations. The overall mean ODC activity was 127.4 (+/- 93.1 SD) pmol/mg protein/hr. There were no differences by age, sex, or race. Tissue handling and storage influenced ODC activity. Specimens collected and transported on Dry Ice had higher ODC activity than specimens initially frozen in a -20 degrees C freezer. After adjusting for storage and collection method, the activity was similar in subjects with adenomas (126.3 pmol/mg/hr) compared to those without adenomas (128.8 pmol/mg/hr). We conclude that variations in assay technique make comparisons between laboratories difficult. Patients with large-bowel adenomas do not necessarily have higher ODC activity in uninvolved rectal mucosa. Further study of the environmental and genetic factors that influence rectal mucosal proliferation may improve our understanding of carcinogenesis in the large bowel.

Adenoma

Nutrient-independent increases in proglucagon and ornithine decarboxylase messenger RNAs after jejunoileal resection.

To assess potential mediators of adaptive bowel growth, ileal proglucagon messenger RNA (mRNA) ornithine decarboxylase (ODC) mRNA, plasma enteroglucagons, and plasma glucagonlike peptide I (GLP-I) were analyzed in rats soon after jejunoileal resection or control transection. Analyses were performed before and after refeeding to establish whether responses are nutrient dependent. The elevation of ileal proglucagon and ODC mRNAs within 12 hours after resection and before refeeding shows a nutrient-independent component of the adaptive response. The onset of adaptive growth of the ileum required luminal nutrient but occurred very rapidly, within 4 hours of refeeding. The onset of adaptive growth was accompanied by transient elevation of ileal ODC mRNAs. Ileal proglucagon mRNA and plasma GLP-I levels were also elevated, and these increases were sustained up to 8 days after resection. These early and sustained increases in proglucagon mRNA and plasma GLP-I indicate that in addition to the enteroglucagons, other intestinal proglucagon-derived peptides must be considered as potential mediators of adaptive growth after jejunoileal resection.

Adaptation, Physiological

Effects of nursing on growth and development of small bowel mucosa in newborn piglets.

Trophic factors in natural milk are potential mediators of the rapid growth of intestine in neonates. To determine whether nursing stimulates growth and development of small bowel mucosa, litters of piglets were divided into suckled and artificially reared groups at birth. The latter animals were raised in an automated feeding device (Autosow) with an artificial diet simulating the nutritional composition of sow milk. At 2, 8, and 15 d of age, animals were killed and 10-cm segments of jejunum, mid-bowel, and ileum were removed. Mucosal homogenates were prepared for enzyme assay and measurement of mucosal mass. Mean body weight, total length of bowel, and circumference of bowel segments did not differ between the two feeding groups at any age studied. As anticipated, mean mucosal ornithine decarboxylase activity decreased (p less than 0.001) and measurements of mucosal mass increased (p less than 0.001) with age; however, mean values for each of these measures were never greater in the nursed animals in comparison to the artificially reared group in any segment at any age. In addition, levels of disaccharidase activity did not correlate with the feeding regimen. To investigate the possibility that unanticipated growth factors in the artificial diet might have accounted for the apparent lack of trophic effect of nursing compared to artificial rearing, we evaluated the effects of this diet and of sow colostrum on 3H-thymidine incorporation in Swiss 3T3 cells in vitro. Colostrum, but not artificial diet, stimulated greater incorporation of 3H-thymidine than culture medium alone (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Nutritional Physiological Phenomena

Immunology of inflammatory bowel disease: summary of the proceedings of the Subcommittee on Immunosuppressive Use in IBD.

As outlined, scanty data exist with regard to immunologic therapy in children with IBD despite the fact that the pediatric population affords a unique opportunity for clinical evaluation. Children are less affected by modifying conditions such as smoking, alcohol ingestion, and the long-term use of medications, and because of their specific needs for ponderal and linear growth, children might benefit most from immunological therapy that has been proven to be steroid sparing. Therefore, clinical trials to evaluate the efficacy of 6-MP and/or azathioprine in growing children with Crohn's disease would appear to provide a fruitful avenue for collaborative research. Efforts to organize a multicenter evaluation of these agents have been initiated. The studies are crucial in evaluating the efficacy and safety of immunosuppressive therapy in the pediatric population with IBD.

Aminosalicylic Acids

Problems identified by secondary review of accepted manuscripts.

To test the hypothesis that no important deficits would be identified on further review of accepted manuscripts, and that such manuscripts would be recommended for publication on rereview, we sent manuscripts that had been accepted for publication, after review and revision, for rereview by new referees who were unaware of the status of the manuscripts. Each review was evaluated independently by two assistant editors to determine whether substantive criticisms were identified by the new reviewers. The majority of manuscripts were thought by the new reviewers to have defects that warranted further revision, but the problems noted were often dissimilar. However, 80% of the manuscripts were recommended for publication and others were judged suitable for publication, although not at a high priority. The assistant editors frequently differed in their judgments whether a given criticism of a reviewer warranted further revision; nevertheless, there was infrequent disagreement regarding the basic decision for acceptance or rejection.

Pediatrics

Effect of acceptance or rejection on the author's evaluation of peer review of medical manuscripts.

To determine whether authors of rejected manuscripts would evaluate the editorial review process less favorably than would authors of manuscripts accepted for publication, a questionnaire was sent to solicit evaluations of the quality of the reviews that had led to the rejection or acceptance of manuscripts submitted to the Journal of Pediatrics. Similar evaluations of the editor's letter were also sought. Authors were more likely to respond to the questionnaire if their manuscripts had been accepted and were more likely to complete the questionnaire thoroughly. Authors of accepted manuscripts evaluated the editor's communication more favorably than did the authors of manuscripts not accepted for publication, but the evaluations of the reviews were not significantly different. Most authors utilized the reviews to modify their manuscripts before submitting them to another journal.

Authorship

Molecular biology of gastrointestinal peptides and growth factors: relevance to intestinal adaptation.

New approaches towards understanding regulation of growth and adaptation of the small intestine are made possible by the isolation and characterization of genes and complementary DNAs (cDNAs) encoding gastrointestinal peptides, growth factors and their receptors. Nucleotide sequencing provides prerequisite structural information. Analyses of gene expression by quantitation and localization of mRNAs provide information about correlations between local alterations in peptide or receptor synthesis and intestinal growth. Analyses of intestinal growth in transgenic animals that overexpress or underexpress growth factor or receptor genes provides direct information about peptide effects on growth. Our recent studies with genes and cDNAs encoding proglucagon and the growth hormone dependent insulin-like growth factor 1 (IGF-I) represent examples of these approaches. Sequences of proglucagon and IGF-I cDNAs provide the primary structures of the peptide precursors. Analyses of proglucagon mRNA during adaptive growth after small bowel resection indicate that increases in proglucagon gene transcription or mRNA stability underly previously observed increases in serum enteroglucagons during adaptive growth. Analyses of IGF-I mRNAs in intestine indicate that small intestine expresses only a subset of the IGF-I mRNAs expressed in liver due to utilization of specific promotors and/or exon splicing mechanisms. Oligomers derived from the 3' end of the rat IGF-I gene detect a novel intestinal specific IGF-I related mRNA that shows an aboral decline in abundance from duodenum to colon and is upregulated in a number of situations of adaptive growth. Transgenic mice that overexpress growth hormone or IGF-I are under analysis to establish the effects of growth hormone and IGF-I on intestinal growth.

Adaptation, Physiological

Site of substrate stimulation of jejunal sucrase in the rat.

To identify the site of stimulation of sucrase by a sucrose diet, changes in sucrase-specific activity of jejunal mucosa were studied after introduction of sucrose diet to carbohydrate-deprived rats. Results were correlated with simultaneous changes in villus gradients of sucrase-specific activity. Simultaneous with the introduction of sucrose diet, [(3)H]thymidine (100 muCi) was administered intravenously, and rates of cell migration measured during adaptation to the new diet. After a 72-h fast, rats fed sucrose diet for 6, 12, or 18 h showed no change in sucrase-specific activity in either whole mucosa or villus gradients. However, within 18-24 h after starting a sucrose diet, there was a marked rise in whole mucosal sucrase-specific activity above fasting values (99 +/- 14 vs. 38 +/- 4 muM glucose/min per g protein, P < 0.001) in association with the development of a region of increased activity at the lower villus (154 +/- 22 vs. 60 +/- 9 muM glucose/min per g protein, P < 0.02, but with no change in villus tip activity (56 +/- 5 vs. 46 +/- 8 muM glucose/min per g protein). Similar changes were seen in animals fed 24 h of sucrose diet after a 72-h carbohydratefree diet. Fasted animals fed sucrose diet for 36 h had increased sucrase-specific activity at the villus tip (144 +/- 11 muM glucose/min per g protein) as well as at the lower villus region, and this pattern persisted at 1 wk of sucrose diet. Maximal activity patterns for isomaltase and maltase paralleled those for sucrase, but the villus gradients for lactase were unaffected by sucrose diet. The region of maximal sucrase-specific activity always coincided with or followed the leading edge of radioactivity as determined by liquid scintillation counting. Therefore, sucrose-mediated changes in sucrase activity of the jejunal mucosa in the rat appear to be initiated at the level of the crypt epithelial cell and are expressed after a latent period of 18-24 h during which these cells mature and migrate toward the villus tip.

Animals

Hepatoxicity with encephalopathy associated with aspirin therapy in rheumatoid arthritis.

Encephalopathy secondary to aspirin-induced hepatoxicity developed in three patients with JRA. In each patient clinical and biochemical resolution occurred after discontinuing the drug, but toxicity appeared on rechallenge. Liver biopsies in two patients showed mild nonspecific changes. Acute hepatic decompensation and encephalopathy may occur as a consequence of aspirin hepatoxicity in JRA and justify sequential observations of liver function tests and salicylate levels in such patients.

Adolescent