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Biomedical subjects

H J Freeman

Publications and source records attributed to H J Freeman.

At least 91 records · Page 5Linked to original sources

Amino acid and peptide absorption in bypassed jejunum following jejunoileal bypass in rats.

The intestinal digestive and absorptive function of the excluded jejunum was evaluated 6 and 12 weeks after jejunoileal bypass in rats. Brush border and cytosol aminopeptidase activities as well as mucosal sucrase activity were measured in self-emptying excluded jejunal segments following bypass surgery. In addition, following in vivo perfusion of equimolar amounts of amino acid (L-leucine) and dipeptide (L-leucyl-L-leucine) solutions through bypassed jejunal segments, the uptake of L-leucine was determined. Mucosal weight, protein, and DNA content were reduced in the bypass segment reflecting jejunal mucosal cell hypoplasia. Hydrolytic activities for all enzymes (including the subcellular fractions of the aminopeptidase activities) and absorption rates from both the free amino acid and peptide solutions were reduced in bypassed jejunal segments. When expressed on the basis of mucosal DNA content, however, no changes were observed. This study indicates that the functional alterations in the excluded jejunum after bypass are due to the reduced mucosal cell content of this segment.

Amino Acids↗

Recent advances in dietary fiber and colorectal diseases.

Dietary fiber has emerged in the past decade as a factor in nutrition that appears to have complex physiological and clinical implications. A great deal of research has focused on its effect on colorectal diseases. Some human epidemiological studies on colon cancer point to a possible preventive role of dietary fiber, but the results are confounded by the difference in the intake of many other food substances such as fat and the overall differences in the dietary pattern of the populations investigated. Animal studies using chemical carcinogens, such as 1,2-dimethylhydrazine, have lent support to a protective role of certain components of fiber, such as purified cellulose. Other fiber polymers, such as pectin, have not shown any protective effect. Perhaps the strongest evidence for a protective role of fiber in the colon comes from studies relating low dietary fiber intake to the higher incidence of diverticular disease of the colon; addition of dietary fiber to the diet of patients with symptomatic diverticular disease seems to relieve pain effectively. Recently, some preliminary studies have shown the possible correlation of low dietary fiber intake with a greater incidence of ulcerative colitis and Crohn's disease, but these studies are too limited in number and scope to allow any conclusion to be reached at this time.

1,2-Dimethylhydrazine↗

Survival after necrotizing enterocolitis of leukemia treated with oral vancomycin.

A 56-yr-old female with chronic lymphocytic leukemia developed hemolytic anemia and thrombocytopenia. Prednisone therapy was instituted, but her disease was further complicated by the development of necrotizing enterocolitis. No specific enteropathogens were identified, and the stools were consistently negative for Clostridium difficile toxin. Treatment with vancomycin was instituted and resulted in complete recovery. In view of the high mortality and poor results of treatment in necrotizing enterocolitis, it is postulated that a further trial of this drug is justified.

Administration, Oral↗

A double-blind study on the effects of differing purified cellulose and pectin fiber diets on 1,2-dimethylhydrazine-induced rat colonic neoplasia.

The incidence, distribution, size, and histopathology of colonic tumors induced by parenteral administration of 1,2-dimethylhydrazine were examined in rats fed a chemically defined fiber-free diet or nutritionally and calorically equivalent diets containing either 4.5 or 9.0% purified cellulose or pectin. This double-blind study indicates that cellulose is protective against experimental colonic neoplasia. Although the precise mechanism for this protective effect remains to be elucidated, it was not cellulose dose dependent and appeared to depend on administration during injection of carcinogen. Furthermore, this study provides strong evidence that identical amounts of cellulose and pectin fed as the sole source of fiber in chemically defined diets exert strikingly different effects in relation to development of intestinal neoplasia in this animal model.

Adenocarcinoma↗

Application of lectins for detection of goblet cell glycoconjugate differences in proximal and distal colon of the rat.

Paraffin-embedded mucosal biopsies from proximal and distal colon of male Wistar rats were examined by fluorescence microscopy after labeling with nine fluorescein-conjugated lectins. These were isolated by affinity column chromatography, conjugated to fluorescein isothiocyanate, and used as specific molecular probes to define the labeling patterns of carbohydrate-containing components of colonic goblet cells at both sites. Differential lectin labeling of goblet cells within the colonic crypts was observed in both regions likely reflecting increasing differentiation of these epithelial cells. Furthermore, marked regional differences in goblet cell mucus labeling were also detected, indicating that the carbohydrate components of these mucosal cells differ significantly between proximal and distal colon of the rat. These regional differences suggest that there are significant differences in the biologic characteristics of colonic mucosa from these two sites.

Animals↗

Use of unscheduled DNA synthesis in freshly isolated human intestinal mucosal cells for carcinogen detection.

Mucosal cells freshly isolated from human intestine with pronase retain the capacity to undergo DNA repair synthesis (unscheduled DNA synthesis) during a 2-hr exposure to the carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine, and the procarcinogen, aflatoxin B1. This procedure combining the use of human intestinal mucosal cells and the measurement of unscheduled DNA synthesis may provide a highly relevant and convenient test system for the detection of cell-specific, direct-acting, and activation-dependent chemical carcinogens. The use of whole-cell preparations in such in vitro studies may be of additional significance in view of growing evidence for artefactual metabolism by subcellular fractions.

Aflatoxins↗

Dietary fibre and colonic neoplasia.

Dietary plant fibre, or plantix, is thought to play a significant role in the pathogenesis of colon cancer in humans. It is a complex polymeric substance that has several distinct components resistant to hydrolysis by the digestive enzymes of humans. These components include cellulose, hemicelluloses, pectins, lignin, gums, mucilages and, in certain instances, algal polysaccharides. These polymers have different physicochemical properties, and recent evidence from experimental studies in animals treated with carcinogens suggests that some may exert protective effects in the intestine and others may enhance colon carcinogenesis. This review synthesizes information on the chemical composition, methods of analysis and physicochemical properties of dietary plant fibre and reviews available studies examining the role of fibre in colonic neoplasia in animals and humans.

Animals↗

Protein digestion and absorption in man. Normal mechanisms and protein-energy malnutrition.

Protein is an essential nutrient normally assimilated in an efficient manner following the action of gastric, pancreatic and small intestinal enzymes. After hydrolysis, protein digestion products in the form of amino acids and small peptides undergo mucosal uptake by distinct transport mechanisms. Although gastric and pancreatic enzymes are important, the small intestine appears to be the critical rate-limiting tissue in this process. Impaired intake, assimilation or excessive enteric protein loss may occur with several diseases leading to protein-energy malnutrition. Although the clinical and laboratory features of this condition are nonspecific and wide ranging in spectrum, their presence may provide a clue to underlying disease and serve as an index of patient nutritional status. Disease of the exocrine pancreas or small intestine may cause significant protein-energy malnutrition which, in turn, can cause major structural and functional abnormalities in these tissues.

Dietary Proteins↗

Amino acid and peptide absorption after proximal small intestinal resection in the rat.

In experimental animals with massive proximal intestinal resection, in vivo ileal absorption of an amino acid mixture containing L-leucine and glycine as well as two different dipeptides, L-leucyl-glycine and glycyl-L-leucine, were compared. Both amino acid and dipeptide absorption were markedly enhanced in the ileal segments. However, the absorption rates from the two perfused dipeptides differed. L-leucine absorption from L-leucyl-glycine was much greater than from glycyl-L-leucine. Brush border amino-peptidase activities after resection were also increased but dissociation between absorption and hydrolytic activity occurred. This study indicates that certain dipeptides are handled differently by adapting ileal segments. Furthermore, the changes observed probably reflect mucosal cellular hyperplasia occurring in association with intestinal adaptation.

Amino Acids↗

beta-Hexosaminidase isoenzymes in tissues, cultured cells, and media from human fetal intestine and colonic adenocarcinoma.

Isoelectric focusing of tissue homogenates revealed a predominance of beta-hexosaminidase B in colonic adenocarcinoma, whereas beta-hexosaminidase A was greater in paired normal-appearing colonic mucosa from the same patients as well as in a specimen of human fetal colonic mucosa. Because of the recognized cellular heterogeneity of these tissues, our studies were extended to an examination of these isoenzymes in 20 cultured epithelial cell lines derived from human fetal intestine and colonic carcinoma as well as the secreted enzymes in their culture media. While the B:A isoenzyme ratio was higher in human cancer cells as compared to fetal cells, some of the cancer cell lines had a greater proportion of the A isoenzyme. Examination of the isoenzyme profiles in the media of these cells revealed a greater B:A ratio whether of fetal or cancer cell origin. These studies parallel the apparent biological differences of neoplastic colonic epithelium occurring in vivo and are reminiscent of reported oncodevelopmental changes in enzymatic properties present in some malignant tissues. The differential stabilities of these two isoenzymes derived from the culture media of both types of cell lines in vitro may limit their value as markers of human colonic neoplasia.

Adenocarcinoma↗

A double-blind study on the effect of purified cellulose dietary fiber on 1,2-dimethylhydrazine-induced rat colonic neoplasia.

The incidence, distribution, size, and histopathology of grossly visible colonic tumors induced by parenteral administration of 1,2-dimethylhydrazine were examined in rats fed either a chemically defined fiber-free diet or a nutritionally and calorically equivalent diet containing a purified fiber component, microcrystalline cellulose. This double-blind study indicates that cellulose ingestion was associated with reduced numbers of animals involved with colonic neoplasia as well as a reduction in the total numbers of colonic tumors. Furthermore, this protective effect of cellulose appears to be time dependent and associated with a shift in tumor distribution from the proximal colon to a more distal site. Cellulose fiber had no apparent effect on colonic tumor size, histopathology, or the incidence of other tumors known to occur in this experimental animal model. This study strongly supports the hypothesis that fiber is an important protective agent against colonic neoplasia development. While the mechanism for this protective effect remains obscure, it appears to be temporally related to the duration of fiber ingestion as well as to a differential fiber effect on either the luminal content or the mucosa of the proximal and distal colon.

Adenocarcinoma↗

Alterations in cell surface membrane components of adapting rat small intestinal epithelium. Studies with lectins after massive proximal jejunoileal resection and jejunoileal transposition.

After proximal resection or transposition of intestinal segments, the small intestinal mucosa of rats was examined with fluorescein-conjugated lectins derived from Ricinus communis and Triticum vulgare (wheat germ). These agglutinins are thought to be specific for the nonreducing end-terminal carbohydrate residues, beta-D-galactose and beta-N-acetyl-D-glucosamine, respectively. After 70% proximal jejunoilealal resection as well as transposition of ileal segments to jejunum, ileal villus cell surface labeling by both lectins was changed to a pattern characteristic of normal rat proximal intestine. Alterations were not detected proximal to the surgical anastomosis after massive resection or in the jejunal segments transposed to ileum. Although the labeling pattern of goblet cell mucin differed in proximal duodenum from the remainder of control small intestine in normal animals, no differences were detected in goblet cell mucin labeling between normal and resected or transposed animals. This study confirms the previously reported differential lectin-labeling patterns of the small intestinal crypt and villus cells and further emphasizes the differences between cell surface carbohydrate and secretory mucins of goblet cells. Furthermore, the changes induced in the cell surface-labeling pattern by massive proximal jejunoileal resection and transposition suggest that cell surface and secretory components may be altered differently during adaptation of the small intestine.

Adaptation, Physiological↗

Cytomegalovirus infection of the gastrointestinal tract in a patient with late onset immunodeficiency syndrome.

An adult with the late onset immunodeficiency syndrome developed intractable diarrhea. Widespread cytomegalovirus (CMV) infection of the gastrointestinal tract was detected antemortem with detailed morphological studies and viral culture. The CMV-type cells were especially numerous in his severely ulcerated colon. Electron microscopy of infected cells in rectal biopsy material revealed the characteristic features of CMV infection. It is likely that the CMV infection contributed to the symptom complex and the mucosal injury. Unusual opportunistic infections as a cause of diarrhea should be considered in patients with late onset immunodefociency, especially if Giardiasis is ruled out.

Adult↗

Alpha1-antitrypsin deficiency and pancreatic fibrosis.

A 39-year-old woman with homozygous ZZ alpha1-antitrypsin deficiency was found to have pancreatic fibrosis in addition to the recognized pulmonary and hepatic abnormalities. Pancreatic exocrine function was normal but endocrine studies showed glucose intolerance. Pancreatic fibrosis may be another manifestation of alpha1-antitrypsin deficiency.

Adult↗

Failure of added dietary gluten to induce small intestinal histopathological changes in patients with watery diarrhea and lymphocytic colitis.

Lymphocytic colitis is a form of microscopic colitis usually characterized by watery diarrhea and often associated with biopsy-defined celiac disease. Two patients with lymphocytic colitis and normal small intestinal biopsies who were administered 40 g of added dietary gluten for four consecutive weeks are presented. Small intestinal biopsies from multiple sites in the proximal small bowel were done after three and four weeks to determine whether pathological changes in latent celiac disease could be induced in these patients with a high gluten-containing diet. In addition, colorectal biopsies were done to determine whether the colitis was sensitive to oral gluten. No alterations in the small intestinal biopsies were detected in either patient and no changes occurred in colitis severity. Although microscopic forms of colitis have been linked to celiac disease, this study indicates that lymphocytic colitis is a heterogeneous clinicopathological disorder that, in some patients, is independent of any gluten-induced intestinal pathological changes.

Biopsy↗