Biomedical subjects

L R Jacobs

Publications and source records attributed to L R Jacobs.

At least 37 records · Page 2Linked to original sources

PubMed1986

Modification of experimental colon carcinogenesis by dietary fibers.

The literature concerning the effect of individual dietary fibers on the experimental induction of colorectal cancer was reviewed. It has become increasingly apparent that the effect of dietary fibers on colon carcinogenesis depends on many factors, including the type and amount of fiber; the other dietary components, particularly fat; animal species, strain, and sex; and the type of carcinogen and its dose and route of administration. Despite such variations in design, most experiments with wheat bran and cellulose have shown evidence of a significant protective effect. In contrast, numerous other fiber supplements have been shown to enhance tumor development. These include pectin, corn bran, undegraded carageenan, agar, Metamucil, and alfalfa. Possible mechanisms by which fibers may inhibit colon tumorigenesis include dilution and adsorption of any carcinogens or promoters contained within the intestinal lumen and faster transit time and therefore less opportunity for carcinogen/promoter interaction with the intestinal epithelium. Modulation of colonic microbial metabolic activity by dietary fibers may also be important in the activation and detoxification of carcinogens and promoters. Dietary fibers produce structural and functional changes in the intestinal epithelium and modify rates of cell proliferation changes in the intestinal epithelium and modify rates of cell proliferation and migration. Evidence suggests that if this stimulus to cell proliferation occurs during the stage of initiation, it may lead to enhancement of the carcinogenic process. Dietary fibers bind not only carcinogens, bile acids, and other potentially toxic agents but also essential nutrients that themselves can modify the carcinogenic process. Fermentation of fibers within the large bowel results in production of volatile fatty acids, which in vitro have been shown to be antineoplastic. Fermentation also produces a lower luminal pH, which in turn affects colonic microbial populations and their metabolic activities. The presence of lignans in higher plants and their bacterial synthesis from precursors present in fiber-rich foods provide an additional source of antineoplastic agents, whose relative importance in colon carcinogenesis is unknown. Because dietary fibers differ in their physiochemical properties, it has been difficult to identify a single mechanism by which fibers prevent or inhibit colon carcinogenesis. Clearly, more investigation is needed regarding the mechanism(s) by which certain fibers inhibit while others enhance experimental colon carcinogenesis.

Animals↗

PubMed1986

Relationship between dietary fiber and cancer: metabolic, physiologic, and cellular mechanisms.

The relationships between fiber consumption and human cancer rates have been examined, together with an analysis of the effects of individual dietary fibers on the experimental induction of large bowel cancer. The human epidemiology indicates an inverse correlation between high fiber consumption and lower colon cancer rates. Cereal fiber sources show the most consistent negative correlation. However, human case-control studies in general fail to confirm any protective effect due to dietary fiber. Case-control studies indicate that if any source of dietary fiber is possibly antineoplastic then it is probably vegetables. These results may mean that purified fibers alone do not inhibit tumor development, whereas it is likely that some other factors present in vegetables are antineoplastic. Experiments in laboratory animals, using chemical induction of large bowel cancer, have in general shown a protective effect with supplements of poorly fermentable fibers such as wheat bran or cellulose. In contrast, a number of fermentable fiber supplements including pectin, corn bran, oat bran, undegraded carageenan, agar, psyllium, guar gum, and alfalfa have been shown to enhance tumor development. Possible mechanisms by which fibers may inhibit colon tumorigenesis include dilution and adsorption of any carcinogens and/or promoters contained within the intestinal lumen, the modulation of colonic microbial metabolic activity, and biological modification of intestinal epithelial cells. Dietary fibers not only bind carcinogens, bile acids, and other potential toxins but also essential nutrients, such as minerals, which can inhibit the carcinogenic process. Fermentation of fibers within the large bowel results in the production of short chain fatty acids, which in vivo stimulate cell proliferation, while butyrate appears to be antineoplastic in vitro. Evidence suggests that if dietary fibers stimulate cell proliferation during the stage of initiation, then this may lead to tumor enhancement. Fermentation also lowers luminal pH, which in turn modifies colonic microbial metabolic acidity, and is associated with increased epithelial cell proliferation and colon carcinogenesis. Because dietary fibers differ in their physiochemical properties it has been difficult to identify a single mechanism by which fibers modify colon carcinogenesis. Clearly, more metabolic and physiological studies are needed to fully define the mechanisms by which certain fibers inhibit while others enhance experimental colon carcinogenesis.

Animals↗

PubMed1986

Relationship between colonic luminal pH, cell proliferation, and colon carcinogenesis in 1,2-dimethylhydrazine treated rats fed high fiber diets.

The comparative effects of different fibers on colonic luminal pH, crypt cell proliferation, and colon carcinogenesis were studied in 120 male Sprague-Dawley rats. The animals were divided into five equal groups and fed either a basal fiber free diet or the basal diet supplemented with 10% pectin, cellulose or guar, or 20% oat bran for up to 30 weeks. 1,2-Dimethylhydrazine was given at 20 mg/kg body weight as a weekly s.c. injection for 12 weeks. Food intake and weight gain were similar in all diet groups. At sacrifice, in vivo pH measurements showed that compared to fiber free rats, all fibers significantly acidified large bowel luminal contents (P less than 0.05). In the guar group 62.5% of rats developed colonic tumors compared to 33.4% of the fiber free rats (P less than 0.05). The yield of proximal colonic adenocarcinomas in the oat bran, pectin, and guar groups was increased by 4.5 to 5 times over the fiber free level (P less than 0.05-0.025). Pectin and guar provided the greatest stimulus to cell proliferation. A lower luminal pH was associated with a higher tumor yield and increased epithelial cell proliferation. Thus, acidification of colonic contents by high fiber diets failed to inhibit rat colon carcinogenesis, while the consumption of soluble fibers, such as oat bran, pectin, and guar, was associated with enhancement of proximal colon carcinogenesis.

1,2-Dimethylhydrazine↗

PubMed1985

Differential effects of dietary fibers on rat intestinal circular muscle cell size.

The relationship between dietary fiber and intestinal circular muscle cell size was investigated in rats by feeding defined diets supplemented with four different sources of fiber. In the first study, a 20% wheat bran supplement was fed to 10 rats for nine weeks. This resulted in larger muscle cell size, with a 22.5% increase in the proximal (P less than 0.02) and 77.9% increase in the distal colon (P less than 0.01) when compared with a control group of 10 rats fed a fiber-free diet. In the second study, which lasted four weeks, a control group of 10 rats was fed a fiber-free diet, while similar sized experimental groups were fed the same basal diet plus either 20% oat bran, 10% pectin, or 10% guar. Muscle cell size was decreased by 20.6% in the proximal jejunum of the oat bran- and pectin-fed groups (P less than 0.05) and by 43% in the proximal colon of the oat bran-fed group, when compared with the controls (P less than 0.05). These results show that the effects of high fiber diets on intestinal muscle cell size depend on the type of fiber consumed.

Animals↗

PubMed1985

Human intestinal folate conjugase: adaptation after jejunoileal bypass.

During intestinal absorption, dietary polyglutamyl folates are hydrolyzed to monoglutamyl folates by pteroylpolyglutamate hydrolase (folate conjugase). This enzyme is present in the brush border and intracellular fractions of human jejunal mucosa. We compared the activities of brush border and intracellular folate conjugase (BBFC and ICFC), and other mucosal enzymes in the jejunum in continuity and bypassed loop in nine patients who underwent intestinal reconstitution operations 3 to 9 yr after jejunoileal bypass. Control jejunum was obtained from seven obese patients undergoing gastric bypass surgery. Jejunal morphometry showed mucosal hyperplasia with taller villi, larger crypts, and no change in cell size in the jejunum in continuity as compared to control or bypass jejunum. In brush border fractions, specific activities of sucrase and BBFC were significantly greater in the jejunum in continuity than in the control or bypass jejunum. In contrast, the specific activities of the other brush border and intracellular enzymes, including ICFC, were similar in all three segments. This is the first evidence that BBFC, like sucrase, adapts to luminal nutrition. The difference in response of BBFC and ICFC to diet and/or pancreato-biliary secretions provides evidence that these are distinct enzymes which are regulated by different mechanisms.

Adaptation, Physiological↗

PubMed1985

Influence of luminal pH on rat large bowel epithelial cell cycle.

The influence of luminal pH on the colonic epithelial cell cycle was studied by means of dietary modification to produce acidification of colonic contents. Forty male Sprague-Dawley rats were fed one of four diets: defined fiber free, fiber free diluted by either 100 g/kg lactulose or sorbitol, or 25 g/kg of MgSO4. After 2 wk, in vivo pH measurements were recorded at laparotomy under ether anesthesia in the cecum and proximal, mid-, and distal colon. Epithelial cells, isolated from these same regions, were measured for DNA content with flow cytometry in order to determine cell cycle stage. The pH values in all intestinal regions were highest with MgSO4 and then fiber free, sorbitol, and lactulose, the most acidic. In contrast, the percentage of cells in S phase (actively synthesizing DNA) was highest with lactulose and least with MgSO4. There was a significant inverse correlation between luminal pH and percent cells in S phase in the cecum (P less than 0.01), proximal colon (P less than 0.05), and distal colon (P less than 0.01). These results show that acidification of colonic contents by diet modification leads to increased epithelial cell proliferation.

Animals↗

PubMed1985

Regional distribution and alterations of lectin binding to colorectal mucin in mucosal biopsies from controls and subjects with inflammatory bowel diseases.

Glycoconjugate composition of colorectal goblet cell mucin was characterized according to the anatomical distribution of lectin-binding sites in mucosal biopsies from 35 control subjects and 55 patients with inflammatory bowel disease. 24 of the controls had mucosal inflammation on biopsy, without clinical evidence of inflammatory bowel disease. These inflamed controls showed a similar rate of presence of lectin-binding sites as the normal noninflamed group. In the controls, the frequency of binding of Ricinus communis agglutinin I to galactosyl residues was consistently higher than that found with either Ulex europaeus agglutinin I to fucosyl or Dolichus biflorus agglutinin to N-acetyl galactosyl groups. A significant proximal to distal gradient for Ulex europaeus agglutinin I binding sites was identified in the controls group. These binding sites were present four times more often in the proximal colon than in the distal colon (P less than 0.025). In the ulcerative and Crohn's colitis groups, this gradient effect was lost, predominantly as a result of decreased availability of fucosyl residues in the proximal colon. In the descending colon of Crohn's colitis tissues, there was a complete absence of Dolichus biflorus agglutinin binding sites compared with the 62.5% incidence in the control group (P less than 0.05). These results demonstrate that the expression of lectin-binding sites in human large intestinal goblet mucin is specifically altered in inflammatory bowel disease, indicating that there are changes in glycosylation of colorectal mucin consistent with alterations in goblet cell differentiation.

Adolescent↗

PubMed1984

Effect of dietary fibers on rat large bowel mucosal growth and cell proliferation.

The effects of three different fibers on large intestinal mucosal mass per unit length, crypt morphometrics, and cytokinetics were compared by feeding fiber supplements to 40 rats for 4 wk. A control group of rats was fed a fiber-free diet and the experimental groups received the same diet, uniformly diluted by the addition (wt/wt) of 20% oat bran, 10% pectin, or 10% guar. All groups of rats exhibited equal caloric intakes and weight gains. Guar consistently produced an increase in cecal and colonic mucosal wet weight, DNA, and RNA when compared with the control group (P less than 0.05). DNA levels were increased in the cecum and proximal colon of the pectin group but remained unaltered in those rats fed oat bran. Autoradiographic measurements demonstrated that epithelial cell turnover time was longer in the distal colon of the guar and pectin groups (P less than 0.001), but shorter in the proximal colon of the oat bran group, when compared with the controls (P less than 0.01). This comparative study provides further insight into the possible mechanisms by which specific dietary fibers elicit a hyperproliferative response in the large bowel.

Animals↗

PubMed1984

Stimulation of rat colonic crypt cell proliferative activity by wheat bran consumption during the stage of 1,2-dimethylhydrazine administration.

The effect on colonic epithelial cytokinetics of feeding a 20% wheat bran dietary supplement, either during and/or after the stage of carcinogen administration with 1,2-dimethylhydrazine, was examined in 48 male Sprague-Dawley rats fed defined diets for up to 31 weeks. Nutrient intake and body weight gain were equivalent in all groups of animals. All subgroups of rats fed bran, either during and/or after carcinogen administration, developed colonic crypt cell hyperplasia (p less than 0.05), this being greater in the proximal than in the distal colon. Autoradiographic studies showed a significant increase in proximal colonic crypt cell-labeling index, proliferation zone size, and migration distance in those rats fed wheat bran during the period of carcinogen administration (p less than 0.05). The increase in epithelial cell proliferation activity was most marked in the upper two-thirds of the crypt. These data show that there is a greater stimulation of crypt cell proliferation activity when wheat bran is consumed during the stage of carcinogen administration as compared to the stage following carcinogen exposure. This alteration in mucosal cytokinetics appears to be the mechanism by which wheat bran consumption enhances rat colon carcinogenesis during the period of dimethylhydrazine treatment.

1,2-Dimethylhydrazine↗

PubMed1983

Cytochemical localization of small intestinal glycoconjugates by lectin histochemistry in controls and subjects with cystic fibrosis.

Human mucosal glycoconjugates were examined in normal small intestinal biopsies from five control subjects using six different fluorescein-conjugated lectins: Triticum vulgare agglutinin (WGA), Ulex europaeus agglutinin I (UEA1), Ricinus communis agglutinin I (RCA1), glycin max-soy bean agglutinin (SBA), Dolichus biflorus agglutinin (DBA), and Arachis hypogaea peanut agglutinin (PNA). These plant agglutinins bind to specific nonreducing end-terminal carbohydrate residues. Only the lectins derived from WGA, which produced the strongest staining, and UEA1 consistently bound to both intestinal goblet cell mucin and epithelial cell microvillar membranes. The intensity of lectin binding was greatest in the upper villus and diminished down towards the crypt, being weakest in the crypt base. Similar histochemical studies carried out on small bowel biopsies from five patients with cystic fibrosis revealed no major qualitative differences between the intestinal glycoconjugates in normal subjects and those with cystic fibrosis. These results suggest that glycoconjugate biosynthesis of human intestinal goblet cell mucin and epithelial cell membranes may be complete and hence full differentiation achieved only when these cells have migrated out of the crypt and onto the villus.

Biopsy↗

PubMed1983

Dietary wheat bran inhibits DNA synthesis and enhances 5-fluorouracil toxicity in rat pancreas.

The effect of a 20% wheat bran dietary supplement on pancreatic growth and on the content and synthesis of pancreatic RNA and DNA was examined in male Sprague-Dawley rats fed defined diets for 4-5 weeks. Nutrient intake and body weight gain were similar in the control group (fed a fiber-free diet) and the groups fed the wheat bran supplement. The wheat bran diet produced no significant change in pancreatic weight, protein, RNA content, or DNA content, but was associated with a 28.8% fall in pancreatic DNA synthesis, measured by [3H]thymidine incorporation into DNA, when compared with the controls (p less than 0.05). When rats were injected with 50 mg/kg of 5-fluorouracil (two injections, one week apart), those fed wheat bran exhibited a 40.1% increase in pancreatic wet weight (p less than 0.005) and a 24.5% decrease in RNA content (p less than 0.001), when compared to controls fed a fiber-free diet. RNA synthesis, measured by the incorporation of 32P into RNA, increased 3.6-fold in rats fed wheat bran, when compared with controls (p less than 0.01). These results suggest that wheat bran should be tested further for any inhibitory action on pancreatic carcinogenesis and for its modifying effect on 5-fluorouracil toxicity.

Animals↗

PubMed1983

Effect of short-term dietary fat on cell growth in rat gastrointestinal mucosa and pancreas.

The effects of high fat diets on gastrointestinal and pancreatic cell growth were examined in order to determine whether short-term high fat consumption leads to pancreatic and colonic cell hyperplasia. Three groups of eight rats were fed defined diets for 4 wk. The controls were fed a 5% corn oil diet (unsaturated fat) while those fed high fat diets received either 27% lard (saturated fat) plus 3% corn oil or 30% corn oil. Body weight gain and total caloric intakes were equal. Both high fat diets produced significant decreases in proximal jejunal mass (p less than 0.05), while in the distal ileum and cecum, the only change was the development of mucosal cell hypoplasia in the group fed the high unsaturated fat diet (p less than 0.05). The high fat diets produced no change in cell growth or the incorporation of [3H]thymidine into DNA of stomach, pancreas, or colon but did result in a higher level of pancreatic lipase and lower levels of amylase activity. These results show that a short-term high fat intake leads to small intestinal hypoplasia without affecting pancreatic or colonic cell growth and therefore do not support the hypothesis that dietary fat promotes pancreatic and colonic carcinogenesis by producing cell hyperplasia.

Amylases↗

PubMed1983

Modulation of mucosal cell proliferation in the intestine of rats fed a wheat bran diet.

The effect of a 20% wheat bran dietary supplement on intestinal mucosal growth and cell proliferation was examined in two sets of male Sprague-Dawley rats fed defined diets for 4 and 9 wk, respectively. Nutrient intake and body weight gain were equivalent in all groups of animals. In the group of rats fed the bran for 4 wk, small intestinal mucosal weight, DNA, and DNA synthesis, as measured by [3H]thymidine incorporation into DNA, did not change. This was in contrast to large intestinal mucosal DNA which increased by 59.1% in the cecum (p less than 0.001), by 28.3% in the proximal colon (p less than 0.001) and by 35.6% in the distal colon (p less than 0.02) when compared with the controls on the fiber-free diet. Measurements of DNA synthesis and cell proliferation, measured autoradiographically in those rats fed bran for 9 wk, provided evidence of decreased exfoliation in the cecum, with a 45.2% decrease in cell migration (p less than 0.05), whereas in the proximal colon cell proliferation was significantly increased with a cell migration rate 114.3% greater than in the controls (p less than 0.005). These results show that the mechanisms by which wheat bran influences large bowel mucosal growth vary according to the anatomical segment of the intestine. The possible implications of these cytokinetic changes on the development of large bowel cancer are discussed.

Animals↗

PubMed1983

Effects of dietary fiber on mucosal growth and cell proliferation in the small intestine of the rat: a comparison of oat bran, pectin, and guar with total fiber deprivation.

The effects of dietary fiber on small intestinal mucosal mass, morphology, and cytokinetics were studied by feeding three qualitatively different forms of fiber to 40 rats for 4 wk. A fiber-free diet was fed to the control group and a similar diet with either a 20% oat bran, 10% pectin, or 10% guar supplement to the other three groups. All groups of rats exhibited similar caloric intakes and weight gains. Only the guar diet produced a significant increase in mucosal mass, as demonstrated by 19.1% increase in mucosal weight (p less than 0.05), a 16.7% increase in RNA (p less than 0.05) and an increase in DNA from 38.3 +/- 1.8 (SEM) to 44.6 +/- 2.3 micrograms/cm intestine/100 g body weight (p less than 0.05) when compared to the controls. The pectin-diet produced a decrease in villus height from 102.1 +/- 2.4 to 94.3 +/- 2.4 cells but an increase in crypt column length from 25.3 +/- 0.6 to 27.4 +/- 0.4 cells when compared to the controls (p less than 0.05). The shift in labeling index distribution curves for pectin and guar to the right and for oat bran to the left indicated an increase and decrease respectively in labeling index. The higher rate of epithelial cell migration in the pectin- and guar-fed groups shortened their estimated villus cell transit times to 36.4 +/- 0.7 and 37.0 +/- 1.4 h, respectively, when compared with 42.6 +/- 1.2 h in the oat bran and 41.1 +/- 1.0 h in the control (p less than 0.05). These results show that the modulation of small intestinal mucosal structure and growth by dietary fiber appears to be mediated through alterations in cell proliferation and that these changes depend not only on the quantity but also the quality of the fiber present in the diet.

Animals↗

PubMed1983

Enhancement of rat colon carcinogenesis by wheat bran consumption during the stage of 1,2-dimethylhydrazine administration.

The effect on intestinal carcinogenesis of feeding a 20% wheat bran dietary supplement, either during and/or after the stage of carcinogen administration with 1,2-dimethylhydrazine, was examined in 48 male Sprague-Dawley rats fed defined diets for 31 weeks. Nutrient intake and body weight gain were equivalent in all groups of animals. In the rats fed bran during carcinogen administration, tumor yield was significantly greater. Benign and malignant tumors increased by 3.4-fold (p less than 0.005), adenomas by 3.5-fold (p less than 0.025), and adenocarcinomas by 3.25-fold (p less than 0.05) over the yield found in the group fed a fiber-free diet. Consumption of wheat bran, after completion of carcinogen exposure, reduced the yield of benign adenomas by 71.4% when compared with the group fed the fiber-free diet (p less than 0.025). Those rats fed a wheat bran supplement during carcinogen administration and then switched to a fiber-free diet afterwards had the highest tumor yield, 4.5 times as many benign and malignant tumors as in those rats consistently fed the fiber-free diet (p less than 0.05) and at least 6 times as many adenomas as any of the other dietary groups (p less than 0.05). These results demonstrate that dietary wheat bran, a fiber which produces a hyperproliferative response in the colon, significantly increases colon carcinogenesis when fed to rats during the stage of carcinogen administration. This effect appears to be further enhanced when the wheat bran is totally removed from the diet following the stage of carcinogen administration. These data indicate that the hyperproliferative effects of wheat bran appear to outweigh any preventive actions that bran may have on colon carcinogenesis by altering the bulk of intestinal contents and their transit time through the bowel.

1,2-Dimethylhydrazine↗

PubMed1983

Biochemical and ultrastructural characterization of the molecular topography of the rat intestinal microvillous membrane. Asymmetric distribution of hydrophilic groups and anionic binding sites.

The topography of the intestinal microvillous membrane and its surface components was examined using biochemical and ultrastructural techniques. Microvillous membrane surface glycoproteins were labeled using everted intact intestinal sacs, prepared from rat proximal small intestine. Galactosyl residues were identified by labeling with galactose oxidase/sodium boro[3H]hydride and free amino groups with pyridoxal phosphate/sodium boro[3H]hydride. Membranes were purified, solubilized in sodium dodecyl sulfate, and protein labeling analyzed by acrylamide electrophoresis. Using the intact intestine, only microvillous membrane surface amino groups were labeled. However, when microvillous membrane vesicles were purified first and then labeled, radioligand binding to galactoproteins and free amino groups substantially increased. Ultrastructural and cytochemical studies with ruthenium red revealed the intact intestinal surface to have a strong electronegative charge due to the presence of anionic sites in both the thick mucopolysaccharide surface coat and its underlying glycocalyx. During purification of microvillous membrane, the mucous coat was detached from the membrane surface, leaving the glycocalyx directly exposed to the external environment. Enzymatic probing of microvillous membrane vesicles with papain left the vesicles intact and revealed the membrane to be asymmetric with the majority of its integral proteins located at the outer membrane surface. This orientation of galactosyl and amino groups towards the intestinal lumen plus the overlying thick mucopolysaccharide coat should theoretically afford a greater degree of protection against destruction by luminal proteases and bile acids. Moreover, the shedding of membrane-bound hydrolases into the mucous layer may allow the "membrane surface" phase of digestion to commence before nutrients have diffused completely through the surface coat to reach the enterocyte surface.

Amino Acids↗

PubMed1982

Bioadhesive and histotoxic properties of ethyl-2-cyanoacrylate.

Ethyl-2-cyanoacrylate was applied to the cortex of rabbits to evaluate its bioadhesive and histotoxic behavior. The animals were killed at 4 or 10 days. Half of the animals were pretreated with dexamethasone. Our results indicate that the application of ethyl-2-cyanoacrylate to brain tissue produced severe superficial cortical necrosis but not bioadhesion. Pretreatment with steroids did not provide a significant protective effect.

Adhesiveness↗

PubMed1982

Response to dietary wheat bran in the exocrine pancreas and intestine of rats.

Rats were fed a fiber-free (FF) mixture or the same diet with a supplement of 20% wheat bran (WB). After 2 weeks, the pancreas contained higher levels of amylase and trypsin in rats fed WB. In response to a meal, the intestine contained more lipase activity in the WB group. The dry weight of material and protein level in the intestinal contents were also elevated in the WB group. The size of the intestinal villi had not changed, but it did contain more goblet cells. The results indicate that consumption of wheat bran can lead to changes in the exocrine pancreas, perhaps associated with shifts in gut hormones, and may effect absorption by increasing the bulk of material as well as enhancing mucus production in the intestine.

Amylases↗