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Biomedical subjects

B L Nichols

Publications and source records attributed to B L Nichols.

At least 19 recordsLinked to original sources
PubMed1992

Expression and different polarity of aminopeptidase N in normal human colonic mucosa and colonic tumors.

Expression and cellular localization of brush-border enzymes (aminopeptidase N, dipeptidylpeptidase IV, lactase, maltase) in normal human colon, colonic polyps and malignant intestinal tumors were investigated with a panel of monoclonal antibodies reacting with either native or denatured proteins. The enzymes were detected on cryostat sections by indirect immunofluorescence staining, or affinity-purified and analyzed by gel electrophoresis and immunoblotting. Dipeptidylpeptidase IV, lactase and maltase were absent from all samples examined, while aminopeptidase N (APN) was detected at the basal membrane of the epithelial cells in most specimens of colon obtained from individuals free of intestinal tumors. In contrast, APN was frequently localized at the luminal membrane of the surface epithelium in large-intestinal mucosa distal to tumors, adenomas and hyperplastic polyps, and from members of hereditary colon cancer syndrome families. APN was also expressed in colonic tumors, where it was present in an apical cell membrane location in 3/23 adenomas and 14/35 adenocarcinomas examined. No correlation was found between tumor-cell invasiveness (classified by "Dukes" stage) and expression or cellular location of aminopeptidase N. Histologically, all positive tumors were moderately or well differentiated. These results suggest that aminopeptidase N is normally expressed in adult human colon, but epithelial cells in the large and small intestine differ in their ways of sorting this enzyme intracellularly and eventually inserting it into different aspects of their surface membrane, a process which may be altered at an early stage of carcinogenesis.

Aminopeptidases↗
PubMed1992

Feeding status affects in vivo prosucrase.isomaltase processing in rat jejunum.

Fed and fasted (18 h) adult male rats received a primed constant infusion of [3H]leucine for 15 to 180 min. Prosucrase-isomaltase (pro-SI) and sucrase were isolated from mixed jejunal mucosal membranes by immunoprecipitation and separated from one another by polyacrylamide gel electrophoresis under denaturing and reducing conditions. The rate at which pro-SI was processed to sucrase was calculated on the assumption that the steady-state specific radioactivity of leucine in pro-SI defined the pool of amino acids used in the formation of brush border sucrase. At isotopic steady state, pro-SI achieved a specific radioactivity that was higher than that of mucosal free leucine in both feeding groups. The relationship between the isotopic equilibrium of the free amino acid pools and pro-SI was sensitive to feeding status; the specific radioactivity of pro-SI was 25 and 55% (P less than 0.05) of the blood specific radioactivity in fed and fasted animals, respectively. The fractional rate of pro-SI processing tended to be higher (P less than 0.07) in fed (407%/d) than in fasted animals (274%/d). We conclude that the general mucosal free amino acid pool is not the amino acid pool from which pro-SI is synthesized and that the rate of pro-SI processing from the endoplasmic reticulum-Golgi membranes to the brush border membrane is sensitive to the feeding status of the animal.

Amino Acids↗
PubMed1992

Mosaic expression of brush-border enzymes in infants with chronic diarrhea and malnutrition.

The chronic diarrhea observed in young malnourished infants that is sensitive to dietary glucose and other carbohydrates is associated with variable degrees of patchy mucosal villous atrophy. To explore intrinsic mucosal function in the pathogenesis of this alimentary intolerance, we have conducted an immunohistologic investigation of brush-border enzyme proteins of clinically obtained, mucosal biopsy samples. We used a group of monoclonal antibodies against human brush-border aminopeptidase, sucrase/isomaltase (SI), maltase, and lactase enzyme proteins. SI was strongly and uniformly expressed in crypts and villi of 11 of the 14 subjects; in 3 subjects, however, SI was expressed in a mosaic pattern. Maltase and lactase were occasionally absent, but more commonly were expressed in a mosaic distribution. The mosaic expression of brush-border enzyme proteins has been reported in congenital enzyme deficiencies associated with normal intestinal histology. We report the mosaic expression of brush-border enzyme proteins as a functional alteration associated with a pathological lesion of the mucosa in infants with chronic diarrhea. Our observation challenges the existing concept of ontogenic regulation of brush-border enzyme activity.

Aminopeptidases↗
PubMed1992

Developmental changes in lactase-phlorizin hydrolase precursor isoforms in the rat.

The purpose of this study was to determine whether the developmental decline in lactase specific activity (mumol/min/g protein) in the rat was associated with (a) changes in the relative quantities of immunoisolated precursor and mature forms of the enzyme purified by SDS-PAGE and/or (b) immunohistologic changes in the jejunal mucosa. We studied 10- and 16-day-old suckling rat pups, 22-day-old weaned rat pups, and adult female rats (nongravid, pregnant, and lactating). Lactase activity was three- to fourfold higher in 10-day-old pups than in adult rats. Lactase activity was 27% greater in lactating compared with nongravid or pregnant rats. Three molecular forms of the enzyme that migrated identically in all animals were observed on SDS-polyacrylamide gels stained with Coomassie blue: 140-kDa (mature brush border form), 200-kDa, and 220-kDa (apparent precursor forms). There was a striking difference in the proportions of the three polypeptides at different ages that was unrelated to animal status, i.e., pregnant or lactating. As the animals aged, the relative amount of the 140-kDa band declined from 86 +/- 1.1% of the total immunoprecipitated lactase in 10-day old suckling pups to 68 +/- 0.7% in adults. Simultaneously, the relative concentration of the 200-kDa band rose from 1.7 +/- 0.4% in the 10-day-old to 19 +/- 0.6% in adults. The relative concentration of the 220-kDa polypeptide did not change as a function of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1979

Lactation.

Explore the source record for details and available documents.

Body Water↗
PubMed1978

Intestinal surface area in infants with acquired monosaccharide intolerance.

Acquired monosaccharide intolerance is characterized by the malabsorption of all carbohydrates, resulting in profuse acidic diarrhea. Five infants with this syndrome, ranging from two to six months of age, were studied by measuring their ability to absorb glucose given by intestinal perfusion. Jejunal biopsies obtained at the time of perfusion were studied by light and electron microscopy, and surface area measurements were obtained. Glucose absorption and surface area were significantly decreased (P less than 0.005) during the acute phase of the disease and improved during convalescence. A linear correlation (r = 0.8757) was observed between the ability to absorb glucose and intestinal surface area. It is concluded that the loss of absorptive surface is a major cause of the reduced carbohydrate absorption and consequent diarrhea.

Atrophy↗
PubMed1978

Magnesium supplementation in protein-calorie malnutrition.

The widespread observation of magnesium depletion in edematous malnutrition has been confirmed in Guatemalan children. The magnesium requirement during initial stages of therapy has been estimated as 2.7 mEq/kg per day. This may be achieved by adding 0.5% MgSO4.7H2O to a solution containing 15% dextromaltase and 1.5% KCl which is used to dilute whole milk; two parts milk and one part dilution mixture. The replacement of magnesium deficits was not essential for recovery from edematous malnutrition, however, the present evidence suggested that the rate of recovery was accelerated by approximately 2 weeks in those children who received the supplement.

Child↗
PubMed1978

Fiber, intestinal sterols, and colon cancer.

It has been postulated that dietary fiber's protective effect against the development of colon cancer, diverticular disease, and atherosclerosis may be due to the adsorption and/or dilution of intestinal sterols such as bile acids and neural sterols and their bacterial metabolites by component(s) of fiber. Dietary fiber is made up of four major components-cellulose, hemicellulose, lignin, and pectin. There is evidence that hemicellulose and pectin may induce an increase in fecal bile acid excretion in man which may be accompanied by a decrease in serum cholesterol. Natural fibers, such as rolled oats, alfalfa, guar gum, and Bengal gram have been shown to have hypocholesterolemic properties of alfalfa, wheat straw, and some other fibers found considerable amounts of bile acids in vitro. On the other hand, wheat bran, oat hulls, and all the synthetic fibers tested bound only negligible amounts of bile acids under the same conditions. Vegetarians in the United States have lower plasma lipids and different plasma lipoprotein patterns than those of comparable control populations on regular mixed diet. They also have smaller daily fractional turnover rates of cholic acid and deoxycholic acid pool size. In addition, populations on a mixed Western diet, where the rate of large bowel cancer is high (North American, English, Scottish, etc.) degraded and excreted cholesterol and bile acid metabolites to a greater degree than populations where the rate of colon cancer is comparatively low (Ugandan, Japanese, etc). It cannot be denied that the fiber theory linking fiber deficiency with the development of colon cancer and other diseases, is simple, attractive and appears to be firmly based in common sense. When subjected to research studies, however, the situation appears much more complex than expected. Although some progress is being made, the data are often contradictory and confusing, probably due to lack of adequate documentation of fiber intake (e.g., use of dietary fiber instead of crude fiber) and/or the absence of detailed information on the chemistry of the fiber itself.

Adult↗
PubMed1977

Cholesterol ester storage disease: clinical, biochemical, and pathological studies.

Of three siblings affected with cholesterol ester storage disease, two died at ages 7 and 9 years, respectively, with hepatic scarring and portal hypertension. Lipid storage was documented in both patients, as were esophageal varices and aortic plaques in the older child. The third affected sibling, followed to 13 years of age, has hepatomegaly, hyperlipidemia, short stature, adrenal calcification, and acid lipase deficiency. Leukocyte extracts demonstrated deficiency of acid lipase in this patient. This autosomal recessive condition may be allelic with Wolman disease with a more malignant course in this family than in most reported cases.

Child↗
PubMed1977

Sequential changes in body composition during infection: electron probe study IV.

Alterations occur in human muscle electrolyte and water composition in response to infection. There appear to be at least two basic mechanisms; the first is an exchange of sodium for potassium without alteration in water content of muscle. The second is an increase in cellular Na and water without a loss of K on a dry weight basis. In a series of studies in monkeys, Salmonella typhimurium sepsis was induced as an experimental model. Both patterns of muscle response to infection were detected. Electron probe microanalysis revealed that the loss of K concentration was due to an accumulation of intracellular saline which dilute the K content. The mechanism of this is unclear; however, a concomitant increase in undertermined osmoles in the serum suggests that there may be an increase in organic osmoles within the cell which leads to the dilution of intracellular K concentration.

Animals↗
PubMed1977

Luminal dilatation and morphologic changes secondary to enterotoxins.

Structural changes in ligated rat small intestinal loops exposed to purified cholera enterotoxin are described. Distention secondary to increased luminal fluid was found to cause the artifactual histologic damage. This finding questions the validity of interpreting mucosal changes in closed intestinal-loop models in the presence of severe distention. An alternative open-loop model is described that eliminates distention as a cause of histologic changes.

Animals↗