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M R Neutra

Publications and source records attributed to M R Neutra.

99 records · Page 6Linked to original sources
PubMed1979

Linear arrays of intramembrane particles on microvilli in primate large intestine.

Distinctive linear arrays of intramembrane particles were present in microvillar membranes of approximately 5% of surface columnar cells observed in freeze-fracture replicas of monkey colon and human rectum. On these cells, longitudinally-oriented rows of P face particles and corresponding E face grooves appeared on all exposed microvilli. The constituent particles varied from round (8-9 nm in diameter) to rod-shaped (18 nm long). Microvilli of the great majority of columnar cells displayed randomly distributed P face particles similar to those previously observed in small and large intestine of birds and small mammals. The significance of the linear arrays is not known. It is postulated that they may represent protein assemblies which are specific to a functionally-distinct subpopulation of primate intestinal columnar cells.

Adult↗
PubMed1979

Intestinal goblet cell mucus release. II. In vivo stimulation by antigen in the immunized rat.

We previously reported that the infusion of certain soluble immune complexes stimulated mucus release from the rat small intestine in vivo. The present studies sought to evaluate the response of the intestine of normal and immunized rats to the infusion of antigen alone. One hour after the intraduodenal infusion of antigen, small intestinal washings were obtained and analyzed for the presence of 35S-labeled, high m.w. glycoprotein of goblet cell origin. The amount of goblet cell glycoprotein released was estimated from the radioactivity present in the void volume of a Sepharose 4B gel filtration column. The release of goblet cell mucus was enhanced by antigen stimulation in orally immunized animals. The discharge of goblet cell mucus was not increased after antigen infusion in animals immunized by the i.p. route despite the induction of high levels of serum antibody. The inability to demonstrate release of mucus after antigen challenge in systemically immunized rats suggests that the amount or the type(s) of antibody required at the mucosal surface is produced only after oral immunization.

Animals↗
PubMed1978

Rectal mucosa in cystic fibrosis. Morphological features before and after short term organ culture.

Histological changes observed in the large intestinal mucosa of cystic fibrosis (CF) patients, including crypt enlargement as well as intracellular and extracellular accumulation of mucus, have been considered by some to be useful diagnostic signs of this disease. The extent of these changes, however, has not been evaluated quantitatively. In this study, quantitative stereological methods were applied to biopsies of rectal mucosa from 5 CF patients, 5 sibling controls, and 2 normal adults, to measure goblet cell numbers, crypt luminal volume, and volume of intracellular mucus. It was found that CF crypt lumina were variably dilated, but that the average relative volume of intracellular mucus and the numbers of goblet cells in CF mucosae were comparable to those of sibling and adult controls. In CF biopsies, however, surface columnar absorptive cells consistently contained putative lipid droplets and rapidly accumulated additional large lipid droplets during short term organ culture. Lipid droplets were not observed in the same cell types of control biopsies before or after short term organ culture.

Adolescent↗
PubMed1977

Membrane interactions between adjacent mucols secretion granules.

In primate goblet cells, the membranes of adjacent mucous granules from contact areas which appear as extensive pentalaminar fusion sites in thin sections. In freeze-fracture replicas, the same membrane areas are smooth, except for a few 6-8-nm particles which adhere to the E face. These protein-poor membrane interaction sites are relatively long-lived, and it is proposed that further stimulus may be required to trigger membrane fission.

Animals↗
PubMed1977

Glycoprotein synthesis, transport, and secretion by epithelial cells of human rectal mucosa: normal and cystic fibrosis.

The synthesis, transport, and secretion of glycoprotein by human rectal epithelium from normal volunteers, patients with cystic fibrosis, and their disease-free siblings were studied by autoradiography of rectal biopsies pulse-labeled with 3H-glucosamine and maintained in organ culture for various intervals of up to 24 hours. Human rectal goblet and columnar cells transported 3H-glucosamine-labeled secretory products at a substantially slower rate than do comparable colonic cells in smaller mammals. Within any one biopsy sample, the movement of labeled mucus in goblet cells varied widely among cells. Even with individual cells, labeled mucous granules often did not move in concert toward the apical cell surface. Average transport time in the cells of six cystic fibrosis patients and six sibling controls did not differ significantly from those of four adult controls. The carbohydrate composition of glycoprotein secretions of rectal epithelial cells was investigated by comparing autoradiographs of 3H-glucosamine-labeled biopsies with those labeled with 3H-fucose, 3H-N-acetylmannosamine, and 35S-sulfate. The patterns of incorporation of these four precrusors into normal goblet and columnar cells suggested that both cell types may alter the quantity and composition of newly synthesized glycoproteins as they migrate, mature, and senesce. Incorporation patterns in cystic fibrosis biopsies were indistinguishable from those of sibling or adult controls. With the techniques used, no abnormalities of epithelial glycoprotein production were detected in cystic fibrosis rectal mucosa.

Adolescent↗
PubMedDate not supplied

Peptomer aluminum oxide nanoparticle conjugates as systemic and mucosal vaccine candidates: synthesis and characterization of a conjugate derived from the C4 domain of HIV-1MN gp120.

Peptomers are polymers composed of peptides that are specifically cross-linked in a head-to-tail fashion. Recently, a peptomer composed of an amphipathic peptide from the C4 domain of HIV-1MN gp120 was shown to display a prominent alpha-helical conformation that, as an immunogen, elicited rabbit antibodies recognizing native and recombinant gp120 [Robey et al. (1995) J. Biol. Chem. 270, 23918-23921]. For the present study, we synthesized a conjugate composed of the C4 peptomer covalently linked to calcinated aluminum oxide nanoparticles. The nanoparticles were first reacted with (3-aminopropy])-triethoxysilane to provide an amine load of 15.9 mmol of R-NH2/g of solid. The amine-modified aluminum oxide nanoparticles then were reacted with N-acetylhomocysteine thiolactone at pH 10 to place a reactive thiol on the nanoparticles. A bromoacetylated C4 peptomer, modified at the epsilon-amines of lysine residues, then was reacted with the thiolated nanoparticles to give the peptomer covalently linked to aluminum oxide via a thioether bond. The peptomer load was determined to be 16 mg of peptomer/g of particles, a 55% theoretical yield. Particle shape and size of the peptomer-conjugated alumina were analyzed by electron microscopy and displayed a mean maximum diameter of 355 nm and a mean minimum diameter of 113 nm, well within the desired size range of 300 nm believed to be optimal for mucosal immunization purposes. Experimentally determined values of mean particle diameters, specific surface area, and specific peptomer load provided the information necessary to calculate the mean antigen load, which was determined to be 53000 +/- 42000 peptomer epitopes per particle. Peptomer-alumina conjugates, such as that described here, could form the basis of a new class of biomaterial that combines a chemically defined organic immunogen with a nontoxic chemically defined inorganic adjuvant.

AIDS Vaccines↗