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Biomedical subjects

G S Ray

Publications and source records attributed to G S Ray.

16 recordsLinked to original sources
PubMed1997

Inhibition of parietal cell acid secretion is mediated by the classical epidermal growth factor receptor.

Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) inhibit gastric acid secretion both in vivo and in vitro. Previous studies have indicated that EGF and TGF-alpha bind to the same EGF/TGF-alpha receptor. Nevertheless, we and others have previously demonstrated that inhibition of acid secretion by these growth factors requires concentrations of the peptides that are 10-fold higher than those necessary for induction of mitogenesis. Therefore, we have sought to investigate whether gastric parietal cells may possess a second EGF/TGF-alpha receptor class. Two systems were studied: First, [125I]TGF-alpha was cross-linked to the receptor in isolated rabbit parietal cell membranes, and labeled species were resolved on SDS-PAGE. Second, acid secretion was evaluated in pylorus-ligated waved-2 mutant mice, which carry a disabling point mutation in their classical EGF/TGF-alpha receptor. In isolated parietal cells, [125I]TGF-alpha was cross-linked into a single species of 170 kDa. Cross-linking was inhibited in the presence of unlabeled TGF-alpha with an IC50 of 80 nM. In the pylorus-ligated mice, control littermate mice demonstrated a dose-dependent inhibition of acid secretion by EGF with an IC50 of 20 micrograms/kg. In contrast, EGF had no inhibitory effect on acid secretion in waved-2 mice at concentrations up to 100 micrograms/kg. No alterations in parietal cell or gastrin cell numbers were observed. These results in both isolated rabbit parietal cells and waved-2 mice support the existence of only a single class of EGF/TGF-alpha receptors in parietal cells. Differences in growth factor affinity are likely due to the modification of the receptor or one of its coordinate regulators.

Animals↗
PubMed1997

Increased immunoreactivity for Rab11, a small GTP-binding protein, in low-grade dysplastic Barrett's epithelia.

Adenocarcinoma of the esophagus develops from metaplastic Barrett's columnar epithelia through the evolution of dysplastic epithelial intermediates. Although the role of dysplasia leading to adenocarcinoma is well established, far less is known regarding the cellular changes involved in this process. Because the development of dysplasia is characterized by the loss of apical secretory specializations, we hypothesized that changes in apical trafficking might be involved in the dysplastic process. We have sought to evaluate the expression of an important candidate regulator of apical trafficking, the small GTP-binding protein, Rab11, in resection and biopsy tissue from patients with Barrett's esophagus. Sections from esophageal resection specimens from 4 patients and endoscopic biopsies from 60 patients were stained with antibodies against Rab11 and Rab25 as well as protein markers of the Golgi apparatus and p53 protein. Rab11 staining in low-grade dysplastic regions was similar to that observed with monoclonal antibodies against Rab25 and gamma-adaptin and colocalized with staining for the Golgi marker, the mannose-6-phosphate receptor. In the esophageal adenocarcinoma resections, prominent Rab11 immunostaining was observed in the supranuclear region of low-grade dysplastic cells. In contrast, regions of high-grade dysplasia demonstrating strong nuclear p53 staining showed only diffuse or absent Rab11 staining. In endoscopic biopsies, 91% of biopsies that were read unanimously as low-grade dysplasia demonstrated supranuclear Rab11 staining. Fourteen percent of biopsies unanimously graded as being without dysplasia demonstrated perinuclear Rab11 staining. No p53 immunostaining was observed in any of the low-grade dysplasia biopsy specimens. An increase in Rab11 immunoreactivity seems to correlate with low-grade dysplasia, whereas p53 immunostaining correlates with high-grade dysplasia. The colocalization of Rab11 staining with increased immunoreactivity for markers of the trans-Golgi system is consistent with a defect in apical trafficking due to an expansion of either the trans-Golgi compartment or the apical recycling vesicle system.

Barrett Esophagus↗
PubMed1996

A somatodendritic distribution of Rab11 in rabbit brain neurons.

Comparisons of subcellular targeting in neurons and epithelial cells have led to suggestions that apical epithelial antigens localize to axons and nerve terminals. We have studied the distribution in brain of the small GTP-binding protein, Rab11, which is localized to apical vesicular populations in epithelial cells. Sections of rabbit brain were examined by immunohistochemistry using a monoclonal antibody against rabbit Rab11. Rab11 immunoreactivity was present exclusively in neurons. In all regions examined, including forebrain, cerebellum, thalamus and brainstem, Rab11 immunoreactivity was observed in cell bodies and dendrites. No staining was observed in hippocampal neurons. These results indicate that the distribution of Rab11 does not support previous suggestions that apical epithelial markers should localize to axons and synaptic endings.

Animals↗
PubMed1996

Foveolar hyperplasia following partial gastrectomy results from expansion of surface mucous cell compartment.

Antrectomy with gastroenterostomy reconstruction is often associated with the development of foveolar hyperplasia and oxyntic atrophy. While a role for bile reflux in the etiology of foveolar hyperplasia is well established, the identity of the mucous cell lineages responsible for this condition have not been well characterized. We have studied three patients who demonstrated foveolar hyperplasia in their gastric remnant following antrectomy and gastroenterostomy. Mucosal samples were stained with antibodies against the trefoil peptides pS2 and hSP, to identify surface mucous and mucous neck cell lineages, respectively. Postoperative biopsies from all three patients showed oxyntic atrophy as documented by staining of parietal cells with antibodies against H/K-ATPase. All three patients demonstrated an exclusive expansion of pS2 immunoreactive mucous cells. The hSP staining cells were located deep in the expanded foveolar region. The results suggest that foveolar hyperplasia following antrectomy with gastroenterostomy results from a reactive hyperplasia of surface mucous cells. This pattern of surface cell hyperplasia is more consistent with a reactive expansion of mucous cells than with a response to chronic injury.

Adult↗
PubMed1996

Overexpression of transforming growth factor-alpha alters differentiation of gastric cell lineages.

Overexpression of transforming growth factor-alpha (TGF-alpha) in the gastric fundic mucosa of metallothionein promoter/enhancer-TGF-alpha(MT-TGF-alpha) transgenic mice produces a phenotype of foveolar hyperplasia similar to that observed in Ménétrier's disease. We have investigated the dynamics involved in the alterations of gastric mucosal morphology in the MT-TGF-alpha mouse model. The fundic mucosa of MT-TGF-alpha mice and nontransgenic littermates was evaluated in animals treated with cadmium sulfate. To mark the mucosal proliferative zone, 8-bromodeoxyuridine (BrdU) was administered 2 hr prior to killing. Gastric mucosa was examined by diastase-resistant, periodic acid-Schiff-positive (DR-PAS) staining and immunohistochemistry for H/K-ATPase an BrdU. MT-TGF-alpha mice demonstrated increased numbers of DR-PAS-staining mucous cells and lower parietal cell numbers per gland unit. While the proliferative zone in nontransgenic mice was located in the upper half of the gland, the zone in MT-TGF-alpha mice was located in the basal region. Overexpression of TGF-alpha in MT-TGF-alpha mice leads to an alteration in the development of mucosal lineages from the fundic progenitor zone, which is biased towards the predominant differentiation of foveolar mucous cells.

Animals↗
PubMed1996

Expression of trefoil peptides in the gastric mucosa of transgenic mice overexpressing transforming growth factor-alpha.

Overexpression of transforming growth factor-alpha (TGF-alpha) in the gastric mucosa of metallothionein-TGF alpha (MT-TGF alpha) transgenic mice leads to a marked alteration in the ontogeny of the fundic cellular lineages. Induction of the transgene leads to the over-production of mucous cells with a concomitant diminution in the development of parietal cell and chief cell lineages. We have sought to define more precisely the mucous cell lineages involved in the mucous cell hyperplasia in MT-TGF alpha mice by investigating the expression of trefoil peptides in MT-TGF alpha mice. MT-TGF alpha mice and their non-transgenic littermates were treated with cadmium sulfate beginning at 13 days of age. Animals were then sacrificed at intervals over the following 2 weeks and gastric mucosa was examined for expression of trefoil peptides and TGF alpha by immunohistochemistry and in situ hybridization. No TGF alpha mRNA expression could be demonstrated by in situ hybridization in non-transgenic mice. In MT-TGF alpha mice, in situ grains for TGF alpha mRNA were detected at the base of fundic glands in 13 day old animals, whereas the expression was observed more widely in the mucosa of older animals (28 days). TGF alpha immunoreactivity was observed in foveolar mucous cells and residual parietal cells in MT-TGF alpha mice at all ages. By in situ hybridization, pS2 mRNA was detected in the surface mucous cells in normal gastric mucosa. In MT-TGF alpha mice, pS2 mRNA was found throughout the expanded foveolar region. By in situ hybridization, spasmolytic peptide (SP) expression was observed in the region of the progenitor zone in both groups of mice. By immunohistochemistry, SP expression was noted in a broad band of mucous neck cells deep to the progenitor zone. No gastric expression of intestinal trefoil factor (ITF) was noted in either group of mice. The results demonstrate that the expansion of the foveolar mucous cell compartment in MT-TGF alpha mice is due to the hyperplasia of normal surface cells expressing their particular mucin-associated trefoil peptide, pS2.

Animals↗
PubMed1982

Source of subretinal fluid on the basis of ascorbate analyses.

Biochemical analyses of subretinal fluid revealed a consistently high ascorbate level in the subretinal fluid of patients with rhegmatogenous retinal detachment. The average values and SDs of ascorbate in anterior chamber aqueous humor, subretinal fluid, and blood were 14.7 +/- 1.8, 27.4 +/- 2.1, and 1.8 +/- 0.2 mg/dL, respectively. The ascorbate concentration in subretinal fluid was always higher than that in aqueous humor. The high ascorbate level in subretinal fluid led to the hypothesis that aqueous humor contributes to the formation of subretinal fluid. Presumably and constant absorption of subretinal fluid by the choroid directs a portion of the aqueous humor from the posterior chamber into the subretinal space. The posterior movement of aqueous humor causes reduced ascorbate concentration in the anterior chamber and relative hypotony of eyes with rhegmatogenous retinal detachment. Closing the retinal break results in an interruption of the posterior movement of aqueous humor and rapid absorption of the remaining subretinal fluid by the choroid.

Aqueous Humor↗
PubMed1980

Lipoproteins in human subretinal fluids.

The lipids in the subretinal fluid of rhegmatogenous retinal detachment are observed mainly in the albumin position following electrophoresis on agarose film. The lipoprotein in the subchoroidal fluid of the same eye is alpha-lipoprotein. The albumin-like lipoprotein in subretinal fluid has no reaction with the antiserum samples specific to alpha-lipoprotein and beta-lipoprotein. Instead, an apoprotein of serum alpha-lipoprotein with slow electrophoretic mobility was observed in subretinal fluid. Heterogeneous degradation products of serum lipoproteins were seen in the subretinal fluid of exudative retinitis, different from the subretinal fluid of rhegmatogenous retinal detachment and uveal effusion.

Apoproteins↗
PubMed1976

Electron microscopy study of cryogenic chorioretinal adhesions.

By electron microscopy, the cryogenic chorioretinal adhesions in eight-day-old lesions from human eyes lacked anatomic adhesion between retina and choroid. In eight-month-old lesions, the neurosensory retina adhered to the retinal pigemtn epithelial layer by both desmosomal attachments and villous interdigitation.

Aged↗
PubMed1975

Gelatin implants in scleral buckling procedures.

The use of gelatin has been evaluated in a series of 59 retinal surgical procedures over a five-year period. When used as a "trapdoor" alone, we conclude that gelatin works as well as any of the currently employed materials for simple cases. The technique gave a 90% primary reattachment rate, which was increased to 100% reattachment by subsequent surgery or photocoagulation. It also gave a desirable absorbable feature in very anterior or very posterior lesions. Used as a meridional implant and combined with one or two layers of solid silicone, the gelatin has proved to be extremely useful in closing holes that were highly elevated or significantly "fish mouthing." We wish to emphasize the value of this use as a meridional implant combined with silicone in complex cases.

Chemical Phenomena↗
PubMed1975

Subretinal fluids: lipid analyses.

Lipid was found to accumulate in the subretinal space during rhegnatogenous retinal detachment. The concentration of lipid in the subretinal fluid varied between 0.1 to 2.4 mg. per milliliter. Based upon a comparison of lipid profiles and lipoprotein profiles, the amount of lipid observed in the subretinal fluids was not directly related to the permeability of the ocular vessels. Thin-layer chromatography analyses of lipid in subretinal fluids showed differences between the lipid composition of the subretinal fluid and blood. The major characteristic of lipid composition of subretinal fluid is the low concentration of lecithin, which is the major lipid compound in the serum. The present data indicate that the lipids of ocular tissues are released into the subretinal space during rhegmatogenous retinal detachment, and are adsorbed on albumin.

Adsorption↗