Biomedical subjects

A Tarnawski

Publications and source records attributed to A Tarnawski.

At least 19 recordsLinked to original sources

PubMed1992

Increased expression of epidermal growth factor receptor during gastric ulcer healing in rats.

Expression of epidermal growth factor receptor (EGFR) was studied immunohistochemically in rat gastric mucosa during healing of acetic acid-induced ulcers. In normal control gastric oxyntic mucosa, EGFR was expressed in proliferative zone cells and in some parietal cells. In mucosa of the ulcer margin, at 3, 7, and 16 days after ulcer induction, there was a 75-fold increase (over controls) in the number of cells expressing EGFR. Seventy percent of ulcers healed by the 16th day, and all were healed by the 25th day. The mucosal scar that replaced the ulcer was composed of dilated glands lined with poorly or aberrantly differentiated cells showing persistence of increased EGFR expression. An increased EGFR expression indicates an important role of EGF in ulcer healing and scar formation.

Analysis of Variance↗

PubMed1992

Prostaglandin but not cimetidine reduces spontaneous degeneration of isolated gastric gland cells.

We studied the effect of either placebo, 16,16-dimethyl-prostaglandin E2 (16,16-dimethyl-PGE2), or cimetidine on spontaneous degeneration of isolated rat gastric glands maintained in vitro in a basic oxygenated medium for 24 h. We assessed the viability of gland cells with fast green exclusion, measured release of lactate dehydrogenase (LDH) into the medium, and assessed the cell ultrastructure using a scanning electron microscope. Gastric glands incubated in medium for 6, 12, and 24 h underwent spontaneous degeneration reflected by a decrease in cell viability, increase in LDH release into the medium, and ultrastructural cell damage. 16,16-Dimethyl-PGE2 either at 0.1, 1, or 10 micrograms/ml significantly reduced the decrease in cell viability, increasing cell survival; reduced LDH release into the medium; and ultrastructural damage. Incubation with cimetidine at 1 or 10 micrograms/ml did not affect cell viability at 6, 12, or 24 h, whereas 100 micrograms/ml reduced cell viability (vs. placebo) at 12 and 24 h. LDH release and ultrastructural damage were not affected (not reduced) by cimetidine. Our study indicates that 16,16-dimethyl-PGE2, but not cimetidine, directly protects isolated gastric gland cells against degeneration in vitro, under conditions independent of systemic, neural, and hormonal factors.

Animals↗

PubMed1992

Adaptation of gastric mucosa to chronic alcohol administration is associated with increased mucosal expression of growth factors and their receptor.

In our previous study we found that chronic, intragastric administration of ethanol to rats produces adaptation of the gastric mucosa to subsequent challenge with an acute dose of 50% ethanol. The mechanism of this mucosal tolerance remains unexplained. Epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) stimulate cells growth and proliferation in the gastric mucosa with noted trophic effect, protect the gastric mucosa against acute injury and accelerate healing of injured mucosa. Many of these effects are exerted through EGF and TGF alpha action on their common receptor (EGFR). The aim of the present study was to determine the effect of chronic alcohol administration on cell proliferation and gastric mucosal expression and distribution of EGF, TGF alpha and EGFR. Chronic administration of ethanol (1 ml, 50% ethanol, twice daily) significantly increased the extent of gastric mucosal mucous and proliferative cell zones, the number of proliferating (DNA synthesizing) cells and mucosal expression of EGF, TGF alpha and EGFR by 13, 6, and 20-fold, respectively. Thus, adaptation of gastric mucosa to chronic alcohol administration is associated with increased cell proliferation and increased expression of mucosal EGF, TGF alpha and EGFR.

Adaptation, Physiological↗

PubMed1992

Direct protective action of epidermal growth factor on isolated gastric mucosal surface epithelial cells.

Epidermal growth factor (EGF) protects gastric mucosa against acute injury produced by a variety of damaging agents, but the mechanism of its protective action is not clear. Since the surface epithelial cells (SEC) are important component of gastric mucosal defence, we studied whether EGF may directly protect isolated gastric SEC against ethanol injury in vitro, in condition independent of systemic factors and whether endogenous prostaglandins may play a role in EGF's protective action. The isolated SEC from rat gastric mucosa were preincubated in medium only, or medium containing 0.0001-10.0 micrograms/ml of h-rEGF for 15 minutes, and incubated with 8% ethanol for 1 hour. In another study the above experiment was repeated but cells were pretreated with 10(-4) or 10(-5) M indomethacin before EGF treatment. The cell viability was assessed by fast green exclusion test. Incubation of SEC with 8% ethanol significantly reduced SEC cell viability to 50 +/- 2%: EGF 0.1 or 1.0 microgram/ml significantly reduced ethanol induced damage (cell viability 59 +/- 3 and 62 +/- 3% respectively). Pretreatment with 10(-4) M indomethacin (the dose which does not affect SEC viability but inhibit PGE2 and PGI2 generation), significantly reduced protective action of EGF against 8% ethanol injury. EGF 1.0 and 10.0 micrograms/ml alone without ethanol increased PGE2 and 6 keto PGF1 alpha generation by SEC. These studies demonstrated: 1) EGF is able to protect gastric surface epithelial cells directly without mediation by systemic factors. 2) EGF induced protection of SEC may in part be mediated by prostaglandins.

6-Ketoprostaglandin F1 alpha↗

PubMed1992

[Secondary prevention of colon cancer].

Each year more than 6000 patients in Poland die from cancer of the colon. Morbidity due to colonic cancer increases rapidly in our country. From 1973 to 1982 there was a three-fold increase in the morbidity due to colonic cancer as compared to the years 1952-1955. Five-year relative survival in the same periods did not improve, either being 28% in men and 27% in women. To compare, in the USA with high morbidity rates due to colonic cancer where each year there are 145,000 new cases of cancer, 5-year relative survival is 42% for men and 54% for women. This raises a question whether our strategy of treatment of colonic cancer is correct. This question is even more justified now when secondary prevention of colonic cancer is of practical value. Total mortality due to colonic cancer is 60%. However, diagnosis and treatment of early forms of colonic cancer reduces mortality to 20% and below. Therefore, effective management colonic cancer should include not only the so-called primary prevention (interfering with etiological factors for instance through high fibers diet) but also secondary prevention through monitoring of precancerous changes in the colon, removal of potentially malignant lesions and early forms of colonic cancer [19]. Secondary prevention interfering with the pathogenesis of colonic cancer is the subject of the present paper. We would like to emphasize the need for a better management program for colonic cancer, especially that the data concerning colonic cancer in Poland may be underestimated due to diagnostic neglect and faulty cancer register.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Immunolocalization of epidermal growth factor (EGF) in human salivary glands detected with the new monoclonal antibody.

Epidermal growth factor (EGF) is biologically active peptide commonly seen in many human tissues and organs. Its high concentration has been found in the salivary glands. The purpose of the present study was to determine EGF immunolocalization in normal human major salivary glands using a new monoclonal antibody anti-EGF. The results were compared with EGF location determined by using two human antibodies (Oncogene, USA and ICI from dr Gregory, UK). Immunohistochemical studies were performed by the PAP method. All antibodies demonstrated EGF expression in the efferent pathways of the salivary glands, especially in their proximal segments.

Antibodies, Monoclonal↗

PubMed1992

Epidermal growth factor (EGF) expression in human salivary glands. An immunohistochemical study.

Epidermal growth factor (EGF) is a biologically active peptide involved in differentiation, growth, regeneration and repair of human and animal tissues. Quantitative biochemical studies showed in man the highest concentration of EGF in the parotid gland. The aim of the present study was to define EGF immunolocalization in the individual segments of the human major salivary glands (salivon). The material consisted of sections obtained from the surgically removed salivary glands: parotid, submaxillary and sublingual. Immunohistochemical studies were performed by PAP method using monoclonal antibody against human epidermal growth factor. EGF expression was found almost exclusively in the efferent pathways of the salivary glands, mostly in the intercalated ducts and Pflüger salivary tubules. These segments of the salivon are most developed in the parotid gland in which the staining was stronger than in other salivary glands.

Epidermal Growth Factor↗

PubMed1992

Epidermal growth factor protects portal hypertensive gastric mucosa in ischemia/reperfusion: the role of capillary endothelia and prostaglandins.

BACKGROUND: Epidermal growth factor (EGF) protects gastric mucosa against a variety of injurious agents, but the mechanism is unclear. Because the abnormal microvasculature of portal hypertensive (PHT) gastric mucosa is a major target of ischemia/reperfusion (I/R) injury, we used this model to assess EGF's protective role at the microvascular level. METHODS: Rats with PHT (staged portal vein ligation) received either EGF, 20 micrograms/kg, or saline solution intravenously, with or without indomethacin pretreatment (20 mg/kg subcutaneously). I/R was produced by withdrawing blood to systemic pressures of 30 mm Hg for 20 minutes and reinfusing it. Stomachs were excised 20 minutes later and evaluated for gross and histologic necrosis, microvascular permeability, mucosal ultrastructure and vimentin, and cyclooxygenase immunofluorescence. RESULTS: In saline-treated rats, gross and histologic damage involved 46% +/- 3% of glandular mucosa and 23% +/- 3% of mucosal sections, respectively. Microvascular permeability was increased 43-fold over that of normal control rats. Vimentin immunofluorescence intensity was reduced to 36% +/- 4% that of normal control rats. EGF pretreatment reduced histologic necrosis to 2% +/- 1% (p less than 0.01). Microvascular permeability and vimentin intensity were almost normalized. Indomethacin partially reversed the mucosal protection induced by EGF. CONCLUSIONS: EGF significantly reduces I/R injury to PHT gastric mucosa. Microvascular endothelia of PHT gastric mucosa are the major target of I/R injury and the site of EGF's protective action. Prostaglandins in part mediate EGF's protective action.

Animals↗

PubMed1991

Gastric injury and invasion of parietal cells by spiral bacteria in rhesus monkeys. Are gastritis and hyperchlorhydria infectious diseases?

The possibility of using the rhesus monkey as a model for studying gastric function in the presence of infection with spiral bacteria was studied. Endoscopic evaluation of the gastric mucosa was performed under general anesthesia in 29 colony-bred rhesus monkeys, and gastric pinch biopsy specimens were obtained from each animal. On a separate day, gastric emptying and acid output were determined using a 99mTc dilution technique. Biopsy samples were fixed for light microscopy (H&E, Gram, and Warthin-Starry stains) and for transmission electron microscopy. The presence of spiral bacteria and gastritis was assessed and rated on coded slides. In 8 of 29 monkeys, Helicobacter pylori-like organisms were observed in close proximity to the mucosal epithelial cells or in the lumen of the gastric pits. In 14 other monkeys, "Gastrospirillum hominis"-like organisms were observed in the mucus covering the surface of epithelial cells, in the lumina of the gastric glands, and overlying parietal cells. Gastritis was present in 8 of 8 animals positive for H. pylori-like organisms, in 2 of 14 animals positive for "G. hominis"-like organisms, and in none of the uninfected monkeys, and the mean gastritis index was significantly greater in animals positive for H. pylori-like organisms. Moreover, acid output was significantly higher in monkeys positive for "G. hominis"-like organisms than in controls or animals positive for H. pylori-like organisms. Gastric emptying was not significantly different in the three groups. In conclusion, (a) H. pylori-like, but not "G. hominis"-like, organisms cause gastritis while not modifying acid output; (b) "G. hominis"-like, but not H. pylori-like organisms, invade and on occasion damage parietal cells while apparently causing hyperchlorhydria; and (c) the rhesus monkey appears to be a good model for the study of gastric infection with spiral bacteria.

Analysis of Variance↗

PubMed1991

Calcium channel blockers and prostaglandin generation by gastric surface epithelial cells.

We investigated the effects of calcium channel blockers on generation of prostaglandin (PG) E2 and 6-keto PGF1 alpha by gastric mucosal surface epithelium. Surface epithelial cells (SEC) isolated from rat gastric mucosa were incubated with either verapamil (1 or 10 micrograms/ml), diltiazem (2.5 or 25 micrograms/ml) or nifedipine (2.5 or 25 micrograms/ml) for 30 min at 37 degrees C in calcium containing or calcium-free medium. Verapamil (both doses) significantly increased PGE2 and 6-keto PGF1 alpha generation by the surface epithelial cells but only in calcium containing medium. Diltiazem did not affect PG generation in calcium containing nor calcium-free medium. Nifedipine 25 micrograms/ml decreased PGE2 but increased 6-keto PGF1 alpha generation. The inhibitory effect of nifedipine on PGE2 generation was abolished in calcium-free medium, while the calmodulin antagonist did not affect verapamil-induced increase in PG generation.

6-Ketoprostaglandin F1 alpha↗

PubMed1991

Increased susceptibility of the portal hypertensive gastric mucosa to damage.

Portal hypertensive gastropathy has recently been recognized as a unique entity distinct from other gastropathies involving the normotensive gastric mucosa. To delineate the pathophysiology of this disorder, we developed a rat model of portal hypertension using two-staged portal vein ligation. In this model, features of the portal hypertensive mucosa include increased luminal hydrogen ion loss, reduced electronegativity of potential difference, and increased submucosal edema. Ultrastructurally, the portal hypertensive gastric mucosa has marked endothelial hypertrophy of capillaries resulting in prominent compromise of microvascular lumina. Combined with the submucosal edema, the microvasculopathy results in reduced oxygenation of the surface gastric mucosa. This is associated with diminished prostaglandin production, which impairs gastric mucosal protection in portal hypertension. These observations are strengthened by experiments that demonstrated significantly increased gastric mucosal damage by alcohol, bile acids, aspirin, and shock/reperfusion in portal hypertensive rats compared to normotensive sham-operated controls. Many of our experimental findings have been confirmed clinically; however, much more research in this area is clearly needed.

Animals↗

PubMed1991

Quality of gastric ulcer healing: a new, emerging concept.

Assessment of gastric ulcer healing is usually based on a visual examination (by endoscopy in patients, or the evaluation of ulcer size in experimental studies), and not on histologic and ultrastructural assessment of subepithelial mucosal healing. This approach has led to the assumption that the mucosa of grossly "healed" gastric and/or duodenal ulcers returns to normal, either spontaneously or following treatment. However, the re-epithelialized mucosa of grossly "healed" experimental gastric ulcer has recently been found to have prominent histologic and ultrastructural abnormalities, including reduced height, marked dilation of gastric glands, poor differentiation and/or degenerative changes in glandular cells, increased connective tissue, and disorganized microvascular network. It has been postulated that these residual abnormalities might interfere with mucosal defense and may be the basis of ulcer recurrence. In the present article, the ulcer healing process and the role of luminal factors, transitional zone at the ulcer margin, and granulation tissue are discussed. The healing of an ulcer is accomplished by filling of the mucosal defect with epithelial cells and connective tissue to reconstruct mucosal architecture. Under influence of growth factors [predominantly epidermal growth factor (EGF) and transforming growth factor (TGF alpha)], the epithelial cells at the ulcer margin dedifferentiate and proliferate, supplying cells for re-epithelialization of the mucosal scar surface and reconstruction of glandular structures. Granulation tissue at the ulcer base supplies connective tissue cells to restore the lamina propria and endothelial cells and microvessels for mucosal microvasculature reconstruction. The final outcome of healing reflects a dynamic interaction between an "epithelial" component from the ulcer margin and a connective tissue component including microvessels originating from granulation tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Is there a role for dietary essential fatty acids in gastroduodenal mucosal protection?

A great deal is known about methods to diminish intragastric acid concentration, but far less is known about the ability of the gastroduodenal mucosa to resist injury or accelerate its healing. One group of compounds that plays a key role in the endogenous ability of the mucosa to protect itself against injury and perhaps to accelerate healing is the prostaglandins (PGs). The gastroduodenal mucosa synthesizes PGs from fatty acids precursors--predominantly linoleic and arachidonic. PGE1 or PGE2 have been shown to possess cytoprotective activity in the stomach and duodenum. In laboratory animals, linoleic acid feeding increased PG synthesis and diminished injury. When presented in a detergent solubilized form, arachidonic acid can also provide acute protection against injury by alcohol, bile acids, and aspirin. Arachidonic acid can also promote angiogenic response and thereby, perhaps, accelerate the healing process. Epidemiological evidence points toward a parallel between the decrease in peptic ulcer disease virulence and incidence and the total ingestion of linoleic acid by the population in the U.S. and the United Kingdom. Therefore, dietary essential fatty acids may play a key role in mucosal defense and restitution, and perhaps in the diminished incidence and virulence of peptic ulcer disease in the Western world.

Animals↗

PubMed1991

Expression of epidermal growth factor receptor in rat gastric oxyntic mucosa.

Epidermal growth factor (EGF) is a mitogenic polypeptide that inhibits gastric acid secretion, protects the gastric mucosa against acute injury, and accelerates ulcer healing. In the present study we demonstrated immunohistochemically, using two different techniques, localization of EGF receptors in normal rat gastric oxyntic mucosa: in proliferative zone cells and in some parietal cells. It is likely that these cells represent the major targets for the EGF [and transforming growth factor alpha (TGF-alpha) which shares a common receptor with EGF] actions, stimulating cell proliferation and inhibiting acid secretion.

Animals↗

PubMed1991

Quality of gastric ulcer healing: histological and ultrastructural assessment.

It has long been assumed that the mucosa in areas of grossly 'healed' gastric or duodenal ulcers returns to normal, either spontaneously or after treatment. This assumption is based almost entirely upon visual, superficial examination by endoscopy. Few, if any, histological and ultrastructural studies examined the deeper mucosa in the areas of grossly healed ulcers. In several experimental studies, we analysed the development, evolution, and healing of acetic acid-induced gastric ulcers in rats and assessed the histological and ultrastructural features (structure and cellular composition) of the gastric mucosa in areas of grossly healed ulcers. The gastric mucosa of grossly 'healed' ulcers showed re-epithelialization of the mucosal surface at every study interval (2 weeks, 2, 3, and 4 months), but the subepithelial mucosa displayed prominent abnormalities. Two patterns of scarring were distinguished: (a) the mucosa in the area of healed ulcer was thinner (25-45% thinner than normal mucosa) with increased connective tissue and poor differentiation and/or degenerative changes in the glandular cells; and (b) the mucosa displayed a marked dilation of gastric glands with poor differentiation of the glandular cells and a reduction in the supportive microvascular network. It is theorized that these abnormalities could interfere with oxygenation, nutrient supply, and mucosal resistance and defence; therefore, they could be a basis for ulcer recurrence. These observations indicate that the quality of mucosal structural restoration rather than the speed of ulcer healing is the most important factor in determining risk of ulcer recurrence. The clinical relevance of these findings is supported by a preliminary study in which marked histological abnormalities were found in the subepithelial mucosa in patients with 'healed' duodenal ulcers.

Animals↗

PubMed1990

16,16-Dimethyl prostaglandin E2 induces villus contraction in rats without affecting intestinal restitution.

In a previous study we found that 16,16-dimethyl prostaglandin E2 protects the small intestine against chenodeoxycholic acid injury in the rat. One possible explanation for prostaglandin's protective action may be that prostaglandin-induced villus contraction accelerates mucosal restitution. This hypothesis was tested in rats by perfusing intestinal segments in vivo in a single-pass fashion with 0.125-0.5 micrograms/L of 16,16-dimethyl prostaglandin E2. These studies showed a dose-dependent, reversible contraction of intestinal villi and crypts. To test the effect of this contraction on mucosal restitution, standardized intestinal injury was produced in indomethacin-pretreated rats perfused in vivo with 5 mmol/L chenodeoxycholic acid. The rats were then perfused with bile acid-free buffer containing either 0.5 microgram/mL of 16,16-dimethyl prostaglandin E2 or vehicle. This study showed that despite decreasing villus height after bile acid injury, 16,16-dimethyl prostaglandin E2 did not significantly affect the rate of morphologic (assessed by villus denudation) or functional (assessed by mannitol and water absorption) restitution of the injured intestinal mucosa. Thus, although 16,16-dimethyl prostaglandin E2 causes villus contraction, this effect does not result in more rapid restitution of the injured intestinal mucosa and is not a likely mechanism for prostaglandin-mediated protection of the intestinal mucosa.

16,16-Dimethylprostaglandin E2↗

PubMed1990

Portal hypertension predisposes the gastric mucosa to hemorrhagic shock/reperfusion injury.

We have previously demonstrated that the portal hypertensive (PHT) gastric mucosa has unique functional and morphologic features which predispose it to increased damage by noxious agents such as aspirin or alcohol. In this study we examine the PHT gastric mucosa following hemorrhagic shock and reperfusion. Portal hypertension was produced in 12 rats using staged portal vein occlusion, and seven animals (controls) underwent sham procedures. All rats received 2 ml 0.1 N HCl intragastrically. Shock was then induced by withdrawing blood to reduce systemic arterial pressures to approximately 30 mm Hg for 20 min. Blood was then reinfused and stomachs were excised 20 min later for gross and microscopic quantitation of injury. We found that gross damage to gastric glandular mucosa was more than doubled in PHT rats over sham-operated controls. In PHT gastric mucosa, deep histologic necrosis involved 22.5 +/- 3.8% of mucosal section lengths compared with 6.9 +/- 2.0% in control mucosa (P less than 0.005). Histologically, mucosal injury patterns were predominantly ischemic, with deep necrosis and disintegration of glands and microvessels, all prominently more extensive in PHT mucosa. We conclude that PHT gastric mucosa has significantly increased susceptibility to damage following hemorrhagic shock/reperfusion compared with portal normotensive mucosa. Since hemorrhagic shock is a frequent complication of portal hypertension, this study suggests clinical investigations of gastric mucosal function and pathophysiology in PHT patients following hemorrhage and resuscitation.

Animals↗

PubMed1990

Impaired generation of prostaglandins from isolated gastric surface epithelial cells in portal hypertensive rats.

We studied generation of prostaglandins E2 and 6-keto F1a by surface epithelial cell isolated from the gastric mucosa of portal hypertensive and sham-operated rats. Oxygenated cell suspensions containing 80 +/- 3% of surface epithelial cells were incubated for 30 min at 37 degrees C and the concentration of prostaglandin E2 and 6-keto-prostaglandin F1a in medium was measured by radioimmunoassay. Viability of the cells was assessed with Fast green exclusion at baseline and after 30-min and 60-min incubation. Within 30 minutes the surface epithelial cells obtained from portal hypertensive rats generated 22.0 +/- 1.6 (mean +/- SE) pg prostaglandin E2 and 40.7 +/- 4.7 pg 6-keto prostaglandin F1a, per 10(6) cells. These were significantly less than prostaglandin generation by cells obtained from sham-operated rats. The viability of the surface epithelial cells from portal hypertensive rats was also significantly reduced compared with sham-operated rats after 60 minute incubation. Reduced ability of the surface epithelial cells to generate prostaglandins may be one mechanism for increased susceptibility of portal hypertensive gastric mucosa to injury by noxious agents.

6-Ketoprostaglandin F1 alpha↗