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H F Helander

Publications and source records attributed to H F Helander.

At least 55 records · Page 3Linked to original sources
PubMed1988

Thioredoxin and thioredoxin reductase show function-related changes in the gastric mucosa: immunohistochemical evidence.

Low levels of thioredoxin and thioredoxin reductase immunoreactivity were demonstrated immunohistochemically in rat gastric epithelial cells. The intensity was influenced by feeding and fasting, the former resulting in diminished reactions. Acute vagotomy, which abolishes basal acid secretion, resulted in a strongly increased thioredoxin immunoreactivity in all gastric epithelial cells. Stimulation of vagotomized rats with pentagastrin and carbachol reduced the levels of thioredoxin and thioredoxin reductase. Atropine and omeprazole (in stimulated, vagotomized rats) completely inhibited acid secretion, but caused different effects on the thioredoxin levels of gastric cells. Atropine restored the thioredoxin immunoreactivity in most gastric epithelial cells to that of the unstimulated, vagotomized controls. Omeprazole, however, did not reverse the effects of stimulation, and, except in the parietal cells, weaker fluorescence was observed. Similar reaction patterns were seen for thioredoxin reductase, although at lower staining intensities. The results demonstrate that thioredoxin and thioredoxin reductase are expressed in resting cells, and to a lower extent in cells with ongoing secretion.

Animals↗
PubMed1988

Function and structure of parietal cells after H+-K+-ATPase blockade.

Omeprazole was administered to rabbits as a single dose or daily for 1 wk. H+-K+-ATPase and isolated gastric glands were prepared from the oxyntic corpus mucosa and used for functional and quantitative morphological studies. Both 10 and 100 mumol omeprazole/kg increased the pH of the gastric content when measured at death. The stimulated oxygen uptake and the rate of aminopyrine (AP) uptake were both inhibited in the isolated gastric gland preparations. Morphometric studies of biopsy specimens taken from the corpus mucosa and isolated gastric glands showed that omeprazole treatment increased the volume density of the acid compartments. This expansion provides an increased accumulation space for AP. Therefore, an increased AP uptake might be seen in glands isolated from omeprazole-treated animals. Blockade of the H2-receptor by ranitidine transformed the morphology of the cell into a more resting type and, furthermore, reduced the omeprazole-induced increase in the volume density of the acid compartments in the parietal cell. The H+-K+-ATPase activity measured in membrane fractions from the omeprazole-treated animals was decreased dose dependently and inhibited by 95% after 100 mumol omeprazole/kg. However, the concentration of the enzyme in these fractions did not change. These results indicate a specific inhibitory action of omeprazole on the H+-K+-ATPase.

Adenosine Triphosphatases↗
PubMed1986

Stereological investigations on human gastric mucosa: I. Normal oxyntic mucosa.

Quantitative morphological data on normal human oxyntic mucosa were obtained from endoscopic biopsies in ten healthy male volunteers. Corpus mucosa was biopsied in the resting state and during maximal acid secretion and then processed for light and electron microscopy. Stereological analyses were carried out on sections comprising the entire thickness of the epithelial layer. About one-third of the mucosal volume was taken up by lamina propria and 15% by parietal cells. Counts of cells that displayed their nucleus in the sections revealed that in average of 12% of the epithelial cells were parietal cells, 43% were mucous cells, 40% were zymogen cells, and 4% were endocrine cells. Parietal cells displaying two nuclei were twice as large as those with only one nucleus. Six percent of the parietal cell volume was taken up by the nucleus, and 33% of the cytoplasmic volume was occupied by mitochondria. Stimulation of acid secretion resulted in a 76% increase in the secretory surface density; simultaneously there was a slight decrease in the mean size of the parietal cells and an increase in the relative volume of the nucleus. During maximal stimulation of acid the parietal cells from the superficial mucosal layers displayed a 40% larger secretory surface than those from the deeper parts of the mucosa. The data, which will serve as a basis for studies of pathological mucosae, are compared with those obtained in other species.

Adult↗
PubMed1986

Oxyntic mucosa histology in omeprazole-treated patients suffering from duodenal ulcer or Zollinger-Ellison syndrome.

Endoscopic biopsies were taken from the oxyntic mucosa in patients with duodenal ulcer (DU) before and after 4 weeks of treatment with omeprazole. Biopsies were also obtained from Zollinger-Ellison (ZE) patients before and during treatment with omeprazole; these patients had previously failed to respond to other therapies aiming at reducing gastric acid secretion. Healthy volunteers served as controls. Light-microscopic studies of biopsy sections revealed superficial gastritis in most of the patients. Endocrine cell volume density (that is, the percentage of mucosal volume occupied by endocrine cells) was 0.3% in the DU patients and 0.7% in the ZE patients before omeprazole treatment. No significant change occurred during omeprazole treatment, which in the ZE patients continued for up to 21 months. In the controls, 0.3% of the mucosal volume was occupied by endocrine cells. Parietal cell volume density was about 15% in both the DU patients and in the controls; in the ZE patients, slightly but not significantly higher values were recorded. No significant change was observed during omeprazole treatment.

Adult↗
PubMed1986

Effects of omeprazole in duodenal ulcer patients.

The efficacy of and tolerance to omeprazole, 40 mg/day, was studied in an open-label study in 18 patients with endoscopically verified duodenal ulcers. The effects of the drug on the oxyntic mucosa and pentagastrin-stimulated acid secretion during and after treatment were also studied. Fifteen patients completed the final endoscopy. The ulcers were healed in all after 4 weeks' treatment. Both basal and peak acid output were significantly reduced during omeprazole treatment, whereas 4 weeks after the cessation of treatment neither basal nor peak acid output differed from the pretreatment levels. Fasting serum gastrin levels rose by 56% during treatment but had returned to pretreatment values when tested again 4 weeks after the end of the treatment period. Histological examination of the biopsy specimens taken before and after treatment showed that omeprazole had no significant effect on the volume densities of either parietal or endocrine cells. We conclude that omeprazole is of value in the treatment of duodenal ulcer and that the effects of the drug on acid output and serum gastrin levels are fully reversible.

Adult↗
PubMed1985

Trophic actions of E2 prostaglandins in the rat gastrointestinal mucosa. A quantitative morphologic study.

Adult, male Sprague-Dawley rats in groups of 10 received one of the following treatments orally twice daily for 3 wk: prostaglandin E2 (PGE2) 7.5 mg X kg-1, 15(R)-15-methyl prostaglandin E2 (MePGE2) at 0.2 or 2.0 mg X kg-1, or vehicle. After 18 h of fasting and 10-12 h after the last dose, the rats were anesthetized, and the gastrointestinal tract was fixed and processed for macroscopic and microscopic investigations. Trophic changes were more pronounced in the gastric antrum than in the gastric corpus or small intestine. The thickness of the antral mucosa was significantly increased by PGE2 and in a dose-related way by MePGE2. The mucosa of the gastric corpus became significantly thicker only with the higher dose of MePGE2. In all the prostaglandin-treated groups, the proportion of endocrine cells was reduced. Small--but sometimes significant--changes were registered in the proportions of the various exocrine cells. The parietal cells became significantly larger (+88%) in the rats treated with high doses of MePGE2. The secretory surface of the parietal cells was markedly increased by PGE2 and MePGE2. The enlargement of the secretory surface in animals treated with prostaglandins corresponded to a marked elevation of the basal gastric acid secretion and an increase in plasma gastrin levels. Hypergastrinemia can explain some, but not all, of the trophic changes observed in this study. Light microscopic examination of the duodenal and jejunal mucosa showed dose-related increases in villus heights and crypt lengths after treatment with MePGE2. Only the duodenal villus heights were increased by PGE2.

Animals↗
PubMed1985

Quantitative morphological methods in intestinal research.

Measurements of intestinal length suffer from considerable errors, because of variable degrees of contraction in the longitudinal muscles. In vitro organ bath techniques may solve these problems. Villi and microvilli amplify the internal surface area; measurements of the amplification factors should be based on stereological methods. Villus height and crypt length provide information on mucosal net growth; such data might be useful when studying hypertrophic and hypotrophic conditions. More precise knowledge on cell turn-over requires autoradiographic studies of 3H-thymidine incorporation into nuclei cell. Ultimately, stereological analyses of mucosal components and cell structures will supply detailed information needed for cell biological research.

Animals↗
PubMed1985

Localization of omeprazole and metabolites in the mouse.

Omeprazole is a substituted benzimidazole which blocks gastric acid secretion by inhibiting H+K+ATPase. Radioactive omeprazole was given intravenously or orally to mice, and the distribution of the drug was investigated at various intervals by scintillation counting and by autoradiography. The half-life for radioactivity in the stomach was 14 hours versus 30-36 hours in the liver, kidneys and blood. At 16 hours after the drug was given, the radioactivity in the stomach was ten times higher than that in the liver and kidneys, and 100 times that in the blood. Whole-body autoradiography showed sustained high levels of radioactivity only in the gastric mucosa. Light microscopic autoradiographic investigations of the gastric mucosa from mice killed 1 or 16 hours after the drug was given revealed radioactivity in the parietal cells. By electron microscopy of gastric mucosa from the mouse killed 16 hours after omeprazole injection the isotope label was found mainly over the secretory surface and the tubulo-vesicles. At these locations H+K+ATPase has previously been demonstrated, and it is suggested that omeprazole--or its metabolites--binds to this enzyme.

Animals↗
PubMed1984

Effect of omeprazole on gastric secretion in H+,K+-ATPase and in pepsinogen-rich cell fractions from rabbit gastric mucosa.

In order to study the effects of the substituted benzimidazole omeprazole on gastric secretory functions, parietal cells and chief cells from rabbit gastric mucosa were separated and enriched by density gradient centrifugation in Percoll. H+,K+-ATPase activity, as well as a 100,000 dalton protein, was found to copurify with a cell fraction morphologically characterized as mainly parietal cells (purity approximately 65%), while pepsinogen copurified with a cell fraction morphologically characterized as chief cells (purity approximately 90%). A spontaneous pepsinogen release (9.9 micrograms/mg cell dry wt X 2 hr), unaffected by both atropine and omeprazole, was found in the chief cell fraction. The release was approximately doubled by both carbacholine (4 X 10(-5)M) and dibutyryl cAMP (db-cAMP, 10(-3)M). The cholinergic stimulation was selectively blocked by atropine, while omeprazole had no effect on pepsinogen release induced by either of the secretagogues. On the other hand, omeprazole inhibited both db-cAMP- and histamine-stimulated acid secretion quantified as [14C]aminopyrine (AP) accumulation in the parietal cell fraction. Cimetidine counteracted only acid secretion induced by histamine. These findings indicate that omeprazole has a specific effect on acid secretion, and are consonant with the hypothesis that the effect is due to H+,K+-ATPase inhibition.

Adenosine Triphosphatases↗
PubMed1984

Surface ultrastructure of the small intestine mucosa in healthy children and adults: a scanning electron microscopic study with some methodological aspects.

Biopsy specimens of light microscopically (LM) normal small intestine mucosa from eight healthy, constitutionally short-statured children without signs of gastrointestinal disease and six healthy adults were studied by scanning electron microscopy (SEM) supplemented by transmission electron microscopy (TEM). The effects on surface morphology of various preparative procedures were also investigated, using small intestine mucosa from cats and rats. Fixation with OsO4--either alone, or following glutaraldehyde fixation--markedly changed the surface ultrastructure compared to that after glutaraldehyde fixation only. By low power SEM, some differences were observed in the appearance of the small gut mucosa between adults and young children. In adults and in children above 3 years of age, the villi were usually shaped like fingers or leaves, but in infants, ridge-shaped villi predominated. The villi showed, however, a smooth surface in both infants and adults, and medium and high power SEM displayed similar pictures, irrespective of age; here the typical structural features of the normal small gut mucosa in humans were (1) distinct extrusion zones at the crests of the villi and almost no signs of enterocyte extrusion along the sides of the villi, and (2) regular enterocytes with polygonal, flat, apical surfaces covered by a thick glycocalyx that obscured the underlying microvilli.

Adolescent↗
PubMed1984

Ultrastructure of inhibited parietal cells in the rat.

In acutely vagotomized rats, gastric acid secretion was stimulated with a combination of carbachol and pentagastrin, and/or inhibited with picoprazole, cimetidine, or l-hyoscyamine. The animals were killed 1 or 3 h later. Using stereologic electron microscopic methods, the relative area of the secretory surface in the parietal cells and the mean size of these cells were estimated. The parietal cells in the superficial quarter of the oxyntic mucosa were larger than those at deeper levels of the mucosa. Moreover, the secretory surface was proportionally larger in the superficial cells than in the deep cells. Stimulation by carbachol and pentagastrin produced an increase in the secretory surface area. Inhibition of stimulated acid secretion by l-hyoscyamine reduced the secretory surface to the level of the unstimulated controls. Cimetidine, given at doses that inhibited stimulated acid secretion, did not alter the mean size of the secretory membrane. After inhibition by picoprazole, stimulated acid secretion was abolished, but the secretory membrane became significantly larger than after cimetidine inhibition. These divergent patterns of morphologic reactions probably reflect the different mechanisms of inhibition at the cellular level.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1984

Parietal cell structure during inhibition of acid secretion.

Acute, pharmacological inhibition of gastric acid secretion is paralleled by a return of the parietal cells to a resting morphology. However, some inhibitors acting on targets in the parietal cells distal to the receptors, may inhibit acid secretion without the return to a resting morphology. This is the case with e.g. picoprazole and thiocyanate. Long-term pharmacological or surgical inhibition of acid secretion may be followed by changes in the number and/or size of the parietal cells.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1983

Stereological studies on the rat small intestinal epithelium. II. Effects of antrectomy and antral exclusion.

Morphological studies were carried out on the absorptive cells of the small intestine to elucidate their reaction to shunt operations and to variations in endogenous gastrin production. Adult rats were subjected to 1) antrectomy with gastro-duodenostomy, 2) antrectomy with gastro-jejunostomy, 3) antral exclusion, or 4) sham operation. Quantitative light microscopy revealed no significant differences among the different groups with regard to the height of the absorptive cells and to the internal surface area of the duodenum or jejunum. In contrast, stereological measurements at electron-microscopical level demonstrated significant differences in the apical surface area of the absorptive cells. After antral exclusion or antrectomy with gastro-jejunostomy the apical surface area in the duodenal blind loop increased by 28% and 78%, respectively, in comparison to the sham-operated rats. A reduction of this area by approximately 30-40% was registered for the jejunal absorptive cells after antrectomy or antral exclusion. Hormone levels as well as intraluminal factors are presumably responsible for these variations in the brush-border surface area.

Animals↗
PubMed1983

Monoclonal antibodies against gastric H+ + K+ ATPase.

Monoclonal antibodies were prepared against a purified membrane fraction from hog gastric mucosa containing the H+ + K+ ATPase. On sodium dodecyl sulfate gels the molecular weight of this fraction corresponds to a single band of about 95,000. In contrast, on isoelectric focusing gels three groups of peptides are resolved with isoelectric points of 5.7, 6.2, and 8.5. One of the monoclonal antibodies (HK111) was shown to react selectively with the acidic peptide, whereas another antibody (HK113) reacted with the alkaline peptide, showing that the three peptides were antigenically distinct. Both monoclonal antibodies selectively labeled the parietal cell, and antibody HK111 labeled the tubulovesicles of the resting parietal cell and the microvilli of the secretory canaliculus of the secreting cell. This finding suggests translocation of membrane from the tubulovesicles to the secretory surface on stimulation.

Adenosine Triphosphatases↗
PubMed1983

Proton secretion by the gastric parietal cell.

The parietal cell occupies a unique niche among eukaryotic cells in that it develops a proton gradient of more than 4 million-fold across the membrane of the secretory canaliculus. At rest, the cell is still able to develop a proton gradient across intracellular membranes, such that the acid compartment has a pH of less than 4. Acidification depends on the simultaneous presence of ATP, K+ and Cl- as demonstrated in permeabilized cells. With acidification of the luminal side of the proton pump, there is a corresponding alkalinization of the cytosolic face as revealed by carboxyfluorescein fluorescence enhancement. Disposal of the resultant alkali depends on carbonic anhydrase activity and the functioning of a coupled Na+:H+ and Cl-:OH-antiport across the basal lateral membrane. Accordingly, with secretion there is an increased cellular Cl- level, which is exported across the apical membrane in association with K+. The Na+ pump dependent secretion of KCl across this membrane is one of the major sites of the gastric ATPase. Membranes isolated from secreting tissue contain a KCl permeation pathway largely absent from membranes isolated from resting tissue. The pump itself acts as an H+ for K+ exchange ATPase which is most probably composed of at least two peptides of 100 000 Mr. That catalytic cycle consists of formation and breakdown of a covalent aspartyl phosphate. Formation of the intermediate depends on loss of K+ from cytosolic binding sites, and breakdown of the intermediate depends on K+ binding to the luminal face of the enzyme. During breakdown, an acid labile E . P is formed, and, at high ATP concentrations, loss of this form of the enzyme is probably the rate limiting step.

Adenosine Triphosphatases↗
PubMed1983

Effects of pyloroplasty, truncal vagotomy, and antrectomy on parietal cell regeneration in experimental gastric wounds in the rat. A light and electron microscopic study.

Parietal cell regeneration in cauterized gastric wounds was studied in rats after antrectomy (Billroth I), pyloroplasty, and truncal vagotomy with pyloroplasty. Six to eight animals in each group were killed 90 or 130 days after operation, and in each rat stereological data were obtained from electron micrographs of 15 to 20 parietal cells from the wound area, from the normal mucosa beside the wounds, and from the mucosa in unoperated controls. Antrectomy reduced parietal cell size and mucosal thickness in normal mucosa and retarded parietal cell maturation and reduced mucosal thickness in the healing wounds. Pyloroplasty slightly reduced parietal cell size in normal mucosa and retarded maturation of the parietal cells in the wounds. If truncal vagotomy was added, the reduction in parietal cell size induced by the pyloroplasty was prevented in normal mucosa.

Animals↗