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Biomedical subjects

H F Helander

Publications and source records attributed to H F Helander.

At least 73 records · Page 4Linked to original sources

Morphological studies on the margin of gastric corpus wounds in the rat.

The serosa of gastric corpus in adult rats was briefly exposed to 80% acetic acid, and as a result wounds appeared in the subjacent mucosa. The rats were killed 2, 3, 6, 10, 14 or 21 days later, and the wound margins were prepared for light and electron microscopy. The marginal glands became cystically dilated, and the gastric pits increased in depth. Many of the mucous cells at the surface contained large lipid droplets. The zymogen cells lost most of their secretory granules and the bottom of the glands became dominated by mucous cells. The tubulo-vesicles disappeared from the parietal cells, and the volume density of mitochondria was reduced from 34% to 23%. The secretory canaliculi also became smaller than normal. The morphological changes in the epithelial cells were so marked that the secretory capacity might be impaired. Measurements on the surface of the wound margins showed neutral pH in stimulated rats, indicating that the parietal cells had discontinued their secretion of acid.

Animals↗

Localization of ouabain-binding sites in frog gastric mucosa.

Autoradiography at the light microscopic level was used to localize sites of [3H]ouabain binding in isolated stimulated frog gastric mucosa. Silver grains denoting binding were located near basal and lateral surfaces in both oxyntic and surface epithelial cells. Binding to oxyntic cells occurred well before inhibition of acid secretion, consistent with the view that inhibition by this drug is indirect, and subsequent to inactivation of oxyntic cell Na+-K+-ATPase and the resulting depression of cellular K+. The presence of Na+-K+-ATPase in surface cells, as shown by binding of labeled ouabain, suggests a role for that transport enzyme in electrical activity and secretion of alkali by these cells.

Animals↗

Inhibition of acid secretion in isolated gastric glands by substituted benzimidazoles.

A new class of gastric acid inhibitors, substituted benzimidazoles (H 83/69 and H 149/94), have been tested in an isolated rabbit gastric gland preparation. Acid formation in the glands was stimulated by histamine, dibutyryl cAMP (DBcAMP), and high extracellular K+ concentrations, and the glandular secretory response was measured by changes in oxygen consumption and in accumulation of the weak base [14C]aminopyrine (AP). The substituted benzimidazoles inhibited AP accumulation induced by all stimulants in a dose-dependent noncompetitive manner. In contrast, cimetidine only inhibited histamine-induced AP accumulation. Basal AP accumulation, not affected by cimetidine, was also inhibited by the substituted benzimidazoles, as was the increase in glandular oxygen consumption produced by the addition of histamine and DBcAMP. Basal oxygen consumption was inhibited by about 15%. The substituted benzimidazoles, like AP, are weak bases and were also found to accumulate in the glands. Semiquantitative morphological studies of glands stimulated by histamine plus theophylline did not show any change in the enlarged secretory surface area after stimulation in the presence of inhibitory concentrations of H 149/94 (10(-4) M). The results suggest that substituted benzimidazoles have a mechanism of action different from that of H2-receptor antagonists and indicate a very distal site of action in the events leading to acid formation.

Aminopyrine↗

Stereological studies on the small intestinal epithelium of the rat. 1. The absorptive cells of the normal duodenum and jejunum.

Quantitative macroscopic, light-microscopic and electron-microscopic studies were performed on the small intestine of fasted and non-fasted adult, male Sprague-Dawley rats. In non-fasted rats the small intestine was longer than in fasted rats. Due to the presence of villi the surface area in the duodenum and the jejunum was enlarged about six times. The microvilli on the villous crests caused a surface enlargement by 13 times in the duodenum (value corrected for overestimation due to section thickness), and 19 times in the jejunum of the fasted rats. At the base of the villi these values were about 50% lower. It was calculated that, in the fasted rats, the total enlargement of the luminal surface area--due to villi and microvilli--was 63 times in the duodenum and 81 times in the jejunum (corrected for section thickness). Differences between the villous crest epithelium and the villous base epithelium were also found with regard to the mean cell height, and the volume densities of the absorptive cell nuclei, the mitochondria, and the paracellular channels.

Animals↗

Quantitative ultrastructural studies on parietal cell regeneration in experimental ulcers in rat gastric mucosa.

The regeneration of parietal cells was studied in rat gastric mucosa. For this purpose wounds were produced by cauterization of the corpus mucosa in adult male Sprague-Dawley rats. The animals were killed at 30, 60, 90, 130, and 260 days postoperatively, six at each time. Sham-operated rats, killed at 60 and 260 days, served as controls. Stereologic data were obtained by electron microscopy of 10-20 parietal cells in each animal. At 90 days immature parietal cells appeared in the center of the wound. These cells were characterized by large nuclei, small mitochondrial volume density, and few tubulo-vesicles. With further regeneration the parietal cells became ultrastructurally mature, but their total volume in the mucosa remained subnormal. Also the epithelial cell volume density was lower than normal after 260 days of healing.

Animals↗

Quantitative electron microscopic studies on rat ileal Paneth cells under various physiological and experimental conditions.

The Paneth cells of the rat ileum were studied with quantitative electron microscopical methods. Estimations were made of the average volume of the cells and the nucleus, and the mean diameter and volume density of the secretory granules. Six groups of rats, each comprising 6-7 animals, were investigated: the rats in the first group were fasted controls, those in the second group non-fasted controls. In the third group the rats were given pilocarpine and in the fourth atropine. In the fifth group the rats were chemically sympathectomized, and the rats in the sixth group were subjected to partial removal of the small intestine. The secretory granules remained unchanged in all groups, except for the atropinized rats which contained significantly increased amounts, presumably indicating a low secretory rate. Moreover, the secretory granules were smaller in the rats treated with pilocarpine and in those operated on; this probably reflects a high secretory rate.

Animals↗

Effect of phospholipase A2 on purified gastric vesicles.

The phospholipid and fatty acid composition and role of phospholipids in enzyme and transport function of gastric (H+ + K+)-ATPase vesicles was studied using phospholipase A2 (bee venom). The composition (%) was phosphatidyl-choline (PC) 33%; sphingomyelin (sph) 25%; phosphatidylethanolamine (PE) 22%; phosphatidylserine (PS) 11%; and phosphatidylinositol (PI) 8%. The fatty acid composition showed a high degree of unsaturation. In both fresh and lyophilized preparations, even with prolonged incubation, only 50% of phospholipids were hydrolyzed, but the amount of PE and PS disappearing was increased following lyophilization. There was a marked decrease in K+-ATPase activity (75%) but essentially no loss of the associated K+ p-nitrophenyl phosphatase was found. ATPase activity could be largely restored by various phospholipids (PE greater than PC greater than PS). There was also an increase in Mg2+-ATPase activity, partially reversed in fresh preparations by the addition of phospholipids (PE greater than PS greater than PC). Proton transport activity of the preparation was rapidly inhibited, initially due to a large increase in the HCl permeability of the preparation. Associated with these enzymatic and functional changes, the ATP-induced conformational changes, as indicated by circular dichroism spectra were inhibited.

Adenosine Triphosphatases↗

Characterization of gastric mucosal membranes. X. Immunological studies of gastric (H+ + K+)-ATPase.

Gastric mucosal homogenates from hog were fractionated by differential and density gradient centrifugation and free-flow electrophoresis. The two major membrane fractions (FI and FII) thus obtained are distinct both enzymically and in terms of transport reactivity. This heterogenicity extends to their antigenic activity. Purified antibodies which were raised against the K+-ATPase-containing H+ transport fraction FI were of two types: inhibitory and non-inhibitory. Inhibitory antibodies reduced the K+-ATPase activity by approximately 80% and the K+-p-nitro-phenylphosphatase activity by approximately 40% in a concentration-dependent manner, while the small Mg++-dependent component of the enzyme activity was unaffected. Antibodies inhibiting the K+-ATPase also inhibited H+ transport. These antibodies did not cross-react with the other major membrane fraction isolated by free-flow electrophoresis, FII, and gave a single band on rocket immunoelectrophoresis. Antibodies against this FII fraction also did not react with the K+-ATPase and were heterogeneous, giving at least four bands with rocket immunoelectrophoresis and inhibiting both the 5'-nucleotidase and Mg++-ATPase of this fraction. Immunofluorescent staining of tissue sections showed that the FI was derived from the parietal cell of gastric tissue and was localized to the supranuclear area of the cell. Staining of isolated rat gastric cell suspensions by FI antibodies confirmed the selectivity of the antibody and showed a polar, plasma membrane localization. FII antibodies also largely stained the parietal cells in tissue sections. In the 16 hog tissues tested, FI antibodies cross-reacted only with gastric fundus, thyroid and weakly with thymus. Immunoelectronmicroscopy showed that FI antibodies reacted strongly with the secretory membrane at the apical cell surface of the parietal cells and at the secretory canaliculi, weakly with the apical surface of the zymogen cell, and not with the basal-lateral surface of the cells. Thus, the protontranslocating ATPase is localized in the parietal cells and in the region postulated to be the site of acid secretion.

Adenosine Triphosphatases↗

Parietal cell structure and acid secretion in the vagally innervated stomach and the vagally denervated fundic pouch in cats.

In seven cats provided with gastric fistula (GF) of the main stomach and a denervated Heidenhain pouch (HP) the structure of the innervated and denervated mucosa was examined by light and electron microscopy. In four of these cats dose-response curves for acid output to pentagastrin were determined before and after vagal denervation of the fundic pouch. Vagal denervation reduced the acid response to pentagastrin by decreasing both the secretory capacity and the sensitivity of the oxyntic glands. Accordingly, in the same cat the parietal cells of the HP were less sensitive to pentagastrin than the cells of the innervated main stomach. Light and electron microscopic investigations revealed that the fundic mucosa was thinner, and the size and proportion of the parietal cells was smaller in the HP than in the GF. It is likely that the morphological changes in the pouch were caused by the vagal denervation rather than by the loss of mucosal contact with food. The secretory and morphological changes produced by the vagotomy are not necessarily related.

Animals↗

A quantitative ultrastructural study of a parotid oncocytoma.

A quantitative electron microscopic study was performed in a case of parotid oncocytoma. The mean nuclear radius was estimated to be 3.4 mu, and the mean nuclear volume 171 cu mu. The mean cell volume was calculated to be 958 cu mu. The mitochondrial volume density value averaged 59% of the cytoplasmic volume, and the mean nuclear volume density was 24% of the cell volume. These findings are compared with previous quantitative electron microscopic data on various epithelial cells from the digestive system, including the salivary glands.

Adenoma↗

Distribution of osmotic flow in stomach and gallbladder.

Stomach and gallbladder actively transport fluids which are nearly isotonic to plasma. Consideration of the measured areas of the appropriate transporting surfaces gives a more realistic view of the osmotic gradient required to account for the observed net flow of water. Simple osmosis may be adequate if the transporting membrane has an osmotic permeability in the range observed for synthetic lecithin-cholesterol bilayer membranes.

Animals↗

Quantitative ultrastructural studies on rat gastric zymogen cells under different physiological and experimental conditions.

Quantitative electron microscopical measurements performed on gastric zymogen cells were aimed at determinations of size and volume density of the zymogen granules, and size of cell and nuclear profiles. 17 groups of rats each comprising 6-8 animals were investigated: five of these groups were used to study the influence of fasting and feeding, three groups were killed at different intervals after a pilocarpine injection, and four other groups were investigated after an atropine injection. The remaining five groups of rats were operated on: vagotomy was performed on one group, vagotomy + pyloroplasty on another, pyloroplasty on the third group, and antrectomy on the last two groups. The operated rats were sacrificed 4 or 10 weeks after the operations. Pilocarpine was more effective than feeding in reducing the size and the amount of zymogen granules. After atropine the size and amount of zymogen granules tended to increase. Ten weeks after pyloroplasty, vagotomy + pyloroplasty, or antrectomy the mean size of the zymogen cells was reduced. Loss of trophic vagal impulses, duodenal regurgitation, and abnormal serum gastrin levels are factors which might be responsible for the zymogen cell hypotrophy in operated rats.

Animals↗

Mast cells of the Mongolian gerbil (Meriones unguiculatus). Morphology, histamine content and role of calcium in the histamine release process.

The fine structure, histamine conten;, and role of calcium in the histamine release process were studied in peritoneal mast cells of the Mongolian gerbil (Meriones unguiculatus). Stereological methods were applied to obtain quantitative data on their structure. The findings were compared with results obtained from the same type of cells in the rat. The gerbil mast cells were smaller in size (mean volume 242 micrometer3 vs 684 micrometer3 in the rat), and the nuclei were also smaller (55 micrometer3 vs 102 micrometer3). There were fewer granules in the gerbil mast cells and their diameter averaged 0.54 micrometer as compared with 0.78 micrometer in the rat). Only 20% of the cytoplasm of the gerbil mast cell was occupied by granules. This figure is approximately one third of that obtained in rat mast cells. The mean total histamine content per cell was 9 pg as compared to an estimated 30 pg/cell in rats. Calculated molar concentration of histamine in the mast granules, however, was higher in the gerbil than in the rat (2.3 M vs. 0.9 M). The mast cells of the gerbil were much more sensitive to the histamine-releasing agent compound 48/80 and in contrast to rat mast cells they were entirely dependent on calcium for their amine release. The fine cellular structure of both species showed multitudinous plasma membrane folds on their surfaces. In addition gerbil mast cells showed extensive surface invaginations. Apart from this were no major differences at the ultrastructural level between unstimulated cells of the two species. During histamine release, however, the mast cells of the gerbil showed a much greater tendency to form large, intracytoplasmic vacuoles and a decreased propensity for fusion of perigranular and plasma membranes (exocytosis) as compared with the corresponding cells in the rat.

Animals↗