Biomedical subjects

W J Krause

Publications and source records attributed to W J Krause.

At least 55 records · Page 3Linked to original sources

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

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↗

PubMed1991

The vestibular apparatus of the opossum (Didelphis virginiana) prior to and immediately after birth.

The vestibular apparatus of the opossum was examined shortly before and immediately after birth. A band of about 20 sensory cells was observed within the forming utricle by 24 h prior to birth. Stereocilia projecting from the apices of the sensory cells appeared intimately associated with a well-defined population of overlying otoliths. These morphological observations suggest that a functional utricle may be present at the time of birth and together with other senses (tactile, olfaction) may aid the newborn of this species in its migration from the birth canal to the pouch.

Animals↗

PubMed1990

Autoradiographic demonstration of specific binding sites for E. coli enterotoxin in various epithelia of the North American opossum.

In the North American opossum, heat-stable specific binding sites for E. coli enterotoxin are observed (i) in epithelial cells lining the small intestine, colon, gall bladder, cystic duct, common bile duct and trachea, and (ii) in epithelial cells forming the duodenal (Brunner's) glands, liver, kidneys (metanephros, mesonephros) and testis, as demonstrated by autoradiography. Enterotoxin-specific binding sites in the intestinal tract are only found in intestinal epithelial cells with the highest concentration in the microvillus border. Enterotoxin-specific binding sites also occur in epithelial cells comprising the secretory tubules and ducts of the duodenal glands. In the kidneys (metanephros and mesonephros), enterotoxin-specific binding sites are confirmed primarily to the proximal tubules, whereas in the testis they are localized in seminiferous tubules. In the liver, enterotoxin-specific binding sites are confined primarily to hepatocytes. E. coli enterotoxin caused a 7-fold increase of cGMP in the liver and a 30-fold increase in the duodenal glands. The liver responded in about half of the animals studied, whereas the duodenal glands gave a consistent response in each case. Likewise, the duodenal glands consistently showed strong labelling for 125I-enterotoxin, whereas receptor labelling of hepatocytes was inconsistent in nearly half the incubations and corresponds to the observed cGMP measurements.

Animals↗

PubMed1990

Morphological, developmental and immunohistochemical observations on the opossum pituitary with emphasis on the pars intermedia.

Development of the pituitary in Didelphis follows the general pattern of that described for most mammalian species. The dorsal region of a multichambered pituitary vesicle, which forms from Rathke's pouch, comes to lie adjacent to the presumptive infundibulum by the 10 1/2 d of gestation. The epithelial wall of this vesicle consists of spindle-shaped cells. The dorsal wall of the upper chamber of the pituitary vesicle forms the pars intermedia; the ventral wall of this chamber gives rise to cells of the pars distalis. Corticotropes, somatotropes, and lactotropes are seen in the presumptive adenohypophysis of the 11 1/2 d embryo. Gonadotropes and thyrotropes appear about 1 d later, shortly after birth. By the 2 postnatal week, the adult distribution of all 5 cell types within the pars distalis appears to have been established. The wall bounding the pituitary cleft in the adult represents an epithelial continuum limited by a basal lamina and corresponds to the upper chamber of the original pituitary vesicle. Ultrastructurally, the limiting walls of the pituitary cleft consists of stellate (marginal) cells, large, bulbous cells, and granulated cells. The latter correspond to the various endocrine cell types normally associated with the pars distalis. Non-granular folliculo-stellate cells also are observed within the epithelial cords of the pars distalis.

Aging↗

PubMed1990

"Healed" experimental gastric ulcers remain histologically and ultrastructurally abnormal.

The present study was designed to assess histologic and ultrastructural features of gastric mucosa in the areas of grossly healed ulcers (acetic acid-induced gastric ulcers) in rats. The specific question we studied was whether the structure and cellular composition of the gastric mucosa in an area of grossly healed ulcer were fully restored. Eighty Sprague-Dawley rats underwent laparotomy; 100% acetic acid was applied to the lower gastric corpus serosa for 30 s and the abdomen was closed. The stomachs were reopened after 2 weeks or after 2, 3, or 4 months. Standardized gastric wall specimens from the area of grossly healed ulcers were obtained, processed, and evaluated by light microscopy and by transmission electron microscopy. The gastric mucosa of grossly healed ulcers demonstrated re-epithelialization at each study time but the mucosa beneath the surface epithelium displayed prominent histologic and ultrastructural abnormalities. Two different patterns of scar could be distinguished: (a) the mucosa in the area of healed ulcer was thinner (25-45% reduction vs. normal), with increased connective tissue and poor differentiation and/or degenerative changes in the glandular cells; or (b) the mucosa displayed ballooning dilatation of gastric glands, reduction in the microvascular network, and poor differentiation of glandular cells. We conclude that (i) the subepithelial mucosa of grossly healed gastric ulcer displays disorganized restoration of glandular and vascular structures and remains histologically and ultrastructurally abnormal; (ii) these abnormalities may interfere with oxygenation, nutrient supply, and with mucosal resistance and defense, and therefore could be the basis for ulcer recurrence.

Acetates↗

PubMed1990

Vascular and microvascular changes--key factors in the development of acetic acid-induced gastric ulcers in rats.

The present study examined the time sequence and histologic and ultrastructural features of the formation and evolution of experimental, acetic acid-induced gastric ulcerations in rats. One hundred percent acetic acid was applied to the gastric serosa of 140 fasted male Sprague-Dawley rats through a polyethylene tube for 30 s. Gastric mucosal changes were evaluated at 1, 5, 15, and 30 min, 1 and 3 h, and 1, 2, 3, 5, 8, and 11 days after acetic acid application by visual inspection, by quantitative and qualitative light microscopy, and by transmission electron microscopy. Following exposure to acetic acid, the earliest morphologic changes occurred at 1 min and consisted of dilatation of large submucosal veins and arteries and mucosal collecting venules. Five to 15 minutes after injury, thrombi developed in submucosal veins and collecting venules, leading to microvascular stasis and mucosal necrosis. By 3 h, necrotic masses started to detach. By 24-48 h, necrotic changes penetrated the submucosa. By 72 h, most ulcers underwent transition into a "chronic" stage characterized histologically by the presence of granulation tissue at the bottom, and the appearance of a transitional healing zone at the margins. By 5 days, an increased amount of granulation tissue was observed and the gastric glands in transitional zones at the ulcer margin displayed cystic dilatation. Based on this study, we conclude that a key feature of acetic acid-induced ulcer formation is the early vascular and microvascular injury, which precedes glandular cell necrosis.

Acetates↗

PubMed1990

Purification and properties of parathyroid hormone-related peptide isolated from milk.

The occurrence and properties of PTH-related peptide (PTH-RP) in milk was investigated. PTH-RP was purified to homogeneity from human and bovine milk using heat and acid to precipitate milk proteins followed by ion exchange chromatography and reverse-phase HPLC. The peak of PTH-RP from HPLC was detected using a sensitive bone cell bioassay. A single band of peptide was detected on silver-stained polyacrylamide gels, which migrated as a 20-21-kDa macromolecule. PTH-RP isolated from either human or bovine milk had similar electrophoretic mobilities on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The partially purified bovine PTH-RP stimulated cAMP production in UMR106-01 and OK cell lines and elicited a concentration-dependent inhibition of sodium-dependent phosphate transport in OK cells. Incubation of milk extracts with an anti-PTH antiserum did not affect their bioactivity, whereas an antihuman PTH-RP 1-34 antiserum markedly reduced the cAMP response of UMR106-01 cells to the immunoabsorbed milk extracts. A PTH antagonist, norleu PTH 3-34, blocked the stimulation of cAMP production in UMR106-01 cells treated with milk extracts. PTH-RP immunoreactivity and bioactivity occurred in milk extracts of diverse animals from both eutherian and metatherian (marsupial) species. Porcine colostrum also had immunoreactive PTH-RP, although the levels were lower than the immunoreactive PTH-RP concentrations observed in milk samples collected at 7 and 14 days of lactation. Thus, a 20-21-KDa PTH-RP is secreted into milk where it could play a role in the development of suckling, newborn animals.

Adenylyl Cyclases↗

PubMed1990

Tyrosine hydroxylase- and corticotropin releasing factor-immunoreactivity in the olfactory bulb of the opossum (Didelphis virgianina).

The nerve fiber layer of the opossum olfactory bulb, formed by axons originating from bipolar neurons in the olfactory epithelium, and glomeruli are intensely immunoreactive for olfactory marker protein. The surrounding extra-glomerular neuropil contains numerous periglomerular neurons immunoreactive for either tyrosine hydroxylase or corticotropin releasing factor. Dendrites of both types of immunoreactive neurons extend into the intraglomerular neuropil. CRF-immunoreactive neurons are fewer in number than TH-immunoreactive neurons and are observed primarily in the periglomerular region. Occasional, scattered TH-immunoreactive neurons are seen in the deeper layers of the olfactory bulb.

Animals↗

PubMed1990

A survey of endocrine cells in the pancreas of the echidna (Tachyglossus aculeatus) with special reference to pancreatic motilin cells.

Pancreatic endocrine cells were examined in a primitive egg-laying mammal, the echidna, using immunohistochemistry. Immunoreactive endocrine cells were observed using antisera to insulin, glucagon, somatostatin, avian pancreatic polypeptide and bovine pancreatic polypeptide. In addition, motilin-immunoreactive cells were identified in both the endocrine and exocrine pancreas of pouch-young and adult echidnas using three types of motilin antisera. Since the motilin-immunoreactive cells did not cross-react with any other pancreatic hormones tested, they are identified as an independent endocrine cell type.

APUD Cells↗

PubMed1990

An immunohistochemical study of endocrine cells in the proximal duodenum of eight marsupial species.

The proximal duodenum of eight marsupial species, (koala, common brushtail possum, ring-tailed possum, common wombat, great grey kangaroo, parma wallaby, short-nosed bandicoot and tiger cat) were investigated immunohistochemically using 12 specific antisera for gut hormones. Several types of immunoreactive cells were seen on the intestinal villi and in crypts of these species: 9 types in the koala; 8 types in the common brushtail possum; 7 types in the common wombat; 6 types in the short-nosed bandicoot and 5 types in the ringtailed possum, great grey kangaroo, parma wallaby and tiger cat. Gastrin-, somatostatin-, motilin- and serotonin-immunoreactive cells were seen in all species examined. A few BPP-, enteroglucagon-, CCK-, secretin-, GIP- and neurotensin-immunoreactive cells were seen but only in few species. A few substance P-immunoreactive cells were detected only in the koala. Immunoreactive cells were also seen in Brunner's glands: 5 types in the parma wallaby; 3 types in the great grey kangaroo and tiger cat; 2 types in the koala and common wombat; 1 type in the short-nosed bandicoot. No immunoreactive cells were found in Brunner's glands of the common brushtail possum.

Animals↗

PubMed1990

An ultrastructural study on gastric endocrine cells in the stomach gland patch of the koala Phascolarctos cinereus.

The endocrine cells in the stomach gland patch of the koala (Phascolarctos cinereus) were studied ultrastructurally. They were classified into 3 types based on the ultrastructural profiles of their endocrine granules and tentatively categorized as type I, II, and III endocrine cells. Type I cells contained round granules that were for the most part larger than those observed in the other 2 cell types. The granules ranged from moderate to relatively high in electron density. Type II cells were angular in shape and characterized by the presence of granules that were polymorphous in profile. Contents of the endocrine granules in type II cells also showed a range of high to moderate electron density. Type III cells were oval or pyramidal in shape. They contained highly polymorphous granules that were round, oval, dumbbell-like or comma in shape and characterized by the presence of a clear space or halo separating the high to low electron-dense core from the limiting membrane of granules. Type III cells were observed most often whereas type I and II cells were a less frequent observation.

Animals↗

PubMed1989

Opossum kidney contains a functional receptor for the Escherichia coli heat-stable enterotoxin.

The Escherichia coli heat-stable enterotoxin (ST1 or STa) binds to specific receptors on mammalian intestinal brush border membranes, and stimulates guanylate cyclase in those membranes. We have found a similar signal transduction system in brush border membranes prepared from kidney cortex of the American opossum (Didelphis virginiana, and in a cell line (OK cell) derived from that tissue. Activation of guanylate cyclase by ST1 is therefore not limited to intestinal cells. Furthermore, since it is unlikely that ST1 which is produced in the intestinal lumen, would have access to kidney receptors, this suggests the existence of an endogenous peptide resembling ST1, at least in marsupials.

Animals↗

PubMed1989

Autotransplantation of avian parathyroid glands: an animal model for studying parathyroid function.

The parathyroid glands of chickens were autotransplanted and the return of parathyroid function following transplantation was determined. Parathyroidectomy (PTX) resulted in a marked hypocalcemia (5.2 +/- 0.2 mg/dl) 4 hr following PTX. Plasma calcium (PCa) had declined to 4.3 +/- 0.2 mg/dl 24 hr after PTX. Parathyroid glands were transplanted subcutaneously 24 hr after removal and 24 hr later, PCa had risen to 8.6 +/- 0.5 mg/dl. Seven days after PTX. PCa increased to 10.3 +/- 0.2 mg/dl and by 14 days was indistinguishable from control levels (10.8 +/- 0.2 mg/dl vs. 11.0 +/- 0.2 mg/dl, respectively). When chicks with transplanted glands were fed a low Ca (0.08%) diet for 2 weeks they were able to maintain plasma PCa at levels comparable to control birds. Removal of the transplanted glands resulted in marked decreases in PCa (from 9.7 +/- 0.3 to 5.6 +/- 0.8 mg/dl), in the fractional excretion of phosphate, in urine cAMP, and in renal 25OH-vitamin D3-1 alpha-hydroxylase activity. Stepwise reductions in PCa and 1 alpha-hydroxylase activity were produced in partially PTX and fully PTX chicks by removing part or all of the parathyroid tissue. These data suggest that the transplanted parathyroid tissue was the major source of circulating PTH and that it may be possible to produce different degrees of acute hypoparathyroidism by varying the amount of transplanted parathyroid tissue removed surgically. Chickens with transplanted parathyroid glands thus provide a convenient animal model in which to study parathyroid function in an avian species.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

PubMed1989

Protection of the rat gastric mucosa against aspirin injury by arachidonic acid: a dietary prostaglandin precursor fatty acid.

We studied aspirin-induced injury to the gastric mucosa in control rats pretreated with a solubilizer, pluronic F-68 (PL), and in rats pretreated with solubilized arachidonic acid (AA). Fasted male rats were pretreated intragastrically with 1 ml of either pluronic or AA and 1 h later acidified ASA (1 ml suspension of 200 mg kg-1 body weight) was administered intragastrically. Grossly apparent mucosal lesions developed 1 h after aspirin in pluronic-pretreated rats, but were significantly reduced in AA-pretreated rats. Histology, scanning and transmission electron microscopy demonstrated that AA pretreatment did not prevent aspirin-induced initial damage to the surface epithelium but did significantly reduce extent of aspirin-induced deep mucosal necrosis at 1, 4 and 18 h after aspirin. Initial aspirin-induced surface epithelial damage was rapidly restituted by two distinct types of re-epithelialization - vertical and horizontal. While the vertical type of re-epithelialization has been reported previously as the first stage of mucosal repair following injury by various noxious agents such as concentrated ethanol, the horizontal type of re-epithelialization, which is described for the first time in this paper, seems to be specific for the repair of aspirin-induced gastric mucosal injury. These studies suggest that dietary factors such as essential fatty acids may play a role in gastric mucosal protection against aspirin injury.

Animals↗

PubMed1989

Clonal sublines that are morphologically and functionally distinct from parental OK cells.

Three clonal subpopulations of opossum kidney (OK) cells were derived from the parental line. The distribution of apical microvilli suggested that the OK cell line was heterogeneous. The clonal OK sublines appeared homogeneous as reflected by microvilli, which were uniformly distributed on the apical surface. Parathyroid hormone (PTH), forskolin (FSK), and prostaglandin E1 (PGE1) increased adenosine 3',5'-cyclic monophosphate (cAMP) formation in OK cells and all of the clones. PTH inhibited sodium-dependent phosphate transport in parental cells and in OK/B and OK/P clones with maximal effects appearing at 4, 2, and 1 h, respectively. PTH had no effect on phosphate transport in OK/H cells. FSK inhibited phosphate transport in parental cells and OK/B and OK/P clones but was relatively ineffective in OK/H cells. PGE1 decreased phosphate transport in OK/B and OK/P cells but was ineffective in the parental line and in OK/H cells. Phorbol 12-myristate 13-acetate, a potent inhibitor of phosphate transport in the parental OK cell line, had little effect in the clonal sublines. These clonal lines have remained phenotypically stable for 10 passages and should prove useful in studying the regulation of phosphate transport by PTH as well as addressing the question of whether PTH receptor subclasses exist which couple to cAMP and/or calcium effector systems in kidney cells.

Animals↗

PubMed1989

Escherichia coli enterotoxin receptors: localization in opossum kidney, intestine, and testis.

The distribution of receptors for Escherichia coli enterotoxin were examined in opossum kidney, intestine, and testis. E. coli enterotoxin stimulated guanosine 3',5'-cyclic monophosphate (cGMP) production in renal cortex, testis, and small intestinal mucosa but had only a small effect in the colon. Atrial natriuretic factor enhanced the cGMP content of renal cortex and small intestine but had no effect on testis or colon. The enterotoxin receptors were observed to be localized in proximal tubules, to epithelial cells of crypts and villi of small intestine, to crypts of colon, and in seminiferous tubules. Both convoluted and straight portions of proximal tubules exhibited specific binding sites for 125I-labeled enterotoxin. Glomeruli and distal tubules did not have receptors. Binding of 125I-enterotoxin to brush-border membranes of kidney cortex or intestinal mucosa and to testis membranes was markedly temperature dependent. The binding affinities of these receptors for E. coli enterotoxin were similar (i.e., IC50 approximately equal to 0.4-0.5 nM). Daily administration of 20 micrograms of enterotoxin intramuscularly to opossums increased urine cGMP excretion with no apparent changes in urine volume, Na+, or K+ excretion. Thus receptors for heat-stable enterotoxins are localized to proximal tubules of kidney and to enterocytes and seminiferous tubules of intestine and testis, respectively. Apical membranes may be the site of enterotoxin receptors in these epithelia.

Animals↗

PubMed1989

Immunohistochemical study of the developing endocrine pancreas of the opossum (Didelphis virginiana).

Cells immunoreactive for insulin, glucagon, somatostatin, bovine pancreatic polypeptide and 5-hydroxytryptamine are found in the pancreas of the newborn opossum and of all later stages examined. All immunoreactive cell types are present in primary and secondary islets and within elements of the exocrine pancreas. Cells immunoreactive for glucagon, bovine pancreatic polypeptide, somatostatin and 5-hydroxytryptamine generally are confined to the periphery of secondary (intralobular) islets, whereas insulin-immunoreactive cells occupy the central region. Endocrine cells within primary (interlobular) islets are randomly scattered. A small number of pancreatic-polypeptide-immunoreactive cells are reactive for the amine 5-hydroxytryptamine also, but the reverse is not observed. The endocrine pancreas continues to differentiate and develop throughout postnatal life and into adulthood. Little difference was observed between the head and tail regions of the opossum pancreas for the measurements made.

Aging↗