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M D Basson

Publications and source records attributed to M D Basson.

At least 73 records · Page 4Linked to original sources
PubMed1992

Independent modulation of enterocyte migration and proliferation by growth factors, matrix proteins, and pharmacologic agents in an in vitro model of mucosal healing.

BACKGROUND: Gastrointestinal mucosa heals by restitution and proliferation. These are difficult to distinguish in vivo. METHODS: Human Caco-2 enterocytes were cultured on matrix proteins (collagen I, laminin, fibronectin) with growth factors (epidermal growth factor [EGF] and transforming growth factor-beta 1 [TGF-beta 1]) and the tyrosine kinase and prostaglandin inhibitors genistein and indomethacin. Healing was modeled by means of monolayer expansion, proliferation by means of 3H-thymidine uptake, and restitution by means of mitomycin-blocked migration. RESULTS: Changing matrix composition failed to alter proliferation, but collagen I stimulated migration more than laminin or fibronectin (laminin/collagen, 68% +/- 2%; p less than 0.05). EGF (30 ng/ml) increased proliferation on both collagen (225% +/- 11% of basal) and laminin (206% +/- 26%) but increased migration only over laminin (210% +/- 17%) (all, p less than 0.05). TGF-beta 1 (200 pg/ml) stimulated migration over laminin (187% +/- 18%, p less than 0.005) but inhibited migration over collagen (89% +/- 3%, p less than 0.01) and did not affect 3H-thymidine uptake. When cultured on laminin, EGF but not TGF-beta 1 altered organization of the alpha 2 integrin subunit. Genistein (100 mumol/L) inhibited basal and EGF-stimulated 3H-thymidine uptake. In addition, it prevented EGF stimulation of replication-blocked migration (81% +/- 10% vs 190% +/- 20% of basal, p less than 0.0001) without altering basal replication-blocked migration. Indomethacin (10(-5) mol/L) did not alter migration but inhibited basal and EGF-stimulated proliferation by 7% +/- 1% (each, p less than 0.005). CONCLUSIONS: Restitution and proliferation appear independently regulated by matrix and growth factors. It may be possible to individually target specific phases of mucosal healing by means of pharmacologic agents.

Cell Division↗
PubMed1992

Current clinical and pathologic perspectives on gastric stromal tumors.

Gastric stromal tumors are heterogeneous and poorly understood. Investigators have studied these tumors by histologic and immunocytochemical characteristics, but interlaboratory variations have impeded clinical application of these techniques. Although many gastric stromal tumors can be categorized as benign or malignant with some certainty, occasional instances may present great difficulty in this distinction. Uncertainty about malignant potential and the biologic factors of the lesion will therefore generally suggest excision with a 1 to 2 centimeter margin for diagnosis and definitive therapy of these tumors. Subsequent prognosis will be dictated primarily by tumor size, histologic factors and mitotic index. Gastric stromal tumors in young women should suggest the possibility of Carney's triad. Functional extra-adrenal paragangliomas and pulmonary chondromas should be sought preoperatively. The paraganglioma should be managed first and the gastric lesion then addressed. Distal gastrectomy of at least 50 percent would seem to represent a reasonable resection limit. Identification of the specific cellular biologic factors of these lesions will be necessary to accurately classify particular tumors, gauge prognosis and individualize their management.

Adult↗
PubMed1991

Redistribution of 23 kDa tubulovesicle-associated GTP-binding proteins during parietal cell stimulation.

Small GTP-binding proteins are important regulators of intracellular traffic. The presence of several small GTP-binding proteins was documented in subfractions of rabbit parietal cells. Upon maximal stimulation of the cells with a combination of histamine and forskolin, one 23 kDa GTP-binding band was observed to decrease in a 50,000 g membrane fraction while increasing in 4000 g membranes. The 23 kDa band resolved into one major and two minor species on two-dimensional gels. GTP-binding species of 23 kDa, 24 kDa and 25 kDa were present in purified preparations of tubulovesicles. The three isoelectric species of the 23 kDa proteins observed in parietal cell 50,000 g microsomes were enriched in tubulovesicle preparations. None of the tubulovesicle-associated GTP-binding proteins were substrates for ADP-ribosylation by a preparation of botulinum D toxin. These results indicate that tubulovesicles contain discrete small GTP-binding proteins which redistribute during parietal cell stimulation.

Adenosine Diphosphate Ribose↗
PubMed1991

Behavioral disturbances in children after trauma.

The psychological effects of nonneurologic trauma on children are poorly recognized. We hypothesized that physical trauma in children, with or without head injury, would result in substantial and persistent psychological and behavioral abnormalities. Using a short telephone survey followed by a detailed behavioral checklist, we studied psychobehavioral dysfunction in children who had experienced trauma either with or without minor head injury (n = 40 each) as well as in a comparative group of children after emergency appendectomy (n = 80). Substantial behavioral disability was identified by the detailed checklist in 35% and 28% of children without and with head injury, respectively, but in none after appendectomy. Dysfunctions included phobias, major scholastic difficulties, rage attacks, and episodic depression that continued for a long period. Even in the 67% of children who eventually fully recovered, the duration of symptoms after the time of injury was an average of 19 months. Demographics, socioeconomic status, severity of injury, and length of hospitalization did not correlate with dysfunction, and these traumatized children's siblings had no reported history of trauma or psychological difficulties. Thus, parental opinion about behavioral dysfunction appears sensitive and specific and is therefore a useful screening index. These results suggest that injured children, even after minor trauma, may suffer substantial and long-lasting behavioral changes to a degree hitherto unrecognized.

Appendectomy↗
PubMed1990

Pepsinogen release and acid secretion from human and guinea pig gastric mucosa compromised by hypoxia, endotoxin, or critical illness.

Despite blockade and neutralization of gastric acid, acute gastric lesions cause substantial morbidity and mortality in critically ill patients. Pepsinogen release in response to noxious stimuli such as hypoxia and endotoxin might contribute to mucosal damage. Guinea pig fundic mucosa was mounted in Ussing chambers. Acid secretion, pepsinogen release, potential difference (PD), and resistance were monitored. Gassing with room air or nitrogen diminished acid secretion and PD but increased pepsinogen release 9.7- and 15.5-fold, respectively (both p less than 0.001). Similarly, endotoxin (0.01 and 0.1 units/ml) dose-dependently inhibited acid secretion and PD but increased pepsinogen release 3.3- and 6.1-fold (both p less than 0.05). Endotoxic and air-gassed tissues were edematous with scattered cellular damage by light and transmission electron microscopy; nitrogen-exposed membranes appeared necrotic. Pepsin release may therefore have resulted from cell damage rather than exocytosis. Intragastric peptic activity in critically ill H2-receptor-blocked patients (n = 20) was 5490 +/- 1701 U/ml. The gastric juice of H2-blocked convalescing surgical patients (n = 20) contained 315 +/- 101 U/ml (p less than 0.0001). Occult blood correlated with intragastric peptic activity (r = 0.59, p less than 0.0001) but not with gastric pH (r = 0.04, p = 0.6). These data suggest that the complex of pathophysiologic abnormalities common in critical illness causes substantial pepsin release. Efflux of this potent mucolytic barrier breaker may damage gastric mucosa in severely stressed patients.

Animals↗
PubMed1990

Effects of cholecystokinin and cholinergic receptor blockade on guinea pig pepsinogen secretion.

Although cholecystokinin (CCK) has been reported to stimulate pepsinogen secretion, this action has been poorly characterized. To assess the ability of CCK to regulate mammalian pepsinogen secretion, guinea pig fundic mucosa was incubated in Ussing chambers with CCK-8, carbamylcholine, and pentagastrin, and with cholinergic and CCK antagonists. CCK-8 stimulated pepsinogen secretion at 10(-10) M, with an ED50 of 10(-9) M and maximally (26-fold over basal) at 10(-8) M. Carbachol stimulated pepsinogen and acid secretion with an ED50 of 3 x 10(-7) M and maximally at 10(-6) M. Pentagastrin (10(-9) M-10(-6) M) did not affect acid or pepsinogen secretion, whereas gastrin-I (10(-6) M) stimulated acid secretion slightly but did not alter pepsinogen secretion. L364, 718 (10(-5) M), a specific CCK peripheral receptor antagonist, abolished all pepsigogic effects of 3 x 10(-9) M CCK-8 without altering basal acid or pepsinogen secretion or mucosal electric characteristics. L364,718-treated tissues unresponsive to CCK-8 nevertheless secreted pepsinogen and acid in response to 3 x 10(-7) M carbachol identically to control carbachol-treated preparations. Atropine (10(-5) M) blocked the response to 3 x 10(-7) M carbachol without inhibiting 10(-9) M CCK stimulation. These results support a specific receptor-mediated role for cholecystokinin in the physiologic regulation of guinea pig pepsinogen secretion.

Animals↗
PubMed1989

Does vasoactive intestinal polypeptide mediate the pathophysiology of bowel obstruction?

We hypothesized that bioactive peptides might be released into the portal circulation and mediate pathophysiologic alterations accompanying small bowel obstruction. We studied this question in a subacute canine small bowel obstruction model using 50 percent diameter occlusion. Control animals underwent sham laparotomy. Vasoactive intestinal peptide (VIP), peptide YY, and gastrin were measured in portal and systemic plasma by specific radioimmunoassays at 24-hour intervals as the obstruction progressed to completion over 5 days. All peptides in both groups demonstrated portal and peripheral gradients. In control dogs, peptide concentrations did not change postoperatively but VIP increased markedly in obstructed dogs, demonstrating a median portal level of 95 pmol/liter at 96 hours compared with 31.5 pmol/liter in control animals. These portal VIP levels are known to cause hypersecretion and splanchnic vasodilation in experimental models. The release of vasoactive compounds such as VIP may mediate local pathophysiology in human small bowel obstruction. A similar explanation of the systemic effects is consistent with the known cardiopulmonary bioactivity of VIP.

Animals↗
PubMed1988

Pepsin release by prostaglandin E1 analogue. A potential therapeutic problem.

Prostaglandins Inhibit gastric acid secretion and are independently "cytoprotective" for gastric mucosa. They are currently under clinical Investigation for the treatment of peptic ulcers. The effects of the prostaglandin E1 analogue misoprostol on pepsinogen and acid secretion were tested in isolated rabbit gastric glands and enriched parietal cells. Pepsinogen concentrations were measured by iodine 125-labeled albumin digestion and acid secretion indirectly by carbon 14-tagged aminopyrine uptake. Misoprostol inhibited histamine-stimulated acid secretion in parietal cells with 50% inhibition at 10(-9) mol/L and maximally (78% inhibition) at 10(-7) mol/L. In contrast, however, misoprostol strongly stimulated pepsinogen secretion by gastric glands with a half-maximal effect at 10(-8) mol/L and maximal stimulation of 227% at 10(-6) mol/L. It is possible that this release of pepsin could compromise the action of prostaglandins in promoting ulcer healing.

Alprostadil↗
PubMed1988

Dissociation of pepsinogen and acid secretion in the guinea pig.

In vivo observations have suggested that acid secretion may potentiate pepsinogen release. We measured pepsinogen and acid secretion by guinea pig fundic mucosal sheets stimulated by 10(-4) M histamine, 10(-8) and 10(-9) M cholecystokinin, and 3 x 10(-7) M carbamylcholine and then investigated the effects of 10(-4) M omeprazole on basal, carbachol-stimulated, and cholecystokinin-stimulated secretion. Histamine increased basal acid secretion fivefold (p less than 0.01) without altering pepsinogen secretion. Cholecystokinin did not stimulate acid secretion but increased pepsinogen secretion by factors of 23.1 at 10(-8) M and 9.1 at 10(-9) M (both p less than 0.01). The combination of 10(-4) M histamine and 10(-9) M cholecystokinin increased acid secretion 3.5-fold and pepsinogen secretion 6.4-fold, statistically equivalent to the sum of the effects of histamine and cholecystokinin alone. Carbachol increased acid secretion and pepsinogen secretion by factors of 4.0 and 10.9, respectively (both p less than 0.01). Pretreatment with 10(-4) M omeprazole abolished basal and carbachol-stimulated acid secretion. However, pepsinogen secretion was unaffected (p greater than 0.05). Furthermore, omeprazole-treated tissues increased pepsinogen secretion by factors of 10.0 with 3 x 10(-7) M carbachol and 9.1 with 10(-9) M cholecystokinin (both p less than 0.01). Thus, basal and secretagogue-stimulated pepsinogen secretion appear independent of acid secretion in intact guinea pig mucosa.

Animals↗
PubMed1987

Pepsinogen. Prolate ellipsoid or unrecognized pathogen?

Pepsin is a potent proteolytic enzyme stored and secreted by chief cells in an inactive precursor form, pepsinogen. Its secretion is modulated by both cAMP and calcium-dependent mechanisms. Abnormalities in levels of pepsinogen and its various isozymogens have been linked clinically, epidemiologically, and experimentally to peptic ulcer disease and gastric carcinoma. The ulcerogenesis of pepsin stems from its ability to breach gastroduodenal mucosal barriers. Furthermore, certain isozymogens seems abundant and hyperactive in patients with peptic ulcer disease. The etiology and significance of low pepsinogen levels with disproportionate elevations of pepsinogen II and pepsin 5 in gastric cancer and its precursors is less clear. Further exploration of the patho-physiologic role of pepsin is likely to be of considerable importance in initiating further advances in the understanding and treatment of upper gastrointestinal disease.

Animals↗
PubMed1983

Bioethical decision-making: a reply to Ackerman.

Terrence Ackerman has suggested that we ought to view general bioethical principles as generalizations which summarize our previous bioethical decisions rather than as moral rules. He would have us derive our ethical views instead principally from the facts of the cases in question and our intuitions about them. The proposal is attractive because of its similarity to medical decision-making, but it fails because it allows for no higher order standard of reference against which conflicting ethical intuitions may be judged.

Bioethics↗
PubMed1982

Defective wound healing in patients with paraplegia and quadriplegia.

Patients with paraplegia and quadriplegia have a startlingly high incidence of healing problems in pressure protected wounds below the level of spinal denervation, suggesting clinically important defects in wound healing below the level of complete spinal neurologic loss. Healing of these wounds was, in fact, comparable with that of decubitus wounds in paraplegic patients in this study. Both groups of denervated wounds had significantly more complications of healing than did wounds above the level of spinal loss or wounds in nonparaplegic patients. Additional investigation is needed to explain and further delineate the apparently defective wound healing in these patients, which should not be attributed solely to pressure injury or chronic infection as it has in the past.

Adult↗
PubMed1981

Histochemical patterns of dehydrogenase activity in the development of free muscle grafts in the rat.

Patterns of activity of six dehydrogenase enzymes were studied histochemically in 42 free muscle grafts in the rat. Within hours, the surviving peripheral muscle fibers can be distinguished from the central ischemic muscle fibers. The surviving muscle fibers retain their characteristic pattern of staining throughout the post-transplantation period. The central ischemic muscle fibers stain abnormally and by five or six days they lose their enzymatic activity. The zone of regeneration, between the surviving and the ischemic muscle fibers, initially shows little dehydrogenase activity, but as the regenerating muscle fibers mature, they develop first a homogeneous staining pattern and, later, differences in staining intensity among different types of muscle fibers.

Animals↗