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Biomedical subjects

B L Bass

Publications and source records attributed to B L Bass.

85 records · Page 5Linked to original sources
PubMed1986

Bile acid accumulation by rabbit esophageal mucosa.

Bile acids are one of the noxious components of the gastroduodenal contents which may injure the esophageal mucosa in clinical reflux esophagitis. Animal models of esophagitis have shown that exposure to low luminal bile acid concentrations can cause increased mucosal permeability to a variety of ions and molecules without causing dramatic gross morphologic damage. In order to explore the mechanism by which bile acids alter mucosal permeability, we measured the esophageal mucosal concentration of taurocholic acid and chenodeoxycholic acid after exposure to these bile acids in anesthetized New Zealand white rabbits. We found that bile acids can accumulate in the esophageal mucosa to levels as high as seven times the initial luminal concentration. Thin-layer chromatography showed that this accumulation was not due to bile acid degradation in the mucosa. Since butyric acid also showed some mucosal accumulation, and is a weak acid like taurocholic acid, intracellular ionization may account for some of the accumulation. Mucosal accumulation of these molecules is not a nonspecific phenomenon, since the four-carbon polyol erythritol did not accumulate at all. Bile acid accumulation occurred under the same conditions and in a parallel temporal relationship to the bile-induced permeability changes. It is hypothesized, therefore, that the presence of high concentrations of bile acids in the esophageal mucosa may be pathophysiologically related to the alterations in mucosal permeability which occur after exposure to bile acids.

Animals↗
PubMed1986

Blood flow to transplanted fetal rat intestine.

Avascular fetal rat intestine becomes vascularized and grows and develops certain properties of normal small intestine when transplanted into the subcutaneous tissues of host syngeneic rats. We quantified the blood flow to this transplanted intestine (called "neogut") to clarify the role of angiogenesis in its growth and development. Additionally, we correlated blood flow and the growth of neogut into either patent tubular segments or large saccular segments with associated strictures. Blood flow was studied using 141Ce or 85Sr labeled microspheres. Blood flows are expressed as mean +/- SEM in (ml/min X g). Neogut blood flow (0.19 +/- 0.02) was greater than that of adjacent subcutaneous tissue (0.03 +/- 0.00, P less than 0.01) but less than that of native small bowel (0.85 +/- 0.07, P less than 0.01). The blood flow to the large saccular segments (0.10 +/- 0.01) was less than that to the tubular portions (0.27 +/- 0.02, P less than 0.01). The weight of neogut was comparable to that of native small bowel. These findings demonstrate that neogut implants stimulate angiogenesis to a degree which may be sufficient for it to absorb nutrients. Furthermore, ischemia is present in large saccular neogut segments with associated strictures. Additional investigation appears warranted to see if neogut can serve as a clinically useful small bowel substitute.

Animals↗
PubMed1986

Somatostatin analog: effects on hypergastrinemia and hypercalcitoninemia.

A somatostatin analog (SMS 201-995) was used to treat symptomatic patients with a residual tumor burden of gastrinoma or medullary thyroid carcinoma and pathologic elevations of circulating marker peptides associated with these neuroendocrine tumors. Possible inhibitory effects of the analog on marker peptides, patients' symptoms, or tumor progression were studied in a dose-response protocol and during several months of self-injection of SMS 201-995. Both patients reported remarkable relief of secretory diarrhea and other symptoms, and serum gastrin was successfully suppressed by increasing doses of the analog. However, no effect was seen in reduction of hypercalcitoninemia. Morphologic imaging of residual tumor showed no progression of medullary thyroid carcinoma during treatment and, in the case of hepatic gastrinoma metastases, remarkable tumor regression was confirmed. No toxicity or glucose intolerance was experienced. Somatostatin analog shows promise for palliative management of endocrinologic symptoms due to neuroendocrine tumors, and an inhibitory effect can be measured in some but not all peptide markers. Further evidence of its negative trophic effect on tumor blood flow may suggest an antineoplastic potential, as well as palliative use of this new treatment.

Adult↗
PubMed1985

Sucralfate prevents experimental peptic esophagitis in rabbits.

Sucralfate was tested in a rabbit model for its ability to prevent experimental esophagitis. Esophagitis was assessed by gross appearance and microscopic examination by an uninformed observer. In addition, the permeability of the esophagus to a number of probe molecules was measured to assess barrier function. Animals were exposed for 1 h to either acid alone (HCl at pH 2), acid plus pepsin (0.8 mg/ml), or acid plus taurocholic acid (5 mM), as well as to the same injurious agents with the addition of 1 g of sucralfate. At the completion of this hour, the perfusate was removed and all animals were again perfused for 1 h with HCl at pH 2 while mucosal permeability was assessed by measuring erythritol, glucose, potassium, and sodium fluxes. The animals were then killed. Sucralfate significantly diminished esophagitis and the attendant mucosal permeability changes induced by pepsin. The viscous sucralfate gel was shown to adhere tenaciously to the esophageal mucosa, but this characteristic of sucralfate was found not to be critical for its protective action because a clear sucrose sulfate solution with no gel present was also protective. Hence, it was not necessary for the gel to be present for the drug to be effective. Several in vitro tests suggested that the clear sucrose sulfate solution, like the sucralfate gel, probably acts through a topical protectant effect, rather than through pepsin inactivation. Although the degree of esophagitis induced by the bile acid was significantly less than that observed with pepsin, the mucosal permeability changes were comparable. Sucralfate did not significantly reduce the flux rates of glucose, potassium, and sodium nor did it affect the morphology of the mucosa after exposure to taurocholic acid. In conclusion, the binding of sucralfate to pepsin substrates in tissue results in this agent being very effective in preventing experimental peptic esophagitis.

Aluminum↗
PubMed1985

Intraluminal pCO2: a reliable indicator of intestinal ischemia.

A reliable, objective method to determine small bowel ischemia intraoperatively has not been developed. These experiments examined the relationship between intraluminal pCO2 (IL pCO2), intestinal blood flow, and degree of ischemic mucosal injury. IL pCO2 was measured with a clinical mass spectrometer using Teflon catheters calibrated in tissue mode; transmural intestinal blood flow was measured with radioactive microspheres. Anesthetized rabbits (N = 24) were cannulated for microsphere injections and mass spectrometer catheters were placed in the lumen of the small bowel. Blood flow was determined prior to superior mesenteric artery occlusion and then at 30, 60, or 180 min after occlusion. In control animals the superior mesenteric artery was not clamped. Intestinal biopsies were taken at the time of each blood flow determination and microscopic injury was graded from 1 (normal) to 4 (complete epithelial slough). There was a strong linear correlation between the IL pCO2 and the histologic grade of injury (r = 0.778, P less than 0.001). These results show that intestinal ischemia due to superior mesenteric artery occlusion causes a rapid, sustained rise in small bowel IL pCO2 that correlates with the degree of mucosal injury. These experiments suggest that this technology may provide a superior method to assess intestinal perfusion.

Animals↗
PubMed1984

Anatomic and physiologic characteristics of transplanted fetal rat intestine.

Avascular segments of fetal rat intestine transplanted to the subcutaneous tissues of host syngeneic rats will become vascularized and grow. This study more fully characterizes this tissue, which we call "neogut," and compares it to normal rat small intestine. Anatomy was studied with light microscopy and scanning and transmission electron microscopy; transport and electrophysiologic parameters were measured in full-thickness pieces of tissue mounted in Ussing chambers; motility patterns, including slow wave and spike activity, were recorded. Subtle anatomic differences (shortened villi and microvilli) were noted in neogut compared to normal small bowel. Both neogut and normal rat ileum demonstrated net mucosal to serosal transport of d-glucose; the magnitudes of the electrophysiologic parameters (PD, Isc, and G) were less in neogut than in ileum. Slow-wave frequency of neogut was slightly less than native small bowel while spike activity was increased. These data show that neogut has structural and physiologic characteristics similar to normal rat small bowel and offers hope that this tissue may provide a nutritionally useful accessory gut for the patient with critical short-gut syndrome.

Animals↗
PubMed1984

Hazards of nonoperative therapy of hepatic injury in children.

Several reports suggest that pediatric patients with stable liver injuries can be managed nonoperatively with few complications. From March 1978 to July 1983 seven children with hepatic injury were managed without surgery at CHNMC. Four children required greater than 50% total blood volume replacement, while the mean PRBC transfusion rate was 28 cc/kg. Eight major complications developed in five patients. Hospitalization averaged 23 days, without a mortality. This morbidity is greater than that described in earlier reports. In view of the limited cumulative clinical experience, we caution against routine nonoperative management of liver trauma in children until data with this new technique become available for analysis.

Blood Transfusion↗
PubMed1984

Bile acid efflux precedes mucosal barrier disruption in the rabbit esophagus.

In a rabbit model of esophagitis, bile acids are one of the agents capable of disrupting the normal esophageal mucosal barrier to diffusion. They are of particular interest because they may play a central role in causing reflux esophagitis, a major clinical problem. Bile acid efflux from the lumen of the esophagus occurs when bile acids disrupt the normal esophageal barrier. Whether this entry of bile acids into the mucosa is a critical step in the pathophysiology of bile acid injury to the mucosa or a result of the injury that is occurring by some other means is unknown. To differentiate these two possibilities, the temporal relation between bile acid efflux from the esophageal lumen and disruption of the mucosal barrier was studied with an in vivo perfused model of esophagitis in anesthetized New Zealand White rabbits. Solutions containing taurocholic acid or chenodeoxycholic acid at pH 2 or 7 were perfused for 4 h while bile acid, hydrogen ion, glucose, and erythritol flux rates were measured. In each case in which the bile acid caused barrier disruption, the highest rate of bile acid efflux occurred during the 1st h of perfusion. In contrast, the increase in flux rates of hydrogen ion, glucose, and erythritol, indicators of mucosal barrier disruption, were the highest during the 2nd or 3rd h of exposure. These data suggest that entry of bile acids into the esophageal mucosa is a cause rather than an effect of the bile-induced increase in mucosal permeability.

Animals↗
PubMed1984

H+ back diffusion interferes with intrinsic reactive regulation of esophageal mucosal blood flow.

The esophageal mucosa maintains a barrier that is relatively impermeable to glucose, H+, and other small molecules. Injury of the mucosa causes disruption of this barrier, manifest initially by increased permeability to small molecules. In the stomach the mucosa is protected from gross ulceration in the presence of bile-induced H+ back diffusion (JH+) by increases in mucosal blood flow (Qm). Qm to the esophagus during injury has never been studied. We explored the possibility that esophageal Qm would increase as a compensatory reaction to early barrier disruption. Rabbits (2 to 4 kg) were anesthetized and the in situ esophagus was luminally perfused for two 1-hour periods with subulcerogenic concentrations of bile salts, pepsin, or trypsin in the presence (pH 2) or absence (pH 7) of acid. Qm was measured with 15 mu radioactive microspheres in nine experimental groups with a total of 62 rabbits. Changes in Qm were compared with changes in permeability of the esophageal barrier to glucose, Na+, and H+. When the mucosal barrier was broken by bile salts or trypsin at a neutral pH, no acid back diffusion occurred and barrier disruption was accompanied by dramatic increases in esophageal mucosal blood flow. In contrast, barrier disruption by bile salts, pepsin, or acid during pH 2 perfusions failed to elicit increases in Qm when significant JH+ (50 microEq/hr) occurred. These results demonstrate a loss in reactive regulation of esophageal Qm in the presence of significant JH+ that may contribute to the injury seen in acid reflux esophagitis.

Animals↗
PubMedDate not supplied

Role of transforming growth factor-beta in growth and injury response of the pancreatic duct epithelium in vitro.

Chronic pancreatitis is characterized by increased levels of expression of transforming growth factor-beta (TGF-beta), particularly in and around the ducts. To examine the consequences of elevated exposure to TGF-beta on the pancreatic duct epithelium, we cultured segments of the main bovine pancreatic duct in the presence of increasing doses of TGF-beta. We also studied the effect of TGF-beta on epithelial injury, produced in this model by exposure to a bile acid. The extent of proliferation, migration, and epithelial damage was measured morphometrically on sections stained with hematoxylin and eosin. Proliferation and apoptosis were qualitatively determined by means of immunohistochemical analysis. In this model of duct cell culture, TGF-beta stimulated cell migration in areas of the explants where the native basement membrane of the duct epithelium was absent. In segments where the native basement membrane remained intact, proliferation was inhibited and apoptosis induced. When the explants were exposed to bile acid, extensive epithelial injury was observed. TGF-beta exposure at high doses (1 nmol/L protected epithelial integrity, but cellular morphology was altered and the process of apoptosis appeared to be increased. Our results suggest that increased periductal levels ot TGF-beta in the setting of pancreatic injury may be intended to promote repair of acute epithelial damage but may have detrimental long-term effects.

Animals↗
PubMedDate not supplied

Extracellular matrix modulates enterocyte growth via downregulation of c-jun but is independent of p21 and p27 expression.

Regulation of the intestinal crypt-villus axis is multifactorial and involves growth factors and extracellular matrix composition. Laminin, a component of the enterocyte basement membrane, induces enterocyte differentiation and inhibits proliferation. To investigate the mechanism of this observation, we examined the expression of cell cycle modulators in enterocytes cultured on laminin. IEC-6 enterocytes were cultured on collagen I or laminin for 24 hours in media with serum followed by 48 hours of culture in serum-free media. Cells were then stimulated with epidermal growth factor, and RNA and protein were extracted before and up to 18 hours after stimulation. c-jun mRNA expression and p21 and p27 protein expression were analyzed. Expression of c-jun was inhibited in cells grown on laminin as compared to collagen I. Expression of p21 and p27 was no different between cells grown on laminin or collagen I. The mechanism of enterocyte growth inhibition mediated by laminin involves downregulation of c-jun expression. In contrast, p21 and p27 levels were unaffected by extracellular matrix indicating that the changes in expression of these cyclin-dependent kinase inhibitors do not contribute to the effect of laminin on enterocyte proliferation.

Animals↗
PubMedDate not supplied

Specific interaction between the self-splicing RNA of Tetrahymena and its guanosine substrate: implications for biological catalysis by RNA.

Splicing of the ribosomal RNA precursor of Tetrahymena has previously been shown to require no protein in vitro; the cleavage-ligation activity is intrinsic to the RNA molecule. Analysis of the reaction kinetics with guanosine, which is a substrate in the reaction, and with several guanosine analogues suggests that guanosine binds to a specific site on the pre-rRNA. It appears that the RNA, like an enzyme, binds its substrate to promote the rate and specificity of a biological reaction.

Animals↗