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Biomedical subjects

C Mandell

Publications and source records attributed to C Mandell.

At least 19 recordsLinked to original sources

Determination of elastase activity by reversed-phase high-performance liquid chromatography.

The action of elastase on elastin was measured by high-performance liquid chromatography with on-line post-column derivatization. After alkaline hydrolysis, a 20-ml sample was injected into a ODS-2 gel column. An elastin-specific dipeptide, Val-Pro, and the internal standard, Gly-Leu, were eluted by a linear gradient of 0 to 10% of 1-propanol in 50 mM heptafluorobutyrate (pH 3) at a flow-rate of 1 ml/min. The eluent was reacted with fluorescamine, and the fluorescent products were measured. Retention times for Val-Pro and Gly-Leu were 17.33 and 23.54 min. The peak areas of 0.2-16 micrograms of Val-Pro gave a straight-line plot. Elastase activity was constant from 6 to 24 h and was 0.95 +/- 0.02 (S.D.) micrograms/h. The method may be useful for the measurement of the elastolytic activity in some diseased tissues.

Chromatography, High Pressure Liquid

Activation of rabbit aortic elastase by nonaortic intraabdominal surgery.

The purpose of this study was to determine whether aortic elastase could be activated by distant operative trauma unrelated to direct aortic injury. One hundred rabbits were divided into five groups: group I - anesthesia only; group II - laparotomy only; group III - cecal resection; group IV - aortic mobilization; and group V - aortotomy with repair. Animals were sacrificed at one hour, three hours, six hours, one day, two days, and five days after surgery, and the aorta was analyzed for elastase activity. Operative trauma such as laparotomy, bowel resection, and mobilization of the aorta without direct aortic injury resulted in a significant increase in rabbit aortic elastase. The pattern of activation of rabbit aortic elastase within the laparotomy, aortic mobilization, and aortotomy groups was one of a slow rise to peak activation at 6-24 hours with a subsequent fall towards baseline at five days after surgery. This pattern differed in the cecal resection group in which activation occurred immediately with a slow fall towards baseline at five days. In none of the four surgical groups did the elastase activity return to baseline by five days after surgery. These data suggest that aortic elastase in rabbits can be activated by intraabdominal surgery unrelated to direct aortic injury.

Abdomen

Elastin metabolism of the infrarenal aorta.

Aortic tissue elastase and alpha 1-antitrypsin were assayed in 67 patients with different types of infrarenal aortic disease; occlusive disease, elective abdominal aortic aneurysms (AAAs), multiple aneurysms, and ruptured aneurysms. Elastase modified by alpha 1-antitrypsin (elastase/alpha 1-antitrypsin) increased significantly as the type of aortic disease changed from occlusive to aneurysmal disease. Aortic elastase was significantly higher in patients with AAAs, multiple aneurysms, and ruptured AAAs compared with occlusive disease. The alpha 1-antitrypsin, was significantly lower in patients with multiple aneurysms and ruptured AAAs. These data suggest that the ratio between elastase and its major serum inhibitor, alpha 1-antitrypsin, is significantly altered in the aortic wall in different types of infrarenal aortic disease. In addition, the ratio between these two enzyme systems changes in favor of more proteolytic activity as the type of infrarenal disease changes from occlusive to aneurysmal.

Aorta, Abdominal

Characterization of human aortic elastase found in patients with abdominal aortic aneurysms.

Recent evidence indicates that the homeostatic balance between elastase and antiprotease activity is altered in the infrarenal aorta of those patients with different types of aortic pathologic findings. The specific properties of elastase found in the aorta of patients with abdominal aortic aneurysms (AAA) are discussed herein. Activity of elastase extracted from ten pooled AAA specimens was observed when incubated with several inhibitors: 13.2 per cent for phenyl-suphonyl flouride (PSF); 43.3 per cent for ethylenediaminetetraacetic acid (EDTA); 77.7 per cent for pepstatin; 137.0 per cent for leupeptin, and 24.0 per cent for alpha-1-antitrypsin. Irreversible inhibition by PSF indicates that the elastase is a serine protease. The elastase is most likely not a metallo enzyme, since it had no absolute requirement for divalent cations as indicated by only partial inhibition by EDTA. Elastase activity is most likely not due to cathepsins B or D, since cathepsins are active in an acid pH and selectively inhibited by leupeptin and pepstatin. The pH curve revealed a maximum activity at pH 8.2 and elastase activity was significantly inhibited by alpha-1-antitrypsin in a dose response manner determining functional elastase activity. These data indicate that the elastase in the aorta of patients with an AAA has the exact properties of the serine elastase found in the smooth muscle cells of the aorta in rats. These results also confirm the critical role of alpha-1-antitrypsin in determining functional elastase activity. Smooth muscle cell regulation of elastin metabolism may be important in determining why some patients have AAA and others have occlusive aortic disease develop.

Aorta, Abdominal

Altered aortic protease and antiprotease activity in patients with ruptured abdominal aortic aneurysms.

Aortic elastase, antiprotease (a-1-antitrypsin) and total protein were assayed in 37 patients who underwent an operation on the abdominal aorta for ruptured abdominal aortic aneurysms (AAA), an elective procedure for AAA or aortofemoral bypass for occlusive disease. Aortic elastase modified by local antiprotease activity (elastase/a-1-antitrypsin) was significantly higher in patients with a ruptured AAA compared with patients with an elective AAA or occlusive aortic disease: 241 nanograms per milligram of tissue in AAA-rupture versus 57 nanograms per milligram of tissue in AAA-elective versus 32 nanograms per milligram of tissue for occlusive (p less than 0.003). Patients with a ruptured AAA had the highest elastase activity (354 nanograms per milligram of tissue) and the lowest a-1-antitrypsin (1.07 nanograms per milligram of tissue) compared with patients with an elective AAA and occlusion (p less than 0.05). These data suggest that the homeostatic balance between elastase and antiprotease may be significantly altered in the aortic wall at the time of aneurysm rupture. Increased elastase unchecked by low antiprotease results in increased elastin breakdown which may be the inciting event for rupture of a compromised, thin aortic aneurysm wall.

Aorta, Abdominal

Changes in bile salt composition after cholecystectomy and ileal resection.

The effect of ileal resection and cholecystectomy on bile salt metabolism was studied in female prairie dogs 4 weeks after either a sham laparotomy, cholecystectomy, ileal resection, or cholecystectomy and ileal resection. Bile was collected from a common bile duct cannula at hourly intervals for 12 hours. Pool sizes and synthetic rates of primary and secondary bile salts were determined from washout curves. Cholate, chenodeoxycholate, deoxycholate, and lithocholate levels were determined by gas chromatography from pooled collections of bile. After cholecystectomy and ileal resection, the pool sizes of primary and secondary bile salts were significantly reduced to amounts that were much less than the pool sizes after either procedure alone. Primary bile salt synthesis was significantly increased after combined cholecystectomy and ileal resection, to the same degree as cholecystectomy alone. After the combined procedures, there was a decrease in the proportion of cholate in hepatic bile associated with an increase in chenodeoxycholate, deoxycholate, and lithocholate levels. The data suggest that after the loss of both ileum and gallbladder the bile salt pool sizes are drastically reduced, the synthesis of primary bile salts is increased, and the proportion of secondary bile salts is increased. Cholecystectomy should be avoided, if possible, in patients with ileal resection in order to conserve the bile salt pool and prevent severe fat malabsorption.

Animals

Nutritional effects of postgastrectomy reconstructions.

To compare the nutritional effects of two modes of reconstruction after total gastrectomy, a Hunt-Lawrence pouch was constructed in five mongrel dogs, whereas five other dogs had a simple Roux-Y esophagojejunostomy performed. Total body weight, daily food intake, serum albumin values, and intestinal absorption of carbohydrates, fats, and amino acids were evaluated in both groups over a period of 3 months. All values decreased postoperatively when compared with the preoperative values; however, there was no significant difference between the two groups. This study suggests that there is no nutritional benefit from a Hunt-Lawrence pouch over a simple Roux-Y esophagojejunostomy after total gastrectomy.

Animals

Discriminability of frequency of food or stimulus presentations in variable-time schedules.

Pigeons responded in a two-alternative forced-choice task in which reinforcement was dependent upon the frequency of events that occurred in an immediately preceding schedule sample. On a given trial the events were either brief food presentations or brief visual and auditory stimulus changes. High levels of stimulus control were obtained by food-presentation schedules only. Discriminative control by frequency or stimulus change was absent. Stimulus control by food frequency was decreased by the imposition of a delay period between the schedule sample and the choice. Moreover, stimulus control by food frequency was related to the ratio of food-presentation schedule pairs when novel schedules were presented in a transfer test.

Animals

Cimetidine, carbenoxolone sodium, and antacids for the prevention of experimental stress ulcers.

Cimetidine, an H2-receptor, antagonist, and carbenoxolone sodium, a drug used to stimulate gastric mucus synthesis and increase the life span of gastric epithelial cells, were studied to determine their possible prophylactic effect on the formation of stress ulcers, gastric transmucosal potential difference and gastric pH in rats, using a restraint stress model. The number of ulcers substantially decreased in the rat groups receiving either cimetidine or carbenoxolone pretreatment for two or more days before stress. When the drugs were used in combination, there was an additive effect, since there was a significant decrease in ulcer formation even after half a day of pretreatment. When antacids were used, there was also decreased ulcer formation with half a day of pretreatment. Gastric pH was significantly increased from control levels in all the groups treated with antacid, cimetidine and carbenoxolone. Both cimetidine and carbenoxolone, either alone or in combination, prevented the decrease in potential difference that was produced in the untreated stressed rats. This study suggests that either cimetidine or carbenoxolone, and particularly their combination, may be a useful prophylactic regimen for the prevention of stress ulceration in patients subjected to severe stress.

Animals

The response of the local immunoglobulin system to malignant lesions of the stomach. A new diagnostic test.

The response of the local secretory immunoglobulin system to tumor antigens was studied in 71 patients suspected of harboring a gastric malignancy. Gastric aspirates were obtained by fiberoptic endoscopy and measured on single radial immunodiffusion plates (Behring Diagnostics). Patients with malignant neoplasms of the stomach were divided into Type I and Type II lesions, based on the extent and stage of the disease. Secretory IgA titers were elevated in all patients with a Type I malignant tumor confirmed by histologic examination; mean 6.1 mg/100 (SD +/- 3.7 mg/100). This leads us to believe that the host's response to malignant cells of the gastrointestinal system is an altered and elevated secretion of IgA. Evaluation of local immunoglobulin titers may be of value when used in conjunction with other diagnostic modalities in determining the nature of gastrointestinal lesions, particularly when the lesion is not metastatic or massively involving the gastric wall.

Adult

Differential reinforcement and signal detection.

Reinforcement was introduced for responses normally treated as errors in signal-detection procedures. The first experiment used a standard two-response discrete-trial procedure with no reinforcement for errors. Results showed that rats altered their response biases but maintained constant sensitivity to visual signals when reinforcement probabilities varied, and that their sensitivity depended on the physical difference between signals, in accordance with the predictions of signal-detection theory. Experiment II, with rats, and Experiment III, with pigeons, demonstrated that sensitivity decreased in this procedure when reinforcement was scheduled for errors with the signals held constant, despite independence of overall number of reinforcers and sensitivity. Experiment IV, with rats, replicated the decrease in sensitivity in a continuous procedure employing only one response. The decrements in sensitivity were similar across Experiments II, III, and IV, and accorded well with earlier research. Thus, contrary to a fundamental assumption of signal-detection theory, estimates of sensitivity are not always invariant with respect to the outcomes of responding, but depend on relative reinforcement of correct responses.

Animals