Molecular biology: the message, its language, and the surgeon.
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Biomedical subjects
Publications and source records attributed to E Passaro.
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Gastrinomas are pancreatic endocrine neoplasms that arise either sporadically or are inherited as part of the multiple endocrine neoplasia type I syndrome (MENI). Loss of heterozygosity (LOH) in the region flanking the MENI gene at chromosome 11q13 has been documented in a few sporadic and familial pancreatic endocrine tumors, but not previously in sporadic gastrinomas. It has therefore been suggested that gastrinomas develop by a mechanism different from other tumors associated with the MENI syndrome. We report LOH on chromosome 11 in 5 of 11 sporadic gastrinomas. Four of these tumors have LOH for markers flanking the MENI region. Molecular evaluation of segments of chromosomes 3, 13, and 17 known to contain cloned or putative tumor suppressor genes fail to show LOH except at one locus in one tumor. These data suggest that a tumor suppressor DNA segment exists at 11q13 that may be involved in the development of sporadic gastrinomas.
Mucosal hemodynamics (by reflectance spectrophotometry) and mucosal damage (by histologic examination) following acute colonic ischemia were evaluated in different anatomic locations in the colon of anesthetized rats. The reflectance spectrophotometer provides an index of mucosal hemoglobin concentration (IHB) and an index of oxygen saturation of hemoglobin (ISO2). The patterns of ischemia without congestion (decreases IHB, decreases ISO2) during superior mesenteric artery occlusion, and ischemia with congestion (increases IHB, decreases ISO2) during portal vein occlusion, previously demonstrated in the stomach and duodenum, are also applicable to the colon. The significant linear correlations between changes (as percent of baseline) in IHB, ISO2, and hydrogen gas clearance suggest that changes in these indices are adequate indicators of changes in colonic mucosal perfusion. Superior mesenteric artery ligation produced significant reductions in both indices, and an increase in damage in the mucosa of the cecum, transverse colon, splenic flexure, and left colon, but not the rectum. Inferior mesenteric artery ligation produced only slight reduction in these indices and minimal damage only in the mucosa of the splenic flexure. These results support the hypothesis that the superior mesenteric artery is more important than the inferior mesenteric artery in maintaining colonic perfusion and colonic mucosal integrity in the rat.
An overview of molecular biology is presented for the practicing surgeon. Definitions of the constructs and activity of DNA, RNA, and protein synthesis are defined. These principles are illustrated in their use in recombinant DNA technologies. A glossary is provided for the terms utilized.
DNA is the fundamental guide for the cell's processes. The alterations in DNA that can lead to abnormal or absent proteins and the role of chromosomal alterations in changing the function of the DNA are reviewed. The role of viruses in derailing a cell's normal functions, the major mechanisms of oncogene action, and tumor suppressor genes are also discussed.
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Ischemia and reperfusion of the small intestine and colon in rats were produced by reversible occlusion (for 30 min and 1 or 3 h) of the superior mesenteric artery and the aorta above the inferior mesenteric artery. Despite a greater reduction of mucosal perfusion in the colon than in the small intestine with 30 min of ischemia, the depth of mucosal damage was significantly smaller in the former than in the latter. Thirty minutes of ischemia followed by 1 h of reperfusion induced an increase in polymorphonuclear leukocyte infiltration in both locations. Exacerbation of mucosal injury occurred only in the small intestine, suggesting that reperfusion injury is independent of polymorphonuclear leukocyte infiltration. Reperfusion after 1 or 3 h of ischemia did not exacerbate mucosal damage in either location. Allopurinol significantly diminished the exacerbation of injury after reperfusion in the small intestine. The protective effect of allopurinol, however, was neither associated with an improvement in perfusion nor a reduction in polymorphonuclear leukocyte infiltration. These data indicate that there is a window (30 min) of reperfusion injury in the small intestine, but there is no evidence of reperfusion injury in the colon.
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With the availability of DNA recombinant technology and DNA and RNA sequencing techniques, diseases can now be studied and treated at a molecular level, while unlimited quantities of a pure protein product can be produced through gene cloning. Before the end of this century, gene therapy will be used to repair genetic defects. This article explains these advances in genetic technology and suggests their relevance in clinical problems and practice.
Among 70 cases of perforated duodenal ulcers treated by plication, eight were complicated by massive postoperative hemorrhage from a syncronous posterior "kissing" duodenal ulcer. Critical analysis revealed that only signs of gastrointestinal (GI) bleeding preoperatively had predictive value for postoperative hemorrhage. Twenty-four patients had one or more predictive signs, and eight actually bled postoperatively. There was a 50% mortality and 75% additional complication rate for the bleeders. In contrast, the nonbleeders had a mortality and a complication rate of only 18% and 35%, respectively. There was no observed superiority of either surgical or medical treatment for postoperative hemorrhage. In perforated duodenal ulcer with evidence of GI blood loss, an intraoperative search for a posterior kissing ulcer is recommended. If a kissing ulcer is found, an acid-reducing operation and suture ligation of the ulcer is indicated.
Lower gastrointestinal bleeding from intestinal varices cannot readily be detected at operation; hence, preoperative identification is important. Our experience with six patients having sudden, massive bleeding per rectum from intestinal varices suggests a group of common findings. These patients had cirrhosis, no blood in the stomach or duodenum, characteristic mucosal imprints on barium enema, or direct visualization of varices on sigmoidscopy or colonoscopy. Only two had demonstrable esophageal varices. The diagnosis was confirmed and the site of the varices localized on the venous phase of selective mesenteric angiography in five patients. Varices were located in the duodenojejunum in two, in the cecum and ascending colon in two, and in the rectum and sigmoid colon in two patients. Three patients were treated nonoperatively with transfusion and intraarterial infusion of vasopressin into the superior mesenteric artery; one died. One patient with cecal varices had a right hemicolectomy that controlled the bleeding, but progressive hepatic failure resulted in postoperative death. The remaining two patients had successful decompression of left colonic varices by portasystemic shunt.
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Basal human pancreatic polypeptide (H.P.P.) concentrations have been measured in 41 pateints with Zollinger-Ellison syndrome (Z.E.S.) and in 100 controls. Basal H.P.P. concentrations in controls varied widely from less than 8 pmol/l (assay detection limit) to 313 pmol/l. In controls, but not in the Z.E.S. patients, there was a highly significant positive correlation between basal H.P.P. and age (P less than 0.01). 4 of the Z.E.S. patients (9.8%) and 3 of the controls (3%) had H.P.P. concentrations over 240 pmol/l. These findings indicate that raised basal H.P.P. concentration is an infrequent finding in patients with gastrinomas and therefore it is not a useful tumour marker.
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