Microcirculation of the islets of Langerhans. Long Beach Veterans Administration Regional Medical Education Center Symposium.
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Animals↗
Biomedical subjects
E Passaro
Publications and source records attributed to E Passaro.
Pancreatic polypeptide immunoreactivity in sporadic gastrinoma: relationship to intraabdominal location.
Sporadic gastrinoma is a pancreatic endocrine tumor whose ontogeny is unknown. The anatomic area where the vast majority of sporadic gastrinomas is found (pancreatic head region) corresponds topographically to the area traversed embryologically by the ventral pancreatic bud. Pancreatic polypeptide (PP), a 36-amino acid hormone, is secreted by pancreatic endocrine cells derived almost exclusively from the ventral pancreatic bud and is proposed as a marker for ventral bud derivation. Based on these observations we postulate that sporadic gastrinomas, found around the head of the pancreas, are derived from ventral bud tissue and should display a high incidence of PP immunoreactivity. Overall, we found PP immunoreactivity in 7 of 14 (50%) gastrinomas. Of those tumors located to the right of the superior mesenteric artery (SMA) (around the head of the pancreas), seven of nine (78%) contained PP, whereas no gastrinoma to the left of the SMA (n = 5) contained PP (p = 0.021; Fisher exact test). Only one other pancreatic endocrine or exocrine tumor, a glucagonoma located to the left of the SMA, stained positively for PP. We conclude that sporadic gastrinomas found around the head of the pancreas (to the right of the SMA) have a high incidence of PP immunoreactivity. These findings are consistent with our hypothesis that sporadic gastrinomas are derived from the ventral pancreatic bud.
Gastrinoma↗
Putative tumor-suppressor gene on chromosome 11 is important in sporadic endocrine tumor formation.
Endocrine tumors arising sporadically or as a manifestation of the multiple endocrine neoplasia type I syndrome (MEN I) have been shown to have mutations on chromosome 11. These mutations can be detected at the molecular level by loss of heterozygosity (LOH) for DNA markers from chromosome 11. This study represents one of the largest collections of sporadic endocrine tumors in which LOH was systematically assessed on chromosome 11 for the loci flanking the proposed MEN I region. DNA was isolated from 39 endocrine tumors and probed with 7 DNA probes spanning the region of chromosome 11q13 from the loci PYGM to INT-2. Eleven tumors demonstrated LOH at any two loci in this region. The remaining 28 tumors showed no LOH or were noninformative at these loci. Thus, nearly 30% of these tumors showed LOH in the region (from PYGM to INT-2) that is thought to contain the MEN I gene(s). Previous studies of sporadic endocrine tumors have suggested that these tumors may arise via the same mechanism as tumors of the MEN I syndrome. Namely, these sporadic tumors are thought to result from mutations leading to genetic loss on the long arm of chromosome 11, thereby inactivating a possible tumor-suppressor gene (or genes). These findings strongly support the hypothesis that sporadic pancreatic endocrine tumors share a similar etiology of tumorigenesis with tumors of the MEN I syndrome, which principally involves deletion of a tumor-suppressor element (or elements).
Blotting, Southern↗
Transplant rejection. Mechanisms and treatment.
In this review, we summarize the cellular and molecular events in the rejection of transplanted allografts, as well as the rationale for the evolving techniques to suppress such rejection. Allogenic major histocompatibility complex antigens expressed on the allograft and/or on the "passenger leukocytes" within the graft are the major antigenic stimuli recognized as being foreign by receptors of CD4+/T helper cells of the host. Host macrophages provide a second signal, interleukin (IL) 1, essential to the activation of T helper cells. Subsequent production of IL-2 by T helper cells leads to activation and proliferation of cytotoxic T cells and lymphokine-activated killer cells and the release of IL-4 and IL-6. In addition, IL-2 promotes release of interferon gamma as well as tumor necrosis factor and other proinflammatory cytokines. Therapeutic options to "downregulate" this cascade have gradually evolved from global nonspecific immunosuppressive techniques (total body irradiation, antilymphocyte serum) to increasingly specific modalities currently being studied, including monoclonal antibodies against the IL-2 receptor (thus targeting only vigorously proliferating T cells), antibodies against specific cytokines (interferon gamma, tumor necrosis factor), and now "designer" antibody-toxin conjugate molecules that deliver toxins to selected receptor targets. Finally, work continues toward inducing preoperative antigen-specific (graft) tolerance, including utilization of gene transfection techniques to transfect donor major histocompatibility complex antigens to recipients before surgery, which has been shown to prolong murine cardiac allografts, perhaps by priming specific suppressor cells. Further understanding of the initiation of, and subsequent events in, transplantation rejection will lead to increasingly effective prolongation of graft survival while minimizing adverse effects on the host.
Graft Rejection↗
Isoproterenol prevents ethanol-induced microvascular stasis and deep histologic injury in rat gastric mucosa.
The effect of topical isoproterenol (5.8 x 10(-5) M) on the microvascular stasis and histologic injury produced in the rat gastric mucosa by absolute ethanol was investigated using in vivo microscopic and histologic techniques. Our findings show that in control animals, absolute ethanol applied to the gastric mucosa caused a rapid decrease in microvascular blood flow, leading to complete stasis by 3 min. In contrast, prior treatment of the gastric mucosa with topical isoproterenol increased microvascular blood flow initially and then maintained microvascular flow in the majority of microvessels studied after the application of absolute ethanol. Treatment with topical isoproterenol also reduced the histologic injury score and percent mucosal necrosis caused by absolute ethanol. Pretreatment of animals with a beta-adrenergic antagonist propranolol (2 mg/kg subcutaneously), completely blocked these protective effects. We observed no systemic effects attributable to the topical use of isoproterenol. These results indicate that prior treatment of the gastric mucosa with topical isoproterenol maintains microvascular blood flow and reduces the deep histologic injury in the stomach caused by 100% ethanol.
Analysis of Variance↗
Regional differences in mucosal hemodynamics in experimental colonic injury in rats.
In rat colon damaged by 10% acetic acid and by dinitrochlorobenzene, we test the following hypotheses: (1) mucosal hemodynamic changes are significantly different at the ulcer base, the ulcer margin, and the inflamed non-ulcer-bearing mucosa; and (2) these mucosal hemodynamic changes also vary with time after induction of the colonic injury. Mucosal hemodynamic changes were documented by reflectance spectrophotometry, and variations in gross mucosal morphology were confirmed by hematoxylin and eosin histologic sections. Results revealed that in the acute stage, the ulcer base, which was covered by necrotic debris, showed ischemia without congestion. The ulcer margin at the edge of the ulcer base showed ischemia with congestion. The nonulcerated mucosa, which appeared erythematous, showed increased perfusion. In the convalescent stage, all the altered perfusion patterns returned to normal. These observations offer plausible explanations for the variability in colonic perfusion observed in experimentally damaged colons.
Acetates↗
Biologic behavior of sporadic gastrinoma located to the right and left of the superior mesenteric artery.
Among a series of 107 closely followed patients with gastrinoma, 60 patients with sporadic type tumors were identified and evaluated. There were 44 patients (73%) with tumors to the right of the superior mesenteric artery (SMA). Of these, 16 (36%) had extrapancreatic tumors, 28 (64%) had tumor within lymph nodes, and 9 (20%) had multiple tumors. In this group of patients, there were 19 (43%) cures, and only 9 (20%) patients had hepatic metastases. In contrast, in 16 patients (27%) with tumors to the left of the SMA, there were no extrapancreatic tumors, only 3 patients (19%) had tumor within lymph nodes, and 7 (44%) had multiple tumors. In this group, there was only one cure (6%), and nine (56%) patients had hepatic metastases. These findings suggest two distinct populations of sporadic gastrinoma, one to the right (gastrinoma triangle) and the other to the left (outside triangle) of the SMA, which appear to have different biologic behaviors. These differences may reflect divergent etiologies for these two groups of tumors.
Female↗
Human Genome Project.
The Human Genome Project is an international effort to clone and sequence the entire human genome. This audacious undertaking, estimated to cost 200 million dollars per year and require 15 years to complete, promises to be one of the most revolutionary and captivating scientific endeavors ever conceived by mankind. By knowing the sequence of the estimated 3 billion base pairs of the haploid human genome and its more than 30,000 genes, many questions will be answered. Moreover, our ability to intervene at the genetic level will be possible. This review outlines the scientific goals and methods of this project and discusses some of its ethical, legal, and social ramifications.
Base Sequence↗
Molecular biology and therapy of disease.
Molecular biology will have a profound impact upon the treatment of disease. Molecular techniques provide protein products for treatment of more diseases each year. The understanding of pathophysiology at the molecular level allows for improved drug design. Antisense technology can selectively control gene expression. Gene therapy is potentially the most important aspect of molecular biology. Physical and viral transduction mechanisms are being developed toward this end. Gene replacement, creation of antisense oligonucleotides, and prodrug strategies are being developed. Currently, gene replacement and prodrug therapy are feasible in at least a few cases, but further study will yield additional applications.
Antisense Elements (Genetics)↗
A review of gene transfer techniques.
The ability to transfer genetic material from one cell to another provides a novel approach for the investigation and potential treatment of a variety of diseases. Several gene transfer techniques have been developed. Of these, the use of retroviruses as vectors has allowed highly efficient and stable introduction of foreign genes into target mammalian cells, thus making gene therapy possible. The current prospects are that some unusual lethal diseases can be corrected and that various forms of cancer will be treated in this manner.
Animals↗
Surgery for duodenal and gastric ulcer disease.
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Duodenal Ulcer↗
Molecular biology: the message, its language, and the surgeon.
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General Surgery↗
Laparoscopic surgery. A difference.
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Humans↗
Loss of heterozygosity on chromosome 11 in sporadic gastrinomas.
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.
Blotting, Southern↗
Superior mesenteric artery is more important than inferior mesenteric artery in maintaining colonic mucosal perfusion and integrity in rats.
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.
Animals↗
Molecular biology: an overview.
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, Recombinant↗
Molecular mechanisms of tumor formation.
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.
DNA, Neoplasm↗