Immunoreactive neuron-specific enolase, bombesin, and chromogranin as markers for neuroendocrine lung tumors.

Sixty-four lung tumors were evaluated for the presence of immunoreactive neuron-specific enolase (NSE), bombesin (Bn), and chromogranin (Cg) to assess their value as markers for neuroendocrine cells in the histologic diagnosis of pulmonary neoplasms. Staining was correlated with the presence and density of neurosecretory granules (number of neurosecretory granules per unit cytoplasmic cross-sectional area) as determined by planimetry on electron micrographs. The cytoplasmic density of neurosecretory granules was significantly greater in the carcinoid tumors than in the small cell carcinomas (P less than 0.001). Neuron-specific enolase was localized in all of the neuroendocrine granule-bearing tumors but was also present in 57 per cent of the nonneuroendocrine carcinomas. Bombesin was present in 68 per cent of the neuroendocrine tumors and in less than 1 per cent of the nonneuroendocrine tumors. Staining for Cg appeared to correlate with the density of neuroendocrine granules, with staining in carcinoid tumors but no staining in small cell anaplastic carcinomas. A panel of antibodies may be required for the reliable identification of neuroendocrine lung tumors by immunohistochemical techniques.

Significance of gastrointestinal cytomegalovirus infection in homosexual males.

Gastrointestinal cytomegalovirus (CMV) infection usually occurs in immunosuppressed patients and has recently been reported in patients with the acquired immune deficiency syndrome (AIDS). Serological evidence of CMV infection and a variety of traumatic and infectious gastrointestinal disorders are known to occur in nonimmunosuppressed homosexual males. However, the significance of gastrointestinal CMV infection in nonimmunosuppressed homosexual males is not well known. Three unusual cases of gastrointestinal CMV infection in homosexual males are presented. Infection of a Kock pouch in one patient and an anal ulcer in another, occurred as part of a CMV mononucleosis syndrome. In the third patient, CMV was found in an acutely inflamed appendix. Although gastrointestinal CMV infection has been reported frequently in patients with AIDS, our patients showed no evidence of immunosuppression or AIDS 6 wk to 1 year later. Gastrointestinal CMV infection in homosexual males with gastrointestinal disease should not be considered indicative of AIDS.

Effects of choledochojejunostomy with Roux-en-Y exclusion on dimethylhydrazine induced neoplasms in rats.

The role of biliary secretions was studied in the development of neoplasms in the small intestine and colon of rats treated with 1,2-dimethylhydrazine (DMH). Sixty-eight female Sprague-Dawley rats underwent either no operative procedure or choledochojejunostomy with or without a Roux-en-Y exclusion. All animals then received weekly subcutaneous injections of DMH at 20 mg/kg for 26 weeks and were subsequently sacrificed. The largest number of neoplasms was found in the proximal duodenum, within 3 cm distal to the pylorus, in the control as well as both operative groups. In addition, only six neoplasms developed in relation to the choledochojejunostomy site in rats undergoing choledochojejunostomy only, and no neoplasms were noted at this location in the animals undergoing choledochojejunostomy with Roux-en-Y exclusion. These results suggest that the distribution of enteric neoplasms in DMH treated rats does not depend on excretion of active carcinogen in bile.

Gastric lymphoreticular neoplasms: an immunologic study of 36 cases.

Thirty-six lymphoreticular neoplasms involving the stomach were studied by immunologic technics (particularly immunoperoxidase on paraffin sections) for the localization of immunoglobulins, lysozyme, and alpha one-antitrypsin. Fifteen of 29 (52%) primary gastric lymphomas marked as B-cell lymphomas and only one primary gastric lymphoma of true histiocytic type was identified. This is in contrast to the high incidence of true histiocytic tumors reported in some recent studies. Immunoperoxidase on paraffin-embedded and frozen tissues from endoscopic biopsies or surgical resections was particularly useful in confirming the diagnosis of five of seven B-cell immunoblastic sarcomas and 8 of 12 small lymphoid proliferations including two pseudolymphomas. Twenty-two of 29 (76%) primary gastric lymphomas were large-cell lymphomas. The previously reported high incidence of plasma cell tumors could not be confirmed. Atrophic gastritis remote from the neoplasm was noted in 8 of 15 (53%) patients, and this relationship is discussed.

Isolation of spontaneous and interferon inducible natural killer like cells from human colonic mucosa: lysis of lymphoid and autologous epithelial target cells.

Viable mononuclear and epithelial cells were dispersed from human colonic tissue by treatment with collagenase and ethylene diamino-tetra acetate (EDTA) and separated by centrifugal elutriation. Using a single cell cytotoxic assay, functional endogenous and interferon responsive mononuclear cytotoxic cells were detected. Compared to peripheral blood lymphocyte associated killer cells that had been exposed to similar treatment, these colonic killer cells demonstrated lower efficiency cytotoxicity of Molt-4 target cells. Furthermore, inefficient, but interferon responsive cytotoxic cells were present which bound and lysed freshly isolated autologous epithelial cells. The cytotoxicity of these colonic mononuclear natural killer (NK) like cells appeared specific in that cells bound but did not lyse NK resistant Raji cells, even after interferon activation.

Dissolution of cholesterol gallstones by bile acids in hamsters.

UNLABELLED: We previously reported a hamster model for cholesterol gallstone formation and prophylaxis. The aim of this study was to validate a model for dissolution of cholesterol gallstones by testing bile acids used in patients. Sixty hamsters were allocated to six groups of ten; Group I received the standard diet (.8mg cholesterol/gram food) and Groups II-VI received the lithogenic regime (2.4 mg cholesterol/gram food and 15 micrograms ethinyl estradiol) for twelve weeks. During the next eight weeks, Group I remained on the standard diet, Group II on the lithogenic regime, while Group III switched to the standard diet. Groups IV-VI remained on the lithogenic regime, and received 20 mg/kg/d of CDC (Group IV), UDC (Group V) or cholic acid (Group VI). Cholesterol gallstones were found in 90% of hamsters on the lithogenic regime, even after return to the standard diet, in 80% of those receiving cholic acid, and in none receiving the standard diet, CDC or UDC. CDC and UDC but not cholic acid inhibited hepatic HMG-CoA reductase activity (p less than 0.01) and desaturated bile (p less than 0.01). The highest HMG-CoA reductase (p less than 0.02) occurred after return from the lithogenic regime to the standard diet. CONCLUSIONS: 1) A new model for cholesterol gallstone dissolution has been validated; 2) CDC and UDC, in contrast to cholic acid, decreased HMG-CoA reductase, desaturated bile and dissolved gallstones as in patients; and 3) Return from the lithogenic regime to the standard diet did not desaturate bile or dissolve gallstones, but did increase HMG-CoA reductase as found in gallstone patients.

Occult medullary carcinoma of thyroid: an unusual clinical and pathologic presentation.

High calcitonin levels noted on a totally healthy 49-year-old man participating in a calcitonin control project led to a presumptive diagnosis of medullary carcinoma. Complete thyroid studies augmented by selective catheterization and quantitative calcitonin studies confirmed the clinical impression of medullary carcinoma. Surgery was recommended and a total thyroidectomy was performed. On gross examination no nodules or tumefactions were palpable. Histopathology showed diffuse C-cell hyperplasia in the midst of which a C-cell tumor and micromedullary carcinoma of the thyroid were found. Morphologically the full spectrum of changes from focal C-cell hyperplasia through the stages of diffuse and nodular hyperplasia to the final development of medullary carcinoma are demonstrated by light and electron microscopy. The patient's postoperative course was benign and for the subsequent three years he had continued asymptomatic with normal calcitonin levels.

Cholesterol gallstone formation and prevention by chenodeoxycholic and ursodeoxycholic acids. A new hamster model.

Prior animal models of cholesterol gallstone formation have been criticized for their dissimilarity to the conditions of humans with gallstones. We present a new hamster model of cholesterol cholelithiasis that more closely approximates the human situation. Sixty female Golden Syrian hamsters (average weight 83.2 +/- 3.4 g) were allocated to six groups of 10 animals each. Groups were fed standard diet (containing 0.8 gm cholesterol/g of food) or increased cholesterol diet (containing 2.4 mg cholesterol/g of food), with or without ethinyl estradiol, 15 micrograms/kg/d. Two groups receiving both increased cholesterol and ethinyl estradiol also received either chenodeoxycholic acid or ursodeoxycholic acid, 20 mg/kg/d. The animsl were sacrificed at 12 wk. Cholesterol gallstones (78.3 +/- 5.0% cholesterol by weight) formed in 30% of the animals fed ethinyl estradiol, 50% of those fed increased cholesterol, and 90% of those fed the combination of both. Bile was saturated in all three groups, with the saturation index of the combination group (2.08 +/- 0.17) being the highest. In both groups receiving bile acid therapy, no gallstones were found, and the bile remained unsaturated. For the bile acid-fed groups, both hepatic HMG-CoAR and hepatic cholesterol 7 alpha-hydroxylase activities were reduced (P less than 0.01) when compared to the group fed standard diet and to the grou fed the combination. Thus, a new animal model of cholesterol gallstone formation has been developed in which chenodeoxycholic acid and ursodeoxycholic acid therapy prevented gallstone formation through mechanisms similar to those reported in cholesterol gallstone patients.