Biomedical subjects
Publications and source records attributed to S Eidelman.
A 24-year-old woman who had immigrated from India 3 years before was referred because of diarrhea, abdominal pain and weight loss. Crohn's disease was suspected, but investigation revealed active pulmonary tuberculosis and tuberculosis of the small and large intestine. She was treated with rifampicin, 600 mg/day, INH 300 mg/day, and ethambutol, 400 mg/day, and recovered fully within 6 months.
BACKGROUND: Interferon gamma (IFN-gamma) induces the interaction of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen type 1 expression, and of HLA-DR antigens by keratinocytes. OBJECTIVE: The aim of the present study was to determine the potential ability of aged versus young skin to respond to intradermal administration of IFN-gamma, as an in vivo immunologic stimulus. METHODS: For 3 consecutive days elderly and young volunteers were injected with 10 micrograms of recombinant IFN-gamma diluted in 0.1 ml of sterile water. On day 5, punch biopsy specimens were obtained from the injected sites. Histologic and immunohistochemical stainings were performed on all sections. RESULTS: ICAM-1 was expressed by keratinocytes in both aged and young skin. An impairment was manifested mainly by the reduced accumulation of mononuclear cells throughout the dermis, the absence of HLA-DR expression by keratinocytes in 7 of 10 elderly volunteers, and the absence of an effect on the Langerhans cell population. CONCLUSION: This observation shows a diminished immune response in aged skin.
We describe five patients who were initially thought to have Crohn's disease and were treated accordingly. The original diagnosis was based upon clinical presentation, roentgenograms, and histological examination, but subsequent follow-up showed that diagnosis to be in error. The following diagnoses were established instead: tuberculosis, Actinomyces Israeli infection, reaction to gold therapy, metastatic cancer, and linitis plastica. We stress the importance of considering conditions that can mimic Crohn's disease.
Injections of murine gamma interferon (IFN-gamma) into BALB/c nude mice induced Ia expression by keratinocytes. The aim of the present study was to use this murine model to determine the effect of ultraviolet radiation (UV) or cyclosporine A (CyA) on Ia expression by keratinocytes. Two sets of experiments were performed. In the first, mice were injected intraperitoneally with IFN-gamma for 6 days. The mice were divided into three groups. One group, with one ear protected by electrical tape, was exposed to UVB radiation for 15 days starting 4 days before the injection. The second group received subcutaneous injections of CyA simultaneously with the IFN-gamma and during the 10 days following the IFN-gamma injection. The third group received only IFN-gamma injections. Fifteen days after the IFN-gamma injection all mice were killed and evaluations of Ia positive cells were performed. In the second set of experiments the nude mice were treated with CyA or UVB only 10 days after the last IFN-gamma injections. In both experiments UVB inhibited and down-regulated Ia expression by keratinocytes. This effect on keratinocytes was not observed in the protected ears. Thus it appears that the effect of UVB on keratinocytes is local and not systemic. CyA failed to inhibit or down-regulate Ia expression. This study may shed some light on understanding the mechanism effect of UV radiation in a variety of skin diseases.
Since many skin diseases characterized by positive Ia keratinocytes show improvement with cyclosporine therapy, the purpose of this study was to determine whether cyclosporine A (CyA) alters the expression of Ia keratinocytes. Nude mice were injected with normal mouse serum (NMS) to induce keratinocyte expression of the Ia antigen. The injected mice were then divided into four groups: one was treated with oral CyA; the second was treated topically with CyA twice a day; the third was treated topically with olive oil; and the fourth was injected with nude mouse serum. The third and fourth groups served as Ia positive and Ia negative controls, respectively. The mice were treated during the first 10 days after the injections. On Day 10, epidermal sheets were analyzed for Ia expression. Analysis was made by an indirect immunoperoxidase staining method using monoclonal antibodies specific for Ia determinants. Quantitation of the number of Langerhans cells was analyzed on epidermal sheets using immunodiagnostic reagents, anti-MHC-Ia, and surface ectoenzyme, ATPase. A significant reduction of Ia-positive keratinocytes was noted in the oral CyA group vs topical and olive oil groups (64.9 +/- 29.9% vs 20.1 +/- 18.7%, respectively, P less than 0.01). In a second set of experiments mice were injected with NMS, but treatment was started only on Day 10 after injections, for 10 days. The results showed that CyA failed to down-regulate Ia expression. Topical and systemic CyA did not modify Langerhans cell population. The present study showed that systemic administration of CyA significantly reduced Ia induction by keratinocytes of nude mice that were injected with NMS.
Previous studies have demonstrated decreased numbers of melanocytes and Langerhans cells (LC) in aged skin. In the present study, we employed dopa and indirect immunoperoxidase techniques in epidermal sheets to determine the fate of melanocytes and LC of aged versus young donors after skin transplantations onto nude mice. The detection of positive homologous leucocytic antibody reaction of degeneration (HLA-DR) of LC indicates an age-associated reduction in sun-protected thigh skin in aged versus young subjects (263 +/- 63 versus 589.25 +/- 142.643, p less than 0.001). The mean number of LC four weeks after transplantation remained almost constant. Prior to skin engraftment, a decreased number of melanocytes was found in aged versus young epidermis (160.77 +/- 51.7 versus 255.83 +/- 81.2, respectively, p less than 0.05). A significantly increased number of melanocytes was noted four weeks following engraftment in epidermis from aged (307.44 +/- 174, p less than 0.05) and young human donors (402.16 +/- 139, p less than 0.02). The marked increase in density of dopa-positive melanocytes following engraftment onto nude mice may indicate the existence of circulating factors in nude mice that perhaps both stimulates and enhances proliferation and activity of these cells.
Explore the source record for details and available documents.
Several diseases are included in the category of hypomelanosis. Their clinical course as well as the pathogenesis are diverse and in many cases poorly understood. The aim of the present study is to use the nude mice model to determine whether the primary defect in various pigmentary skin disorders is inherent to the tissue itself or is secondary to systemic factors. Split-thickness skin grafts obtained from patients with vitiligo, acquired hypomelanosis guttata, and tyrosinase-negative albinism were grafted onto nude mice. Histologic examination and dopa staining were performed prior to and following the engraftment. The dopa staining was performed on the epidermal sheet following separation from the dermis. The depigmented area of the vitiligo became completely pigmented 6 to 10 weeks after skin transplantation. The dopa reaction that was negative prior to skin engraftment became completely positive after the transplantation. The number of melanocytes (expressed per square millimeter of skin surface) 8 weeks after transplantation was 197 +/- 73 mm2. Dopa reaction in acquired hypomelanosis guttata showed reduction of the number of melanocytes in the depigmented macula as compared with the surrounding area (55.25 +/- 18.00 mm2 vs 220 +/- 28.28 mm2. Twenty days after skin transplantation, repigmentation of the area was observed. The number of melanocytes increased significantly (388.75 +/- 213 mm2). The grafted skin obtained from patients with tyrosinase-negative albinism showed persistence of the depigmentation after skin transplantation. Dopa reaction was negative prior to and 8 weeks after transplantation. The results of the present study suggest that systemic factors may play a role in the pathogenesis of vitiligo and acquired hypomelanosis guttata.
We report the case of a woman with symptomatic right heart failure. Despite lack of the characteristic features of the carcinoid syndrome, echocardiographic and histologic investigations confirmed the diagnosis of carcinoid disease with cardiac involvement.
A 43 year old woman presented with attacks of abdominal pain, haematemesis and hyperamylasaemia. Gastrointestinal X-rays and repeated upper gastrointestinal endoscopy failed to reveal the source of bleeding. Ultrasound and computed tomographic scan demonstrated a calcified mass in the tail of the pancreas. Surgical exploration revealed a solitary mass in the pancreas and histological examination showed cystadenocarcinoma. The patient died 2 years later because of local recurrence, but haematemesis and melaena did not recur. This case presents an unusual manifestation of cystadenocarcinoma of the pancreas with massive bleeding from the tumour via the pancreatic duct and associated pancreatitis. Other possible reasons for bleeding with cystadenocarcinoma of the pancreas are discussed.
We studied the expression of the human c-myc proto-oncogene in normal human colon epithelium by both in situ hybridization and immunohistochemistry. c-myc was found to be expressed uniformly throughout the entire thickness of the colon epithelium. The present findings do not support the contention that the c-myc proto-oncogene is primarily expressed in proliferating intestinal epithelial cell compartments.
Polyclonal and monoclonal antibodies raised to the 80 kd glycoprotein component of the cell to cell adhesion molecule cell-CAM 120/80 were used to map its distribution immunohistochemically in normal human tissues and in benign and malignant tumors. Cell-CAM 120/80 was found in all normal epithelial tissues, but was not expressed on neural, lymphoid, smooth, striated and cardiac muscle, connective tissue, or the germ cells in either sex. The expression of this adhesion molecule was polarized in ductal and glandular epithelia and evenly circumferential in squamous and transitional epithelia. Some organs, such as the kidney, liver and endocrine glands, showed unique organ to tissue specific patterns. Maturation-dependent loss of cell-CAM 120/80 was noticed in superficial layers of squamous epithelium and the placenta. Benign epithelial tumors expressed cell-CAM 120/80 in a manner comparable with their tissue of origin. Malignant tumors expressed cell-CAM 120/80 either in a manner similar to the tissue of their origin or assumed a less polarized phenotype. Overall, the immunoreactivity in many malignant tumors appeared weaker and the polarization was less pronounced. Thus, cell-CAM 120/80 is a universal marker of human epithelial cells, but its mode of expression differs in various anatomic sites, and may be influenced by maturation or malignant transformation of cells.
Spontaneous bacterial peritonitis (SBP) is an infectious process that usually occurs in patients with cirrhosis. There are few reports of SBP in patients with other pathologies such as nephrotic syndrome, acute and chronic hepatitis, cardiac ascites, and ascites secondary to neoplastic disease. We report a patient with polycythemia vera in whom recurrent episodes of SBP occurred 8 months following a portacaval shunt operation for Budd-Chiari syndrome. Conceivably, the polycythemia vera (PV) complicated by hepatic vein thrombosis and portacaval shunt resulted in significant loss of hepatic reticuloendothelial system function and predisposed the patient to bacterial peritonitis.
We studied a series of 40 rats at various stages of colorectal carcinoma, as induced by N-methyl-N-nitro-Nitrosoguanidine. Lymphokine containing supernatants were obtained simultaneously from splenic and peripheral lymphocytes, after exposure to rat colon cancer antigen in vitro. The lymphokine was found capable of performing Macrophage Migration Inhibition (MIF) when obtained from rats with: carcinoma through serosa, carcinoma of submucosa, carcinoma of the mucosa and carcinoma in situ. All control rats were free of cancer and were MIF negative. The MIF response in this study was evaluated as a marker of chemically induced colorectal carcinoma in rats in order to better understand the lymphocyte response to tumor progression from atypia to adenocarcinoma of the colon.
A specific macrophage migration inhibition assay, using patient lymphocytes incubated with a human colonic cancer extract, was studied in 92 patients with proven colorectal cancer and in 134 other individuals (20 normal controls, 80 patients with various nonmalignant gastrointestinal diseases, and 34 patients with extracolonic malignancies). A positive response was obtained in 78 of 92 colorectal cancer patients, but in none of the 20 normal controls. A positive response occurred in four of 34 patients with extracolonic malignancies and in approximately half of patients with colonic adenomas and in one third of patients with ulcerative colitis. The significance of positive results in these patients (with diseases considered premalignant) is unclear, and is being studied further. In patients with previous resection of colorectal cancers, positive responses were frequent during the first year following resection, and rare thereafter. The results suggest that this method may be useful as a clinical marker for colorectal cancer, and warrants further technical refinement and study of specific patient populations.
Explore the source record for details and available documents.
Previous studies in our laboratory on 92 patients with colonic cancer have suggested a promising degree of specificity and sensitivity for a macrophage migration inhibition factor (MIF) test using patient's lymphocytes incubated with a human colon cancer extract. This study compares the results of the MIF technique with serum carcinoembryonic antigen (CEA) levels and with the lymphocyte adherence inhibition (LAI) test in 18 colon cancer patients and 27 patients with conditions considered to predispose to colon cancer (colonic adenomas, ulcerative colitis, and Crohn's disease). Among colonic cancer patients, MIF and LAI were positive in 17 out of 18, but CEA was elevated in eight. MIF and CEA were negative in all 16 normal control subjects; LAI was negative in 13. Among patients with colonic adenomas, MIF and LAI were positive in three of five; CEA was negative in all. In the ulcerative colitis and Crohn's disease group, MIF was positive in seven of 22, LAI was positive in 11, and CEA was negative in all 22. Thus, MIF and LAI appear to be sensitive marker's for human colonic cancer. More extensive studies and precise characterization of these groups are warranted.