Characterization of opioid peptides in human thyroid medullary carcinoma

A thyroid medullary carcinoma from a man with the multiple endocrine neoplasia syndrome Type IIB was examined for the presence of opioid peptides. The tumor contained peptides derived from all three opioid precursors: pro-opiomelanocortin (POMC), pro-dynorphin, and pro-enkephalin. The tissue concentrations of the various opioid peptides varied considerably. beta-Endorphin, a POMC-derived peptide, was present in concentrations between 9 to 12 pmoles/g tissue; 8 pmoles/g tissue of alpha-neo-endorphin, a pro-dynorphin-derived product, were seen, whereas the pro-enkephalin-associated peptides were present in much lower concentrations (0.6-2.1 pmoles/g tissue). Immunohistochemical studies showed scattered opioid-positive cells in the tumor tissue and in two other thyroid medullary carcinomas. These data demonstrate that malignant neuroendocrine tumors may contain peptides derived from all three families of the endogenous opioids.     

Infantile autism—fragile X: Molecular findings support genetic heterogeneity

Twenty-two members of 18 families with autism have been examined for the presence of mutations and abnormal methylation in the FMR-1 region at Xq27.3. All patients fulfilled diagnostic criteria of infantile autism. A characteristic pattern of insertion and methylation were detected after Southern blot analysis in 7 autistic individuals expressing the fragile site at Xq27.3. Normal DNA patterns were observed in 15 autistic boys cytogenetically negative for the fragile site. The results indicate a lack of involvement of the FMR-1 region in infantile autists negative for fragile X expression. © 1992 Wiley-Liss, Inc.     

Expression of opioid peptides in tumors

We looked for opioid peptides and their precursors in 108 tumors of both neuroendocrine and nonneuroendocrine origin, using a monoclonal "pan-opioid" antibody, 3-E7, which recognizes the tetrapeptide Tyr-Gly-Gly-Phe (the sequence responsible for pharmacologic activity in all known opioid peptides), in conjunction with polyclonal antibodies directed against representative peptides of each of the three precursors (alpha-endorphin, [met]enkephalin-Arg-Gly-Leu, and dynorphin B). Using the avidin-biotin immunoperoxidase technique, we observed consistent cytoplasmic immunoreactivity (at least focally) in all of 15 adrenal pheochromocytomas, all of 6 thyroid medullary carcinomas, and all of 5 pituitary adenomas. Opioid staining was also observed in parathyroid adenomas (8 of 9), pancreatic islet-cell tumors (7 of 10), carcinoid tumors from various sites (18 of 26), and paragangliomas (1 of 2). There was no immunoreactivity in pulmonary small-cell carcinomas, Merkel-cell tumors of skin, neuroblastomas, or any of the non-neuroendocrine tumors examined. The expression of alpha-endorphin, [met]enkephalin-Arg-Gly-Leu, and dynorphin B varied from tumor to tumor; however, positive staining with the "pan-opioid" antibody was found in each tumor containing at least one of the three precursors. Opioid peptide immunoreactivity was also detected in non-neoplastic cells of the adrenal medulla, pancreatic islets, pituitary, intestinal and bronchial mucosa, and intestinal myenteric plexuses. We conclude that opioid expression within tumors is most likely due to enhanced expression of a normal cell product and that opioid peptides are useful markers of neuroendocrine differentiation in many tumors.     

Gastrin-releasing peptide, a mammalian analog of bombesin, is present in human neuroendocrine lung tumors.

Several reports have indicated that the amphibian peptide bombesin is present in oat-cell carcinoma of the human lung. The recent observation that gastrin-releasing peptide (GRP), a 27-amino acid peptide isolated from porcine intestine, may be the mammalian analog of bombesin led the authors to look for this peptide in human pulmonary tumors. Examination of 36 human lung tumors (8 carcinoids, 8 oat-cell carcinomas, and 20 non-oat-cell carcinomas) by immunohistochemistry and radioimmunoassay demonstrated the presence of high, although variable, levels of GRP in neuroendocrine tumors, and not in other histologic types. These findings indicate that bombesin immunoreactivity in human lung tumors should be attributed to GRP or GRP-like molecules and that GRP may be a useful marker of neuroendocrine differentiation.     

Noninfectious immunologic disorders in adults

This article covers a variety of immunologic defects and discusses their potential side effects, with an emphasis on immunodeficiencies with survival into adulthood. To organize the approach to immunodeficiencies, the immune system is broken down broadly into four major components: the complement cascade, antibody (B cell)-mediated immunity, cellular (T cell)-mediated immunity, and phagocytosis.     

A transgenic model to study the pathogenesis of somatic mtDNA mutation accumulation in β-cells

Low levels of somatic mutations accumulate in mitochondrial DNA (mtDNA) as we age; however, the pathogenic nature of these mutations is unknown. In contrast, mutational loads of >30% of mtDNA are associated with electron transport chain defects that result in mitochondrial diseases such as mitochondrial encephalopathy lactic acidosis and stroke-like episodes. Pancreatic β-cells may be extremely sensitive to the accumulation of mtDNA mutations, as insulin secretion requires the mitochondrial oxidation of glucose to CO₂. Type 2 diabetes arises when β-cells fail to compensate for the increased demand for insulin, and many type 2 diabetics progress to insulin dependence because of a loss of β-cell function or β-cell death. This loss of β-cell function/β-cell death has been attributed to the toxic effects of elevated levels of lipids and glucose resulting in the enhanced production of free radicals in β-cells. mtDNA, localized in close proximity to one of the major cellular sites of free radical production, comprises more than 95% coding sequences such that mutations result in changes in the coding sequence. It has long been known that mtDNA mutations accumulate with age; however, only recently have studies examined the influence of somatic mtDNA mutation accumulation on disease pathogenesis. This article will focus on the effects of low-level somatic mtDNA mutation accumulation on ageing, cardiovascular disease and diabetes.     

Hyaline‐vascular type Castleman’s disease of the pararenal retroperitoneum: Multidetector CT findings

We describe the case of a 40‐year‐old woman who presented with a pararenal hyaline‐vascular type Castleman’s disease that had an arterial supply from the renal artery and a draining vein as showed by multidetector CT. Identification of the renal artery relationship to the feeding vessel of the mass is critical to prevent potential surgical complications.     

原发性肝癌自发性破裂出血26例临床分析

目的探讨总结肝癌自发性破裂出血的诊治经验。方法回顾性分析海口市人民医院自1992年1月～2004年5月收治26例原发性肝癌破裂出血的临床资料。结果该组原发性肝癌自发性破裂出血病例中，行肝癌切除术者，生存时间长。结论原发性肝癌破裂出血行肝叶切除和肝局部切除不但可以彻底有效地止血，而且可以达到切除肿瘤的目的，是首选的方法，是一种安全、可行的方法．如果病人情况不允许，可先行保守治疗或介入治疗（TAE），争取行Ⅱ期或延期肝切除术。而肝动脉结扎加胃网膜右静脉插管化疗，注入无水酒精等癌灶综合治疗为一种有效的辅助措施。