Gastrointestinal stromal tumors and other mesenchymal lesions of the gut.

In the past 5 years, there has been a paradigm shift in our understanding of gastrointestinal stromal tumors (GISTs). Once thought to be smooth muscle tumors, these uncommon neoplasms are now thought to differentiate along the lines of interstitial cells of Cajal, the pacemaker cells of the gut. Along with this understanding comes an exciting new drug therapy (Gleevec) that for the first time offers real hope to patients with malignant stromal tumors. Overall, approximately 60-70% of stromal tumors are from the stomach, 20-30% are from the small intestine, and <10% come from the esophagus, colon, rectum, omentum, and mesentery. Between 10 and 30% of GISTs are malignant. Stromal tumors should be studied in a site-specific fashion, as tumors from a given location in the gut have unique growth patterns and corresponding behaviors. Although the most important tool needed to diagnose a GIST is still a hematoxylin and eosin-stained section, a confirmatory CD117 stain is recommended (and may be required for drug therapy). True smooth muscle tumors, inflammatory fibroid polyps, fibromatoses, schwannomas, inflammatory myofibroblastic tumors, and solitary fibrous tumors all enter into the differential diagnosis of GISTs. This article reviews the histologic features of these tumors in the context of recent molecular genetic and immunohistochemical advances.     

Detergent enhances binding of a secreted HLA-A2 molecule to solid phase peptides.

We have constructed a secreted analogue (sA2) of the human class I molecule HLA-A2. sA2 was affinity purified both in the presence and absence of detergent and the effects of detergent on the magnitude and specificity of A2 binding to solid phase peptides tested. sA2 purified in the presence of detergent and detergent-solubilized A2 are shown to function comparably in the binding of the synthetic peptide M.Y + 57-68, a known T-cell epitope derived from the influenza A matrix protein. The molecules binding to M.Y + 57-68 typically represent 8% to 10% of the added protein. In contrast, less than 1% of sA2 protein purified in the absence of detergent binds M.Y + 57-68. This reduced binding is not due to a change in the affinity of sA2 for M.Y + 57-68. Addition of detergent at various stages of the purification and iodination procedures indicates that the longer the sA2 molecules are exposed to detergent the better they bind. However, the concentration of detergent during the actual binding assay does not appear to be critical. We also find that while the sA2-detergent and the sA2-no detergent molecules differ in the extent to which they bind various peptides, they do not differ in their patterns of binding. We conclude that detergent probably does not influence the specificity of class I/peptide binding but does increase the number of sA2 molecules that can participate in the binding of peptide either by generating and stabilizing "empty" sA2 molecules or by stabilizing a structure that is more amenable to binding peptide.     

Brain tumors induced in hamsters by intracerebral inoculation of SR-RSV-infected embryonic brain cells.

Brain tumors were induced in Syrian hamsters by intracerebral inoculation of brain cells which were obtained from 12-day old syngeneic hamster and infected with Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV) in vitro. A total of 212 tumors were developed in all 25 recipients within 19 to 125 days after transplantation. On the basis of light and electron microscopic study, they were classified into four main groups: astrocytoma (45.8%), pleomorphic glioma (50.0%), sarcoma (3.8%), unclassified (0.4%). The morphological features of these tumors were described, and the advantages of this brain tumor model were discussed.     

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.     

Appetite signaling: from gut peptides and enteric nerves to brain

The signaling systems underlying eating behavior control are complex. The current review focuses on gastrointestinal (GI) signaling systems as physiological key functions for metabolic control. Many of the peptides that are involved in the regulation of food intake in the brain are also found in the enteric nervous system and enteroendocrine cells of the mucosa of the GI tract. The only identified hunger-driving signal from the GI tract is ghrelin, which is mainly found in the mucosa of the stomach. Neuropeptides in the brain that influence food intake, of which neuropeptide Y, agouti gene-related peptide and orexins are stimulatory, while melanocortins and alpha-melanocortin stimulating hormone are inhibitory, are influenced by peptide signaling from the gut. These effects may take place directly through action of gut peptide in the brain or through nervous signaling from the periphery to the brain. The criteria for considering a gut hormone or neurotransmitter in a satiety signal seem to be fulfilled for cholecystokinin, glucagon-like peptide-1 and peptide YY(3-36). Other endogenous gut signals do not fulfill these criteria as they do not increase food intake in knock-out animals or in response to receptor antagonism, or display an inconsistent temporal profile with satiety and termination of the meal. Satiety signals from the GI tract act through the arcuate nucleus of the hypothalamus and the solitary tract nucleus of the brain stem, where neuronal networks directly linked to hypothalamic centers for food intake and eating behavior are activated. We have primarily focused on GI effects of various gut peptides involved in the regulation of food intake, using motor activity as a biomarker for the understanding of gut peptide effects promoting satiety.     

Brain tumors in hamsters induced by murine sarcoma virus (Moloney)

Murine sarcoma virus, CS-Moloney substrain, was inoculated intracranially into 2 litters of newborn Syrian hamsters within 24 h of birth. Seven of 12 hamsters which survived more than 30 days developed brain tumors in the cerebral cortex 104 to 153 days, 139 days on the average, after the virus inoculation. The tumors consisted of spindle-shaped, round or polygonal astrocytes which showed a positive reaction for glial fibrillary acidic protein by the immunoperoxidase method.     

The 18-kilodalton antigen secreted by Aspergillus fumigatus.

One of the major antigens secreted in vitro by Aspergillus fumigatus is an 18-kDa basic protein which has been purified by cation-exchange chromatography. It is recognized by sera from aspergilloma patients. It is also the major circulating antigen found in urine of patients with invasive aspergillosis. Our results indicated that this antigen has potential for the diagnosis of both aspergilloma and invasive aspergillosis.     

Brain tumors in children: a review

Brain tumors are the second most common malignancy of children. In contrast to adults, childhood brain tumors are usually of glial origin; metastases and meningiomas are rare. Some tumors, i.e., medulloblastomas, are found almost exclusively in children. The posterior fossa is the most frequent site of occurrence. The prognosis for childhood neoplasms tends to be more favorable than in adults, and some lesions are curable. New techniques, including immunostaining, tumor markers, and cytogenetics, have improved diagnostic accuracy. A review of some of the most important brain tumors of children is presented along with an upgrade on recent developments in diagnoses and treatment.     

An 88-kilodalton antigen secreted by Aspergillus fumigatus.

An 88-kDa component secreted in vitro by Aspergillus fumigatus has been purified by sequential chromatographic procedures. The molecule is a glycoprotein with an N-linked sugar moiety composed of mannose glucose, and galactose (16:10:1). It is recognized by antibodies from patients with aspergilloma and has potential for the immunodiagnosis of aspergilloma. The antigenicity is associated with the polypeptide part of the molecule (79 kDa).