Malignant granular cell tumor at the retrotracheal space

We report a case of an extremely rare neoplasm, malignant granular cell tumor (MGCT). The patient was a 21-year-old woman, who was 5 months pregnant. The tumor occurred in the retrotracheal space, extending from the level of the larynx to the thoracic inlet. In addition, there were multiple, variable-sized tumor nodules within both lung fields on chest CT scan. Histologically, tissue biopsied from the periphery of the tumor consisted of solid sheets of large ovoid cells with ample, eosinophilic cytoplasm, eccentric nuclei, and prominent nucleoli. Each cell showed slight atypism of the nuclei. There was a focal necrosis at the periphery of the lesion. These cells stained strongly for S-100 protein, neuron-specific enolase (NSE) and CD68. On electron microscopy, the tumor cells contained autophagic vacuoles. The patient refused further treatment and died 7 months later. The exact cause of death was not known. Until now, the diagnosis of MGCTs has been made only when metastasis and an aggressive clinical course are identified, although some observers advocate that some histologic features such as nuclear pleomorphism, necrosis, and the presence of any mitotic activity are indicative of malignancy. These histologic findings are not easily detectable in every case of MGCT, as in our case. So the diagnosis of a MGCT should be considered in cases with aggressive clinical findings and some histologic features, such as necrosis, nuclear atypism, and mitotic activities, which could suggest the malignant behavior of this neoplasm.     

Production of monoclonal antibody to a phenolic glycolipid of Mycobacterium tuberculosis and its use in detection of the antigen in clinical isolates.

A monoclonal antibody (MAbIII604) specific to phenolic glycolipid Tb (PGL-Tb), a Mycobacterium tuberculosis-specific antigen, was produced and used in the detection of the antigen. MAbIII604 reacted with the PGL-Tb antigen but not with other phenolic glycolipids from Mycobacterium leprae, M. bovis, and M. kansasii, thus indicating the specificity of the monoclonal antibody to PGL-Tb. A dot enzyme-linked immunosorbent assay with MAbIII604 was employed to detect the PGL-Tb antigen in lipids purified from M. tuberculosis clinical isolates. Of 50 isolates, 32 (64.0%) showed clear evidence of the PGL-Tb antigen by the dot enzyme-linked immunosorbent assay, but there were marked variations in the intensities and sizes of spots. This suggests differences in PGL-Tb antigen production among M. tuberculosis strains even when they are grown in the same culture media and conditions. This was most evident from the fact that in only eight (16.0%) of the isolates examined was the PGL-Tb antigen detectable by thin-layer chromatography, which is much less sensitive for the detection of glycolipid antigens. This study shows that monoclonal antibodies specific to PGL-Tb are useful in detecting the antigen in lipid extracts and that there is a marked variation in the PGL-Tb production among M. tuberculosis clinical isolates.     

Hypertrophic obstructive cardiomyopathy with infundibular stenosis treated by alcohol ablation therapy

This report describes an uncommon case of hypertrophic obstructive cardiomyopathy (HOCM) accompanying infundibular stenosis of the right ventricle treated by alcohol ablation therapy, in a 28-yr-old male patient presenting with dyspnea on exertion. HOCM with infundibular stenosis was detected by echocardiogram and cardiac catheterization and patient has dynamic obstructions of both ventricular outflow tracts. We performed alcohol ablation therapy to improve clinical symptoms and to relieve dynamic obstructions of both ventricular outflow tracts. This is the first case in which HOCM with infundibular stenosis of the right ventricle was treated by alcohol ablation therapy.     

Galactosylated chitosan as a synthetic extracellular matrix for hepatocytes attachment

Galactose moiety as the hepatocyte anchorage was covalently coupled with chitosan for the development of synthetic extracellular matrix. Hepatocytes adhesion to galactosylated chitosan (GC)-coated polystyrene (PS) dish became as high as 94.7% after 2 h incubation whereas the hepatocytes adhesion to chitosan-coated PS dish was 69.1%, indication of galactose-specific recognition between GC molecules and asialoglycoprotein receptors of hepatocytes. The DNA synthesis of the hepatocytes adhered to GC-coated dish was increased in the presence of epidermal growth factor (EGF) at low concentration of GC (0.05 microg/ml) whereas the DNA synthesis of the hepatocytes adhered to GC-coated dish was decreased in the presence of EGF at high concentration of GC (5 microg/ml). The spreading shapes of the hepatocytes adhered to the surface in the presence of EGF at low concentration of GC (0.05 microg/ml) were enhanced than in the absence of EGF. The hepatocytes adhered to the surface at high concentration of GC (5 microg/ml) showed round shapes and exhibited many spheroid formation after 24 h in the presence of EGF.     

Molecular and genetic characterizations of five pathogenic and two non-pathogenic monoclonal antiphospholipid antibodies

Antiphospholipid syndrome (APS) is an autoimmune disease that is characterized by thrombosis, recurrent fetal loss and thrombocytopenia. Antiphospholipid antibodies, detected by enzyme-linked immunoabsorbent assays (aCL) and/or in vitro blood clotting assays (LAC) are strongly associated with APS. Both the molecular structures used by pathogenic antiphospholipid antibodies and the genetic mechanisms leading to their production are unknown. We describe here the variable region genes of seven IgG antiphospholipid antibodies derived from two APS patients. Of these, five are pathogenic as defined in a mouse model of thrombosis and two are not. Analyses of the expressed variable region genes show no preferential V gene usage. However, similar to anti-DNA antibodies, pathogenic antiphospholipid antibodies contain an increased number of arginine residues in the third complimentarity-determining region (CDR3) of their H chains. The increased accumulation of arginine residues in the V(H) CDR3 may act to enhance antigen binding, promote disease and point to the importance of the H chain in the pathogenic potential of certain antiphospholipid antibodies.     

A proposed mechanism for the induction of cytotoxic T lymphocyte production by heat shock fusion proteins

A 65 kDa mycobacterial heat shock protein (hsp65), fused to a polypeptide that contains an octapeptide (SIYRYYGL) agonist for a particular T cell receptor (2C TCR), stimulated C57BL/6 mice as well as CD4-deficient mice to produce CD8+ cytolytic T lymphocytes (CTL) to the fusion partner's octapeptide. This and other hsp65 fusion proteins but not native hsp65 itself stimulated dendritic cells in vitro and in vivo to upregulate the levels of MHC (class I and II) and costimulatory (B7.2) molecules. The results suggest a mechanism for the general finding that hsp fusion proteins, having fusion partners of widely differing lengths and sequences, elicit CD8 CTL to peptides from the fusion partners without requiring exogenous adjuvants or the participation of CD4+ T cells.     

DNA ploidy patterns in gastric adenocarcinoma

To assess the value of DNA ploidy, flow cytometric analysis was performed on unfixed fresh materials obtained from 86 patients with gastric cancer who underwent stomach resection. We evaluated the DNA content of gastric carcinoma cells from four different sites and compared it with Ki-67 proliferating activity, and other pathologic parameters. The incidence of aneuploid and diploid was similar (48.8% vs. 51.1%). Early gastric carcinoma showed a higher rate of the diploid pattern (75%) compared to that of advanced gastric carcinoma (47.3%). DNA diploidy was noted increasingly in diffuse-type tumors according to Lauren, in signet ring cell type tumor according to WHO classification and in poorly differentiated tumors (p<0.05). Well and moderately differentiated carcinomas revealed the aneuploid pattern more frequently than poorly differentiated tumors. The aneuploidy was associated with high S phase fraction and high proliferative index. Aneuploidy was noted in the mucosa adjacent to the tumor (26%), in the close normal-looking mucosa (7%) and in the remote normal-looking mucosa (3%). This result suggest the possible role of field cancerization in the development of gastric adenocarcinoma.     

A rat model for radiation-induced proctitis

Radiation proctitis is a frequent acute complication encountered with pelvic irradiation. This study was aimed at establishing the optimal radiation dose for radiation-induced proctitis in rats. Female Wistar rats were used. The rectal specimens were examined morphologically at 5th and 10th day following 10-30 Gy irradiation in single fraction. With increasing dose, mucosal damage became worse, and there was a prominent reaction after > or =15 Gy. We selected 17.5 Gy as an optimal dose for radiation proctitis and examined specimens at day 1-14 and at week 4, 6, 8, and 12 after 17.5 Gy. The rectal mucosa revealed characteristic histological changes with time. An edema in lamina propria started as early as 1-2 days after irradiation and progressed into acute inflammation. On day 7 and 8, regeneration was observed with or without ulcer. Four weeks later, all regeneration processes have been completed with end result of either fibrosis or normal appearing mucosa. This study showed that the radiation injury of the rectum in rat develops in dose-dependent manner as it has reported in previous studies and suggested that 17.5 Gy in single fraction is the optimum dose to evaluate the protective effect of various medications for radiation proctitis in face of the clinical situation.