A case of sarcomatoid carcinoma of the thymus

A 57-year-old woman presented with a 10×10 cm anterior mediations mass. The tumor had Invaded the pericardium, both lungs and the left brachiocephallc vein, and was treated by partial resection and postoperative radiation therapy. Pathological examination of the tumor revealed squamous cell carcinoma with a spindle cell sarcomatous component. Immunohistochemically, keratin and epithelial membrane antlgen were posltive In both the spindle cell sarcomatous areas and the squamous cell carcinomatous area and thus, a diagnosis of thymic carcinoma of sarcomatoid type was made. The patient died of recurrent disease 1 year after surgery. This case is the seventh reported In the English literature Because of the poor outcome, adjuvant therapy is recommended.     

Dna ploidy of pheochromocytoma on cytology specimen by image analysis

Pheochromocytoma usually shows prominent nuclear atypia, but the presence of such atypical cells is known to be an unreliable predictor of malignancy. DNA ploidy of pheochromocytomas has been analyzed by flow cytometry or photospectrometry on paraffinem-bedded tissue, but the results were controversial. We performed DNA analysis on cytology specimens of 11 pheochromocytomas using an image analysis system. All tumors had a mixed pattern of a large population of diploid cells and a small population of polyploid cells. DNA content correlated with nuclear size, and larger cells had more DNA content. Such larger tumor cells had polyploid nuclei, such as 4 C, 8 C, 16 C, and 32 C, in both malignant and benign pheochromocytomas. The larger polyploid nuclei may result from difficulty of duplication at the mitotic phase of the cell cycle.     

Expression profiles and functional analyses of Wnt-related genes in human joint disorders

Rheumatoid arthritis (RA) and osteoarthritis (OA) are joint disorders that cause major public health problems. Previous studies of the etiology of RA and OA have implicated Wnt genes, although the exact nature of their involvement remains unclear. To further clarify the relationship between RA, OA, and the Wnt gene family, gene expression analyses were performed on articular cartilage, bone, and synovial tissues in knee joints taken from RA, OA, and nor-mal/control patients. Cytokine assays were also performed in cells transfected with Wnt-7b, a member of the gene family most closely linked to RA and OA. Of the human Wnt genes, real-time PCR analysis revealed significant up-regulation of Wnt-7b in OA cartilage and RA synovium. In situ hybridization and immunohistochemistry also revealed that Wnt-7b was present in articular cartilage, bone, and synovium of RA samples and in osteophytes, articular cartilage, bone marrow, and synovium of OA samples. The levels of the cytokines tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 were significantly increased in RA synovium and Wnt-7b-transfected normal synovial cells when compared with normal samples. These results point to the potential involvement of Wnt signaling in the pathobiology of both RA and OA.     

The Costello syndrome: Are nasal papillomata essential?

Summary Two patients with the Costello syndrome are presented. One was a 7-year-old girl with a history of infantile hypotonia and feeding difficulties. The other was a 3 5/12-year-old boy with a history of neonatal sepsis and respiratory problems. Both had relative macrocephaly at birth, curly hair, large ear lobes, epicanthic folds, a low nasal bridge, thick lips, a short and wide nose, a short neck, a barrel chest, redundant skin, tight Achilles tendons, and pes equinovarus. Nasal papillomata, as described in Costello's two patients, were absent in both patients. Borochowitzet al. (1992) described five patients with what we interpreted as the Costello syndrome but without nasal papillomata. In view of these findings, nasal papillomata are not likely to be essential in the diagnosis of the Costello syndrome.     

Effect of ethanol treatment on metabolic activation and detoxification of esophagus carcinogenic N-nitrosamines in rat liver

In order to elucidate the mechanism underlying enhancement by ethanol of N-nitrosodiethylamine (DEN)- and N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in rats, hepatic levels of cytochrome P-450 (CYP) enzymes, mutagenic activation of several N-nitrosamines and three kinds of UDP-glucuronyltransferase (UDPGT) activities were assayed in F344 rats. Immunoblot analyses of microsomal CYP proteins revealed induction of CYP2E1 (approximately 2-fold), but not CYP2B1/2, 1A1/2 or 3A2, by treatment with 10% ethanol in the drinking water for 2 weeks. In contrast, s.c. treatment with 0.5 mg/kg NMBA three times per week for 2 weeks produced no significant alterations in the levels of these CYP species. Ethanol treatment also elevated the mutagenic activities of N-nitrosodimethylamine (DMN), DEN and N-nitrosopyrrolidine (NPYR) in strain TA100 up to 2.1-, 1.6- and 2.3-fold above each control, respectively. However, this was not the cases for four N-nitrosamines, including NMBA, in strain TA100 and two heterocyclic amines and aflatoxin B(1) in strain TA98. In addition, ethanol did not affect UDPGT activities towards 4-nitrophenol, bilirubin and testosterone. Hepatic CYP species responsible for mutagenic activation of selected N-nitrosodialkylamines were confirmed by use of specific CYP inducers and inhibitors with the liver from F344 and Wistar rats, indicating that DMN, DEN and NMBA are selectively activated by CYP2E1, predominantly by CYP2E1 with a slight contribution by CYP2B2 and selectively by CYP2B1/2, respectively. These results demonstrate that ethanol exerts an enhancing effect on mutagenic activation by CYP2E1 of DMN, DEN and NPYR, but does not affect that of NMBA and the other carcinogens by CYP2B1/2, 1A1/2 and 3A2 and UDPGT1A1, 1A6 and 2B1 activities. Consequently, this suggests that enhancement by ethanol of DEN-induced esophageal carcinogenesis in F344 rats can be attributed to an increase in hepatic activation during the initiation phase, but that of NMBA-induced tumorigenesis is not attributable to metabolic activation and inactivation via glucuronidation in liver.     

Neuronal protein NP25 interacts with F-actin

Neuronal protein NP25 is a neuron-specific protein present in highly differentiated neural cells, but its functional properties have not been well characterized. NP25 shows high amino acid sequence homology with the smooth muscle cell cytoskeleton-associated proteins, SM22, mp20, and calponin. To gain an insight into the biological functions of NP25, we first examined its subcellular localization in the human neuroblastoma cell line, SK-N-SH. NP25 diffusely distributed in the cytoplasm and fiber-like staining was also observed. It showed that NP25 co-localized with F-actin on stress fibers. A co-sedimentation assay demonstrated that NP25 bound to filamentous actin. Further investigations using fluorescence resonance energy transfer (FRET) technique revealed intracellular binding of NP25 and actin. The significance of the interaction between NP25 and F-actin is discussed.