Toshio Iwase

CYP1A1 and CYP2E1 polymorphism and lung cancer, case-control study in Rio de Janeiro, Brazil

Msp I polymorphism and exon 7 Ile-Val polymorphism of CYP1A1, and Rsa I polymorphism of CYP2E1 were studied in lung cancer patients and controls in Rio de Janeiro, Brazil. Of the three polymorphisms studied, only the exon 7 polymorphism of CYP1A1 (Val-containing genotypes) had a distribution which was statistically significant in the patients and controls. The contribution of Val containing genotypes of CYP1A1 exon 7 was greater in the subpopulation of squamous cell carcinoma patients with a lower life-time smoking consumption (OR, 2.92 vs 1.97). This association is consistent with the previous findings by Kawajiri et al. and the first observation of the positive association of this locus with lung cancer in a Western population (Kawajiri K, Nakachi K, Imai K, Yoshii A, Shimada N, Watanabe J. FEBS Let 1990; 263, 131-133). Furthermore, together with the lack of association of Msp I polymorphism in the non-coding region of CYP1A1, the locus truly responsible for lung cancer risk among pleural polymorphisms of CYP1A1 appeared to be exon 7 Ile-Val polymorphism. In the future, investigations of multiple markers in different ethnic populations may reveal cancer risk markers common to all mankind.

Localization of Menkes gene expression in the mouse brain; its association with neurological manifestations in Menkes model mice

Abstract Menkes gene (Mc1 or MNK, encoding putative copper-transporting ATPase) expression was investigated and compared in normal and macular mutant mouse brain. Northern blot analysis showed a distinct 8.3-kb transcript and no obvious difference in size or extent in normal mice and macular mutants on postnatal days 0, 4, 7, 10 or 13. In situ hybridization revealed that certain specific populations of cells in the brain express Menkes mRNA, and that their localization in normal and mutant mice did not differ and was conserved on days 4, 10 and 13. The most intense hybridization signals were observed in the hippocampal CA1 region and dentate gyrus, the olfactory bulb nuclei, the cerebellar granular cell layer, the choroid plexus and the ependyma, with less intense signals in the hippocampal CA3 region and cerebellar Purkinje cells. In addition, necrotic neuronal cell death was predominantly observed in the CA3 region and the Purkinje cells of macular mice after postnatal day 10. The finding that the regions that had lower expression level of Menkes mRNA corresponded to those showing neuronal necrosis suggests that the Menkes gene may be responsible for the neuronal degeneration in some specific portions of the brain and clinical manifestations in this mutant.

Benign schwannoma of the esophagus: Report of two cases with immunohistochemical and ultrastructural studies

Two cases of benign schwannoma of the esophagus are presented. The tumors were found in the thoracic esophagus of women of 56 and 64 years of age, respectively, who had complained of dysphagia and back pain. Tumorectomies were performed and the tumors were found to be located within the esophageal wall arising from the muscularis propria. The tumors were examined immunohistochemically and ultrastructurally. These tumors were identical in gross, histological and electron microscopic features. Grossly, the tumors showed yellowish‐white cut surfaces without hemorrhage or necrosis. Microscopically, they were composed of spindle‐shaped cells showing moderate variation in size and shape, and nuclear palisading. Lymphoid aggregates with germinal centers surrounded the tumors. Immunohistochemically, strong reactions for S‐100 protein and neuron‐specific enolase were observed in the cytoplasm of spindle cells, whereas reactions for muscle actin and desmin were negative. These findings, together with electron microscopic observations, supported the Schwann cell origin of these tumors.

Intrasellar neuronal choristoma associated with growth hormone-producing pituitary adenoma containing amyloid deposits

The histological, immunocytochemical, and ultrastructural features of an intrasellar neuronal choristoma associated with pituitary growth hormone (GH)-producing adenoma are reported. Immunohistochemistry studies and electron microscopy examination showed the adenoma cells to be positive for GH but negative for prolactin, and the neurons of the choristoma to have GH-releasing factor (GRF) neurosecretory activity. The adenoma also had many amyloid deposits in its extracellular space immunoreactive to GRF. This is the first report of the tumor containing amyloid deposits.