Genetic and epigenetic alterations of the PTEN gene in soft tissue sarcomas

The PTEN/MMAC1 ( PTEN ) gene was identified as a tumor suppressor gene encoding a cytoplasmic protein that controls cellular processes. To investigate the potential role and the alteration of the PTEN gene in soft tissue sarcomas (STSs), we searched for homozygous deletion and promoter hypermethylation in a series of 48 STSs that was composed of malignant fibrous histiocytoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, including 2 cases with a mutation that we previously reported; differential polymerase chain reaction and methylation-specific polymerase chain reaction, respectively, were used for the analyses. Furthermore, to determine whether PTEN gene alterations are involved in the down-regulation of PTEN expression, we examined the expression of PTEN protein in 38 cases in which paraffin-embedded tissues were available for immunohistochemical analysis. In addition to our previous results showing that 2 (4%) of 51 cases had a PTEN mutation, promoter methylation was recognized in 6 (13%) of 48 cases, and homozygous deletion was detected in 1 (2%) of 48 cases in the current study. Of 6 cases with promoter methylation of PTEN gene, 5 were malignant peripheral nerve sheath tumor. Decreased expression of PTEN protein was recognized in 11 (29%) of 38 STS cases. Of 9 cases with PTEN alterations (6 cases with promoter methylation, 2 with mutation, and 1 with homozygous deletion), 3 (33%) showed decreased expression of PTEN protein. Furthermore, decreased expression of the PTEN gene showed a statistically significant correlation with high MIB-1 labeling index in 38 STS cases examined ( P = .0441). In conclusion, promoter methylation and homozygous deletion of the PTEN gene were found to be relatively rare events in cases of STS, as is mutation of the gene. Of 9 cases with a PTEN alteration, 3 (33%) showed a decrease in PTEN expression, indicating that PTEN gene alterations seem to play a minor role in the inactivation of PTEN in these tumors. Furthermore, although a further detailed analysis of a larger number of cases is still necessary, the present results suggest that PTEN expression may be a useful indicator of cell proliferation in patients with STS.     

Genetic mapping of genes regulating the thymus size in back-cross rats between the laboratory BUF/Mna strain and the MITE strain derived from the wild rat, Rattus norvegicus

The thymoma prone BUF/Mna (B) rat is a useful model for Studying the genes responsible for thymus enlargement during the stage of young growth. Among the strains of rats, B rats have the largest thymuses at al stages of life. A locus, Ten-1 , which contributes to thymus enlargement in back-cross (BC) rats between the B and WKY/NCrj (W) strains, was mapped on chromosome 1. To determine the precise location of the bus, (B×(B×MITE)F1) BC rats were generated by crossing the B strain with the Inbred MITE (M) strain, which was established from captured, Japanese wild rats, and were examined by linkage study using polymerase chain reaction with 67 microsatellite markers. Linkages with thymus enlargements were found In genotypes of seven markers, BSIS, LSN, MYL2, IGF2, PBPC2, D1Mgh11 , and D1Mit6 , by X^2-test and Student's t -test, which confirmed the presence of the genetic locus associated with thymus enlargement, Ten-1 , in this region. Paradoxically, a suppressive locus, Tsu-1 , to thymus enlargement was also found on chromosome 3, showing linkages of phenotype of the small thymus with genotypes of SCN2A, CAT D3Mit16 , and D3Mit13 . By analyses of mapmaker/exp and mapmaker/qtl, Ten-1 was mapped at 4.6 cM proximal from IGF2 locus on chromosome 1 and Tsu-1 at 4.0 cM proximal from CAT locus on chromosome 3, respectively.     

A clinicopathological review of 12 autopsied cases of adult T-cell leukemia

Twelve autopsied cases with adult T-cell leukemia (ATL) were reviewed clinicopathologically. The prognosis of three cases who had suffered from severe cutaneous lesions was much better than that of the other nine cases with no or negligible cutaneous lesions. The surface marker of leukemic cells from six cases was ordinary inducer/helper phenotype (OKT4+ and 8-), but in one case leukemic cells showed OKT4+ and 8+. In another case, a significant amount of leukemic cell infiltration was found in the thymic cortex. Calcium content in the bone of ATL cases was lower than that of the patients without ATL (control group), and six cases with ATL (50%) were complicated by severe hypercalcemia. Neither adenoma nor hyperplasia of the parathyroid glands was found in any case. In most severely hypercalcemic patients, bone trabeculae were actively absorbed by numerous osteoclasts and partly replaced by fibrous tissues. In two normocalcemic patients, skeletal calcium content was also markedly reduced by osteoporosis, but the activation of osteoclasts was inconspicuous. It was speculated that the manner of bone resorption in ATL cases was diverse and there were some clinicopathological subtypes in ATL from the viewpoints of cutaneous lesions, hypercalcemia, and bone lesions.     

Hepatoblastoma in an 82-year-old man. An autopsy case report

An autopsy case of adult hepatoblastoma is presented. The patient was an 82-year-old male with chronic hepatitis of 7 years' duration. The liver tumor was detected 6 months before death. Autopsy revealed a large hepatic tumor occupying about 80% of the entire liver. Histologically, the tumor showed typical features of mixed epithelial- and mesenchymal-type hepatoblastoma. The epithelial component consisted of fetal and embryonal cell types. The mesenchymal component showed primitive spindle-shaped cells with various degrees of cellularity. Chondroid areas and a few foci of osteoid formation were also present.     

Uneven distribution of enzymatic alterations on the liver cell surface in experimental extrahepatic cholestasis of rat.

The effect of bile duct ligation on enzyme activities in the subfractions of the rat liver plasma membrane was investigated. Two subfractions were isolated from the rat liver plasma membrane by homogenization and subsequent centrifugation in a discontinuous sucrose gradient. The light subfraction contained fragments of the bile canalicular surface and the heavy fraction contained fragments of the sinusoidal and lateral surfaces of the hepatocyte. Bile duct ligation decreased NaK ATPase and Mg-ATPase activity in the light subfraction, whereas it had no significant effect on these enzyme activities in the heavy fraction. Leucyl-β-naphthylamidase activity was reduced and alkaline phosphatase activity was increased in both subfractions. These facts suggested that ligation of the bile duct led to loss of the secretory polarity of the liver cell. The in vitro effects of some bile acids on the membranebound enzymes in the light subfraction were investigated, and a possible involvement of chenodeoxycholic acid in the alteration of enzyme activities in the bile canalicular membrane was suggested.     

Clinical significance of determination of serum RNase activities in patients with eosinophilia--II. Measurements using polyuridylic acid and polycytidylic acid as substrates

The activities of RNase (RNase-U and RNase-C) were determined in the serum and leukocytes of 277 patients with 14 cases of various kinds of eosinophilia (not less than 10(3)/microliters), 28 cases of chronic myelocytic leukemia (CML), using polyuridylic acid and polycytidylic acid as synthetic substrates according to the method of Raddi et al. Serum RNase-U activity, serum RNase-C activity and the activity ratio (U/C x 10(-3)) were 55 +/- 14 U, 1,280 +/- 235 U and 44 +/- 11 (mean +/- SD), 196 +/- 137, 1,992 +/- 1,134 U and 97 +/- 38, and 110 +/- 50 U, 1,854 +/- 625 U and 65 +/- 13 for normal subjects, eosinophilia and CML (untreated), respectively. U/C ratio in eosinophilia and CML (untreated) showed a highly significant positive correlation (p less than 0.001) with peripheral eosinophil count; the activity of serum RNase-U per cells in the supernatant of eosinophil homogenate rose significantly (p less than 0.001) compared with that of lymphocytes or granulocytes. Besides, serum and eosinophil RNase-U had a similar optimal pH. These results suggested that serum RNase-U in eosinophilia originated mostly from eosinophils and its rise was correlated strongly with the increase in eosinophils.