Involvement of cell-cell adhesion molecules in liver colonization by metastatic murine lymphoma/lymphosarcoma variants

Metastatic variant sublines of the murine RAW117 large cell lymphoma or lymphosarcoma have been established in vitro by sequential cycles of harvesting of liver tumor nodules after intravenous inoculation of tumor cell suspensions into syngeneic BALB/c mice. After five and tenin vivo selections for liver colonization, variant sublines RAW117-H5 and -H10, respectively, were established, and these formed significantly more surface liver tumors than the parental RAW117-P line. RAW117 sublines were tested for their abilities to adhere to embryonic mouse liver or brain cells in anin vitro cell-cell adhesion assay. Liver colonizing RAW117-H10 cells adhered with greater selectivity to liver cells than to brain cells. Parental RAW 117-P cells were more homotypically adhesive, but they were nonselective in their organ cell adhesion properties. We examined RAW117 cells for the presence of liver cross-reactive antigens using polyclonal xenoantibody preparations directed against embryonic murine liver cells. These antibody preparations block organ-specific homotypic adhesion of embryonic murine liver cellsin vitro. The amount of fetal liver antigen(s) expressed on RAW117 sublines correlated with liver colonization potentials (H10 > H5 > P) in quantitative absorption assays. Treatment of the highly metastatic RAW117-H10 subline with polyclonal anti-embryonic murine liver F(ab)₂ or Fab antibody fragments had no effect on RAW117-H10 cell viability or growthin vitro orin vivo, but inhibited liver colonization (median liver tumor colonies reduced from > 200 to 0) and prolonged life expectancy. In contrast, pretreatment of RAW 117-H 10 cells with polyclonal anti-H-2 did not modify thein vivo biologic properties of these metastatic cells.Address correspondence to this author in Houston.     

Morphogenesis and variants of remodeling of atherosclerotic heart

Morphogenesis of atherosclerotic heart is presented on the basis of complex pathomorphological analysis of 1000 autopsies. Special attention was paid to the dilatation and hypertrophic variants and to structural mechanisms of heart and coronary vessel remodeling under conditions of atherosclerotic process. Predominant remodeling of atherosclerotic heart and coronary arteries by the dilatation variant determines unfavorable prognosis of heart failure. Compensatory and adaptive processes (cardiomyocyte hypertrophy and collateral circulation) developing in the heart compensate for functional insufficiency of the organ for some time. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 6, pp. 692–698, June, 2006     

Immunoblastic lymphosarcoma in chronic lympholeukemia and prolymphocytic lymphosarcoma (Richter's syndrome)

Available are three cases of Richter's syndrome, i.e. immunoblastic lymphosarcoma with plasmocytic differentiation which developed in patients with chronic lymphocytic leukemia and prolymphocytic (lymphocytic) lymphosarcoma. Clinical, anatomical and autopsy findings are analysed. The immunoblastic lymphosarcoma is suggested to arise either because of transformation of the tumor prolymphocytes (lymphocytes) due to the disease progression or can be promoted by a second tumor.     

Genetic variants in rheumatic fever and rheumatic heart disease

Genetic association studies in rheumatic heart disease (RHD) have the potential to contribute toward our understanding of the pathogenetic mechanism, and may shed light on controversies about RHD etiology. Furthermore, genetic association studies may uncover biomarkers that can be used to identify susceptible individuals, and contribute toward developing vaccine and novel therapeutic targets. Genetic predisposition to rheumatic fever and RHD has been hypothesized by findings from familial studies and observed associations between genes located in the human leukocyte antigens on chromosome 6p21.3 and elsewhere in the genome. We sought to summarize, from published Genetic association studies in RHD, evidence on genetic variants implicated in RHD susceptibility. Using HuGENet? systematic review methods, we evaluated 66 studies reporting on 42 genes. Existing meta‐analyses of candidate gene studies suggest that TGF‐β1 [rs1800469], and IL‐1β [rs2853550] single nucleotide polymorphisms (SNPs) contribute to susceptibility to RHD, whereas the TNF‐α [rs1800629 and rs361525], TGF‐β1 [rs1800470 and rs4803457], IL‐6 [rs1800795], IL‐10 [rs1800896] were not associated with RHD. However, candidate gene studies in RF/RHD are relatively small, thus lacking statistical power to identify reliable and reproducible findings, emphasizing the need for large‐scale multicenter studies with different populations.     

Congenital heart defects and genetic variants in the methylenetetrahydroflate reductase gene

Background

Most non‐syndromic congenital heart defects (CHD) are caused by a complex interaction between maternal lifestyle factors, environmental exposures, and maternal and fetal genetic variants. Maternal periconceptional intake of folic acid containing vitamin supplements is reported to decrease the risk of CHD. The 677C→T and 1298A→C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene decrease enzyme activity.

Objective

To examine the relation between CHD and maternal and fetal MTHFR polymorphisms

Methods

375 nuclear families were studied. The transmission/disequilibrium test was used to test for transmission distortion in complete triads. A log‐linear approach was used to test for associations between CHD and maternal and offspring polymorphisms, and to estimate independently the contributions of maternal and fetal variants to relative risks. Haplotype frequencies were estimated and a haplotype transmission disequilibrium test carried out.

Results

The 1298C allele was transmitted less often than expected (p = 0.0013). There was no distortion in the transmission of the 677T allele, neither was there evidence of a parent of origin effect in the transmission of either of the single nucleotide polymorphisms. The 677C–1298C haplotype was also transmitted less often than expected (p = 0.0020). The relative risk associated with inheriting one copy of the 1298C allele was 0.64 (95% confidence interval, 0.48 to 0.87) and the that associated with inheriting two copies of the 1298C allele, 0.38 (0.21 to 0.70).

Conclusions

The apparent protective effect of the MTHFR 1298C allele against CHD could have several explanations and further study is needed.