Chronic lymphocytic leukemia (CLL) is the most common leukemia in the world. The TCL1 gene, responsible for prolymphocytic T cell leukemia, is also overexpressed in human B cell malignancies and overexpression of the Tcl1 protein occurs frequently in CLL. Aging transgenic mice that overexpress TCL1 under control of the m immunoglobulin gene enhancer, develop a CD5+ B cell lymphoproliferative disorder mimicking human CLL and implicating TCL1 in the pathogenesis of CLL. In the current study, we exploited this transgenic mouse to investigate two different CLL-related issues: potential treatment of CLL and characterization of neoplasms that accompany CLL. We successfully transplanted CLL cells into syngeneic mice that led to CLL development in the recipient mice. This approach allowed us to verify the involvement of the Tcl1/Akt/mTOR biochemical pathway in the disease by testing the ability of a specific pharmacologic agent, rapamycin, to slow CLL. We also showed that 36% of these transgenic mice were affected by solid malignancies, in which the expression of the Tcl1 protein was absent. These findings indicate that other oncogenic mechanism(s) may be involved in the development of solid tumors in Em-TCL1 transgenic mice. (Cancer Res 2006; 66(2): 915-20)

In confirmation and extension of observations by Carp and his associates, brain tissue and sera from patients with multiple sclerosis (MS) were found to harbor an agent which induces a transitory depression in polymorphonuclear leukocytes (PMN) in mice as well as in rats, hamsters, and guinea pigs. All of eight MD brains contained this agent at titers as high as 10(-9)/g of brain tissue. The agent was found in MS sera at titers up to 10(-3)/ml of serum, but its presence depended to some extent on the clinical status of the patients; it was observed more frequently in sera of patients with active disease (73%) thatn in sera of patients with quiescent disease (31%). Control brain tissues or sera failed to induce PMN depression. The apparently MS-associated agent (MSAA) passed through 50-nm but not 25-nm membrane filters (Millipore Corp.) and was largely sedimented at 105,000 X g but not at 50,000 X g for 1 h. It multiplied to high titers in the central nervous tissue of the inoculated animals and could be serially transmitted from animal to animal by passage of brain homeganates. Various observations and considerations appear to preclude that MS-associated agent represents an indigenous animal virus. Although its role in MS remains to be determined, it should be considered a candidate for the etiology of this disease.

Abstract. Serum obtained from guinea pigs immunized with unfertilized C57BL/6 mouse eggs was found to be cytotoxic in the presence of complement for eggs obtained from syngeneic and allogeneic mice. The anti-egg serum was not cytotoxic for rat eggs, lymph node cells, methylcholanthrene-induced tumor cells, or 3T3 cells obtained either from syngeneic or allogeneic mice. The anti-egg serum was, however, cytotoxic for SV40-transformed 3T3 cells and C57BL/6 cells. After absorption with SV40-transformed cells, anti-egg serum lost its cytotoxicity for mouse eggs.The antigenicity of mammalian ova has been studied primarily in immunologic reactions against fertilized eggs. The results of these investigations indicate that mouse embryos apparently can divide unhampered when implanted in nonimmunized allogeneic,1 2 single skin-graft immunized, or even xenogeneic hosts,3 4 and that only hyperimmunization of the recipient animals may prevent their growth. ',6 Blastocysts grown in vitro without zona pellucida were found to be immunosensitive to the action of cells and serum obtained from an immunized animal,7'8 but the presence of the zona pellucida seemed to decrease their immunosensitivity to immune serum7'8 without affecting their susceptibility to the effect of immune cells.7 In addition to evidence for the presence of adult alloantigens, the existence of embryo-specific antigens has been postulated because repeated transfer of allogeneic blastocysts into male mice caused inhibition of development of subsequently implanted allogeneic and syngeneic blastocysts.9In contrast to the above studies, we have investigated in this paper unfertilized mouse eggs with heteroimmune sera, hoping to gain information about antigenic properties of a mammalian ovum at the earliest stage of development.Materials and Methods. Egg cells: Unfertilized eggs were obtained either from 8-to 10-week-old C57BL/6 or BALB-C virgin mice according to the technique described elsewhere.10 The cumulus o6phorus was removed by treatment with hyaluronidase."1 For immunization, the cells were washed twice in Brinster's medium (BMOC2),12 resuspended in 0.25 ml of BMOC2, and disrupted by squeezing back and forth through a syringe. The contents of approximately 100 eggs were then mixed with 0.25 ml of complete Freund's adjuvant (Difco, catalog no. 0638-59).For cytotoxicity tests, additional eggs were obtained from 5-week-old Wistar virgin rats treated with hormones for superovulation.13 After removal of the cumulus oophorus, the zona pellucida was removed from mouse and rat eggs by treatment with a 0.25% 193

Summary Chromophilic renal cell carcinoma is a distinct type of human renal cancer, only recently recognised and defined by its characteristic histomorphological aspect and cytogenetic aberrations. We are the first to report on the establishment and cytogenetic characterisation of a panel of four permanent cell lines, i.e. chromphi-l, -2, -3 and -4, derived from strictly defined renal cell carcinomas (RCCs) of the chromophilic type and kept in continuous culture for up to 5 years. Immunohistochemistry revealed coexpression of vimentin and cytokeratins in all cell lines -the cytokeratin polypeptide patterns, however, varying between the different cell lines. By light and transmission electron microscopy, various amounts of cytoplasmatic glycogen deposition were observed, being most pronounced in chromphi-3 and -4. The mean population doubling time ranged from 24 h (chromphi-1) to 51 h (chromphi-4). Chromphi-1 tumour cells produced slowly growing tumours in nude mice using the subrenal capsule assay. In all cell lines, cytogenetic analysis revealed numerical chromosomal aberrations known to be characteristic for chromophilic RCCs, i.e. loss of the Y chromosome, tri-or tetrasomy of chromosomes 7 and 17 as well as various combinations of additional structural and numerical chromosomal aberrations. Karyological aberrations were least pronounced in chromphi-2 and most complex in chromphi-1.Chromosomal aberrations typically affecting the short arm of chromosome 3 in clear cell RCCs were not observed in any of our cell lines.