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Sam Litwin

Publications and source records attributed to Sam Litwin.

3 recordsLinked to original sources
PubMed2005

Generation of a unique strain of multiple intestinal neoplasia (Apc(+/Min-FCCC)) mice with significantly increased numbers of colorectal adenomas.

The relevance of the Apc(+/Min) mouse model in the study of human colorectal cancer remains uncertain due to the predominance of small intestinal adenomas and few, if any, colorectal adenomas. A new strain of Apc(+/Min) mice (Apc(+/Min-FCCC)) with significantly greater numbers of colorectal adenomas has been generated and characterized. Male C57BL/6J-Apc(+/Min) mice (the Jackson Laboratory, Bar Harbor, ME) were crossed with wild-type (Apc(+/+)) C57BL/6J females from an independent colony at this institution (offspring=Apc(+/Min-FCCC)) and 233 animals were evaluated over 20 generations. In order to determine the contribution of genetics to the enhanced colorectal adenoma phenotype, breeding pairs (Apc(+/Min) male x wild type female C57BL/6J) were purchased from the Jackson Laboratory and offspring (Apc(+/Min-JAX)) were maintained in our facility under identical conditions (n=98). Animals were fed Purina Rodent chow (#5013) diet containing 5% fat. The entire intestinal tract was examined histopathologically in both strains. Both the Apc and Pla2g2a (candidate for Mom1) genes were sequenced and found to be identical for both the Apc(+/Min-FCCC) and Apc(+/Min-JAX) mouse strains. The multiplicity of colorectal adenomas in the Apc(+/Min-FCCC) mice was much higher than reported in the literature and significantly greater than the multiplicity of colorectal adenomas in Apc(+/Min-JAX) mice maintained in our facility (P=0.01). Apc(+/Min-FCCC) had a significantly greater incidence of rectal prolapse (P = 0.02) and small intestinal adenocarcinomes (P=0.001), and multiplicity of small intestinal adenocarcinomas (P=0.001) compared to Apc(+/Min-JAX) mice. Male Apc(+/Min-FCCC) mice had significantly greater numbers of colorectal adenomas compared to female Apc(+/Min-FCCC) mice (P=0.0002), as did male Apc(+/Min-JAX) mice vs. female Apc(+/Min-JAX) mice (P< 0.0001). These results allow us to conclude: (1) Apc(+/Min-FCCC) mice are unique in that they develop significantly greater numbers of colorectal adenomas and small intestinal cancers, and a significantly greater incidence of small intestinal cancers and rectal prolapse than Apc(+/Min-JAX) mice. (2) This study represents the first report of a significant gender difference in multiplicity of colorectal adenomas. (3) Differences between Apc(+/Min-FCCC) and Apc(+/Min-JAX) mice in currently undefined genetic modifiers may contribute to the enhanced colorectal phenotype. (4) The Apc(+/Min-FCCC) strain is highly suited for the investigation of colorectal neoplastic disease and chemoprevention studies.

Adenoma↗
PubMed2002

Analysis of B cell receptor production and rearrangement. Part I. Light chain rearrangement.

A probabilistic model of allelic exclusion fails to explain the status of receptor genes and the receptor phenotype of most B cells. A large proportion of B cells have incompletely rearranged H and/or L chain genes (e.g. kappa0/kappa+) and most B cells express only one receptor. These properties seem to require deterministic features of B cell development such as special mechanisms that stop rearrangement. However, receptor editing has revealed that rearrangement-stop is not stable and that multi-receptor lymphocytes make up a significant fraction of certain B and T cell populations. Consequently we have revived the purely probabilistic approach in a model that now includes receptor editing and allows for some multi-receptor B cells. We find that this model can explain the observed properties of B cells when the frequency of self-reactive B cells is high. Indeed, as we illustrate for anti-DNA, this is the case. Hence the probabilistic model has life and assiduous use of the model suggests unexpected but not unrealistic features of lymphocyte development.

Algorithms↗