Expression of CD138 (Syndecan-1) in renal cell carcinoma is reduced with increasing nuclear grade.

CD138/Syndecan-1 is a cell-surface heparan sulfate proteoglycan expressed on most epithelial cells, and decreased CD138 expression is associated with increased invasive and metastatic potential in carcinomas. CD138 expression has not been investigated previously in renal neoplasms. Formalin-fixed, paraffin-embedded tissue sections of 50 renal cell carcinomas (RCCs) (40 clear-cell RCCs of various nuclear grades, 10 of which harbored metastases; 6 papillary RCCs, 4 chromophobe RCCs) and 4 oncocytomas were stained immunohistochemically for CD138 using the monoclonal antibody B-B4 (CD138). Staining intensity and distribution were scored and results related to histologic type, nuclear grade, and local stage (pT). Immunoreactivity was membranous in all clear-cell RCCs, chromophobe RCCs, and oncocytomas and was located at the basal aspect of cytoplasm in papillary RCCs. In clear-cell RCCs, the extent of CD138 immunoreactivity decreased with increasing nuclear grade (P<0.001). No significant correlation was found between CD138 immunoreactivity and histologic type (P=0.2) or local stage (P=0.7). Metastatic foci showed a mild to moderate decrease in intensity compared with primary tumor. Decreased expression of CD138 may have a role in more aggressive behavior of clear-cell RCC.     

Familial testicular cancer: interest in genetic testing among high-risk family members.

PURPOSE: This study is part of an ongoing National Cancer Institute multidisciplinary, etiologically-focused, cross-sectional study of Familial Testicular Cancer (FTC). The current report targets interest in clinical genetic testing for susceptibility to FTC. METHODS: Demographics, knowledge, health beliefs, and psychological and social factors were evaluated as covariates related to interest in genetic testing. RESULTS: The majority (66%) of 229 participants (64 affected men, 66 unaffected men, and 99 women) from 47 multiple-case FTC families expressed interest in having a genetic test within 6 months, should such a test become available. Interest was similar among the three subgroups mentioned above. Worries about insurance discrimination based on genetic test results were associated with a significantly lower interest in testing. Alternatively, participants were more likely to be interested in genetic testing if they were younger and had higher levels of family support, a physician's recommendation supporting testing, cancer distress, and a need for information to inform the health care of their children. CONCLUSIONS: This study reveals social and relationship factors that FTC survivors and their relatives considered important when contemplating the use of new genetic technologies. This is the first study describing hypothetical interest in genetic testing for familial testicular cancer.     

Stereoselectivity of L-baclofen in hippocampal slices of the rat

Extra- and intracellular recording from hippocampal slices of the rat revealed the following effects when baclofen (BF) (0.1-10 microM) was added to the perfusion fluid: a block of synaptic potentials evoked by stimulation of stratum radiatum; a direct hyperpolarization and a conductance increase (for potassium ions) of CA1 pyramidal cells. All this activity was found in the L- none in the D-enantiomer. D-BF did not antagonize the action of L-BF.     

Neu (c-erbB-2), a tumor marker in carcinoma of the female breast

The c-erbB-2 oncogene encodes a transmembrane phosphoglycoprotein. This molecule appears to be a growth factor receptor in the family of tyrosine kinase growth factor receptors; however, its ligand has not yet been identified. Amplification and/or overexpression of c-erbB-2 in breast adenocarcinomas occurs frequently and its occurrence implies a more advanced malignancy. This functional tumor marker is readily identified by appropriate DNA and antibody probes. The large external domain of the c-erbB-2 gene product is a promising target for immunodiagnostic and immunotherapeutic modalities.     

Inhibition of abnormal T cell development and autoimmunity in gld mice by transgenic T cell receptor beta chain.

Mice homozygous for the gld (generalized lymphoproliferative disease) mutation developed systemic autoimmune disease and severe lymphadenopathy due to an age-related accumulation in the peripheral lymphoid organs of polyclonal T cells bearing a unique phenotype (CD4-CD8-TCR alpha beta+B220+). These T cells overexpress T cell receptor (TcR) alpha beta chain RNA, proto-oncogenes c-myb and fyn, and proliferate poorly in response to TcR-mediated stimulation. The origin of these T cells is poorly understood. To study the influence of a functionally rearranged TcR beta chain on the T cell developmental abnormality of the gld mutation and autoimmunity, we have backcrossed TcR V beta 8.1-transgenic mice to C3H-gld/gld to homozygosity (transgenic gld mice). In transgenic gld mice, lymphadenopathy was markedly inhibited and the accumulation of CD4-CD8- T cells did not occur, although the remaining T cells overexpressed c-myb and proliferated poorly in response to TcR occupancy. These features indicate that the pattern of proto-oncogene expression and abnormal function persist in phenotypically normal T cells in transgenic gld mice, and that these characteristics can be dissociated from the accumulation of CD4-CD8- T cells. The hypergammaglobulinemia and anti-double-stranded DNA (anti-dsDNA) antibody production was partially improved in transgenic gld mice, supporting the critical role of T cells in abnormal B cell activation described in autoimmunity-prone mice. To investigate further the mechanisms underlying the inhibition of CD4-CD8- T cell accumulation in transgenic gld mice, the fetal ontogeny of T cells in transgenic mice was compared with that of non-transgenic mice. In transgenic thymus, development of TcR alpha beta+ cells was accelerated as detected by earlier expression of CD4, CD8 and TcR in fetal thymus. In contrast, the number of TcR gamma delta+ cells was reduced. We suggest that altered T cell development in transgenic mice directly or indirectly inhibits the accumulation of abnormal T cells in gld mice.     

Effect of advanced age on p-aminohippurate-induced inhibition of renal tubular secretion in male Fischer 344 rats

The effect of aging on glomerular filtration, effective renal plasma flow and on the responsiveness of the renal tubular anion secretory system to inhibition by 4-aminobenzoylglycine (p-aminohippurate, PAH) was examined in young (5-month) and old (22-month) Fischer 344 male rats. Plasma clearance, protein binding and renal extraction of [131I]o-iodohippurate, [125I]iothalamate and HPLC-purified [99mTc]mercaptoacetyltriglycine (MAG3), were used as in vivo probes of renal function. The effect of advanced age, without concomitant PAH, on the disposition of these markers was initially determined in ketamine anesthetized, temperature-maintained male rats, ages 5, 14 and 22 months by means of constant infusion clearance studies. Aging per se decreased (P less than 0.05) the kidney-weight normalized or body weight-normalized GFR and effective renal plasma flow rates. GFR values averaged 1.67, 1.43 and 1.32 ml/min per g kidney for the 5-, 14- and 22-month-old rats, respectively. Kidney- or body weight-normalized clearances of MAG3 and o-iodohippurate showed similar (25-27%) decreases, whereas the absolute values (ml/min) for GFR, o-iodohippurate and MAG3 clearance rates were not altered by aging. The effective filtration fraction, extraction ratio and plasma protein binding were also unchanged by advanced age. Overall, the age-related decreases in renal function were minimal in Fischer-344 rats, compared to other species. Differences in data normalization, species and gender account, in part, for discrepancies observed when comparing results in different studies on the effects of advanced age on renal function. Subsequently, we examined the effect of aging on the renal responsiveness to inhibition of tubular anion secretion using constant rate PAH infusion studies, adjusted for age-related changes in renal function. Aging did not alter PAH-induced inhibition of iodohippurate secretion. Inhibition of MAG3 elimination was more pronounced in the old rats compared to the young controls.