Citations

Transitional cell carcinoma was induced in the bladders of male Fischer rats by 12 oral doses of the carcinogen N -butyl- N -(4-hydroxybutyl)nitrosamine. Feeding of 13-cis-retinoic acid after completion of carcinogen treatment diminished the number and severity of cancers and other proliferative lesions of the bladder.

Dopamine-β-hydroxylase activity is released into the blood with catecholamines from the adrenal medulla and sympathetic nerves. This enzyme activity has been measured in the blood of 317 normal children and 227 normal adults. A significant sibling-sibling correlation of serum dopamine-β-hydroxylase values was found in the 94 sibling pairs tested. Frequency distributions of serum enzyme values in both children and adults suggest the existence of two populations with regard to serum activity of this enzyme.

Abstract Profound disruption of immune function is an established risk factor for non-Hodgkin lymphoma. We report here a large-scale evaluation of common genetic variants in immune genes and their role in lymphoma. We genotyped 57 single nucleotide polymorphisms (SNP) from 36 candidate immune genes in 1,172 non-Hodgkin lymphoma cases and 982 population-based controls from a US multicenter study. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) for the association between individual SNP and haplotypes with non-Hodgkin lymphoma overall and five well-defined subtypes. A haplotype comprising SNPs in two proinflammatory cytokines, tumor necrosis factor-α and lymphotoxin-α (rs1800629, rs361525, rs1799724, rs909253, and rs2239704), increased non-Hodgkin lymphoma risk overall (OR, 1.31; 95% CI, 1.06-1.63; P = 0.01) and notably for diffuse large B cell (OR, 1.64; 95% CI, 1.23-2.19; P = 0.0007). A functional nonsynonymous SNP in the innate immune gene Fcγ receptor 2A (FCGR2A; rs1801274) was also associated with non-Hodgkin lymphoma; AG and AA genotypes were associated with a 1.26-fold (95% CI, 1.01-1.56) and 1.41-fold (95% CI, 1.10-1.81) increased risk, respectively (Ptrend = 0.006). Among non-Hodgkin lymphoma subtypes, the association with FCGR2A was pronounced for follicular and small lymphocytic lymphomas. In conclusion, common variants in genes influencing proinflammatory and innate immune responses were associated with non-Hodgkin lymphoma risk overall and their effects could vary by subtype. Our results require replication but potentially provide important clues for investigating common genetic variants as susceptibility factors and in disease outcomes, treatment responses, and immunotherapy targets. (Cancer Res 2006; 66(19): 9771-80)

Abstract A leading theory suggests that decreasing activity and muscle mass is the main cause of age-related bone loss. However, in a population-based study of 375 women and 325 men (age, 21–97 years), we failed to find a close correspondence between these variables and changes in bone strength with aging. Introduction: It has been suggested that bone strength is homeostatically adapted to habitual skeletal loading conditions and that bone loss could, therefore, result simply from age-related reductions in physical activity and muscle mass, but this notion has not been explored in detail. Materials and Methods: In a stratified random sample of Rochester, MN, women and men 21–97 years of age, indices of bone strength, flexural rigidity (EI), and axial rigidity (EA) were estimated from central QCT measurements at the femoral neck and lumbar spine and pQCT measurements at the ultradistal radius, whereas habitual skeletal loading was assessed using lean body mass, total skeletal muscle mass (TSM), body weight, and physical activity. Using regression analysis, we tested the hypothesis (Ho) that bone strength per unit load did not vary with age. Results and Conclusions: In these cross-sectional data, the null hypothesis of no age-related change was rejected in 72% of the strength-to-load ratios tested. For example, the ratio of femoral neck EI to TSM increased by 0.19%/year in women (p =0.008) and by 0.49%/year in men (p < 0.001). There was no close correspondence between changes in habitual load and changes in bone strength, nor any consistent pattern. Moreover, interindividual variation in the strength-to-load ratios was substantial. These data suggest that the notion of reduced skeletal loading as the primary basis for age-related bone loss is oversimplified.