The effect of exercise on pQCT parameters of bone structure and strength in postmenopausal women--a systematic review and meta-analysis of randomized controlled trials.

UNLABELLED: Inconsistent study findings of exercise on areal bone density highlight the need to include parameters of bone geometry and volumetric bone density measurements. Using a systematic review and meta-analysis, we found a decrease in bone loss through the maintenance of cortical and trabecular volumetric bone mineral density (BMD). Studies with longer exercise durations and larger sample sizes are needed. INTRODUCTION: Exercise has long been recommended to prevent age-related loss of bone mass in postmenopausal women. However, inconsistent study findings on the effect of exercise on BMD preservation have highlighted the importance of extending the evaluation of bone to include the parameters of bone geometry. We conducted both a systematic review and meta-analysis of the effects of exercise on bone geometry and volumetric BMD in postmenopausal women. METHODS: We searched MEDLINE, PubMed, and EMBASE from 1950 to April 2009 and included prospective, randomized controlled trials of healthy postmenopausal women where the intervention involved exercise or sport and outcomes included quantitative or peripheral quantitative computed tomography bone parameters. Outcome variables included: total volumetric BMD, cortical volumetric BMD (CvBMD), trabecular volumetric BMD (TrvBMD), total bone mineral content, cortical BMC, total bone area, cortical area, polar stress-strain index, and bone strength index. RESULTS: Six studies satisfied our inclusion and exclusion criteria. Lower extremity exercises resulted in small (∼0.9%) but significant improvements in TrvBMD of the distal tibia (p = 0.0006) and in CvBMD of the tibial shaft (p = 0.0007). Studies with longer durations of exercise (12 months) and those in early postmenopausal women showed significant changes in CvBMD at the tibial shaft. CONCLUSIONS: We conclude that exercise in postmenopausal women may decrease bone loss by maintaining cortical and trabecular volumetric BMD. To better understand the effect of exercise on bone geometric structure and strength, more studies of longer duration and larger sample sizes are needed.

Altered tumor growth in vivo after immunization of mice with antitumor antibodies.

A comparison has been made between the growth patterns of two spontaneously appearing mammary adenocarcinomas in murine bone marrow radiation chimeras and in mice preimmunized with monoclonal antibodies (MAb) detecting embryo-associated antigenic determinants. A correlation was seen between the ability of the embryo-immunized chimeras to produce cytotoxic antibody to the tumors, as assessed by an antibody-dependent cellular cytotoxic assay, and the permissiveness of the mice for growth of a tumor transplant. In addition, mice deliberately preimmunized with cytotoxic MAb (antibody-dependent cellular cytotoxic assay) allowed more rapid growth specifically of that tumor earlier found to be most sensitive to the MAb used for immunization. By comparing the changing antigenic phenotype of tumor cells serially passaged through different immunized, nonimmunized mice, evidence was found suggesting that immunization could cause either antigen modulation of transferred tumor cells or a (transient) selective advantage to antigenically discrete subpopulations within the heterogeneous tumor population. Finally, we have studied the growth pattern of tumor cells transplanted into mice immunized with rabbit antibodies directed against the murine MAb. In this case, tumor growth was slowed preferentially for the tumor reactive with the specific MAb, and again, predictable changes in the antigenic spectrum of tumor cells harvested from these animals were observed. Our overall findings are interpreted in terms of the involvement of networks of antibodies reacting with embryo-associated antigens in the regulation of growth of the murine mammary adenocarcinomas studied.

Noncovalent association of heavy and light chains of human immunoglobulins. III. Specific interactions between VH and VL.

Mildly reduced monoclonal human IgM proteins have been cleaved at cysteinyl residues to give VH fragments after S-cyanylation with 2-nitro-5-thiocyanobenzoic acid. The noncovalent interaction between the VH fragments and autologous kappa-chains was studied by ultraviolet difference spectroscopy and circular dichroism. A bimolecular complex was formed with an association constant in excess of 10(7) M-1 at 23 degrees C. Complex formation was accompanied by burial of tryptophan and tyrosine side-chains. In contrast to the studies with autologous species, the VH fragments did not associate with heterologous kappa-chains as judged both by difference spectroscopy and gel filtration using radiolabeled VH fragments. This specificity in the association between VH and VL has been attributed to interactions contributed to by residues in the third hypervariable region of VH encoded by the DH and JH genes.