Health beliefs and attitudes toward the prevention of osteoporosis in older women

OBJECTIVE: A pilot study to determine health belief factors associated with osteoporosis prevention behaviors in peri-and postmenopausal women. DESIGN: We administered a survey to a convenience sample of 60 women aged 40-95 years old in an urban family practice center and an associated retirement community. The self-reported questionnaire addressed demographics, osteoporosis risk factors, current preventive behaviors for osteoporosis, and health beliefs. RESULTS: The majority of women (89%) believed that osteoporosis is a serious condition, but only 29% perceived a personal susceptibility. Women were less concerned about osteoporosis when compared with cancer, cardiovascular disease, and neurologic disorders. Only 40% of women were taking active measures to prevent osteoporosis. There was no significant relationship between active osteoporosis prevention behaviors and five health belief factors (motivation, barrier, active participant in health care, frustration, and benefit) (p >or= 0.43). However, active behaviors to prevent osteoporosis were found to correlate with the single item "I am worried about developing osteoporosis" (p = 0.03). Most women surveyed would be willing to exercise and take calcium and a multivitamin to prevent osteoporosis. CONCLUSION: Few women are taking active measures to prevent osteoporosis despite their belief that it is a serious condition. Our data suggest that most women do not perceive a personal susceptibility to the disease. Only women who reported actively worrying about developing osteoporosis were more likely to be engaged in significant osteoporosis preventive behaviors.     

The effect of membrane fixed charges on diffusion potentials and streaming potentials

1. Electrical potential differences (p.d.''s) have been measured across an in vitro preparation of rabbit gall-bladder.2. When the gall-bladder separates identical bathing solutions, the p.d. is always zero, regardless of the composition of the bathing solution. Hence the gall-bladder is symmetrical: i.e. the mucosal and serosal cell membranes have the same relative permeability coefficients.3. Osmotic water flow causes streaming potentials of up to 20 mV, of a sign indicating greater permeability to cations than to anions.4. At constant osmolarity, streaming potentials increase slightly with NaCl concentration. Streaming potentials decrease considerably with changes in osmolarity resulting from changes in NaCl concentration.5. Diffusion potentials resulting from electrolyte concentration gradients are fitted well by the constant-field equation with the relative permeability coefficients P_Na = 1·00, P_Cl = 0·33, P_K = 2·3. These permeability coefficients are independent of osmolarity and of salt concentration.6. Relative to 0·25 mM-Ca, 5 mM-Ca reduces streaming potentials by 40%, NaCl diffusion potentials by 62%, and potassium diffusion potentials by 43%.7. The aqueous channels through which water and electrolytes traverse the cell membranes of the gall-bladder contain negative fixed charges, which are blocked by Ca. The physiological significance of the charges may be to reduce chloride permeability and thereby to increase the effectiveness of the gall-bladder in concentrating bile.8. The effect of pH, and analogy with surface charges of other cells, suggest that the charges are organic acids of low pK_a.     

Induction of CTL response by a minimal epitope vaccine in HLA A*0201/DR1 transgenic mice: dependence on HLA class II restricted T(H) response

CTL play a pivotal role in the immune response during viral infections. In this study, the HLA class II restricted T(H) requirement for optimal in vivo induction of HLA class I restricted CTL responses has been investigated. Towards this goal, transgenic mice expressing both HLA class I (A*0201 or A2.1) and class II (DRB1*0101 or DR1) molecules have been derived. Immunization of these mice with an HLA A*0201-restricted and CMV-specific CTL epitope (pp65(495-503)), and either of three different tetanus toxin-derived MHC class II-binding T(H) epitopes, resulted in a vigorous CTL response. CTL specific for the pp65(495-503) epitope were dramatically enhanced in mice expressing both the HLA-DR1 and HLA-A*0201 transgenes. Notably, preinjection of three TT peptides (TT(639-652), TT(830-843), and TT(947-967)) increased the capability of HLA A*0201/DR1 Tg mice to respond to subsequent immunization with the T(H) + CTL peptide mixture. These results indicate that the use of HLA A*0201/DR1 Tg mice constitute a versatile model system (in lieu of immunizing humans) for the study of both HLA class I and class II restricted T-cell responses. These studies provide a rational model for the design and assessment of new minimal-epitope vaccines based on their in vivo induction of a pathogen-specific CTL response.     

Characterization of anti-DNA B cells that escape negative selection

One of the challenges in the study of autoimmunity is to understand which autoreactive cells are subject to regulation and what mechanisms of regulation are operative. In mice transgenic for the R4A-gamma2b heavy chain of an anti-double stranded (ds) DNA antibody, the gamma2b heavy chain can pair with the full spectrum of endogenous light chains to produce a multitude of antibodies, including anti-dsDNA antibodies of different affinities and fine specificities. We have previously demonstrated the existence of two populations of anti-DNA B cells in non-autoimmune hosts: a high-affinity population which is rendered anergic in vivo, and a second high-affinity population which is deleted. We have now identified a third population of dsDNA-binding B cells. These cells produce germ-line-encoded antibodies with an apparent affinity for dsDNA that is 1 to 4 logs lower than the apparent affinities of antibodies made by anergic or deleted B cells, and represent a non-tolerized population which escapes regulation. Based on its characterization, we can define a molecular threshold for tolerance induction, and can speculate on the fate of these B cells when they are recruited to an immune response and undergo somatic mutation to become high-affinity anti-DNA B cells.     

Predominant type 1 CMV-specific memory T-helper response in humans: evidence for gender differences in cytokine secretion

Cell-mediated memory immune responses to viral antigens are important for protection against viruses causing persistent or acute infections. This study compared the cytokine profile of memory T-helper cells specific for cytomegalovirus (CMV) in healthy CMV-seropositive men and women. The cytokine response reflected T(H)1 bias, with dominant secretion of interferon (IFN)-gamma along with moderate levels of tumor necrosis factor-alpha, interleukin (IL)-10, and IL-2. Analyzed by gender, women had higher and significant spontaneous release of IFN-gamma and CMV-specific IL-2 secretion. Similar analysis with herpes simplex virus-1 showed a trend toward higher cytokine responsiveness in women, but the differences were not statistically significant. In contrast, men had statistically significant higher influenza virus-specific tumor necrosis factor-alpha secretion. IL-4 and IL-5, both T(H)2 cytokines, were low for all three viruses. The results show a predominant T(H)1 antiviral cytokine T-help memory response with significant differences linked to gender. Such differences may have an impact in the design of immunization strategies against CMV.     

Inositol 1,4,5-trisphosphate receptor function in human oocytes: calcium responses and oocyte activation-related phenomena induced by photolytic release of InsP(3) are blocked by a specific antibody to the type I receptor

Type I inositol 1,4,5-trisphosphate-sensitive receptors (InsP(3)R) are expressed in human oocytes and may be involved in operating the Ca(2+) release triggered by the fertilizing sperm. This study examines the contribution of type I InsP(3)R in operating Ca(2+) release in human oocytes secondary to InsP(3) itself, using a specific function-blocking antibody in conjunction with photolytic release of microinjected InsP(3). Intracellular Ca(2+) responses were assessed in oocytes microinjected with only caged InsP(3) in experiment set A, while in experiment sets B and C, sibling oocytes were injected with caged InsP(3) and the blocking antibody or a corresponding volume of medium, prior to flash photolysis. In experiment set C, certain fertilization-related phenomena (cortical granule exocytosis and chromatin configurations) were assessed using optical sections and three-dimensional image reconstructions obtained from a confocal laser scanning microscope. In experiment set A, photolytic release of InsP(3) triggered a Ca(2+) response (increase from approximately 100 to 220 nmol/l followed by an exponential recovery, n = 8) and a wave in the oocytes that spread from the stimulation point to the opposite pole. In set B, photolytic InsP(3) release generated Ca(2+) responses in control oocytes (n = 9), but not in the antibody-injected oocytes (n = 7). In set C, cortical granule exocytosis and anaphase chromosome configurations were noted in the control oocytes after flash photolysis (n = 6). These changes were completely absent in antibody injected oocytes as their cortical granules were intact and the chromosomes were in metaphase. These oocytes had also lacked Ca(2+) responses as in set B (n = 5). This study demonstrates the functional presence of type I InsP(3)R-operated Ca(2+) channels in human oocytes and further suggests an active role of InsP(3) in triggering the Ca(2+) rise and secondary activation phenomena at fertilization.     

Detection of beta-defensins secreted by human oral epithelial cells

Human beta-defensins are antimicrobial peptides that may be critical in the innate immune response to infection. hBD1 and hBD2 are expressed in oral epithelial cells and are detected near the surface of oral tissue, consistent with a role in the epithelial protective barrier function. In this report, we examine secretion of beta-defensins in vitro and in biological fluid using ProteinChip(R) Array, surface enhanced laser desorption/ionization (SELDI) technology combined with time-of-flight mass spectrometry. We show that the 47-amino acid form of hBD1 and the 41-amino acid form of hBD2 are the major secreted forms. These forms are both expressed and secreted under conditions anticipated from previous analysis of beta-defensin mRNAs; specifically, hBD1 is detected in culture supernatant from both unstimulated and stimulated cells, and hBD2 is detected only in stimulated cells. Identity of hBD1 and hBD2 was confirmed by immunocapture on the ProteinChip surface. Both peptides are also present in gingival crevicular fluid that accumulates between the tissue and tooth surface, although hBD1 is also found in several smaller forms suggesting extracellular proteolysis. This methodology offers several technical advantages for detection of defensins in biological fluids, including ease and speed of screening, no need for HPLC preliminary processing, and small sample size.