Osteoarthritis of the knee is associated with vertebral and nonvertebral fractures in the elderly: the Rotterdam Study

OBJECTIVE: To study the association between prevalent radiographic osteoarthritis (ROA) of the knee and incident vertebral and nonvertebral fractures. METHODS: A sample of 2,773 subjects was drawn from the Rotterdam Study, a prospective population-based cohort study of the elderly. Status on knee ROA was assessed at baseline using the Kellgren score. Incident nonvertebral fractures were scored for all subjects, and for 1,466 subjects additional data on incident vertebral fractures were available. RESULTS: Although people with ROA had a higher bone mineral density (BMD), their incident fracture risk was increased as compared with those without ROA. After adjustment for potential confounding factors, including parameters of postural stability, the relative risks for incident vertebral and nonvertebral fractures in the presence of knee ROA were 2.0 (95% confidence interval [95% CI] 1.1-3.4) and 1.5 (95% CI 1.1-2.0), respectively. CONCLUSIONS: Knee ROA is associated with an increased risk of incident vertebral and nonvertebral fractures, independent of BMD and parameters of postural stability.     

Temporal patterns of bone marrow cell differentiation following transplantation in doxorubicin-induced cardiomyopathy

OBJECTIVE: Recent studies have suggested benefits of bone marrow cell transplantation for the regeneration of ischemic cardiac tissue. To extend the potential of cell transplantation, we assessed this treatment in a mouse model of acute nonischemic doxorubicin-induced cardiomyopathy. METHODS: To allow detection of engrafted cells, we used transgenic mice expressing the nuclear-located LacZ under the control of either desmin or vimentin promoters, which identify muscle lineage and mesenchymal cells, respectively. All transplanted cells were also labeled with the fluorescent dye DIL. One week after the administration of doxorubicin (15 mg/kg), mice were intramyocardially injected with either allogeneic unpurified bone marrow cells (6 x 10(6) in 30 microl, n=59) or purified sca-1(pos) cells (4 x 10(5) in 30 microl, n=22). In parallel, control normal mice received only unpurified bone marrow cells (n=28). Hearts were harvested at serial intervals until 2 weeks after transplantation and analyzed by immunohistochemistry to assess the degree of engraftment and transplanted cell differentiation. RESULTS: In control mice, no differentiation of bone marrow cells was detected. In contrast, unpurified bone marrow cells grafted into diseased myocardium featured two successive phases of cell differentiation. The first yielded cells with a mesenchymal phenotype (44.1+/-10.1 cells/3 x 10(-2) mm(3) at 2 days), was transient and lasted 1 week. The second phase was characterized by cells with a muscular phenotype detected in a small number of cells (5.6+/-2.3 cells/3 x 10(-2) mm(3) at 7 days). Two weeks after transplantation, some of these cells appeared phenotypically close to cardiomyocytes, as evidenced by morphology and positive staining for myosin binding protein C, vinculin and myosin heavy chain. In sca-1(pos) hematopoietic progenitor grafted mice hearts, no transdifferentiation into cardiac cells was detected at any time point. CONCLUSION: These data support the hypothesis of the potential for a myogenic differentiation of bone marrow cells following engraftment in a nonischemic model of global cardiomyopathy. Bone marrow-derived cells amenable to cardiac differentiation are present in total unpurified bone marrow but not in the sca-1(pos) hematopoietic progenitor cell population. However, the very small number of transdifferentiated cells raises concerns over their functional efficacy.     

The Effect of Psychiatric Rehabilitation on the Activity and Participation Level of Clients with Long-Term Psychiatric Disabilities

During the last decades of the 20th century, many psychiatric hospitals changed the living environments of their clients with long-term psychiatric disabilities. We investigated the effect of this environmental psychiatric rehabilitation and normalization process on the activity and participation level of such clients residing in one Dutch psychiatric hospital. The seven years of panel research demonstrated that more normal living environments have a positive effect on clients' activity and participation level. This is controlled for the fact that younger clients, and clients with a relative high activity and participation level were selected for these normal living environments.     

Evidence for the production of trioxygen species during antibody-catalyzed chemical modification of antigens

Recent work in our laboratory showed that products formed by the antibody-catalyzed water-oxidation pathway can kill bacteria. Dihydrogen peroxide, the end product of this pathway, was found to be necessary, but not sufficient, for the observed efficiency of bacterial killing. The search for further bactericidal agents that might be formed along the pathway led to the recognition of an oxidant that, in its interaction with chemical probes, showed the chemical signature of ozone. Here we report that the antibody-catalyzed water-oxidation process is capable of regioselectively converting antibody-bound benzoic acid into para-hydroxy benzoic acid as well as regioselectively hydroxylating the 4-position of the phenyl ring of a single tryptophan residue located in the antibody molecule. We view the occurrence of these highly selective chemical reactions as evidence for the formation of a short-lived hydroxylating radical species within the antibody molecule. In line with our previously presented hypothesis according to which the singlet-oxygen ((1)O*(2)) induced antibody-catalyzed water-oxidation pathways proceeds via the formation of dihydrogen trioxide (H(2)O(3)), we now consider the possibility that the hydroxylating species might be the hydrotrioxy radical HO(3)*, and we point to the remarkable potential of this either H(2)O(3)- or O(3)-derivable species to act as a masked hydroxyl radical HO* in a biological environment.