Mayo Clinic

About: Mayo Clinic is a healthcare organization based out in Rochester, Minnesota, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 63387 authors who have published 169578 publications receiving 8114006 citations.

The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption.

Abstract: Although multiple hormones and cytokines regulate various aspects of osteoclast formation, the final two effectors are osteoprotegerin ligand (OPG-L)/osteoclast differentiation factor (ODF), a recently cloned member of the tumor necrosis factor superfamily, and macrophage colony-stimulating factor. OPG-L/ODF is produced by osteoblast lineage cells and exerts its biological effects through binding to its receptor, osteoclast differentiation and activation receptor (ODAR)/receptor activator of NF-kappa B (RANK), on osteoclast lineage cells, in either a soluble or a membrane-bound form, the latter of which requires cell-to-cell contact. Binding results in rapid differentiation of osteoclast precursors in bone marrow to mature osteoclasts and, at higher concentrations, in increased functional activity and reduced apoptosis of mature osteoclasts. The biological activity of OPG-L/ODF is neutralized by binding to osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF), a member of the TNF-receptor superfamily that also is secreted by osteoblast lineage cells. The biological importance of this system is underscored by the induction in mice of severe osteoporosis by targeted ablation of OPG/OCIF and by the induction of osteopetrosis by targeted ablation of OPG-L/ODF or overexpression of OPG/OCIF. Thus, osteoclast formation may be determined principally by the relative ratio of OPG-L/ODF to OPG/OCIF in the bone marrow microenvironment, and alterations in this ratio may be a major cause of bone loss in many metabolic disorders, including estrogen deficiency and glucocorticoid excess. That changes in but two downstream cytokines mediate the effects of large numbers of upstream hormones and cytokines suggests a regulatory mechanism for osteoclastogenesis of great efficiency and elegance.

Initial genome sequencing and analysis of multiple myeloma

Abstract: Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumour genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the data set. These include the mutation of genes involved in protein translation (seen in nearly half of the patients), genes involved in histone methylation, and genes involved in blood coagulation. In addition, a broader than anticipated role of NF-κB signalling was indicated by mutations in 11 members of the NF-κB pathway. Of potential immediate clinical relevance, activating mutations of the kinase BRAF were observed in 4% of patients, suggesting the evaluation of BRAF inhibitors in multiple myeloma clinical trials. These results indicate that cancer genome sequencing of large collections of samples will yield new insights into cancer not anticipated by existing knowledge.

Addition of ifosfamide and etoposide to standard chemotherapy for Ewing's sarcoma and primitive neuroectodermal tumor of bone.

Abstract: Background Ewing's sarcoma and primitive neuroectodermal tumor of bone are closely related, highly malignant tumors of children, adolescents, and young adults. A new drug combination, ifosfamide and etoposide, was highly effective in patients with Ewing's sarcoma or primitive neuroectodermal tumor of bone who had a relapse after standard therapy. We designed a study to test whether the addition of these drugs to a standard regimen would improve the survival of patients with newly diagnosed disease. Methods Patients 30 years old or younger with Ewing's sarcoma, primitive neuroectodermal tumor of bone, or primitive sarcoma of bone were eligible. The patients were randomly assigned to receive 49 weeks of standard chemotherapy with doxorubicin, vincristine, cyclophosphamide, and dactinomycin or experimental therapy with these four drugs alternating with courses of ifosfamide and etoposide. Results A total of 518 patients met the eligibility requirements. Of 120 patients with metastatic disease, 62 were random...

Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study.

Abstract: Objective A high frequency of infections complicating rheumatoid arthritis (RA) has been described in reports of case series. This retrospective longitudinal cohort study was undertaken to compare the frequency of infections in a population-based incidence cohort of RA patients with that in a group of individuals without RA from the same population. Methods RA patients included all members of an incidence cohort of Rochester, Minnesota residents ages ≥18 years who were first diagnosed as having RA between 1955 and 1994. One age- and sex-matched subject without RA was selected for each patient with RA. Study subjects were followed up by review of their entire medical record until death, migration from the area, or study end (January 1, 2000), and details of all documented infections, along with information on potential risk factors for infection, were recorded. Hazard ratios for infections were estimated using stratified Andersen-Gill proportional hazards models, with adjustment for potential confounders. Results The 609 RA patients and 609 non-RA study subjects (mean age 58.0 years; 73.1% female) were followed up for a mean of 12.7 years and 15.0 years, respectively, reflecting higher mortality among the group with RA. Hazards ratios for objectively confirmed infections, infections requiring hospitalization, and any documented infection in patients with RA were 1.70 (95% confidence interval [95% CI] 1.42–2.03), 1.83 (95% CI 1.52–2.21), and 1.45 (95% CI 1.29–1.64), respectively, after adjustment for age, sex, smoking status, leukopenia, corticosteroid use, and diabetes mellitus. Sites of infection with the highest risk ratios were bone, joints, skin, soft tissues, and the respiratory tract. Conclusion In this study, patients with RA were at increased risk of developing infections compared with non-RA subjects. This may be due to immunomodulatory effects of RA, or to agents with immunosuppressive effects used in its treatment.