Biomedical subjects

Marci D Jones

Publications and source records attributed to Marci D Jones.

5 recordsLinked to original sources

PubMed2004

1,25-dihydroxyvitamin D3 down-regulation of PHEX gene expression is mediated by apparent repression of a 110 kDa transfactor that binds to a polyadenine element in the promoter.

The PHEX gene encodes an endopeptidase expressed in osteoblasts that inactivates an uncharacterized peptide hormone, phosphatonin, which suppresses bone mineralization as well as renal phosphate reabsorption and vitamin D bioactivation. We demonstrate that 1alpha-25-dihydroxyvitamin D (1,25(OH)2D3), the, active renal vitamin D metabolite, decreases PHEX mRNA in the rat osteoblastic cell line, UMR-106, as well as in mouse calvaria. Promoter/reporter construct analysis of the murine PHEX gene in transfected UMR-106 cells localized the repressive effect of 1,25(OH)2D3 to the -133 to -74 bp region, and gel mobility shift experiments revealed that 1,25(OH)2D3 treatment of the cells diminished the binding of a nuclear protein(s) to a stretch of 17 adenines from bp -116 to -100 in the proximal PHEX promoter. Either overexpression of a dominant-negative vitamin D receptor (VDR) or deletion of this sequence of 17 A-T base pairs abolished the repressive effect of 1,25(OH)2D3 by attenuating basal promoter activity, indicating that this region mediates the 1,25(OH)2D3 response and is involved in basal transcription. South-western blot analysis and DNA affinity purification show that an unidentified 110 kDa nuclear protein binds to the poly(A) element. Because 1,25(OH)2D3-liganded VDR neither binds to the polyadenine region of the PHEX promoter nor directly influences the association of the 110 kDa transfactor, we conclude that 1,25(OH)2D3 indirectly decreases PHEX expression via VDR-mediated repression (or modification) of this novel transactivator. Thus, we have identified a cis-element required for PHEX gene transcription that participates in negative feedback control of PHEX expression and thereby modulates the actions of phosphatonin.

Adenine↗

PubMed2002

Wrist fractures.

The benefits of a well-reduced and well-healed wrist fracture are predictable. This knowledge has prompted the development of myriad treatment methods and fixation devices. The choice of open versus closed reduction and the devices used to maintain that reduction could most often be determined with a well-defined and reproducible closed reduction maneuver. With this maneuver, the integrity of the critical volar ulnar corner of the radius is determined as is articular stepoff, metaphyseal comminution, and distal radionular joint (DRUJ) stability. Reconstruction of the subluxed or dislocated DRUJ starts with the reduction of the radius, frequently obviating the need to address fractures involving the ulnar head and styloid. Most importantly, the results of treatment reflect surgical decision over the fixation method.

Bone Nails↗

PubMed2002

Glucocorticoid regulation of the murine PHEX gene.

The phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) is a member of the neutral endopeptidase family, which is expressed predominantly on the plasma membranes of mature osteoblasts and osteocytes. Although it is known that the loss of PHEX function results in X-linked hypophosphatemic rickets, characterized by abnormal bone matrix mineralization and renal phosphate wasting, little is known about how PHEX is regulated. We therefore sought to determine whether the murine PHEX gene is regulated by glucocorticoids (GCs), which are known to influence phosphate homeostasis and bone metabolism. Northern blot analysis revealed increased PHEX mRNA expression in GC-treated suckling mice (1.5-fold) and in rat osteogenic sarcoma (UMR-106) cells (2.5-fold). An increase was also seen in PHEX promoter activity in transiently transfected UMR-106 cells with GC treatment. Analysis of nested promoter deletions revealed that an atypical GC response element was located between -337 and -315 bp. Mutational analysis and electrophoretic mobility shift assays further identified -326 to -321 bp as a site involved in GC regulation. Supershift analyses and electrophoretic mobility shift assay competition studies indicated that the core binding factor alpha1-subunit transcription factor is able to bind to this region and may therefore play a role in the GC response of the murine PHEX gene.

Animals↗

PubMedDate not supplied

Joint arthroplasties and prostheses.

Joint arthroplasty is the most frequently performed orthopedic procedure after fracture fixation. The major indications for any joint replacement are degenerative joint disease, inflammatory arthropathy, avascular necrosis, and complicated fractures. The major contraindications for any joint arthroplasty are systemic and joint infection and a neuropathic joint. The interpretation of radiographs in cases of joint arthroplasty is a significant part of many radiology practices, and correct recognition of the prosthetic devices and their complications by the radiologist is important. The article reviews the most common types of joint arthroplasties and prostheses of the upper and lower extremities and discusses the most frequent complications associated with their placement.

Arthroplasty, Replacement↗

PubMedDate not supplied

Fracture fixation.

The basic goal of fracture fixation is to stabilize the fractured bone, to enable fast healing of the injured bone, and to return early mobility and full function of the injured extremity. Fractures can be treated conservatively or with external and internal fixation. Conservative fracture treatment consists of closed reduction to restore the bone alignment. Subsequent stabilization is then achieved with traction or external splinting by slings, splints, or casts. Braces are used to limit range of motion of a joint. External fixators provide fracture fixation based on the principle of splinting. There are three basic types of external fixators: standard uniplanar fixator, ring fixator, and hybrid fixator. The numerous devices used for internal fixation are roughly divided into a few major categories: wires, pins and screws, plates, and intramedullary nails or rods. Staples and clamps are also used occasionally for osteotomy or fracture fixation. Autogenous bone grafts, allografts, and bone graft substitutes are frequently used for the treatment of bone defects of various causes. For infected fractures as well as for treatment of bone infections, antibiotic beads are frequently used.

Casts, Surgical↗