Biomedical subjects

M Witcher

Publications and source records attributed to M Witcher.

4 recordsLinked to original sources

PubMed2001

BAG-1 p50 isoform interacts with the vitamin D receptor and its cellular overexpression inhibits the vitamin D pathway.

Human BAG-1 is an anti-apoptotic protein with four protein isoforms (BAG-1 p50, p46, p33, and p29). BAG-1 p46 was originally isolated in a screen for proteins binding to the glucocorticoid receptor; it binds and modulates the action of several members of the nuclear steroid hormone receptor superfamily. The vitamin D receptor (VDR) is another member of this superfamily, and the vitamin D pathway is important for prevention and therapy of osteoporosis, renal failure, cancer, and psoriasis. Therefore, we investigated the effect of the recently isolated BAG-1 p50 on the vitamin D pathway. By use of Far Western blot analysis and glutathione S-transferase BAG-1 p50 binding assays, BAG-1 p50 was demonstrated to interact with the VDR, and the BAG-1 p50 N-terminus was required. In U87 cells that were stably transfected with BAG-1 p50, binding of the VDR to its response element in electrophoretic mobility shift assays was blocked, enhancement of transcriptional activation was inhibited, cell growth rate was enhanced, cell growth inhibition induced by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] was blocked, and 1,25(OH)2D3-mediated VDR induction was inhibited. These results suggest that BAG-1 p50 is a novel regulator of the vitamin D signaling pathway, and its overexpression may lead to cellular resistance to 1,25(OH)2D3 therapy.

Calcitriol↗

PubMed1993

Biotechnology: an introduction to recombinant DNA technology and product availability.

Exciting advances in biotechnology have led to the development of innovative biological products to improve health care. In this review article, the major techniques of product development and manufacturing in biotechnology are discussed, with a focus on recombinant DNA technology. In addition, monoclonal antibody, nucleotide blockade, polymerase chain reaction, antisense, and gene therapy technologies will be defined briefly. For recombinant-DNA technology, the issues of gene isolation, gene cloning, protein expression, scale-up (manufacturing), and quality assurance are addressed. The 16 approved products and the research pipeline are characterized. In addition, major usage issues for biological products are noted. This review serves as an introduction to the science and applications of biotechnology present and future.

Biotechnology↗

PubMed1990

Urologic changes after cauda equina compression in dogs.

Relative degrees (25%, 50% or 75%) of constriction of the entire cauda equina at the seventh lumbar level were performed on eighteen pure bred female beagle hounds by surgically implanting a circular polyethylene loop with an imbedded stainless steel wire. The wire was mechanically constricted by external control and the degree of compression was confirmed by pre- and postoperative magnetic resonance imaging or computed tomography scanning. A control group of two dogs had laminectomy only. Neurologic function was evaluated daily. Cystometrics were performed on each dog after constriction had been present for three months. Cortical evoked potentials (CEPs) were obtained on all dogs preoperatively, immediately following constriction and at monthly intervals for three months. Dogs were sacrificed at three months and the cauda equina and spinal cord were examined histopathologically. Cystometric tracings were noted to become a flat line with 75% compression of the cord. Less compression had minimal effect on the cystometric curves. The mean latency, determined by cortical evoked potentials, was noted to increase by 3.2%, 7.8%, and 17.2% immediately after 25%, 50% and 75% constriction, respectively. Histologic changes ranged from occasional enlargement of the axons on the periphery of the cauda equina with 25% constriction to severe loss of all axons and atrophic roots at the level of the constricting band with 75% constriction.

Animals↗

PubMed1990

Application of office ultrasound in the management of the spinal cord injury patient.

The effectiveness of office ultrasonography of the bladder and kidneys to provide routine urological followup was assessed in the outpatient spinal cord injury clinic. A total of 86 asymptomatic spinal cord injury patients underwent office ultrasonography of the kidneys and bladder as part of the routine urological followup. There were 106 ultrasound scans performed. Of the patients 68 had a blinded excretory urogram for comparison, including 20 who underwent additional studies (computerized tomography scans of the abdomen and pelvis, and/or radiologist-performed ultrasound examinations of the kidneys and bladder). All 18 patients who underwent office ultrasound but not excretory urography each underwent computerized tomography scans of the abdomen and pelvis and/or radiologist-performed ultrasound examinations of the kidneys and bladder. Office ultrasound detected 5 of 6 kidney stones, 6 of 6 hydronephrotic kidneys, 5 of 7 renal masses (4 of 6 cysts and 1 of 1 renal tumor), 3 of 3 bladder stones and 3 of 3 bladder diverticula. Subtle changes of chronic renal infection noted on excretory urography in 4 patients were not detected on corresponding ultrasound scans but voiding cystourethrograms revealed no reflux, and comparison to prior studies confirmed that these renal units were stable. Outpatient ultrasonography performed by the urologist proved to be a cost-effective and sensitive screening examination for urological disorders in the spinal cord injury population. The technique is easily learned, well tolerated and indicated when further urological evaluation is required.

Cost-Benefit Analysis↗