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Biomedical subjects

Mark D Johnson

Publications and source records attributed to Mark D Johnson.

24 records · Page 2Linked to original sources

Proteomic analysis in the neurosciences.

Proteomics is a field of study directed toward providing a comprehensive view of the characteristics and activity of every cellular protein. Rapid innovations in the core technologies required to characterize proteins on a global scale are poised to bring about a comprehensive understanding of how dynamic changes in protein expression, post-translational modification, and function affect complex signaling and regulatory networks. These advances have significant implications for understanding the multitude of pathways that govern behavior and cognition and the response of the nervous system to injury and disease.

Animals↗

Investigation of the mechanism of enhancement of central nervous system delivery of 2'-beta-fluoro-2',3'-dideoxyinosine via a blood-brain barrier adenosine deaminase-activated prodrug.

Enhanced central nervous system (CNS) delivery of certain poorly penetrating 2',3'-dideoxynucleosides has been achieved by designing prodrugs that are substrates for enzymes, such as adenosine deaminase (ADA), that are present at high activities in brain tissue. In this study, the potential role of adenosine deaminase localized within the endothelial cells of the blood-brain barrier (BBB) in providing enhanced intracellular and CNS delivery of an ADA-activated prodrug is assessed in vitro using cell culture models of the BBB. The kinetics of uptake and bioconversion of 2'-beta-fluoro-2',3'-dideoxyadenosine (F-ddA), a model ADA-activated prodrug of 2'-beta-fluoro-2',3'-dideoxyinosine, were determined in primary cultured bovine brain microvascular endothelial cells. Model-based simulations of CNS availability derived from in vitro estimates of parameters for simple passive diffusion and ADA-catalyzed deamination suggest that ADA that is localized within the BBB plays an important role in the conversion of F-ddA to 2'-beta-fluoro-2',3'-dideoxyinosine during its passage across the BBB. Consistent with in vivo observations, these simulations demonstrate that elevated levels of certain enzymes, such as ADA, in the brain microvascular endothelial cells of the BBB may be exploited in the design of brain-targeted prodrugs or drug-carrier conjugates, which brain tissue selectively converts.

Adenosine Deaminase↗

Surgical resection for patients with solid brain metastases: current status.

Brain metastases occur in up to 40% of patients with cancer. Their management has been revolutionized in the last decade by three developments: improved imaging and detection of metastases, better treatment of systemic disease with the result that metastases occur more often; and improved surgical techniques including image-guided surgery to treat metastatic lesions. Class 1 data suggest that surgery is a better treatment for metastases than whole brain radiation. Other data suggest that metastases even in eloquent cortex can be removed safely. The complication rate is low and the recurrence rate is less than 10%. In general, indications for surgery include a mass with an unknown primary; a symptomatic mass including one in eloquent areas; a mass with considerable edema requiring high dose steroids; a mass greater than 3 cm; or patient preference when radiosurgery may also be an option. The question of radiosurgery or whole brain radiation as adjunct to surgical removal requires further evaluation.

Brain Neoplasms↗

Transcranial Doppler: an introduction for primary care physicians.

Transcranial Doppler (TCD) is a diagnostic tool that can be used at bedside to assess the cerebral vasculature noninvasively. It is inexpensive, safe, and reliable when compared with other techniques. It can be repeated multiple times and can be used for continuous monitoring if needed. Screening of children with sickle cell disease to assess and prevent ischemic strokes and monitoring for vasospasm after subarachnoid hemorrhage are well established, evidenced based utilizations of TCD. It is useful for the evaluation of occlusive intracranial vascular lesions with many emerging indications in the management of ischemic stroke. TCD with micro-bubble enhancement has comparable sensitivity to transesophageal echocardiogram in detecting right-to-left atrial cardiac shunts. TCD is underused as a clinical tool despite well established indications. The pressure to contain increasing medical cost will likely result in increased utilization of this test in future.

Cerebral Veins↗