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Education ?

Medical School Score
George Washington University (1991)

Awards & Distinctions ?

American Board of Internal Medicine

Affiliations ?

Dr. Brady is affiliated with 1 hospitals.

Hospital Affiliations



  • Valley Hospital
    2500 S Woodworth Loop, Palmer, AK 99645
    Top 50%
  • Publications & Research

    Dr. Brady has contributed to 7 publications.
    Title Adaptive Reshaping of Objects in (multiparameter) Hilbert Space for Enhanced Detection and Classification: an Application of Receiver Operating Curve Statistics to Laser-based Mass Spectroscopy.
    Date July 2008
    Journal Journal of the Optical Society of America. A, Optics, Image Science, and Vision

    We propose a new approach to the classical detection problem of discrimination of a true signal of interest from an interferent signal, which may be applied to the area of chemical sensing. We show that the detection performance, as quantified by the receiver operating curve (ROC), can be substantially improved when the signal is represented by a multicomponent data set that is actively manipulated by means of a shaped laser probe pulse. In this case, the signal sought (agent) and the interfering signal (interferent) are visualized by vectors in a multidimensional detection space. Separation of these vectors can be achieved by adaptive modification of a probing laser pulse to actively manipulate the Hamiltonian of the agent and interferent. We demonstrate one implementation of the concept of adaptive rotation of signal vectors to chemical agent detection by means of strong-field time-of-flight mass spectrometry.

    Title A Bacterial E3 Ubiquitin Ligase Targets a Host Protein Kinase to Disrupt Plant Immunity.
    Date August 2007
    Journal Nature

    Many bacterial pathogens of plants and animals use a type III secretion system to deliver diverse virulence-associated 'effector' proteins into the host cell. The mechanisms by which these effectors act are mostly unknown; however, they often promote disease by suppressing host immunity. One type III effector, AvrPtoB, expressed by the plant pathogen Pseudomonas syringae pv. tomato, has a carboxy-terminal domain that is an E3 ubiquitin ligase. Deletion of this domain allows an amino-terminal region of AvrPtoB (AvrPtoB(1-387)) to be detected by certain tomato varieties leading to immunity-associated programmed cell death. Here we show that a host kinase, Fen, physically interacts with AvrPtoB(1-387 )and is responsible for activating the plant immune response. The AvrPtoB E3 ligase specifically ubiquitinates Fen and promotes its degradation in a proteasome-dependent manner. This degradation leads to disease susceptibility in Fen-expressing tomato lines. Various wild species of tomato were found to exhibit immunity in response to AvrPtoB(1-387 )and not to full-length AvrPtoB. Thus, by acquiring an E3 ligase domain, AvrPtoB has thwarted a highly conserved host resistance mechanism.

    Title Regulation by Complement C3a and C5a Anaphylatoxins of Cytokine Production in Human Umbilical Vein Endothelial Cells.
    Date June 2003
    Journal The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology

    C3a and C5a anaphylatoxins are cytokine-like polypeptides generated during complement (C) system activation and released at the inflammatory site. They exert several biological activities through binding to the G-protein-coupled receptors C3aR and C5aR, respectively. Cloning and Northern blot experiments have indicated that both receptors are expressed by myeloid as well as nonmyeloid cells (e.g., endothelial and epithelial cells). To better understand the roles of C anaphylatoxins during inflammation, we investigated their effects on the expression of cytokine and chemokine genes by cultured human umbilical cord endothelial cells (HUVEC). HUVEC constitutively expressed both anaphylatoxin receptors, and addition of physiological concentrations of C3a or C5a (nM range) caused a strong up-regulation of IL-8, IL-1beta, and RANTES mRNA in a time- and dose-dependent manner. Conversely, a decrease in IL-6 mRNA was observed, but only with C5a stimulation. These variations in mRNA levels were inhibited by pretreatment with anti-C5aR and anti-C3aR antibodies as well as pertussis toxin, indicating that G-proteins are involved in anaphylatoxin-activated signal transduction pathways. Finally, we showed that C3a and C5a both strongly activate downstream MAP kinase signaling pathways (p44 and p42 Erk kinases).

    Title Co-inheritance of Mutations in the Uroporphyrinogen Decarboxylase and Hemochromatosis Genes Accelerates the Onset of Porphyria Cutanea Tarda.
    Date December 2000
    Journal The Journal of Investigative Dermatology

    Porphyria cutanea tarda is a skin disease caused by photosensitization by porphyrins whose accumulation is caused by deficiency of hepatic uroporphyrin- ogen decarboxylase activity. Mutations in the uroporphyrinogen decarboxylase gene are present in the low-penetrant, autosomal dominant familial form but not in the commoner sporadic form of porphyria cutanea tarda. We have investigated the relationship between age of onset of skin lesions and mutations (C282Y, H63D) in the hemochromatosis gene in familial (19 patients) and sporadic porphyria cutanea tarda (65 patients). Familial porphyria cutanea tarda was identified by mutational analysis of the uroporphyrinogen decarboxylase gene. Five previously described and eight novel mutations (A80S, R144P, L216Q, E218K, L282R, G303S, 402-403delGT, IVS2 + 2 delTAA) were identified. Homozygosity for the C282Y hemochromatosis mutation was associated with an earlier onset of skin lesions in both familial and sporadic porphyria cutanea tarda, the effect being more marked in familial porphyria cutanea tarda where anticipation was demonstrated in family studies. Analysis of the frequencies of hemochromatosis genotypes in each type of porphyria cutanea tarda indicated that C282Y homozygosity is an important susceptibility factor in both types but suggested that heterozygosity for this mutation has much less effect on the development of the disease.

    Title Diffusive Vs. Convective Therapy: Effects on Mediators of Inflammation in Patient with Severe Systemic Inflammatory Response Syndrome.
    Date January 1999
    Journal Critical Care Medicine

    OBJECTIVE: To compare two forms of continuous renal replacement therapy, continuous venovenous hemofiltration (CVVH) vs. continuous venovenous hemodialysis (CVVHD), in terms of the removal of inflammatory mediators from the blood of patients with systemic inflammatory response syndrome and acute renal failure. DESIGN: Randomized crossover, clinical study. SETTING: University teaching hospital. PATIENTS: Thirteen patients with systemic inflammatory response syndrome and acute renal failure receiving continuous renal replacement therapy. INTERVENTION: Patients were randomized to receive either convective clearance using CVVH or diffusive clearance using CVVHD for the first 24 hrs, followed by the other modality for 24 hrs. All treatments utilized AN69 hemofilters. CVVH was performed with an ultrafiltration rate of 2 L/hr and CVVHD with a dialysis outflow rate of 2 L/hr. MEASUREMENTS AND MAIN RESULTS: Plasma and ultrafiltrate concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, and sL-selectin were measured at 0, 1, 3, 6, 12, and 24 hrs by radioimmunoassay. Plasma endotoxin concentrations were also measured at 0, 12, and 24 hrs by chromogenic assay. CVVH was associated with a 13% decrease in plasma TNF-alpha concentrations compared with a 23% increase while on CVVHD (p < .05). Mean plasma concentrations of IL-6, IL-10, and sL-selectin were unchanged over time and between therapies. Only minimal amounts of mediators were recovered in the effluents with either therapy except for IL-6. The clearances for IL-6 were different between therapies, 1.9+/-0.8 (SD) mL/min for CVVHD and 3.3+/-1.5 mL/min for CVVH, (p< .01). Plasma endotoxin concentrations were not different between therapies. CONCLUSION: CVVH resulted in a decrease in plasma TNF-alpha concentrations as compared with CVVHD, while the type of transport mechanism used did not influence plasma concentrations of IL-6, IL-10, soluble L-selectin, or endotoxin. Differences in clearance for IL-6 between CVVH and CVVHD did not translate into significant changes in circulating IL-6 concentrations.

    Title Use of the Peabody Picture Vocabulary Test with Preschool Children.
    Date July 1969
    Journal The Training School Bulletin
    Title Use of the Peabody Picture Vocabulary Test with Preschool Children.
    Date May 1968
    Journal Psychological Reports

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