1660 S Albion St Suite 223
Denver CO 80222
Medical School: Other - Unknown
Accepts Medicare: No
Participates In eRX: No
Participates In PQRS: No
Participates In EHR: No
License #: 5715
Request Appointment Information
Awards & Recognitions
Medical Malpractice Cases
Medical Board Sanctions
Comparative Proteomic Analysis of Brassica napus in Response to Drought Stress. - Journal of proteome research
Drought is one of the most widespread stresses leading to retardation of plant growth and development. We examined proteome changes of an important oil seed crop, canola (Brassica napus L.), under drought stress over a 14-day period. Using iTRAQ LC-MS/MS, we identified 1976 proteins expressed during drought stress. Among them, 417 proteins showed significant changes in abundance, and 136, 244, 286, and 213 proteins were differentially expressed in the third, seventh, 10th, and 14th day of stress, respectively. Functional analysis indicated that the number of proteins associated with metabolism, protein folding and degradation, and signaling decreased, while those related to energy (photosynthesis), protein synthesis, and stress and defense increased in response to drought stress. The seventh and 10th-day profiles were similar to each other but with more post-translational modifications (PTMs) at day 10. Interestingly, 181 proteins underwent PTMs; 49 of them were differentially changed in drought-stressed plants, and 33 were observed at the 10th day. Comparison of protein expression changes with those of gene transcription showed a positive correlation in B. napus, although different patterns between transcripts and proteins were observed at each time point. Under drought stress, most protein abundance changes may be attributed to gene transcription, and PTMs clearly contribute to protein diversity and functions.
Role of type I interferon signaling in human metapneumovirus pathogenesis and control of viral replication. - Journal of virology
Type I IFN signaling, which is initiated through activation of the alpha interferon receptor (IFNAR), regulates the expression of proteins that are crucial contributors to immune responses. Paramyxoviruses, including human metapneumovirus (HMPV), have evolved mechanisms to inhibit IFNAR signaling, but the specific contribution of IFNAR signaling to the control of HMPV replication, pathogenesis, and adaptive immunity is unknown. We used IFNAR-deficient (IFNAR(-/-)) mice to assess the effect of IFNAR signaling on HMPV replication and the CD8(+) T cell response. HMPV-infected IFNAR(-/-) mice had a higher peak of early viral replication but cleared the virus with kinetics similar to those of wild-type (WT) mice. However, IFNAR(-/-) mice infected with HMPV displayed less airway dysfunction and lung inflammation. CD8(+) T cells of IFNAR(-/-) mice after HMPV infection expressed levels of the inhibitory receptor programmed death 1 (PD-1) similar to those of WT mice. However, despite lower expression of inhibitory programmed death ligand 1 (PD-L1), HMPV-specific CD8(+) T cells of IFNAR(-/-) mice were more functionally impaired than those of WT mice and upregulated the inhibitory receptor Tim-3. Analysis of the antigen-presenting cell subsets in the lungs revealed that the expansion of PD-L1(low) dendritic cells (DCs), but not PD-L1(high) alveolar macrophages, was dependent on IFNAR signaling. Collectively, our results indicate a role for IFNAR signaling in the early control of HMPV replication, disease progression, and the development of an optimal adaptive immune response. Moreover, our findings suggest an IFNAR-independent mechanism of lung CD8(+) T cell impairment.Human metapneumovirus (HMPV) is a leading cause of acute respiratory illness. CD8(+) T cells are critical for clearing viral infection, yet recent evidence shows that HMPV and other respiratory viruses induce CD8(+) T cell impairment via PD-1-PD-L1 signaling. We sought to understand the role of type I interferon (IFN) in the innate and adaptive immune responses to HMPV by using a mouse model lacking IFN signaling. Although HMPV titers were higher in the absence of type I IFN, virus was nonetheless cleared and mice were less ill, indicating that type I IFN is not required to resolve HMPV infection but contributes to pathogenesis. Further, despite lower levels of the inhibitory ligand PD-L1 in mice lacking type I IFN, CD8(+) T cells were more impaired in these mice than in WT mice. Our data suggest that specific antigen-presenting cell subsets and the inhibitory receptor Tim-3 may contribute to CD8(+) T cell impairment.Copyright Â© 2015, American Society for Microbiology. All Rights Reserved.
Programmed death-1 impairs secondary effector lung CD8âº T cells during respiratory virus reinfection. - Journal of immunology (Baltimore, Md. : 1950)
Reinfections with respiratory viruses are common and cause significant clinical illness, yet precise mechanisms governing this susceptibility are ill defined. Lung Ag-specific CD8(+) T cells (T(CD8)) are impaired during acute viral lower respiratory infection by the inhibitory receptor programmed death-1 (PD-1). To determine whether PD-1 contributes to recurrent infection, we first established a model of reinfection by challenging B cell-deficient mice with human metapneumovirus (HMPV) several weeks after primary infection, and found that HMPV replicated to high titers in the lungs. A robust secondary effector lung TCD8 response was generated during reinfection, but these cells were more impaired and more highly expressed the inhibitory receptors PD-1, LAG-3, and 2B4 than primary T(CD8). In vitro blockade demonstrated that PD-1 was the dominant inhibitory receptor early after reinfection. In vivo therapeutic PD-1 blockade during HMPV reinfection restored lung T(CD8) effector functions (i.e., degranulation and cytokine production) and enhanced viral clearance. PD-1 also limited the protective efficacy of HMPV epitope-specific peptide vaccination and impaired lung T(CD8) during heterotypic influenza virus challenge infection. Our results indicate that PD-1 signaling may contribute to respiratory virus reinfection and evasion of vaccine-elicited immune responses. These results have important implications for the design of effective vaccines against respiratory viruses.Copyright Â© 2014 by The American Association of Immunologists, Inc.
Surgical treatment of symptomatic superior labrum anterior-posterior tears in patients older than 40 years: a systematic review. - The American journal of sports medicine
Successful arthroscopic repair of symptomatic superior labral tears in young athletes has been well documented. Superior labral repair in patients older than 40 years is controversial, with concerns for residual postoperative pain, stiffness, and higher rates of revision surgery.To analyze the published data on the surgical treatment of superior labral injuries in patients aged â‰¥40 years, including those with concomitant injuries to the rotator cuff.Systematic review.A systematic review of the literature was performed using the Preferred Reporting Items of Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The MEDLINE database via PubMed and the Cochrane Database of Systematic Reviews were searched for articles related to superior labrum anterior-posterior (SLAP) tears. Studies were included if they met the following criteria: the study contained at least 1 group of patients who had undergone arthroscopic repair of a type II or IV SLAP lesion with a minimum 2-year follow-up, objective and/or functional scoring systems were used to evaluate postoperative outcomes, and the mean patient age was â‰¥40 years for at least 1 treatment arm or subgroup analysis. Studies were excluded if the article was a review or if the article included data for SLAP type I, III, or V to X tears or Bankart lesions.While several authors reported equivalent outcomes of SLAP repair in patients both older than 40 years and younger than 40 years, others demonstrated significantly higher failure rates in the older cohort. Decreased patient satisfaction and increasing complications, including postoperative stiffness and reoperations, occur at higher rates as the patient age increases. The literature demonstrates that biceps tenotomy and tenodesis are reliable alternatives to SLAP repair and that biceps tenotomy is a viable revision procedure for failed SLAP repair. With concomitant rotator cuff tears, the evidence favors debridement or biceps tenotomy over SLAP repair.While studies show that good outcomes can be obtained with SLAP repair in an older cohort of patients, age older than 40 years and workers' compensation status are independent risk factors for increased surgical complications. The cumulative evidence supports labral debridement or biceps tenotomy over labral repair when an associated rotator cuff injury is present.Â© 2014 The Author(s).
Human metapneumovirus virus-like particles induce protective B and T cell responses in a mouse model. - Journal of virology
Human metapneumovirus (HMPV) is a leading cause of respiratory disease in infants, children, and the elderly worldwide, yet no licensed vaccines exist. Live-attenuated vaccines present safety challenges, and protein subunit vaccines induce primarily antibody responses. Virus-like particles (VLPs) are an attractive alternative vaccine approach because of reduced safety concerns compared with live vaccines. We generated HMPV VLPs by expressing viral proteins in suspension-adapted human embryonic kidney epithelial (293-F) cells and found that the viral matrix (M) and fusion (F) proteins were sufficient to form VLPs. We previously reported that the VLPs resemble virus morphology and incorporate fusion-competent F protein (R. G. Cox, S. B. Livesay, M. Johnson, M. D. Ohi, and J. V. Williams, J. Virol. 86:12148-12160, 2012), which we hypothesized would elicit F-specific antibody and T cell responses. In this study, we tested whether VLP immunization could induce protective immunity to HMPV by using a mouse model. C57BL/6 mice were injected twice intraperitoneally with VLPs alone or with adjuvant and subsequently challenged with HMPV. Mice were euthanized 5 days postinfection, and virus titers, levels of neutralizing antibodies, and numbers of CD3(+) T cells were quantified. Mice immunized with VLPs mounted an F-specific antibody response and generated CD8(+) T cells recognizing an F protein-derived epitope. VLP immunization induced a neutralizing-antibody response that was enhanced by the addition of either TiterMax Gold or Î±-galactosylceramide adjuvant, though adjuvant reduced cellular immune responses. Two doses of VLPs conferred complete protection from HMPV replication in the lungs of mice and were not associated with a Th2-skewed cytokine response. These results suggest that nonreplicating VLPs are a promising vaccine candidate for HMPV.Human metapneumovirus (HMPV) is a leading cause of acute respiratory infection in infants, children, and the elderly worldwide, yet no licensed vaccines exist. Live-attenuated vaccines present safety challenges, and protein subunit vaccines induce primarily antibody responses. Virus-like particles (VLPs) are an attractive alternative vaccine approach. We generated HMPV VLPs by expressing the viral matrix (M) and fusion (F) proteins in mammalian cells. We found that mice immunized with VLPs mounted an F-specific antibody response and generated CD8(+) T cells recognizing an F protein-derived epitope. VLP immunization induced a neutralizing-antibody response that was enhanced by the addition of either TiterMax Gold or Î±-galactosylceramide adjuvant. Two doses of VLPs conferred complete protection against HMPV replication in the lungs of mice and were not associated with a Th2-skewed cytokine response. These results suggest that nonreplicating VLPs are a promising vaccine candidate for HMPV.
Reliability and accuracy of templating humeral and ulnar components for total elbow arthroplasty. - American journal of orthopedics (Belle Mead, N.J.)
We conducted a study to examine intraobserver reliability, interobserver reliability, and accuracy of preoperative templating in approximating humeral and ulnar component sizes in total elbow arthroplasty (TEA). Twenty-two patients underwent cemented TEA with 1 of 2 commonly used implants. Four independent reviewers performed templating in 2 separate sessions spaced a minimum of 2 weeks apart. Reviewers were blinded to patient information and used appropriately magnified templates provided by the implant manufacturer. Preoperative and postoperative films were assessed for humeral and ulnar stem width and length. For both implants combined, there was substantial (Îº > 0.7) intraobserver reliability for humeral width, humeral length, and ulnar length. Interobserver reliability was fair for humeral width (Îº = 0.28), substantial for humeral length (Îº = 0.64), and moderate for both ulnar width (Îº = 0.44) and ulnar length (Îº = 0.49). Preoperative templating accurately predicted exact stem size 72.7% of the time and within 1 size variation 96.9% of the time. Attending surgeons were slightly more accurate than fellows (75.5% vs 71.5%) in predicting stem sizes. Preoperative templating is moderately reliable and largely accurate in planning TEA.
B cell-intrinsic and -extrinsic regulation of antibody responses by PARP14, an intracellular (ADP-ribosyl)transferase. - Journal of immunology (Baltimore, Md. : 1950)
The capacity to achieve sufficient concentrations of Ag-specific Ab of the appropriate isotypes is a critical component of immunity that requires efficient differentiation and interactions of Ag-specific B and Th cells along with dendritic cells. Numerous bacterial toxins catalyze mono(ADP-ribosyl)ation of mammalian proteins to influence cell physiology and adaptive immunity. However, little is known about biological functions of intracellular mammalian mono(ADP-ribosyl)transferases, such as any ability to regulate Ab responses. poly-(ADP-ribose) polymerase 14 (PARP14), an intracellular protein highly expressed in lymphoid cells, binds to STAT6 and encodes a catalytic domain with mammalian mono(ADP-ribosyl)transferase activity. In this article, we show that recall IgA as well as the STAT6-dependent IgE Ab responses are impaired in PARP14-deficient mice. Whereas PARP14 regulation of IgE involved a B cell-intrinsic process, the predominant impact on IgA was B cell extrinsic. Of note, PARP14 deficiency reduced the levels of Th17 cells and CD103âº DCs, which are implicated in IgA regulation. PARP14 enhanced the expression of RORÎ±, Runx1, and Smad3 after T cell activation, and, importantly, its catalytic activity of PARP14 promoted Th17 differentiation. Collectively, the findings show that PARP14 influences the class distribution, affinity repertoire, and recall capacity of Ab responses in mice, as well as provide direct evidence of the requirement for protein mono-ADP-ribosylation in Th cell differentiation.
Direct and indirect effects of elevated atmospheric CO2 on net ecosystem production in a Chesapeake Bay tidal wetland. - Global change biology
The rapid increase in atmospheric CO2 concentrations (Ca ) has resulted in extensive research efforts to understand its impact on terrestrial ecosystems, especially carbon balance. Despite these efforts, there are relatively few data comparing net ecosystem exchange of CO2 between the atmosphere and the biosphere (NEE), under both ambient and elevated Ca . Here we report data on annual sums of CO2 (NEE(net) ) for 19 years on a Chesapeake Bay tidal wetland for Scirpus olneyi (C3 photosynthetic pathway)- and Spartina patens (C4 photosynthetic pathway)-dominated high marsh communities exposed to ambient and elevated Ca (ambient + 340 ppm). Our objectives were to (i) quantify effects of elevated Ca on seasonally integrated CO2 assimilation (NEE(net) = NEE(day) + NEE(night) , kg C m(-2) y(-1) ) for the two communities; and (ii) quantify effects of altered canopy N content on ecosystem photosynthesis and respiration. Across all years, NEE(net) averaged 1.9 kg m(-2) y(-1) in ambient Ca and 2.5 kg m(-2) y(-1) in elevated Ca , for the C3 -dominated community. Similarly, elevated Ca significantly (P < 0.01) increased carbon uptake in the C4 -dominated community, as NEE(net) averaged 1.5 kg m(-2) y(-1) in ambient Ca and 1.7 kg m(-2) y(-1) in elevated Ca . This resulted in an average CO2 stimulation of 32% and 13% of seasonally integrated NEE(net) for the C3 - and C4 -dominated communities, respectively. Increased NEE(day) was correlated with increased efficiencies of light and nitrogen use for net carbon assimilation under elevated Ca , while decreased NEE(night) was associated with lower canopy nitrogen content. These results suggest that rising Ca may increase carbon assimilation in both C3 - and C4 -dominated wetland communities. The challenge remains to identify the fate of the assimilated carbon.Published 2013. This article is a U.S. Government work and is in the public domain in the U.S.A.
Scapula fractures: interobserver reliability of classification and treatment. - Journal of orthopaedic trauma
There is substantial variation in the classification and management of scapula fractures. The first purpose of this study was to analyze the interobserver reliability of the OTA/AO classification and the New International Classification for Scapula Fractures. The second purpose was to assess the proportion of agreement among orthopaedic surgeons on operative or nonoperative treatment.Web-based reliability study.Independent orthopaedic surgeons from several countries were invited to classify scapular fractures in an online survey.One hundred three orthopaedic surgeons evaluated 35 movies of three-dimensional computerized tomography reconstruction of selected scapular fractures, representing a full spectrum of fracture patterns.Fleiss kappa (Îº) was used to assess the reliability of agreement between the surgeons.The overall agreement on the OTA/AO classification was moderate for the types (A, B, and C, Îº = 0.54) with a 71% proportion of rater agreement (PA) and for the 9 groups (A1 to C3, Îº = 0.47) with a 57% PA. For the New International Classification, the agreement about the intraarticular extension of the fracture (Fossa (F), Îº = 0.79) was substantial and the agreement about a fractured body (Body (B), Îº = 0.57) or process was moderate (Process (P), Îº = 0.53); however, PAs were more than 81%. The agreement on the treatment recommendation was moderate (Îº = 0.57) with a 73% PA.The New International Classification was more reliable. Body and process fractures generated more disagreement than intraarticular fractures and need further clear definitions.
RNA interference suppression of lignin biosynthesis increases fermentable sugar yields for biofuel production from field-grown sugarcane. - Plant biotechnology journal
The agronomic performance, cell wall characteristics and enzymatic saccharification efficiency of transgenic sugarcane plants with modified lignin were evaluated under replicated field conditions. Caffeic acid O-methyltransferase (COMT) was stably suppressed by RNAi in the field, resulting in transcript reduction of 80%-91%. Along with COMT suppression, total lignin content was reduced by 6%-12% in different transgenic lines. Suppression of COMT also altered lignin composition by reducing syringyl units and p-coumarate incorporation into lignin. Reduction in total lignin by 6% improved saccharification efficiency by 19%-23% with no significant difference in biomass yield, plant height, stalk diameter, tiller number, total structural carbohydrates or brix value when compared with nontransgenic tissue culture-derived or transgenic control plants. Lignin reduction of 8%-12% compromised biomass yield, but increased saccharification efficiency by 28%-32% compared with control plants. Biomass from transgenic sugarcane lines that have 6%-12% less lignin requires approximately one-third of the hydrolysis time or 3- to 4-fold less enzyme to release an equal or greater amount of fermentable sugar than nontransgenic plants. Reducing the recalcitrance of lignocellulosic biomass to saccharification by modifying lignin biosynthesis is expected to greatly benefit the economic competitiveness of sugarcane as a biofuel feedstock.Â© 2013 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.
Map & Directions
1660 S Albion St Suite 223 Denver, CO 80222
1805 S Bellaire St Suite 585
5290 E Yale Circle Suite 207
1720 S Bellaire St Ste 406