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Biomedical subjects

Michael Porter

Publications and source records attributed to Michael Porter.

5 recordsLinked to original sources

Ambient particulate matter directs nonclassic dendritic cell activation and a mixed TH1/TH2-like cytokine response by naive CD4+ T cells.

BACKGROUND: Dendritic cells (DCs) translate environmental cues into T-cell activating signals, and are centrally involved in allergic airway inflammation. Ambient particulate matter (APM) is ubiquitous and associated with allergic diseases, but it is unknown whether APM directly activates DCs. OBJECTIVE: To study comprehensively the effects of APM on myeloid DC phenotype and function. METHODS: Development of DC was modeled using human CD34(+) progenitor cells. APM was collected from ambient outdoor air in Baltimore city. We studied the effects of APM on DC activation in vitro, compared with LPS. RESULTS: Ambient particulate matter enhanced DC expression of costimulatory receptors but suppressed the expression of both the endocytosis receptor CD206 and uptake of fluorescein isothiocyanate-conjugated dextran. The expression of the Toll-like pattern-recognition receptors Toll-like receptor 2 and Toll-like receptor 4 was also blunted. APM-exposed DCs secreted less IL-12 and IL-6 but exhibited increased secretion of IL-18 and IL-10 compared with LPS stimulation. A T(H)2-like pattern of cytokine production was seen in cocultures of APM-stimulated DCs and alloreactive naive CD4(+) T cells where the IL-13 to IFN-gamma ratio was reversed. This contrasted with the T(H)1 polarizing effects of LPS on DCs. CONCLUSION: We report for the first time that APM-exposed DCs direct a complex T(H)1/T(H)2-like pattern of T-cell activation by mechanisms that involve nonclassic activation of DCs. CLINICAL IMPLICATIONS: Inhaled APM can act directly on DCs as a danger signal to direct a proallergic pattern of innate immune activation.

Antigen Presentation↗

Urban asthma and the neighbourhood environment in New York City.

Asthma is now the leading cause of emergency room visits, hospitalizations, and missed school days in New York City's poorest neighbourhoods. While most research focuses on the influence of the indoor environment on asthma, this study examines the neighbourhood effects on childhood asthma, such as housing and ambient environmental hazards. Using Geographic Information Science (GI Science) we identify neighbourhoods with elevated concentrations of childhood asthma hospitalizations between 1997 and 2000 in US census tracts, analyze the sociodemographic, housing characteristics, and air pollution burdens from stationary, land use and mobile sources in these areas. The paper reveals the importance of distinguishing the specific and often different combinations of poor housing conditions, outdoor air pollution and noxious land uses that contribute to the high incidence of asthma in impoverished urban neighbourhoods.

Adolescent↗

Robotic versus conventional laparoscopic skill acquisition: implications for training.

BACKGROUND AND PURPOSE: Despite the growing interest in surgical robotics, very little study has been done regarding the acquisition of the skills needed to perform robotic surgery safely. The purpose of this study was to determine whether skills are transferred between conventional laparoscopy and robotically assisted surgery. SUBJECTS AND METHODS: Intracorporeal knot tying was used for evaluating laparoscopic skills for time and error performance. Twenty medical students without any laparoscopic experience were randomized into two groups. Group A initially performed knot tying with conventional laparoscopic instruments, were trained with the daVinci Robotic System, and then performed knot tying with conventional laparoscopy. Group B performed knot tying with robotics, trained with standard laparoscopy, and completed post-training knot tying with robotics. Pretraining and post-training tasks were videotaped and analyzed using a detailed scoring system by one independent referee, who was blinded to the subjects' experience. RESULTS: Pre-training knot tying was faster with robotics (4.4 v 9.9 minutes; P < 0.001). The mean composite scores were 27.4 for group A and 57.4 for group B (P = 0.09), and the error scores were 57.1 and 42.1 (P = 0.29), respectively. Post-training time for knot completion decreased to 6.7 minutes and 3.4 minutes for groups A and B, respectively. Composite scores increased significantly, from 27.4 to 66.1 for group A and 57.4 to 81.8 for group B. Error scores decreased to 32.9 for group A (P = 0.1) and 16.2 in group B (P = 0.02). CONCLUSIONS: There appears to be reciprocal transfer of skills between conventional laparoscopy and robotically assisted surgery. However, this transference is incomplete. Our results suggest that training with either technique or conventional laparoscopy is superior to training with robotics alone.

Clinical Competence↗

Alterations in protein kinase C isoenzyme expression and autophosphorylation during the progression of pressure overload-induced left ventricular hypertrophy.

Cardiomyocytes express several isoenzymes of protein kinase C (PKC), which as a group have been implicated in the induction of left ventricular hypertrophy (LVH) and its transition to heart failure. Individual PKC isoenzymes also require transphosphorylation and autophosphorylation for enzymatic activity. To determine whether PKC isoenzyme expression and autophosphorylation are altered during LVH progression in vivo, suprarenal abdominal aortic coarctation was performed in Sprague-Dawley rats. Quantitative Western blotting was performed on LV tissue 1, 8 and 24 weeks after aortic banding, using antibodies specific for total PKCalpha, PKCdelta and PKCepsilon, and their C-terminal autophosphorylation sites. Aortic banding produced sustained hypertension and gradually developing LVH that progressed to diastolic heart failure over time. PKCepsilon levels and autophosphorylation were not significantly different from sham-operated controls during any stage of LVH progression. PKCalpha expression levels were also unaffected during the induction of LVH, but increased 3.2 +/- 0.8 fold during the transition to heart failure. In addition, there was a high degree of correlation between PKCalpha levels and the degree of LVH in 24 week banded animals. However, autophosphorylated PKCalpha was not increased at any time point. In contrast, PKCdelta autophosphorylation was increased prior to the development of LVH, and also during the transition to heart failure. The increased PKCdelta autophosphorylation in 1 week banded rats was not accompanied by an increase in total PKCdelta, whereas total PKCdelta levels were markedly increased (6.0 +/- 1.7 fold) in 24 week banded animals. Furthermore, both phosphorylated and total PKCdelta levels were highly correlated with the degree of LVH in 24 week banded rats. In summary, we provide indirect evidence to indicate that PKCdelta may be involved in the induction of pressure overload LVH, whereas both PKCdelta and PKCalpha may be involved in the transition to heart failure.

Animals↗