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Biomedical subjects

Philip T Diaz

Publications and source records attributed to Philip T Diaz.

8 recordsLinked to original sources

Two-dimensional gel proteome reference map of blood monocytes.

BACKGROUND: Blood monocytes play a central role in regulating host inflammatory processes through chemotaxis, phagocytosis, and cytokine production. However, the molecular details underlying these diverse functions are not completely understood. Understanding the proteomes of blood monocytes will provide new insights into their biological role in health and diseases. RESULTS: In this study, monocytes were isolated from five healthy donors. Whole monocyte lysates from each donor were then analyzed by 2D gel electrophoresis, and proteins were detected using Sypro Ruby fluorescence and then examined for phosphoproteomes using ProQ phospho-protein fluorescence dye. Between 1525 and 1769 protein spots on each 2D gel were matched, analyzed, and quantified. Abundant protein spots were then subjected to analysis by mass spectrometry. This report describes the protein identities of 231 monocyte protein spots, which represent 164 distinct proteins and their respective isoforms or subunits. Some of these proteins had not been previously characterized at the protein level in monocytes. Among the 231 protein spots, 19 proteins revealed distinct modification by protein phosphorylation. CONCLUSION: The results of this study offer the most detailed monocyte proteomic database to date and provide new perspectives into the study of monocyte biology.

Journal Article↗

Correlation of HIV-1 detection and histology in AIDS-associated emphysema.

HIV-seropositive individuals are at an increased risk for an accelerated form of emphysema. The purpose of this study was to determine the distribution of HIV-1 RNA in lung tissues and correlate this with the histologic findings and expression of matrix metalloproteases (MMPs). Reverse transcriptase (RT) in situ PCR analysis was performed on 11 AIDS lung autopsy specimens which showed varying degrees of emphysematous changes. In each lung, HIV-1 RNA was detected. In areas of histologically normal lung, very rare HIV-1-infected cells were evident. In contrast, many HIV-1-infected cells were noted in areas of emphysema. HIV-1 gag RNA was evident primarily in macrophages; infected pneumocytes were also seen. Similarly, MMP mRNA and protein, primarily MMP-9, localized to the areas of emphysema. Colabeling experiments documented that MMP expression was found primarily in cells that were HIV-1 negative and adjacent to HIV-1-infected macrophages. These results suggest that AIDS-related emphysema may be due, in part, to direct infection by HIV-1 of, primarily, alveolar macrophages, and concomitant up-regulation of MMP expression in the neighboring, noninfected cells.

Acquired Immunodeficiency Syndrome↗

Lung CD4 lymphocytes predict survival in asymptomatic HIV infection.

BACKGROUND: Plasma viral load and blood CD4 counts are accepted indicators of severity of illness in patients with HIV-1. Lung CD4 counts have not been evaluated in asymptomatic HIV-1 patients as indicators of disease severity. OBJECTIVE: To determine if lung lymphocyte counts in asymptomatic subjects with HIV compare with plasma viral loads and blood CD4 counts in predicting survival. DESIGN: Retrospective, cross-sectional analysis. SETTING: Midwestern urban community, December 1996 to August 1998. PARTICIPANTS: HIV-seropositive subjects (n = 95) without AIDS-related pulmonary complications. MEASUREMENTS: Plasma viral load, blood hemoglobin and blood lymphocyte subtypes, lung lymphocyte subtypes from BAL, body mass index, and mortality. RESULTS: Eight of the 95 subjects (8.4%) had died at the 4-year follow-up. Lung CD4 counts were significantly related to mortality by univariable analysis (2.5 x 10(3)/mL vs 0.9 x 10(3)/mL, median values for survivors vs nonsurvivors, respectively, p = 0.010). Modeling using exact methods further showed lung CD4 counts to be a significant predictor of survival after individually adjusting for potential confounders, including plasma viral load and blood CD4 count. CONCLUSIONS: Lung CD4 counts in patients with HIV-1 infection may provide an independent predictor of survival.

Adult↗

Improved neurobehavioral functioning in emphysema patients following lung volume reduction surgery compared with medical therapy.

STUDY OBJECTIVES: The goal of this study was to evaluate the neuropsychological and psychological functioning of emphysema patients following lung volume reduction surgery (LVRS) compared with patients receiving only medical therapy (MT). DESIGN: Patients with moderate-to-severe emphysema who were enrolled in the National Emphysema Treatment Trial at two sites (National Jewish Medical and Research Center and Ohio State University) were given a neuropsychological battery at baseline, 6 to 10 weeks later (following participation in pulmonary rehabilitation), and at 6 months following randomization to either LVRS or MT treatment. SUBJECTS AND MEASUREMENTS: Twenty patients randomized to MT, 19 patients randomized to LVRS, and 39 matched, healthy control subjects completed a battery of tests that measured cognitive functioning, depression, anxiety, and quality of life (QoL). RESULTS: Controlling for practice, patients in the LVRS treatment arm at the 6-month follow-up demonstrated significant improvement compared with MT patients in cognitive tasks involving sequential skills and verbal memory. The LVRS patients also showed significant reductions in depression compared with the MT patients, as well as improved physical and psychosocial QoL. Correlational analysis indicated that improved immediate verbal memory in the LVRS group was related to improved QoL. No associations were found between changes in cognitive function and changes in depression, exercise performance, or pulmonary functioning. CONCLUSION: Patients who received LVRS demonstrated improvement in specific neuropsychological functions, depression, anxiety, and QoL scores compared with patients with continued MT treatment 6 months following randomization. However, mechanisms for these neurobehavioral changes are unclear. Improved verbal memory and sequential skills following LVRS were not directly associated with depression or exercise capacity. Nonetheless, LVRS led to a strong and likely clinically significant improvement in neuropsychological functioning over and above that explained by practice effects or MT. This finding adds to the growing list of clinical benefits of LVRS over MT, and supports additional research into the underlying mechanisms of this therapeutic effect.

Colorado↗

Regional differences in emphysema scores and BAL glutathione levels in HIV-infected individuals.

STUDY OBJECTIVES: Evidence exists that HIV-seropositive individuals may be at increased risk for the development of precocious pulmonary emphysema. HIV infection is also associated with antioxidant deficiency in both the serum and lungs, and it is therefore possible that increased oxidant stress may contribute to parenchymal lung injury occurring in the setting of HIV. We sought to determine the regional distribution of emphysema and regional distribution of glutathione (GSH) concentrations among HIV-seropositive subjects with emphysema. DESIGN: Cross-sectional evaluation of a prospective, longitudinal study. SETTING: University teaching hospital. SUBJECTS/MEASUREMENTS: HIV-seropositive subjects without AIDS-related pulmonary complications participating in a descriptive study of lung biology in HIV-seropositive individuals. Emphysema scoring and evaluation of emphysema lobar distribution was performed among 40 subjects with emphysema. Eleven subjects underwent BAL of the right middle lobe (RML) and right upper lobe (RUL) with measurement of epithelial lining fluid (ELF) GSH in each lobe. RESULTS: We found that the mean emphysema scores were much higher in the upper lobes compared to the rest of the lung. Mean GSH levels were significantly greater in the RUL compared to the RML. The regional differences were present in both smokers and nonsmokers. CONCLUSIONS: We conclude that in the setting of HIV, emphysema is more prominent and lung GSH concentrations are higher in the upper lobes. We hypothesize that the increased GSH may represent a compensatory response to increased oxidant stress in the upper lobes.

Adult↗

Respiratory symptoms among HIV-seropositive individuals.

STUDY OBJECTIVES: Recent evidence suggests that chronic or latent viral infection may be an important predisposing factor in the development of COPD among smokers. As such, understanding if HIV-seropositive smokers are at heightened risk for respiratory symptoms may have relevance with regard to COPD pathogenesis. The current study was done to systematically identify the prevalence of respiratory symptoms among an HIV-seropositive population and to identify associated clinical features. DESIGN AND SETTING: Cross-sectional analysis at an academic medical center. PARTICIPANTS: Three hundred twenty-seven HIV-seropositive individuals without a history of AIDS-related pulmonary complications. Fifty-two HIV-negative individuals with a similar age and smoking history served as a comparison group. MEASUREMENTS: Administration of the American Thoracic Society Division of Lung Diseases respiratory questionnaire, and pulmonary function studies. RESULTS: Respiratory symptoms including dyspnea (41.6% vs 7.7%), cough (40% vs 25%), and phlegm production (41.9% vs 23.1%) were extremely common in the HIV-group and significantly more common than in the HIV-negative group. Current or prior cigarette smoking was the most important predictor of respiratory symptoms among the HIV-seropositive group. The use of the antiretroviral agent lamivudine was associated with a significant reduction in dyspnea. CONCLUSION: HIV-seropositive individuals are at increased risk for the development of respiratory symptoms even prior to the onset of AIDS-related pulmonary complications. This may reflect a heightened susceptibility to the effects of cigarette smoking.

Adult↗

Feasibility of distractive auditory stimuli on upper extremity training in persons with chronic obstructive pulmonary disease.

OBJECTIVE: To determine the feasibility of distractive auditory stimuli (DAS) used during an upper extremity training (UET) program on perceived dyspnea, functional performance, and health-related quality of life. In addition, to determine the appropriate music tempo used during the UET. DESIGN: Experimental, randomized, 3-group design with testing at baseline and 4 weeks. SETTING: Outpatient. PATIENTS: Thirty patients (13 male and 17 female) with moderate to severe chronic obstructive pulmonary disease (FEV1 41.27% +/- 18% predicted). INTERVENTION: Moderate DAS group (n = 10) and slow DAS group (n = 10) subjects were instructed to perform UET for up to 15 minutes 3 to 5 times a week using DAS (walkman, audiocassettes). The control group (n = 10) received the same instructions, but no DAS. MEASURES AND RESULTS: Primary outcome measures were perceived dyspnea, functional performance using the 6-minute peg and ring board (6MRPB) count and health-related quality of life. In addition, all subjects recorded the time of UET performance using self-report (daily logs). A significant increase was seen in 6MRPB count (P = .002) between groups. Moderate DAS subjects increased 6MPRB count 46 +/- 21 rings and slow DAS subjects increased 46 +/- 20 rings from baseline to 4 weeks whereas control subjects increased only 5 +/- 4 rings. No significant differences were noted for the remaining variables. CONCLUSION: Subjects who used DAS (music) while performing UET improved functional performance whereas controls failed to continue improvement. The DAS is a feasible adjunct to UET that may have the potential to augment the effectiveness of pulmonary rehabilitation training.

Acoustic Stimulation↗