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Biomedical subjects

Mark Schuyler

Publications and source records attributed to Mark Schuyler.

11 recordsLinked to original sources
PubMed2006

Characterization of myeloid and plasmacytoid dendritic cells in human lung.

Dendritic cells (DCs) are bone marrow-derived mononuclear cells that play a central role in the initiation of immune responses. Because human lung DCs have been incompletely characterized, we enumerated and phenotyped mononuclear cell populations from excess lung tissue obtained at surgery. Myeloid DCs (MDCs) were identified as CD1c(+)CD11c(+)CD14(-)HLA-DR(+) cells and comprised approximately 2% of low autofluorescent (LAF) mononuclear cells. Plasmacytoid DCs (PDCs) were characterized as CD123(+)CD11c(-)CD14(-)HLA-DR(+) cells and comprised approximately 1.0% of the LAF mononuclear cells. Cells enriched in MDCs expressed CD86, moderate CD80, and little CD40, but cells enriched in PDCs had little to no expression of these three costimulatory molecules. CD11c(+)CD14(-) lineage-negative (MDC-enriched) LAF cells were isolated and shown to be much more potent in stimulating an alloreaction than CD11c(+)CD14(+) lineage-negative (monocyte-enriched) LAF cells. PDC-enriched cells were more capable of responding to a TLR-7 agonist by secreting IFN-alpha than MDC-enriched cells. MDC-enriched cells were either CD123(+) or CD123(-), but both subsets secreted cytokines and chemokines typical of MDC upon stimulation with a TLR-4 agonist and both subsets failed to secrete IFN-alpha upon stimulation with a TLR-7 agonist. By immunohistochemistry, we identified MDCs throughout different anatomical locations of the lung. However, our method did not allow the localization of PDCs with certainty. In conclusion, in the human lung MDCs were twice as numerous and expressed higher levels of costimulatory molecules than PDCs. Our data suggest that both lung DC subsets exert distinct immune modulatory functions.

Antigens, CD↗
PubMed2005

Emotional responses to APO E genotype disclosure for Alzheimer disease.

The purpose of our study is to assess the emotional responses to disclosing APO E genotype to asymptomatic older adults at increased risk for Alzheimer disease (AD). This is a longitudinal cohort study of volunteer subjects who were aged 50 years or over, asymptomatic for (AD), had a family history of AD, passed a psychological assessment, and participated in pre- and post-test genetic counseling and three follow-up visits over 10 months. We analyzed responses by three emotional constructs: depressed, worried, and relieved. Three hundred and twenty-eight subjects were screened, 76 received their APO E genotype. When emotional responses occurred it was immediate, between baseline and the 1 month follow-up. Emotional reactions did not change significantly past 1 month. Our results suggest that for emotionally stable persons, disclosing results of their APO E genotype, high risk subjects did not report more depression or worry and low risk subjects felt relieved by knowing the results. Future studies should evaluate the risks of disclosure to family members involved in the diagnostic work-up of a relative and include subjects from a broader range of emotional stability and socioeconomic background.

Affect↗
PubMed2005

Effect of electronic charting on the patient-psychiatrist relationship.

The impending implementation of an electronic medical record (EMR) within Behavioral Health facilities at the University of New Mexico (UNM) offers a unique opportunity to study the effects of EMR usage on a psychiatric patient population. A pre-test and post-test design using a satisfaction survey will test for changes to the patient-psychiatrist relationship before and after implementation. To date, 48 subjects have participated in the pre-implementation portion of the study.

Attitude to Computers↗
PubMed2003

Clinical diagnosis of hypersensitivity pneumonitis.

The diagnosis of hypersensitivity pneumonitis (HP) is difficult and often relies on histopathology. Our objective was to identify diagnostic criteria and to develop a clinical prediction rule for this disease. Consecutive patients presenting a condition for which HP was considered in the differential diagnosis underwent a program of simple standardized diagnostic procedures. High-resolution computed tomography scan and bronchoalveolar lavage (BAL) defined the presence or absence of HP. Patients underwent surgical lung biopsy when the computed tomography scan, BAL, and other diagnostic procedures failed to yield a diagnosis. A cohort of 400 patients (116 with HP, 284 control subjects) provided data for the rule derivation. Six significant predictors of HP were identified: (1) exposure to a known offending antigen, (2) positive precipitating antibodies to the offending antigen, (3) recurrent episodes of symptoms, (4) inspiratory crackles on physical examination, (5) symptoms occurring 4 to 8 hours after exposure, (6) and weight loss. The area under the receiver operating characteristic curve was 0.93 (95% confidence interval: 0.90-0.95). The rule retained its accuracy when validated in a separate cohort of 261 patients. The diagnosis of HP can often be made or rejected with confidence, especially in areas of high or low prevalence, respectively, without BAL or biopsy.

Algorithms↗
PubMed2003

Immune response to hepatitis B vaccine in asthmatic children.

Asthma is a disease that demonstrates chronic Th2 lymphocyte-mediated pulmonary inflammation. We hypothesized that cytokines produced by asthmatic lung inflammation bias the immune response to antigens administered systemically toward a Th2 response, as assessed by serum IgE antibody and lymphocyte-secreted IL-4 and IL-5. We also hypothesized that treatment of asthmatic children with local anti-inflammatory agents reduces this cytokine-mediated Th2 influence. We systemically immunized groups of asthmatic children (n=29) who were participating in a long-term, randomized, placebo-controlled clinical trial of inhaled anti-inflammatory therapy (Childhood Asthma Management Program) and nonasthmatic children (n=12) with hepatitis B (Hep B) antigen, and examined their antigen-specific antibody and lymphocyte cytokine secretion profiles. The asthmatic population demonstrated an increased amount of Th2-mediated serum IgE anti-Hep B antibody, as compared to nonasthmatic children; but comparable amounts of IgG1, IgG2, IgG3, IgA, and IgM anti-Hep B antibody and lymphocyte IFNgamma, IL4, and IL5. There was no significant difference of antibody isotype or cytokine production between asthmatic subjects receiving treatment with budesonide or nedocromil, as compared to placebo. In conclusion, there is a subtle bias in responses to systemic immunization in children with asthma, but anti-inflammatory therapy does not affect this bias. The findings support the concept that the Th2 bias may be largely genetic. Importantly, we confirmed that children with asthma, including even those on inhaled corticosteroids, responded to Hep B immunization as well as did nonasthmatic children with the major isotypes of anti-Hep B antibody, suggesting that vaccine protection against hepatitis B is not influenced by inhaled steroid therapy.

Administration, Inhalation↗
PubMed2003

Experimental hypersensitivity pneumonitis: role of MCP-1.

Inhalation of Saccharopolyspora rectivirgula causes "farmer's lung" disease, a classic example of hypersensitivity pneumonitis (HP). Monocyte chemoattractant protein-1 (MCP-1) is increased in the bronchoalveolar lavage fluid of mice challenged with S rectivirgula, and S rectivirgula induces MCP-1 secretion by alveolar macrophages. We tested the hypothesis that MCP-1 and its receptor CC chemokine receptor-2 (CCR2) are essential to the development of experimental HP by treating mice with MCP-1 antibody and using CCR2(-/-) mice. Administration of anti-MCP-1 did not change the response to intratracheally administered S rectivirgula. CCR2(-/-) animals responded in a fashion similar to that of wild-type animals to intratracheally administered.S rectivirgula. To determine the influence of the MCP-1-CCR2 interaction in vitro, we transferred S rectivirgula-cultured spleen cells from S rectivirgula-sensitized mice, to naïve recipients. Later, challenge of the recipients with intratracheal S rectivirgula and examination of both lung histology and bronchoalveolar lavage fluid characteristics were used to determine whether adoptive transfer had occurred. We found that cultured cells from CCR2(-/-) animals were fully capable of adoptive transfer. We conclude that interaction of MCP-1 with CCR2 is not necessary for the development of pulmonary inflammation in response to intratracheally administered S rectivirgula or cells able to adoptively transfer experimental HP.

Adoptive Transfer↗
PubMed2002

Is IL12 necessary in experimental hypersensitivity pneumonitis?

Inhalation of Saccharopolyspora rectivirgula (SR) can cause the disease Farmer's Lung, a classic example of hypersensitivity pneumonitis. Th1, but not Th2, cell lines can adoptively transfer experimental hypersensitivity pneumonitis (EHP). Substantial amounts of IL12 appear in bronchoalveolar lavage fluid (BALF) after a single intratracheal (IT) injection of SR, and SR-induced IL12 secretion by both a macrophage cell line and alveolar macrophages. We tested the hypothesis that IL12 is essential for the development of EHP by addition of anti-IL12 to cultured cells, and adoptive transfer of EHP in IL12p40-/- animals. We transferred SR cultured spleen and lung associated lymph node cells from SR sensitized mice (both IL12p40-/- and wild type), to naïve recipients (both wild type and IL12p40-/-). The addition of anti-IL12 to cultures of sensitized cells could not ablate the ability of these cells to transfer EHP. Cultured cells from IL12p40-/- animals were fully capable of transferring EHP. In contrast, IL12p40-/- recipients of both wild type and IL12p40-/--cultured cells were less able to express EHP (lung histology and BALF characteristics) than wild type mice, and had more eosinophils in both lung tissue and BALF. We conclude that IL12 is not necessary for development of cells able to adoptively transfer EHP, but that it is required for full expression of EHP in recipient animals.

Adoptive Transfer↗
PubMed2002

The APO E4 allele and cognition in New Mexico Hispanic elderly.

OBJECTIVE: To determine if the apolipoprotein E E4 (APO E4) allele is associated with cognitive performance in New Mexico Hispanic elderly. METHOD: We performed a cross-sectional survey of 105 community volunteers, aged 60 years and older, born in New Mexico, with both parents of Hispanic descent. Subjects were excluded for medical conditions that could influence cognitive performance. We also performed a longitudinal analysis on 18 participants who were re-tested over a 3-year interval. The main outcome measures for both the cross-sectional and longitudinal analysis were scores on 5 cognitive tests comparing subjects with the E4 allele to those without the E4 allele. RESULTS: The mean age was 69 years, with a range of 60 to 91. For the cross-sectional analysis, there were no significant differences between the 2 groups on the cognitive tests, although subjects with an E4 allele did not perform as well on color trails A (P=.09). In the longitudinal analysis we found that the variability of cognitive test scores tended to be higher in the E4 group on most cognitive measures. The time needed to complete color trails A (indicating slower performance) was significantly greater (P<.05) in the E4 group. For the total recall portion of the Fuld Object Memory test, the E4 group did not perform as well on follow-up (P=.08). CONCLUSION: We found no significant cross-sectional association between the APO E4 allele and cognitive performance. In our longitudinal analysis, the time needed to complete color trails A was significantly greater in the E4 group, and the E4 group did not perform as well on total recall.

Aged↗