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Biomedical subjects

Mary K Dahmer

Publications and source records attributed to Mary K Dahmer.

5 recordsLinked to original sources
PubMed2006

Beta2-adrenergic receptor polymorphisms in African American children with status asthmaticus.

BACKGROUND: The beta2-adrenergic receptor plays a central role in the bronchodilator response to beta2-agonists in patients with asthma. Genetic polymorphisms within the gene coding for this receptor influence responsiveness of the receptor. A number of these polymorphisms differ in frequency in the African American and white populations. OBJECTIVE: To determine the frequency of specific beta2-adrenergic receptor polymorphisms in African American children with status asthmaticus and to examine whether a specific genotype is associated with the clinical response to therapy. DESIGN: Cohort of African American children diagnosed with status asthmaticus. SETTING: Tertiary care children's hospital. PATIENTS: A total of 31 African American children with status asthmaticus. INTERVENTION: Blood samples were obtained from children at admission. Genotypes were determined by polymerase chain reaction amplification and restriction enzyme digestion. MAIN OUTCOME MEASURES: The requirement for admission to the pediatric intensive care unit, need for mechanical ventilation, institution of various therapies, and length of stay. RESULTS: The genotypes of the polymorphic sites at amino acid positions 16 and 27 in the beta2-adrenergic receptor were determined. There were no significant differences between the various genotypes in the percentage of children requiring pediatric intensive care unit admission, mechanical ventilation, terbutaline treatment, or length of stay. However, in children heterozygous for Glu at position 27 of the beta2-adrenergic receptor, the percentage of patients requiring aminophylline treatment, in addition to beta2-agonist therapy, was significantly higher than that seen in patients homozygous for Gln at that position (5/10 [50%] vs. 1/21 [5%], respectively; p = .002). CONCLUSIONS: African American children with status asthmaticus who have the Gln/Glu genotype at amino acid position 27 of the beta2-adrenergic receptor may benefit from aminophylline treatment in addition to beta2-agonist therapy.

Adolescent↗
PubMed2005

Caspases-2, -3, and -7 are involved in thapsigargin-induced apoptosis of SH-SY5Y neuroblastoma cells.

Caspase-2 has been reported to play a role in the cell death observed under a number of different conditions; however, it is unclear whether caspase-2 plays a role in cell death triggered by endoplasmic reticulum (ER) stress. The purpose of this study was to determine whether caspase-2 is involved in SH-SY5Y neuroblastoma cell death caused by thapsigargin-induced ER stress. Thapsigargin treatment (1 microM, 16 hr) stimulated the proteolytic processing of caspases-2, -3, and -7, suggesting that these caspases are activated by ER stress. The role of these caspases in thapsigargin-induced cell death was examined by using cell-permeable caspase inhibitors. In the absence of pretreatment with caspase inhibitors, thapsigargin (0.1 microM, 20 hr) reduced the number of viable cells to 53.9% +/- 3.3% of starting-time control. Pretreatment for 90 min with either the pan-caspase inhibitor Z-VAD-FMK or the caspase-2-selective inhibitor Z-VDVAD-FMK inhibited thapsigargin-stimulated cell death, resulting in the number of viable cells being 115.6% +/- 5.3% (P < 0.001) and 69.3% +/- 2.9% (P < 0.01), respectively, of starting-time control. Neither the caspase-3- and -7-selective inhibitor Z-DEVD-FMK nor the caspase-9-selective inhibitor Z-LEHD-FMK significantly affected thapsigargin-stimulated cell death. An anticaspase-12-reactive protein was also identified in SH-SY5Y cells, but thapsigargin had no effect on proteolysis of this protein. These data demonstrate that caspases-2, -3, and -7 are involved in ER stress-mediated death of SH-SY5Y cells.

Analysis of Variance↗
PubMed2005

Genetic polymorphisms in sepsis.

CONTEXT: Wide variability exists in the susceptibility to and outcome from sepsis even within similar intensive care unit populations. Some of this variability in the host may be due to genetic variation in genes coding for components of the innate immune response. OBJECTIVE: To review the evidence for a genetic influence on the susceptibility to and outcome from sepsis. DESIGN: Literature review. PATIENTS: Variety of adult and pediatric patients with various critical illnesses and infections. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Susceptibility to clinical symptoms of sepsis and outcome as measured by severity of disease and mortality. RESULTS: Polymorphisms in genes coding for proteins involved in the recognition of bacterial pathogens (Toll-like receptor 4, CD14, Fc(gamma)RIIa, and mannose-binding lectin) and the response to bacterial pathogens (tumor necrosis factor-alpha, interleukin (IL)-1alpha, IL-1beta, IL-1 receptor agonist, IL-6, IL-10, heat shock proteins, angiotensin I converting enzyme, plasminogen activator inhibitor-1) can influence the amount or function of the protein produced in response to bacterial stimuli. Evidence is discussed suggesting that some of these genetic polymorphisms influence the susceptibility to and outcome from sepsis. CONCLUSION: Host genetic variability in the regulatory and coding regions of genes for components of the innate immune system may influence the susceptibility to and/or outcome from sepsis. The disparate results observed in many studies of polymorphisms in sepsis emphasize the need for future studies to be larger, to include the analysis of multiple polymorphisms, and to be better designed with respect to control populations to identify the degree of influence that genetic variability has on sepsis.

Adult↗
PubMed2004

Association between surfactant protein B + 1580 polymorphism and the risk of respiratory failure in adults with community-acquired pneumonia.

OBJECTIVE: Pulmonary surfactant protein (SP)-B plays a vital role in the formation and function of surfactant in the lung. A genetic polymorphism (SP-B + 1580) is postulated to result in diminished activity of SP-B. The objective was to determine whether the SP-B + 1580 CC genotype is associated with an increased risk of respiratory failure and ARDS in adults with community-acquired pneumonia. DESIGN: Prospective cohort of adults diagnosed with community-acquired pneumonia. SETTING: Hospital system. PATIENTS: We enrolled 402 adults > or = 18 yrs of age with community-acquired pneumonia; 158 were white, 243 were African American, and one was Asian. INTERVENTIONS: Genotypic analysis was performed on DNA isolated from whole blood using polymerase chain reaction amplification and DdeI restriction enzyme digestion. MEASUREMENTS AND MAIN RESULTS: We recorded the requirement for mechanical ventilation, the presence of acute respiratory distress syndrome (ARDS) or septic shock, and mortality. Sixty-three patients required mechanical ventilation, 12 patients developed ARDS, and 35 patients developed septic shock. Genotypic frequencies at the SP-B + 1580 site were T/T 183 of 402 (0.45), T/C 160 of 402 (0.40), and C/C 59 of 402 (0.15). Of the 59 patients who were C/C at the SP-B + 1580 site, 21 (0.356) required mechanical ventilation, compared with 26 of 160 patients (0.163) who were T/C and 16 of 183 (0.087) patients who were T/T (p < .001). ARDS developed in five of 59 (0.085) patients with the C/C genotype, compared with six of 160 (.038) patients with T/C and one of 183 patients with T/T (0.005, p < .009). Septic shock occurred in 12 of 59 (0.203) patients with the C/C genotype, compared with 13 of 160 (0.081) patients with T/C and ten of 183 (0.055) patients with T/T (p < .001). Mortality rate was not different between the three genotypes. CONCLUSION: Carriage of the C allele at the SP-B + 1580 site is associated with ARDS, septic shock, and the need for mechanical ventilation in adults with community-acquired pneumonia.

Adolescent↗