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Sean M Studer

Publications and source records attributed to Sean M Studer.

11 recordsLinked to original sources
PubMed2007

Towards systems biology of human pulmonary fibrosis.

The integrated effect of multiple pathways, molecules, genetic polymorphisms, environmental stimuli, and possible infection determines the lung phenotype in idiopathic pulmonary fibrosis (IPF), a chronic progressive and often lethal lung disease. Systems biology approaches aim to provide a systemwide view of biological process using computational tools and high-throughput technologies. Although much of the analysis of genome-level transcriptional high-resolution profiles of IPF was reductionist, usually focusing on a single factor in the disease process, there are some studies that implement systems approaches. We discuss these analyses and provide examples of the global analysis of IPF, hypersensitivity pneumonitis, and nonspecific interstitial pneumonia. Detailed quantitative phenotyping and correlation with microarray results as well as high-throughput genotyping should provide us with the datasets to implement systems biology approaches in fibrosis research. Interdisciplinary teams and training of junior investigators in the vocabulary of systems biology should allow us to use these datasets integratively and generate a global model of human pulmonary fibrosis.

Animals↗
PubMed2006

Unfolding of mRNA secondary structure by the bacterial translation initiation complex.

Translation initiation is a key step for regulating the level of numerous proteins within the cell. In bacteria, the 30S initiation complex directly binds to the translation initiation region (TIR) of the mRNA. How the ribosomal 30S subunit assembles on highly structured TIR is not known. Using fluorescence-based experiments, we assayed 12 different mRNAs that form secondary structures with various stabilities and contain Shine-Dalgarno (SD) sequences of different strengths. A strong correlation was observed between the stability of the mRNA structure and the association and dissociation rate constants. Interestingly, in the presence of initiation factors and initiator tRNA, the association kinetics of structured mRNAs showed two distinct phases. The second phase was found to be important for unfolding structured mRNAs to form a stable 30S initiation complex. We show that unfolding of structured mRNAs requires a SD sequence, the start codon, fMet-tRNA(fMet), and the GTP bound form of initiation factor 2 bound to the 30S subunit.

Codon, Initiator↗
PubMed2006

Cadaveric donor selection and management.

While there is little doubt that proper donor selection is extremely important to achieve good outcomes from transplantation, there are only limited data regarding the current criteria utilized to select the "ideal donor". Importantly, there are not enough donor lungs available for all of those in need. Until an adequate supply of donor organs exists, lives will be lost on the transplant waiting list. While efforts have been made to increase donor awareness, additional transplants can be realized by improving donor utilization. This can be achieved by active participation of transplant teams in donor management and by utilizing "extended criteria" organs. Further studies are needed to assess the impact of using "extended criteria" donors, as this practice could result in increased posttransplant morbidity and mortality. This article summarizes the approach to identification of potential lung donors, optimal donor management, and the clinical importance of various donor factors upon recipient outcomes.

Cadaver↗
PubMed2004

Cadaveric donor selection and management.

The current availability of lung donors is far exceeded by the number of potential transplant recipients who are waiting for an organ. This disparity results in significant morbidity and mortality for those on the waiting list. Although it is desirable to increase overall consent rates for organ donation, doing so requires an intervention to affect societal response. In contrast, increased procurement of organs from marginal donors and improved donor management may be realized through increased study and practice changes within the transplant community. Transplantation of organs from marginal or extended-criteria donors may result in some increase in complications or mortality, but this possibility must be weighed against the morbidity and risk of death risk faced by individuals on the waiting list. The effects of this trade-off are currently being studied in kidney transplantation, and perhaps in the near future lung transplantation may benefit from a similar analysis. Until that time, the limited data regarding criteria for donor acceptability must be incorporated into practice to maximize the overall benefits of lung transplantation.

Adult↗
PubMed2004

The course of neurofibromatosis type 1 on immunosuppression after lung transplantation: report of 2 cases.

We describe 2 patients with neurofibromatosis type 1 (NF1) who underwent lung transplantation. Case 1 reports a patient with NF1 with no complications 5 years after bilateral lung transplantation. Case 2 details a patient with NF1 diagnosed with both post-transplant lymphoproliferative disorder (PTLD) and massive intra-abdominal sarcoma consistent with a malignant nerve sheath tumor 9 months after lung transplantation. There was no clinical evidence of sarcoma preceding or immediately following lung transplant as demonstrated by a normal abdominal sonogram 3 months post-transplantation. Although an increased risk for cancer has been documented in NF1, the rapid malignant degeneration of a neurofibroma following transplantation raises concern about immunosuppression and transplantation candidacy among individuals with NF1.

Abdominal Neoplasms↗
PubMed2003

Rapid kinetic analysis of EF-G-dependent mRNA translocation in the ribosome.

Precise and coordinated movement of the tRNA-mRNA complex within the ribosome is a fundamental step during protein biosynthesis. The molecular mechanism for this process is still poorly understood. Here we describe a new sensitive method for monitoring elongation factor G-dependent translocation of the mRNA in the ribosome. In this method, the fluorescent probe pyrene is covalently attached to the 3' end of a short mRNA sequence at position +9. Translocation of the mRNA by one codon results in a significant decrease in the fluorescence emission of pyrene and can be used to directly monitor mRNA movement using rapid kinetic methods. Importantly, this method offers the flexibility of using any tRNA or tRNA analog in order to elucidate the molecular mechanism of translocation. Our results show that the mRNA is translocated at the same rate as the tRNAs, which is consistent with the view that the movement of the tRNAs and the mRNA are coupled in the ribosome. Furthermore, an anticodon stem-loop analog of tRNA is translocated from the ribosomal A site at a rate constant that is 350-fold lower than peptidyl tRNA, indicating that the D stem, T stem and acceptor stem of A site tRNA contribute significantly to the rate of translocation.

DNA Primers↗
PubMed2002

Mediastinal abscess due to passage of a broncholith.

We report a case of a 32-year-old woman who, after passage of broncholiths, developed a mediastinal abscess that required surgical drainage for treatment. Previously reported infectious complications resulting from broncholiths include obstructive pneumonitis and recurrent aspiration pneumonitis secondary to bronchoesophageal fistulas. Because radiographic evidence of abnormal calcification in the chest is common, but rarely is associated with broncholithiasis, the patient's history of lithoptysis was crucial to determining the underlying etiology of her abscess.

Adult↗