Biomedical subjects

Jeffrey D Lande

Publications and source records attributed to Jeffrey D Lande.

4 recordsLinked to original sources

PubMed2007

Novel insights into lung transplant rejection by microarray analysis.

Gene expression microarrays can estimate the prevalence of mRNA for thousands of genes in a small sample of cells or tissue. Organ transplant researchers are increasingly using microarrays to identify specific patterns of gene expression that predict and characterize acute and chronic rejection, and to improve our understanding of the mechanisms underlying organ allograft dysfunction. We used microarrays to assess gene expression in bronchoalveolar lavage cell samples from lung transplant recipients with and without acute rejection on simultaneous lung biopsies. These studies showed increased expression during acute rejection of genes involved in inflammation, apoptosis, and T-cell activation and proliferation. We also studied gene expression during the evolution of airway obliteration in a murine heterotopic tracheal transplant model of chronic rejection. These studies demonstrated specific patterns of gene expression at defined time points after transplantation in allografts, whereas gene expression in isografts reverted back to that of native tracheas within 2 wk after transplantation. These studies demonstrate the potential power of microarrays to identify biomarkers of acute and chronic lung rejection. The application of new genetic, genomic, and proteomic technologies is in its infancy, and the microarray-based studies described here are clearly only the beginning of their application to lung transplantation. The massive amount of data generated per tissue or cell sample has spawned an outpouring of invention in the bioinformatics field, which is developing methodologies to turn data into meaningful and reproducible clinical and mechanistic inferences.

Animals↗

PubMed2005

Gene expression profiling in murine obliterative airway disease.

Lung and heart-lung transplantation are effective treatments for many diseases unresponsive to other therapy. However, long-term survival of recipients is limited by the development of obliterative bronchiolitis (OB). In this study, microarray analysis of a heterotopic mouse model of obliterative airway disease (OAD) was used to test the hypothesis that the expression and patterns of genes will correlate with specific changes in tracheal tissue developing a response to allotransplantation and the infiltrating cells manifesting these changes. Expression profiles observed were in accordance with the current paradigm of a predictable sequence of events, beginning with airway injury; an innate immune response followed by an adaptive immune response, including both cell-mediated and humoral components; and eventual loss of airway epithelial cells. These observations confirm and expand the list of genes and molecular processes that can be studied as potential surrogate markers or targets for intervention of OB.

Animals↗

PubMed2004

Gene profiling links SCA1 pathophysiology to glutamate signaling in Purkinje cells of transgenic mice.

Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease caused by the expansion of a polyglutamine repeat within the disease protein, ataxin 1. To elucidate cellular pathways involved in SCA1, we used DNA microarrays to determine the pattern of gene expression in SCA1 transgenic mice at two specific times in the disease process; 5 weeks, a timepoint prior to onset of pathology, and 12 weeks, at the midpoint of the disease progression. Taking advantage of the availability of three SCA1 transgenic mouse lines, each expressing a different form of ataxin-1, we utilized a strategy that resulted in the identification of a limited number of genes with an altered pattern of expression specific to the development of disease. By comparing the pattern of gene expression in the SCA1 ataxic B05-ataxin-1[82Q] transgenic mouse line with those seen in two non-ataxic lines, A02-ataxin-1[30Q] and K772T-[82Q], nine genes were identified whose expression was consistently altered in the cerebellum of B05[82Q] mice at 5 and 12 weeks of age. Interestingly, five of the genes in this group form a biological cohort centered on glutamate signaling pathways in Purkinje cells.

Animals↗

PubMed2003

Gene expression profiling of bronchoalveolar lavage cells in acute lung rejection.

Lung transplantation is effective for many diseases that are unresponsive to other therapy. However, long-term survival of recipients is limited by the development of bronchiolitis obliterans syndrome. Acute rejection is a major risk factor for bronchiolitis obliterans syndrome, but noninvasive biomarkers have not been identified. To address this deficiency, gene expression microarrays were performed using bronchoalveolar lavage cells of lung transplant recipients with acute rejection (n = 7) and with no rejection (n = 27). The cell and differential counts were similar. Signal values for genes between groups were compared using t tests. One hundred thirty-five genes were upregulated in the acute-rejection group, including genes involved in acute rejection, immune response genes with an unknown role in rejection, genes not known to have a role in rejection, and genes of unknown function. Two-dimensional hierarchical clustering grouped all acute rejection samples into one cluster and the majority of the no-rejection samples into a second cluster. The acute-rejection samples showed significant changes in gene expression for seven biological pathways. Bronchoalveolar lavage cells are a reliable RNA source for microarray analysis, which is powerful in identifying acute-rejection genes. The individual genes, patterns of gene expression, or biologic pathways identified may represent novel biomarkers for acute rejection.

Acute Disease↗