PubMed Health⌕ Search

Biomedical subjects

Marshall I Hertz

Publications and source records attributed to Marshall I Hertz.

At least 19 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↗
PubMed2006

Analysis of chronic lung transplant rejection by MALDI-TOF profiles of bronchoalveolar lavage fluid.

While lung transplant is an effective therapy for advanced lung disease, chronic allograph rejection remains a primary basis for lower survival rates than those for other solid organ transplants. This study used carefully controlled Zip-Tip extraction of bronchoalveolar lavage fluid (BALF) followed by MALDI-TOF MS to identify biomarkers of chronic lung transplant rejection. Many differences were observed between controls, those who did not develop chronic rejection within 100 months, and patients who had developed chronic rejection, diagnosed as bronchiolitis obliterans syndrome (BOS). Intensity ratios of peaks within the same MALDI-TOF profile were used to quantify the result. One of the best identifiers of BOS was a lowered ratio of clara cell protein (CCP m/z = 15,835) to lysozyme (m/z = 14,700), which gave 94% specificity and 74% sensitivity for diagnosis. Furthermore, low values for CCP/Lysozyme (<0.3) were observed in 66% of samples taken at 1 to 15 months prior to the diagnosis of BOS. Many other components of the profile gave similar or better outcomes for diagnosis but tended to be less valuable for the prediction of future disease. Overall, this study demonstrated the feasibility of this approach for the detection of disease biomarkers.

Biomarkers↗
PubMed2005

Colon and rectal complications after heart and lung transplantation.

BACKGROUND: Gastrointestinal complications of solid organ transplantation have been well described, but little attention has been paid to colorectal disorders in particular. The purpose of this study was to identify the incidence and severity of colorectal complications among a large cohort of heart and lung transplant recipients. STUDY DESIGN: We reviewed the medical records of heart, lung, and heart-lung transplant recipients at a single institution between 1978 and 2004. Complications were identified based on need for consultation, endoscopy, or operation by a colorectal surgeon after transplantation. RESULTS: Of 1,012 patients who received transplantations (530 heart, 435 lung, 47 heart-lung), 56 patients (6%) required evaluation for 84 colorectal problems. Incidence of complications was 7% in lung transplant recipients, 6% in heart-lung transplant recipients, and 4% in heart transplant recipients. Forty-four events (52%) were considered major (diverticulitis, perforation, malignancy, and other) and 40 (48%) were minor (polyps, pseudo-obstruction treated medically or endoscopically, benign anorectal disease, and other). Twenty-three (27%) required colectomy and 9 (10%) necessitated anal operation. Thirty-six (43%) required less-invasive interventions (endoscopy, minor anorectal procedures, and other). Eighteen (21%) were treated with medical therapy alone. Six patients died from colorectal disease (7%). CONCLUSIONS: Colorectal complications are a considerable source of morbidity and mortality after heart and lung transplantation. These complications occur more frequently in patients who undergo lung and heart-lung transplantation as compared with heart transplantation alone.

Adult↗
PubMed2005

Proteomic identification of human neutrophil alpha-defensins in chronic lung allograft rejection.

Chronic allograft rejection remains a leading cause of morbidity and mortality in lung transplant recipients. Currently, diagnosis is based on lung biopsies or the presence of bronchiolitis obliterans syndrome (BOS). To identify a biomarker of rejection we performed a proteome survey of archived bronchoalveolar lavage fluid (BALF) acquired from lung transplant recipients between 1993 and 1996 using mass spectrometry (MS). A total of 126 BALF samples from 57 individuals were tested. Initial MS assessment revealed numerous differences in a majority of individuals who experienced BOS, but three unusually intense peaks at m/z = 3373, 3444, and 3488. These were identified as human neutrophil peptides 1-3 (HNP). Quantification by enzyme-linked immunoabsorbent assay showed an elevated HNP level (>0.3 ng/microg protein) in 89% of patients who developed BOS2-3 within 15 months, reaching as high as 6% of the total BALF protein. In control patients, 35% demonstrated a slightly elevated HNP level that declined in all who had subsequent BALF available for testing. HNP levels did not correlate with episodes of acute rejection, cytomegalovirus or fungal infection. In conclusion, elevated HNP levels are associated with the onset of BOS and can predate the clinical onset of disease up to 15 months.

Bronchiolitis Obliterans↗
PubMed2005

Allograft rejection after lung transplantation.

Lung transplantation has become an accepted therapy for selected patients with advanced lung disease. One of the main limitations to successful lung transplantation is rejection of the transplanted organ. This article discusses the clinical presentation, treatment, and prevention of hyperacute, acute, and chronic rejection in the lung transplant recipient.

Graft Rejection↗
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↗
PubMed2005

Incomplete event documentation in medical records of lung transplant recipients.

CONTEXT: The medical record is frequently used in clinical studies as a source of information on illness events experienced by patients; however, it may be incomplete. OBJECTIVE: To estimate the extent of incompletely documented acute bronchopulmonary events in a transplant clinic medical record at a single university medical center, using home monitoring data. DESIGN, SETTING, AND SUBJECTS: Trends in daily home monitoring data were compared to contemporaneous medical record documentation at 150 different times in 30 lung transplant recipients over 45 subject-years. OUTCOME MEASURE: Proportion of acute bronchopulmonary illness events documented in clinic medical record. RESULTS: By using home monitoring data in a new way, we found that 40% of events actually suffered by lung recipients could not be ascertained to have occurred from the clinic medical record alone. All missed encounters occurred away from the transplant clinic, and involved hospitalizations and telephone prescriptions. CONCLUSIONS: Using the clinic medical record alone to identify acute bronchopulmonary events in lung transplant recipients may result in missing 40% of events. This has important ramifications for studies relying on the medical record for acute event ascertainment in lung transplantation and possibly other chronic diseases.

Academic Medical Centers↗
PubMed2004

Indirect minor histocompatibility antigen presentation by allograft recipient cells in the draining lymph node leads to the activation and clonal expansion of CD4+ T cells that cause obliterative airways disease.

Ag recognition by OVA-reactive OT-II (I-Ab restricted) and DO11.10 (I-Ad restricted) TCR-Tg CD4+ T cells after heterotopic transplantation of OVA transgene-expressing tracheal grafts was examined as a model of minor histocompatibility Ag (mHAg)-induced chronic allograft rejection. In response to airway allotransplantation with grafts expressing the OVA transgene, these TCR-Tg CD4+ T cells expressed the activation markers CD69 and CD44, demonstrated evidence of blastogenesis, underwent multiple rounds of cell division leading to their clonal expansion in the draining lymph node, and proceeded to differentiate to a effector/memory T cell phenotype based on a reduction in the expression of CD45RB. These mHAg-specific TCR-Tg CD4+ T cells responded equally well to fully MHC-mismatched tracheas and to class II-deficient allografts, demonstrating that donor mHAg recognition by recipient CD4+ T cells does not rely on Ag presentation by donor-derived APC. The activation of mHAg-specific TCR-Tg CD4+ T cells after their adoptive transfer into recipient mice given MHC-matched, but mHAg-disparate, airway allografts was associated with their movement into the allograft and the near uniform destruction of the transplanted airway tissue secondary to the development of obliterative airways disease. These results demonstrate that an activation of mHAg-reactive CD4+ T cells in the draining lymph node by recipient APC that indirectly express graft mHAg-derived peptide/class II MHC complexes precedes responder T cell proliferation and differentiation, and leads to the eventual migration of these alloreactive T cells to the transplanted airway tissue and the promotion of chronic graft rejection.

Animals↗