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Biomedical subjects

Peter J Mogayzel

Publications and source records attributed to Peter J Mogayzel.

7 recordsLinked to original sources
PubMed2003

Cyclosporin and tacrolimus do not potentiate oxidative damage in pulmonary epithelial cells.

Oxidative stress can lead to cellular injury and apoptosis within the pulmonary allograft. We investigated the effects of oxidative damage on the growth and survival of cultured human pulmonary epithelial cells treated with hydrogen peroxide (H(2)O(2)) in the presence and absence of cyclosporin A (CsA) and tacrolimus. Treatment of A549 cells with 1 mmol/l H(2)O(2) for 48 h led to a 39% decrease in cell growth. Treatment with 500 ng/ml CsA for 48 h reduced cell survival by 68%, and treatment with 30 ng/ml tacrolimus reduced cell survival by 32%. The addition of CsA or tacrolimus to cells grown in H(2)O(2) did not further diminish cell survival. These studies demonstrated that H(2)O(2), CsA, and tacrolimus treatments decrease survival of pulmonary epithelial cells. However, CsA and tacrolimus do not further potentiate H(2)O(2)-induced toxicity.

Adenocarcinoma↗
PubMed2003

Modulation of Sp1 and Sp3 in lung epithelial cells regulates ClC-2 chloride channel expression.

ClC-2 is a pH- and voltage-activated chloride channel, which is highly expressed in fetal airways and downregulated at birth. The ClC-2 promoter contains consensus binding sites within the first 237 bp, which bind transcription factors Sp1 and Sp3(1). This study directly links Sp1 and Sp3 with ClC-2 protein expression by demonstrating: (i) induction of ClC-2 protein by transient overexpression of each transcription factor in adult rat Type II cells, which have low levels of ClC-2; and (ii) reduction of ClC-2 expression by incubation with a competitive inhibitor of Sp1 and Sp3 in fetal rat Type II cells, which have high levels of endogenous ClC-2. Endogenous fetal lung Sp1 is differentially expressed as two major species of 105 kD and 95 kD. Although low-level expression of Sp1 in adult cells is almost exclusively the 105-kD species, overexpression of Sp1 results in increased expression of the 95-kD band. These experiments suggest that the mechanism for postnatal reduction of ClC-2 expression in lung epithelia is based on decreased interaction of Sp1 and Sp3 with the ClC-2 promoter.

Aging↗
PubMed2003

Effect of adeno-associated virus-specific immunoglobulin G in human amniotic fluid on gene transfer.

Intra-amniotic administration of adeno-associated virus (AAV) vector may be an effective way to deliver gene therapy for treatment of congenital pulmonary and intestinal disorders. In an effort to understand potential barriers to intra-amniotic gene therapy better, we determined whether human amniotic fluid (AF) could act as an inhibitor of AAV2-mediated gene transfer. AF samples were obtained from 21 different human pregnancies during routine amniocentesis at 16-20 weeks of gestation. An immortalized fetal human tracheal epithelial cell line (FHTE) was infected with AAV2 containing a luciferase reporter gene driven by the SV40 promoter in the presence and absence of each AF sample. Inhibition of transgene expression was observed in 8 (38%) of the AF samples (inhibitory AF) and resulted in luciferase levels of only 1.4% +/- 0.6% of those obtained with infection in normal media. Infections in 13 samples (62%) resulted in transgene expression comparable or in excess of infection in media alone (noninhibitory AF). Removal of immunoglobulin G (IgG) from inhibitory AF samples with Protein A returned luciferase expression to control levels (119% +/- 37% of control), suggesting the possible presence of inhibiting antibody. Eleven of the AF samples were evaluated by enzyme-linked immunosorbent assay (ELISA) for specific anti-AAV antibodies. All noninhibitory AF samples were negative (titers of < 1:20; n = 3), and 6 of the 8 inhibitory samples contained specific anti-AAV antibodies at titers ranging from 1:40 to 1:160. These studies demonstrate that AF from some individuals contains AAV-specific IgG that can inhibit gene transfer.

Amniotic Fluid↗
PubMed2003

Extracorporeal photopheresis in the treatment of persistent rejection in a pediatric lung transplant recipient.

Lung transplantation is an accepted therapy for children with end-stage lung disease. One-year lung transplant survival rates of 86% have been reported by the United Network for Organ Sharing. Allograft rejection is a common cause of death following transplantation. Extracorporeal photopheresis is a novel therapy used to treat solid-organ rejection; this therapy involves separating the leukocyte-rich fraction from whole blood, treating with psoralen and ultraviolet light A exposure. The objective of therapy is to reverse progressive and persistent rejection. Working collaboratively with an institution that offers extracorporeal photopheresis may provide an alternative or additional therapy in the management of ongoing rejection following solid-organ transplantation.

Acute Disease↗
PubMed2002

cis-Acting elements within CFTR 5'-flanking DNA are not sufficient to decrease gene expression in response to phorbol ester.

The cystic fibrosis transmembrane conductance regulator gene (CFTR) is regulated in a tissue-specific and developmental fashion. Although it has been known for some time that phorbol esters decrease CFTR expression in cell lines that have high CFTR mRNA levels, the cis-acting elements that control this down-regulation remain ill-defined. The role of cis-acting elements within the CFTR minimal promoter in modulating responses to phorbol 12-myristate 13-acetate (PMA) and forskolin was assessed using luciferase reporter gene (luc)-containing plasmids transfected into Calu-3 and HT-29 cells. PMA treatment had no effect on luciferase activity in Calu-3 cells transiently transfected with plasmids containing luc driven by up to 2.3 kb of CFTR 5'-flanking DNA. PMA increased luciferase activity in transfected HT-29 cells. A more extensive region of DNA was evaluated using a yeast artificial chromosome (YAC) containing luc driven by approximately 335 of CFTR 5'-flanking DNA (y5'luc) stably introduced into HT-29 cells. Clonal cell lines containing y5'luc were created and assessed for luciferase activity at baseline and in response to forskolin and PMA. There was a wide range of baseline luciferase activities among the clones (42-1038 units/microg protein) that was not entirely due to the number of luc copies present within the cells. Treatment with both PMA and forskolin led to increased luciferase activity in six randomly selected clonal cell lines. As expected, endogenous CFTR expression increased in response to forskolin and decreased in response to PMA. These studies demonstrate that luc-containing YAC vectors can be used to study CFTR expression in human cells. In addition, these data suggest that important regulatory elements responsible for decreased CFTR expression in response to PMA are not located upstream of CFTR in the approximately 335 kb 5'-flanking sequence included in this YAC construct.

5' Flanking Region↗
PubMed2002

Bilateral diaphragm paralysis following lung transplantation and cardiac surgery in a 17-year-old.

Bilateral diaphragm paralysis is a rare complication of lung transplantation. This report describes the development of chronic respiratory failure due to bilateral diaphragm paralysis following bilateral lung transplantation and closure of a patent foramen ovale. This patient required prolonged mechanical ventilation post-operatively; however, he eventually had adequate recovery of diaphragm function to wean from mechanical ventilation.

Adolescent↗