Jeff Edelson - Academia.edu (original) (raw)

Papers by Jeff Edelson

The Lancet, 1987

Pfizer (unrestricted investigator-initiated research grant for pneumococcal pneumonia) and the NI... more Pfizer (unrestricted investigator-initiated research grant for pneumococcal pneumonia) and the NIHR (corticosteroids in pandemic influenza clinical trial).

American Journal of Respiratory and Critical Care Medicine, 2003

Cilomilast (Ariflo), a new oral phosphodiesterase-4 selective inhibitor, improves lung function i... more Cilomilast (Ariflo), a new oral phosphodiesterase-4 selective inhibitor, improves lung function in chronic obstructive pulmonary disease (COPD). We have evaluated its antiinflammatory effects in 59 patients with COPD randomized to receive cilomilast, 15 mg two times a day, or placebo for 12 weeks. Induced sputum differential cell counts were obtained at baseline and at five further visits. Interleukin-8 and neutrophil elastase were measured in sputum supernatant. Bronchial biopsies obtained at baseline and at Week 10 were immunostained and counted for neutrophils, CD8ϩ and CD4ϩ T-lymphocyte subsets, and CD68ϩ macrophages. Cells expressing the genes for interleukin-8 and tumor necrosis factor-␣ were identified by in situ hybridization and quantified. Compared with placebo, analysis of variance (ANOVA) of the change from baseline showed that cilomilast did not alter any sputum endpoint or FEV 1. However, bronchial biopsies demonstrated that cilomilast treatment was associated with reductions in CD8ϩ (p ϭ 0.001; ANOVA) and CD68ϩ cells (p Ͻ 0.05; ANOVA). In addition, by Poisson analysis, comparison of cell counts analyzed as a ratio of active to placebo demonstrated reductions of CD8ϩ (48% p Ͻ 0.01) and CD68ϩ (47% p ϭ 0.001) cells. This is the first demonstration of reduction by any agent of airway tissue inflammatory cells characteristic of COPD. Phosphodiesterase-4 inhibitors represent a promising new class of substances for use in antiinflammatory treatment of this disease.

American Journal of Respiratory Cell and Molecular Biology, 1994

Using flow cytometry, thymidine uptake into DNA, and expression of two growth-related genes, hist... more Using flow cytometry, thymidine uptake into DNA, and expression of two growth-related genes, histone 3 and c-myc, we found an increase in the proportion of distal lung epithelial cells in the G0/G1 phase of the cell cycle with advancing gestation. Since our previous studies had demonstrated that platelet-derived growth factor (PDGF) is essential for the progression of these cells from the G0/G1 to the S phase of cell cycle, we investigated the gene and protein expression of PDGF-related genes (PDGF-A, PDGF-B, alpha-receptor, and beta-receptor) in distal fetal lung epithelial cells. The cells transcribed all the PDGF-related genes and translated the PDGF-A and PDGF-B mRNAs into protein, as demonstrated by immunocytochemistry and immunoprecipitation. To explore an autocrine role for PDGF in distal fetal lung epithelial cells, intervention studies using PDGF-A and -B chain-specific antisense oligodeoxynucleotides (ODN) were carried out. Antisense PDGF-B ODN, but not antisense PDGF-A ODN, significantly reduced the DNA synthesis of these cells. The inhibitory effect of antisense PDGF-B ODN on DNA synthesis was reversed by the addition of exogenous PDGF-BB, which supports an autocrine role in the DNA synthesis of these cells. We also examined the expression of PDGF genes in distal fetal lung epithelial cells during late gestation. PDGF-A chain and beta-receptor gene expressions declined with advancing gestation, whereas expression of message for PDGF-B chain and alpha-receptor increased. The increases in message for PDGF-B chain and alpha-receptor with advancing gestation were due to a greater rate of transcription, whereas the developmental decrease of PDGF-A chain and beta-receptor mRNAs was caused by a decrease in RNA stability. Taken together with the ODN data, these results suggest that the G0/G1 cell cycle arrest of distal lung epithelial cells during late fetal gestation is due to a decrease in PDGF beta-receptor expression by the cells.

Canadian Respiratory Journal, 1994

OBJECTIVE: Efficient gas exchange across the alveolar membrane requires a dry air space. At birth... more OBJECTIVE: Efficient gas exchange across the alveolar membrane requires a dry air space. At birth, active Na+transport provides the major driving force for absorption of fetal lung liquid, and during adult life, similar transport mechanisms balance fluid exchange across the alveolarcapillary membrane. A cation channel, previously identified in fetal alveolar epithe lium, may represent one of several pathways which regulate apical-basal transepithelial Na+flux. The purpose of this study was to determine if cation channels are also present in adult alveolar epithelial cells.DESIGN: Standard inside-out patch-clamp recording techniques were used to study channels present in patches of membrane from adult rat alveolar epithelium.POPULATION: Alveolar epithelial cells were obtained from adult male Sprague-Dawley rats and studied in primary cell culture.MAIN RESULTS: A 23 pS nonselective cation channel was identified in 68% of patches voltage clamped to -60 mV. The probability of channel op...

Cmaj Canadian Medical Association Journal Journal De L Association Medicale Canadienne, Mar 10, 2000

This article has been peer reviewed.

$Research paper thumbnail of Alkaline phosphatase: a marker of alveolar type II cell diffraction$

The American Review of Respiratory Disease, 1988

In an effort to identify type II cells by a method independent of staining phospholipid inclusion... more In an effort to identify type II cells by a method independent of staining phospholipid inclusions, we evaluated a histochemical technique for alkaline phosphatase activity in normal rat lung, in freshly isolated type II cells, and in primary culture of type II cells. In the adult rat alveolus, alkaline phosphatase staining selectively identified type II cells, although nonciliated bronchiolar (Clara) cells and loose perivascular connective tissue also stained for alkaline phosphatase activity. In cell suspensions of type II cells and other dissociated lung cells, alkaline phosphatase staining correlated closely with the modified Papanicolaou technique and was particularly useful in distinguishing type II cells from alveolar macrophages. To determine if alkaline phosphatase was related to the differentiated phenotype of type II cells, we studied conditions known to affect other type II cell functions. When type II cells were cultured on plastic substrata, the intensity of alkaline phosphatase staining decreased with increasing time in culture. To quantitate the apparent decrease in alkaline phosphatase activity, we used a biochemical assay to study the expression of alkaline phosphatase by type II cells. The specific activity of alkaline phosphatase in type II cells declined with increasing time in tissue culture on plastic substrata. Alkaline phosphatase activity was maintained, however, by culturing cells on Englebreth-Holm-Swarm (EHS) tumor matrix. Cells that had reduced levels of alkaline phosphatase activity following 48 h of culture on plastic substrata could be "rescued" by removing them from the plastic substratum and reculturing them for 48 h on EHS matrix. Alkaline phosphatase activity was also increased by culturing type II cells in the presence of cAMP or sodium butyrate.(ABSTRACT TRUNCATED AT 250 WORDS)

The American journal of physiology

ABSTRACT

Esterases, Lipases, and Phospholipases, 1994

The American review of respiratory disease, 1988

Healthcare quarterly (Toronto, Ont.), 2005

The novel proposal outlined by Glenn Brimacombe suggests that the federal government directly par... more The novel proposal outlined by Glenn Brimacombe suggests that the federal government directly participate in funding incremental venture capital investment in Canadian biotechnology, with the goal of facilitating commercialization of Canadian biotechnology and health sciences intellectual property. In this way, they suggest, the economic development benefits of the Canadian current investment in health sciences will be increased. The proposal is based on two premises that need further evaluation: (1) the biotechnology sector in Canada presently underperforms in terms of value creation; (2) this underperformance is due to inadequate venture capital investment. It is the author's view that, although several measures do suggest relative system underperformance, this is likely due to structural differences rather than inadequate venture capital investment. The absence of large, integrated, global biopharmaceutical firms based in Canada, the large number of very small biotech firms a...

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne, Jan 23, 1999

Completion of treatment of active cases of tuberculosis (TB) is the most important priority of TB... more Completion of treatment of active cases of tuberculosis (TB) is the most important priority of TB control programs. This study was carried out to assess treatment completion for active cases of pulmonary TB in Toronto. Consecutive cases of culture-proven pulmonary TB were obtained from the microbiology laboratories of 5 university-affiliated tertiary care centres in Toronto in 1992/93. A standard data-collection tool was used to abstract information from inpatient and outpatient charts. For patients who were transferred to other treatment centres or lost to follow-up, the local health unit was contacted for information about treatment completion. If incomplete information was obtained from these sources, data from the provincial Reportable Disease Information System were also reviewed. The main outcome analysed was treatment outcome, with cases classified as completed (record of treatment completion noted), transferred (patient transferred to another centre but no treatment results ...

American Review of Respiratory Disease, 1993

This study examined the hypothesis that transient, whole-body hyperthermia would reduce lung dama... more This study examined the hypothesis that transient, whole-body hyperthermia would reduce lung damage and/or mortality in a previously described animal model of acute lung injury. Normal, adult Sprague-Dawley rats were randomly assigned either to a heated (n = 40) or to a sham-heated (n = 49) group. Heated animals were warmed to 41 to 42 degrees C 18 h before intratracheal instillation of phospholipase A2. Forty-eight hours after phospholipase A2 exposure, the two groups were compared in a blinded fashion for mortality rate, PaO2, AaPO2, lung wet/dry weight ratio, alveolar inflammatory cell number, and lung histopathology. Heated, injured animals exhibited a reduced mortality rate and less lung damage than did unheated animals: mortality (zero versus 27%, p &amp;lt; 0.001); AaPO2 (22 +/- 3 versus 36 +/- 15 mm Hg, p &amp;lt; 0.002); lung lavage cell counts (5.3 +/- 3 versus 16.9 +/- 7 x 10(6)/ml, p &amp;lt; 0.05); lung wet/dry weight ratio (4.1 +/- 0.6 versus 5.1 +/- 0.7, p &amp;lt; 0.025); parenchymal lung injury fraction (0.10 versus 0.51, p &amp;lt; 0.001). Transcription and translation of heat shock proteins (HSP70) were examined by Northern and Western analysis. Pulmonary tissue HSP70 mRNA was elevated 1 h after heating. HSP72 protein levels were increased over baseline levels between 12 and 72 h after whole-body hyperthermia, but they were unchanged in sham-heated animals. These data indicate that thermal pretreatment associated with the induction of HSP72 protein synthesis, attenuates tissue damage and mortality in experimental lung injury.

Journal of lipid mediators, 1993

Human non-pancreatic PLA2 has been the object of intense scrutiny for a relatively short period o... more Human non-pancreatic PLA2 has been the object of intense scrutiny for a relatively short period of time. Its role in physiology remains enigmatic. While PLA2 may serve to remodel or remove peroxidised or senescent phospholipids, the enormous magnitude of its upregulation during infectious or inflammatory episodes is consistent with a role in host defense. However, the nature of this role remains elusive. Attempts to relegate this enzyme to the genre of acute phase reactants have not been helpful in unravelling its role. Difficulty in obtaining adequate amounts of native snp-PLA2 prior to the availability of recombinant snp-PLA2 led to the widespread use of snake venom homologs, particularly in studies of the biology of PLA2. This review has underscored the pitfalls inherent in that approach given the major differences between some venom PLA2s as compared to snp-PLA2. In addition, it bears reiterating that the complex composition of venom allows for potentiation of PLA2 activity by o...

The American journal of physiology, 1993

The adult mature fetal, but not immature fetal, lung is capable of actively transporting Na+ from... more The adult mature fetal, but not immature fetal, lung is capable of actively transporting Na+ from the alveolar space. The reason for the impaired Na+ transport in the immature lung is not known; however, the apical membrane Na+ channel is the rate-limiting step for epithelial Na+ transport. This study determined whether transcripts coding for the adult rat colonic epithelial Na+ channel (alpha rENaC) were present in the fetal and adult lung and whether they were developmentally regulated. Similarly sized alpha rENaC transcripts were identified in RNA isolated from fetal and adult whole rat lung, primary cultures of fetal and adult alveolar epithelium, and adult rat whole kidneys, suggesting that the lung alpha rENaC is a similar transcript to that found in the salt-deprived rat colonic epithelium. There were low mRNA levels in 17- to 18-day gestational age (GA) fetal lungs and epithelium (term GA = 22 days), but these levels increased markedly during the saccular stage of lung devel...

New horizons (Baltimore, Md.), 1995

More than a quarter century has passed since Ashbaugh and colleagues postulated that abnormalitie... more More than a quarter century has passed since Ashbaugh and colleagues postulated that abnormalities of surfactant are causally related to the abrupt and severe organ dysfunction that occurs in individuals with acute lung injury (ALI). In this time, much progress has been made in expanding our understanding of the normal functions of the alveolar epithelium and how these functions may be disrupted in the context of ALI. Alveolar epithelial cells are a key structural component of the spatial separation of gas and plasma, essential for normal gas exchange in the lung. In addition, alveolar epithelial cells synthesize, secrete, and take up surfactant, which, by reducing surface tension, is a key determinant of intra-alveolar pressure. Surfactant is qualitatively and quantitatively abnormal in lung injury due to changes in synthesis, secretion, intra-alveolar metabolism, and biophysical inhibition by protein and lipid inhibitors. Alveolar epithelial cells also subserve additional host def...