Search PubMed⌕ Search

Biomedical subjects

R J Mason

Publications and source records attributed to R J Mason.

At least 73 records · Page 4Linked to original sources
PubMed1998

Leptospira interrogans antibodies in feral pigs from New South Wales.

The sera of 195 hunter-killed feral pigs (Sus scrofa), collected in New South Wales (Australia) from April to November 1995, were screened against a reference panel of 14 Leptospira interrogans serovars using a microscopic agglutination test (MAT). The panel represented those serovars previously isolated from wild and domestic mammals in mainland Australia. Antileptospiral agglutinins were detected in 20% of the sera tested and included nine L. interrogans serovars. The majority of serological reactors (63%) were to L. interrogans serovar pomona. Sera from 26% of immunoreactors cross reacted with antigens from one or more serovars. No differences were noted in the prevalence of L. interrogans antibodies between the sexes, or between pigs from areas of low and high rainfall. The implications of leptospirosis in feral pigs on the transmission of leptospires to wildlife, livestock, and humans are discussed.

Agglutination Tests↗
PubMed1998

The columnar-lined (Barrett's) oesophagus in black patients.

OBJECTIVE: To determine the prevalence of a columnar-lined Barrett's oesophagus in black patients. DESIGN: In the present study we retrospectively reviewed the records of all black patients with Barrett's oesophagus. SETTING: Johannesburg Hospital's referral-based oesophageal clinic. SUBJECTS: Eleven black patients with Barrett's oesophagus from a series of 216 consecutive patients with Barrett's oesophagus who were referred to the oesophageal clinic from 1970 to 1993. MAIN OUTCOME MEASURES: Prevalence, demographics and characteristics of black patients with a columnar-lined Barrett's oesophagus. RESULTS: Only 5% of the total series of Barrett's patients were black. Because the ratio of black to white in Johannesburg is about 5:1, the comparative prevalence of Barrett's oesophagus in blacks is extremely low when compared with that of whites. Although the number of patients is small, this series demonstrates that a columnar-lined oesophagus does occur in blacks. When compared with Caucasians, blacks had far fewer associated hiatus hernias (33%). The presentation of blacks is also different in that a greater proportion presented with adenocarcinoma (36%). CONCLUSIONS: Gastro-oesophageal reflux and related conditions such as a columnar-lined oesophagus are uncommon conditions in African blacks. This series demonstrates however that a columnar-lined oesophagus does occur in black patients. It is possible that in black patients an inherent defect of the lower oesophageal sphincter rather than a hiatus hernias is the cause of the reflux. A greater proportion of this small group of patients presented with adenocarcinoma than would have been expected. The reasons for the low prevalence of Barrett's oesophagus in black South Africans are unknown.

Adult↗
PubMed1997

Nissen fundoplication prevents shortening of the sphincter during gastric distention.

OBJECTIVE: To determine the dynamic effects of a Nissen fundoplication on a volume-stressed lower esophageal sphincter (LES). DESIGN: Before and after experimental study in 10 baboons. SETTING: University animal research unit. INTERVENTIONS: Continuous manometric evaluation of the esophagus, cardia, and stomach during distention of the stomach with water. Slow motorized pull-through of the LES after each successive intragastric increment of 50 mL of water. Tests were performed again after a Nissen fundoplication. MAIN OUTCOME MEASURES: Lower esophageal sphincter length and frequency of common cavity episodes after each volume increment. The pressure and intragastric volume at the yield point are defined as the point of permanent loss of the gastroesophageal pressure gradient. RESULTS: Gastric distention of the stomach with water resulted in a progressive decrease in LES length and competency. The median +/- interquartile range LES length decreased by 1.5 +/- 0.3 mm for every 1-mm Hg increase in gastric pressure before fundoplication and by 0.2 +/- 0.1 mm after fundoplication (P < .02). With gastric distention there was an indirect correlation between the degree of LES length and the frequency of reflux episodes (r = -0.70). This correlation was abolished by a Nissen fundoplication (r = -0.31). The median +/- interquartile range frequency of common cavity episodes (2.19 +/- 2.05 episodes per minute) before fundoplication decreased significantly (P < .001) to 0 +/- 0.59 episodes per minute after fundoplication. The median +/- interquartile range yield pressure (13 +/- 9 mm Hg) and yield volume (825 +/- 855 mL) were significantly (P < .01) improved after Nissen fundoplication to 39 +/- 36 mm Hg and 1250 +/- 750 mL, respectively. CONCLUSION: By preventing sphincter shortening, a Nissen fundoplication improves competency of the LES to progressive degrees of gastric distention.

Animals↗
PubMed1997

A new intraluminal antigastroesophageal reflux procedure in baboons.

BACKGROUND: A new endoscopic intraluminal procedure (valvuloplasty) was designed to provide a simple, easy approach to the cardia and to correct and augment any mechanical deficiencies present. The feasibility, durability, and efficacy of this procedure was tested in 13 baboons. METHODS: The valvuloplasty consisted of an intussusception of the gastroesophageal junction into the stomach to create a nipple-type valve. The configuration of the valve was maintained with eight staples and stability was aided by an intramural injection of sodium morrhuate. Gastrointestinal endoscopy and esophageal manometry were performed before and after the procedure. Competency was determined as the intragastric pressure (yield pressure) and volume (yield volume) needed to result in equalization of gastric and esophageal pressure while distending the stomach with water. Comparisons were made with a group of normal baboons (n = 10). RESULTS: All baboons had a normal eating pattern with none showing any evidence of vomiting or regurgitation. Endoscopic circumferential integrity of the valves was 86% at 6 months. The median lower esophageal sphincter length in the valvuloplasty group was significantly (p < 0.01) increased after the procedure from 21 mm to 30 mm. The median yield pressure (22.1 mm Hg) and yield volume (1,525 ml) of the valvuloplasty group was significantly (p < 0.01) greater than the controls (14 mm Hg and 859 ml). CONCLUSIONS: The valvuloplasty is simple, safe, and durable. It augments mechanical function of the cardia and improves competency.

Animals↗
PubMed1997

Inflammation and specialized intestinal metaplasia of cardiac mucosa is a manifestation of gastroesophageal reflux disease.

OBJECTIVE: The purpose of the study was to test the hypothesis that cardiac mucosa, carditis, and specialized intestinal metaplasia at an endoscopically normal-appearing cardia are manifestations of gastroesophageal reflux disease. SUMMARY BACKGROUND DATA: In the absence of esophageal mucosal injury, the diagnosis of gastroesophageal reflux disease currently rests on 24-hour pH monitoring. Histologic examination of the esophagus is not useful. The recent identification of specialized intestinal metaplasia at the cardia, along with the observation that it occurs in inflamed cardiac mucosa, led the authors to focus on the type and condition of the mucosa at the gastroesophageal junction and its relation to gastroesophageal reflux disease. METHODS: Three hundred thirty-four consecutive patients with symptoms of foregut disease, no evidence of columnar-lined esophagus, and no history of gastric or esophageal surgery were evaluated by 1) endoscopic biopsies above, at, and below the gastroesophageal junction; 2) esophageal motility; and 3) 24-hour esophageal pH monitoring. The patients were divided into groups depending on the histologic presence of cardiac epithelium with and without inflammation or associated intestinal metaplasia. Markers of gastroesophageal reflux disease were compared between groups (i.e., lower esophageal sphincter characteristics, esophageal acid exposure, the presence of endoscopic erosive esophagitis, and hiatal hernia). RESULTS: When cardiac epithelium was found, it was inflamed in 96% of the patients. The presence of cardiac epithelium and carditis was associated with deterioration of lower esophageal sphincter characteristics and increased esophageal acid exposure. Esophagitis occurred more commonly in patients with carditis whose sphincter, on manometry, was structurally defective. Specialized intestinal metaplasia at the cardia was only seen in inflamed cardiac mucosa, and its prevalence increased both with increasing acid exposure and with the presence of esophagitis. CONCLUSION: The findings of cardiac mucosa, carditis, and intestinal metaplasia in an endoscopically normal-appearing gastroesophageal junction are histologic indicators of gastroesophageal reflux disease. These findings may be among the earliest signs of gastroesophageal reflux and contribute to the authors understanding of the pathophysiology of the disease process.

Adolescent↗
PubMed1997

Heparin-binding EGF-like growth factor is a mitogen for rat alveolar type II cells.

Alveolar type II cells proliferate and differentiate into type I epithelial cells to restore the alveolar epithelium after lung injury. Since mitogens that bind the epidermal growth factor (EGF), EGF, receptor and transforming growth factor alpha (TGF alpha) have been shown to stimulate type II cell proliferation, studies were undertaken to determine whether the recently described protein, heparin-binding EGF-like growth factor (HB-EGF), was a mitogen for rat alveolar type II cells in primary culture. In addition, since HB-EGF is produced by macrophages, it was of interest to determine whether mitogenic activity for type II cells present in macrophage conditioned medium was due to HB-EGF. Rat and human recombinant HB-EGF stimulated thymidine incorporation into rat type II cells in a concentration-dependent manner up to 10-50 ng/ml then became inhibitory. The nuclear labeling index of type II cells increased from 2% to 16% with 10 ng/ml HB-EGF. However, HB-EGF induced only a small increase in cell number after 48 h and did not support low-density proliferation of alveolar type II cells. Conditioned medium from the human monocytic cell line, U937, stimulated type II cell DNA synthesis, and stimulatory activity could be partially purified by S-sepharose and heparin-sepharose chromatography. The growth-promoting activity from U937 cells that bound to heparin-sepharose was inhibited by a neutralizing antibody to human HB-EGF. Immunoblot analysis of active fractions also verified the presence of HB-EGF. However, the neutralizing antibody to rat HB-EGF did not inhibit mitogenic activity for type II cells found in rat bronchoalveolar lavage fluid. HB-EGF mRNA was found to be expressed in human alveolar macrophages to similar levels as differentiated U937 cells but was not detected in rat alveolar macrophages by Northern analysis of total mRNA. There was no difference in the level of HB-EGF mRNA expression in human alveolar macrophages from patients with interstitial lung disease compared with macrophages from normal subjects. The results demonstrate that HB-EGF is a mitogen for rat alveolar type II cells but appears to show species-specific differences with regard to its production by macrophages. Leslie, C. C., K. McCormick-Shannon, J. M. Shannon, B. Garrick, D. Damm, J. A. Abraham, and R. J. Mason. 1997. Heparin-binding EGF-like growth factor is a mitogen for rat alveolar type II cells. Am. J. Respir. Cell Mol. Biol. 16:379-387.

Adult↗
PubMed1997

Prevention of bleomycin-induced lung injury in rats by keratinocyte growth factor.

Intratracheal instillation of bleomycin produces pulmonary fibrosis in rats. Alveolar type II cell proliferation is thought to minimize the fibrotic response after lung injury. Because keratinocyte growth factor (KGF) stimulates type II cell proliferation in the rat, we designed experiments to evaluate whether intratracheal KGF before or after intratracheal bleomycin would prevent pulmonary fibrosis. Intratracheal bleomycin without KGF resulted in moderate to severe lung injury and subsequent fibrosis. Conversely, intratracheal KGF pretreatment at 48 or 72 hr before bleomycin resulted in minimal to no visible lung injury. Rats pretreated with phosphate buffered saline before bleomycin had significantly more neutrophils and protein in bronchoalveolar lavage fluid at 4 and 6 days and higher hydroxyproline levels after bleomycin as compared to KGF-pretreated rats. Pretreatment with KGF at 48 hr protected against bleomycin-induced alterations in pulmonary physiology and increased surfactant protein C-positive (SP-C)-positive cells and SP-A, SP-B, SP-C, and SP-D mRNA levels after bleomycin instillation when compared to saline pretreated rats on day 1 or day 7. KGF posttreatment protocols did not prevent bleomycin lung injury and fibrosis. We conclude that KGF pretreatment attenuates bleomycin lung injury and increases type II cell proliferation and surfactant protein gene expression after bleomycin instillation in the rat.

Animals↗
PubMed1996

Calcium dependent association of surfactant protein A with pulmonary surfactant: application to simple surfactant protein A purification.

Surfactant protein A (SP-A) is an abundant lipoprotein component of pulmonary surfactant that plays multiple roles in surfactant homeostasis within the lung. A simple and rapid purification procedure for SP-A is described. Purified surfactant is washed by centrifugation with Ca2+ containing buffer to remove residual soluble proteins. Following the Ca2+ buffer wash, the surfactant pellet is washed in buffer containing EGTA and Mg2+ which releases the bound SP-A in almost pure form. Subsequent chromatography of the SP-A on Sephacryl S-500 yields homogeneous preparations of the protein. The SP-A purified using this procedure requires no exposure to either detergents or organic solvents to remove lipid. SP-A prepared by this new method inhibits lipid secretion from alveolar type II cells as effectively as SP-A prepared by other methods. In addition, the SP-A depleted surfactant produced in the first step of this procedure is capable of binding exogenous SP-A in a time dependent, saturable and Ca2+ dependent manner.

Animals↗
PubMed1996

Hepatocyte growth factor is a mitogen for alveolar type II cells in rat lavage fluid.

Proliferation of type II cells is required for maintenance of the alveolar epithelium and for restoration after lung injury. Although various known growth factors have been reported to stimulate type II cell proliferation in vitro, there is very little knowledge on which growth factors are present in the lung in vivo. We have previously reported that rat lavage fluid contains a mitogen(s) for type II cells, and this study was de signed to identify the growth factor(s) in this biological fluid for type II cells. The mitogenic activity was purified by sequential chromatography on blue Sepharose and heparin Sepharose. Hepatocyte growth factor (HGF) and acidic fibroblast growth factor by Western analysis. The amount of HGF recovered by lavage was approximately 6 ng/rat. By a use of neutralizing antibodies for different growth factors, HGF was found to be responsible for most of the stimulatory activity for rat type II cells in the partially purified lavage fluid. In addition to HGF, rat lavage fluid also contained potent mitogenic activity for fibroblasts. Finally, we have demonstrated that much of the mitogenic activity in salt extracts of human lung is HGF. We conclude that HGF is found in rat lavage fluid and is possibly an important mitogen for adult type II cells in vivo.

Animals↗
PubMed1996

Increased surface tension of the lung and surfactant in bleomycin-induced pulmonary fibrosis in rats.

The increased elastic recoil of the lung in bleomycin-induced pulmonary fibrosis in the rat is due in part to increased surface forces. This study was designed to determine the role of surface tension in situ and in vitro 21 d after instillation of bleomycin. Using sequentially measured pressure-volume curves generated with air, saline, air after lavage with Tween 20, and saline, surface tension was significantly higher in bleomycin-treated lungs than in untreated lungs (4.7 +/- 1.1 versus 1.8 +/- 0.2 dyne/cm, p < 0.01). Surface tension was determined in vitro with a Wilhelmy balance using bronchoalveolar lavage fluid, surfactant, and organic solvent lipid extracts of surfactant. Bleomycin treatment resulted in elevated minimal surface tensions: BALF (20.7 +/- 0.6 versus 13.6 +/- 3.8 dyne/cm, p < 0.02), isolated surfactant (12.0 +/- 1.3 versus 3.0 +/- 0.5 dyne/cm, p < 0.02), and the organic solvent lipid extracted surfactant (11.0 versus 3.2 dyne/cm). These results indicate that the physical properties of surfactant in lungs of rats treated with bleomycin are abnormal and contribute to the increased elastic recoil in this model of pulmonary fibrosis.

Animals↗
PubMed1996

Keratinocyte growth factor reduces lung damage due to acid instillation in rats.

Acid aspiration is a serious complication of anesthesia and other forms of unconsciousness that can result in the adult respiratory distress syndrome (ARDS), which continues to have a very high mortality despite our current therapeutic interventions. This type of injury damages the alveolar epithelium, principally alveolar type I cells, and requires proliferation of alveolar type II cells to restore gas exchange units. Since keratinocyte growth factor (KGF) has been shown to be a potent mitogen for alveolar type II cells, we evaluated whether intrabronchial administration of KGF would minimize lung injury due to the unilateral instillation of 0.1 N hydrochloric acid (HCl). Rats were pretreated or post-treated by intrabronchial instillation of KGF (5 mg/kg) into the left lung before HCl instillation. All rats receiving KGF at 48 or 72 h before HCl instillation survived for the 7-day observation period, whereas the mortality rate for those receiving HCl alone or saline followed by HCl was 31% and 33%, respectively. Pretreatment with KGF at 72 h but not at 24 or 48 h considerably ameliorated morphologic damage produced by HCl. Inflammatory cells in bronchoalveolar lavage were markedly decreased 3 and 7 days after HCl instillation by the 72-h KGF pretreatment. Pretreatment with KGF at 72 h also attenuated the reduction of total lung capacity, decreased the alpha 1(I) procollagen mRNA levels, and diminished hydroxyproline accumulation due to HCl instillation. Saline pretreatment at 72 h had no significant effect on the HCl injury and subsequent physiologic abnormalities. Our attempts to improve outcome with post-treatment instillation of KGF were unsuccessful. We conclude that KGF pretreatment reduces lung injury due to acid instillation and can prevent subsequent pulmonary fibrosis.

Administration, Inhalation↗
PubMed1995

Keratinocyte growth factor increases mRNAs for SP-A and SP-B in adult rat alveolar type II cells in culture.

The production of pulmonary surfactant, a complex of phospholipids and lung-specific surfactant proteins, is a primary function of alveolar type II cells. Although previous studies have demonstrated a role for cell-extracellular matrix interactions and normal cell shape in the maintenance of differentiated function in primary cultures of adult rat type II cells, a positive role for growth factors in surfactant protein gene expression in isolated normal adult type II cells has not been reported. In the present study, we have examined the effects of a panel of hormones, growth factors, and cytokines on the expression of mRNAs for surfactant proteins A, B, and C (SP-A, SP-B, and SP-C). Our results show that keratinocyte growth factor (KGF) induced a two- to threefold increase in steady-state levels of mRNAs for SP-A and SP-B, but had no effect on or decreased SP-C mRNA. The increase in SP-A mRNA was accompanied by an increase in SP-A protein. The effects of KGF were both dose and time dependent, and they could be neutralized by a monoclonal antibody against KGF. The effects of KGF were mimicked by acidic fibroblast growth factor, which will bind the KGF receptor. We conclude that KGF can support differentiation of alveolar type II cells as well as act as a mitogen, thus suggesting an important role for KGF in maintenance of the alveolar epithelium.

Animals↗
PubMed1995

Surfactant protein A predicts survival in idiopathic pulmonary fibrosis.

The purpose of this study was to determine if the measurement of surfactant protein A (SP-A) in bronchoalveolar lavage (BAL) fluid predicts survival in patients with idiopathic pulmonary fibrosis (IPF). We performed BAL on 44 patients with IPF and 33 healthy volunteers. SP-A and total phospholipid (PL) were measured in the surfactant pelleted by centrifugation and expressed as a ratio to account for differences in the alveolar surface area sampled. The mean SP-A/PL was lower in patients with IPF than in healthy volunteers (31.8 +/- 2.8 versus 63.9 +/- 6.4 micrograms/mumol, p = 0.006) and in patients who died within 2 yr than in those who survived (23.4 +/- 2.6 versus 37.5 +/- 4.2 micrograms/mumol, p = 0.015). Using Cox's proportional hazard model, we found that SP-A/PL modeled continuously was associated with survival time (p = 0.002). The 5-yr survival of patients with SP-A/PL above the median level for all patients with IPF (29.7 micrograms/mumol) was more than twice that of patients below the median (68 versus 30%, p = 0.007). SP-A/PL improved upon prediction of survival modeled by most routine physiologic variables with the exception of percent predicted TLC or the multifarious clinical-radiographic-physiologic score (CRP). Cellular analysis of lavage did not predict survival in this cohort of patients. We conclude that SP-A/PL is a biochemical marker in lavage that predicts survival in patients with IPF.

Adult↗
PubMed1995

Immunolocalization of SPARC, tenascin, and thrombospondin in pulmonary fibrosis.

Several biochemically unrelated multifunctional extracellular proteins, SPARC, thrombospondin 1, and tenascin-C (TN), have been grouped as antiadhesive glycoproteins because they inhibit the spreading of cells on extracellular matrix in vitro. Migration of fibroblasts and epithelial cells into the air spaces to organize inflammatory exudate is a feature common to several fibrosing lung diseases. We hypothesized that migration would be facilitated by loosening the adhesive interactions between cells and the pericellular matrix components of the alveolar wall and that one or more of the anti-adhesive glycoproteins could be involved. Immunohistochemistry was used to localize SPARC, TN, and thrombospondin 1 in biopsies of organizing pneumonia, idiopathic pulmonary fibrosis (nine cases of usual interstitial pneumonia, one of desquamative interstitial pneumonia), and control lungs. Each antigen had a distinctive distribution. Only TN was expressed in control lungs, where it strongly stained the basement membrane of large bronchi and weakly stained alveolar entrance rings and small veins. In organizing pneumonia, TN was heavily stained through the entire extracellular matrix of the Masson bodies. In idiopathic pulmonary fibrosis, TN was abundant in the fibroblast foci of active fibrosis but was also present in the basement membrane regions beneath the metaplastic epithelium lining honeycomb cysts. TN was abundant in the interstitium in desquamative interstitial pneumonia. SPARC was observed only intracellularly where it occurred in the fibroblasts of Masson bodies of organizing pneumonia and the fibroblast foci of usual interstitial pneumonia. In desquamative interstitial pneumonia, expression of SPARC was minimal, in rare interstitial fibroblasts. Thrombospondin 1 was found consistently in organizing pneumonia but only infrequently in idiopathic pulmonary fibrosis. In both, it was localized in the extracellular matrix immediately beneath reparative epithelium. These results are consistent with a role for SPARC in fibroblast migration. TN may function in both fibroblast migration and the adhesion of metaplastic bronchial-type epithelium. However, these proteins also have other activities that may be important in pulmonary fibrosis. The localization of thrombospondin 1 suggests that it may be synthesized by regenerating epithelium where it may aid in the adhesion or migration of the epithelial cells.

Antibodies, Monoclonal↗