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Biomedical subjects

G S Davis

Publications and source records attributed to G S Davis.

At least 19 recordsLinked to original sources
PubMed1992

Serum and bronchoalveolar lavage of N-terminal type III procollagen peptides in idiopathic pulmonary fibrosis.

Collagen deposition is a prime determinant of clinical course in idiopathic pulmonary fibrosis (IPF). Identification of a marker of connective tissue metabolism would significantly enhance the ability to stage the disease and monitor the course of these patients. Prior studies of IPF have indicated that N-terminal Type III procollagen peptide (N-PIIIP) levels in blood and bronchoalveolar lavage BAL fluid are elevated. We hypothesized that elevated levels of procollagen peptides are a marker of enhanced collagen deposition, which is associated with interstitial fibrosis characterizing active disease. The purpose of the present study was to explore the relationship between N-PIIIP recovery and physiologic parameters of lung function. N-PIIIP levels in sera and bronchoalveolar lavage (BAL) from 24 patients with IPF and 29 volunteers were measured by radioimmunoassay. The extent of disease in IPF was assessed by clinical history, physical examination, chest radiograph, pulmonary physiology evaluation, and confirmatory open-lung biopsy. The severity of disease was graded using a previously described clinical, radiologic, and physiologic (CRP) scoring system. N-PIIIP normalized to albumin was higher in BAL than in serum for both volunteers (1.6-fold; p less than 0.05) and IPF patients (24-fold; p less than 0.05), consistent with local pulmonary production. BAL N-PIIIP was significantly elevated in IPF patients, whether expressed as concentration (healthy volunteer 0.11 +/- 0.06 ng/ml; IPF, 5.0 +/- 14.4; mean +/- SD; p less than 0.05) or normalized to albumin (healthy volunteer, 2.8 +/- 1.2; IPF, 73 +/- 106; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Enhanced release of prostaglandin E2 from macrophages of rats with silicosis.

The pathogenesis of silicosis results, in part, from interactions between silica particles and alveolar macrophages (AM) with release of cytokines and other mediators. Different arachidonic acid metabolites have been shown to promote or to suppress inflammation and fibrosis. We designed experiments to study the production of cyclooxygenase metabolites and tumor necrosis factor-alpha (TNF-alpha) from macrophages during active silicosis. Macrophages were harvested from rats 5 to 7 mo after an 8-day silica aerosol exposure. Upon in vitro culture of AM, the spontaneous release of prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and prostaglandin D2 (PGD2) of silica-exposed animals was higher than that of sham-exposed animals. Moreover, AM from silicotic rats displayed an increased sensitivity to low concentrations of lipopolysaccharide (LPS, 10 ng/ml) and released copious amounts of PGE2 and TXB2. When compared with similarly enhanced release of TNF-alpha from AM of silica-exposed rats, PGE2 production occurred later and started to increase when TNF-alpha production declined. Addition of the cyclooxygenase blocker indomethacin augmented TNF-alpha production, whereas the addition of PGE2 counteracted TNF-alpha release. Also peritoneal macrophages, which did not have direct contact with silica particles, released enhanced levels of PGE2 in response to low LPS doses. We conclude that AM and other macrophages from silica-exposed rats are preactivated and display an enhanced prostanoid production that could serve anti-inflammatory or immunomodulating roles in silicosis.

Animals↗
PubMed1992

Reduced release of leukotrienes B4 and C4 from alveolar macrophages of rats with silicosis.

Silicosis leads to altered release of fibrogenic and immunomodulating mediators from alveolar macrophages (AM). Since 5-lipoxygenase metabolites have been shown to possess proinflammatory effects and to promote the release of cytokines such as tumor necrosis factor-alpha (TNF-alpha) from mononuclear phagocytes, we determined leukotriene secretion from silica-exposed AM. Rats were exposed to an aerosol of silica particles for 8 days and AM were harvested by bronchoalveolar lavage 5 to 7 mo after exposure. AM from both air-sham control and silica-exposed rats displayed minimal spontaneous leukotriene release upon in vitro culture. Stimulation with opsonized zymosan particles induced leukotriene B4 (LTB4) and leukotriene C4 (LTC4) secretion, which was much greater in control AM than in AM from silica-dusted rats. The reverse was found for zymosan-induced TNF-alpha production, which was higher in AM from silica-exposed than from control rats. To study the interrelation between leukotriene and TNF-alpha release, we incubated zymosan-stimulated AM with the 5-lipoxygenase inhibitor VZ 65. VZ 65 suppressed zymosan-induced TNF-alpha release from AM in a dose-dependent manner, and TNF-alpha production could be restored almost completely by addition of LTB4. These experiments demonstrate that silica exposure resulted in a decreased LTB4 and LTC4 production from AM, which may represent a regulatory mechanism to counterbalance enhanced TNF-alpha production during silicosis.

Animals↗
PubMed1991

Effects of work exposure, retirement, and smoking on bronchoalveolar lavage measurements of lung dust in Vermont granite workers.

Estimation of the exposure to respirable dust in the workplace is an important aspect of industrial hygiene. We performed bronchoalveolar lavage (BAL) on 42 healthy nonindustrial control subjects and 44 workers in the Barre, Vermont granite industry to determine whether BAL materials reflected occupational exposure. The granite workers held jobs with a range of dust exposure intensities and had employment histories from 1 to 43 yr; 12 workers were retired. None of the workers had radiologic evidence of silicosis. The granite dust content of BAL materials was measured by enumerating the percentage of cells positive for particulates by polarized light microscopy, by analysis for silicon by scanning electron microscopy with energy-dispersive X-ray spectrometry, and by chemical analysis. Minerals were present in greater quantity in the BAL cells from granite workers than from nonindustrial control subjects. Polarized light microscopy was comparable in sensitivity, specificity, and overall accuracy to electron microscopy; chemical analysis was less accurate than either microscopic technique. Tobacco smoking did not interfere with the detection of the occupationally related minerals or influence the quantity of dust present. The mineral in BAL cells was partially related to the intensity of exposure within the granite industry and to the duration of employment, but there was great individual variation among subjects. Retirement led to a decrease in BAL mineral content, but substantial dust remained for many years.

Bronchoalveolar Lavage Fluid↗
PubMed1991

Systemic macrophage stimulation in rats with silicosis: enhanced release of tumor necrosis factor-alpha from alveolar and peritoneal macrophages.

In silicosis, alveolar macrophages (AM) are thought to induce chronic inflammation and fibrosis by release of cytokines. Rats were exposed to aerosols of alpha-quartz and examined 4 to 9 mo later for persistence of silica particles and release of tumor necrosis factor-alpha (TNF-alpha) from macrophages. Silica particles were detected in AM, lung parenchyma, and thoracic lymphoid organs, whereas extrathoracic lymphoid tissues and organs were free of the mineral. When AM were tested functionally, no spontaneous release of TNF-alpha was observed. However, upon in vitro stimulation of AM from silicotic rats with a low concentration of lipopolysaccharide (10 ng/ml), abundant TNF-alpha production was found that was higher and occurred more rapidly than with AM from sham-exposed animals. Peritoneal macrophages, which did not have contact with silica particles, displayed a similarly enhanced TNF-alpha release in response to low doses of lipopolysaccharide. These data demonstrate a state of systemic preactivation ("priming") of macrophages that supports the notion that silicosis is associated with a general immunostimulation.

Animals↗
PubMed1990

Clinical role of bronchoalveolar lavage in adults with pulmonary disease.

BAL remains a powerful investigative tool. In a short span of 20 yr, it has helped tremendously in understanding some of the aspects of the pathogenesis of diseases involving the lower respiratory tract. To realize its full potential in the diagnosis and management of diseases involving the lower respiratory tract, there is a great need for standardization of the technical aspects of BAL as well as processing and analysis of the BAL cellular- and fluid-phase components. Despite these hurdles, BAL has been found to be diagnostic in several infectious and noninfectious diseases involving the lower respiratory tract, and it provides valuable information that may be helpful in characterizing the prognosis and response to therapy in certain interstitial diseases of the lung. It is expected that with future research, in particular long-term prospective epidemiologic and clinical studies in pneumoconioses and in other interstitial lung disease, BAL will prove more valuable in the diagnosis and management of such disease.

Bronchoalveolar Lavage Fluid↗
PubMed1989

Rat alveolar macrophage production of chemoattractants for neutrophils: response to Escherichia coli endotoxin.

Endotoxemia in rats is associated with the accumulation of neutrophils (polymorphonuclear leukocytes) within the airspaces of the lung. Polymorphonuclear leukocyte influx appears to be regulated by the intrapulmonary accumulation of chemotactic activity. Since alveolar macrophages (AMS) are prevalent cells in the airspace and are known to release a variety of chemotactic factors, we investigated the effect of endotoxin exposure on AM production of chemotactic activity. We tested the hypothesis that endotoxin-exposed AMs have an augmented ability to produce chemoattractants. We recovered AMs by bronchoalveolar lavage from control rats and from rats treated in vivo with a "low dose" (2.5 mg/kg) or a "high dose" (5.0 mg/kg) of Escherichia coli endotoxin. These AMs were then cultured in vitro for 15 h in the absence or the presence of endotoxin (15 and 30 micrograms/ml) to stimulate the cells to produce chemoattractants. We found that in vitro endotoxin stimulated normal AMs to secrete chemoattractants in a dose-dependent fashion. AMs from rats treated with endotoxin in vivo spontaneously secreted more chemoattractants than AMs from control rats. Exposure to in vivo endotoxin followed by in vitro stimulation with endotoxin resulted in an even greater production of chemoattractants by AMs. We found a significant association between the percent polymorphonuclear leukocytes recovered by bronchoalveolar lavage from the airspaces and the production of chemoattractants by AMs from the same specimen. The level of chemotactic activity spontaneously produced by AMs predicted the degree of stimulated production of chemotactic activity. Partial purification indicated that this chemotactic activity has two molecular weight peaks, one near 1,000 and the other near 50,000. The activity was stable at 100 degrees C for at least 30 min and was degradable by trypsinization. We conclude that endotoxin can induce AM production of chemoattractants and that prior exposure to endotoxin in vivo affects the response of AM to in vitro endotoxin exposure. By inference, it is possible that this endotoxin-macrophage interaction may serve as a biologic amplifier of the effects of endotoxin and may have a role in the pathogenesis of septic lung injury in humans.

Animals↗
PubMed1989

Ontogeny of daily rhythmicity in plasma corticosterone and variation in sensitivity of the corticosterone response in turkey poults.

Two trials were conducted with turkey poults to examine the ontogeny of daily rhythmicity of plasma corticosterone (CS), and to determine the plasma CS response to adrenocorticotropic hormone (ACTH) injections and temperature stress at different times during a light-dark cycle. In Trial 1, CS levels were determined at 3-h intervals over a 24-h period in 3, 10, and 14-day-old tom and hen poults maintained on a 12 h light: 12 h dark (12L:12D) light-dark cycle. Plasma CS levels of tom and hen poults were similar. A robust daily rhythm in plasma CS occurred by 10 days of age, with maximal levels of CS occurring during the scotophase. In Trial 2, daily variation in plasma CS sensitivity to cold treatment or ACTH in 2-wk-old toms was examined. Tom poults were exposed to cold water immersion (5 C for 1 min), porcine ACTH injection (1 IU/kg), or saline injection at 1100 h in midphotophase and at 2300 h in midscotophase. Treatments significantly increased plasma CS in both the photophase and scotophase, with the levels being significantly higher in the scotophase. At midphotophase cold or ACTH treatment induced respectively, a 489 and 546% increase in plasma CS above that of controls. During midscotophase, 746 and 695% increases in CS above levels for controls were induced by cold stress or ACTH, respectively. Differences between percent changes for times of day were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1989

The absence of sex and age effects on the corticosterone response of turkey poults to adrenocorticotropic hormone and temperature stressors.

A study was undertaken to assess the role of sex and age on the adrenal cortical response of turkey poults during the time period associated with idiopathic poult mortality. Three and 14-day-old tom and hen turkey poults were subjected to the following treatments: saline injection (control), cool water immersion (20 C) for 1 min, cold water immersion (5 C) for 1 min, and 1 IU/kg adrenocorticotrophic hormone (ACTH) injection. Blood was collected 1 and 4 h posttreatment for plasma corticosterone (CS) assay. Temperature treatments did not affect plasma CS in either age or sex. Plasma CS was increased by ACTH after 4 h postinjection in both sexes and at both ages. The hypothalamic-pituitary-adrenal cortical axis of the turkey poult was functional but appeared to be insensitive to temperature stress.

Adrenocorticotropic Hormone↗
PubMed1989

Relationship between plasma corticosterone levels and poult mortality and the effects of feeding corticosterone on poult performance.

The study examined the relationship between plasma corticosterone (CS) levels and early mortality in Large White tom turkey poults. Trial 1 was conducted to compare the plasma CS levels of 3-day-old poults that subsequently lived or died during the first 2 wk posthatch. Blood samples were obtained from 100 poults at 3 days of age. By 2 wk of age 9% mortality had occurred. Plasma CS of poults that lived (7.1 ng/mL) was significantly greater (P less than .05) than in poults that died (3.2 ng/mL) between 3 and 14 days of age. A second trial was conducted to test the effects of feed-induced elevation of plasma CS on poult performance under stressful conditions. This trial consisted of three treatment groups: 1) control (C), poults placed immediately after removal from the hatcher with feed and water; 2) control-held (CH), poults held without feed and water at 28.9 C for 3 days posthatch; and 3) 40 mg CS/kg feed-held (40H), poults held without feed and water at 28.9 C for 3 days posthatch then fed 40 mg CS/kg feed. Mortality was monitored daily and body weights, feed consumption, and plasma CS levels were measured at 1 and 2 wk of age. The only performance parameter that was significantly affected was body weight; a significant reduction occurred at 2 wk of age in poults given the 40H treatment. It was concluded that poult death is associated with low plasma CS levels, but diet-induced increases in plasma CS did not significantly improve livability following a stressful condition.

Animals↗
PubMed1988

Gas volume quantitation during argon ion laser ablation of atheromatous aorta in blood and 0.9% saline media with an optically shielded catheter.

Using an optically shielded fiber optic laser catheter, the amount of gas produced when firing an argon ion laser into 0.9% saline solution or blood alone and into atheromatous aorta in either a blood or 0.9% saline medium was quantitated. Energies from 0.25 to 4 joules (J) were used at powers of 2, 5, and 8 W. We found that total volume of gas produced is small not only at equilibrium (0.3 +/- 0.1 microliter/J when firing in blood alone and also when ablating aorta in blood or saline media) but also at peak (2.5 +/- 0.2 microliters/J firing in blood alone and 1.0 +/- 0.1 microliter/J or 0.9 +/- 0.1 microliter/J when ablating aorta in saline or blood, respectively). Because these volumes are small, a clinically significant event from a gas embolus is unlikely during intravascular laser ablation of atheromatous plaque in the energy and power range studied. No gas was quantitated when firing the argon ion laser into 0.9% saline solution alone. The peak gas volume when firing in blood alone was significantly greater than that produced in the other chamber environments. This is thought to be due to increased absorption of argon laser light by hemoglobin. The gas volumes produced by lasing aorta in 0.9% saline or blood were not statistically different.

Angioplasty, Balloon↗
PubMed1988

Small bowel edema: mosaic pattern.

We report an unusual radiographic appearance of small bowel submucosal edema produced by obstruction from metastatic colorectal carcinoma. The distinctive muscosal pattern of raised polygonal plaques is the same mosaic pattern described in the colon and referred to as "urticaria." This mosaic pattern in the small bowel has not previously been reported.

Aged↗
PubMed1988

Alveolar macrophage function is selectively altered after endotoxemia in rats.

The alveolar macrophage (AM) is exquisitely sensitive to activation by gram-negative bacterial endotoxin, an agent associated with adult respiratory distress syndrome. We tested the hypothesis that specific functions of the AM are activated selectively by in vivo endotoxin while others remain unaffected. AMs were recovered from the airspaces of control and endotoxin-treated (5.0 mg/kg) rats, and functional assays were performed. We measured macrophage adherence, viability, and survival; chemotactic movement; hydrogen peroxide production; phagocytic function; and the secretion of representative biological response modifiers. Endotoxemia enhanced AM adherence during a 15-h incubation period, while not affecting cell number or viability. There was a 60% reduction in AM chemotactic movement and a 65% augmentation of hydrogen peroxide production, but no effect on AM phagocytosis of Staphylococcus aureus. Endotoxemia enhanced AM production of macrophage-derived chemotactic activity for neutrophils by 70% and interleukin-1 activity by 100%, but did not affect the production of macrophage-derived growth factor activity for fibroblasts. We conclude that endotoxemia alters the functions of the AM in a selective manner; certain functions are enhanced, while others are inhibited or not affected. We believe that this selective effect on AM functional capacity may be an important mechanism explaining certain aspects of the course, duration, or outcome of adult respiratory distress syndrome associated with gram-negative sepsis.

Animals↗
PubMed1987

Lipids in bronchoalveolar lavage fluid from patients with sarcoidosis.

The recovery of protein and two specific surfactant lipids, phosphatidylcholine and phosphatidylglycerol, from bronchoalveolar lavage fluid is altered in chronic and acute non-granulomatous interstitial lung disease. This study set out to determine whether the same is true for patients with sarcoidosis. The median value for recovery of protein from lavage fluid was significantly higher in 21 patients with sarcoidosis than in 19 normal subjects (18 v 11 mg), while the median value for phospholipid recovery was significantly lower (4 v 1.7 mg). There were no changes in the proportions of phosphatidylcholine and phosphatidylglycerol. In addition, significantly less of the neutral lipid, cholesterol, was recovered (3.2 v 1.5 mg). The combined values of three biochemical measurements, non-phospholipid polar lipid, non-polar lipid, and protein, correctly classified all 40 subjects in our series; in a further group of nine normal subjects and 11 patients with sarcoidosis it allowed all but one normal subject to be classified correctly. These results are discussed in terms of alterations in epithelial cell function in interstitial disease.

Bronchoalveolar Lavage Fluid↗
PubMed1987

Plasma corticosterone response of turkeys to adrenocorticotropic hormone: age, dose, and route of administration effects.

Three trials were conducted to investigate plasma corticosterone (B) levels in Large White turkey hens in response to adrenocorticotropic hormone (ACTH) injections at different ages, doses, and routes of administration. In Trial 1, hens were subjected to one of the following treatments at 10, 15, and 20 wk of age: cold water immersion (5 C for 1 min), ACTH injection (10 IU/kg), or saline injection. The plasma B responses to ACTH and cold water immersion followed the same general pattern in all three age groups. Plasma B levels of hens in the ACTH treatment were depressed below control B levels until 6 h postinjection, when they became elevated. Plasma B levels of hens in the cold water treatment were either similar to or increased above those of controls by 2 h posttreatment and were depressed below control levels at .5 h posttreatment at 10 and 15 wk of age. In Trial 2, three dose levels of ACTH (1, 5, and 10 IU/kg) were injected either intramuscularly (IM) or intravenously (IV) in 10-wk-old hens. There was both a dose and route of administration effect. Of the IM-injected hens, only those in the 1-IU ACTH treatment group had significantly (P less than .05) increased plasma B levels and this occurred 4 h postinjection. However, plasma B levels of the 1 and 5-IU IV-ACTH treatment hens were significantly (P less than .05) elevated at .5 h postinjection. Plasma B of the 10-IU IM and IV-ACTH treatments were consistently, but not significantly, lower than controls through 4 h postinjection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1987

Legionnaires' disease: respiratory infections caused by Legionella bacteria.

This article provides a review of Legionnaire's Disease, a bacterial pneumonia caused by Legionella species, and of Pontiac Fever, the flu-like illness caused by these microorganisms. The authors draw on their personal experience with major human outbreaks of Legionnaire's Disease and with animal models of Legionella pneumonia. Emphasis is placed on the sources in nature from which legionellosis is acquired, the means of dissemination of bacteria, the epidemiology of human infections, the pathogenetic mechanisms of disease and host defense, the clinical manifestations, and the treatment.

Anti-Bacterial Agents↗