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Biomedical subjects

L L Fan

Publications and source records attributed to L L Fan.

At least 19 recordsLinked to original sources

Chronic ethanol feeding alters the epithelial cell proliferation and apoptosis in rat gastric mucosa.

We developed a chronic drinking rat model to investigate the long-term effects of ethanol feeding on cell proliferation and apoptosis in rat stomach. Adult male Sprague-Dawley (SD) rats received either an isocaloric control or drinking water containing 6% (v/v) ethanol as their only water intake for 1, 3, 7, 14 and 28 days. At the end of each feeding period, animals were sacrificed and the stomach was dissected for the sample preparation. The cell proliferation and apoptosis in gastric mucosa of rats in different groups were analyzed by flow cytometer, immunohistochemistry and computer image analysis. In the flow cytometric study, compared with the control, the cell apoptosis in gastric mucosa of the rats was enhanced during the exposure to the ethanol in 3rd to 28th day. Otherwise the cell proliferation was increased in 3rd to 14th days, and decreased in 28th days, respectively. The results were confirmed by immunohistochemistry and computer image analysis studied. This finding suggested that short-term chronic adequate alcohol intake may enhance the cell turnover of gastric mucosa. Long-term stimulus with the low concentration ethanol may cause the impairment of the cell turnover function of the gastric mucosa and may be one of the mechanisms underlying the gastric pathology associated with alcohol abuse.

Alcohol Drinking↗

Time course of hemosiderin production by alveolar macrophages in a murine model.

STUDY OBJECTIVES: The diagnosis of alveolar hemorrhage is assisted by the presence of hemosiderin-laden macrophages (HLMs) in the BAL fluid or lung tissue. Despite the importance of this diagnostic method in clinical settings, limited information is available on the formation and clearance of HLMs as a function of time. The objectives of this study are to determine the time course of HLMs within the BAL and lung tissue, and to evaluate the effect of a single blood aspiration on the recruitment of inflammatory cells within the BAL. DESIGN: Under light anesthesia, Balb/c mice received a single intranasal instillation of species-specific blood (50 microL). Control animals received heparinized sterile saline solution in a similar manner. At several time points after blood aspiration, BAL was recovered for cell differentials and determination of HLMs. The time course for HLMs was also established in the lung tissue. RESULTS: Hemosiderin staining within alveolar macrophages was first detected in the BAL and lung tissue at day 3, peaked at day 7, and persisted through 2 months. The analysis of the BAL revealed an increased number of total cells, with an acute inflammatory reaction that resolved within 2 weeks. CONCLUSIONS: Our findings demonstrate the validity of this model for the study of HLM production after blood aspiration. Additional work using animal models of lung hemorrhage is needed to further characterize the cellular events leading to clearance of erythrocytes within the lung.

Animals↗

Pulmonary infiltrates with eosinophilia syndromes in children.

Pulmonary infiltrates with eosinophilia (PIE) are a group of heterogeneous disorders having the common findings of lung disease and eosinophilia in the peripheral blood, bronchoalveolar lavage fluid, or pulmonary interstitium. Eleven cases of PIE syndromes were identified through a retrospective and prospective chart review: drug-induced (2), acute eosinophilic pneumonia (3), infant pulmonary eosinophilia (2), parasite-induced (2), Churg-Strauss syndrome (1), and atypical chronic PIE (1). Patient demographics, clinical presentation, and disease severity varied considerably among groups. Therapeutic interventions included bronchodilators (10), oxygen (7), corticosteroids (9), and mechanical ventilation (3). A single patient with acute eosinophilic pneumonia died. Our experience suggests that PIE syndromes are rare in childhood and that clinical presentation can vary widely. Because of the potential for significant morbidity and mortality, aggressive diagnostic evaluations are warranted, particularly in children with respiratory failure of unknown etiology.

Adolescent↗

A novel diagnostic method for pulmonary aspiration in a murine model. Immunocytochemical staining of milk proteins in alveolar macrophages.

Aspiration of foreign material into the lungs has been implicated in the etiology of a variety of pulmonary disorders. Although aspiration is a common clinical problem, its diagnosis represents a major challenge due to the lack of sensitive and/or specific tests. In this study, we evaluated the sensitivity and specificity of a novel diagnostic method in a murine model of milk aspiration. Under light anesthesia, BALB/c mice received either single or repeated intranasal instillation of milk. Control animals received sterile physiologic saline or were infected with respiratory pathogens in a similar manner. After isolation and cannulation of the trachea, mouse lungs were lavaged with PBS at various time points after the last aspiration event. Cells were recovered for Oil Red O (ORO) staining as well as immunocytochemistry for milk proteins: alpha-lactalbumin and beta-lactoglobulin. After single aspiration of milk, a large number of alveolar macrophages displayed a strong immunoreactivity for alpha-lactalbumin for 2-96 h. After single and repeated aspiration, the percentage of positive cells for alpha-lactalbumin was significantly higher when compared with ORO staining at 24, 48, and 72 h (p < 0.05). No immunoreactivity for milk proteins was found in alveolar macrophages obtained from our control groups. These findings demonstrate that immunocytochemical staining of milk proteins within alveolar macrophages represents a novel, sensitive, and specific test for the diagnosis of aspiration in a murine model.

Animals↗

Recurrent milk aspiration produces changes in airway mechanics, lung eosinophilia, and goblet cell hyperplasia in a murine model.

Recurrent aspiration of milk into the respiratory tract has been implicated in the pathogenesis of a variety of inflammatory lung disorders including asthma. However, the lack of animal models of aspiration-induced lung injury has limited our knowledge of the pathophysiological characteristics of this disorder. This study was designed to evaluate the effects of recurrent milk aspiration on airway mechanics and lung cells in a murine model. Under light anesthesia, BALB/c mice received daily intranasal instillations of whole cow's milk (n = 7) or sterile physiologic saline (n = 9) for 10 d. Respiratory system resistance (Rrs) and dynamic elastance (Edyn,rs) were measured in anesthetized, tracheotomized, paralyzed and mechanically ventilated mice 24 h after the last aspiration of milk. Rrs and Edyn,rs were derived from transrespiratory and plethysmographic pressure signals. In addition, airway responses to increasing concentrations of i.v. methacholine (Mch) were determined. Airway responses were measured in terms of PD(100) (dose of Mch causing 100% increase from baseline Rrs) and Rrs,max (% increase from baseline at the maximal plateau response) and expressed as % control (mean +/- SE). We found recurrent milk aspiration did not affect Edyn and baseline Rrs values. However, airway responses to Mch were increased after milk aspiration when compared with control mice. These changes in airway mechanics were associated with an increased percentage of lymphocytes and eosinophils in the bronchoalveolar lavage, mucus production, and lung inflammation. Our findings suggest that recurrent milk aspiration leads to alterations in airway function, lung eosinophilia, and goblet cell hyperplasia in a murine model.

Administration, Intranasal↗

Selective inhibition of inducible nitric oxide in ischemia-reperfusion of rat small intestine.

PURPOSE: We investigated the role of constitutive and inducible nitric oxide (NO) synthases in intestinal ischemia-reperfusion (I/R) injury by observing the alterations in hemodynamics and intestinal microcirculation in response to I/R in rats, with or without inhibitors of NO synthases. METHODS: Adult male Sprague-Dawley rats (n = 9/group) received a standard I/R procedure alone: I/R plus intravenous administration of aminoguanidine (an inhibitor of inducible NO synthase); I/R plus L-NAME (NG-nitro-L-arginine methyl ester, an inhibitor of constitutive and inducible NO synthase); IR + L-Arg (L-arginine, an NO precursor); or a sham operation plus the vehicle. The I/R procedure was performed by clamping the perfusion vessels of a segment of the terminal ileum, and medication was administered intravenously before and after intestinal ischemia. The intestinal perfusion and leukocyte-endothelial interactions were evaluated with in vivo microscopy and laser Doppler flowmetry. Surface expression of CD11b (an adhesion molecule) of circulating granulocytes was measured with flow cytometry. RESULTS: Intestinal I/R produced circulatory alterations, intestinal microcirculatory derangement, energy depletion, and lipid peroxidation. Aminoguanidine significantly attenuated the reperfusion-related depression of mean arterial pressure (MAP), the decrease in intestinal perfusion index, the decrease in tissue ATP preservation, the increase in tissue malondialdehyde (MDA) level, and the expression of CD11b of circulating granulocytes. Administration of L-NAME had only minor and transient effects on reperfusion-related changes of MAP, intestinal flux, numbers of adherent leukocytes, and CD11b expression, but had some protective effects on tissue MDA and adenosine triphosphate levels and flow velocity. L-Arg further decreased the MAP but did not affect reperfusion-related variables. CONCLUSIONS: Our results show that the selective inhibition of inducible NO synthase by aminoguanidine attenuates the hemodynamic and microcirculatory derangement that results from intestinal I/R.

Animals↗

[Preventive effect of cardiomyopeptidin on rat heart injured by ischemia-reperfusion].

OBJECTIVE: To investigate the preventive effect of cardiomyopeptidin of small molecular weight polypeptide on rat hearts injured by ischemia-reperfusion. METHODS: In a rat model injured by ischemia-reperfusion in the heart, observation was made on the influence of cardiomyopeptidin on the activities of creatine kinase (CK) and lactate dehydrogenase(LDH), as well as on the content of MDA in plasma after the preventive drug was used. RESULTS: Cardiomyopeptidin could obviously prevent the injury caused by ischemia-reperfusion, reduce the activities of CK and LDH and the content of MDA in a dose-dependent manner. CONCLUSION: Cardiomyopeptidin has a preventive effect on myocardium injured by ischemia-reperfusion and this may be related to its reducing the release of myocardial enzyme and anti-lipoperoxidation.

Animals↗

Neutrophil elastase inhibitor (ONO-5046) attenuates reperfusion-induced hepatic microcirculatory derangement, energy depletion and lipid peroxidation in rats.

UNLABELLED: Microcirculatory derangement, energy depletion, and lipid peroxidation are associated with the development of ischemia-reperfusion injury in the liver. This study investigated the effects of a neutrophil elastase inhibitor (ONO-5046) on hepatic ischemia-reperfusion injury. Adult, male Sprague-Dawley rats were divided into four treatment groups: 1) sham-operated control (laparotomy only, no ischemia) and saline injection (1 mL/kg), n = 6; 2) ischemia control (1-h ischemia, 2-h reperfusion) and saline injection (1 mL/kg), n = 6; 3) intravenous injection with ONO-5046 at a dose of 1 mg/kg 5 min before ischemia and immediately after reperfusion plus 1-h ischemia and 2-h reperfusion, n = 6; and 4) intravenous injection with ONO-5046 at a dose of 10 mg/kg 5 min before ischemia and immediately after reperfusion plus 1-h ischemia and 2-h reperfusion, n = 6. A laser-Doppler flowmeter and in vivo microscopy were used to investigate hepatic microcirculation. Tissue malondialdehyde (MDA) and adenosine triphosphate (ATP) levels were determined at the end of the experiment. RESULTS: Compared with ischemia alone, ONO-5046 significantly reduced the extent of microcirculatory and hemodynamic derangement after ischemia-reperfusion. ONO-5046 at both doses significantly attenuated decreases in mean arterial pressure. ONO-5046 lessened adherent leukocyte count and improved flow velocity in the sinusoids and postsinusoidal venules. ONO-5046 at the dose of 10m/kg reduced MDA (1.97 +/- 0.54 micromol/g protein vs. 3.58 +/- 1.21 micromol/g protein in the ischemia and reperfusion group) and increased ATP levels (2.62 +/- 0.19 micromol/g wet wt vs. 0.57 +/- 0.37 pmol/g wet wt in the ischemia and reperfusion group), whereas ONO-5046 at a smaller dose (1 mg/kg) had lesser but significant effects on MDA and ATP alterations. This study demonstrates that treatment with ONO-5046, a neutrophil elastase inhibitor, can ameliorate ischemia-reperfusion injury of the rat liver.

Adenosine Triphosphate↗

Isolation of Stachybotrys from the lung of a child with pulmonary hemosiderosis.

Recently, Stachybotrys atra, a toxigenic fungus, has been implicated as a potential cause of pulmonary hemorrhage/hemosiderosis in infants living in water-damaged homes. Although epidemiologic evidence supports this association, neither the organism nor its toxic products has ever been recovered from humans. We report the first case in which Stachybotrys was isolated from the bronchoalveolar lavage fluid of a child with pulmonary hemorrhage. Stachybotrys was also recovered from his water-damaged home. The patient recovered completely after his immediate removal from the environment and subsequent cleaning of his home. This case provides further evidence that this fungus is capable of causing pulmonary hemorrhage in children.

Air Microbiology↗

Pediatric diffuse lung disease: diagnosis and classification using high-resolution CT.

OBJECTIVE: Our purpose was to categorize high-resolution CT findings in children with diffuse lung disease and to evaluate the accuracy of diagnoses made using CT. MATERIALS AND METHODS: The chest radiographs and high-resolution CT scans of 20 children (1-16 years old; median, 9 years old) with biopsy-proven chronic diffuse lung diseases were reviewed separately by two independent chest radiologists. Thirteen types of diffuse lung disease were included in the study. Radiographic and CT features were noted, and three choices of diagnosis were recorded, with the confidence level. RESULTS: Diagnoses were made with a high degree of confidence (definite or probable) in 25 of 40 interpretations of CT scans, compared with only five of 40 interpretations of chest radiographs (p < .001). Fourteen (56%) of the 25 confident first-choice diagnoses on CT scans were correct, compared with two (40%) of the five interpretations on chest radiographs. Diseases were classified as belonging to one of five distinct groups on the basis of dominant CT features. Airway disease (n = 5) (bronchiolitis obliterans or bronchocentric granulomatosis) showed geographic hyperlucency on CT. Septal disease (n = 4) (lymphangiomatosis, hemangiomatosis, or microlithiasis) showed septal thickening. Infiltrative lung disease (n = 7) (desquamative interstitial pneumonitis, hypersensitivity pneumonitis, or lymphoid interstitial pneumonitis) showed ground-glass opacity. Air-space disease (n = 3) (aspiration, vasculitis, or bronchiolitis obliterans organizing pneumonia) showed lung consolidation. Langerhans' histiocytosis (n = 1) showed cysts and nodules. Surprisingly little overlap was seen among these groups. CONCLUSION: CT increases the level of diagnostic confidence for pediatric infiltrative lung disease, improves diagnostic accuracy, and provides a useful classification system.

Child↗

Evaluation of a diagnostic approach to pediatric interstitial lung disease.

OBJECTIVE: To evaluate the value of a systematic approach to the diagnosis of pediatric interstitial lung disease (ILD). METHODS: In this descriptive, observational, prospective study, we evaluated 51 children presenting with ILD of unknown etiology during a 3-year period. Specific clinical information regarding history, physical examination, diagnostic evaluation, and final diagnosis was recorded on each patient. RESULTS: A specific diagnosis was established by history and physical examination alone in 1 patient, noninvasive tests alone in 8 others, and invasive tests, including lung biopsy, in another 26. Of the remaining patients, 8 had a suggestive diagnosis, and 8 had no specific diagnosis. CONCLUSIONS: A systematic approach to the diagnosis of pediatric ILD is useful, and not all patients need lung biopsy for diagnosis.

Adolescent↗