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Biomedical subjects

W J Martin

Publications and source records attributed to W J Martin.

At least 145 records · Page 8Linked to original sources
PubMed1988

Induction of angiotensin converting enzyme in cultured human monocytes by a factor present in the bronchoalveolar lavage fluid of sarcoidosis patients.

Human peripheral blood monocytes synthesize a low level of angiotensin converting enzyme (ACE) when cultured in vitro for six days. If cell-free bronchoalveolar lavage fluid from sarcoidosis patients was included with the monocytes during culture, the monocyte ACE level increased significantly in a dose dependent manner. In contrast, the cell-free bronchoalveolar lavage fluid from control subjects and patients with idiopathic pulmonary fibrosis or hypersensitivity pneumonitis raised basal monocyte levels little, if at all. These results suggested that sarcoid lavage fluid contains a soluble ACE-inducing factor (AIF) that was absent or present in much lower concentrations in the bronchoalveolar lavage fluid of the other patients studied. Initial attempts to characterize this AIF indicated an apparent molecular weight of greater than 5000 daltons as determined by Amicon ultrafiltration. The AIF was stable to heating at 56 degrees for 1 hour. This finding demonstrated that lavage ACE was not responsible for the AIF activity since lavage ACE is inactivated under these conditions. Gamma-interferon (macrophage-activating factor) was also eliminated as the agent responsible for AIF activity since gamma-interferon decreased rather than increased monocyte ACE. In summary, bronchoalveolar lavage fluid from sarcoid patients contains a soluble factor (AIF) that induces ACE in cultured monocytes. Action of this factor in vivo may be responsible for the increased ACE levels seen in the monocyte-derived epithelioid granuloma cells of sarcoidosis.

Adult↗
PubMed1988

Detection of human papillomavirus in normal and dysplastic tissue by the polymerase chain reaction.

Detection of human papilloma virus (HPV) types 16 and 18 in formalin-fixed, paraffin-embedded tissue by a new in vitro DNA amplification method, the polymerase chain reaction, was compared with detection with genomic DNA probes using in situ hybridization. The polymerase chain reaction replicates exponentially HPV DNA sequences present in a single 5- to 10-micron paraffin-embedded tissue section. The amplified sequences are detected with a DNA hybridization probe in a dot blot assay. The HPV polymerase chain reaction was able to detect on the average less than one HPV genome/cell as determined by tests of paraffin sections of cell pellets with known HPV genomic content. Cervical sections from 21 patients with HPV types 16, 18, or 31 as determined by in situ DNA hybridization were analyzed by the polymerase chain reaction. No disagreements between the two methods were detected. The sections comprising normal and dysplastic epithelium were further analyzed by the HPV polymerase chain reaction. The presence of virus correlated with the presence of dysplasia in the sections, though 3 of 10 normal sections contained HPV, and 1 of 21 sections with dysplasia lacked HPV 16 or 18. The polymerase chain reaction can specifically detect HPV 16 or 18 with high sensitivity from paraffin-embedded tissues.

Autoradiography↗
PubMed1988

Enhanced cytotoxic potential of alveolar macrophages from cigarette smokers.

Cigarette smoking increases the numbers and oxidative metabolism of alveolar macrophages. Increased production of superoxide (O2-) and H2O2 by alveolar macrophages may contribute to the pathogenesis of cigarette-induced lung diseases. The cytotoxicity mediated by alveolar macrophages from smokers (n = 11) and nonsmokers (n = 13) was compared in an in vitro assay in which the target cells were chromium 51-labeled lung explants. The spontaneous cellular cytotoxicity mediated by smoker macrophages was significantly greater than that of nonsmoker macrophages (cytotoxic index 20.3% +/- 1.9% compared with 5.5% +/- 0.9%, P less than 0.001). Phorbol myristate acetate significantly increased the cytotoxic index of nonsmoker macrophages but did not cause further increases in smoker macrophage killing. The antioxidants superoxide dismutase and catalase produced partial inhibition of smoker macrophage cytotoxicity, suggesting that target cell killing was mediated in part by oxidant mechanisms. Supplementation of smokers' diets with high-dose oral vitamin E failed to decrease smoker alveolar macrophage cytotoxicity. These findings demonstrate that smoker alveolar macrophages possess enhanced cytotoxic potential for normal lung parenchymal cells.

Adult↗
PubMed1988

Amiodarone pulmonary toxicity: biochemical evidence for a cellular phospholipidosis in the bronchoalveolar lavage of human subjects.

Amiodarone pulmonary toxicity represents an example of a life-threatening adverse drug reaction. Our study examined 10 subjects with amiodarone pulmonary toxicity by bronchoalveolar lavage (BAL) and determined that cells obtained by BAL demonstrated marked increases in various phospholipids compared to control subjects (n = 7). Bis monoacylglycerol phosphate and phosphatidylglycerol were significantly increased in both relative and absolute amounts (P less than .01). Several other phospholipids also were significantly increased in absolute amounts within the cell fraction. In contrast, the cell-free BAL fluid revealed only minor differences in phospholipid content. There was a strong direct correlation between concentration of amiodarone and its primary metabolite, desethylamiodarone in BAL cells (r = 0.98), and also a direct correlation between either the concentration of amiodarone or desethylamiodarone and the accumulation of phospholipids in the cells (r = 0.97, both determinations). This study indicates that findings from BAL in human subjects may provide specific and quantifiable evidence of pulmonary phospholipidosis, and suggests the concentration of the drug or its primary metabolite in BAL cells is a major determinant for the degree of phospholipid accumulation in the lung.

Amiodarone↗
PubMed1988

Importance of hydrogen peroxide in nitrofurantoin-induced cytotoxicity: evidence from an inbred catalase-deficient strain of mice.

Significant pulmonary toxicity is associated with the use of nitrofurantoin; however, the mechanism of cellular toxicity remains poorly characterized. By using a novel in vitro red blood cell (RBC) chromium 51 cytotoxicity assay, cell injury induced by nitrofurantoin was quantified with normocatalasemic BALB/c RBCs and hypocatalasemic (but otherwise genetically identical) CCN RBCs as target cell populations. Nitrofurantoin at concentrations of 2 x 10(-4) and 4 x 10(-4) mol/L resulted in significant injury to normocatalasemic RBCs with a cytotoxic index (CI) of 21.7% +/- 3.7% and 65.3% +/- 3.7% (p less than 0.05, both comparisons). This injury was substantially increased when nitrofurantoin (2 x 10(-4) and 4 x 10(-4) mol/L was incubated with hypocatalasemic RBCs, resulting in CIs of 59.0% +/- 7.4% and 91.0% +/- 2.0% respectively (p less than 0.05, both comparisons with normocatalasemic RBCs). Direct oxidant-mediated cytotoxicity induced by either H2O2 or the superoxide anion radical (as generated by xanthine-xanthine oxidase) also resulted in more significant injury to hypocatalasemic RBCs than to normocatalasemic RBCs (p less than 0.05, both comparisons). Catalase levels of CCN RBCs were approximately 7% of control BALB/c RBC values; however, the activities of superoxide dismutase and glutathione peroxidase were identical in both populations of RBCs. This model, using genetically defined target cell populations, clearly demonstrates the importance of endogenous catalase in protecting against nitrofurantoin-induced cytotoxicity, suggesting that H2O2 is a critical intermediary in the direct cell injury mediated by the drug.

Acatalasia↗
PubMed1987

Role of bronchoalveolar lavage in the assessment of opportunistic pulmonary infections: utility and complications.

We prospectively evaluated the diagnostic role of bronchoalveolar lavage in the assessment of opportunistic pulmonary infections and the incidence of associated complications in 100 immunocompromised patients during a 9-month period. Bronchoalveolar lavage was useful in detecting the presence of Pneumocystis carinii, viruses, fungi, bacteria, and mycobacteria in the lower respiratory tract. P. carinii was diagnosed by bronchoalveolar lavage in 17 patients and by open-lung biopsy in 1. Other organisms detected by lavage, lung biopsy, or both included viruses (eight patients), fungi (four patients), bacteria (six patients), and mycobacteria (three patients). Of the 100 patients studied, 33 had infectious agents detected in the lung; in 6 of these patients, more than one organism was present. Bronchoalveolar lavage detected the infectious organisms in 30 of the patients, in many of whom an open-lung biopsy was likely avoided because of the lavage studies. Although no major complications of bronchoalveolar lavage were noted in this critically ill population, five patients did require short-term mechanical ventilation after bronchoscopy. When correctly used, bronchoalveolar lavage is a safe and useful procedure for the assessment of immunocompromised subjects with suspected opportunistic pulmonary infections.

Bacterial Infections↗
PubMed1987

Intravenous tubing containing burettes can be safely changed at 72 hour intervals.

No studies testing the safety of changing intravenous systems containing in-line burettes at 72 hours in an intensive care setting have been performed. Patients entering a medical or surgical intensive care unit were alternatively assigned to have any line with an in-line burette changed at either 48 hour (105 patients) or 72 hour (65 patients) intervals. Daily quantitative cultures with a 2 ml aliquot of burette fluid were obtained. Contaminated burette fluid was detected in 60 of 1181 (5.0%, 95% confidence interval, 3.7% to 6.3%) samples from the burettes changed at 48 hour intervals, and in 40 of 901 (4.4%, 95% confidence interval, 3.0% to 5.8%) samples from 72 hour interval burettes. Significant bacterial contamination of burette fluid, defined as ten or more colonies per milliliter, occurred in only seven (0.6%) cultures from patients in the 48 hour interval group compared with only three (0.3%) cultures in the 72 hour group. None of the contaminated burette fluids was associated with a primary bacteremia. Change of in-line burettes in patients in intensive care at 72-hour intervals is safe and should result in substantial cost savings to hospitals.

Adult↗
PubMed1987

Pulmonary disease in polymyositis/dermatomyositis: a clinicopathological analysis of 65 autopsy cases.

The clinical and autopsy records of 65 patients with either polymyositis (24) or dermatomyositis (41) and pulmonary disease were reviewed. Pulmonary symptoms were recorded in 43 of the cases and included dyspnoea in 31, cough in 23, and chest pain in six. Interstitial lung disease was noted at autopsy in 27 patients; almost half of these had arthritis. Bronchopneumonia was found in 35 patients, 31 of these had received prednisone. Dysphagia was present in a similar proportion of patients with and without pneumonia. Pulmonary vasculitis was seen in five patients; pulmonary symptoms, arthritis, and raised erythrocyte sedimentation rate were present in four of these cases and all five had associated interstitial lung disease. Other pulmonary manifestations included pulmonary oedema, primary pulmonary malignancy, diffuse alveolar damage, fibrinous pleuritis, pulmonary emboli, and diaphragmatic atrophy. The mean survival after disease onset was 29 months but was much less for those with interstitial lung disease and pulmonary vasculitis.

Adult↗
PubMed1987

Bleomycin-induced pulmonary endothelial cell injury: evidence for the role of iron-catalyzed toxic oxygen-derived species.

Bleomycin, an effective cancer chemotherapeutic agent, is associated with serious pulmonary toxicity. As an in vitro model of bleomycin pulmonary toxicity, this study examined the ability of bleomycin to injure chromium 51-labeled bovine pulmonary artery endothelial (BPAE) cells in an 18-hour cytotoxicity assay. The data indicate that bleomycin-mediated injury to cultured BPAE cells can be quantified by 51Cr release, expressed as cytotoxic index (CI). Bleomycin-mediated injury to 51Cr-labeled BPAE cells (CI 19.4 +/- 1.6) could be significantly reduced by the iron chelator deferoxamine, 10(-3) mol/L (CI 7.5 +/- 1.1, P less than 0.001), but not by ethylenediaminetetraacetic acid, 10(-5) mol/L (CI 19.8 +/- 2.2). Similarly, bleomycin-mediated injury to BPAE cells (monitored by lactate dehydrogenase release) with a CI 27.1 +/- 4.8 could be reduced by 10(-3) mol/L deferoxamine to CI 10.5 +/- 2.6 (P less than 0.01). In contrast, hyperoxia (95% O2) accelerated bleomycin (1 to 100 mU/ml) toxicity to BPAE cells (P less than 0.01, all comparisons). This study suggests that bleomycin-induced injury of pulmonary endothelial cells may be dependent in part on two critical factors in the cellular environment: the availability of iron to the cell and the ambient O2 concentration.

Animals↗
PubMed1987

Iprindole reverses the lamellar body deficiency of cultured L-2 cells. Possible implications in the reversal of surfactant deficiency.

Type II alveolar epithelial cells in long-term culture typically lose the ability to synthesize surfactant together with a loss of the characteristic lamellar bodies in the cytoplasm of the cells. Iprindole, a cationic amphiphilic drug, induces lamellar body formation in cultured L-2 cells, a cell line derived from rat Type II cells, but devoid of lamellar bodies. With concentrations of 10(-7)-10(-5) M iprindole, which approximate therapeutic plasma concentrations in human subjects, the drug induced the formation of lamellar bodies within 8 hours of incubation. This effect on cell morphology was rapidly lost after withdrawal of the drug. At concentrations of iprindole which induced lamellar body formation, there was a significant increase in phospholipid content of the L-2 cells as well as an increase in disaturated phosphatidylcholine, an important constituent of surfactant. These studies suggest that the use of drugs such as iprindole may represent a novel approach in the augmentation of phospholipid (and possibly surfactant) content of Type II cells in the lung.

Animals↗
PubMed1986

Rapid detection of cytomegalovirus in bronchoalveolar lavage specimens by a monoclonal antibody method.

Cytomegalovirus (CMV), a common cause of pneumonia in immunocompromised subjects, is conventionally diagnosed in the laboratory by tube cell culture assays or by detection of characteristic inclusions in histologic sections. Of 160 immunocompromised patients, CMV infection was diagnosed in 19 subjects by bronchoalveolar lavage (BAL), using a monoclonal antibody directed against an early nuclear antigen of the virus. Cytospin preparations from BAL and MRC-5 cell cultures inoculated with the BAL specimens yielded positive results for 6 (31.6%) and 18 (94%) of the 19 subjects, respectively, within hours of the bronchoscopic procedure, whereas conventional tube cell cultures were positive for 11 of the 19 subjects (57.9%) only after an average of 9.3 days. The monoclonal antibody method permitted easy and rapid detection of CMV in BAL specimens.

Adult↗
PubMed1986

Chronic nitrofurantoin reaction associated with T-lymphocyte alveolitis.

Nitrofurantoin use was associated with the development of severe interstitial lung disease which was characterized by bronchoalveolar lavage with a marked increase in lymphocytes to 60 percent (compared to normal of 7 +/- 1 percent). Lymphocytes were predominantly of the T-helper subset. Lavage may prove useful in the assessment of the immune response in drug-induced lung disease.

Aged↗
PubMed1986

Oxidant-mediated ciliary dysfunction. Possible role in airway disease.

The effects of reactive species of oxygen on the airway are not well known. This study examined the effects of hydrogen peroxide (H2O2) on the structure and function of the airway epithelium. Tracheal rings were prepared from 200 g male rats. Damage to the airway epithelium was assayed by monitoring the ciliary beat frequency, the release of 51Cr, and histology. H2O2 at concentrations of 1.0 mM and above caused a very rapid decrease in ciliary beat frequency. After ten minutes' exposure to 1.0 mM, the ciliary beat frequency was 72 +/- 20 percent of control. Release of 51Cr was a less sensitive measure with significant release occurring after four hours of exposure to ciliotoxic concentrations of H2O2. Histologic changes were not evident within the experimental time period. All toxic effects of H2O2 were completely blocked by catalase. This study shows that H2O2 causes a rapid decline in ciliary activity and suggests that oxidant-mediated ciliary dysfunction could play a role in the pathogenesis of airway disease. The ciliary beat frequency provides a sensitive, physiologically relevant parameter for the in vitro study of these diseases.

Animals↗
PubMed1985

Markedly decreased expression of class I histocompatibility antigens, protein, and mRNA in human small-cell lung cancer.

We have found markedly deficient expression of the class I major histocompatibility antigens HLA-A,B,C and beta 2m on human small-cell lung cancer (SCLC) lines and fresh tumor samples. The deficit of HLA-A,B,C and beta 2-microglobulin (beta 2m) antigen expression was demonstrated with both radiobinding assays and indirect immunofluorescence assays. Immunoprecipitation of metabolically labeled cells with antibodies to class I antigens showed most SCLC lines to have synthesized almost no beta 2m and HLA-A,B,C proteins. Northern blot analysis, using human HLA-A,B, and beta 2m cDNA probes, showed that almost all SCLC lines tested had markedly decreased amounts of HLA and beta 2m mRNA, but both gene products could be induced with interferon treatment of SCLC lines. We conclude that human SCLC, in contrast to other lung cancer types, is characterized by greatly reduced transcription of HLA-A,B,C and beta 2m genes, which suggests the existence of a mechanism for evading the host immune response to the tumor and of an E1a-like product in this type of tumor cell.

Antigens, Surface↗
PubMed1985

Determination of cimetidine and metabolites in plasma by reversed-phase high-performance liquid chromatographic radial compression technique.

A high-performance liquid chromatographic method for the detection of cimetidine and its metabolites in plasma was developed which has a short analysis time and good resolution. The total analysis time was approximately 11 min. The standard curves were linear over the concentrations used for all compounds and the sensitivity limits were good. The coefficient of variation for within-day and between-day analysis was less than 4.2% for all compounds with the exception of guanyl urea cimetidine, which was approximately 10%. Currently, this assay is being used in a pharmacokinetic study of plasma and gastric aspirate samples obtained from a critically ill pediatric population.

Biotransformation↗
PubMed1985

Repeat subculture of known positive blood cultures: costly and ineffective in detecting polymicrobial bacteremias.

Reincubation and subsequent subculture at 72 h of previously positive blood cultures failed to demonstrate an increase in detection of polymicrobial bacteremia as has been previously reported. These procedures increased the cost of blood cultures between 140-192% without yielding new organisms. No new information was gained in 94.7% of cultures and, in 11.1% of the cultures, less information was obtained either because the cultures were sterile or because the original organisms could not be reisolated.

Bacteria↗