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Biomedical subjects

A Slutsky

Publications and source records attributed to A Slutsky.

9 recordsLinked to original sources
PubMed2006

Crystallization and preliminary X-ray analysis of cytochrome c nitrite reductase from Thioalkalivibrio nitratireducens.

A novel cytochrome c nitrite reductase (TvNiR) was isolated from the haloalkalophilic bacterium Thioalkalivibrio nitratireducens. The enzyme catalyses nitrite and hydroxylamine reduction, with ammonia as the only product of both reactions. It consists of 525 amino-acid residues and contains eight haems c. TvNiR crystals were grown by the hanging-drop vapour-diffusion technique. The crystals display cubic symmetry and belong to space group P2(1)3, with unit-cell parameter a = 194 A. A native data set was obtained to 1.5 A resolution. The structure was solved by the SAD technique using the data collected at the Fe absorption peak wavelength.

Crystallization↗
PubMed2000

Mechanical strain and dexamethasone selectively increase surfactant protein C and tropoelastin gene expression.

Physical forces derived from fetal breathing movements and hormones such as glucocorticoids are implicated in regulating fetal lung development. To elucidate whether the different signaling pathways activated by physical and hormonal factors are integrated and coordinated at the cellular and transcriptional levels, organotypic cultures of mixed fetal rat lung cells were subjected to static culture or mechanical strain in the presence and absence of dexamethasone. Tropoelastin and collagen type I were used as marker genes for fibroblasts, whereas surfactant protein (SP) A and SP-C were used as marker genes for distal epithelial cells. Mechanical strain, but not dexamethasone, significantly increased SP-C mRNA expression. Tropoelastin mRNA expression was upregulated by both mechanical strain and dexamethasone. No additive or synergistic effect was observed when cells were subjected to mechanical stretch in the presence of dexamethasone. Neither mechanical strain nor dexamethasone alone or in combination had any significant effect on the expression of SP-A mRNA. Dexamethasone decreased collagen type I mRNA expression, whereas mechanical strain had no effect. The increases in tropoelastin and SP-C mRNA levels induced by mechanical strain and/or dexamethasone were accompanied by increases in their heterogeneous nuclear RNA. In addition, the stretch- and glucocorticoid-induced alterations in tropoelastin and SP-C mRNA expression were abrogated with 10 microg/ml actinomycin D. These findings suggest that tropoelastin and SP-C genes are selectively stimulated by physical and/or hormonal factors at the transcriptional level in fetal lung fibroblasts and distal epithelial cells, respectively.

Animals↗
PubMed2000

A novel cell culture model for studying ischemia-reperfusion injury in lung transplantation.

Many cell culture models have been developed to study ischemia-reperfusion injury; however, none is specific to the conditions of lung preservation and transplantation. The objective of this study was to design a cell culture model that mimics clinical lung transplantation, in which preservation is aerobic and hypothermic. A549 cells, a human pulmonary epithelial cell line, were preserved in 100% O(2) at 4 degrees C for varying periods in low-potassium dextran glucose solution, simulating ischemia, followed by the introduction of warm (37 degrees C) DMEM plus 10% fetal bovine serum to simulate reperfusion. Cultures were assayed for cell attachment and viability. Sequential extension of ischemic times to 24 h showed a time-dependent loss of cells. There was a further decrease in cell number after simulated reperfusion. Cell detachment was due mainly to cell death, as determined by cell viability. The effects of chemical components such as dextran 40 and calcium in the preservation solution and various preservation gas mixtures were examined by use of this model system. With its design and validation, this model could be used to study mechanisms related to ischemia-reperfusion injury at the cellular and molecular level.

Cell Adhesion↗
PubMed1998

Effect of inhaled furosemide in acute asthma.

We assessed the acute bronchodilator effect of nebulized furosemide when added to conventional therapy of acute emergency department (ED) asthma. Using a double-blind design, 42 patients with acute asthma were randomized to receive 2.5 mg nebulized salbutamol and either 40 mg of nebulized furosemide or saline solution. We recorded clinical variables (respiratory rate, heart rate, and pulsus paradoxus) and peak expiratory flow rates (PEFR) before and 15 and 30 min after therapy. We found no significant difference in PEFR between salbutamol/furosemide and salbutamol/saline-treated patients 15 and 30 min following inhalation. Other endpoints were equally unaffected. However, when we examined separately those patients whose exacerbations were of relative short duration (< 8 hr), PEFR improved significantly more in the furosemide-treated group. At 15 min, PEFR increased by 82 +/- 48% in the furosemide group compared to 35 +/- 40% in the control group (p = 0.03), an effect that was also evident at 30 min when PEFR had increased by 113 +/- 49% in the furosemide group versus 61 +/- 35% in the control group (p = 0.014). Respiratory rate, heart rate, and pulsus paradoxus improved with no differences between the groups. The beneficial effect of furosemide was not evident in patients who reported more prolonged duration (> 8 hr) of asthmatic symptoms. The response to furosemide appeared to be unrelated to concomitant ED therapy with corticosteroids, to baseline pulmonary function, or to patient demographic variables. We conclude that furosemide may offer additive bronchodilator benefits in acute naturally occurring asthma of relative short duration.

Adult↗
PubMed1994

Liver abscess in Crohn's disease.

Liver abscess is a rare but serious complication of Crohn's disease. Intra-abdominal abscesses, fistulous disease, and metronidazole or steroid therapy have all been reported to be important predisposing factors in the pathogenesis of the disease, and the mortality has been reported to be high. We report six patients who developed a liver abscess as a complication of Crohn's disease. Three patients presented with a liver abscess as the first manifestation of Crohn's disease and two others had quiescent disease at presentation. The diagnosis was delayed by 1-8 wk after the onset of fever because of the paucity of signs indicating a hepatic infection. None of the patients had intra-abdominal abscesses, active fistulas, or metronidazole therapy before the onset of symptoms. The only predisposing conditions identified were two minor skin infections in patients developing staphylococcal liver abscesses. Nonoperative catheter drainage was successful in four of the six patients. One patient required surgical placement of drains, and the patient with the longest delay before diagnosis required hepatic lobectomy because of extensive necrosis. Shaking chills, fever with leukocytosis, and an elevated alkaline phosphatase are suggestive of a liver abscess and should prompt an ultrasound examination. Catheter drainage with antibiotic therapy is effective if the liver abscess is diagnosed before extensive necrosis has occurred. Minor skin infections may predispose to staphylococcal liver abscess in some cases.

Adolescent↗
PubMed1993

Genetic diversity among strains of Mycobacterium avium causing monoclonal and polyclonal bacteremia in patients with AIDS.

To define the genetic diversity among Mycobacterium avium isolates from human immunodeficiency virus-infected patients, specimens were cultured prospectively, and isolates obtained from 14 patients (4 with positive blood, stool, and sputum; 6 with positive blood and stool; 3 with positive blood only; and 1 with positive stool only) were studied. Both serotyping and ribotyping had limited ability to discriminate among isolates from different patients, whereas the distinctive restriction fragment profiles resolved by pulsed-field gel electrophoresis indicated that each patient was infected by a unique strain. Of the 13 bacteremic patients, 2 were bacteremic concurrently with 2 distinct strains. The fact that M. avium isolates from AIDS patients exhibit considerable genetic diversity supports the hypothesis that the infection is acquired from various environmental sources. Further, individual patients are not infrequently bacteremic with > 1 strain simultaneously, which may need to be considered in protocols for the diagnosis and management of M. avium disease.

AIDS-Related Opportunistic Infections↗
PubMed1990

The effect and optimal time of administration of verapamil on lung preservation.

Calcium channel blockers have recently been shown to improve pulmonary and myocardial preservation. The effect of verapamil on hypothermic lung preservation was investigated using an isolated ventilated rabbit lung perfusion model. In phase 1, preserved lungs were not flushed prior to extraction. Four groups of five animals were studied: group 1 (no verapamil), group 2 (verapamil administration prior to extraction), group 3 (verapamil at reperfusion only), group 4 (verapamil both prior to extraction and at reperfusion). In phase 2, two groups of five animals received pulmonary artery flush with low potassium (4 mmol/L), 2% low-potassium dextran (LPD) solution; group 1 (without verapamil), group 2 (flush and reperfusion with verapamil). As in phase 1, lungs were stored for 30 hr at 10 degrees C prior to reperfusion. In phase 3, the protocol was identical to phase 2, except that the storage time was extended to 48 hr. PO2 (mean +/- SE) of effluent blood in lungs treated with verapamil prior to extraction (122.8 +/- 5.0 mmHg) was significantly increased in comparison with lungs not receiving verapamil (69.0 +/- 3.3 mmHg) or only receiving verapamil at the time of reperfusion (87.1 +/- 11.9 mmHg). Gas exchange after 30 hr storage was equivalent in lungs flushed with LPD with or without verapamil. However verapamil did provide an advantage when preservation times were extended to 48 hr (62.3 +/- 8.5 mmHg, 46.9 +/- 2.3 mmHg). Verapamil administered prior to lung extraction provides better lung function following preservation, but has benefit over LPD flush only with extended periods of preservation (48 hr).

Animals↗
PubMed1986

Celiprolol, atenolol and propranolol: a comparison of pulmonary effects in asthmatic patients.

Celiprolol, a new beta-adrenoceptor antagonist, blocks serotonin- and methacholine-mediated bronchoconstriction in animals, even in the presence of propranolol. In two, randomized, placebo-controlled, 5-way crossover trials, the pulmonary effects of celiprolol 200 and 400 mg, propranolol 40 mg and atenolol 100 mg were compared in 34 asthmatic patients. Pulmonary function was measured after single doses of each agent, and again following subsequent, graded doses of albuterol or isoproterenol aerosol. Changes in one-second forced expiratory volume (FEV1) and maximal midexpiratory flow rate (FEF25-75) prior to albuterol or isoproterenol were positive after placebo and both doses of celiprolol. Propranolol, and to a lesser extent, atenolol, caused significant reductions in both measures of pulmonary function. Overall changes in FEV1 following each drug plus isoproterenol or albuterol were positive, in the rank order, celiprolol approximately placebo greater than atenolol greater than propranolol. Propranolol pretreatment caused a significant reduction in the effect of bronchodilator. Unlike atenolol and propranolol, celiprolol was highly bronchosparing and did not antagonize sympathomimetic bronchodilators.

Adrenergic beta-Antagonists↗