FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy.

Gene copy number alterations, tumor cell stemness, and the development of platinum chemotherapy resistance contribute to high-grade serous ovarian cancer (HGSOC) recurrence. Stem phenotypes involving Wnt-β-catenin, aldehyde dehydrogenase activities, intrinsic platinum resistance, and tumorsphere formation are here associated with spontaneous gains in , and (KMF) genes in a new aggressive murine model of ovarian cancer. Adhesion-independent FAK signaling sustained KMF and human tumorsphere proliferation as well as resistance to cisplatin cytotoxicity.

Insulin-induced lipid body accumulation is accompanied by lipid remodelling in model mast cells.

Mast cell lipid bodies are key to initiation, maintenance and resolution of inflammatory responses in tissue. Mast cell lines, primary bone marrow-derived mast cells and peripheral blood basophils present a 'steatotic' phenotype in response to chronic insulin exposure, where cells become loaded with lipid bodies. Here we show this state is associated with reduced histamine release, but increased capacity to release bioactive lipids.

Fluorescent Triazole Urea Activity-Based Probes for the Single-Cell Phenotypic Characterization of Staphylococcus aureus.

Phenotypically distinct cellular (sub)populations are clinically relevant for the virulence and antibiotic resistance of a bacterial pathogen, but functionally different cells are usually indistinguishable from each other. Herein, we introduce fluorescent activity-based probes as chemical tools for the single-cell phenotypic characterization of enzyme activity levels in Staphylococcus aureus. We screened a 1,2,3-triazole urea library to identify selective inhibitors of fluorophosphonate-binding serine hydrolases and lipases in S.

Transcriptional and Functional Plasticity Induced by Chronic Insulin Exposure in a Mast Cell-Like Basophilic Leukemia Cell Model.

Objective: Secretory granules (SG) and lipid bodies (LB) are the primary organelles that mediate functional responses in mast cells. SG contains histamine and matrix-active proteases, while LB are reservoirs of arachidonic acid and its metabolites, precursors for rapid synthesis of eicosanoids such as LTC. Both of these compartments can be dynamically or ontologically regulated, with metabolic and immunological stimuli altering lipid body content and granule numbers responding to contextual signals from tissue.

Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial.

Importance: Eritoran is a synthetic lipid A antagonist that blocks lipopolysaccharide (LPS) from binding at the cell surface MD2-TLR4 receptor. LPS is a major component of the outer membrane of gram-negative bacteria and is a potent activator of the acute inflammatory response.

Objective: To determine if eritoran, a TLR4 antagonist, would significantly reduce sepsis-induced mortality.

Permanent respiratory impairment and upper airway symptoms despite clinical improvement in patients with reactive airways dysfunction syndrome.

We previously reported clinical findings for 19 patients who developed symptomatic airways hyperactivity following an acute exposure to an inhaled irritant and who were given the diagnosis of reactive airways dysfunction syndrome (RADS). We now report on nine of these patients who have been followed for a mean of 9 years, allowing assessment of function, symptoms, and comorbidity beyond the early phase of acute airway injury and inflammation. None of the patients have resolved their airway hyper-responsiveness and symptoms completely, although only in one subject, who had a premorbid history of asthma, has the condition progressed.

Concentric tracheal and subglottic stenosis. Management using the Nd-YAG laser for mucosal sparing followed by gentle dilatation.

Treatment of tracheal stenosis varies with the type and extent of the disease. Tracheostomy with stents, end-to-end anastomosis, or extensive reconstructive procedures often is required, especially when tracheomalacia is present. High recurrence rate is associated with relatively less invasive endotracheal treatments, such as bougie dilatation or total laser ablation.

Demographics of long-term ventilator-dependent patients outside the intensive care unit.

Continued management of clinically stable ventilator-dependent patients in the intensive care unit is controversial, given the expense and limitations of intensive care resources. A proposed alternative, which could reduce the cost of care, has been "noninvasive respiratory units." We review the management of 99 ventilator-dependent patients on routine nursing floors to define our case mix and the outcome of long-term care.

Hypersensitivity pneumonitis versus invasive pulmonary aspergillosis: two cases with unusual pathologic findings and review of the literature.

Two brothers simultaneously exposed to moldy hay, who developed differing forms of Aspergillus-related lung disease, are presented. Patient 1 developed a true case of hypersensitivity lung disease, whereas his brother developed invasive aspergillosis with bronchoalveolar lavage eosinophilia and unusual pathologic features including tissue eosinophilia. The possible overlap between hypersensitivity pneumonitis and invasive aspergillosis in the immunocompetent host is discussed.

Quantitation of abnormal 67Ga uptake in pulmonary interstitial vascular disease--a new test to detect diffuse lung disease.

Gallium 67 has been used as a modality to diagnose and follow the clinical course of diseases such as tumors, infections, inflammatory disorders, and interstitial lung disease. It has been appreciated, however, that mild to moderate changes in scan activity, when these disorders are followed over time, are less than optimal. SPECT (single-photon emission computed tomography) scanning is a new technique designed to obviate this problem.

Lymphangiomyomatosis--newer concepts in pathogenesis and management--case reports.

Lymphangiomyomatosis was first reported more than forty years ago. Although its incidence is rare, its occurrence is being increasingly recognized and has been the subject of a growing number of cases reports in recent years. This study adds 2 more cases to the file.

The effects of steroid therapy on pulmonary hypertension secondary to fibrosing mediastinitis.

Mediastinal fibrosis, a rare cause of pulmonary hypertension, may produce cough, dyspnea, and hemoptysis. Steroid therapy has been suggested for individuals with progressive symptoms, but data demonstrating the efficacy of such therapy are lacking. We present a case of pulmonary hypertension secondary to fibrosing mediastinitis.

Clinical features of the yellow nail syndrome.

The yellow nail syndrome is a rare cause of exudative pleural effusions. Diagnosis is based on the presence of typical clinical features, striking nail changes, lymphedema, and pleural effusions of undetermined etiology. There is no direct relationship between the syndrome and primary immunologic disorders, malignancies, endocrine abnormalities, or connective tissue diseases.

Multiplane gallium tomography in assessment of occupational chest diseases.

Gallium-67 scintigraphy is helpful in the evaluation of inflammatory, respiratory diseases. Single-photon emission computed tomography (SPECT) provides three-dimensional tomographic reconstruction of radioisotope distribution in the body. The addition of SPECT to gallium-67 scanning in 27 patients demonstrated an improvement in the sensitivity for detecting the presence and extent of interstitial occupational lung disease.

An angiographic dilemma: bronchopulmonary sequestration versus pseudosequestration: case reports.

Bronchopulmonary sequestration is a congenital anomaly in which part of the pulmonary tissue is detached from the normal lung and is supplied by anomalous systemic arteries. The sequestered, aberrant lung tissue does not have normal connections with the tracheobronchial tree or pulmonary arteries. In some patients with angiographic characteristics of this disorder, no sequestration is found at the time of surgery.

Hyperventilation syndrome and asthma.

Hyperventilation syndrome is a common and often disabling condition. Traditional treatment consists of reassurance and anxiolytic drugs. Hyperventilation is known to precipitate an asthmatic reaction.

Pulmonary edema of environmental origin--newer concepts.

Pulmonary edema of non-cardiac origin is usually an urgent clinical problem, which has recently increased in frequency throughout the world in the past few years. This is partly due to sociological factors and to pre-eminent advances in industrial technology. Recent severe massive toxic gas explosions have had national and worldwide implications.

Home care ventilation: the Cleveland Clinic experience from 1977 to 1985.

A need for long-term ventilation in the home has created a demand for home care services that has been a source of growth for an industry. Evaluation of the patient and family who will guarantee successful home care requires careful psychological and psychiatric evaluation. Beyond this evaluation, long-term success is possible if appropriate financial resources are available.

Transdermal scopolamine in the treatment of asthma: a preliminary report.

The use of atropine has emerged over the past few years as a treatment for asthma. Scopolamine is pharmacologically similar to atropine and, as such, was used in a study of nine patients as a bronchodilator. These nine patients had diverse types of lung diseases.