Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two laminin-derived peptides containing either YIGSR or IKVAV (single amino acid code) sequences were radiolabeled with 99mTc and their biological distribution evaluated in rodents. Both 99mTc-peptides cleared rapidly from the circulation though the kidney, and to a lesser extent, through the liver. 99mTc-YIGSR peptide did not accumulate in any organ examined in normal, tumored, and emphysemic mice. The 99mTc-IKVAV peptide localized within 10 min to the lung of normal animals, resulting in lung-to-blood ratios of approximately 23:1. The 99mTc-IKVAV peptide localized to lung after submicron filtration and after intraperitoneal injection, suggesting that particulates do not major role in localization. Pre-incubation of 99mTc-IKVAV peptide in whole blood decreased lung localization, suggesting that margination of radiolabeled cells does not play a major role in the lung localization. When 99mTc-IKVAV was injected into mice with tumored lungs (melanoma), the lung uptake was markedly increased (up to 20% injected dose higher than control lungs) at all time points examined (10, 30, and 120 min). When 99mTc-IKVAV was injected into mice with genetic emphysema, the lung uptake was markedly decreased at all time points. The localization of the 99mTc-IKVAV-containing peptide to the lung is consistent with a receptor-based mechanism.
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PMID:Biological distribution of 99mTc-labeled YIGSR and IKVAV laminin peptides in rodents: 99mTc-IKVAV peptide localizes to the lung. 835 51

Pulmonary lymphangioleiomyomatosis (PLAM) is a rare disease with poor prognosis, characterized by an abnormal proliferation of smooth muscle. The patients are females and recurrent pneumothorax is a frequent complication. HMB45 is a monoclonal antibody with specific immunoreactivity for malignant melanoma. Recently, it was reported that some of the smooth muscle cells in PLAM had reactivity for HMB45. The aim of this study was to assess the sensitivity and specificity of HMB45 for the diagnosis of PLAM in cystic pulmonary diseases that cause recurrent pneumothorax. We compared immunoreactivity of the specimens obtained by open lung biopsy at surgical resection of bullae in 72 patients. The specimens of five females with PLAM, one female with suspected PLAM, 49 patients with primary spontaneous pneumothorax (19 females and 30 males), four with pulmonary eosinophilic granuloma (2 females and 2 males), seven with pulmonary emphysema (7 males), and six with idiopathic pulmonary fibrosis with apical bullous change (2 females and 4 males) were stained with HMB45 and anti-smooth muscle actin. All PLAM cases had HMB45 positive cells, which also stained with anti-smooth muscle actin. The biopsy specimens of a PLAM suspected case also stained with HMB45. None of the specimens from other diseases reacted with HMB45. HMB45 appears to provide a highly specific and highly sensitive diagnosis for PLAM in females. It may also be useful in patients with subtle smooth muscle proliferation. where the diagnosis of PLAM is difficult to confirm by conventional histological examination.
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PMID:Diagnosis of pulmonary lymphangioleiomyomatosis by HMB45 in surgically treated spontaneous pneumothorax. 862 Sep 56

Hyperpolarized (3)He images of mouse lung are presented. Ventilation images and measurements of (3)He apparent diffusion coefficient (ADC) are reported in healthy mice, and preliminary studies of emphysema and lung cancer in mice are described using these techniques. The design and operation of an electronically controlled small-animal ventilator to deliver the hyperpolarized gas and control animal respiration are described. Images are acquired using an asymmetric gradient echo imaging method to enhance the signal-to-noise ratio of the rapidly diffusing (3)He. In mice with elastase-induced emphysema, the whole-lung average ADC is greater by approximately 25%, a statistically significant difference, compared to healthy animals. By contrast, mice exposed to cigarette smoke for up to 12 months reveal no statistically relevant increases in ADC, although emphysema was not confirmed in these mice. A study of lung cancer (melanoma) in mice is also presented. While tumors are shown to cause substantial ventilation defects in the lung, these defects appear confined to the cancerous regions and do not extend to large-scale regions of the lung distal to the tumors.
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PMID:Hyperpolarized (3)He MRI of mouse lung. 1556 78

Recent advances have defined a role for abnormally short telomeres in a broad spectrum of genetic disorders. They include rare conditions such as dyskeratosis congenita as well pulmonary fibrosis and emphysema. Now, there is new evidence that some familial cancers, such as melanoma, are caused by mutations that lengthen telomeres. Here, we examine the significance of these short and long telomere length extremes for understanding the molecular basis of age-related disease and cancer.
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PMID:The short and long telomere syndromes: paired paradigms for molecular medicine. 2623 16

Ultraviolet radiation (UVR) exposure and family history are major associated risk factors for the development of non-melanoma skin cancer (NMSC). The objective of this study was to develop and validate a multi-parameterized artificial neural network based on available personal health information for early detection of NMSC with high sensitivity and specificity, even in the absence of known UVR exposure and family history. The 1997-2015 NHIS adult survey data used to train and validate our neural network (NN) comprised of 2,056 NMSC and 460,574 non-cancer cases. We extracted 13 parameters for our NN: gender, age, BMI, diabetic status, smoking status, emphysema, asthma, race, Hispanic ethnicity, hypertension, heart diseases, vigorous exercise habits, and history of stroke. This study yielded an area under the ROC curve of 0.81 and 0.81 for training and validation, respectively. Our results (training sensitivity 88.5% and specificity 62.2%, validation sensitivity 86.2% and specificity 62.7%) were comparable to a previous study of basal and squamous cell carcinoma prediction that also included UVR exposure and family history information. These results indicate that our NN is robust enough to make predictions, suggesting that we have identified novel associations and potential predictive parameters of NMSC.
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PMID:Predicting non-melanoma skin cancer via a multi-parameterized artificial neural network. 2937 96

Interstitial lung disease (ILD) is a life-threating complication, commonly associated with polymyositis (PM), and dermatomyositis (DM). A subset of acute ILD associated with PM/DM patients are refractory to conventional treatment, and leads to a high rate of mortality. The efficacy of therapeutic plasma-exchange (TPE) as a PM/DM treatment to improve muscle involvement is controversial due to a lack of evidence. However, in recent reports, TPE has been effective in improving lung involvement. To evaluate the efficacy of this therapy, we retrospectively studied TPE treatment outcomes for in 18 acute PM/DM-ILD patients who were resistant to conventional therapies. Five patients were diagnosed with DM (27.8%), 11 with CADM (61.1%), and two with PM (11.1%). Among 18 patients, 11 (61.1%) achieved satisfactory improvement after four or more rounds of TPE, whereas seven died due to respiratory failure. We also analyzed risk factors to predict unresponsiveness to TPE in these patients. Notably, the prevalence of subcutaneous/mediastinal emphysema was significantly higher in the non-responsive group (6/7, 85.7%) than in the responsive group (2/11, 18.2%; P = 0.013); moreover, patients with this complication were mainly in the CADM subgroup (6/8, 75%). Subcutaneous/mediastinal emphysema and increased serum ferritin levels were shown to be poor prognostic factors, predictive of unresponsiveness to TPE, in PM/DM patients. No autoantibodies were found to be associated with TPE outcome, although we only investigated anti-Jo-1 and anti-Ro antibodies; the clinical significance of other myositis-specific autoantibodies, especially anti-melanoma differentiation-associated gene 5 (MDA5) antibody, is not known. Our results indicate that TPE might be an alternative treatment for acute PM/DM-ILD patients resistant to conventional therapies, except for those with subcutaneous/mediastinal emphysema and high serum ferritin levels.
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PMID:Efficiency of Therapeutic Plasma-Exchange in Acute Interstitial Lung Disease, Associated With Polymyositis/Dermatomyositis Resistant to Glucocorticoids and Immunosuppressive Drugs: A Retrospective Study. 3178 64

Anti-melanoma differentiation-associated gene 5 juvenile dermatomyositis (anti-MDA5 JDM) is associated with high risk of developing rapidly progressive interstitial lung disease (RP-ILD). Here we report an 11-year-old girl with anti-MDA5 JDM and RP-ILD which led to a fatal outcome, further aggravated by SARS-CoV-2 infection. She was referred to our hospital after being diagnosed with anti-MDA5 JDM and respiratory failure due to RP-ILD. On admission, fibrobronchoscopy with bronchoalveolar lavage (BAL) revealed Pneumocystis jirovecii infection so treatment with intravenous trimethoprim-sulfamethoxazole was initiated. Due to RP-ILD worsening, immunosuppressive therapy was intensified using methylprednisolone pulses, cyclophosphamide, tofacitinib and intravenous immunoglobulin without response. She developed severe hypoxemic respiratory failure, pneumomediastinum and pneumothorax, further complicated with severe RP-ILD and cervical subcutaneous emphysema. Three real-time RT-PCR for SARS-CoV-2 were made with a negative result. In addition, she was complicated with a secondary hemophagocytic lymphohistiocytosis and a fourth real-time PCR for SARS-CoV-2 performed in BAS sample was positive. Despite aggressive treatment of RP-ILD due to anti-MDA5 JDM, there was no improvement of respiratory failure in the following days and patient developed refractory septic shock and died. Anti-MDA5 JDM patients with RP-ILD have a poor prognosis with a high mortality rate. For this reason, intensive immunosuppressive therapy is essential including the use of promising drugs such as tofacitinib. COVID-19 in children with underlying health conditions like anti-MDA5 JDM may still be at risk for disease and severe complications.
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PMID:Fatal outcome of anti-MDA5 juvenile dermatomyositis in a paediatric COVID-19 patient: a case report. 3301 94