Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010200 (cough)
 23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present 25 cases of a primary pulmonary sarcoma bearing histological, immunohistochemical, and ultrastructural features indistinguishable from those of monophasic synovial sarcoma of soft tissue. The patients were 11 men and 14 women between the ages of 16 and 77 years. Clinically, the most common symptoms were chest pain, cough, shortness of breath, and hemoptysis. The lesions involved all lung segments. Grossly, they varied in size from 0.6 to 20 cm and were described as soft to rubbery tumors with areas of necrosis and hemorrhage, some with cystic changes. Two lesions involved the bronchial wall and in one case the tumor was described as encircling the bronchial tree. Histologically, all of the lesions were characterized by an atypical spindle cell proliferation with a solid growth pattern. Areas of myxoid, neural, hemangiopericytic, and epithelial-like growth pattern were observed. Mitoses, necrosis, and hemorrhage were seen in all lesions in varying proportions. Immunohistochemical studies for epithelial membrane antigen (EMA) and keratin showed strong focal positivity in 25 of 25 and 23 of 25 lesions, respectively. Immunohistochemical study for vimentin showed diffuse strong positivity in all lesions. Other immunostains, including desmin, smooth muscle actin, and S-100 protein, were negative. Electron microscopy in three cases showed spindle cells with elongated nuclei containing abundant cytoplasmic rough endoplasmic reticulum and well developed desmosome type intercellular junctions. Follow-up information ranging from 2 to 20 years was obtained in 18 patients. Six patients died of their tumors, whereas four patients died of unrelated causes without evidence of recurrence or metastases. Eight patients were alive with disease (recurrence and/or metastases) from 1 to 7 years after diagnosis. Four patients were alive and well without evidence of recurrence or metastases from 2 to 20 years (mean follow-up, 12.5 years). The present group of lesions appears to constitute a distinctive and as yet previously undescribed primary sarcoma of the lung, which probably represents the visceral counterpart of monophasic synovial sarcoma of soft tissue in a pulmonary location. Because of their distinctive biology these lesions should be distinguished from a variety of primary and metastatic malignancies of the lung.
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PMID:Primary pulmonary sarcomas with features of monophasic synovial sarcoma: a clinicopathological, immunohistochemical, and ultrastructural study of 25 cases. 775 Sep 31

An electron-microscopic study of the sensory innervation of human epiglottis was undertaken. The nerve supply of this structure was abundant; numerous free unmyelinated nerve endings of 2.5-3 microns were observed in the stratified epithelium of the epiglottis associated with clear cells containing mitochondria, rough endoplasmic reticulum, microtubules and dense-cored granules. The nerve and cell complex resembled a corpuscular structure, probably of a quimiosensitive character. In the submucosa, unmyelinated nerves were observed which may come from deeper myelinated trunks, and some of them entered the epithelium. Encapsulated corpuscles were also found in the submucosa. Four elements could be distinguished: nerve endings, lamellar cells, interlamellar substance, and capsule. Our observations at an ultrastructural level complete previous observations by means of light microscopy indicating that the epiglottis is a zone with an important innervation in the epithelium as well as in the submucosa. This sensory innervation probably bears a relation to reflexes, such as cough and deglution, to protect the airways.
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PMID:Nerve endings in the epithelium and submucosa of human epiglottis. 797 19

Pulmonary structure and function change significantly between young adulthood and old age. Elastic elements of the lung degenerate, parenchymal tissue is lost, alveolar ducts and bronchioles dilate, chest wall compliance decreases, intercostal muscle mass and force are reduced and gas exchange surface lessens. Disturbances of innate immunity predispose the elderly to pulmonary inflammation. These changes affect pulmonary function tests and gas exchange, but adaptive changes in breathing frequency and tidal volume serve to maintain adequate ventilation. Aging depresses cough reflexes and ventilatory responsiveness to hypoxia and hypercapnia. Sleep-associated apnea and periodic breathing occur more frequently in the elderly, implying that neural feed back and feed-forward control (loop gain) are impaired. Low loop gain may contribute to sleep apnea but not to periodic breathing. A likely cause of age related pulmonary tissue degeneration and a future therapeutic target is defective protein folding in the endoplasmic reticulum. Nervous system adaptations that accompany structural and functional changes in the elderly are poorly understood.
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PMID:The aging respiratory system--pulmonary structure, function and neural control. 2357 Sep 57

The best-studied store-operated Ca2+ channels (SOCs), Ca2+ release activated Ca2+ (CRAC) channels, are activated by depleting endoplasmic reticulum Ca2+ pool and mediate Ca2+ influx vitally important for Ca2+ restoration and many cellular function. CRAC channels were identified on immune and airway smooth muscle (ASM) cells. Emerging evidence points to its involvement in allergic airways diseases. This article evaluated therapeutic potency of CRAC antagonist in experimental animal model of allergic asthma. Allergic asthma, induced by repetitive exposure of guinea pigs to ovalbumine, was followed by 14 days therapy by CRAC antagonist (3-fluoropyridine-4-carboxylic acid, FPCA). In vivo changes of specific airways resistance (sRaw) evaluated bronchodilatory effect of FPCA and salbutamol. The method of citric acid-induced cough reflex assessed antitussive activity of FPCA and codeine. The measurement of exhaled NO (ENO), expression of inducible NO-synthase (iNOS) by RT-PCR and immunohistochemical staining of airways tissue verified anti-inflammatory effect of FPCA. Long-term administration of FPCA resulted in significant cough suppression and bronchodilation, both comparable to the effect of control drugs. FPCA significantly decreased ENO and iNOS expression, which together with immunohistochemical analysis validated its anti-inflammatory effect. Presented data confirmed CRAC channels as a promising target for treatment of respiratory diseases associated with allergic inflammation.
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PMID:The long-term administration of Orai 1 antagonist possesses antitussive, bronchodilatory and anti-inflammatory effects in experimental asthma model. 2368 25

Asthma is a common disorder characterized, in part, by airway smooth muscle (ASM) hyperresponsiveness. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel expressed on airway nerve fibers that modulates afferent signals, resulting in cough, and potentially bronchoconstriction. In the present study, the TRPV1 transcript was detected by RT-PCR in primary cultured human ASM cells, and the TRPV1 protein was detected in ASM of human trachea by immunohistochemistry. Proximity ligation assays suggest that TRPV1 is expressed in the sarcoplasmic reticulum membrane of human ASM cells in close association with sarco/endoplasmic reticulum Ca2+-ATPase-2. In guinea pig tracheal ring organ bath experiments, the TRPV1 agonist capsaicin led to ASM contraction, but this contraction was significantly attenuated by the sodium channel inhibitor bupivacaine (n = 4, P < 0.05) and the neurokinin-2 receptor antagonist GR-159897 (n = 4, P < 0.05), suggesting that this contraction is neutrally mediated. However, pretreatment of guinea pig and human ASM in organ bath experiments with the TRPV1 antagonist capsazepine inhibited the maintenance phase of an acetylcholine-induced contraction (n = 4, P < 0.01 for both species). Similarly, capsazepine inhibited methacholine-induced contraction of peripheral airways in mouse precision-cut lung slice (PCLS) experiments (n = 4-5, P < 0.05). Although capsazepine did not inhibit store-operated calcium entry in mouse ASM cells in PCLS (n = 4-7, P = nonsignificant), it did inhibit calcium oscillations (n = 3, P < 0.001). These studies suggest that TRPV1 is expressed on ASM, including the SR, but that ASM TRPV1 activation does not play a significant role in initiation of ASM contraction. However, capsazepine does inhibit maintenance of contraction, likely by inhibiting calcium oscillations.
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PMID:Role of transient receptor potential vanilloid 1 in the modulation of airway smooth muscle tone and calcium handling. 2833 10

Coronavirus disease 2019 (COVID-19), the seventh human coronavirus infectious disease, was first reported in Wuhan, China, in December 2019, followed by its rapid spread globally (251,059 deaths, on May 5, 2020, by Johns Hopkins University). An early clinical report showed that fever, cough, fatigue, sputum production, and myalgia were initial symptoms, with the development of pneumonia as the disease progressed. Increases in the level of serum liver enzymes, D-dimer, cardiac troponin I, and creatinine have been observed in severely ill patients, indicating that multiple organ failure had occurred in these cases. Lymphopenia and an increase in interleukin-6 (IL-6) were also observed. Although COVID-19 patients are administered glucocorticoid therapy to treat the excessive immune response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, the efficacy of this form of therapy is unclear. Viremia is observed in severe cases, suggesting that in addition to type II alveolar epithelial cells, many cell types, such as vascular endothelial cells, cardiomyocytes, renal tubular cells, neuronal cells, and lymphocytes, may be damaged. The improvement of survival rates requires elucidation of the mechanism by which cellular damage occurs during viral infection. Cellular therapy, along with organ support systems such as oxygen therapy, artificial ventilation, extra corporeal membrane oxygenation and dialysis, as well as antiviral therapy, are required. Viral replication in infected host cells may perturb protein folding in the endoplasmic reticulum (ER), causing ER stress. Although an adaptive cellular response, i.e. the unfolded protein response, can compensate for the misfolded protein burden to some extent, continued viral proliferation may induce inflammation and cell death. Therefore, we propose that proteostasis dysfunction may cause conformational disorders in COVID-19. The application of pharmacological chaperone therapy to treat COVID-19 patients is additionally discussed.
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PMID:Pathological Aspects of COVID-19 as a Conformational Disease and the Use of Pharmacological Chaperones as a Potential Therapeutic Strategy. 3275 41

Interstitial lung disease (ILD) is a large group of disorders, most of which lead to progressive scarring of lung tissue. The scarring associated with ILD eventually affects your ability to breathe and get enough oxygen into your bloodstream. The typical symptoms of ILD are shortness of breath at rest or aggravated by exertion and dry cough. In this study, we enrolled a family with ILDs from central south region of China. Three patients suffered from repeated cough and shortness of breath. The high resolution computed tomography (HRCT) testing further confirmed the diagnosis of interstitial lung lesions. Whole exome sequencing (WES) and Sanger sequencing were applied to detect the genetic lesion of the family. By employing WES, a novel heterozygous mutation (NM_001098668: c.554C>T/p.A185V) of surfactant protein A2 (SFTPA2) was identified in the affected individuals and absent in the healthy members. Bioinformatics analysis predicted that this mutation is disease-causing mutation and located in an evolutionarily conserved site of SFTPA2 protein. The novel mutation may disrupt the stability of SFTPA2 protein and induce endoplasmic reticulum stress, finally leading to ILD under the influence of microorganisms. Our study not only expands the spectrum of SFTPA2 mutations but also helps the family members to mitigate ILD risk factors. The study also supplements and improves genetic testing strategies and ILD risk estimation methodologies for China.
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PMID:Identification of a Missense Mutation in the Surfactant Protein A2 Gene in a Chinese Family with Interstitial Lung Disease. 3318 Oct 27