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1.
Osric A. Forrest Daniel M. Chopyk Yael Gernez Milton R. Brown Carol K. Conrad Richard B. Moss Vin Tangpricha Limin Peng Rabindra Tirouvanziam 《Journal of cystic fibrosis》2019,18(1):64-70
Background
Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease.Methods
Resistin levels were measured in plasma and sputum from three retrospective CF cohorts spanning a wide range of disease. We also assessed the ability of neutrophils to secrete resistin upon activation in vitro. Finally, we constructed a multivariate model assessing the relationship between resistin levels and lung function.Results
Plasma resistin levels were only marginally higher in CF than in healthy control subjects. By contrast, sputum resistin levels were very high in CF, reaching 50–100 fold higher levels than in plasma. Among CF patients, higher plasma resistin levels were associated with allergic bronchopulmonary aspergillosis, and higher sputum resistin levels were associated with CF-related diabetes. Mechanistically, in vitro release of neutrophil primary granules was concomitant with resistin secretion. Overall, sputum resistin levels were negatively correlated with CF lung function, independently of other variables (age, sex, and genotype).Conclusions
Our data establish relationships between resistin levels in the plasma and sputum of CF patients that correlate with disease status, and identify resistin as a novel mechanistic link between neutrophilic inflammation and lung disease in CF. 相似文献2.
3.
Béla Nagy Zsolt Bene Zsolt Fejes Sonya L. Heltshe David Reid Nicola J. Ronan Yvonne McCarthy Daniel Smith Attila Nagy Elizabeth Joseloff György Balla János Kappelmayer Milan Macek Scott C. Bell Barry J. Plant Margarida D. Amaral István Balogh 《Journal of cystic fibrosis》2019,18(2):271-277
Background
We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.Methods
In this retrospective clinical study, 3 independent CF patient cohorts (US-American: 29, Australian: 12 and Irish: 19 cases) were enrolled carrying at least one Class III CFTR CF-causing mutation (p.Gly551Asp) and being treated with CFTR potentiator ivacaftor. Plasma HE4 was measured by immunoassay before treatment (baseline) and 1–6?months after commencement of ivacaftor, and were correlated with FEV1 (% predicted), sweat chloride, C-reactive protein (CRP) and body mass index (BMI).Results
After 1?month of therapy, HE4 levels were significantly lower than at baseline and remained decreased up to 6?months. A significant inverse correlation between absolute and delta values of HE4 and FEV1 (r?=??0.5376; P?<?.001 and r?=??0.3285; P?<?.001), was retrospectively observed in pooled groups, including an independent association of HE4 with FEV1 by multiple regression analysis (β?=??0.57, P?=?.019). Substantial area under the receiver operating characteristic curve (ROC-AUC) value was determined for HE4 when 7% mean change of FEV1 (0.722 [95% CI 0.581–0.863]; P?=?.029) were used as classifier, especially in the first 2?months of treatment (0.806 [95% CI 0.665–0.947]; P?<?.001).Conclusions
This study shows that plasma HE4 levels inversely correlate with lung function improvement in CF patients receiving ivacaftor. Overall, this potential biomarker may be of value for routine clinical and laboratory follow-up of CFTR modulating therapy. 相似文献4.
目的利用人肝门部胆管癌细胞系(FRH-0201)接种裸鼠脾脏,建立肝、肺转移模型。方法将FRH-0201细胞系(120代)接种于7只Balb/c裸小鼠脾脏。出现转移时,将转移瘤行组织病理学及超微结构观察。将转移的肿瘤行细胞培养,再次接种裸鼠脾脏,观察转移成瘤情况。结果脾脏局部成瘤率为100%(7/7),转移瘤发生率14.3%(1/7)。转移瘤细胞再次接种于裸小鼠脾脏,转移发生率100%。转移瘤电镜显示典型恶性细胞特征。转移瘤细胞染色体众数19条,主流范围18~44条。结论该实验所建立的肝门部胆管癌转移瘤,符合恶性肿瘤的特点,与人肝门部胆管癌生物学特性一致。 相似文献
5.
C. M. Gordon E. Binello M. S. LeBoff M. E. Wohl C. J. Rosen A. A. Colin 《Osteoporosis international》2006,17(5):783-790
Introduction Patients with cystic fibrosis (CF) are known to be at risk for early osteoporosis, and the mechanisms that mediate bone loss
are still being delineated. The aim of the present investigation was to investigate if a correlation exists in these patients
between skeletal measurements by dual-energy x-ray absorptiometry (DXA) and two anabolic factors, dehydroepiandrosterone (DHEA)
and insulin-like growth factor I (IGF-I), and proresorptive factors such as the cytokines interleukin-1β, tumor necrosis factor α,
and interleukin-6.
Methods We studied 32 outpatients (18 females; mean age: 26.2 ± 7.9 years) at a tertiary care medical center. The subjects had venous
samples obtained, underwent anthropometric and bone mineral density (BMD) measurements, and completed a health survey. Serum
IGF-I concentrations were below the age-adjusted mean in 78% of the participants, and DHEA sulfate (DHEAS) concentrations
were low in 72%. Serum concentrations of all cytokines were on the low side of normal; nonetheless, there was a modest inverse
correlation between IL-1β and BMD at all sites.
Results In univariate analyses, IGF-I and DHEAS were significant correlates of BMD or bone mineral content. In final multivariate
models controlling for anthropometric and other variables of relevance to bone density, only IGF-I was identified as a significant
independent skeletal predictor. While alterations in DHEAS, IGF-I, and specific cytokines may contribute to skeletal deficits
in patients with CF, of these factors a low IGF-I concentration appears to be most strongly correlated with BMD.
Conclusions These findings may have therapeutic implications for enhancing bone density in these patients. 相似文献
6.
Cystic Fibrosis has effects on many body systems, including the skeletal system. In this case, we describe the impact of respiratory and endocrine disease on bone healing following orthopedic trauma in a 22-year-old woman. Limitations to mobility resulting from trauma complicated her respiratory condition. Disease-related effects on bone health and healing delayed her recovery from the trauma. It is important to recognize the multisystemic nature of CF, even when managing acute orthopedic injuries. 相似文献
7.
CFTR was reported to regulate ENaC channel opening, decreasing ENaC activity in airways and increasing it in sweat ducts. We generated MDCK-I cell lines stably expressing tagged alphabetagammaENaC+CFTR or ENaC alone, and developed an assay to quantify cell-surface half-life of ENaC. Surprisingly, we found that co-expressed CFTR stabilizes ENaC at the plasma membrane, suggesting that CFTR regulates ENaC stability, not just opening. 相似文献
8.
Myriam Costa Stphanie Potvin Imane Hammana Arnaud Malet Yves Berthiaume Alphonse Jeanneret Annick Lavoie Rene Lvesque Joëlle Perrier Danielle Poisson Antony D. Karelis Jean-Louis Chiasson Rmi Rabasa-Lhoret 《Journal of cystic fibrosis》2007,6(6):376-383
BACKGROUND: Abnormal glucose tolerance is a frequent co-morbidity in cystic fibrosis patients (CF), and is associated with a worse prognosis. The objectives are to investigate (a) the relative contribution of insulinopenia and insulin resistance (IR) for glucose tolerance and (b) the association between various glucose parameters and CF clinical status. METHODS: Oral glucose tolerance tests were performed in 114 consecutive CF patients not known to be diabetic as well as 14 controls similar for age and BMI. RESULTS: Abnormal glucose tolerance was found in 40% of patients with CF: 28% had impaired glucose tolerance (IGT) and 12% had new cystic fibrosis related diabetes (CFRD). Compared to control subjects, all CF patients were characterized by an increased glucose excursion (AUC). While reduced early insulin release characterised CF, IGT and CFRD patients also present IR thus both mechanisms significantly contribute to glucose tolerance abnormalities. Increased glucose AUC and reduced early insulin release but not glucose tolerance categories were associated with a reduced pulmonary function (FEV(1)). CONCLUSION: In CF, early insulin secretion defect but also IR contribute to glucose intolerance. Early in the course of the disease, increased glucose AUC and reduced early insulin secretion are more closely associated with a worse clinical status than conventional glucose tolerance categories. 相似文献
9.
我院治疗66例心间隔缺损的病例中,有4例合并哑性动脉导管未闭(简称PDA),发生率6%。全组病例术前均无PDA临床体征,1例术前再次复查心脏彩超时发现,其余3例均漏诊。1例先处理PDA,3例在纠正心内畸形同时处理PDA。心间隔缺损合并哑性PDA容易漏诊,但有其临床特点,手术可先处理PDA,或在体外循环下处理PDA。 相似文献
10.
A. G. Douglas-Jones H. Navabi J. M. Morgan B. Jasani 《Virchows Archiv : an international journal of pathology》1997,430(5):373-379
Immunocytochemically detectable MT and p53 have been found more commonly in comedo DCIS of the breast with high-grade cytology.
The aim of this study is to confirm these findings and to investigate the relationship between MT and p53 in a single large
series of cases of DCIS of the breast. To this end, 127 cases of DCIS were classified histologically according to architecture,
cytonuclear differentiation (grade), presence and extent of intraduct necrosis, and using the Van Nuys system. Sections were
immunostained for p53 and MT (E9) using established techniques, and the extent and intensity of staining were assessed semi-quantitively.
The results confirmed that there was generally more MT and p53 positivity in poorly differentiated (grade 3) DCIS with extensive
necrosis and that MT expression was greater in grade 2 lesions than p53 expression. However, overall there was no statistically
significant correlation between p53 and MT staining. The results indicate that MT and p53 overexpression may arise from independent
mechanisms in early breast neoplasia.
Received: 3 July 1996 / Accepted: 5 November 1996 相似文献