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Impact of basal heart rate on long-term prognosis of heart transplant patients.

Sat, 03/16/2013 - 10:27

Impact of basal heart rate on long-term prognosis of heart transplant patients.

Transpl Int. 2013 Mar 15;

Authors: Melero-Ferrer JL, Sánchez-Lázaro IJ, Almenar-Bonet L, Martínez-Dolz L, Buendía-Fuentes F, Portolés-Sanz M, Rivera-Otero M, Salvador-Sanz A

Abstract
Previous studies in patients with heart failure have shown that an elevated basal heart rate (HR) is associated with a poor outcome. Our aim with this study was to investigate if this relationship is also present in heart transplantation (HTx) recipients. From 2003 until 2010, 256 HTx performed in our center were recruited. Patients who required pacemaker, heart-lung transplants, pediatrics, retransplants, and those patients with a survival of less than 1 year were excluded. The final number included in the analysis was 191. Using the HR obtained by EKG during elective admission at 1 year post-HTx and the survival rate, an ROC-curve was performed. The best point under the curve was achieved with 101 beats per minute (bpm), so patients were divided in two groups according to their HR. A comparison between survival curves of both groups was performed (Kaplan-Meier). Subsequently, a multivariate analysis considering HR and other variables with influence on survival according to the literature was carried out. A total of 136 patients were included in the group with HR ≤100 bpm, and 55 in the one with HR >100 bpm. There were no basal differences in both groups except for primary graft failure, which was more frequent in the >100 bpm group (30.9 vs. 17%, P = 0.033). Patients with ≤100 bpm had a better long prognosis (P < 0.001). The multivariate analysis proved that high HR was an independent predictor of mortality. Our study shows that HR should be considered as a prognosis factor in HTx patients.

PMID: 23489468 [PubMed - as supplied by publisher]

Liver transplantation in cystic fibrosis: A report from Baylor College of Medicine and the Texas Children's Hospital.

Sat, 03/16/2013 - 10:27

Liver transplantation in cystic fibrosis: A report from Baylor College of Medicine and the Texas Children's Hospital.

Pediatr Transplant. 2013 Mar 15;

Authors: Harring TR, Nguyen NT, Liu H, Karpen SJ, Goss JA, O'Mahony CA

Abstract
CF affects one of 2000 Caucasians, and approximately 25% are found to have CFLD for which OLT may be indicated. Timing of transplantation, contraindications, and survival are still widely debated. We report the outcomes of OLT for pediatric patients with CFLD from the largest children's hospital in the United States. Our records since September 1998 were analyzed for all patients undergoing OLT for CFLD. Nine patients were then compared to similar patients in the UNOS/OPTN database (n = 155). Survivals were calculated with the Kaplan-Meier method and compared using the log-rank test. All statistics were performed in SPSS 15.0. We performed OLT on nine pediatric patients with CFLD, with age ranging from nine to 17 yr at the time of transplant. Mean survival was 69.2 months; patient and allograft survivals at one and five yr were 88.9%, with one death at day 21 due to Aspergillus fumigatus sepsis. Two patients underwent concurrent multi-organ transplantation. One patient required double lung transplantation four yr after isolated OLT. Comparison to the UNOS/OPTN database revealed a trend toward improved survival. Patients with CF can achieve favorable outcomes after OLT, as we report excellent survivals for pediatric patients with CFLD.

PMID: 23489441 [PubMed - as supplied by publisher]

Matrix Metalloproteinase 1 promotes tumor formation and lung metastasis in an intratibial injection osteosarcoma mouse model.

Fri, 03/15/2013 - 10:21
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Matrix Metalloproteinase 1 promotes tumor formation and lung metastasis in an intratibial injection osteosarcoma mouse model.

Biochim Biophys Acta. 2013 Feb;1832(2):347-54

Authors: Husmann K, Arlt MJ, Muff R, Langsam B, Bertz J, Born W, Fuchs B

Abstract
Proteolytic degradation of the extracellular matrix (ECM) is an important process during tumor invasion. Matrix Metalloproteinase 1 (MMP-1) is one of the proteases that degrade collagen type I, a major component of bone ECM. In the present study, the biological relevance of MMP-1 in osteosarcoma (OS) tumor growth and metastasis was investigated in vitro and in vivo. Human OS cells in primary culture expressed MMP-1 encoding mRNA at considerably higher levels than normal human bone cells. In addition, MMP-1 mRNA and protein expression in the highly metastatic human osteosarcoma 143-B cell line was remarkably higher than in the non-metastatic parental HOS cell line. Stable shRNA-mediated downregulation of MMP-1 in 143-B cells impaired adhesion to collagen I and anchorage-independent growth, reflected by a reduced ability to grow in soft agar. Upon intratibial injection into SCID mice, 143-B cells with shRNA-downregulated MMP-1 expression formed smaller primary tumors and significantly lower numbers of lung micro- and macrometastases than control cells. Conversely, HOS cells stably overexpressing MMP-1 showed an enhanced adhesion capability to collagen I and accelerated anchorage-independent growth compared to empty vector-transduced control cells. Furthermore, and most importantly, individual MMP-1 overexpression in HOS cells enabled the formation of osteolytic primary tumors and lung metastasis while the HOS control cells did not develop any tumors or metastases after intratibial injection. The findings of the present study reveal an important role of MMP-1 in OS primary tumor and metastasis formation to the lung, the major organ of OS metastasis.

PMID: 23195950 [PubMed - indexed for MEDLINE]

[Clinical analysis of early postoperative pulmonary infection in children after living donor liver transplantation].

Fri, 03/15/2013 - 10:21
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[Clinical analysis of early postoperative pulmonary infection in children after living donor liver transplantation].

Zhonghua Er Ke Za Zhi. 2012 Aug;50(8):612-6

Authors: Han HL, Huang Y, Zhang MM, Guo CB, Pu CL

Abstract
OBJECTIVE: To analyze the condition of early (≤ 30 d) postoperative pulmonary infection in children after living donor liver transplantation (LDLT).
METHOD: The clinical data of 36 cases undergoing LDLT in Children's Hospital of Chongqing Medical University were analyzed retrospectively from June 2006 to December 2009.
RESULT: Of 36 cases without preoperative respiratory disease, 17 were boys, 19 were girls. Their age ranged from 2 months to 14 years. Pulmonary infection developed in 24 patients, of whom 4 cases died (17%) and 3 deaths were related to pulmonary infection. Pulmonary infection occurred in 17 of 20 infants (85%) and 10 of 11 cases (91%) with liver function of Child-Pugh grade C. Twenty cases (83%) developed pulmonary infection within first 2 weeks after LDLT. Totally 65 pathogenic strains of microorganisms were isolated, in which Gram-negative bacteria, Gram-positive bacteria and fungi were 46 strains, 5 strains, 14 strains respectively. The most frequently isolated bacteria were Pseudomonas aeruginosa (14 strains), Klebsiella pneumoniae (8 strains) and Acinetobacter baumannii (8 strains). Pseudomonas aeruginosa showed a resistance rate of almost 100% to cotrimoxazole, tetracycline, chloramphenicol, ampicillin, the first, the second and some of the third generation cephalosporins. Klebsiella pneumoniae producing extended spectrum beta-lactamase had a resistance rate of almost 100% to beta-lactams except carbapenems. Acinetobacter baumannii was exquisitely susceptible to carbapenems, but showed a high resistance to penicillins and cephalosporins. Candida albicans, which was the most common fungus, showed a susceptibility rate of 100% to amphotericin B. In the LDLT recipients of pulmonary infection, cytomegalovirus (CMV) infections occurred in 2 patients and Epstein Barr virus (EBV) infection in 1 patient.
CONCLUSION: The incidence of early postoperative pulmonary infection was high in children undergoing LDLT, especially in infants. And the mortality should not be ignored. The high risk period for infection was within the first 2 weeks after operation. The pathogens were mainly Gram-negative bacteria, which showed high and multidrug resistance.

PMID: 23158740 [PubMed - indexed for MEDLINE]

Dasatinib, a small molecule inhibitor of the Src kinase, reduces the growth and activates apoptosis in pre-neoplastic Barrett's esophagus cell lines: evidence for a noninvasive treatment of high-grade dysplasia.

Fri, 03/15/2013 - 10:21
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Dasatinib, a small molecule inhibitor of the Src kinase, reduces the growth and activates apoptosis in pre-neoplastic Barrett's esophagus cell lines: evidence for a noninvasive treatment of high-grade dysplasia.

J Thorac Cardiovasc Surg. 2013 Feb;145(2):531-8

Authors: Inge LJ, Fowler AJ, Paquette KM, Richer AL, Tran N, Bremner RM

Abstract
BACKGROUND: Only local ablation (radiofrequency ablation, cryotherapy) or esophagectomy currently is available to treat high-grade dysplasia in Barrett's esophagus. Alternative treatments, specifically chemopreventive strategies, are lacking. Our understanding of the molecular changes of high-grade dysplasia in Barrett's esophagus offers an opportunity to inhibit neoplastic progression of high-grade dysplasia in Barrett's esophagus. Increased activity of the Src kinase and deregulation of the tumor suppressor p27 are features of malignant cells and high-grade dysplasia in Barrett's esophagus. Src phosphorylates p27, inhibiting its regulatory function and increasing cell growth and proliferation. We hypothesized that a small molecule inhibitor of Src might reduce the growth and reverse Src-mediated deregulation of p27 in Barrett's esophagus cells.
METHODS: Immortalized Barrett's esophagus cell lines established from patient biopsies were treated with the Src kinase inhibitor dasatinib and evaluated for p27 localization and protein levels, as well as for effects on the cell cycle and apoptosis using flow cytometry, viability assays, and protein and RNA markers.
RESULTS: Dasatinib reduced both Src activation and p27 phosphorylation and increased p27 protein levels and nuclear localization. These effects correlated with decreased proliferation, cell-cycle arrest, and activation of apoptosis. Analysis of biopsies of patients with Barrett's esophagus revealed the presence of phosphorylated p27 in high-grade dysplasia, consistent with in vitro findings.
CONCLUSIONS: Dasatinib has considerable antineoplastic effects on Barrett's esophagus cell lines carrying genetic markers associated with dysplasia, which correlates with the reversal of p27 deregulation. These findings suggest that dasatinib has potential as a treatment for patients with high-grade dysplasia and Barrett's esophagus and that p27 holds promise as a biomarker in the clinical use of dasatinib in patients with high-grade dysplasia and Barrett's esophagus.

PMID: 23142123 [PubMed - indexed for MEDLINE]

Pulmonary congestion and physical functioning in peritoneal dialysis patients.

Fri, 03/15/2013 - 10:21
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Pulmonary congestion and physical functioning in peritoneal dialysis patients.

Perit Dial Int. 2012 Sep-Oct;32(5):531-6

Authors: Enia G, Tripepi R, Panuccio V, Torino C, Garozzo M, Battaglia GG, Zoccali C

Abstract
PURPOSE: Decline in physical function is commonly observed in patients with kidney failure on dialysis. Whether lung congestion, a predictable consequence of cardiomyopathy and fluid overload, may contribute to the low physical functioning of these patients has not been investigated.
METHODS: In 51 peritoneal dialysis (PD) patients, we investigated the cross-sectional association between the physical functioning scale of the Kidney Disease Quality of Life Short Form (KDQOL-SF: Rand Corporation, Santa Monica, CA, USA) and an ultrasonographic measure of lung water recently validated in dialysis patients. The relationship between physical functioning and lung water was also analyzed taking into account the severity of dyspnea measured using the New York Heart Association (NYHA) classification currently used to grade the severity of heart failure.
RESULTS: Evidence of moderate-to-severe lung congestion was evident in 20 patients, and this alteration was asymptomatic (that is, NHYHA class I) in 11 patients (55%). On univariate analysis, physical functioning was inversely associated with lung water (r = -0.48, p < 0.001), age (r = -0.44, p = 0.001), previous cardiovascular events (r = -0.46, p = 0.001), and fibrinogen (r = -0.34, p = 0.02). Physical functioning was directly associated with blood pressure, the strongest association being with diastolic blood pressure (r = 0.38, p = 0.006). The NYHA class correlated inversely with physical functioning (r = -0.51, p < 0.001). In multiple regression analysis, only lung water and fibrinogen remained independent correlates of physical functioning. The NYHA class failed to maintain its independent association.
CONCLUSIONS: This cross-sectional study supports the hypothesis that symptomatic and asymptomatic lung congestion is a relevant factor in the poor physical functioning of patients on PD.

PMID: 22942271 [PubMed - indexed for MEDLINE]

Isolation, culture, and potentiality assessment of lung alveolar stem cells.

Fri, 03/15/2013 - 10:21
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Isolation, culture, and potentiality assessment of lung alveolar stem cells.

Methods Mol Biol. 2012;916:23-30

Authors: Oeztuerk-Winder F, Ventura JJ

Abstract
The cellular and molecular elements involved in the turnover and regeneration of the lung alveolar epithelium remain largely unknown (Kim, Am J Physiol Lung Cell Mol Physiol 293:L1092-1098, 2007). Isolation and characterization of putative stem cells with limited and nonspecific markers have made necessary the use, in parallel, of culture restrictive conditions and optimized reagents to allow selection and long-term expansion of this population.

PMID: 22914930 [PubMed - indexed for MEDLINE]

[Establishment and characterization of lung adenocarcinoma cell line XLA-07].

Fri, 03/15/2013 - 10:21
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[Establishment and characterization of lung adenocarcinoma cell line XLA-07].

Zhonghua Bing Li Xue Za Zhi. 2012 May;41(5):335-9

Authors: Ma LJ, Wang HZ, Bian L, Shao WP, Tang RZ, Wang QQ, Jin KW

Abstract
OBJECTIVE: To establish and characterize a lung adenocarcinoma cell line from a female patient in Xuanwei, Yunnan province.
METHODS: Surgical specimen of the lung adenocarcinoma was obtained and cultured immediately in RPMI 1640 medium with 10% fetal bovine serum and 10(5) U/L penicillin and 100 mg/L streptomycin. When stable proliferation of the cells was achieved after over 40 passages in culture, the biological features of the cell line were investigated by cell morphology, karyotyping, protein marker expression [cytokeratins (CKs), epithelial membrane antigen (EMA) and CD proteins], growth kinetics, cell cycle phase distribution, mitotic index, colony formation in soft agar, cell invasion and tumorigenicity in Balb/c nude mice.
RESULTS: The established cell line was stably cultured for over 80 passages during a one-year period as an anchorage-dependent monolayer of short spindle, polygonal to epithelioid cells under phase contrast microscope. Microglandular cavities and disordered microfilaments were observed under transmission electron microscope. The growth curve presented in an "S" shape with the cell population doubled every 46.7 hours. The mitotic index was 1.5% and the colony formation rate was 8.3%. The cell cycle distribution included 76.9% in G(0)/G(1), 15.1% in S and 8.0% in G(2)/M. The cell line displayed a hypotriploid karyotype with a mode of 66 chromosomes and a median of 64 chromosomes. The cells expressed CK7, CK8, CK (Pan) and EMA by immunohistochemistry. A high level of cell surface expression of CD13 and CD59 was evident by flow cytometry. The cells were able to penetrate Matrigel in vitro but failed to form a stable xenograft in nude mice.
CONCLUSION: A new human lung adenocarcinoma cell line, designated as XLA-07, is successfully established from a Xuanwei lung cancer patient.

PMID: 22883674 [PubMed - indexed for MEDLINE]

[Influence of human mesenchymal stem cells on hyperoxia-exposed newborn rats by RAGE-NF-κB signaling in lung].

Fri, 03/15/2013 - 10:21
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[Influence of human mesenchymal stem cells on hyperoxia-exposed newborn rats by RAGE-NF-κB signaling in lung].

Zhonghua Er Ke Za Zhi. 2012 May;50(5):356-60

Authors: Tian ZF, Ji P, Li YH, Zhao S, Wang X

Abstract
OBJECTIVE: To investigate the influence of high oxygen exposure on signaling pathway of the receptor for advanced glycation end products (RAGE)-NF-κB of lung in newborn rats and the mechanisms of protecting lung injury for human mesenchymal stem cells (hMSC).
METHODS: Twenty-four newborn Sprague-Dawley rats from three litters were randomly divided into three groups, as hyperoxia exposed + hMSC group (group A), hyperoxia exposed group (group B), and air-exposed group (group C). The rats from the group A and B were placed in a sealed Plexiglas chamber with a minimal in-and outflow, providing six to seven exchanges per hour of the chamber volume and maintaining O(2) levels above 95%, while rats in the group C only exposed to air simultaneously. Seven days later, rats in the group A were injected intravenously with hMSC (5×10(4)) after hyperoxia exposure, but rats in group B and C received subcutaneous injection with PBS alone at the same time point. Then all the rats were exposed to air, and were sacrificed three days later. Immunohistochemistry was used to evaluate the expression of RAGE in lung tissue. The levels of TNF-α and sRAGE in bronchoalveolar lavage fluid (BALF) and in serum were detected by ELASA, RAGE mRNA and NF-κB mRNA in tissue homogenates were detected by RT-PCR, RAGE and NF-κB by Western blotting; also the value of lung damage score were calculated with histology under light microscope.
RESULTS: There were significant differences among three groups in the fields of lung damage score (F = 51.59, P = 0.000), mRNA and protein of RAGE (F = 37.21, P = 0.000; F = 15.88, P = 0.000) and NF-κB (F = 5.695, P = 0.011; F = 4.223, P = 0.0288) in lung tissue homogenates, and the level of TNF-α (F = 38.29, P = 0.000) in BALF, all these parameters in group A and group B were higher than that in group C. While sRAGE in BALF in group A and group B were less than that in group C (F = 4.804, P = 0.0191). There were also significant differences between group A and group B in these parameters (P < 0.05). There were also no significant differences neither in TNF-α nor in sRAGE in serum among three groups.
CONCLUSIONS: hMSC protects hyperoxia-induced lung injury via downregulating the signaling pathway of RAGE-NF-κB.

PMID: 22883037 [PubMed - indexed for MEDLINE]

[Humanized monoclonal antibody TNT-3-mediated truncated tissue factor for the treatment of H22 hepatoma-bearing mice].

Fri, 03/15/2013 - 10:21
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[Humanized monoclonal antibody TNT-3-mediated truncated tissue factor for the treatment of H22 hepatoma-bearing mice].

Zhonghua Zhong Liu Za Zhi. 2012 Apr;34(4):249-53

Authors: Huang ZJ, Wang R, Liu ZZ, Wang SY, Yan JH, Luo Q

Abstract
OBJECTIVE: To investigate the inhibitory effects of humanized monoclonal antibody-3 (huTNT-3) mediated truncated tissue factor (tTF) on the H(22) hepatoma-bearing mice, and to explore its mechanisms.
METHODS: The coagulation activity of the huTNT-3/tTF fusion protein was detected by clotting assay and clotting factor X (FX) activation test in vitro. Mouse hepatoma cell line H(22) cells were inoculated subcutaneously into mice to establish the mouse models of hepatoma. The mice were randomly divided into two groups to be injected once with huTNT-3/tTF fusion protein or tTF protein labeled with rhodamine B isothiocyanate (RBITC), respectively. The localization of huTNT-3/tTF fusion protein in the mouse hepatoma tissue was analyzed by confocal laser scanning microscopy 24 hour after the injection. Fifteen mice were randomly divided into three groups to be injected with the huTNT-3/tTF fusion protein, tTF protein or phosphate buffered saline (PBS) once, respectively. The tumor size was measured every two days to calculate the tumor volume. Ten days after the injection the mice were sacrificed. Samples of the tumor, heart, livers, spleen, lung, kidney and brains of the mice were taken for histopathological examination.
RESULTS: Both the huTNT-3/tTF fusion protein and tTF protein effectively promoted blood coagulation. Under the conditions of Ca(2+), the coagulation time in the 1.5, 3, 6 µmol/L huTNT-3/tTF groups was (12.90 ± 0.60) min, (10.39 ± 0.40) min and(8.15 ± 0.24) min, respectively, and the coagulation time of the 1.5, 3, 6 µmol/L tTF groups was (14.23 ± 0.46) min, (12.10 ± 0.49) min and (9.83 ± 0.52) min, respectively, the difference between the two groups was not significant (F = 0.145, P = 0.705). The huTNT-3/tTF fusion protein was similar to the tTF protein in the ability of activating FX (t = 0.101, P > 0.05). The confocal laser scanning microscopic analysis showed that RBITC-fluorescence labeled huTNT-3/tTF fusion protein was enriched in the hepatoma tissue. The tumor volume of the huTNT-3/tTF fusion protein group was significantly lower than that of the tTF and PBS groups (both P < 0.001), however, there was not significant difference between the tTF and PBS groups (t = -0.616, P > 0.05). The survival time of the huTNT-3/tTF group was (25.5 ± 2.5) d, significantly longer than that of the PBS group (17.3 ± 1.9) d and the tTF group (18.6 ± 1.9) d, (both P < 0.05).
CONCLUSION: The huTNT-3/tTF fusion protein retains the coagulation ability and has the capability of targeting to tumor vasculature, and induces thrombosis in the tumor vessels, thus to suppress the growth of hepatoma in the mice.

PMID: 22781034 [PubMed - indexed for MEDLINE]

Late Respiratory Infection after Lung Transplantation.

Thu, 03/14/2013 - 11:50

Late Respiratory Infection after Lung Transplantation.

Tuberc Respir Dis (Seoul). 2013 Feb;74(2):63-69

Authors: Kim SY, Shin JA, Cho EN, Byun MK, Kim HJ, Ahn CM, Haam SJ, Lee DY, Paik HC, Chang YS

Abstract
BACKGROUND: Aiming to improve outcome of lung transplantation (LTx) patients, we reviewed risk factors and treatment practices for the LTx recipients who experienced respiratory infection in the late post-LTx period (>1 month after LTx).
METHODS: We analyzed the clinical data of 48 recipients and donors from 61 LTx, who experienced late respiratory infections. Late respiratory infections were classified according to the etiology, time of occurrence, and frequency of donor-to-host transmission or colonization of the recipient prior to transplantation.
RESULTS: During the period of observation, 42 episodes of respiratory infections occurred. The organisms most frequently involved were gram (-) bacteria: Acinetobacter baumannii (n=13, 31.0%), Pseudomonas aeruginosa (n=7, 16.7%), and Klebsiella pneumoniae (n=4, 10.0%). Among the 42 episodes recorded, 14 occurred in the late post-LTx period. These were bacterial (n=6, 42.9%), fungal (n=2, 14.3%), viral (n=4, 28.5%), and mycobacterial (n=2, 14.3%) infections. Of 6 bacterial infections, 2 were from multidrug-resistant (MDR) A. baumannii and one from each of MDR P. aeruginosa, extended spectrum β-lactamase (+) K. pneumoniae, methicillin-resistant Staphylococcus aureus and Streptococcus pneumoniae. Infection-related death occurred in 6 of the 14 episodes (43%).
CONCLUSION: Although the frequency of respiratory infection decreased sharply in the late post-LTx period, respiratory infection was still a major cause of mortality. Gram (-) MDR bacteria were the agents most commonly identified in these infections.

PMID: 23483760 [PubMed - as supplied by publisher]

Intratracheal Transplantation of Bone Marrow-Derived Mesenchymal Stem Cells Reduced Airway Inflammation and up-regulated CD4 + CD25 + regulatory T cells in chronic asthmatic mouse.

Thu, 03/14/2013 - 11:50

Intratracheal Transplantation of Bone Marrow-Derived Mesenchymal Stem Cells Reduced Airway Inflammation and up-regulated CD4 + CD25 + regulatory T cells in chronic asthmatic mouse.

Cell Biol Int. 2013 Mar 9;

Authors: Ge X, Bai C, Yang J, Lou G, Li Q, Chen R

Abstract
Mesenchymal stem cells attenuate the severity of lung injury due to their immunomodulatory properties. The effect of bone marrow-derived mesenchymal stem cells on asthma is seldom reported. We have examined the effect of BMSCs on airway inflammation in asthma. Forty female BALB/c mice were equally randomized into PBS group, BMSCs treatment group, BMSCs control group and asthmatic group. Reactivity of the airway to acetylcholine was measured by barometric plethysmography. Cytokine profiles of bronchoalveolar lavage fluid and serum were determined by enzyme-linked immunosorbent assay. Morphometric analysis was done with hematoxylin and periodic-acid Schiff staining. Engraftment of BMSCs in asthmatic mice significantly decreased the number of eosinophils and mononuclear cells in bronchoalveolar lavage fluid and the airway (p < 0.05). Both goblet cell hyperplasia and responsiveness to acetylcholine were significantly reduced in BMSCs treatment groups. Moreover, BMSCs engraftment caused significant increases the ratio of treg in pulmonary lymph node and interleukin-10 (IL-10) and interleukin-12 levels in BALF and serum. We conclude that BMSCs engraftment ameliorated airway inflammation and improved lung function in asthmatic mouse and the protective effect might be mediated by upregulating treg and partly involved with increasing IL-10.

PMID: 23483727 [PubMed - as supplied by publisher]

Influence of hemodialysis on clinical outcomes after lung transplantation.

Thu, 03/14/2013 - 11:50

Influence of hemodialysis on clinical outcomes after lung transplantation.

J Surg Res. 2013 Feb 26;

Authors: Hennessy SA, Gillen JR, Hranjec T, Kozower BD, Jones DR, Kron IL, Lau CL

Abstract
BACKGROUND: Chronic renal failure after lung transplantation is associated with significant morbidity. However, the significance of acute kidney injury (AKI) after lung transplantation remains unclear and poorly studied. We hypothesized that hemodialysis (HD)-dependent AKI after lung transplantation is associated with significant mortality. MATERIALS AND METHODS: We performed a retrospective review of all patients undergoing lung transplantation from July 1991 to July 2009 at our institution. Recipients with AKI (creatinine > 3 mg/dL) were identified. We compared recipients without AKI versus recipients with and without HD-dependent AKI. Kaplan-Meier survival curves were compared by log rank test. RESULTS: Of 352 lung transplant recipients reviewed at our institution, 17 developed non-HD-dependent AKI (5%) and 16 developed HD-dependent AKI (4.6%). Cardiopulmonary bypass was significantly higher in patients with HD-dependent AKI. None of the recipients who required HD had recovery of renal function. The 30-day mortality was significantly greater in recipients requiring HD (63% versus 0%; P < 0.0001). One-year mortality after transplantation was significantly increased in recipients with HD-dependent AKI compared with those with non-HD-dependent AKI (87.5% versus 17.6%; P < 0.001). CONCLUSIONS: Hemodialysis is associated with mortality after lung transplantation. Fortunately, AKI that does not progress to HD commonly resolves and has a better overall survival. Avoidance, if possible, of cardiopulmonary bypass may attenuate the incidence of AKI. Aggressive measures to identify and treat early postoperative renal dysfunction and prevent progression to HD may improve outcomes after lung transplantation.

PMID: 23481566 [PubMed - as supplied by publisher]

Scientific Registry of Transplant Recipients: Collecting, analyzing, and reporting data on transplantation in the United States.

Thu, 03/14/2013 - 11:50

Scientific Registry of Transplant Recipients: Collecting, analyzing, and reporting data on transplantation in the United States.

Transplant Rev (Orlando). 2013 Mar 4;

Authors: Leppke S, Leighton T, Zaun D, Chen SC, Skeans M, Israni AK, Snyder JJ, Kasiske BL

Abstract
Founded in 1987, the Scientific Registry of Transplant Recipients (SRTR) operates under a contract from the US government administered by the Health Resources and Services Administration (HRSA). SRTR maintains a database of comprehensive information on all solid organ transplantation in the US. The registry supports the ongoing evaluation of the clinical status of solid organ transplantation, including kidney, heart, liver, lung, intestine, pancreas, and multi-organ transplants. Data in the registry are from multiple sources, but most are collected by the Organ Procurement and Transplantation Network (OPTN) from hospitals, organ procurement organizations, and immunology laboratories. The data include information on current and past organ donors, transplant candidates, transplant recipients, transplant outcomes, and outcomes of living donors. SRTR uses these data to create reports and analyses for HRSA, OPTN committees that make organ allocation policy, and the Centers for Medicare & Medicaid Services to carry out quality assurance surveillance activities; SRTR also creates standard analysis files for scientific investigators. In addition, SRTR and OPTN produce an Annual Data Report and provide information upon request for the general public. Thus, SRTR supports the transplant community with information services and statistical analyses to improve patient access to and outcomes of organ transplant.

PMID: 23481320 [PubMed - as supplied by publisher]

Anti-inflammatory role of PGD2 in acute lung inflammation and therapeutic application of its signal enhancement.

Wed, 03/13/2013 - 12:44

Anti-inflammatory role of PGD2 in acute lung inflammation and therapeutic application of its signal enhancement.

Proc Natl Acad Sci U S A. 2013 Mar 11;

Authors: Murata T, Aritake K, Tsubosaka Y, Maruyama T, Nakagawa T, Hori M, Hirai H, Nakamura M, Narumiya S, Urade Y, Ozaki H

Abstract
We investigated the role of prostaglandin D2 (PGD2) signaling in acute lung injury (ALI), focusing on its producer-effector interaction in vivo. Administration of endotoxin increased edema and neutrophil infiltration in the WT mouse lung. Gene disruption of hematopoietic PGD synthase (H-PGDS) aggravated all of the symptoms. Experiments involving bone marrow transplantation between WT and H-PGDS-deficient mice showed that PGD2 derived from alveolar nonhematopoietic lineage cells (i.e., endothelial cells and epithelial cells) promotes vascular barrier function during the early phase (day 1), whereas neutrophil-derived PGD2 attenuates its own infiltration and cytokine expression during the later phase (day 3) of ALI. Treatment with either an agonist to the PGD2 receptor, DP, or a degradation product of PGD2, 15-deoxy-Δ12,14-PGJ2, exerted a therapeutic action against ALI. Data obtained from bone marrow transplantation between WT and DP-deficient mice suggest that the DP signal in alveolar endothelial cells is crucial for the anti-inflammatory reactions of PGD2. In vitro, DP agonism directly enhanced endothelial barrier formation, and 15-deoxy-Δ12,14-PGJ2 attenuated both neutrophil migration and cytokine expression. These observations indicate that the PGD2 signaling between alveolar endothelial/epithelial cells and infiltrating neutrophils provides anti-inflammatory effects in ALI, and suggest the therapeutic potential of these signaling enhancements.

PMID: 23479612 [PubMed - as supplied by publisher]

P. aeruginosa in the paranasal sinuses and transplanted lungs have similar adaptive mutations as isolates from chronically infected CF lungs.

Wed, 03/13/2013 - 12:44

P. aeruginosa in the paranasal sinuses and transplanted lungs have similar adaptive mutations as isolates from chronically infected CF lungs.

J Cyst Fibros. 2013 Mar 8;

Authors: Ciofu O, Johansen HK, Aanaes K, Wassermann T, Alhede M, von Buchwald C, Høiby N

Abstract
BACKGROUND: Pseudomonas aeruginosa cells are present as biofilms in the paranasal sinuses and the lungs of chronically infected cystic fibrosis (CF) patients. Since different inflammatory responses and selective antibiotic pressures are acting in the sinuses compared with the lungs, we compared the adaptive profiles of mucoid and non-mucoid isolates from the two locations. METHODS: We studied the genetic basis of phenotypic diversification and gene expression profiles in sequential lung and sinus P. aeruginosa isolates from four chronically infected CF patients, including pre- and post-lung transplantation isolates. RESULTS: The same phenotypes caused by similar mutations and similar gene expression profiles were found in mucoid and non-mucoid isolates from the paranasal sinuses and from the lungs before and after transplantation. CONCLUSION: Bilateral exchange of P. aeruginosa isolates between the paranasal sinuses and the lungs occurs in chronically infected patients and extensive sinus surgery before the lung transplantation might prevent infection of the new lung.

PMID: 23478131 [PubMed - as supplied by publisher]

Memory CD4+ T cells are required for optimal NK cell effector functions against the opportunistic fungal pathogen Pneumocystis murina.

Wed, 03/13/2013 - 12:44
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Memory CD4+ T cells are required for optimal NK cell effector functions against the opportunistic fungal pathogen Pneumocystis murina.

J Immunol. 2013 Jan 1;190(1):285-95

Authors: Kelly MN, Zheng M, Ruan S, Kolls J, D'Souza A, Shellito JE

Abstract
Little is known about the role of NK cells or their interplay with other immune cells during opportunistic infections. Using our murine model of Pneumocystis pneumonia, we found that loss of NK cells during immunosuppression results in substantial Pneumocystis lung burden. During early infection of C57B/6 CD4(+) T cell-depleted mice, there were significantly fewer NK cells in the lung tissue compared with CD4(+) T cell-intact animals, and the NK cells present demonstrated decreased upregulation of the activation marker NKp46 and production of the effector cytokine, IFN-γ. Furthermore, coincubation studies revealed a significant increase in fungal killing when NK cells were combined with CD4(+) T cells compared with either cell alone, which was coincident with a significant increase in perforin production by NK cells. Finally, however, we found through adoptive transfer that memory CD4(+) T cells are required for significant NK cell upregulation of the activation marker NK group 2D and production of IFN-γ, granzyme B, and perforin during Pneumocystis infection. To the best of our knowledge, this study is the first to demonstrate a role for NK cells in immunity to Pneumocystis pneumonia, as well as to establish a functional relationship between CD4(+) T cells and NK cells in the host response to an opportunistic fungal pathogen.

PMID: 23203926 [PubMed - indexed for MEDLINE]

Multiple redundant effector mechanisms of CD8+ T cells protect against influenza infection.

Wed, 03/13/2013 - 12:44
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Multiple redundant effector mechanisms of CD8+ T cells protect against influenza infection.

J Immunol. 2013 Jan 1;190(1):296-306

Authors: Hamada H, Bassity E, Flies A, Strutt TM, Garcia-Hernandez Mde L, McKinstry KK, Zou T, Swain SL, Dutton RW

Abstract
We have previously shown that mice challenged with a lethal dose of A/Puerto Rico/8/34-OVA(I) are protected by injection of 4-8 × 10(6) in vitro-generated Tc1 or Tc17 CD8(+) effectors. Viral load, lung damage, and loss of lung function are all reduced after transfer. Weight loss is reduced and survival increased. We sought in this study to define the mechanism of this protection. CD8(+) effectors exhibit multiple effector activities, perforin-, Fas ligand-, and TRAIL-mediated cytotoxicity, and secretion of multiple cytokines (IL-2, IL-4, IL-5, IL-9, IL-10, IL-17, IL-21, IL-22, IFN-γ, and TNF) and chemokines (CCL3, CCL4, CCL5, CXCL9, and CXCL10). Transfer of CD8(+) effectors into recipients, before infection, elicits enhanced recruitment of host neutrophils, NK cells, macrophages, and B cells. All of these events have the potential to protect against viral infections. Removal of any one, however, of these potential mechanisms was without effect on protection. Even the simultaneous removal of host T cells, host B cells, and host neutrophils combined with the elimination of perforin-mediated lytic mechanisms in the donor cells failed to reduce their ability to protect. We conclude that CD8(+) effector T cells can protect against the lethal effects of viral infection by means of a large number of redundant mechanisms.

PMID: 23197262 [PubMed - indexed for MEDLINE]

MiR-29c suppresses invasion and metastasis by targeting TIAM1 in nasopharyngeal carcinoma.

Wed, 03/13/2013 - 12:44
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MiR-29c suppresses invasion and metastasis by targeting TIAM1 in nasopharyngeal carcinoma.

Cancer Lett. 2013 Feb 28;329(2):181-8

Authors: Liu N, Tang LL, Sun Y, Cui RX, Wang HY, Huang BJ, He QM, Jiang W, Ma J

Abstract
Based on microarray analysis, we previously reported that miR-29c is significantly downregulated in nasopharyngeal carcinoma (NPC). However, little is known about the effect and molecular mechanisms of action of miR-29c deregulation during the development and progression of NPC. Quantitative RT-PCR demonstrated that miR-29c was significantly downregulated in NPC cell lines and clinical specimens. Wound healing, Transwell migration and lung metastasis assays demonstrated that ectopic expression of miR-29c inhibited NPC cell migration and invasion in vitro and suppressed the formation of lung metastases in vivo. T cell lymphoma invasion and metastasis 1 (TIAM1) was confirmed as a miR-29c target gene using luciferase reporter assays, quantitative RT-PCR and Western blotting. Ectopic expression of TIAM1 significantly promoted the migration and invasion of SUNE-1 cell line stably overexpressing miR-29c. The prognostic value of TIAM1 was analyzed in 217 NPC patients using immunohistochemistry. Strikingly, patients with high TIAM1 expression had poorer overall, disease-free and distant metastasis-free survival than patients with low TIAM1 expression. Furthermore, multivariate Cox regression analysis revealed that TIAM1 could serve as an independent prognostic factor in NPC. The newly identified miR-29c/TIAM1 pathway further elucidates the molecular mechanisms regulating invasion and metastasis in NPC, and may provide novel prognostic and treatment strategies for NPC patients.

PMID: 23142282 [PubMed - indexed for MEDLINE]

Profile of respiratory evaluation through surface electromyography, manovacuometry, and espirometry in candidates on the liver transplant waiting list.

Wed, 03/13/2013 - 12:44
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Profile of respiratory evaluation through surface electromyography, manovacuometry, and espirometry in candidates on the liver transplant waiting list.

Transplant Proc. 2012 Oct;44(8):2403-5

Authors: da Silva AM, Cliquet A, Boin IF

Abstract
INTRODUCTION: Electromyography (EMG) is the examination of skeletal muscle membrane electrical activity in response to physiologic activation. In healthy muscles, the square root (root mean square [RMS] is related to the amplitude of the obtained signal. Respiratory muscles are studied, especially those important for compliance, the diaphragm and the rectus abdominis. An evaluation to detect respiratory muscle deficits among liver disease patients on the waiting list for transplantation may serve as an alternative to providing specific treatments reducing the possibility of respiratory complications after transplantation.
OBJECTIVE: To study muscle activity by evaluating respiratory and surface EMG of the right diaphragm and right rectus abdominis muscles in patients on the liver transplant waiting list.
METHOD: Respiratory evaluation of muscle strength (maximum inspiratory pressure [MIP] and maximum expiratory pressure [MEP]) with a manometer -300, +300 from Gen-air; spirometry with Easyware Spirometer version 2.20; pulse oximetry with Nonim oximeter; Model for End-Stage Liver Disease (MELD) score as well as surface EMG of the diaphragm and rectus abdominis muscles from EMG/Brazil were applied in healthy and liver diseased subjects.
RESULTS: The 87 liver disease patients showed a mean age of 53.9 ± 7.3 years, mean body mass index of 28.21 ± 5.04 kg/m2 with 24.14% smokers (n = 21) and 43.68% physically active (n = 38 p) showing Diaphragm RMS of 61.05 ± 68.48 μV; rectus abdominis RMS of 45.28 ± 53.82 μV; MEP of 100.28 ± 27.85 cm H(2)O; and MIP of 92.41 ± 29.77 cm H2O. The average MELD of studied patients was 16.5 ± 0.71.
CONCLUSION: The respiratory profiles of patients on the liver transplant waiting list concerning muscle support were precarious owing to ascites and motor adynamia.

PMID: 23026606 [PubMed - indexed for MEDLINE]

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