De novo erythropoietin receptor (EPO-R) expression in human neoplastic glial cells decreases with grade of malignancy but is favourably associated with patient survival

2007 ◽  
Vol 33 (3) ◽  
pp. 299-307 ◽  
Author(s):  
M. Mittelbronn ◽  
D. Capper ◽  
B. Bunz ◽  
K. Dietz ◽  
B. Goeppert ◽  
...  
Keyword(s):  
Glial Cells ◽  
Patient Survival ◽  
De Novo ◽  
Erythropoietin Receptor ◽  
Grade Of Malignancy

scholarly journals Nonalcoholic steatohepatitis in posttransplantation liver: Review article

2018 ◽  
Vol 64 (2) ◽  
pp. 187-194 ◽  
Author(s):  
Antônio Ricardo Cardia Ferraz de Andrade ◽  
Helma P. Cotrim ◽  
Paulo L. Bittencourt ◽  
Carolina G. Almeida ◽  
Ney Christian Amaral Boa Sorte
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
Clinical Characteristics ◽  
Metabolic Disorders ◽  
Patient Survival ◽  
De Novo ◽  
Review Article ◽  
Liver Transplants ◽  
The Third ◽  
High Prevalence ◽  
The World

Summary Introduction: Nonalcoholic steatohepatitis (NASH) associated or not with cirrhosis is the third leading indication for liver transplantation (LT) around the world. After transplants, NASH has a high prevalence and occurs as both recurrent and de novo manifestations. De novo NASH can also occur in allografts of patients transplanted for non-NASH liver disease. Objective: To evaluate recurrent or de novo NASH in post-LT patients. Method: A literature review was performed using search engines of indexed scientific material, including Medline (by PubMed), Scielo and Lilacs, to identify articles published in Portuguese and English until August 2016. Eligible studies included: place and year of publication, prevalence, clinical characteristics, risk factors and survival. Results: A total of 110 articles were identified and 63 were selected. Most of the studies evaluated recurrence and survival after LT. Survival reached 90-100% in 1 year and 52-100% in 5 years. Recurrence of NAFLD (steatosis) was described in 15-100% and NASH, in 4-71%. NAFLD and de novo NASH were observed in 18-67% and 3-17%, respectively. Metabolic syndrome, diabetes mellitus, dyslipidemia and hypertension were seen in 45-58%, 18-59%, 25-66% and 52-82%, respectively. Conclusion: After liver transplants, patients present a high prevalence of recurrent and de novo NASH. They also show a high frequence of metabolic disorders. Nevertheless, these alterations seem not to influence patient survival.

scholarly journals Clinical Presentation, Outcomes, and Treatment of Membranous Nephropathy after Transplantation

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Artur Q. B. da Silva ◽  
Taina V. de Sandes-Freitas ◽  
Juliana B. Mansur ◽  
Jose Osmar Medicina-Pestana ◽  
Gianna Mastroianni-Kirsztajn
Keyword(s):  
Membranous Nephropathy ◽  
Clinical Presentation ◽  
Patient Survival ◽  
De Novo ◽  
Immunosuppressive Regimen ◽  
Graft Dysfunction ◽  
Class V ◽  
Clinical Presentations ◽  
Number Of Patients ◽  
Standard Strategy

There are scarce data about clinical presentation and outcomes of posttransplant membranous nephropathy (MN), and few reports include a large number of patients. This was a retrospective cohort including adult patients with posttransplant MN transplanted between 1983 and 2015 in a single center (n=41). Only patients with histological diagnosis of MN in kidney grafts were included. Clinical and laboratory presentation, histological findings, treatment, and outcomes were detailed. Patients were predominantly male (58.5%), with a mean age of 49.4 ± 13.2 years; 15 were considered as recurrent primary MN; 3 were class V lupus nephritis; 14 were considered as de novo cases, 7 secondary and 7 primary MN; and 9 cases were considered primary but it was not possible to distinguish between de novo MN and recurrence. Main clinical presentations were proteinuria (75.6%) and graft dysfunction (34.1%). Most patients with primary recurrent and de novo primary MN were submitted to changes in maintenance immunosuppressive regimen, but no standard strategy was identified; 31 patients presented partial or complete remission, and glomerulopathy appeared not to impact graft and patient survival.

High MFI De Novo MHC Class II Donor Specific Antibody Formation Impairs Patient Survival after Liver Transplantation

2012 ◽  
Vol 94 (10S) ◽  
pp. 131
Author(s):  
J. G. OʼLeary ◽  
H. Kaneku ◽  
B. M. Susskind ◽  
L. W. Jennings ◽  
G. B. Klintmalm ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Mhc Class Ii ◽  
Specific Antibody ◽  
Antibody Formation ◽  
Patient Survival ◽  
De Novo ◽  
Class Ii

Recurrent De Novo Mutations of EPOR Gene in Primary Congenital Polycythemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1297-1297
Author(s):  
Mariluz P. Mojica-Henshaw ◽  
Caroline Laverdiere ◽  
Jaroslav F. Prchal ◽  
Josef T. Prchal
Keyword(s):  
De Novo ◽  
Stop Codon ◽  
Cell Mass ◽  
Hemoglobin Concentration ◽  
Erythropoietin Receptor ◽  
De Novo Mutations ◽  
Erythroid Progenitors ◽  
Increased Risk ◽  
Genetic Mosaicism

Abstract Primary familial and congenital polycythemia (PFCP) is a rare inherited disorder presenting with elevated red blood cell mass, elevated hemoglobin concentration and low levels of erythropoietin. Ten mutations in the erythropoietin receptor (EPOR) gene to date have been associated with PFCP. All of these mutations result in deletion of 59 to 82 amino acids from the carboxy terminal of EpoR which has been shown to contain a negative regulatory domain. Here, we describe a 2-year old boy of French-Canadian descent presenting with polycythemia and splenomegaly. Sequencing of the EPOR gene showed the proband to be heterozygous for a G to A transition in nucleotide 6002 (G6002A). The mutation generates a stop codon instead of tryptophan at amino acid 439, leading to a truncated EpoR. The association of the G6002A mutation in the EPOR gene with PFCP has been previously described in a large Finnish family (dela Chapelle et al., Proc Natl Acad Sci USA1993; 90: 4495) and in a 16-year old boy of English descent (Percy et al., Br J Hematol1998; 100:407). The G6002A mutation in both cases was considered to have arisen independently based on differences in a microsatellite polymorphism in the 5′UT of EPOR and the absence of the mutation in the immediate family of the English boy. We studied our proband’s parents for the G6002A EPOR mutation and did not find it. Their parentage was confirmed using 24 different microsatellite markers. This indicates that the G6002A mutation in the proband arose de novo. Since the mutation arose de novo, in vitro methycellulose cultures of erythroid progenitors isolated from peripheral blood of the proband were grown in the presence of increasing concentrations of Epo to rule out genetic mosaicism. The erythroid progenitors showed hypersensitivity to Epo as is characteristic of PFCP. However, we did not find evidence supportive of genetic mosaicism as all 70 BFU-E colonies analyzed were heterozygous for the G6002A mutation. Previously, two other polycythemia-associated EPOR mutations, 5974insG (Sokol et al., Blood1995; 86:15) and 5959G>T (Kralovics et al., Am J Hematol2001; 68:115) were shown to have arisen de novo. This case is thus the fourth instance out of 13 reported cases of polycythemia-associated EPOR mutations that has arisen de novo. Because of the rarity of polycythemia-associated EPOR mutations, their frequent de novo occurrence suggests that these mutations do not have a selective advantage but are detrimental. Their possible association with increased risk of thromboembolic and atherosclerotic disease due to chronically augmented Epo signaling is being explored by ongoing clinical studies.

DE NOVO HEPATITIS C DECREASES PATIENT SURVIVAL AFTER LIVER TRANSPLANTATION.

2000 ◽  
Vol 69 (Supplement) ◽  
pp. S314
Author(s):  
Elisa Prados ◽  
Sonia Garcia-Vizuete ◽  
Angel Garcia-Villalon ◽  
Jose M. Moreno ◽  
Clara Salas ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Hepatitis C ◽  
Patient Survival ◽  
De Novo

SLCO1B3 polymorphisms and clinical outcomes in kidney transplant recipients receiving mycophenolate

2021 ◽  
Author(s):  
Lauren Schumacher ◽  
Fang Fang ◽  
Kelley M Kidwell ◽  
Faisal Shakeel ◽  
Daniel L Hertz ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Acute Rejection ◽  
Kidney Transplant ◽  
Patient Survival ◽  
De Novo ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Primary Analysis ◽  
Adult Kidney ◽  
Increased Risk

Aim: Determine the influence of SLCO1B3 polymorphisms on outcomes in kidney transplant recipients. Materials & methods: We retrospectively evaluated 181 adult kidney transplant recipients receiving mycophenolate. Outcomes included treated biopsy-proven acute rejection (tBPAR), de novo donor specific antibody (dnDSA) formation, graft survival, patient survival and mycophenolate-related adverse effects among SLCO1B3 genotypes. Results: The presence of SLCO1B3 variants was not associated with increased risk of tBPAR (HR: 1.45, 95% CI: 0.76–2.74), dnDSA (HR: 0.46, 95% CI: 0.16–1.36) or composite of tBPAR or dnDSA (HR: 1.14, 95% CI: 0.64–2.03). Graft and patient survival were reduced among variant carriers; however, inconsistent findings with the primary analysis suggest these associations were not due to genotype. Adverse effects were similar between groups. Conclusion: Presence of SLCO1B3 polymorphisms were not predictive of rejection or dnDSA in kidney transplant recipients.

scholarly journals The Impact of Sirolimus on hepatitis C Recurrence after Liver Transplantation

2011 ◽  
Vol 25 (1) ◽  
pp. 28-34 ◽  
Author(s):  
Sonal Asthana ◽  
Christian Toso ◽  
Glenda Meeberg ◽  
David L Bigam ◽  
Andrew Mason ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Hepatitis C ◽  
Patient Survival ◽  
De Novo ◽  
Survival Rates ◽  
Area Under The Curve ◽  
Immunosuppressive Drugs ◽  
Initial Recurrence ◽  
The Impact

BACKGROUND: While some immunosuppression strategies may accelerate hepatitis C virus (HCV) recurrence after liver transplantation (LT), the impact of sirolimus (SRL) is not known.OBJECTIVE: To assess the risk of biopsy-proven HCV recurrence and patient survival using known and suspected risk factors for HCV recurrence as covariates.METHODS: A retrospective analysis of 141 consecutive patients, including 88 who received de novo SRL therapy, who had undergone a first LT for HCV cirrhosis was conducted. Known and suspected risk factor covariates including transplant era, donor and recipient age, Model for End-stage Liver Disease score, cold ischemia time, immunosuppressive drugs and steroid treatment rejection rates were used in the assessment.RESULTS: Overall, 72.3% of the cohort developed biopsy-proven HCV recurrence. The incidence of HCV recurrence was not significantly different for patients treated with SRL (75% versus 69.8%; P=0.5). There was no difference found for time to recurrence, nor did mean activity or fibrosis scores differ at the time of initial recurrence. However, on follow-up using serial biopsies in patients with recurrence, the mean activity and fibrosis scores were significantly lower in the SRL group. Donor age and acute rejection episodes were the only factors affecting the HCV recurrence rate (expB 1.02 [95% CI 1.01 to 1.03]); P=0.03; and expB 2.8 [95% CI 1.8 to 4.3]; P<0.01], respectively). SRL treatment did not alter patient survival rates. Among patients treated with SRL-based immunosuppression, higher drug area under the curve levels were associated with a trend to lower disease activity and fibrosis at diagnosis; however, higher SRL levels were associated with shorter recurrence-free survival (P=0.038).CONCLUSION: Results of the present analysis suggest that de novo SRL-based immunosuppression can be safely used in patients undergoing LT for HCV-associated liver disease; however, SRL-based immunosuppression did not significantly affect the timing or severity of post-transplant HCV recurrence. HCV recurrence in SRL-treated patients had lower progressive activity and fibrosis levels on serial biopsy.

scholarly journals GDNF, A Neuron-Derived Factor Upregulated in Glial Cells during Disease

2020 ◽  
Vol 9 (2) ◽  
pp. 456 ◽  
Author(s):  
Marcelo Duarte Azevedo ◽  
Sibilla Sander ◽  
Liliane Tenenbaum
Keyword(s):  
Glial Cell ◽  
Glial Cells ◽  
Motor Neurons ◽  
Cell Activation ◽  
De Novo ◽  
Adult Brain ◽  
Enteric Neurons ◽  
Complex Signals ◽  
Glial Cell Activation ◽  
Injured Brain

In a healthy adult brain, glial cell line-derived neurotrophic factor (GDNF) is exclusively expressed by neurons, and, in some instances, it has also been shown to derive from a single neuronal subpopulation. Secreted GDNF acts in a paracrine fashion by forming a complex with the GDNF family receptor α1 (GFRα1), which is mainly expressed by neurons and can act in cis as a membrane-bound factor or in trans as a soluble factor. The GDNF/GFRα1 complex signals through interactions with the “rearranged during transfection” (RET) receptor or via the neural cell adhesion molecule (NCAM) with a lower affinity. GDNF can also signal independently from GFRα1 by interacting with syndecan-3. RET, which is expressed by neurons involved in several pathways (nigro–striatal dopaminergic neurons, motor neurons, enteric neurons, sensory neurons, etc.), could be the main determinant of the specificity of GDNF’s pro-survival effect. In an injured brain, de novo expression of GDNF occurs in glial cells. Neuroinflammation has been reported to induce GDNF expression in activated astrocytes and microglia, infiltrating macrophages, nestin-positive reactive astrocytes, and neuron/glia (NG2) positive microglia-like cells. This disease-related GDNF overexpression can be either beneficial or detrimental depending on the localization in the brain and the level and duration of glial cell activation. Some reports also describe the upregulation of RET and GFRα1 in glial cells, suggesting that GDNF could modulate neuroinflammation.

Sign in / Sign up

Export Citation Format

Share Document