scholarly journals Long-term follow-up failed to detect in vitro transmission of full-length porcine endogenous retroviruses from specific pathogen-free pig islets to human cells

Diabetologia ◽  
2001 ◽  
Vol 44 (11) ◽  
pp. 2044-2055 ◽  
Author(s):  
B. Cl�menceau ◽  
D. J�gou ◽  
L. Martignat ◽  
P. Sa�
Keyword(s):  
Human Cells ◽  
Full Length ◽  
Endogenous Retroviruses ◽  
Specific Pathogen Free ◽  
Porcine Endogenous Retroviruses ◽  
Specific Pathogen ◽  
Long Term Follow Up

scholarly journals Absence of Replication-Competent Human-Tropic Porcine Endogenous Retroviruses in the Germ Line DNA of Inbred Miniature Swine

2004 ◽  
Vol 78 (5) ◽  
pp. 2502-2509 ◽  
Author(s):  
Linda Scobie ◽  
Samantha Taylor ◽  
James C. Wood ◽  
Kristen M. Suling ◽  
Gary Quinn ◽  
...  
Keyword(s):  
Genomic Dna ◽  
Germ Line ◽  
Human Cells ◽  
Endogenous Retroviruses ◽  
Open Reading Frames ◽  
Miniature Swine ◽  
Dna Libraries ◽  
Porcine Endogenous Retroviruses ◽  
Perv Transmission

ABSTRACT The potential transmission of porcine endogenous retroviruses (PERVs) has raised concern in the development of porcine xenotransplantation products. Our previous studies have resulted in the identification of animals within a research herd of inbred miniature swine that lack the capacity to transmit PERV to human cells in vitro. In contrast, other animals were capable of PERV transmission. The PERVs that were transmitted to human cells are recombinants between PERV-A and PERV-C in the post-VRA region of the envelope (B. A. Oldmixon, J. C. Wood, T. A. Ericsson, C. A. Wilson, M. E. White-Scharf, G. Andersson, J. L. Greenstein, H. J. Schuurman, and C. Patience, J. Virol. 76:3045-3048, 2002); these viruses we term PERV-A/C. This observation prompted us to determine whether these human-tropic replication-competent (HTRC) PERV-A/C recombinants were present in the genomic DNA of these miniature swine. Genomic DNA libraries were generated from one miniature swine that transmitted HTRC PERV as well as from one miniature swine that did not transmit HTRC PERV. HTRC PERV-A/C proviruses were not identified in the germ line DNAs of these pigs by using genomic mapping. Similarly, although PERV-A loci were identified in both libraries that possessed long env open reading frames, the Env proteins encoded by these loci were nonfunctional according to pseudotype assays. In the absence of a germ line source for HTRC PERV, further studies are warranted to assess the mechanisms by which HTRC PERV can be generated. Once identified, it may prove possible to generate animals with further reduced potential to produce HTRC PERV.

scholarly journals Establishment and Characterization of Molecular Clones of Porcine Endogenous Retroviruses Replicating on Human Cells

2000 ◽  
Vol 74 (9) ◽  
pp. 4028-4038 ◽  
Author(s):  
Frank Czauderna ◽  
Nicole Fischer ◽  
Klaus Boller ◽  
Reinhard Kurth ◽  
Ralf R. Tönjes
Keyword(s):  
Reverse Transcriptase Activity ◽  
Human Cells ◽  
Endogenous Retroviruses ◽  
Start Codon ◽  
293 Cells ◽  
Porcine Endogenous Retroviruses ◽  
Class B ◽  
Pig Genome ◽  
Genetic Recombinant

ABSTRACT The use of pig xenografts is being considered to alleviate the shortage of allogeneic organs for transplantation. In addition to the problems overcoming immunological and physiological barriers, the existence of numerous porcine microorganisms poses the risk of initiating a xenozoonosis. Recently, different classes of type C porcine endogenous retoviruses (PERV) which are infectious for human cells in vitro have been partially described. We therefore examined whether completely intact proviruses exist that produce infectious and replication-competent virions. Several proviral PERV sequences were cloned and characterized. One molecular PERV class B clone, PERV-B(43), generated infectious particles after transfection into human 293 cells. A second clone, PERV-B(33), which was highly homologous to PERV-B(43), showed a G-to-A mutation in the first start codon (Met to Ile) of the env gene, preventing this provirus from replicating. However, a genetic recombinant, PERV-B(33)/ATG, carrying a restoredenv start codon, became infectious and could be serially passaged on 293 cells similar to virus clone PERV-B(43). PERV protein expression was detected 24 to 48 h posttransfection (p.t.) using cross-reacting antiserum, and reverse transcriptase activity was found at 12 to 14 days p.t. The transcriptional start and stop sites as well as the splice donor and splice acceptor sites of PERV mRNA were mapped, yielding a subgenomic env transcript of 3.1 kb. PERV-B(33) and PERV-B(43) differ in the number of copies of a 39-bp segment in the U3 region of the long terminal repeat. Strategies to identify and to specifically suppress or eliminate those proviruses from the pig genome might help in the production of PERV-free animals.

In vitro characterization of commercial factor VIII concentrates: Long-term follow-up

1984 ◽  
Vol 49 (1) ◽  
pp. 53-59 ◽  
Author(s):  
C. Miyashita ◽  
P. Hellstern ◽  
M. K�hler ◽  
G. Blohn ◽  
E. Wenzel
Keyword(s):  
Factor Viii ◽  
In Vitro Characterization ◽  
Long Term Follow Up ◽  
Factor Viii Concentrates

scholarly journals Should chloroquine and hydroxychloroquine be used to treat COVID-19? A rapid review

BJGP Open ◽  
2020 ◽  
Vol 4 (2) ◽  
pp. bjgpopen20X101069 ◽  
Author(s):  
Kome Gbinigie ◽  
Kerstin Frie
Keyword(s):  
Clinical Trials ◽  
Relevant Literature ◽  
Safety Data ◽  
World Health ◽  
Rapid Review ◽  
Current Evidence ◽  
Long Term Follow Up

BackgroundOn the 11 March 2020, the World Health Organization (WHO) declared that COVID-19 was a pandemic. To date, there are no medical treatments for COVID-19 with proven effectiveness. Novel treatments and/or vaccines will take time to be developed and distributed to patients. In light of this, there has been growing interest in the use of existing medications, such as chloroquine (CQ) and hydroxychloroquine (HCQ), as potential treatments of this disease.AimTo establish the current evidence for the effectiveness of CQ and HCQ in treating COVID-19.Design & settingA rapid review of the literature was conducted.MethodElectronic searches in PubMed and Google Scholar were conducted on 21 March 2020. A further search was conducted in Google for relevant literature on 28 March 2020.ResultsThere is limited evidence of in vitro activity of CQ/HCQ against SARS-CoV-2. A number of in vivo clinical trials are underway. The empirical data available from two of these trials reveal conflicting results. Both trials are characterised by small numbers of participants (n = 30 and n = 36) and suffer methodological limitations. No medium or long-term follow-up data is available.ConclusionAt present, there is insufficient evidence to determine whether CQ/HCQ are safe and effective treatments for COVID-19. High quality, adequately powered randomised clinical trials in primary and secondary care settings are urgently required to guide policymakers and clinicians. These studies should report medium- and long-term follow-up results, and safety data.

Clinical course of rhinitis and changes in vivo and in vitro of allergic parameters in elderly patients: a long-term follow-up study

2012 ◽  
Vol 13 (1) ◽  
pp. 67-73 ◽  
Author(s):  
Gabriele Di Lorenzo ◽  
Maria Stefania Leto-Barone ◽  
Simona La Piana ◽  
Vito Ditta ◽  
Gaetana Di Fede ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Clinical Course ◽  
Follow Up Study ◽  
Long Term Follow Up

scholarly journals Study of Full-Length Porcine Endogenous Retrovirus Genomes with Envelope Gene Polymorphism in a Specific-Pathogen-Free Large White Swine Herd

2000 ◽  
Vol 74 (18) ◽  
pp. 8575-8581 ◽  
Author(s):  
Steffi Bösch ◽  
Claire Arnauld ◽  
André Jestin
Keyword(s):  
Endogenous Retrovirus ◽  
Amino Acid Sequences ◽  
Full Length ◽  
Endogenous Retroviruses ◽  
Envelope Gene ◽  
Specific Pathogen Free ◽  
Large White ◽  
Porcine Endogenous Retrovirus ◽  
Specific Pathogen

ABSTRACT Specific-pathogen-free (SPF) swine appear to be the most appropriate candidate for pig to human xenotransplantation. Still, the risk of endogenous retrovirus transmission represents a major obstacle, since two human-tropic porcine endogenous retroviruses (PERVs) had been characterized in vitro (P. Le Tissier, J. P. Stoye, Y. Takeuchi, C. Patience, and R. A. Weiss, Nature 389:681–682, 1997). Here we addressed the question of PERV distribution in a French Large White SPF pig herd in vivo. First, PCR screening for previously described PERV envelope genes envA, envB, and envC(D. E. Akiyoshi, M. Denaro, H. Zhu, J. L. Greenstein, P. Banerjee, and J. A. Fishman, J. Virol. 72:4503–4507, 1998; Le Tissier et al., op. cit.). demonstrated ubiquity of envAand envB sequences, whereas envC genes were absent in some animals. On this basis, selective out-breeding of pigs of remote origin might be a means to reduce proviral load in organ donors. Second, we investigated PERV genome carriage inenvC negative swine. Eleven distinct full-length PERV transcripts were isolated. The sequence of the complete envelope open reading frame was determined. The deduced amino acid sequences revealed the existence of four clones with functional and five clones with defective PERV PK-15 A- and B-like envelope sequences. The occurrence of easily detectable levels of PERV variants in different pig tissues in vivo heightens the need to assess PERV transmission in xenotransplantation animal models.

scholarly journals Antiretroviral Agents Inhibit Infection of Human Cells by Porcine Endogenous Retroviruses

2000 ◽  
Vol 44 (12) ◽  
pp. 3432-3433 ◽  
Author(s):  
S. K. Powell ◽  
M. E. Gates ◽  
G. Langford ◽  
M.-L. Gu ◽  
C. Lockey ◽  
...  
Keyword(s):  
Nucleoside Analogs ◽  
Antiretroviral Drugs ◽  
Human Cells ◽  
Endogenous Retroviruses ◽  
Antiretroviral Agents ◽  
Porcine Endogenous Retroviruses

ABSTRACT The efficacy of antiretroviral drugs against porcine endogenous retroviruses (PERV) that may be harbored in pig organs intended for transplantation was examined in human cells in vitro. The nucleoside analogs zidovudine and dideoxyinosine were found to effectively inhibit PERV replication.

A Phase I Study with Long-Term Follow-Up of Autologous Stem Cell Transplantation Using Photodynamic Treatment of Marrow Grafts for Relapsed/Refractory Acute Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2201-2201
Author(s):  
David Allan ◽  
Robert Belanger ◽  
Lambert Busque ◽  
Douglas Fish ◽  
Jeannine Kassis ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Leukemia ◽  
Autologous Transplantation ◽  
Disease Free Survival ◽  
Allogeneic Transplantation ◽  
Photodynamic Treatment ◽  
Long Term Follow Up

Abstract Autologous transplantation for acute leukemia is complicated by an elevated risk of leukemia relapse. Effective purging of stem cell grafts along with dose-intensive consolidation may be beneficial to patients who are ineligible for allogeneic transplantation. In pre-clinical studies, the photosensitizing agent benzoporphyrin derivative-monoacid A (BPD-MA) (QLT, Vancouver, Canada) demonstrated the ability to selectively target leukemia cells, generating fluorescence levels 2- to 20-fold higher on these cells than on normal cells. When exposed to light, BPD-MA induced in vitro photodynamic killing that was drug-dose, light-dose and cell-density dependent. This agent eliminated 3 to 6 logs of leukemia cell lines among normal hematopoietic cells as evaluated using in vitro limiting dilution assays and in vivo infusion of such treated grafts in murine recipients. In contrast, BPD-MA used in the same conditions was toxic to only one log of normal hematopoietic progenitors. These impressive results prompted us to perform a clinical Phase I trial to address the feasibility and safety of BPD-MA photodynamic therapy (PDT) for purging of marrow grafts prior to autologous transplantation in patients with high risk acute leukemia. Patients with acute leukemia in second or subsequent complete remission (CR), or with initial refractory disease were eligible. We evaluated 11 patients (6 female) with relapsed (n=10) or refractory (n=1) acute leukemia (acute myeloid leukemia = 10 pts; acute lymphoblastic leukemia = 1 pt) who were ineligible for allogeneic transplantation due to lack of an appropriate donor (8 patients) or age > 55 (3 patients). Median age at transplant was 44 years (range 17–63). All patients were transplanted with marrow grafts harvested immediately before the transplant and exposed to increasing doses of BPD-MA (10, 20 and 25 ng/ml) under a constant light dose (15 joules/cm2). Photodynamic treatment reduced mononuclear cell number by 28 ± 4.9%. Hematopoietic precursors in the graft were decreased by 59–81% (CFU-GM: 10.3 to 4.2x104/kg, p=0.018; BFU-E: 6.0 to 2.1x104/kg, p=0.007; and CFU-GEMM: 2.0 to 0.4x103/kg, p=0.015). Patients received busulphan (16 mg/kg) and cyclophosphamide (150 mg/kg) as myeloablative conditioning followed by infusion of the PDT treated stem cell graft. Median time to neutrophil (>0.5 x 109/l) and platelet engraftment (>20 x 109/l) was 27 days (range 17–68) and 81 days (51–224), respectively. Failure to engraft with neutrophils (>0.5 x 109/l) on day 40 occurred in 2 patients at 25 ng/ml BPD-MA, and maximum tolerated PDT dose was defined as 20 ng/ml BPD-MA. There was no procedure-related mortality, we observed usual rates of infectious complications, and non-hematologic toxicity was not identified. The estimated 5-year overall and disease-free survival is identical at 36 ± 14% with 4 patients alive in CR 41 to 91 months (median, 60 months) after transplantation. These results show that marrow purging with BPD-MA allows hematopoietic engraftment and adds no significant toxicity to the transplant procedure. The long-term follow-up in our study indicates that autologous marrow transplantation with photodynamic purging using BPD-MA is feasible and associated with encouraging rates of disease-free survival for patients with relapsed or refractory acute leukemia.

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