scholarly journals Immunological and physiological observations in baboons with life-supporting genetically engineered pig kidney grafts

2017 ◽  
Vol 24 (2) ◽  
pp. e12293 ◽  
Author(s):  
Hayato Iwase ◽  
Hidetaka Hara ◽  
Mohamed Ezzelarab ◽  
Tao Li ◽  
Zhongqiang Zhang ◽  
...  
Keyword(s):  
Genetically Engineered ◽  
Pig Kidney

scholarly journals Bringing Home The Bacon: Update on The State of Kidney Xenotransplantation

2018 ◽  
Vol 45 (1-3) ◽  
pp. 254-259 ◽  
Author(s):  
David K.C. Cooper ◽  
H. Iwase ◽  
L. Wang ◽  
T. Yamamoto ◽  
Qi Li ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Kidney Transplantation ◽  
Graft Survival ◽  
Cellular Response ◽  
Genetic Manipulation ◽  
Immunosuppressive Agents ◽  
Cross Reactivity ◽  
Genetically Engineered ◽  
Kidney Graft ◽  
Pig Kidney

Background: There is a continuing critical shortage of organs from deceased human donors for transplantation, particularly for patients awaiting kidney transplantation. Efforts are being made to resolve the donor kidney shortage by the transplantation of kidneys from genetically-engineered pigs. Summary: This review outlines the pathobiological barriers to pig organ xenotransplantation in primates, which include (i) antibody-dependent complement-mediated rejection, (ii) a T cell-mediated elicited antibody and cellular response, (iii) coagulation dysregulation between pigs and primates, and (iv) a persistent inflammatory response. As a result of increasing genetic manipulation of the pig and the introduction of novel immunosuppressive agents, pig kidney graft survival has increased from minutes to months, and even to >1 year in some cases. Aspects of the selection of the patients for a first clinical trial are discussed. Although there would appear to be some cross-reactivity between anti-human leukocyte antigen (HLA) antibodies and swine leukocyte antigens expressed in pigs, some HLA-sensitized patients will be at no disadvantage if they receive a pig kidney. Furthermore, the current limited evidence is that, even if the patient becomes sensitized to pig antigens (after a pig organ transplant), this would not be detrimental to a subsequent allotransplant. The potential risk of infection with a pig microorganism, and the function of a pig kidney in a primate are also discussed. Key Message: The recent encouraging results of pig kidney transplantation in nonhuman primates suggest the likelihood of a successful (and safe) initial clinical trial, with graft survival for months or possibly years.

scholarly journals The Role of Interleukin-6 (IL-6) in the Systemic Inflammatory Response in Xenograft Recipients and in Pig Kidney Xenograft Failure

2021 ◽  
Vol 12 ◽  
Author(s):  
Guoqiang Zhang ◽  
Hayato Iwase ◽  
Qi Li ◽  
Takayuki Yamamoto ◽  
Abhijit Jagdale ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Systemic Inflammation ◽  
Graft Function ◽  
Genetically Engineered ◽  
Inflammatory Factors ◽  
Kidney Graft ◽  
Amyloid A ◽  
Pig Kidney ◽  
Tnf Α

BackgroundIn pig-to-baboon transplantation models, there is increasing evidence of systemic inflammation in xenograft recipients (SIXR) associated with pig xenograft failure. We evaluated the relationship between systemic inflammatory factors and pig kidney xenograft failure.MethodsBaboons received kidney transplants from genetically engineered pigs (n=9), and received an anti-CD40mAb-based (n=4) or conventional (n=5) immunosuppressive regimen. The pig kidney grafts were monitored by measurements of serum creatinine, serum amyloid A (SAA), white blood cell (WBC) and platelet counts, plasma fibrinogen, and pro-inflammatory cytokines (baboon and pig IL-6, TNF-α, IL-1β).ResultsSix baboons were euthanized or died from rejection, and 3 were euthanized for infection. Changes in serum creatinine correlated with those of SAA (r=0.56, p<0.01). Serum baboon IL-6 was increased significantly on day 1 after transplantation and at euthanasia (both p<0.05) and correlated with serum creatinine and SAA (r=0.59, p<0.001, r=0.58, p<0.01; respectively). but no difference was observed between rejection and infection. Levels of serum pig IL-6, TNF-α, IL-1β were also significantly increased on day 1 and at euthanasia, and serum pig IL-6 and IL-1β correlated with serum creatinine and SAA. The level of serum baboon IL-6 correlated with the expression of IL-6 and amyloid A in the baboon liver (r=0.93, p<0.01, r=0.79, p<0.05; respectively).ConclusionEarly upregulation of SAA and serum IL-6 may indicate the development of rejection or infection, and are associated with impaired kidney graft function. Detection and prevention of systemic inflammation may be required to prevent pig kidney xenograft failure after xenotransplantation.

scholarly journals Clinical Pig Kidney Xenotransplantation: How Close Are We?

2019 ◽  
Vol 31 (1) ◽  
pp. 12-21 ◽  
Author(s):  
David K. C. Cooper ◽  
Hidetaka Hara ◽  
Hayato Iwase ◽  
Takayuki Yamamoto ◽  
Abhijit Jagdale ◽  
...  
Keyword(s):  
Immune Response ◽  
Kidney Transplant ◽  
Adaptive Immune Response ◽  
Infectious Complications ◽  
Genetically Engineered ◽  
Kidney Graft ◽  
Human Donor ◽  
Adaptive Immune ◽  
Pig Kidney ◽  
Group B

Patients with ESKD who would benefit from a kidney transplant face a critical and continuing shortage of kidneys from deceased human donors. As a result, such patients wait a median of 3.9 years to receive a donor kidney, by which time approximately 35% of transplant candidates have died while waiting or have been removed from the waiting list. Those of blood group B or O may experience a significantly longer waiting period. This problem could be resolved if kidneys from genetically engineered pigs offered an alternative with an acceptable clinical outcome. Attempts to accomplish this have followed two major paths: deletion of pig xenoantigens, as well as insertion of “protective” human transgenes to counter the human immune response. Pigs with up to nine genetic manipulations are now available. In nonhuman primates, administering novel agents that block the CD40/CD154 costimulation pathway, such as an anti-CD40 mAb, suppresses the adaptive immune response, leading to pig kidney graft survival of many months without features of rejection (experiments were terminated for infectious complications). In the absence of innate and adaptive immune responses, the transplanted pig kidneys have generally displayed excellent function. A clinical trial is anticipated within 2 years. We suggest that it would be ethical to offer a pig kidney transplant to selected patients who have a life expectancy shorter than the time it would take for them to obtain a kidney from a deceased human donor. In the future, the pigs will also be genetically engineered to control the adaptive immune response, thus enabling exogenous immunosuppressive therapy to be significantly reduced or eliminated.

Mitochondrial Oxidation of p-N, N-Dimethylamino-β-Phenethylamine (DAPA)

1975 ◽  
Vol 33 ◽  
pp. 458-459
Author(s):  
W. Allen Shannon ◽  
Hannah L. Wasserkrug ◽  
andArnold M. Seligman
Keyword(s):  
Guinea Pig ◽  
Oxidase Activity ◽  
Amine Oxidase ◽  
Histochemical Demonstration ◽  
Guinea Pig Heart ◽  
Pig Kidney ◽  
Cytoplasmic Vacuoles ◽  
Liver And Kidney ◽  
Mitochondrial Oxidation ◽  
Amine Oxidase Activity

The synthesis of a new substrate, p-N,N-dimethylamino-β-phenethylamine (DAPA)3 (Fig. 1) (1,2), and the testing of it as a possible substrate for tissue amine oxidase activity have resulted in the ultracytochemical localization of enzyme oxidase activity referred to as DAPA oxidase (DAPAO). DAPA was designed with the goal of providing an amine that would yield on oxidation a stronger reducing aldehyde than does tryptamine in the histochemical demonstration of monoamine oxidase (MAO) with tetrazolium salts.Ultracytochemical preparations of guinea pig heart, liver and kidney and rat heart and liver were studied. Guinea pig kidney, known to exhibit high levels of MAO, appeared the most reactive of the tissues studied. DAPAO reaction product appears primarily in mitochondrial outer compartments and cristae (Figs. 2-4). Reaction product is also localized in endoplasmic reticulum, cytoplasmic vacuoles and nuclear envelopes (Figs. 2 and 3) and in the sarcoplasmic reticulum of heart.

Reproductive health issues in patients with psoriasis (literature review)

2019 ◽  
Vol 1 (7) ◽  
pp. 5-8
Author(s):  
L. S. Kruglova ◽  
A. A. Osina ◽  
A. A. Khotko
Keyword(s):  
Drug Therapy ◽  
Reproductive Health ◽  
Literature Review ◽  
Pregnancy Outcomes ◽  
Adverse Pregnancy Outcome ◽  
Certolizumab Pegol ◽  
Genetically Engineered ◽  
Health Issues ◽  
Degree Of Confidence ◽  
Adverse Pregnancy

Among patients with psoriasis, approximately 50% are women and almost 75 % of them are under the age of 40 years. Thus, most women with psoriasis have childbearing potential. When pregnancy occurs in 22 % of patients, the activity of psoriasis persists, characteristic of the course before pregnancy, in 23 % of women, the course of the disease worsens. The article provides up-to-date data on the management of pregnant patients with psoriasis. To improve pregnancy outcomes in patients with psoriasis, it is important to prevent exacerbation of the disease. The choice of drug therapy in this case is based on an assessment of the ratio of the risk of undesirable effects of the drugs on the developing fetus and the risk of the development of exacerbation of psoriasis, which can cause an adverse pregnancy outcome. Despite the fact that the available clinical experience of using genetically engineered drugs is still limited, with a certain degree of confidence we can say that there is no increase in the risk of adverse pregnancy outcomes associated with therapy with certolizumab pegol.

Quantum Dot Bioconjugates as Energy Donors in Fluorescence Resonance Energy Transfer Assays

2003 ◽  
Vol 773 ◽  
Author(s):  
Aaron R. Clapp ◽  
Igor L. Medintz ◽  
J. Matthew Mauro ◽  
Hedi Mattoussi
Keyword(s):  
Energy Transfer ◽  
Quantum Dot ◽  
Organic Dyes ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Genetically Engineered ◽  
Molar Ratio ◽  
Binding Assays ◽  
Specific Sequence ◽  
Donor Acceptor

AbstractLuminescent CdSe-ZnS core-shell quantum dot (QD) bioconjugates were used as energy donors in fluorescent resonance energy transfer (FRET) binding assays. The QDs were coated with saturating amounts of genetically engineered maltose binding protein (MBP) using a noncovalent immobilization process, and Cy3 organic dyes covalently attached at a specific sequence to MBP were used as energy acceptor molecules. Energy transfer efficiency was measured as a function of the MBP-Cy3/QD molar ratio for two different donor fluorescence emissions (different QD core sizes). Apparent donor-acceptor distances were determined from these FRET studies, and the measured distances are consistent with QD-protein conjugate dimensions previously determined from structural studies.

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