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Sample records for primate xenograft transplantation

  1. Protection against hyperacute xenograft rejection of transgenic rat hearts expressing human decay accelerating factor (DAF) transplanted into primates.

    PubMed Central

    Charreau, B.; Ménoret, S.; Tesson, L.; Azimzadeh, A.; Audet, M.; Wolf, P.; Marquet, R.; Verbakel, C.; Ijzermans, J.; Cowan, P.; Pearse, M.; d'Apice, A.; Soulillou, J. P.; Anegon, I.

    1999-01-01

    BACKGROUND: Production of transgenic pigs for multiple transgenes is part of a potential strategy to prevent immunological events involved in xenograft rejection. Use of a genetically engineerable rodent as a donor in primates could allow testing in vivo of the effects of different transgenes on controlling xenograft rejection. As a first step in the development of a donor containing multiple transgenes, transgenic rats for human decay-accelerating factor (DAF) were used as heart donors to test their resistance against complement (C)-mediated rejection by non-human primates. MATERIALS AND METHODS: Transgenic rats were generated by using a construct containing the human DAF cDNA under the transcriptional control of the endothelial cell (EC)-specific human ICAM-2 promoter. DAF expression was evaluated by immunohistology and by FACS analysis of purified ECs. Resistance of transgenic hearts against C-mediated damage was evaluated by ex vivo perfusion with human serum and by transplantation into cynomolgus monkeys. RESULTS: Immunohistological analysis of DAF expression in several organs from two transgenic lines showed uniform expression on the endothelium of all blood vessels. ECs purified from transgenic hearts showed 50% DAF expression compared to human ECs and >70% reduction of C-dependent cell lysis compared to control rat ECs. Hemizygous transgenic hearts perfused with human serum showed normal function for >60 min vs. 11. 2 +/- 1.7 min in controls. Hemi- or homozygous transgenic hearts transplanted into cynomolgus monkeys showed longer survival (15.2 +/- 7 min and >4.5 hr, respectively) than controls (5.5 +/- 1.4 min). In contrast to hyperacutely rejected control hearts, rejected homozygous DAF hearts showed signs of acute vascular rejection (AVR) characterized by edema, hemorrhage, and an intense PMN infiltration. CONCLUSIONS: We demonstrate that endothelial-specific DAF expression increased heart transplant survival in a rat-to-primate model of

  2. Pre-transplant antibody screening and anti-CD154 costimulation blockade promote long-term xenograft survival in a pig-to-primate kidney transplant model

    PubMed Central

    Higginbotham, Laura; Mathews, Dave; Breeden, Cynthia A.; Song, Mingqing; Farris, Alton Brad; Larsen, Christian P.; Ford, Mandy L.; Lutz, Andrew J.; Tector, Matthew; Newell, Kenneth A.; Tector, A. Joseph; Adams, Andrew B.

    2016-01-01

    Xenotransplantation has the potential to alleviate the organ shortage that prevents many patients with end-stage renal disease from enjoying the benefits of kidney transplantation. Despite significant advances in other models, pig-to-primate kidney xenotransplantation has met limited success. Preformed anti-pig antibodies are an important component of the xenogeneic immune response. To address this, we screened a cohort of 34 rhesus macaques for anti-pig antibody levels. We then selected animals with both low and high titers of anti-pig antibodies to proceed with kidney transplant from galactose-α1,3-galactose knockout/CD55 transgenic pig donors. All animals received T-cell depletion followed by maintenance therapy with costimulation blockade (either anti-CD154 mAb or belatacept), mycophenolate mofetil, and steroid. The animal with the high titer of anti-pig antibody rejected the kidney xenograft within the first week. Low-titer animals treated with anti-CD154 antibody, but not belatacept exhibited prolonged kidney xenograft survival (>133 and >126 vs. 14 and 21 days, respectively). Long-term surviving animals treated with the anti-CD154-based regimen continue to have normal kidney function and preserved renal architecture without evidence of rejection on biopsies sampled at day 100. This description of the longest reported survival of pig-to-non-human primate kidney xenotransplantation, now >125 days, provides promise for further study and potential clinical translation. PMID:25847130

  3. Primate models in organ transplantation.

    PubMed

    Anderson, Douglas J; Kirk, Allan D

    2013-09-01

    Large animal models have long served as the proving grounds for advances in transplantation, bridging the gap between inbred mouse experimentation and human clinical trials. Although a variety of species have been and continue to be used, the emergence of highly targeted biologic- and antibody-based therapies has required models to have a high degree of homology with humans. Thus, the nonhuman primate has become the model of choice in many settings. This article will provide an overview of nonhuman primate models of transplantation. Issues of primate genetics and care will be introduced, and a brief overview of technical aspects for various transplant models will be discussed. Finally, several prominent immunosuppressive and tolerance strategies used in primates will be reviewed. PMID:24003248

  4. Nonhuman Primate Infections after Organ Transplantation

    PubMed Central

    Haustein, Silke V.; Kolterman, Amanda J.; Sundblad, Jeffrey J.; Fechner, John H.; Knechtle, Stuart J.

    2016-01-01

    Nonhuman primates, primarily rhesus macaques (Macaca mulatta), cynomolgus macaques (Macaca fascicularis), and baboons (Papio spp.), have been used extensively in research models of solid organ transplantation, mainly because the nonhuman primate (NHP) immune system closely resembles that of the human. Nonhuman primates are also frequently the model of choice for preclinical testing of new immunosuppressive strategies. But the management of post-transplant nonhuman primates is complex, because it often involves multiple immunosuppressive agents, many of which are new and have unknown effects. Additionally, the resulting immunosuppression carries a risk of infectious complications, which are challenging to diagnose. Last, because of the natural tendency of animals to hide signs of weakness, infectious complications may not be obvious until the animal becomes severely ill. For these reasons the diagnosis of infectious complications is difficult among post-transplant NHPs. Because most nonhuman primate studies in organ transplantation are quite small, there are only a few published reports concerning infections after transplantation in nonhuman primates. Based on our survey of these reports, the incidence of infection in NHP transplant models is 14%. The majority of reports suggest that many of these infections are due to reactivation of viruses endemic to the primate species, such as cytomegalovirus (CMV), polyomavirus, and Epstein-Barr virus (EBV)–related infections. In this review, we address the epidemiology, pathogenesis, role of prophylaxis, clinical presentation, and treatment of infectious complications after solid organ transplantation in nonhuman primates. PMID:18323582

  5. Long-Term Lung Transplantation in Nonhuman Primates

    PubMed Central

    Aoyama, A.; Tonsho, M.; Ng, C. Y.; Lee, S.; Millington, T.; Nadazdin, O.; Wain, J. C.; Cosimi, A. B.; Sachs, D. H.; Smith, R. N.; Colvin, R. B.; Kawai, T.; Madsen, J. C.; Benichou, G.; Allan, J. S.

    2015-01-01

    Despite advances in surgical technique and clinical care, lung transplantation still remains a short-term solution for the treatment of end-stage lung disease. To date, there has been limited experience in experimental lung transplantation using nonhuman primate models. Therefore, we have endeavored to develop a long-term, nonhuman primate model of orthotopic lung transplantation for the ultimate purpose of designing protocols to induce tolerance of lung grafts. Here, we report our initial results in developing this model and our observation that the nonhuman primate lung is particularly prone to rejection. This propensity toward rejection may be a consequence of 1) upregulated nonspecific inflammation, and 2) a larger number of pre-existing alloreactive memory T cells, leading to augmented deleterious immune responses. Our data show that triple-drug immunosuppression mimicking clinical practice is not sufficient to prevent acute rejection in nonhuman primate lung transplantation. The addition of horse-derived anti-thymocyte globulin and a monoclonal antibody to the IL-6 receptor allowed six out of six lung recipients to be free of rejection for over 120 days. PMID:25772308

  6. Using non-human primates to benefit humans: research and organ transplantation.

    PubMed

    Shaw, David; Dondorp, Wybo; de Wert, Guido

    2014-11-01

    Emerging biotechnology may soon allow the creation of genetically human organs inside animals, with non-human primates (henceforth simply "primates") and pigs being the best candidate species. This prospect raises the question of whether creating organs in primates in order to then transplant them into humans would be more (or less) acceptable than using them for research. In this paper, we examine the validity of the purported moral distinction between primates and other animals, and analyze the ethical acceptability of using primates to create organs for human use. PMID:24807743

  7. Limited immune diversity in urodela: chronic transplantation responses occur even with family-disparate xenografts.

    PubMed

    Kinefuchi, Kenjiroh; Kushida, Yoshihiro; Touma, Maki; Hosono, Masamichi

    2013-07-01

    Urodele amphibians are thought to have poorer immune responses than evolutionary more ancestral vertebrate classes, such as bony fish. We investigated skin graft rejection and transplantation immunity in Urodele amphibians, Japanese newts, and Asiatic salamanders, and compared these findings to those from transplants in several species of frogs. The skin grafts used in this study were either allogeneic or xenogeneic. The mean survival time of the first set of allografts at 20°C was approximately 60 days for chronic responses in Urodela and 20 days for acute responses in Anura. As the graft survival times of urodeles were significantly longer than those of anurans, even when urodeles were repeatedly grafted from identical donors, there appear to be substantial differences in transplantation immunity between Urodela and Anura. These slow responses in Urodela may not be accompanied by the expansion of cytotoxic T cells, as observed in fish and anuran species, which are known to have functional major histocompatibility complex (MHC)-class I systems. In our study, approximately five histo-incompatible immunogenic components were found to be involved in chronic responses in newts. Similar chronic responses were also observed in xenograft rejection in newts. In contrast, xenografts were rejected in frogs due to an accelerated acute response, possibly involving natural killer cells. Our findings that some anti-allogeneic components appear to be shared with xenogeneic components indicate that the diversification of the acquired immune system is poorly developed in Urodela. PMID:23829218

  8. Uterine transplantation in primates: a mini-review of the literature.

    PubMed

    Kisu, I; Banno, K; Mihara, M; Hara, H; Kato, Y; Suganuma, N; Aoki, D

    2014-05-01

    Assisted reproductive technology has improved markedly in recent years, and many infertile patients have had children with the use of this technology. However, women with infertility due to an absent or nonfunctional uterus currently have no option of having a genetically linked child other than gestational surrogacy. Uterus transplantation (UTx) is now a possible approach for women with uterine-factor infertility to deliver a child. UTx studies have been performed in many animals, and accumulation of data from these studies has brought UTx within reach of clinical application. This has led to performance of UTx in humans in Saudi Arabia, Turkey, and Sweden. However, there has yet to be a delivery after allogeneic UTx in primates. More basic studies in primates are needed, and data from research in primates can provide important information for establishment of UTx in humans. In this review, we summarize the literature on UTx studies, with a focus on primates, both human and nonhuman. PMID:24815163

  9. Nonhuman Primate Models of Type 1 Diabetes Mellitus for Islet Transplantation

    PubMed Central

    Yu, Liang; He, Yayi

    2014-01-01

    Islet transplantation is an attractive treatment of type 1 diabetes mellitus (T1DM). Animal models of diabetes mellitus (DM) contribute a lot to the experimental studies of islet transplantation and to evaluations of isolated islet grafts for future clinical applications. Diabetic nonhuman primates (NHPs) represent the suitable models of DMs to better evaluate the effectiveness of islet transplantation, to assess new strategies for controlling blood glucose (BG), relieving immune rejection, or prolonging islet survival, and eventually to translate the preclinical data into tangible clinical practice. This review introduces some NHP models of DM, clarifies why and how the models should be used, and elucidates the usefulness and limitations of the models in islet transplantation. PMID:25389531

  10. Induction of transplantation tolerance in non-human primate preclinical models

    PubMed Central

    Hale, Douglas A; Dhanireddy, Kiran; Bruno, David; Kirk, Allan D

    2005-01-01

    Short-term outcomes following organ transplantation have improved considerably since the availability of cyclosporine ushered in the modern era of immunosuppression. In spite of this, many of the current limitations to progress in the field are directly related to the existing practice of relatively non-specific immunosuppression. These include increased risks of opportunistic infection and cancer, and toxicity associated with long-term immunosuppressive drug exposure. In addition, long-term graft loss continues to result in part from a failure to adequately control the anti-donor immune response. The development of a safe and reliable means of inducing tolerance would ameliorate these issues and improve the lives of transplant recipients, yet given the improving clinical standard of care, the translation of new therapies has become appropriately more cautious and dependent on increasingly predictive preclinical models. While convenient and easy to use, rodent tolerance models have not to date been reliably capable of predicting a therapy's potential efficacy in humans. Non-human primates possess an immune system that more closely approximates that found in humans, and have served as a more rigorous preclinical testing ground for novel therapies. Prior to clinical adaptation therefore, tolerance regimens should be vetted in non-human primates to ensure that there is sufficient potential for efficacy to justify the risk of its application. PMID:16147537

  11. Long-term survival of dopamine neurons derived from parthenogenetic primate embryonic stem cells (cyno-1) after transplantation.

    PubMed

    Sánchez-Pernaute, Rosario; Studer, Lorenz; Ferrari, Daniela; Perrier, Anselme; Lee, Hyojin; Viñuela, Angel; Isacson, Ole

    2005-08-01

    Dopamine (DA) neurons can be derived from human and primate embryonic stem (ES) cells in vitro. An ES cell-based replacement therapy for patients with Parkinson's disease requires that in vitro-generated neurons maintain their phenotype in vivo. Other critical issues relate to their proliferative capacity and risk of tumor formation, and the capability of migration and integration in the adult mammalian brain. Neural induction was achieved by coculture of primate parthenogenetic ES cells (Cyno-1) with stromal cells, followed by sequential exposure to midbrain patterning and differentiation factors to favor DA phenotypic specification. Differentiated ES cells were treated with mitomycin C and transplanted into adult immunosuppressed rodents and into a primate (allograft) with out immunosuppression. A small percentage of DA neurons survived in both rodent and primate hosts for the entire term of the study (4 and 7 months, respectively). Other neuronal and glial populations derived from Cyno-1 ES cells showed, in vivo, phenotypic characteristics and growth and migration patterns similar to fetal primate transplants, and a majority of cells (>80%) expressed the forebrain transcription factor brain factor 1. No teratoma formation was observed. In this study, we demonstrate long-term survival of DA neurons obtained in vitro from primate ES cells. Optimization of differentiation, cell selection, and cell transfer is required for functional studies of ES-derived DA neurons for future therapeutic applications. PMID:15941857

  12. Heart xenotransplantation in primate models.

    PubMed

    Postrach, Johannes; Bauer, Andreas; Schmoeckel, Michael; Reichart, Bruno; Brenner, Paolo

    2012-01-01

    Xenotransplantation is a potential solution for the worldwide persisting donor organ shortage. However, immunological and physiological barriers need to be overcome before the first clinical trials can be started. Nonhuman primates are considered the most suitable recipients in preclinical xenotransplantation models. Heterotopic abdominal cardiac xenotransplantation is a well-established nonworking heart model for immunological and biological studies on acute and delayed xenograft rejection and xenograft survival. Nevertheless, orthotopic life-supporting pig-to-baboon heart transplantation is the only accepted model for future cardiac xenotransplantation in humans so far. Survival times of 3 months in at least 60% of consecutive experiments have to be achieved and a minimum number of ten nonhuman primates have to survive for this period of time before clinical transplantation may be started. We recently introduced the heterotopic thoracic technique of pig-to-baboon heart transplantation. We believe that this technique combines the advantages of a working heart model with the safety of heterotopic transplantation. We describe the technical procedure of the three different pig-to-baboon models and give detailed information on perioperative care of the recipients. PMID:22565995

  13. Rejection of Cardiac Xenografts Transplanted from α 1,3-Galactosyltransferase Gene-Knockout (GalT-KO) Pigs to Baboons

    PubMed Central

    Hisashi, Y.; Yamada, K.; Kuwaki, K.; Tseng, Y.-L; Dor, F. J. M. F.; Houser, S. L; Robson, S. C.; Schuurman, H.-J.; Cooper, D. K. C.; Sachs, D. H.; Colvin, R. B.; Shimizu, A.

    2010-01-01

    The use of α 1,3-galactosyltransferase gene-knockout (GalT-KO) swine donors in discordant xenotransplantation has extended the survival of cardiac xenografts in baboons following transplantation. Eight baboons received heterotopic cardiac xenografts from GalT-KO swine and were treated with a chronic immunosuppressive regimen. The pathologic features of acute humoral xenograft rejection (AHXR), acute cellular xenograft rejection (ACXR) and chronic rejection were assessed in the grafts. No hyperacute rejection developed and one graft survived up to 6 months after transplantation. However, all GalT-KO heart grafts underwent graft failure with AHXR, ACXR and/or chronic rejection. AHXR was characterized by interstitial hemorrhage and multiple thrombi in vessels of various sizes. ACXR was characterized by TUNEL+ graft cell injury with the infiltration of T cells (including CD3 and TIA-1+ cytotoxic T cells), CD4+ cells, CD8+ cells, macrophages and a small number of B and NK cells. Chronic xenograft vasculopathy, a manifestation of chronic rejection, was characterized by arterial intimal thickening with TUNEL+ dead cells, antibody and complement deposition, and/or cytotoxic T-cell infiltration. In conclusion, despite the absence of the Gal epitope, acute and chronic antibody and cell-mediated rejection developed in grafts, maintained by chronic immunosupression, presumably due to de novo responses to non-Gal antigens. PMID:19032222

  14. Transplantation of human embryonic stem cell-derived retinal tissue in two primate models of retinal degeneration

    PubMed Central

    Shirai, Hiroshi; Mandai, Michiko; Matsushita, Keizo; Kuwahara, Atsushi; Yonemura, Shigenobu; Nakano, Tokushige; Assawachananont, Juthaporn; Kimura, Toru; Saito, Koichi; Terasaki, Hiroko; Eiraku, Mototsugu; Sasai, Yoshiki; Takahashi, Masayo

    2016-01-01

    Retinal transplantation therapy for retinitis pigmentosa is increasingly of interest due to accumulating evidence of transplantation efficacy from animal studies and development of techniques for the differentiation of human embryonic stem cells (hESCs) and induced pluripotent stem cells into retinal tissues or cells. In this study, we aimed to assess the potential clinical utility of hESC-derived retinal tissues (hESC-retina) using newly developed primate models of retinal degeneration to obtain preparatory information regarding the potential clinical utility of these hESC-retinas in transplantation therapy. hESC-retinas were first transplanted subretinally into nude rats with or without retinal degeneration to confirm their competency as a graft to mature to form highly specified outer segment structure and to integrate after transplantation. Two focal selective photoreceptor degeneration models were then developed in monkeys by subretinal injection of cobalt chloride or 577-nm optically pumped semiconductor laser photocoagulation. The utility of the developed models and a practicality of visual acuity test developed for monkeys were evaluated. Finally, feasibility of hESC-retina transplantation was assessed in the developed monkey models under practical surgical procedure and postoperational examinations. Grafted hESC-retina was observed differentiating into a range of retinal cell types, including rod and cone photoreceptors that developed structured outer nuclear layers after transplantation. Further, immunohistochemical analyses suggested the formation of host–graft synaptic connections. The findings of this study demonstrate the clinical feasibility of hESC-retina transplantation and provide the practical tools for the optimization of transplantation strategies for future clinical applications. PMID:26699487

  15. Transplanted dopamine neurons derived from primate ES cells preferentially innervate DARPP-32 striatal progenitors within the graft.

    PubMed

    Ferrari, Daniela; Sanchez-Pernaute, Rosario; Lee, Hyojin; Studer, Lorenz; Isacson, Ole

    2006-10-01

    The correct identity and functional capacity of transplanted dopamine (DA) neurons derived in vitro from embryonic stem (ES) cells is a critical factor for the development of an ES cell-based replacement therapy for Parkinson's disease. We transplanted primate Cyno-1 ES cells differentiated in vitro for 4 (progenitor ES cells) or 6 (differentiated ES cells) weeks, or control fetal primate cells into the striatum of hemi-parkinsonian rats. Partial behavioral recovery in amphetamine-induced rotation was correlated with the number of ES-derived tyrosine hydroxylase-positive (TH+) neurons in the grafts (r=0.5, P<0.05). Post mortem analysis of ES-derived grafts revealed TH+neurons with mature morphology, similar to fetal DA neurons, and expression of midbrain transcription factors, such as Engrailed (En) and Nurr-1. While the total number of TH+neurons was not different between the two groups, TH/En co-expression was significantly higher (>90%) in grafts from differentiated ES cells than in grafts derived from progenitor cells (<50%), reflecting a more heterogeneous cellular composition. Within the grafts there was an overlap between ES-derived TH+axonal arbors and clusters of primate ES-derived striatal neurons expressing brain factor 1 (Bf-1, Foxg1) and DA and cAMP-regulated phosphoprotein (DARPP-32). Such overlap was never observed for other regional transcription factors that define neighboring forebrain domains in the developing brain, such as Nkx2.1 (medial ganglionic eminence), Nkx2.2 (pallidal and diencephalic progenitors) or Pax6 (dorsal telencephalic progenitors). Despite the heterogeneity of ES-derived graft cell composition, these results demonstrate normal phenotypic specification, conserved natural axonal target selectivity and functionality of DA neurons derived from primate ES cells. PMID:17067292

  16. Endometrial stem cell transplantation in MPTP- exposed primates: an alternative cell source for treatment of Parkinson's disease.

    PubMed

    Wolff, Erin F; Mutlu, Levent; Massasa, Efi E; Elsworth, John D; Eugene Redmond, D; Taylor, Hugh S

    2015-01-01

    Parkinson's disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons in the substantia nigra. Cell-replacement therapies have emerged as a promising strategy to slow down or replace neuronal loss. Compared to other stem cell types, endometrium-derived stem cells (EDSCs) are an attractive source of stem cells for cellular therapies because of their ease of collection and vast differentiation potential. Here we demonstrate that endometrium-derived stem cells may be transplanted into an MPTP exposed monkey model of PD. After injection into the striatum, endometrium-derived stem cells engrafted, exhibited neuron-like morphology, expressed tyrosine hydroxylase (TH) and increased the numbers of TH positive cells on the transplanted side and dopamine metabolite concentrations in vivo. Our results suggest that endometrium-derived stem cells may provide a therapeutic benefit in the primate model of PD and may be used in stem cell based therapies. PMID:25283241

  17. Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft

    PubMed Central

    Mohiuddin, Muhammad M.; Singh, Avneesh K.; Corcoran, Philip C.; Thomas III, Marvin L.; Clark, Tannia; Lewis, Billeta G.; Hoyt, Robert F.; Eckhaus, Michael; Pierson III, Richard N.; Belli, Aaron J.; Wolf, Eckhard; Klymiuk, Nikolai; Phelps, Carol; Reimann, Keith A.; Ayares, David; Horvath, Keith A.

    2016-01-01

    Preventing xenograft rejection is one of the greatest challenges of transplantation medicine. Here, we describe a reproducible, long-term survival of cardiac xenografts from alpha 1-3 galactosyltransferase gene knockout pigs, which express human complement regulatory protein CD46 and human thrombomodulin (GTKO.hCD46.hTBM), that were transplanted into baboons. Our immunomodulatory drug regimen includes induction with anti-thymocyte globulin and αCD20 antibody, followed by maintenance with mycophenolate mofetil and an intensively dosed αCD40 (2C10R4) antibody. Median (298 days) and longest (945 days) graft survival in five consecutive recipients using this regimen is significantly prolonged over our recently established survival benchmarks (180 and 500 days, respectively). Remarkably, the reduction of αCD40 antibody dose on day 100 or after 1 year resulted in recrudescence of anti-pig antibody and graft failure. In conclusion, genetic modifications (GTKO.hCD46.hTBM) combined with the treatment regimen tested here consistently prevent humoral rejection and systemic coagulation pathway dysregulation, sustaining long-term cardiac xenograft survival beyond 900 days. PMID:27045379

  18. Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft.

    PubMed

    Mohiuddin, Muhammad M; Singh, Avneesh K; Corcoran, Philip C; Thomas, Marvin L; Clark, Tannia; Lewis, Billeta G; Hoyt, Robert F; Eckhaus, Michael; Pierson, Richard N; Belli, Aaron J; Wolf, Eckhard; Klymiuk, Nikolai; Phelps, Carol; Reimann, Keith A; Ayares, David; Horvath, Keith A

    2016-01-01

    Preventing xenograft rejection is one of the greatest challenges of transplantation medicine. Here, we describe a reproducible, long-term survival of cardiac xenografts from alpha 1-3 galactosyltransferase gene knockout pigs, which express human complement regulatory protein CD46 and human thrombomodulin (GTKO.hCD46.hTBM), that were transplanted into baboons. Our immunomodulatory drug regimen includes induction with anti-thymocyte globulin and αCD20 antibody, followed by maintenance with mycophenolate mofetil and an intensively dosed αCD40 (2C10R4) antibody. Median (298 days) and longest (945 days) graft survival in five consecutive recipients using this regimen is significantly prolonged over our recently established survival benchmarks (180 and 500 days, respectively). Remarkably, the reduction of αCD40 antibody dose on day 100 or after 1 year resulted in recrudescence of anti-pig antibody and graft failure. In conclusion, genetic modifications (GTKO.hCD46.hTBM) combined with the treatment regimen tested here consistently prevent humoral rejection and systemic coagulation pathway dysregulation, sustaining long-term cardiac xenograft survival beyond 900 days. PMID:27045379

  19. Demonstration of clonable alloreactive host T cells in a primate model for bone marrow transplantation

    SciTech Connect

    Reisner, Y.; Ben-Bassat, I.; Douer, D.; Kaploon, A.; Schwartz, E.; Ramot, B.

    1986-06-01

    The phenomenon of marrow rejection following supralethal radiochemotherapy was explained in the past mainly by non-T-cell mechanisms known to be resistant to high-dose irradiation. In the present study a low but significant number of radiochemoresistant-clonable T cells was found in the peripheral blood and spleen of Rhesus monkeys following the cytoreductive protocol used for treatment of leukemia patients prior to bone marrow transplantation. More than 95% of the clonable cells are concentrated in the spleen 5 days after transplant. The cells possess immune memory as demonstrated by the generation of alloreactive-specific cytotoxicity. The present findings suggest that host-versus-graft activity may be mediated by alloreactive T cells. It is hoped that elimination of such cells prior to bone marrow transplantation will increase the engraftment rate of HLA-nonidentical marrow in leukemia patients.

  20. Transplantation tolerance in primates after total lymphoid irradiation and allogeneic bone marrow injection

    SciTech Connect

    Smit, J.A.; Hill, R.R.H.; Myburgh, J.A.; Browde, S.

    1980-08-01

    After total lymphoid irradiation (TLI), allogeneic bone marrow (BM) injection, and organ transplantation in baboons, there is a prolonged period of reduced lymphocyte proliferative responsiveness to polyclonal mitogens and allogeneic lymphocytes. The effect observed is greater with the use of fractionated TLI than after single doses of irradiation. Suppressor cell activity can be demonstrated in vitro in most animals by inhibition of mixed lymphocyte reactivity (MLR) by mitomycin-treated recipient lymphocytes harvested after TLI, with or without allogeneic BM injection, and organ transplantation. Preliminary data suggest the presence of both donor-specific and nondonor-specific suppression, although other interpretations are possible, and suppressor phenomena may not be responsible for the transplantation tolerance observed.

  1. Prevention of EBV lymphoma development by oncolytic myxoma virus in a murine xenograft model of post-transplant lymphoproliferative disease

    SciTech Connect

    Kim, Manbok; Rahman, Masmudur M.; Cogle, Christopher R.

    2015-07-10

    Epstein–Barr virus (EBV) has been associated with a variety of epithelial and hematologic malignancies, including B-, T- and NK cell-lymphomas, Hodgkin's disease (HD), post-transplant lymphoproliferative diseases (LPDs), nasopharyngeal and gastric carcinomas, smooth muscle tumors, and HIV-associated lymphomas. Currently, treatment options for EBV-associated malignancies are limited. We have previously shown that myxoma virus specifically targets various human solid tumors and leukemia cells in a variety of animal models, while sparing normal human or murine tissues. Since transplant recipients of bone marrow or solid organs often develop EBV-associated post-transplant LPDs and lymphoma, myxoma virus may be of utility to prevent EBV-associated malignancies in immunocompromised transplant patients where treatment options are frequently limited. In this report, we demonstrate the safety and efficacy of myxoma virus purging as a prophylactic strategy for preventing post-transplant EBV-transformed human lymphomas, using a highly immunosuppressed mouse xenotransplantation model. This provides support for developing myxoma virus as a potential oncolytic therapy for preventing EBV-associated LPDs following transplantation of bone marrow or solid organ allografts. - Highlights: • Myxoma virus effectively infects and purges EBV lymphoma cells in vivo. • Oncolytic myxoma virus effectively eradicates oncogenic EBV tumorigenesis. • Ex vivo pre-treatment of myxoma virus can be effective as a preventive treatment modality for post-transplant lymphoproliferative diseases.

  2. AZ17: a new bispecific drug targeting IL-6 and IL-23 with potential clinical use--improves psoriasis in a human xenograft transplantation model.

    PubMed

    Stenderup, Karin; Rosada, Cecilia; Shanebeck, Kurt; Brady, William; Van Brunt, Michael P; King, Gordon; Marelli, Marcello; Slagle, Paul; Xu, Hengyu; Nairn, Natalie W; Johnson, Jeffrey; Wang, Aijun A; Li, Gary; Thornton, Kenneth C; Dam, Tomas N; Grabstein, Kenneth H

    2015-10-01

    Targeting more than one molecule in multifactorial diseases involving several disease mediators may provide improved therapeutic efficacy. Psoriasis is a multifactorial disease in which interleukin (IL)-6 and IL-23 are important disease mediators because they facilitate development of Th17 cells; widely accepted to be associated with psoriasis. To meet the need for new therapeutics, we aimed to create a clinically relevant bispecific drug, by combining the inhibitory properties of anti-IL-6 and anti-IL-23 antibodies, exhibiting high affinity, high stability and the ability to be produced in high yield. The bispecific molecule AZ17 was created by combining high affinity binding domains originating from monoclonal antibodies targeting human IL-6 and IL-23. To allow for high and efficient production, AZ17 was assembled by site-specific bioconjugation from two individual single chain fragment variables that were synthesized separately in Escherichia coli. To improve stability and extend pharmacokinetics, a flexible poly-ethylene glycol molecule was used as linker. In preclinical psoriasis models, AZ17 reduced IL-23-induced ear inflammation and improved psoriasis in a xenograft transplantation model where psoriasis skin is transplanted onto immune-deficient mice. The data presented here suggest AZ17 to be a promising drug candidate in psoriasis and other inflammatory diseases associated with Th17 cell development. PMID:26271488

  3. Influence of cell preparation and target location on the behavioral recovery after striatal transplantation of fetal dopaminergic neurons in a primate model of Parkinson's disease.

    PubMed

    Redmond, D E; Vinuela, A; Kordower, J H; Isacson, O

    2008-01-01

    Surgeries involving transplantation of fetal dopamine (DA) neurons into the caudate-putamen of patients with Parkinson's disease (PD) have been performed in various clinical trials to examine a potential restoration of motor function. The absence of studies in non-human primates to define the best transplantation protocols have lead to the use of a broad variety of techniques that potentially could have a major impact on the clinical outcome. The effects of using different cell and tissue preparation, and surgical targets, remain unknown. For this purpose, 20 St. Kitts African Green Monkeys (AFG) rendered parkinsonian by i.m. injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were balanced into 4 groups and unilaterally grafted in the (a) caudate or (b) putamen with fetal ventral mesencephalic (VM) tissue as (c) solid pieces or as a (d) cell suspension. By 9 months post-transplantation all animals showed significant and similar behavioral improvement as determined by a UPDRS based PD scale. Postmortem analyses showed that VM transplants survived in all animals. They were located in both surgical target sites, producing a broad DA reinnervation of the targeted nuclei that could also extend to the non-grafted nucleus on the ipsilateral side. Although no differences between groups were found in survival of DA neurons or degree of DA reinnervation, there was a significant correlation between striatal reinnervation and behavioral recovery only in animals transplanted in the putamen surgical target. Additionally, there was in general a stronger glial reaction to solid grafts than to cell suspensions. These studies provide data for the optimal time course, cell preparation and surgical targets for systematic examinations of both potential benefits and side effects of dopamine neuron cell transplantation in primate models of PD. PMID:17920901

  4. Successful function of autologous iPSC-derived dopamine neurons following transplantation in a non-human primate model of Parkinson's disease.

    PubMed

    Hallett, Penelope J; Deleidi, Michela; Astradsson, Arnar; Smith, Gaynor A; Cooper, Oliver; Osborn, Teresia M; Sundberg, Maria; Moore, Michele A; Perez-Torres, Eduardo; Brownell, Anna-Liisa; Schumacher, James M; Spealman, Roger D; Isacson, Ole

    2015-03-01

    Autologous transplantation of patient-specific induced pluripotent stem cell (iPSC)-derived neurons is a potential clinical approach for treatment of neurological disease. Preclinical demonstration of long-term efficacy, feasibility, and safety of iPSC-derived dopamine neurons in non-human primate models will be an important step in clinical development of cell therapy. Here, we analyzed cynomolgus monkey (CM) iPSC-derived midbrain dopamine neurons for up to 2 years following autologous transplantation in a Parkinson's disease (PD) model. In one animal, with the most successful protocol, we found that unilateral engraftment of CM-iPSCs could provide a gradual onset of functional motor improvement contralateral to the side of dopamine neuron transplantation, and increased motor activity, without a need for immunosuppression. Postmortem analyses demonstrated robust survival of midbrain-like dopaminergic neurons and extensive outgrowth into the transplanted putamen. Our proof of concept findings support further development of autologous iPSC-derived cell transplantation for treatment of PD. PMID:25732245

  5. Anti-Leukocyte Function-Associated Antigen 1 Therapy in a Nonhuman Primate Renal Transplant Model of Costimulation Blockade-Resistant Rejection.

    PubMed

    Anderson, D J; Lo, D J; Leopardi, F; Song, M; Turgeon, N A; Strobert, E A; Jenkins, J B; Wang, R; Reimann, K A; Larsen, C P; Kirk, A D

    2016-05-01

    Costimulation blockade with the fusion protein belatacept provides a desirable side effect profile and improvement in renal function compared with calcineurin inhibition in renal transplantation. This comes at the cost of increased rates of early acute rejection. Blockade of the integrin molecule leukocyte function-associated antigen 1 (LFA-1) has been shown to be an effective adjuvant to costimulation blockade in a rigorous nonhuman primate (NHP) model of islet transplantation; therefore, we sought to test this combination in an NHP renal transplant model. Rhesus macaques received belatacept maintenance therapy with or without the addition of LFA-1 blockade, which was achieved using a murine-derived LFA-1-specific antibody TS1/22. Additional experiments were performed using chimeric rhesus IgG1 (TS1/22R1) or IgG4 (TS1/22R4) variants, each engineered to limit antibody clearance. Despite evidence of proper binding to the target molecule and impaired cellular egress from the intravascular space indicative of a therapeutic effect similar to prior islet studies, LFA-1 blockade failed to significantly prolong graft survival. Furthermore, evidence of impaired protective immunity against cytomegalovirus was observed. These data highlight the difficulties in translating treatment regimens between organ models and suggest that the primarily vascularized renal model is more robust with regard to belatacept-resistant rejection than the islet model. PMID:26602755

  6. Establishment and Characterization of Baboon Embryonic Stem Cell Lines An Old World Primate Model for Regeneration and Transplantation Research

    PubMed Central

    Simerly, Calvin R.; Navara, Christopher S.; Castro, Carlos A.; Turpin, Janet C.; Redinger, Carrie J.; Mich-Basso, Jocelyn D.; Jacoby, Ethan S.; Grund, Kevin J.; McFarland, David A.; Oliver, Stacie L.; Ben-Yehudah, Ahmi; Carlisle, Diane L.; Frost, Patricia; Penedo, Cecilia; Hewitson, Laura; Schatten, Gerald

    2010-01-01

    Here we have developed protocols using the baboon as a complementary alternative Old World Primate to rhesus and other macaques which have severe limitations in their availability. Baboons are not limited as research resources, they are evolutionarily closer to humans and the multiple generations of pedigreed colonies which display complex human disease phenotypes all support their further optimization an invaluable primate model. Since neither baboon assisted reproductive technologies nor baboon embryonic stem cells (ESCs) have been reported, here we describe the first derivations and characterization of baboon ESC lines from IVF-generated blastocysts. Two ESCs lines (BabESC-4 and BabESC-15) display ESC morphology, express pluripotency markers (Oct-4, hTert, Nanog, Sox-2, Rex-1, TRA1–60, TRA1–81), and maintain stable euploid female karyotypes with parentage confirmed independently. They have been grown continuously for >430 and 290 days, respectively. Teratomas from both lines have all three germ layers. Availabilities of these BabESCs represent another important resource for stem cell biologists. PMID:19393591

  7. XENOTRANSPLANTATION – THE FUTURE OF CORNEAL TRANSPLANTATION?

    PubMed Central

    Hara, Hidetaka; Cooper, David K.C.

    2010-01-01

    Although corneal transplantation is readily available in the USA and certain other regions of the developed world, the need for human donor corneas worldwide far exceeds supply. There is currently renewed interest in the possibility of using corneas from other species, especially pigs, for transplantation into humans (xenotransplantation). The biomechanical properties of human and pig corneas are similar. Studies in animal models of corneal xenotransplantation have documented both humoral and cellular immune responses that play roles in xenograft rejection. The results obtained from the Tx of corneas from wild-type (i.e., genetically-unmodified) pigs into nonhuman primates have been surprisingly good and encouraging. Recent progress in the genetic manipulation of pigs has led to the prospect that the remaining immunological barriers will be overcome. There is every reason for optimism that corneal xenoTx will become a clinical reality within the next few years. PMID:21099407

  8. Transplantation tolerance in primates following total lymphoid irradiation and allogeneic bone marrow injection. I. Orthoptic liver allographs

    SciTech Connect

    Myburgh, J.A.; Smit, J.A.; Browde, S.; Hill, R.R.H.

    1980-05-01

    Fractionated total lymphoid irradiation (TLI) and allogeneic bone marrow (BM) injection have been reported to produce stable chimerism without graft-versus-host disease (GVHD) in inbred mice and rats and mongrel dogs, and transplantation tolerance for skin and heart grafts in rodents. This concept has been studied in outbred chacma baboons receiving orthotopic liver allografts with the use of five different irradiation protocols. Eight fractions of 200 rad to the whole torso, followed immediately by allogeneic BM injections, and liver grafts from the BM donors 3 to 4 weeks later resulted in markedly prolonged survivals of 63 to 106 days in four baboons (median survival of untreated controls 19 days). Only one of the four animals died directly from the effects of rejection. BM chimerism was demonstrated in two baboons. There were no clinical or histological signs of GVHD in any of the animals. Two fractions of TLI, totaling 800 rad, 23 hr apart and followed immediately by BM injection and liver grafting resulted in profound thrombocytopenia and death form intraperitoneal hemorrhage in four of five baboons. In one animal BM injection and liver transplantation were delayed for 75 days. The baboon is still alive more than 6 months later. Three groups received single doses of 300, 400, and 500 rad to the whole torso, followed by allogeneic BM injections 1 and 2 weeks later, and liver transplants from their BM donors after an additional 3 to 4 weeks. The four baboons receiving 300 rad survived for 42, 86, 123, and >180 days. Two of the four baboons receiving 400 rad died of septic intraabdominal complications with minimal or no evidence of rejection. Fourh of the five baboons receiving 500 rad died from rejection.

  9. Autologous iPSC-derived dopamine neuron transplantation in a nonhuman primate Parkinson’s disease model

    PubMed Central

    Wang, Shuyan; Zou, Chunlin; Fu, Linlin; Wang, Bin; An, Jing; Song, Gongru; Wu, Jianyu; Tang, Xihe; Li, Mo; Zhang, Jian; Yue, Feng; Zheng, Chengyun; Chan, Piu; Zhang, Y Alex; Chen, Zhiguo

    2015-01-01

    Autologous dopamine (DA) neurons are a new cell source for replacement therapy of Parkinson’s disease (PD). In this study, we tested the safety and efficacy of autologous induced pluripotent stem cell (iPSC)-derived DA cells for treatment of a cynomolgus monkey PD model. Monkey bone marrow mesenchymal cells were isolated and induced to iPSCs, followed by differentiation into DA cells using a method with high efficiency. Autologous DA cells were introduced into the brain of a cynomolgus monkey PD model without immunosuppression; three PD monkeys that had received no grafts served as controls. The PD monkey that had received autologous grafts experienced behavioral improvement compared with that of controls. Histological analysis revealed no overgrowth of grafts and a significant number of surviving A9 region-specific graft-derived DA neurons. The study provided a proof-of-principle to employ iPSC-derived autologous DA cells for PD treatment using a nonhuman primate PD model.

  10. Testicular recovery after irradiation differs in prepubertal and pubertal non-human primates, and can be enhanced by autologous germ cell transplantation

    PubMed Central

    Jahnukainen, Kirsi; Ehmcke, Jens; Quader, Mubina A.; Saiful Huq, M.; Epperly, Michael W.; Hergenrother, Scott; Nurmio, Mirja; Schlatt, Stefan

    2011-01-01

    BACKGROUND Although infertility is a serious concern in survivors of pediatric cancers, little is known about the influence of the degree of sexual maturation at the time of irradiation on spermatogenic recovery after treatment. Thus, we address this question in a non-human primate model, the rhesus monkey (Macaca mulatta). METHODS Two pubertal (testis size 3 and 6.5 ml, no sperm in ejaculate) and four prepubertal (testis size 1 ml, no sperm in ejaculate) macaques were submitted to a single fraction of testicular irradiation (10 Gy). Unilateral autologous transfer of cryopreserved testis cells was performed 2 months after irradiation. Testicular volume, histology and semen parameters were analyzed to assess irradiation effects and testicular recovery. RESULTS Irradiation provoked acute testis involution only in the two pubertal monkeys. Subsequently, testis sizes recovered and sperm was present in the ejaculates. Longitudinal outgrowth of seminiferous tubules continued, and, in testes without autologous cell transfer, 4–22% of tubular cross sections showed spermatogenesis 2 years after irradiation. In contrast, the four prepubertal monkeys showed neither a detectable involution as direct response to irradiation, nor a detectable growth of seminiferous tubules later. However, two of these animals showed spermarche 2 years after irradiation, and 8–12% of tubules presented spermatogenesis. One prepubertally irradiated monkey presented fast growth of one testis after cell transfer, and showed spermarche 1 year after irradiation. The infused testis had spermatogenesis in 70% of the tubules. The contralateral testis remained smaller. CONCLUSION We conclude that irradiation before puberty has a severe detrimental effect on outgrowth of seminiferous tubules. But, within the seminiferous epithelium, spermatogenetic recovery occurs at a low rate with no detectable relation to the maturity of the epithelium at irradiation. We also show that autologous testis cell

  11. Transplantation.

    PubMed

    Faro, Albert; Weymann, Alexander

    2016-08-01

    Despite improvement in median life expectancy and overall health, some children with cystic fibrosis (CF) progress to end-stage lung or liver disease and become candidates for transplant. Transplants for children with CF hold the promise to extend and improve the quality of life, but barriers to successful long-term outcomes include shortage of suitable donor organs; potential complications from the surgical procedure and immunosuppressants; risk of rejection and infection; and the need for lifelong, strict adherence to a complex medical regimen. This article reviews the indications and complications of lung and liver transplantation in children with CF. PMID:27469184

  12. The Primates.

    ERIC Educational Resources Information Center

    Naturescope, 1986

    1986-01-01

    Presents information about primates, including definitions and examples. Includes the activities "Thumbless Relay" and "Face It," which relate attributes of primates. Includes a story about chimpanzees along with discussion questions about the story. Reproducible worksheets and a quiz are also provided. (TW)

  13. Xenogeneic lung transplantation models

    PubMed Central

    Burdorf, Lars; Azimzadeh, Agnes M.; Pierson, Richard N.

    2014-01-01

    Summary Study of lung xenografts has proven useful to understand the remaining barriers to successful transplantation of other organ xenografts. In this chapter, the history and current status of lung xenotransplantation will be briefly reviewed and two different experimental models, the ex vivo porcine-to-human lung perfusion and the in vivo xenogeneic lung transplantation, will be presented. We will focus on the technical details of these lung xenograft models in sufficient detail, list the needed materials and mention analysis techniques to allow others to adopt them with minimal learning curve. PMID:22565996

  14. Transplantation: a brief history.

    PubMed

    Dangoor, Joseph Yoav; Hakim, David N; Singh, Rajinder Pal; Hakim, Nadey S

    2015-02-01

    Developments in transplantation have progressed dramatically over the past century. Current research is underway to optimize immune modulation, genetically engineering animals for xenografting, and breakthroughs are occurring in regenerative medicine. However, pioneering live-donor transplantation has transformed transplantation in the organ shortage, and these contribute an increased proportion of transplanted organs. Live-donor transplantation is associated with better long-term outcomes, and techniques to recover organs have become less invasive. We set out to examine the evolution of transplantation from its historic beginnings to the developments that make it successful today. PMID:25542855

  15. Antibody-mediated Xenograft Injury: Mechanisms and Protective Strategies

    PubMed Central

    Pierson, Richard N.

    2009-01-01

    The use of porcine organs for clinical transplantation is a promising potential solution to the shortage of human organs. Preformed anti-pig antibody is the primary cause of hyperacute rejection, while elicited antibody can contribute to subsequent “delayed” xenograft rejection. This article will review recent progress to overcome antibody mediated xenograft rejection, through modification of the host immunity and use of genetically engineered pig organs. PMID:19376229

  16. Establishment and characterization of five new human renal tumor xenografts.

    PubMed Central

    Beniers, A. J.; Peelen, W. P.; Schaafsma, H. E.; Beck, J. L.; Ramaekers, F. C.; Debruyne, F. M.; Schalken, J. A.

    1992-01-01

    Ten different human renal cell carcinoma (RCC) primary tumors were xenografted into BALB/c nu/nu mice. Five of the tumors (NU-10, NU-12, NU-20, NU-22, and NU-28) gave rise to serially transplantable tumors that were further characterized. Histology, DNA index, immunohistochemical characteristics, growth rate, and clonogenic potential were followed from primary tumor to the 5th to 15th transplant passage. Only one of the tumors (NU-20) showed remarkable instability for all tested parameters in the first five transplant passages. Histology of the other tumors was essentially the same to the histology of the primary tumors, although differences between human and host-derived vessels were apparent. DNA index values in general showed a trend toward an aneuploid character of the xenografts. Immunohistochemical analyses showed a loss of intensity of staining but a concomitant rise in the fraction of positively staining cells with antibodies against cytokeratins, vimentin, tumor-associated antigens, and human leukocyte antigen (HLA) class I antigens. Human leukocyte antigen class II antigen expression showed a loss of intensity as well as a decrease in the fraction of positive cells. Tumor doubling time was lowest in transplant passage number 0, and stable growth was noticed in transplant passages 1 through 4. Clonogenic potential of four of the lines was higher for the xenografts than for the primary tumors. The authors conclude that, on xenografting, histologic characteristics of the primary tumor are essentially conserved. Progression in the first transplant passages, however, results in tumors with a more aggressive character. Images Figure 1 PMID:1739137

  17. Total lymphoid irradiation and discordant cardiac xenografts

    SciTech Connect

    Kaplan, E.; Dresdale, A.R.; Diehl, J.T.; Katzen, N.A.; Aronovitz, M.J.; Konstam, M.A.; Payne, D.D.; Cleveland, R.J. )

    1990-01-01

    Total lymphoid irradiation can prolong concordant cardiac xenografts. The effects of total lymphoid irradiation in a discordant xenograft model (guinea pig to rat) were studied with and without adjuvant pharmacologic immunosuppression. Inbred Lewis rats were randomly allocated to one of four groups. Group 1 (n = 6) served as a control group and rats received no immunosuppression. Group 2 (n = 5) received triple-drug therapy that consisted of intraperitoneal azathioprine (2 mg/kg), cyclosporine (20 mg/kg), and methylprednisolone (1 mg/kg) for 1 week before transplantation. Group 3 animals (n = 5) received 15 Gy of total lymphoid irradiation in 12 divided doses over a 3-week period. Group 4 (n = 6) received both triple-drug therapy and total lymphoid irradiation as described for groups 2 and 3. Complement-dependent cytotoxicity assay was performed to determine if a correlation between complement-dependent cytotoxicity and rejection-free interval existed. Rejection was defined as cessation of graft pulsation and was confirmed by histologic test results. Only groups 1 and 2 showed a difference in survival (group 1, 6.9 +/- 1.0 minutes; group 2, 14.2 +/- 2.7 minutes, p = 0.02). Although total lymphoid irradiation did decrease complement-dependent cytotoxicity, linear regression revealed no correlation between complement-dependent cytotoxicity and graft survival (coefficient of correlation, 0.30). Unlike concordant cardiac xenografts, total lymphoid irradiation with or without triple-drug therapy does not prolong graft survival.

  18. Development and characterization of xenograft model systems for adenoid cystic carcinoma

    PubMed Central

    Moskaluk, Christopher A.; Baras, Alexander S.; Mancuso, Stefani; Fan, Hao; Davidson, Robert; Dirks, Dawn; Golden, Wendy; Frierson, Henry F.

    2014-01-01

    Adenoid Cystic Carcinoma (ACC) is one of the most common malignancies to arise in human salivary glands, and also arises in glandular tissue of other organ systems. To address the paucity of experimental model systems for this tumor type, we have undertaken a program of transplanting tissue samples of human ACC into immunodeficient nu/nu mice to create xenograft model systems. In 17 of 23 attempts (74%) xenograft tumors were successfully grown. In all cases, the histologic appearance of the donating tumor was recapitulated in the subsequent xenograft. Characterization of a subset of xenograft models by immunohistochemical biomarkers and by RNA transcript microarray analysis showed good fidelity in the recapitulation of gene expression patterns in the xenograft tumors compared to the human donor tumors. Since ACC is known to frequently contain a t(6;9) translocation that fuses the MYB and NFIB genes, fluorescence in situ hybridization (FISH) of twelve ACC xenograft models was performed that assayed MYB locus break-apart and MYB-NFIB locus fusion. 11/12 (92%) xenograft models revealed MYB locus rearrangement and 10/12 (83%) xenograft models showed evidence of fusion of the MYB and NFIB loci. The two related xenograft models (derived from primary and metastatic tumors, respectively, of the same human subject) were karyotyped, showing a t(1;6) translocation, suggesting MYB translocation to a novel fusion partner gene. Overall, our results indicate that ACC is amenable to xenografting and that ACC xenograft models recapitulate the molecular and morphologic characteristics of human tumors, suggesting utility as valid experimental and preclinical model systems for this disease. PMID:21709671

  19. Persistence of Indirect but Not Direct T Cell Xenoresponses in Baboon Recipients of Pig Cell and Organ Transplants.

    PubMed

    Buhler, L; Illigens, B M-W; Nadazdin, O; Tena, A; Lee, S; Sachs, D H; Cooper, D K C; Benichou, G

    2016-06-01

    We investigated the contributions of direct and indirect T cell antigen recognition pathways to the immune response to porcine antigens in naïve baboons and baboon recipients of pig xenografts. In naïve baboons, in vitro culture of peripheral blood T cells with intact pig cells (direct xenorecognition pathway) or pig cell sonicates and baboon antigen-presenting cells (indirect xenorecognition pathway) induced the activation and expansion of xenoreactive T cells producing proinflammatory cytokines, interleukin-2 and interferon-γ. Primary indirect xenoresponses were mediated by preexisting memory T cells, whose presence is not typically observed in primary alloresponses. Next, baboons were conditioned with a nonmyeloablative regimen before short-term immunosuppression and transplantation of xenogeneic peripheral blood progenitor cells and a kidney, heart, or pancreatic islets from a miniature swine. All transplants were rejected acutely within 30 days after their placement. Posttransplantation, we observed an inhibition of the direct xenoresponse but a significant expansion of indirectly activated proinflammatory T cells. These results suggest that additional treatment to suppress indirect T cell immunity in primates may be required to achieve tolerance of pig xenografts through hematopoietic chimerism. PMID:26718119

  20. Moral sensibilities and moral standing: Caplan on xenograft "donors".

    PubMed

    Nelson, James Lindemann

    1993-07-01

    [I]nterest in animals as a source of organs and tissues for human beings remains strong. New developments in immunosuppression technology promise to lower the technical barriers to a routine use of nonhumans as organ donors, and the image of colonies of animals kept at the ready for supplying the growing human need for new organs seems a much more plausible scenario now than it did when broached by transplantation specialists in the Sixties. As Arthur Caplan has powerfully argued, the prospects that other sources of organs may resolve the supply problem are grim.... In the face of these "pro-xenograft" pressures, it becomes all the more signficant to assess arguments against the practice that rest on considerations of the moral status of the nonhumans from whom the organs are taken. To be sure, xenograft faces other moral difficulties -- for example, concerns about the quality of informed consent obtained for recipients, worries about the possibility that xenografting will serve as a vector by which new and possibly virulent viruses become established in humans, and problems about whether such spending is equitable in the light of other unresolved human needs. Yet whether we morally wrong animals in taking their organs and their lives remains a decidedly central issue here, one that cannot be finessed away by developing better informed consent procedures, better anti-viral strategies, or by situating transplantation medicine in a just health care system. PMID:11651606

  1. Reliable Establishment of Human Sarcoma Xenografts in the Nude Rat

    PubMed Central

    Tinkey, Peggy T.; Milas, Mira

    1999-01-01

    Purpose. The ability to establish consistent human tumor xenografts in experimental animals is a crucial part of preclinical investigations.The goal of this study was to develop a method of establishing a human tumor xenograft in the leg of a nude rat for evaluation of new surgical and molecular methods of treatments of human extremity sarcoma. Methods and results. Initial attempts to produce sarcoma nodules by subcutaneous injection of a human leiomyosarcoma tumor cell suspension (SKLMS-1) resulted in tumor nodule formation in only four of 10 sites (40%).The xenograft method was modified to include younger nude rats of a different source and substrain (HSD:rnu/rnu, 5–9 weeks old), treated with 500 cGy whole-body irradiation, and the transplantation of tumor cells or small tumor fragments which had been embedded in Matrigel.These changes improved the tumor take rate per site to 52/52 (100%).Tumor nodules demonstrated rapid and progressive growth and histological features consistent with the original human sarcoma. Discussion. Successful human leiomyosarcoma establishment in these nude rats permits the investigation of sarcoma biology and treatment with surgical procedures for which a mouse model would be inadequate. In this study we identified modifications in technique which enhanced the xenografting of a leiomyosarcoma cell line in nude rats; these techniques may increase tumor take rates for other tumor types as well. PMID:18521275

  2. Human Immunodeficiency Virus Type 1 Infection of Neural Xenografts

    NASA Astrophysics Data System (ADS)

    Cvetkovich, Therese A.; Lazar, Eliot; Blumberg, Benjamin M.; Saito, Yoshihiro; Eskin, Thomas A.; Reichman, Richard; Baram, David A.; del Cerro, Coca; Gendelman, Howard E.; del Cerro, Manuel; Epstein, Leon G.

    1992-06-01

    Human immunodeficiency virus type 1 (HIV-1) infection is highly specific for its human host. To study HIV-1 infection of the human nervous system, we have established a small animal model in which second-trimester (11 to 17.5 weeks) human fetal brain or neural retina is transplanted to the anterior chamber of the eye of immunosuppressed adult rats. The human xenografts vascularized, formed a blood-brain barrier, and differentiated, forming neurons and glia. The xenografts were infected with cell-free HIV-1 or with HIV-1-infected human monocytes. Analysis by polymerase chain reaction revealed HIV-1 sequences in DNA from xenograft tissue exposed to HIV-1 virions, and in situ hybridization demonstrated HIV-1 mRNA localized in macrophages and multinucleated giant cells. Pathological damage was observed only in neural xenografts containing HIV-1-infected human monocytes, supporting the hypothesis that these cells mediate neurotoxicity. This small animal model allows the study of direct and indirect effects of HIV-1 infection on developing human fetal neural tissues, and it should prove useful in evaluating antiviral therapies, which must ultimately target HIV-1 infection of the brain.

  3. Property in Nonhuman Primates

    ERIC Educational Resources Information Center

    Brosnan, Sarah F.

    2011-01-01

    Property is rare in most nonhuman primates, most likely because their lifestyles are not conducive to it. Nonetheless, just because these species do not frequently maintain property does not mean that they lack the propensity to do so. Primates show respect for possession, as well as behaviors related to property, such as irrational decision…

  4. Xenograft survival in two species combinations using total-lymphoid irradiation and cyclosporine

    SciTech Connect

    Knechtle, S.J.; Halperin, E.C.; Bollinger, R.R.

    1987-02-01

    Total lymphoid irradiation (TLI) has profound immunosuppressive actions and has been applied successfully to allotransplantation but not xenotransplantation. Cyclosporine (CsA) has not generally permitted successful xenotransplantation of organs but has not been used in combination with TLI. TLI and CsA were given alone and in combination to rats that were recipients of hamster or rabbit cardiac xenografts. Combined TLI and CsA prolonged survival of hamster-to-rat cardiac xenografts from three days in untreated controls to greater than 100 days in most recipients. TLI alone significantly prolonged rabbit to rat xenograft survival with doubling of survival time. However, combined treatment did not significantly prolong rabbit-to-rat cardiac xenograft survival compared with TLI alone. The hamster and rat are phylogenetically closely related. Transplants from hamsters to rat are concordant xenografts since the time course of unmodified rejection is similar to first-set rejection of allografts. Although the rabbit-to-rat transplant is also between concordant species (average survival of untreated controls: 3.2 days) the rabbit and rat are more distantly related. These results suggest that TLI is an effective immunosuppressant when applied to cardiac xenotransplants in these animal models; that the choice of species critically affects xenograft survival when TLI and/or CsA are used for immunosuppression; and that the closely related species combination tested has markedly prolonged (greater than 100 days) survival using combined TLI and CsA.

  5. Nonhuman primate models in translational regenerative medicine.

    PubMed

    Daadi, Marcel M; Barberi, Tiziano; Shi, Qiang; Lanford, Robert E

    2014-12-01

    Humans and nonhuman primates (NHPs) are similar in size, behavior, physiology, biochemistry, structure and function of organs, and complexity of the immune system. Research on NHPs generates complementary data that bridge translational research from small animal models to humans. NHP models of human disease offer unique opportunities to develop stem cell-based therapeutic interventions that directly address relevant and challenging translational aspects of cell transplantation therapy. These include the use of autologous induced pluripotent stem cell-derived cellular products, issues related to the immune response in autologous and allogeneic setting, pros and cons of delivery techniques in a clinical setting, as well as the safety and efficacy of candidate cell lines. The NHP model allows the assessment of complex physiological, biochemical, behavioral, and imaging end points, with direct relevance to human conditions. At the same time, the value of using primates in scientific research must be carefully evaluated and timed due to expense and the necessity for specialized equipment and highly trained personnel. Often it is more efficient and useful to perform initial proof-of-concept studies for new therapeutics in rodents and/or other species before the pivotal studies in NHPs that may eventually lead to first-in-human trials. In this report, we present how the Southwest National Primate Research Center, one of seven NIH-funded National Primate Research Centers, may help the global community in translating promising technologies to the clinical arena. PMID:25457970

  6. Nonhuman Primate Models in Translational Regenerative Medicine

    PubMed Central

    Daadi, Marcel M.; Barberi, Tiziano; Shi, Qiang; Lanford, Robert E.

    2014-01-01

    Abstract Humans and nonhuman primates (NHPs) are similar in size, behavior, physiology, biochemistry, structure and function of organs, and complexity of the immune system. Research on NHPs generates complementary data that bridge translational research from small animal models to humans. NHP models of human disease offer unique opportunities to develop stem cell–based therapeutic interventions that directly address relevant and challenging translational aspects of cell transplantation therapy. These include the use of autologous induced pluripotent stem cell–derived cellular products, issues related to the immune response in autologous and allogeneic setting, pros and cons of delivery techniques in a clinical setting, as well as the safety and efficacy of candidate cell lines. The NHP model allows the assessment of complex physiological, biochemical, behavioral, and imaging end points, with direct relevance to human conditions. At the same time, the value of using primates in scientific research must be carefully evaluated and timed due to expense and the necessity for specialized equipment and highly trained personnel. Often it is more efficient and useful to perform initial proof-of-concept studies for new therapeutics in rodents and/or other species before the pivotal studies in NHPs that may eventually lead to first-in-human trials. In this report, we present how the Southwest National Primate Research Center, one of seven NIH-funded National Primate Research Centers, may help the global community in translating promising technologies to the clinical arena. PMID:25457970

  7. Primate molecular divergence dates.

    PubMed

    Steiper, Michael E; Young, Nathan M

    2006-11-01

    With genomic data, alignments can be assembled that greatly increase the number of informative sites for analysis of molecular divergence dates. Here, we present an estimate of the molecular divergence dates for all of the major primate groups. These date estimates are based on a Bayesian analysis of approximately 59.8 kbp of genomic data from 13 primates and 6 mammalian outgroups, using a range of paleontologically supported calibration estimates. Results support a Cretaceous last common ancestor of extant primates (approximately 77 mya), an Eocene divergence between platyrrhine and catarrhine primates (approximately 43 mya), an Oligocene origin of apes and Old World monkeys (approximately 31 mya), and an early Miocene (approximately 18 mya) divergence of Asian and African great apes. These dates are examined in the context of other molecular clock studies. PMID:16815047

  8. Primate taxonomy: species and conservation.

    PubMed

    Rylands, Anthony B; Mittermeier, Russell A

    2014-01-01

    Primatology as a discrete branch of science involving the study of primate behavior and ecology took off in the 1960s after discovery of the importance of primates as models for biomedical research and the realization that primates provide insights into the evolutionary history of humans. Osman Hill's unfortunately incomplete monograph series on the comparative anatomy and taxonomy of the primates(1) and the Napiers' 1967 A Handbook of Living Primates(2) recorded the world's view of primate diversity at this time. This taxonomy remained the baseline for nearly three decades, with the diversity of each genus being represented by some species, but extensively as subspecies. PMID:24591133

  9. Prevention of pancreatic islet xenograft rejection by dietary vitamin E.

    PubMed Central

    Vajkoczy, P.; Lehr, H. A.; Hübner, C.; Arfors, K. E.; Menger, M. D.

    1997-01-01

    In pancreatic islet transplantation, the adhesion of activated leukocytes to endothelial cells and the loss of microvascular integrity represent the critical microcirculatory events, which promote loss of graft function due to rejection. With the view that oxygen radicals may contribute to graft rejection, we studied the effect of the antioxidant vitamin E on microvascular rejection of islet grafts. Islets were transplanted syngeneically and xenogeneically (rat) into dorsal skin-fold chambers of hamsters, which received a non-vitamin-E-supplemented laboratory chow. Treated animals with xenografts were fed with a diet supplemented with vitamin E in a low (150 mg/kg) and high (8000 mg/kg) concentration. Intravital fluorescence microscopy demonstrated complete vascularization of syngeneic grafts at day 10 after transplantation, intact islet microcirculation at day 20 with a functional capillary density of 653 +/- 6 cm-1, and only few leukocytes adherent to the endothelial lining of the islets' microvasculature (88 +/- 23 mm-2). Xenogeneic islets showed initial signs of rejection at day 6, including adhesion of leukocytes to the microvascular endothelium (610 +/- 110 mm-2) and loss of endothelial integrity. After 20 days, functional capillary density was significantly lower (173 +/- 68 cm-1) when compared with syngeneic grafts, indicating failure of graft acceptance. Supplementation of the diet with low and high concentrations of vitamin E resulted in a significant (P < 0.05) reduction of xenograft leukocyte-endothelium interaction (146 +/- 29 mm-2 and 109 +/- 42 mm-2) at day 6 after transplantation and and adequate development of functional capillary density at day 20 (478 +/- 36 cm-1 and 539 +/- 86 cm-1; P < 0.05), indicating prevention of microvascular rejection. We conclude that dietary supplementation of the lipophilic antioxidant vitamin E attenuates leukocyte-endothelial cell interactions, preserves microvascular integrity, and thus inhibits microvascular

  10. Bone marrow transplant

    MedlinePlus

    Transplant - bone marrow; Stem cell transplant; Hematopoietic stem cell transplant; Reduced intensity nonmyeloablative transplant; Mini transplant; Allogenic bone marrow transplant; Autologous bone marrow transplant; ...

  11. Bone marrow transplant

    MedlinePlus

    Transplant - bone marrow; Stem cell transplant; Hematopoietic stem cell transplant; Reduced intensity, nonmyeloablative transplant; Mini transplant; Allogenic bone marrow transplant; Autologous bone marrow transplant; Umbilical ...

  12. Busulfan depletes neutrophils and delays accelerated acute rejection of discordant xenografts in the guinea pig-to-rat model.

    PubMed

    Brauer, Robert B; Beck, Tino; Stehle, Ingo; Kremer, Marcus; Heidecke, Claus-Dieter

    2003-01-01

    Complement factor C6 plays a critical role in mediating hyperacute rejection of discordant xenografts. In order to explore the mechanism of discordant xenograft rejection, we investigated kinetics and phenotypes of the cellular infiltrate in xenografts in untreated and leukocyte-depleted recipients, in relation to graft survival. Guinea pig cardiac xenografts were heterotopically transplanted to totally C6-deficient PVG (C-) rats. Grafts were removed after 0, 6, 12, and 24 h ( n = 6). Histological evaluation was performed with hematoxylin and eosin (H & E) and immunoperoxidase staining. The agents fucoidin and busulfan were applied to delay xenograft rejection further. Within 6 h, minimal perivascular edema with isolated infiltrating CD11b/c- and ED1-positive cells were found. An intense infiltration of CD11b/c- and ED1-positive cells with interstitial hemorrhage was present after 24 h, though with little CD161 and CD3 cell infiltration. Inhibition of cell adhesion by fucoidin did not prolong xenograft survival (34 +/- 15 h, n = 4, P<0.47), but the depletion of granulocytes by injection of busulfan did prolong survival of the discordant xenografts, to 62 +/- 22 h ( n = 7, P < or = 0.0039). These results demonstrate a significant effect of specific depletion of granulocytes and macrophages by busulfan therapy on guinea pig cardiac xenograft survival in PVG (C-) rats, suggesting the participation of these infiltrating cells in the xenoreactive rejection process. PMID:12545340

  13. Hands of early primates.

    PubMed

    Boyer, Doug M; Yapuncich, Gabriel S; Chester, Stephen G B; Bloch, Jonathan I; Godinot, Marc

    2013-12-01

    Questions surrounding the origin and early evolution of primates continue to be the subject of debate. Though anatomy of the skull and inferred dietary shifts are often the focus, detailed studies of postcrania and inferred locomotor capabilities can also provide crucial data that advance understanding of transitions in early primate evolution. In particular, the hand skeleton includes characteristics thought to reflect foraging, locomotion, and posture. Here we review what is known about the early evolution of primate hands from a comparative perspective that incorporates data from the fossil record. Additionally, we provide new comparative data and documentation of skeletal morphology for Paleogene plesiadapiforms, notharctines, cercamoniines, adapines, and omomyiforms. Finally, we discuss implications of these data for understanding locomotor transitions during the origin and early evolutionary history of primates. Known plesiadapiform species cannot be differentiated from extant primates based on either intrinsic hand proportions or hand-to-body size proportions. Nonetheless, the presence of claws and a different metacarpophalangeal [corrected] joint form in plesiadapiforms indicate different grasping mechanics. Notharctines and cercamoniines have intrinsic hand proportions with extremely elongated proximal phalanges and digit rays relative to metacarpals, resembling tarsiers and galagos. But their hand-to-body size proportions are typical of many extant primates (unlike those of tarsiers, and possibly Teilhardina, which have extremely large hands). Non-adapine adapiforms and omomyids exhibit additional carpal features suggesting more limited dorsiflexion, greater ulnar deviation, and a more habitually divergent pollex than observed plesiadapiforms. Together, features differentiating adapiforms and omomyiforms from plesiadapiforms indicate increased reliance on vertical prehensile-clinging and grasp-leaping, possibly in combination with predatory behaviors in

  14. Infection of Nonhuman Primate Cells by Pig Endogenous Retrovirus

    PubMed Central

    Blusch, Juergen H.; Patience, Clive; Takeuchi, Yasuhiro; Templin, Christian; Roos, Christian; Von Der Helm, Klaus; Steinhoff, Gustav; Martin, Ulrich

    2000-01-01

    The ongoing shortage of human donor organs for transplantation has catalyzed new interest in the application of pig organs (xenotransplantation). One of the biggest concerns about the transplantation of porcine grafts into humans is the transmission of pig endogenous retroviruses (PERV) to the recipients or even to other members of the community. Although nonhuman primate models are excellently suited to mimic clinical xenotransplantation settings, their value for risk assessment of PERV transmission at xenotransplantation is questionable since all of the primate cell lines tested so far have been found to be nonpermissive for PERV infection. Here we demonstrate that human, gorilla, and Papio hamadryas primary skin fibroblasts and also baboon B-cell lines are permissive for PERV infection. This suggests that a reevaluation of the suitability of the baboon model for risk assessment in xenotransplantation is critical at this point. PMID:10906227

  15. What Is a Primate?

    ERIC Educational Resources Information Center

    McGee, Elizabeth

    2003-01-01

    Describes a series of hands-on experiments that engage students in hypothesis testing and promotes active learning of the concepts of evolution and adaptation. Laboratory exercises demonstrate how features of the hands and eyes distinguish primates from other mammals. (SOE)

  16. Nonhuman Primate Ocular Biometry

    PubMed Central

    Augusteyn, Robert C.; Maceo Heilman, Bianca; Ho, Arthur; Parel, Jean-Marie

    2016-01-01

    Purpose To examine ocular growth in nonhuman primates (NHPs) from measurements on ex vivo eyes. Methods We obtained NHP eyes from animals that had been killed as part of other studies or because of health-related issues. Digital calipers were used to measure the horizontal, vertical, and anteroposterior globe diameters as well as corneal horizontal and vertical diameters of excised globes from 98 hamadryas baboons, 551 cynomolgus monkeys, and 112 rhesus monkeys, at ages ranging from 23 to 360 months. Isolated lens sagittal thickness and equatorial diameter were measured by shadowphotogrammetry. Wet and fixed dry weights were obtained for lenses. Results Nonhuman primate globe growth continues throughout life, slowing toward an asymptotic maximum. The final globe size scales with negative allometry to adult body size. Corneal growth ceases at around 20 months. Lens diameter increases but thickness decreases with increasing age. Nonhuman primate lens wet and dry weight accumulation is monophasic, continuing throughout life toward asymptotic maxima. The dry/wet weight ratio reaches a maximum of 0.33. Conclusions Nonhuman primate ocular globe and lens growth differ in several respects from those in humans. Although age-related losses of lens power and accommodative amplitude are similar, lens growth and properties are different indicating care should be taken in extrapolating NHP observations to the study of human accommodation. PMID:26780314

  17. Efficient Generation of Nonhuman Primate Induced Pluripotent Stem Cells

    PubMed Central

    Zhong, Bonan; Trobridge, Grant D.; Zhang, Xiaobing; Watts, Korashon L.; Ramakrishnan, Aravind; Wohlfahrt, Martin; Adair, Jennifer E.

    2011-01-01

    Induced pluripotent stem (iPS) cells have great potential for regenerative medicine and gene therapy. Thus far, iPS cells have typically been generated using integrating viral vectors expressing various reprogramming transcription factors; nonintegrating methods have been less effective and efficient. Because there is a significant risk of malignant transformation and cancer involved with the use of iPS cells, careful evaluation of transplanted iPS cells will be necessary in small and large animal studies before clinical application. Here, we have generated and characterized nonhuman primate iPS cells with the goal of evaluating iPS cell transplantation in a clinically relevant large animal model. We developed stable Phoenix-RD114-based packaging cell lines that produce OCT4, SOX2, c-MYC, and KLF4 (OSCK) expressing gammaretroviral vectors. Using these vectors in combination with small molecules, we were able to efficiently and reproducibly generate nonhuman primate iPS cells from pigtailed macaques (Macaca nemestrina). The established nonhuman primate iPS cells exhibited pluripotency and extensive self-renewal capacity. The facile and reproducible generation of nonhuman primate iPS cells using defined producer cells as a source of individual reprogramming factors should provide an important resource to optimize and evaluate iPS cell technology for studies involving stem cell biology and regenerative medicine. PMID:21058905

  18. Mixed chimerism to induce tolerance: lessons learned from nonhuman primates

    PubMed Central

    Murakami, Toru; Cosimi, A. Benedict; Kawai, Tatsuo

    2013-01-01

    The mixed chimerism approach has been demonstrated to be an effective means of inducing allograft tolerance. Based on our rodent studies on mixed chimerism, we previously developed a clinically relevant nonmyeloablative preparative regimen that permits the induction of mixed chimerism and renal allograft tolerance following donor bone marrow transplantation in major histocompatibility complex fully mismatched cynomolgus monkeys. This approach has been successfully extended to HLA matched or mismatched kidney transplant recipients. In the manuscript, we summarize some of the important conclusions made in our laboratories regarding induction of mixed chimerism and allograft tolerance in a nonhuman primate model. PMID:19027614

  19. Hair Transplants

    MedlinePlus

    ... How to Choose the Best Skin Care Products Hair Transplants What are hair transplants? In punch transplanting, a plug containing hair ... What should first be done before considering a hair transplant? Before the procedure, an ASDS doctor will ...

  20. Heart transplant

    MedlinePlus

    ... 10 years. Alternative Names Cardiac transplant; Transplant - heart; Transplantation - heart Images Heart, section through the middle Heart, ... 28. Bernstein D. Pediatric heart and heart-lung transplantation. In: Kliegman RM, Behrman RE, Jenson HB, Stanton ...

  1. Current status of animal-to-human transplantation*

    PubMed Central

    Zhong, Robert; Platt, Jeffrey L.

    2006-01-01

    The transplantation of animal organs into humans as a way of treating organ failure has been pursued for 100 years. Clinical xenotransplantation, as such, has always failed because the transplanted organ is rejected by the recipient. Recent advances in transplant immunology have revealed some mechanisms underlying the rejection of xenografts, and these discoveries have sparked efforts to use genetic engineering of animals and therapeutics directed at the recipient to overcome this problem. This communication reviews current understanding of the mechanisms of xenograft rejection and efforts to overcome rejection and other hurdles. PMID:16255645

  2. Establishing Prostate Cancer Patient Derived Xenografts: Lessons Learned From Older Studies

    PubMed Central

    Russell, Pamela J; Russell, Peter; Rudduck, Christina; Tse, Brian W-C; Williams, Elizabeth D; Raghavan, Derek

    2015-01-01

    46, XY, dic(1;12)(p11;p11), der(3)t(3:?5)(q13;q13), -5, inv(7)(p15q35) x2, +add(7)(p13), add(8)(p22), add(11)(p14), add(13)(p11), add(20)(p12), -22, +r4[cp8]. Conclusions Xenografts provide a clinically relevant model of prostate cancer, although establishing serially transplantable prostate cancer patient derived xenografts is challenging and requires rigorous characterization and high quality starting material. Xenografting from advanced prostate cancer is more likely to succeed, as xenografting from well differentiated, localized disease has not been achieved in our experience. Strong translational correlations can be demonstrated between the clinical disease state and the xenograft model. Prostate 75: 628–636, 2015. © The Authors. The Prostate published by Wiley Periodicals, Inc. PMID:25560784

  3. Heart Xenograft Survival With Chimeric Pig Donors and Modest Immune Suppression

    PubMed Central

    Beschorner, William E.; Sudan, Debra L.; Radio, Stanley J.; Yang, Tianyu; Franco, Kenneth L.; Hill, Arthur C.; Shearon, C. Carson; Thompson, Scott C.; Dixon, Robert S.; Johnson, Noel D.; Kuszynski, Charles A.; Rubocki, Ronald J.; Lechtenberg, Kelly F.; Matamoros, Aurelio; Goertzen, Timothy C.; Fox, Ira J.; Langnas, Alan N.

    2003-01-01

    Objective To assess the use of donor pigs with cellular chimerism for prevention of acute rejection with modest immune suppression. The clinical use of pig organ xenografts is currently precluded by severe acute rejection, which resists standard immune suppression. Summary Background Data For long-term survival of pig organ xenografts, immune suppression significantly greater than used with allografts would currently be necessary, leaving the recipient immune deficient and at increased risk for infections. Induction of immune tolerance and tissue accommodation could enhance xenograft survival but would lead to complications and frequent graft failure. Induction of cellular chimerism within the donor pigs, however, could accomplish these goals before transplantation, significantly reducing the risk. Methods Marrow cells from sheep were infused into fetal pigs. Heart xenografts from chimeric or nonchimeric pigs were transplanted heterotopically into recipient sheep, simultaneous with infusion of splenocytes. Posttransplant suppression consisted of cyclosporine and tapered corticosteroids, comparable with allotransplants. Results All of the control grafts (n = 12) were rejected by acute vascular rejection in 4 to 8 days. In contrast, only one episode of vascular rejection was observed in the experimental group (n = 13). Four experimental recipients had an episode of moderate diffuse cellular rejection (grade 3) and one had moderate focal cellular rejection (grade 2). Each episode responded to pulse steroids. Seven grafts showed no significant rejection. There was little evidence of immune deficiency, infection, or toxicity. Conclusions Acute vascular rejection was prevented in a large animal model without the need for severe immune suppression. PMID:12560785

  4. Bone marrow transplant - discharge

    MedlinePlus

    Transplant - bone marrow - discharge; Stem cell transplant - discharge; Hematopoietic stem cell transplant - discharge; Reduced intensity; Non-myeloablative transplant - discharge; Mini transplant - discharge; Allogenic bone marrow transplant - ...

  5. The primate seahorse rhythm.

    PubMed

    Campos, L M G; Cruz-Rizzolo, Roelf J; Pinato, L

    2015-07-10

    The main Zeitgeber, the day-night cycle, synchronizes the central oscillator which determines behaviors rhythms as sleep-wake behavior, body temperature, the regulation of hormone secretion, and the acquisition and processing of memory. Thus, actions such as acquisition, consolidation, and retrieval performed in the hippocampus are modulated by the circadian system and show a varied dependence on light and dark. To investigate changes in the hippocampus' cellular mechanism invoked by the day and night in a diurnal primate, this study analyzed the expression of PER2 and the calcium binding proteins (CaBPs) calbindin, calretinin and parvalbumin in the hippocampus of Sapajus apella, a diurnal primate, at two different time points, one during the day and one during the dark phase. The PER2 protein expression peaked at night in the antiphase described for the suprachiasmatic nucleus (SCN) of the same primate, indicating that hippocampal cells can present independent rhythmicity. This hippocampal rhythm was similar to that presented by diurnal but not nocturnal rodents. The CaBPs immunoreactivity also showed day/night variations in the cell number and in the cell morphology. Our findings provide evidence for the claim that the circadian regulation in the hippocampus may involve rhythms of PER2 and CaBPs expression that may contribute to the adaptation of this species in events and activities relevant to the respective periods. PMID:25862571

  6. Update on Islet Transplantation

    PubMed Central

    McCall, Michael; James Shapiro, A.M.

    2012-01-01

    Clinical islet transplantation has progressed considerably over the past 12 years, and >750 patients with type 1 diabetes have received islet transplants internationally over this time. Many countries are beginning to accept the transition from research to accepted and funded clinical care, especially for patients with brittle control that cannot be stabilized by more conventional means. Major challenges remain, including the need for more than one donor, and the requirement for potent, chronic immunosuppression. Combining immunological tolerance both to allo- and autoantigens, and a limitless expandable source of stem cell- or xenograft-derived insulin-secreting cells represent remaining hurdles in moving this effective treatment to a potential cure for all those with type 1 or 2 diabetes. PMID:22762022

  7. Orthotopic xenografts of human melanoma and colonic and ovarian carcinoma in sheep to evaluate radioimmunotherapy.

    PubMed Central

    Turner, J. H.; Rose, A. H.; Glancy, R. J.; Penhale, W. J.

    1998-01-01

    Extrapolation to humans from experimental radioimmunotherapy in nude mouse xenograft models is confounded by large relative tumour size and small volume of distribution in mice allowing tumour uptake of radiolabelled antibodies unattainable in patients. Our large animal model of human tumours in cyclosporin-immunosuppressed sheep demonstrated tumour uptake of targeted radiolabelled monoclonal antibodies comparable with uptakes reported in clinical trials. Sheep immunosuppression with daily intravenous cyclosporin augmented by oral ketoconazole maintained trough blood levels of cyclosporin within the range 1000-1500 ng ml(-1). Human tumour cells were transplanted orthotopically by inoculation of 10(7) cells: SKMEL melanoma subcutaneously; LS174T and HT29 colon carcinoma into bowel, peritoneum and liver; and JAM ovarian carcinoma into ovary and peritoneum. Tumour xenografts grew at all sites within 3 weeks of inoculation, preserving characteristic morphology without evidence of necrosis or host rejection. Lymphatic metastasis was demonstrated in regional nodes draining xenografts of melanoma and ovarian carcinoma. Colonic LS1 74T xenografts produced mucin and carcinoembryonic antigen (CEA). The anti-CEA IgG1 monoclonal antibody A5B7 was radiolabelled with iodine-131 and administered intravenously to sheep. Peak uptake at 5 days in orthotopic human tumour transplants in gut was 0.027% DI g(-1) (percentage of injected dose per gram) and 0.034% DI g(-1) in hepatic metastases with tumour to blood ratios of 2-2.5. Non-specific tumour uptake in melanoma was 0.003% DI g(-1). Uptake of radiolabelled monoclonal antibody in human tumours in our large animal model is comparable with that observed in patients and may be more realistic than nude mice xenografts for prediction of clinical efficacy of radioimmunotherapy. Images Figure 1 Figure 2 Figure 3 PMID:9716032

  8. Transplant services

    MedlinePlus

    ... to determine if you meet the criteria for organ transplantation. Most types of organ transplants have guidelines detailing ... you may have. References Herman M, Keaveny AP. Organ transplantation. In: Walsh D, Caraceni AT, Fainsinger R, et ...

  9. Lung Transplant

    MedlinePlus

    ... the NHLBI on Twitter. What Is a Lung Transplant? A lung transplant is surgery to remove a person's diseased lung ... a healthy lung from a deceased donor. Lung transplants are used for people who are likely to ...

  10. Kidney transplant

    MedlinePlus

    ... infections Side effects from medicines used to prevent transplant rejection Loss of transplanted kidney ... tries to destroy it. In order to avoid rejection, almost all kidney transplant recipients must take medicines that suppress their immune ...

  11. Heart transplant

    MedlinePlus

    ... have symptoms. You must take drugs that prevent transplant rejection for the rest of your life. You will ... heart transplant. The main problem, as with other transplants, is rejection. If rejection can be controlled, survival increases to ...

  12. History of Clinical Transplantation

    PubMed Central

    Starzl, Thomas E.

    2010-01-01

    The emergence of transplantation has seen the development of increasingly potent immunosuppressive agents, progressively better methods of tissue and organ preservation, refinements in histocompatibility matching, and numerous innovations in surgical techniques. Such efforts in combination ultimately made it possible to successfully engraft all of the organs and bone marrow cells in humans. At a more fundamental level, however, the transplantation enterprise hinged on two seminal turning points. The first was the recognition by Billingham, Brent, and Medawar in 1953 that it was possible to induce chimerism-associated neonatal tolerance deliberately. This discovery escalated over the next 15 years to the first successful bone marrow transplantations in humans in 1968. The second turning point was the demonstration during the early 1960s that canine and human organ allografts could self-induce tolerance with the aid of immunosuppression. By the end of 1962, however, it had been incorrectly concluded that turning points one and two involved different immune mechanisms. The error was not corrected until well into the 1990s. In this historical account, the vast literature that sprang up during the intervening 30 years has been summarized. Although admirably documenting empiric progress in clinical transplantation, its failure to explain organ allograft acceptance predestined organ recipients to lifetime immunosuppression and precluded fundamental changes in the treatment policies. After it was discovered in 1992 that long-surviving organ transplant recipients had persistent microchimerism, it was possible to see the mechanistic commonality of organ and bone marrow transplantation. A clarifying central principle of immunology could then be synthesized with which to guide efforts to induce tolerance systematically to human tissues and perhaps ultimately to xenografts. PMID:10833242

  13. Establishment and characterization of novel xenograft models of human biliary tract carcinomas.

    PubMed

    Emura, Fabian; Kamma, Hiroshi; Ghosh, Mila; Koike, Naoto; Kawamoto, Toru; Saijo, Kaoru; Ohno, Tadao; Ohkohchi, Nobuhiro; Todoroki, Takeshi

    2003-11-01

    In order to develop new therapeutic regimens for biliary tract cancers, which carry dismal prognoses, the establishment of a human biliary tract cancer xenograft model is essential. Herein, we report the successful establishment and characterization of two xenograft models of human biliary tract cancers. An adenosquamous gallbladder cancer cell line (TGBC-44) and a bile duct adenocarcinoma cell line (TGBC-47) were obtained from fresh surgical specimens in our department and subcutaneously inoculated into nude mice. The overall tumor take rate was 100% and solid tumors grew measurable after 5 and 7 days for TGBC-44 and TGBC-47, respectively. Tumor doubling time was 3.9+/-1.1 and 4.1+/-0.5 days in the exponential growth phase in TGBC-44 and TGBC-47 xenografts, respectively. Isozyme test and karyotype analysis confirmed the human origin. Histopathology analysis revealed that the TGBC-44 xenograft retained both the squamous and the adenocarcinoma components, and the TGBC-47 xenograft exhibited poorly differentiated adenocarcinoma as in the corresponding original tumors. Immunohistochemistry and Western blotting studies revealed positive and similar expression of platelet derived endothelial growth factor/thymidine phosphorylase (PDGF/TP), thymidylate synthase (TS), and cyclooxygenase-2 (COX-2) in both original tumors and xenograft models. No macroscopic metastases were found at the time of sacrifice. We have successfully established two models of human biliary tract cancer, gallbladder and bile duct cancer. Models retained the morphological and biochemical characteristics of the original tumor and demonstrated constant biological behavior in all transplanted mice. These models could be useful tools for developing new diagnostic and therapeutic strategies against biliary tract cancers. PMID:14532968

  14. Ethics of primate use

    NASA Astrophysics Data System (ADS)

    Prescott, M. J.

    2010-11-01

    This article provides an overview of the ethical issues raised by the use of non-human primates (NHPs) in research involving scientific procedures which may cause pain, suffering, distress or lasting harm. It is not an exhaustive review of the literature and views on this subject, and it does not present any conclusions about the moral acceptability or otherwise of NHP research. Rather the aim has been to identify the ethical issues involved and to provide guidance on how these might be addressed, in particular by carefully examining the scientific rationale for NHP use, implementing fully the 3Rs principle of Russell and Burch (1959) and applying a robust "harm-benefit assessment" to research proposals involving NHPs.

  15. Brains, Genes and Primates

    PubMed Central

    Belmonte, Juan Carlos Izpisua; Callaway, Edward M.; Churchland, Patricia; Caddick, Sarah J.; Feng, Guoping; Homanics, Gregg E.; Lee, Kuo-Fen; Leopold, David A.; Miller, Cory T.; Mitchell, Jude F.; Mitalipov, Shoukhrat; Moutri, Alysson R.; Movshon, J. Anthony; Okano, Hideyuki; Reynolds, John H.; Ringach, Dario; Sejnowski, Terrence J.; Silva, Afonso C.; Strick, Peter L.; Wu, Jun; Zhang, Feng

    2015-01-01

    One of the great strengths of the mouse model is the wide array of genetic tools that have been developed. Striking examples include methods for directed modification of the genome, and for regulated expression or inactivation of genes. Within neuroscience, it is now routine to express reporter genes, neuronal activity indicators and opsins in specific neuronal types in the mouse. However, there are considerable anatomical, physiological, cognitive and behavioral differences between the mouse and the human that, in some areas of inquiry, limit the degree to which insights derived from the mouse can be applied to understanding human neurobiology. Several recent advances have now brought into reach the goal of applying these tools to understanding the primate brain. Here we describe these advances, consider their potential to advance our understanding of the human brain and brain disorders, discuss bioethical considerations, and describe what will be needed to move forward. PMID:25950631

  16. INTESTINAL TRANSPLANTATION

    PubMed Central

    Tzakis, Andreas G.; Todo, Satoru; Starzl, Thomas E.

    2010-01-01

    Intestinal transplantation is often the only alternative form of treatment for patients dependent on total parenteral nutrition for survival. Although a limited number of intestinal transplantations have been performed, results with FK 506 immunosuppression are comparable to those for other organ transplants. The impact of successful intestinal transplantation on gastroenterology will likely be similar to the impact of kidney and liver transplantation on nephrology and hepatology. PMID:7515221

  17. Histopathologic insights into the mechanism of anti-non-Gal antibody-mediated pig cardiac xenograft rejection

    PubMed Central

    Byrne, Guerard W; Azimzadeh, Agnes M; Ezzelarab, Mohamed; Tazelaar, Henry D; Ekser, Burcin; Pierson, Richard N; Robson, Simon C; Cooper, David K C; McGregor, Christopher G A

    2013-01-01

    The histopathology of cardiac xenograft rejection has evolved over the last 20 yr with the development of new modalities for limiting antibody-mediated injury, advancing regimens for immune suppression, and an ever-widening variety of new donor genetics. These new technologies have helped us progress from what was once an overwhelming anti-Gal-mediated hyperacute rejection to a more protracted anti-Gal-mediated vascular rejection to what is now a more complex manifestation of non-Gal humoral rejection and coagulation dysregulation. This review summarizes the changing histopathology of Gal- and non-Gal-mediated cardiac xenograft rejection and discusses the contributions of immune-mediated injury, species-specific immune-independent factors, transplant and therapeutic procedures, and donor genetics to the overall mechanism(s) of cardiac xenograft rejection. PMID:25098626

  18. Leopard predation and primate evolution.

    PubMed

    Zuberbühler, Klaus; Jenny, David

    2002-12-01

    Although predation is an important driving force of natural selection its effects on primate evolution are still not well understood, mainly because little is known about the hunting behaviour of the primates' various predators. Here, we present data on the hunting behaviour of the leopard (Panthera pardus), a major primate predator in the Tai; forest of Ivory Coast and elsewhere. Radio-tracking data showed that forest leopards primarily hunt for monkeys on the ground during the day. Faecal analyses confirmed that primates accounted for a large proportion of the leopards' diet and revealed in detail the predation pressure exerted on the eight different monkey and one chimpanzee species. We related the species-specific predation rates to various morphological, behavioural and demographic traits that are usually considered adaptations to predation (body size, group size, group composition, reproductive behaviour, and use of forest strata). Leopard predation was most reliably associated with density, suggesting that leopards hunt primates according to abundance. Contrary to predictions, leopard predation rates were not negatively, but positively, related to body size, group size and the number of males per group, suggesting that predation by leopards did not drive the evolution of these traits in the predicted way. We discuss these findings in light of some recent experimental data and suggest that the principal effect of leopard predation has been on primates' cognitive evolution. PMID:12473487

  19. Captivity humanizes the primate microbiome.

    PubMed

    Clayton, Jonathan B; Vangay, Pajau; Huang, Hu; Ward, Tonya; Hillmann, Benjamin M; Al-Ghalith, Gabriel A; Travis, Dominic A; Long, Ha Thang; Tuan, Bui Van; Minh, Vo Van; Cabana, Francis; Nadler, Tilo; Toddes, Barbara; Murphy, Tami; Glander, Kenneth E; Johnson, Timothy J; Knights, Dan

    2016-09-13

    The primate gastrointestinal tract is home to trillions of bacteria, whose composition is associated with numerous metabolic, autoimmune, and infectious human diseases. Although there is increasing evidence that modern and Westernized societies are associated with dramatic loss of natural human gut microbiome diversity, the causes and consequences of such loss are challenging to study. Here we use nonhuman primates (NHPs) as a model system for studying the effects of emigration and lifestyle disruption on the human gut microbiome. Using 16S rRNA gene sequencing in two model NHP species, we show that although different primate species have distinctive signature microbiota in the wild, in captivity they lose their native microbes and become colonized with Prevotella and Bacteroides, the dominant genera in the modern human gut microbiome. We confirm that captive individuals from eight other NHP species in a different zoo show the same pattern of convergence, and that semicaptive primates housed in a sanctuary represent an intermediate microbiome state between wild and captive. Using deep shotgun sequencing, chemical dietary analysis, and chloroplast relative abundance, we show that decreasing dietary fiber and plant content are associated with the captive primate microbiome. Finally, in a meta-analysis including published human data, we show that captivity has a parallel effect on the NHP gut microbiome to that of Westernization in humans. These results demonstrate that captivity and lifestyle disruption cause primates to lose native microbiota and converge along an axis toward the modern human microbiome. PMID:27573830

  20. Hair transplantation.

    PubMed

    Avram, Marc R

    2012-12-01

    Hair transplantation is a purely dermatologic surgical procedure that dermatologists should be able to perform in appropriate candidates with hair loss. Hair transplantation techniques performed in the 1960s through the 1990s utilized large grafts that created an unfortunate public image of unnatural-appearing transplanted hair. Over the last 15 years, hair transplantation has been performed using follicular units to create consistently natural-looking transplanted hair in both men and women. This article provides an overview of candidate selection and state-of-the-art techniques for performing hair transplantation. PMID:23409484

  1. The major histocompatibility complex of primates.

    PubMed

    Heise, E R; Cook, D J; Schepart, B S; Manning, C H; McMahan, M R; Chedid, M; Keever, C A

    1987-08-31

    The major histocompatibility complex (MHC) encodes cell surface glycoproteins that function in self-nonself recognition and in allograft rejection. Among primates, the MHC has been well defined only in the human; in the chimpanzee and in two species of macaque monkeys the MHC is less well characterized. Serologic, biochemical and genetic evidence indicates that the basic organization of the MHC linkage group has been phylogenetically conserved. However, the number of genes and their linear relationship on the chromosomes differ between species. Class I MHC loci encode molecules that are the most polymorphic genes known. These molecules are ubiquitous in their tissue distribution and typically are recognized together with nominal antigens by cytotoxic lymphocytes. Class II MHC loci constitute a smaller family of serotypes serving as restricting elements for regulatory T lymphocytes. The distribution of class II antigens is limited mainly to cell types serving immune functions, and their expression is subject to up and down modulation. Class III loci code for components C2, C4 and Factor B (Bf) of the complement system. Interspecies differences in the extent of polymorphism occur, but the significance of this finding in relation to fitness and natural selection is unclear. Detailed information on the structure and regulation of MHC gene expression will be required to understand fully the biologic role of the MHC and the evolutionary relationships between species. Meanwhile, MHC testing has numerous applications to biomedical research, especially in preclinical tissue and organ transplantation studies, the study of disease mechanisms, parentage determination and breeding colony management. In this review, the current status of MHC definition in nonhuman primates will be summarized. Special emphasis is placed on the CyLA system of M. fascicularis which is a major focus in our laboratory. A highly polymorphic cynomolgus MHC has been partially characterized and consists

  2. Pancreas Transplantation

    MedlinePlus

    ... Text Size: A A A Listen En Español Pancreas Transplantation Some patients with type 1 diabetes have ... weigh the potential benefits and risks. Benefits of Pancreas Transplants You may be able to maintain a ...

  3. Lung transplant

    MedlinePlus

    ... nih.gov/pubmed/20675678 . Kotloff RM, Keshavjee S. Lung transplantation. In: Broaddus VC, Mason RJ, Ernst MD, et ... 58. Solomon M, Grasemann H, Keshavjee S. Pediatric lung transplantation. Pediatr Clin North Am . 2010; 57(2):375- ...

  4. Kidney transplant

    MedlinePlus

    ... series References Barry JM, Conlin MJ. In: Renal transplantation. Wein AJ, ed. Campbell-Walsh Urology . 10th ed. ... M. Editorial team. Related MedlinePlus Health Topics Kidney Transplantation Browse the Encyclopedia A.D.A.M., Inc. ...

  5. Liver transplant

    MedlinePlus

    ... series References Keefe EB. Hepatic failure and liver transplantation. In: Goldman L, Schafer AI, eds. Goldman's Cecil ... 2011:chap 157. Martin P, Rosen HR. Liver transplantation. In: Feldman M, Friedman LS, Brandt LJ, eds. ...

  6. Pancreas transplant

    MedlinePlus

    ... liver cells, where it can be used as fuel. In people with type 1 diabetes , the pancreas ... and kidney for the rest of your life. Alternative Names Transplant - pancreas; Transplantation - pancreas Images Endocrine glands ...

  7. Hair transplant

    MedlinePlus

    ... this procedure: Scarring Unnatural-looking tufts of new hair growth It is possible that the transplanted hair will ... Most hair transplants result in excellent hair growth within several ... may be needed to create best results. The replaced hairs are ...

  8. Organ Transplantation

    MedlinePlus

    ... donors to recipients to reduce the risk of transplant rejection. Rejection happens when your immune system attacks the new organ. If you have a transplant, you must take drugs the rest of your ...

  9. Evaluation of the Retinoids with Cisplatin and Vincristine in Xenograft Models of Neuroblastoma

    PubMed Central

    Norris, Robin E.; Nguyen, Vu T.; Adamson, Peter C.

    2013-01-01

    Retinoids have been studied for the treatment of children with neuroblastoma for more than 25 years. Post-transplant administration of isotretinoin is standard of care for children with high-risk neuroblastoma, while fenretinide remains investigational. Previous preclinical studies have evaluated the interaction of retinoids and cytotoxic agents with conflicting results. We evaluated the schedule dependent interaction of the cytotoxics, vincristine and cisplatin, with the retinoids, isotretinoin and fenretinide, in xenograft models of neuroblastoma. Concomitant administration of isotretinoin or fenretinide with the cytotoxics did not result in any clear potentiation of cytotoxicity. PMID:23669732

  10. Activation of Cytomegalovirus in Pig-to-Primate Organ Xenotransplantation

    PubMed Central

    Mueller, Nicolas J.; Barth, Rolf N.; Yamamoto, Shin; Kitamura, Hiroshi; Patience, Clive; Yamada, Kazuhiko; Cooper, David K. C.; Sachs, David H.; Kaur, Amitinder; Fishman, Jay A.

    2002-01-01

    Xenotransplantation of porcine organs carries the risk of reactivation of latent virus in donor and recipient tissues as well as transmission of viruses between species. We have investigated the activation of baboon cytomegalovirus (BCMV) and porcine CMV (PCMV) in a pig-to-primate model of xenotransplantation. Tissues originating from a series of six swine-to-baboon composite thymokidney xenotransplants were investigated. Four immunosuppressed baboons died (survival range, 7 to 27 days) with the graft in situ. Increases in BCMV DNA copy numbers occurred in three (75%) of these baboons and was thought to be responsible for pneumonitis and the death of one animal. In two baboons, disseminated intravascular coagulation was successfully treated by graftectomy and discontinuation of immunosuppression. PCMV was upregulated in five of six xenografts (83%). PCMV infection was associated with ureteric necrosis in one xenograft. Although significantly increased in native tissues, low levels of BCMV and PCMV were also detected in tissues other than that of the native viral host species. The cross-species presence of CMV did not appear to cause clinical or histological signs of invasive disease. Thus, viral infections with clinical disease were restricted to tissues of the native species of each virus. Intensive immune suppression currently required for xenotransplantation results in a significant risk of reactivation of latent infections by BCMV and PCMV. It is not yet known whether viral DNA detected across species lines represents cellular microchimerism, ongoing viral infection, or uptake of free virus. The observation of graft injury by PCMV demonstrates that CMV will be an important pathogen in immunosuppressed xenograft recipients. Strategies must be developed to exclude CMV from porcine organ donors. PMID:11967290

  11. Organ Transplantation

    MedlinePlus

    ... have to wait a long time for an organ transplant. Doctors must match donors to recipients to reduce the risk of transplant rejection. Rejection happens when your immune system attacks the new organ. If you have a transplant, you must take ...

  12. Preservation and transplantation of porcine testis tissue.

    PubMed

    Zeng, W; Snedaker, A K; Megee, S; Rathi, R; Chen, F; Honaramooz, A; Dobrinski, I

    2009-01-01

    Grafting of immature mammalian testis tissue to mouse hosts can preserve the male germline. To make this approach applicable to a clinical or field situation, it is imperative that the testis tissue and/or spermatozoa harvested from grafted tissue are preserved successfully. The aim of the present study was to evaluate protocols for the preservation of testis tissue in a porcine model. Testis tissue was stored at 4 degrees C for short-term preservation or cryopreserved by slow-freezing, automated slow-freezing or vitrification for long-term storage. Preserved tissue was transplanted ectopically to mouse hosts and recovered xenografts were analysed histologically. In addition, spermatozoa were harvested from xenografts and cryopreserved. Total cell viability and germ cell viability remained high after tissue preservation. Complete spermatogenesis occurred in xenografts preserved by cooling up to 48 h, whereas spermatogenesis progressed to round spermatids in the xenografts that were frozen-thawed before grafting. Approximately 50% of spermatozoa harvested from xenografts remained viable after freezing and thawing. The in vivo developmental potential of cryopreserved tissue was reduced despite high post-thaw viability. Therefore, it is important to evaluate germ cell differentiation in vivo in addition to cell viability in vitro when optimising freezing protocols for testis tissue. PMID:19261226

  13. A Molecular Phylogeny of Living Primates

    PubMed Central

    Perelman, Polina; Johnson, Warren E.; Roos, Christian; Seuánez, Hector N.; Horvath, Julie E.; Moreira, Miguel A. M.; Kessing, Bailey; Pontius, Joan; Roelke, Melody; Rumpler, Yves; Schneider, Maria Paula C.; Silva, Artur; O'Brien, Stephen J.; Pecon-Slattery, Jill

    2011-01-01

    Comparative genomic analyses of primates offer considerable potential to define and understand the processes that mold, shape, and transform the human genome. However, primate taxonomy is both complex and controversial, with marginal unifying consensus of the evolutionary hierarchy of extant primate species. Here we provide new genomic sequence (∼8 Mb) from 186 primates representing 61 (∼90%) of the described genera, and we include outgroup species from Dermoptera, Scandentia, and Lagomorpha. The resultant phylogeny is exceptionally robust and illuminates events in primate evolution from ancient to recent, clarifying numerous taxonomic controversies and providing new data on human evolution. Ongoing speciation, reticulate evolution, ancient relic lineages, unequal rates of evolution, and disparate distributions of insertions/deletions among the reconstructed primate lineages are uncovered. Our resolution of the primate phylogeny provides an essential evolutionary framework with far-reaching applications including: human selection and adaptation, global emergence of zoonotic diseases, mammalian comparative genomics, primate taxonomy, and conservation of endangered species. PMID:21436896

  14. Gene expression in human ovarian tissue after xenografting.

    PubMed

    Van Langendonckt, A; Romeu, L; Ambroise, J; Amorim, C; Bearzatto, B; Gala, J L; Donnez, J; Dolmans, M M

    2014-06-01

    Cryobanking and transplantation of ovarian tissue is a promising approach to restore fertility in cancer patients. However, ischemic stress following avascular ovarian cortex grafting is known to induce stromal tissue fibrosis and alterations in follicular development. The aim of the study was to analyze the impact of freeze-thawing and grafting procedures on gene expression in human ovarian tissue. Frozen-thawed ovarian tissue from 14 patients was xenografted for 7 days to nude mice and one ungrafted fragment was used as a control. Immediately after recovery, grafts were processed for RNA extraction and histological analysis. Their expression profile was screened by whole-genome oligonucleotide array (n = 4) and validated by reverse-transcriptase polymerase chain analysis (n = 10). After data filtering, the Limma package was used to build a linear regression model for each gene and to compute its fold change between tissues on Days 0 and 7. After adjusting the P-value by the Sidak method, 84 of the transcripts were significantly altered after 7 days of grafting, including matrix metalloproteinase-9 and -14 and angiogenic factors such as placental growth factor and C-X-C chemokine receptor type 4 (CXCR4). Major biological processes were related to tissue remodeling, including secretory processes, cellular adhesion and response to chemical and hormonal stimuli. Angiopoietin signaling, the interleukin-8 pathway and peroxisome proliferator-activated receptor activation were shown to be differentially regulated. On Day 7, overexpression was confirmed by PCR for interleukin-8, transforming growth factor-beta 1, matrix metalloproteinase-14 and CXCR4, compared with ungrafted controls. In conclusion, new as well as known genes involved in tissue restructuring and angiogenesis were identified and found to play a key role during the first days after human ovarian tissue transplantation. This will facilitate the development of strategies to optimize grafting techniques. PMID

  15. Retinal connectivity and primate vision

    PubMed Central

    Lee, Barry B.; Martin, Paul R.; Grünert, Ulrike

    2012-01-01

    The general principles of retinal organization are now well known. It may seem surprising that retinal organization in the primate, which has a complex visual behavioral repertoire, appears relatively simple. In this review, we primarily consider retinal structure and function in primate species. Photoreceptor distribution and connectivity are considered as are connectivity in the outer and inner retina. One key issue is the specificity of retinal connections; we suggest that the retina shows connectional specificity but this is seldom complete, and we consider here the functional consequences of imprecise wiring. Finally, we consider how retinal systems can be linked to psychophysical descriptions of different channels, chromatic and luminance, which are proposed to exist in the primate visual system. PMID:20826226

  16. Retinal connectivity and primate vision.

    PubMed

    Lee, Barry B; Martin, Paul R; Grünert, Ulrike

    2010-11-01

    The general principles of retinal organization are now well known. It may seem surprising that retinal organization in the primate, which has a complex visual behavioral repertoire, appears relatively simple. In this review, we primarily consider retinal structure and function in primate species. Photoreceptor distribution and connectivity are considered as are connectivity in the outer and inner retina. One key issue is the specificity of retinal connections; we suggest that the retina shows connectional specificity but this is seldom complete, and we consider here the functional consequences of imprecise wiring. Finally, we consider how retinal systems can be linked to psychophysical descriptions of different channels, chromatic and luminance, which are proposed to exist in the primate visual system. PMID:20826226

  17. Picosecond pulsed electric fields induce apoptosis in a cervical cancer xenograft.

    PubMed

    Jia, Jia; Xiong, Zheng-Ai; Qin, Qin; Yao, Chen-Guo; Zhao, Xiao-Zhen

    2015-03-01

    The aim of the present study was to evaluate the efficacy of picosecond pulsed electric fields (psPEF) on a cervical cancer xenograft. Human cervical cancer xenografts were established in nude mice by transplantation of HeLa cells, and the tumors were then treated with psPEF. The histological changes were observed by hematoxylin‑eosin staining and transmission electron microscopy. The rate of tumor cell apoptosis was determined using a terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling assay. The mitochondrial transmembrane potential of the tumor cells was detected by laser scanning confocal microscopy, and the activity of caspase‑3, ‑8, ‑9 and ‑12 was determined. The inhibitory rate seven days post‑psPEF treatment was also calculated. The results showed that exposure to psPEF led to an increased rate of apoptosis, collapse of mitochondrial transmembrane potential, and activation of caspases. The inhibitory rate was 9.11% at day 7. The results of the present study indicate that psPEF may induce apoptosis in a cervical cancer xenograft through the endoplasmic reticulum stress and caspase‑dependent signaling pathways. PMID:25405328

  18. Human skeletal muscle xenograft as a new preclinical model for muscle disorders.

    PubMed

    Zhang, Yuanfan; King, Oliver D; Rahimov, Fedik; Jones, Takako I; Ward, Christopher W; Kerr, Jaclyn P; Liu, Naili; Emerson, Charles P; Kunkel, Louis M; Partridge, Terence A; Wagner, Kathryn R

    2014-06-15

    Development of novel therapeutics requires good animal models of disease. Disorders for which good animal models do not exist have very few drugs in development or clinical trial. Even where there are accepted, albeit imperfect models, the leap from promising preclinical drug results to positive clinical trials commonly fails, including in disorders of skeletal muscle. The main alternative model for early drug development, tissue culture, lacks both the architecture and, usually, the metabolic fidelity of the normal tissue in vivo. Herein, we demonstrate the feasibility and validity of human to mouse xenografts as a preclinical model of myopathy. Human skeletal muscle biopsies transplanted into the anterior tibial compartment of the hindlimbs of NOD-Rag1(null) IL2rγ(null) immunodeficient host mice regenerate new vascularized and innervated myofibers from human myogenic precursor cells. The grafts exhibit contractile and calcium release behavior, characteristic of functional muscle tissue. The validity of the human graft as a model of facioscapulohumeral muscular dystrophy is demonstrated in disease biomarker studies, showing that gene expression profiles of xenografts mirror those of the fresh donor biopsies. These findings illustrate the value of a new experimental model of muscle disease, the human muscle xenograft in mice, as a feasible and valid preclinical tool to better investigate the pathogenesis of human genetic myopathies and to more accurately predict their response to novel therapeutics. PMID:24452336

  19. [Research proceedings on primate comparative genomics].

    PubMed

    Liao, Cheng-Hong; Su, Bing

    2012-02-01

    With the accomplishment of genome sequencing of human, chimpanzee and other primates, there has been a great amount of primate genome information accumulated. Primate comparative genomics has become a new research field at current genome era. In this article, we reviewed recent progress in phylogeny, genome structure and gene expression of human and nonhuman primates, and we elaborated the major biological differences among human, chimpanzee and other non-human primate species, which is informative in revealing the mechanism of human evolution. PMID:22345018

  20. Differentiation of xenografted human fetal lung parenchyma

    PubMed Central

    Pavlovic, Jelena; Floros, Joanna; Phelps, David S.; Wigdahl, Brian; Welsh, Patricia; Weisz, Judith; Shearer, Debra A.; Pree, Alphonse Leure du; Myers, Roland; Howett, Mary K.

    2009-01-01

    The goal of this study was to characterize xenografted human fetal lung tissue with respect to developmental stage-specific cytodifferentiation. Human fetal lung tissue (pseudoglandular stage) was grafted either beneath the renal capsule or the skin of athymic mice (NCr-nu). Tissues were analyzed from 3 to 42 days post-engraftment for morphological alterations by light and electron microscopy (EM), and for surfactant protein mRNA and protein by reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry (ICC), respectively. The changes observed resemble those seen in human lung development in utero in many respects, including the differentiation of epithelium to the saccular stage. Each stage occurred over approximately one week in the graft in contrast to the eight weeks of normal in utero development. At all time points examined, all four surfactant proteins (SP-A, SP-B, SP-C, and SP-D) were detected in the epithelium by ICC. Lamellar bodies were first identified by EM in 14 day xenografts. By day 21, a significant increase in lamellar body expression was observed. Cellular proliferation, as marked by PCNA ICC and elastic fiber deposition resembled those of canalicular and saccular in utero development. This model in which xenografted lung tissue in different stages of development is available may facilitate the study of human fetal lung development and the impact of various pharmacological agents on this process. PMID:17555893

  1. Lung transplantation

    PubMed Central

    Afonso, José Eduardo; Werebe, Eduardo de Campos; Carraro, Rafael Medeiros; Teixeira, Ricardo Henrique de Oliveira Braga; Fernandes, Lucas Matos; Abdalla, Luis Gustavo; Samano, Marcos Naoyuki; Pêgo-Fernandes, Paulo Manuel

    2015-01-01

    ABSTRACT Lung transplantation is a globally accepted treatment for some advanced lung diseases, giving the recipients longer survival and better quality of life. Since the first transplant successfully performed in 1983, more than 40 thousand transplants have been performed worldwide. Of these, about seven hundred were in Brazil. However, survival of the transplant is less than desired, with a high mortality rate related to primary graft dysfunction, infection, and chronic graft dysfunction, particularly in the form of bronchiolitis obliterans syndrome. New technologies have been developed to improve the various stages of lung transplant. To increase the supply of lungs, ex vivo lung reconditioning has been used in some countries, including Brazil. For advanced life support in the perioperative period, extracorporeal membrane oxygenation and hemodynamic support equipment have been used as a bridge to transplant in critically ill patients on the waiting list, and to keep patients alive until resolution of the primary dysfunction after graft transplant. There are patients requiring lung transplant in Brazil who do not even come to the point of being referred to a transplant center because there are only seven such centers active in the country. It is urgent to create new centers capable of performing lung transplantation to provide patients with some advanced forms of lung disease a chance to live longer and with better quality of life. PMID:26154550

  2. Overcoming Memory T cell Responses for Induction of Delayed Tolerance in Nonhuman Primates

    PubMed Central

    Yamada, Y.; Boskovic, S.; Aoyama, A.; Murakami, T.; Putheti, P.; Smith, R. N.; Ochiai, T.; Nadazdin, O.; Koyama, I.; Boenisch, O.; Najafian, N.; Bhasin, M.K.; Colvin, R. B.; Madsen, J. C.; Strom, T. B.; Sachs, D. H.; Benichou, G.; Cosimi, A. B.; Kawai, T.

    2011-01-01

    The presence of alloreactive memory T cells is a major barrier for induction of tolerance in primates. In theory, delaying conditioning for tolerance induction until after organ transplantation could further decrease the efficacy of the regimen, since pre-existing alloreactive memory T cells might be stimulated by the transplanted organ. Here, we show that such “delayed tolerance” can be induced in nonhuman primates through the mixed chimerism approach, if specific modifications to overcome/avoid donor-specific memory T cell responses are provided. These modifications include adequate depletion of CD8+ memory T cells and timing of donor bone marrow administration to minimize levels of pro-inflammatory cytokines. Using this modified approach, mixed chimerism was induced successfully in 11 of 13 recipients of previously placed renal allografts and long-term survival without immunosuppression could be achieved in at least 6 of these 11 animals. PMID:22053723

  3. Pathogenesis of Varicelloviruses in primates

    PubMed Central

    Ouwendijk, Werner J.D.; Verjans, Georges M.G.M.

    2014-01-01

    Varicelloviruses in primates comprise the prototypic human varicella-zoster virus (VZV) and its non-human primate homologue simian varicella virus (SVV). Both viruses cause varicella as a primary infection, establish latency in ganglionic neurons and reactivate later in life to cause herpes zoster in their respective hosts. VZV is endemic worldwide and although varicella is usually a benign disease in childhood, VZV reactivation is a significant cause of neurological disease in the elderly and in immunocompromised individuals. The pathogenesis of VZV infection remains ill-defined, mostly due to the species restriction of VZV that impedes studies in experimental animal models. SVV infection of non-human primates parallels virological, clinical, pathological and immunological features of human VZV infection, thereby providing an excellent model to study the pathogenesis of varicella and herpes zoster in its natural host. In this review, we discuss recent studies that provided novel insight in both the virus and host factors involved in the three elementary stages of Varicellovirus infection in primates: primary infection, latency and reactivation. PMID:25255989

  4. Neuroethology of primate social behavior

    PubMed Central

    Chang, Steve W. C.; Brent, Lauren J. N.; Adams, Geoffrey K.; Klein, Jeffrey T.; Pearson, John M.; Watson, Karli K.; Platt, Michael L.

    2013-01-01

    A neuroethological approach to human and nonhuman primate behavior and cognition predicts biological specializations for social life. Evidence reviewed here indicates that ancestral mechanisms are often duplicated, repurposed, and differentially regulated to support social behavior. Focusing on recent research from nonhuman primates, we describe how the primate brain might implement social functions by coopting and extending preexisting mechanisms that previously supported nonsocial functions. This approach reveals that highly specialized mechanisms have evolved to decipher the immediate social context, and parallel circuits have evolved to translate social perceptual signals and nonsocial perceptual signals into partially integrated social and nonsocial motivational signals, which together inform general-purpose mechanisms that command behavior. Differences in social behavior between species, as well as between individuals within a species, result in part from neuromodulatory regulation of these neural circuits, which itself appears to be under partial genetic control. Ultimately, intraspecific variation in social behavior has differential fitness consequences, providing fundamental building blocks of natural selection. Our review suggests that the neuroethological approach to primate behavior may provide unique insights into human psychopathology. PMID:23754410

  5. hESC-derived neural progenitors prevent xenograft rejection through neonatal desensitisation.

    PubMed

    Heuer, Andreas; Kirkeby, Agnete; Pfisterer, Ulrich; Jönsson, Marie E; Parmar, Malin

    2016-08-01

    Stem cell therapies for neurological disorders are rapidly moving towards use in clinical trials. Before initiation of clinical trials, extensive pre-clinical validation in appropriate animal models is essential. However, grafts of human cells into the rodent brain are rejected within weeks after transplantation and the standard methods of immune-suppression for the purpose of studying human xenografts are not always sufficient for the long-term studies needed for transplanted human neurons to maturate, integrate and provide functional benefits in the host brain. Neonatal injections in rat pups using human fetal brain cells have been shown to desensitise the host to accept human tissue grafts as adults, whilst not compromising their immune system. Here, we show that differentiated human embryonic stem cells (hESCs) can be used for desensitisation to achieve long-term graft survival of human stem cell-derived neurons in a xenograft setting, surpassing the time of conventional pharmacological immune-suppressive treatments. The use of hESCs for desensitisation opens up for a widespread use of the technique, which will be of great value when performing pre-clinical evaluation of stem cell-derived neurons in animal models. PMID:27235932

  6. Efficacy of an Fc-modified anti-CD123 antibody (CSL362) combined with chemotherapy in xenograft models of acute myelogenous leukemia in immunodeficient mice

    PubMed Central

    Lee, Erwin M.; Yee, Dean; Busfield, Samantha J.; McManus, Julie F.; Cummings, Nik; Vairo, Gino; Wei, Andrew; Ramshaw, Hayley S.; Powell, Jason A.; Lopez, Angel F.; Lewis, Ian D.; McCall, Martin N.; Lock, Richard B.

    2015-01-01

    The prognosis of older patients with acute myelogenous leukemia is generally poor. The interleukin-3 receptor α-chain (CD123) is highly expressed on the surface of acute leukemia cells compared with normal hematopoietic stem cells. CSL362 is a fully humanized, CD123-neutralizing monoclonal antibody containing a modified Fc structure, which enhances human natural killer cell antibody-dependent cell-mediated cytotoxicity. Six continuous acute myelogenous leukemia xenografts established from patient explants and characterized by cell and molecular criteria, produced progressively lethal disease 42-202 days after transplantation. CSL362 alone reduced engraftment of one of four and three of four acute myelogenous leukemia xenografts in the bone marrow and peripheral organs, respectively. A cytarabine and daunorubicin regimen was optimized using this model to identify potentially synergistic interactions with CSL362. Cytarabine/daunorubicin improved the survival of mice engrafted with four of four acute myelogenous leukemia xenografts by 31–41 days. Moreover, CSL362 extended the survival of cytarabine/daunorubicin-treated mice for two of two acute myelogenous leukemia xenografts, while augmentation of natural killer cell-deficient NSG mice with adoptively transferred human natural killer cells improved survival against a single xenograft. Interestingly, this enhanced CSL362 efficacy was lost in the absence of chemotherapy. This study shows that acute myelogenous leukemia xenografts provide a platform for the evaluation of new therapeutics, simulating complex in vivo interactions, and that the in vivo efficacy of CSL362 supports continued clinical development of this drug. PMID:26130514

  7. pO{sub 2} Fluctuation Pattern and Cycling Hypoxia in Human Cervical Carcinoma and Melanoma Xenografts

    SciTech Connect

    Ellingsen, Christine; Ovrebo, Kirsti Marie; Galappathi, Kanthi; Mathiesen, Berit; Rofstad, Einar K.

    2012-07-15

    Purpose: Blood perfusion in tumors is spatially and temporally heterogeneous, resulting in local fluctuations in tissue oxygen tension (pO{sub 2}) and tissue regions showing cycling hypoxia. In this study, we investigated whether the pO{sub 2} fluctuation pattern and the extent of cycling hypoxia differ between tumor types showing high (e.g., cervical carcinoma xenograft) and low (e.g., melanoma xenograft) fractions of connective tissue-associated blood vessels. Methods and Materials: Two cervical carcinoma lines (CK-160 and TS-415) and two melanoma lines (A-07 and R-18) transplanted into BALB/c nu/nu mice were included in the study. Tissue pO{sub 2} was measured simultaneously in two positions in each tumor by using a two-channel OxyLite fiber-optic oxygen-sensing device. The extent of acute and chronic hypoxia was assessed by combining a radiobiological and a pimonidazole-based immunohistochemical assay of tumor hypoxia. Results: The proportion of tumor regions showing pO{sub 2} fluctuations, the pO{sub 2} fluctuation frequency in these regions, and the relative amplitude of the pO{sub 2} fluctuations were significantly higher in the melanoma xenografts than in the cervical carcinoma xenografts. Cervical carcinoma and melanoma xenografts did not differ significantly in the fraction of acutely hypoxic cells or the fraction of chronically hypoxic cells. However, the ratio between fraction of acutely hypoxic cells and fraction of chronically hypoxic cells was significantly higher in melanoma than in cervical carcinoma xenografts. Conclusions: Temporal heterogeneity in blood flow and tissue pO{sub 2} in tumors may depend on tumor histology. Connective tissue surrounding microvessels may stabilize blood flow and pO{sub 2} and, thus, protect tumor tissue from cycling hypoxia.

  8. Counting primates for conservation: primate surveys in Uganda.

    PubMed

    Plumptre, Andrew J; Cox, Debby

    2006-01-01

    Primate census techniques have been developed over the past 35-40 years yet there is still some confusion and great variation in the methods used. This precludes comparisons between sites where different techniques have been used. This paper discusses the variations between the methods that seem to be practiced currently and then describes a census of primates in the forests of western Uganda. Primate density and biomass varied greatly between forests as well as within forests and this is probably related to food availability. Chimpanzee (Pan troglodytes) density was strongly correlated with nest encounter rates from reconnaissance walks in the forest. This result can be used to estimate chimpanzee density in forests where it is difficult to survey this species (e.g., due to security reasons). A total of 4,980 chimpanzee was estimated for Uganda which is higher than previously guessed, but still of conservation concern. Only four forests had more than 500 individuals which gives concern for long-term population viability. PMID:16132166

  9. Pulmonary transplantation.

    PubMed Central

    Davis, R D; Pasque, M K

    1995-01-01

    OBJECTIVE: More than 2700 lung transplants have been performed since the initial clinical success in 1983. The evolution in the techniques of lung transplantation and patient management and the effects on results are reviewed. SUMMARY BACKGROUND DATA: Improvements in donor management, lung preservation, operative techniques, immunosuppression management, infection prophylaxis and treatment, rejection surveillance, and long-term follow-up have occurred in the decade following the first clinically successful lung transplant. A wider spectrum of diseases and patients treated with lung transplant have accentuated the shortage of suitable lung donors. The organ shortage has led to the use of marginal donors and a limited experience using living, related donors. METHODS: Changes in techniques and patient selection and management are reviewed and controversial issues and problems are highlighted. RESULTS: One-year survival of greater than 90% for single-lung transplant recipients and greater than 85% for bilateral lung transplant recipients have been achieved. Complications caused by airway complications has been reduced greatly. Obliterative bronchiolitis develops in 20% to 50% of long-term survivors and is the leading cause of morbidity and mortality after the first year after transplant. CONCLUSIONS: Lung transplantation has evolved into an effective therapy for a wide variety of causes of end-stage lung disease. Wider applicability requires solutions to the problems of donor shortage and development of obliterative bronchiolitis. Images Figure 1. PMID:7826157

  10. Transplant rejection

    MedlinePlus

    ... Wood K, Shankar S, Mittal S. Concepts and challenges in organ transplantation. In: Rich RR, Fleisher TA, Shearer WT, et ... A.M. Editorial team. Related MedlinePlus Health Topics Organ Transplantation Browse the Encyclopedia A.D.A.M., Inc. ...

  11. Intestine Transplant

    MedlinePlus

    ... intestine segment, most intestine transplants involve a whole organ from a deceased donor. In addition, most intestine transplants are performed in ... blood before surgery. I am looking for ... allocation About UNOS Being a living donor Calculator - CPRA Calculator - KDPI Calculator - LAS Calculator - MELD ...

  12. Optogenetics in the nonhuman primate

    PubMed Central

    Han, Xue

    2013-01-01

    The nonhuman primate brain, the model system closest to the human brain, plays a critical role in our understanding of neural computation, cognition, and behavior. The continued quest to crack the neural codes in the monkey brain would be greatly enhanced with new tools and technologies that can rapidly and reversibly control the activities of desired cells at precise times during specific behavioral states. Recent advances in adapting optogenetic technologies to monkeys have enabled precise control of specific cells or brain regions at the millisecond timescale, allowing for the investigation of the causal role of these neural circuits in this model system. Validation of optogenetic technologies in monkeys also represents a critical preclinical step on the translational path of new generation cell-type-specific neural modulation therapies. Here, I discuss the current state of the application of optogenetics in the nonhuman primate model system, highlighting the available genetic, optical and electrical technologies, and their limitations and potentials. PMID:22341328

  13. Intestinal transplantation.

    PubMed

    Rege, Aparna; Sudan, Debra

    2016-04-01

    Intestinal transplantation has now emerged as a lifesaving therapeutic option and standard of care for patients with irreversible intestinal failure. Improvement in survival over the years has justified expansion of the indications for intestinal transplantation beyond the original indications approved by Center for Medicare and Medicaid services. Management of patients with intestinal failure is complex and requires a multidisciplinary approach to accurately select candidates who would benefit from rehabilitation versus transplantation. Significant strides have been made in patient and graft survival with several advancements in the perioperative management through timely referral, improved patient selection, refinement in the surgical techniques and better understanding of the immunopathology of intestinal transplantation. The therapeutic efficacy of the procedure is well evident from continuous improvements in functional status, quality of life and cost-effectiveness of the procedure. This current review summarizes various aspects including current practices and evidence based recommendations of intestinal transplantation. PMID:27086894

  14. Transplant psychiatry.

    PubMed

    Potts, S G

    2009-12-01

    Transplant units increasingly recognise a need for assistance from psychiatrists and psychologists in the assessment and management of potential transplant recipients and live donors. This arises from the various known associations between mental disorder and the need for transplantation; the intensifying requirement to select carefully among the potential recipients and donors of scarce human organs; and the drive to maximise transplant outcomes by optimising all aspects of treatment after surgery. There is good evidence that careful, protocol-guided selection among potential candidates for transplantation with alcoholic liver disease helps ensure outcomes at least as good as for other forms of liver disease. The evidence base in other areas is less robust, but the principles guiding the psychiatric assessment are broadly the same. There is an increasing need for psychiatric assessment of potential live organ donors, in order to minimise the risks they run, and in the case of altruistic donation this is now mandatory in UK law. PMID:21152475

  15. Primate Experiments on SLS-1

    NASA Technical Reports Server (NTRS)

    Aochi, J.

    1985-01-01

    Experiments to study how certain body systems are affected by the space environment are described. These experiments are to be conducted on space shuttle flights. How weightlessness affects two body systems of primates are the prime concern. Thermoregulation and fluid and electrolyte homeostasis are the two systems concerned. The thermoregulation project will provide data on how body temperature and circadian rhythms are affected in a weightlessness environment and the homeostasis in fluids and electrolyte levels will address the problem of body fluid shifts.

  16. Soils, time, and primate paleoenvironments

    USGS Publications Warehouse

    Bown, T.M.; Kraus, M.J.

    1993-01-01

    Soils are the skin of the earth. From both poles to the equator, wherever rocks or sediment are exposed at the surface, soils are forming through the physical and chemical action of climate and living organisms. The physical attributes (color, texture, thickness) and chemical makeup of soils vary considerably, depending on the composition of the parent material and other variables: temperature, rainfall and soil moisture, vegetation, soil fauna, and the length of time that soil-forming processes have been at work. United States soil scientists1 have classified modern soils into ten major groups and numerous subgroups, each reflecting the composition and architecture of the soils and, to some extent, the processes that led to their formation. The physical and chemical processes of soil formation have been active throughout geologic time; the organic processes have been active at least since the Ordovician.2 Consequently, nearly all sedimentary rocks that were deposited in nonmarine settings and exposed to the elements contain a record of ancient, buried soils or paleosols. A sequence of these rocks, such as most ancient fluvial (stream) deposits, provides a record of soil paleoenvironments through time. Paleosols are also repositories of the fossils of organisms (body fossils) and the traces of those organisms burrowing, food-seeking, and dwelling activities (ichnofossils). Indeed, most fossil primates are found in paleosols. Careful study of ancient soils gives new, valuable insights into the correct temporal reconstruction of the primate fossil record and the nature of primate paleoenvironments. ?? 1993 Wiley-Liss, Inc.

  17. Assessing Anxiety in Nonhuman Primates

    PubMed Central

    Coleman, Kristine; Pierre, Peter J.

    2014-01-01

    Anxiety can be broadly described as a psychological state in which normally innocuous environmental stimuli trigger negative emotional expectations. Human anxiety disorders are multidimensional and may be organic or acquired, situational or pervasive. The broad ranging nature of the anxiety phenotype speaks to the need for models that identify its various components and root causes to develop effective clinical treatments. The cross-species comparative approach to modeling anxiety disorders in animals aims to understand mechanisms that both contribute to and modulate anxiety. Nonhuman primate models provide an important bridge from nonprimate model systems because of the complexity of nonhuman primates’ biobehavioral capacities and their commonalities with human emotion. The broad goal of this review is to provide an overview of various procedures available to study anxiety in the nonhuman primate, with a focus on the behavioral aspects of anxiety. Commonly used methods covered in this review include assessing animals in their home environment or in response to an ethologically relevant threat, associative conditioning and startle response tests, and cognitive bias tests. We also discuss how these procedures can help veterinarians and researchers care for captive nonhuman primates. PMID:25225310

  18. [Reasons for not using primates in research].

    PubMed

    Sauer, U G

    2000-01-01

    In terms of physiological development, non-human primates are our next of kin in the animal kingdom. Scientists who oppose the use of primates for experimental purposes argue that due to the high degree of similarity between primates and humans, experiments that may not be performed on humans due to ethical reasons also should not be performed on primates. Taking neurophysiological experiments with primates as an example, it is discussed which consequences it would have for medical progress if the use of primates in research were abandoned altogether. Taking into account the alternatives available and the results gained with the animal tests, it is concluded that medical progress would be unimpeded, even though in some instances the exact same questions that currently are evaluated with the animal tests might no longer be pursued with the alternatives. PMID:11178554

  19. Spheroid culture of LuCaP 136 patient-derived xenograft enables versatile preclinical models of prostate cancer.

    PubMed

    Valta, Maija P; Zhao, Hongjuan; Saar, Matthias; Tuomela, Johanna; Nolley, Rosalie; Linxweiler, Johannes; Sandholm, Jouko; Lehtimäki, Jaakko; Härkönen, Pirkko; Coleman, Ilsa; Nelson, Peter S; Corey, Eva; Peehl, Donna M

    2016-04-01

    LuCaP serially transplantable patient-derived xenografts (PDXs) are valuable preclinical models of locally advanced or metastatic prostate cancer. Using spheroid culture methodology, we recently established cell lines from several LuCaP PDXs. Here, we characterized in depth the features of xenografts derived from LuCaP 136 spheroid cultures and found faithful retention of the phenotype of the original PDX. In vitro culture enabled luciferase transfection into LuCaP 136 spheroids, facilitating in vivo imaging. We showed that LuCaP 136 spheroids formed intratibial, orthotopic, and subcutaneous tumors when re-introduced into mice. Intratibial tumors responded to castration and were highly osteosclerotic. LuCaP 136 is a realistic in vitro-in vivo preclinical model of a subtype of bone metastatic prostate cancer. PMID:26873136

  20. Transplantation tolerance.

    PubMed

    Salisbury, Emma M; Game, David S; Lechler, Robert I

    2014-12-01

    Although transplantation has been a standard medical practice for decades, marked morbidity from the use of immunosuppressive drugs and poor long-term graft survival remain important limitations in the field. Since the first solid organ transplant between the Herrick twins in 1954, transplantation immunology has sought to move away from harmful, broad-spectrum immunosuppressive regimens that carry with them the long-term risk of potentially life-threatening opportunistic infections, cardiovascular disease, and malignancy, as well as graft toxicity and loss, towards tolerogenic strategies that promote long-term graft survival. Reports of "transplant tolerance" in kidney and liver allograft recipients whose immunosuppressive drugs were discontinued for medical or non-compliant reasons, together with results from experimental models of transplantation, provide the proof-of-principle that achieving tolerance in organ transplantation is fundamentally possible. However, translating the reconstitution of immune tolerance into the clinical setting is a daunting challenge fraught with the complexities of multiple interacting mechanisms overlaid on a background of variation in disease. In this article, we explore the basic science underlying mechanisms of tolerance and review the latest clinical advances in the quest for transplantation tolerance. PMID:24213880

  1. Induction of midbrain dopaminergic neurons from primate embryonic stem cells by coculture with sertoli cells.

    PubMed

    Yue, Fengming; Cui, Li; Johkura, Kohei; Ogiwara, Naoko; Sasaki, Katsunori

    2006-07-01

    The aim of this study was to produce dopaminergic neurons from primate embryonic stem (ES) cells following coculture with mouse Sertoli cells. After 3 weeks of induction, immunostaining revealed that 90% +/- 9% of the colonies contained tyrosine hydroxylase-positive (TH(+)) neurons, and 60% +/- 7% of the tubulin beta III-positive (Tuj III(+)) neurons were TH(+). Reverse transcription-polymerase chain reaction analyses showed that Sertoli-induced neurons expressed midbrain dopaminergic neuron markers, including TH, dopamine transporter, aromatic amino acid decarboxylase (AADC), receptors such as TrkB and TrkC, and transcription factors NurrI and Lmx1b. Neurons that had been differentiated on Sertoli cells were positive for Pax2, En1, and AADC, midbrain-related markers, and negative for dopamine-beta-hydroxylase, a marker of noradrenergic neurons. These Sertoli cell-induced dopaminergic cells can release dopamine when depolarized by high K(+). Sertoli cell-conditioned medium contained glial cell line-derived neurotrophic factor (GDNF) and supported neuronal differentiation. After pretreatment with anti-GDNF antibody, the percentage of Tuj III(+) colonies was reduced to 14%. Thus, GDNF contributed significantly to inducing primate ES cells into dopaminergic neurons. When transplanted into a 6-hydroxydopamine-treated Parkinson's disease model, primate-derived dopaminergic neurons integrated into the mouse striatum. Two weeks after transplantation, surviving TH(+) cells were present. These TH(+) cells survived for 2 months. Therefore, the induction method of coculture ES cells with Sertoli cells provides an unlimited source of primate cells for the study of pathogenesis and transplantation in Parkinson's disease. PMID:16822882

  2. Facial Transplantation.

    PubMed

    Russo, Jack E; Genden, Eric M

    2016-08-01

    Reconstruction of severe facial deformities poses a unique surgical challenge: restoring the aesthetic form and function of the face. Facial transplantation has emerged over the last decade as an option for reconstruction of these defects in carefully selected patients. As the world experience with facial transplantation grows, debate remains regarding whether such a highly technical, resource-intensive procedure is warranted, all to improve quality of life but not necessarily prolong it. This article reviews the current state of facial transplantation with focus on the current controversies and challenges, with particular attention to issues of technique, immunology, and ethics. PMID:27400850

  3. [Heart transplantation].

    PubMed

    Fukushima, Norihide; Matsuda, Hikaru

    2005-11-01

    While nearly 4,000 patients undergo heart transplantation (HTx) every year in the world, only 27 HTx were performed since February, 1999, because of very strict Organ Transplantation Law in Japan. All were treated with triple immunosuppressive regimen. Although two patients died of infection 4 months and 4 years after HTx, respectively, 23 were discharged and 16 returned to work or go to school. New immunosuppressive drugs, such as sirolimus and everolimus, treatment of presensitized patients before transplantation using cyclophosphamide and intravenous globulin infusion, compact implantable left ventricular assist supports and the future of pediatric HTx in Japan are discussed. PMID:16277260

  4. A brief history of cross-species organ transplantation

    PubMed Central

    2012-01-01

    Cross-species transplantation (xenotransplantation) offers the prospect of an unlimited supply of organs and cells for clinical transplantation, thus resolving the critical shortage of human tissues that currently prohibits a majority of patients on the waiting list from receiving transplants. Between the 17th and 20th centuries, blood was transfused from various animal species into patients with a variety of pathological conditions. Skin grafts were carried out in the 19th century from a variety of animals, with frogs being the most popular. In the 1920s, Voronoff advocated the transplantation of slices of chimpanzee testis into aged men whose “zest for life” was deteriorating, believing that the hormones produced by the testis would rejuvenate his patients. Following the pioneering surgical work of Carrel, who developed the technique of blood vessel anastomosis, numerous attempts at nonhuman primate organ transplantation in patients were carried out in the 20th century. In 1963–1964, when human organs were not available and chronic dialysis was not yet in use, Reemtsma transplanted chimpanzee kidneys into 13 patients, one of whom returned to work for almost 9 months before suddenly dying from what was believed to be an electrolyte disturbance. The first heart transplant in a human ever performed was by Hardy in 1964, using a chimpanzee heart, but the patient died within 2 hours. Starzl carried out the first chimpanzee-to-human liver transplantation in 1966; in 1992, he obtained patient survival for 70 days following a baboon liver transplant. With the advent of genetic engineering and cloning technologies, pigs are currently available with a number of different manipulations that protect their tissues from the human immune response, resulting in increasing pig graft survival in nonhuman primate models. Genetically modified pigs offer hope of a limitless supply of organs and cells for those in need of a transplant. PMID:22275786

  5. Primate communities: past, present, and possible future.

    PubMed

    Reed, Kaye E; Bidner, Laura R

    2004-01-01

    An understanding of the fundamental causes of the structure of primate communities is important for studies of primate evolutionary history, primate behavioral ecology, and development of conservation strategies. Research into these structuring factors has benefited from new perspectives such as consideration of primate phylogenetic history, metacommunities, and interactions with predators and nonprimate competitors. This review presents the underlying factors of primate community structure within the biogeographic regions of Madagascar, the Neotropics, Africa, and Asia. One of the major differences among these locations likely resulted from the initial primate taxa that colonized each region (a single colonization event in the case of Madagascar and South America, and multiple radiations of higher-level taxa in Africa and Asia). As most primates live in forests, the differences among the forests in these locations, caused by various climatic influences, further influenced speciation and the development of primate communities. Within these habitats, species interactions with different groups of organisms were also instrumental in developing community dynamics. Through an investigation of these fundamental factors, we identify some of the most important effects on primate communities in each region. These findings suggest that low primate richness in Asia may be caused by either the abundance of dipterocarp trees or high levels of monsoon rains. High numbers of frugivores and a lack of folivores in neotropical communities may be associated with competition with sloths that were already present at the time of initial radiation. Climatic patterns which affect forest structure and productivity in Madagascar may be responsible for high numbers of folivorous lemurs. The identification of these factors are important for the conservation of existing primate communities, and indicate directions for future studies. PMID:15605389

  6. Pancreas Transplantation

    MedlinePlus

    The pancreas is a gland behind your stomach and in front of your spine. It produces the juices that ... hormones that help control blood sugar levels. A pancreas transplant is surgery to place a healthy pancreas ...

  7. Intestine Transplant

    MedlinePlus

    ... with any one product nor does UNOS assume responsibility for any error, omissions or other discrepancies. Share this: Was this information helpful? Talk to your doctor The process of being admitted and preparing for transplant surgery ...

  8. Hepatocyte Transplantation

    PubMed Central

    Mitry, Ragai R; Hughes, Robin D; Dhawan, Anil

    2011-01-01

    Hepatocyte transplantation (HTx) has been developed for use in liver-based metabolic disorders and in acute liver failure. Worldwide, there are around 80 patients that have been transplanted with hepatocytes. Almost all reported studies prove feasibility and safety of the procedure with short- to medium-term success. Availability of good quality hepatocytes (HCs) is the main limiting factor, and therefore alternative sources of cells such as stem cells are being investigated. Other limiting factors include cell engraftment, survival, and function of transplanted cells. It remains to be seen if progress in HTx research can overcome these hurdles leading to the wider use of the technique as an alternative to liver transplantation in the future. PMID:25755322

  9. Transplant services

    MedlinePlus

    ... an option for patients with short bowel or short gut syndrome or advanced liver disease, or who must receive all nutrients through a feeding line. See: Total parenteral nutrition (TPN) Kidney transplant is an option for someone ...

  10. Pancreas transplant

    MedlinePlus

    ... pancreas from a donor into a person with diabetes. Pancreas transplants give the person a chance to ... used as fuel. In people with type 1 diabetes , the pancreas does not make enough, or sometimes ...

  11. Lung transplant

    MedlinePlus

    ... diseases that may require a lung transplant are: Cystic fibrosis Damage to the arteries of the lung because ... BC; Clinical Practice Guidelines for Pulmonary Therapies Committee; ... Therapies Committee. Cystic fibrosis pulmonary guidelines: ...

  12. Transplant rejection

    MedlinePlus

    Abbas AK, Lichtman AH, Pillai S. Transplantation immunology. In: Abbas AK, Lichtman AH, Pillai S, eds. Cellular and Molecular Immunology. 8th ed. Philadelphia, PA: Elsevier Saunders; 2015:chap 17. Adams AB, ...

  13. Liver Transplantation

    MedlinePlus

    ... patient who has poor kidney function is on dialysis. The PELD score is calculated based on the ... example, a person who had cirrhosis caused by long-term alcohol abuse resumes drinking after the transplant. Recurrence ...

  14. Liver transplant

    MedlinePlus

    Risks for any anesthesia are: Problems breathing Reactions to medications Risks for any surgery are: Bleeding Heart attack or stroke Infection Liver transplant surgery and management after surgery carry major risks. There is ...

  15. Corneal transplant

    MedlinePlus

    ... clear outer lens on the front of the eye. A corneal transplant is surgery to replace the cornea with tissue ... years. Rejection can sometimes be controlled with steroid eye drops. Other ... are: Bleeding Cataracts Infection of the eye Glaucoma ( ...

  16. Interstitial Fluid Pressure and Vascularity of Intradermal and Intramuscular Human Tumor Xenografts

    SciTech Connect

    Gulliksrud, Kristine; Galappathi, Kanthi; Rofstad, Einar K.

    2011-05-01

    Purpose: High interstitial fluid pressure (IFP) in tumors has been shown to be associated with poor prognosis. Mechanisms underlying the intertumor heterogeneity in IFP were investigated in this study. Methods and Materials: A-07 melanoma xenografts were transplanted intradermally or intramuscularly in BALB/c nu/nu mice. IFP was measured in the center of the tumors with a Millar catheter. Tumor blood perfusion and extracellular volume fraction were assessed by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). The necrotic fraction, vascular density, and vessel diameters of the tumors were determined by image analysis of histological preparations. Results: Significant intertumor heterogeneity in IFP, blood perfusion, and microvascular morphology was observed whether the tumors were transplanted intradermally or intramuscularly. High IFP was mainly a consequence of high resistance to blood flow caused by low vessel diameters in either transplantation site. IFP decreased with increasing blood perfusion in intradermal tumors and increased with increasing blood perfusion in intramuscular tumors, mainly because the morphology of the tumor microvasculature differed systematically between the two tumor models. Conclusion: The potential of DCE-MRI as a noninvasive method for assessing the IFP of tumors may be limited because any relationship between IFP and blood perfusion may differ with the tumor growth site.

  17. Meniscus transplantation.

    PubMed

    Frank, Rachel M; Cole, Brian J

    2015-12-01

    Understanding the structure and function of the meniscus is critical to understanding its role in overall knee joint function. Injury to, or removal of, meniscal tissue may be associated with articular cartilage wear, knee instability, and, ultimately, the progression of osteoarthritis. While every effort is made for preserving and/or repairing damaged meniscal tissue, in some cases, the meniscus is not amenable to repair after injury. For appropriately indicated patients with symptomatic meniscal deficiency, meniscus allograft transplantation is an excellent surgical solution aimed at reducing pain and improving function. Indications for meniscus allograft transplantation are limited, and concomitant procedures such as osteotomy for malalignment, ligamentous, and/or articular cartilage restoration may be necessary in order to ensure an optimal result following meniscus allograft transplantation. Surgical techniques for meniscus allograft transplantation are variable and include soft-tissue fixation versus bone plug fixation versus bone bridge fixation. Outcomes following meniscus allograft transplantation are generally good to excellent, though reoperation rates are relatively high. The purpose of this article is to provide a concise review of recently published data on meniscus allograft transplantation, with a focus on recent outcomes studies. PMID:26431702

  18. Lung transplantation

    PubMed Central

    2013-01-01

    Lung transplantation may be the only intervention that can prolong survival and improve quality of life for those individuals with advanced lung disease who are acceptable candidates for the procedure. However, these candidates may be extremely ill and require ventilator and/or circulatory support as a bridge to transplantation, and lung transplantation recipients are at risk of numerous post-transplant complications that include surgical complications, primary graft dysfunction, acute rejection, opportunistic infection, and chronic lung allograft dysfunction (CLAD), which may be caused by chronic rejection. Many advances in pre- and post-transplant management have led to improved outcomes over the past decade. These include the creation of sound guidelines for candidate selection, improved surgical techniques, advances in donor lung preservation, an improving ability to suppress and treat allograft rejection, the development of prophylaxis protocols to decrease the incidence of opportunistic infection, more effective therapies for treating infectious complications, and the development of novel therapies to treat and manage CLAD. A major obstacle to prolonged survival beyond the early post-operative time period is the development of bronchiolitis obliterans syndrome (BOS), which is the most common form of CLAD. This manuscript discusses recent and evolving advances in the field of lung transplantation. PMID:23710330

  19. Bion 11 mission: primate experiments.

    PubMed

    Ilyin, E A; Korolkov, V I; Skidmore, M G; Viso, M; Kozlovskaya, I B; Grindeland, R E; Lapin, B A; Gordeev, Y V; Krotov, V P; Fanton, J W; Bielitzki, J T; Golov, V K; Magedov, V S; Hines, J W

    2000-01-01

    A summary is provided of the major operations required to conduct the wide range of primate experiments on the Bion 11 mission, which flew for 14 days beginning December 24, 1996. Information is given on preflight preparations, including flight candidate selection and training; attachment and implantation of bioinstrumentation; flight and ground experiment designs; onboard life support and test systems; ground and flight health monitoring; flight monkey selection and transport to the launch site; inflight procedures and data collection; postflight examinations and experiments; and assessment of results. PMID:11543472

  20. Noninvasive Test for Tuberculosis Detection among Primates

    PubMed Central

    Mugisha, Lawrence; Shoyama, Fernanda Miyagaki; O’Malley, Melanie J.; Flynn, JoAnne L.; Asiimwe, Benon; Travis, Dominic A.; Singer, Randall S.; Sreevatsan, Srinand

    2015-01-01

    Traditional testing methods have limited epidemiologic studies of tuberculosis among free-living primates. PCR amplification of insertion element IS6110 of Mycobacterium tuberculosis from fecal samples was evaluated as a noninvasive screening test for tuberculosis in primates. Active tuberculosis was detected among inoculated macaques and naturally exposed chimpanzees, demonstrating the utility of this test. PMID:25695329

  1. American Society of Transplantation

    MedlinePlus

    ... Trials in Transplantation September 13, 2016 The American Society of Transplantation and its Transplantation & Immunology Research Network ... Learn More Donate Donate Donate to the American Society of Transplantation Advertisement member spotlight View all Joanna ...

  2. Meniscal allograft transplantation

    MedlinePlus

    Meniscus transplant; Surgery - knee - meniscus transplant; Surgery - knee - cartilage; Arthroscopy - knee - meniscus transplant ... you are a good candidate for a meniscus transplant, x-rays of your knee are usually taken ...

  3. Islet xenograft destruction in the hu-PBL-severe combined immunodeficient (SCID) mouse necessitates anti-CD3 preactivation of human immune cells

    PubMed Central

    Gysemans, C; Waer, M; Laureys, J; Depovere, J; Pipeleers, D; Bouillon, R; Mathieu, C

    2000-01-01

    Introduction of the hu-PBL-SCID mouse model has yielded a potentially useful tool for research in transplantation. The aim of this study was to define the conditions necessary for a reconstituted human immune system to destroy in a consistent manner rat islet xenografts in the alloxan-diabetic hu-PBL-SCID mouse. We examined different time points of hu-PBL reconstitution, different transplantation sites of the islets and several hu-PBL reconstitution protocols. Major differences in graft destruction were observed between the different hu-PBL reconstitution protocols, irrespective of timing of hu-PBL reconstitution or site of transplantation. Although preactivation of hu-PBL did not improve the level of hu-PBL chimerism, histological and immunohistochemical analysis of the grafts revealed a severe human lymphocytic infiltration and β cell destruction only in the grafts of mice receiving preactivated hu-PBL. This β cell injury resulted in impaired glucose tolerance, with in some animals recurrence of hyperglycaemia, and decreased insulin and C-peptide levels after glucose stimulation. Therefore, we conclude that activation of hu-PBL prior to transfer is essential in achieving xenograft infiltration and destruction in hu-PBL-SCID mice. The need for immune manipulation suggests that interactions between hu-PBL and xenografts in this model may be hampered by incompatibilities in cross-species adhesion and/or activation signals. PMID:10971525

  4. Modeling Olfactory Bulb Evolution through Primate Phylogeny

    PubMed Central

    Heritage, Steven

    2014-01-01

    Adaptive characterizations of primates have usually included a reduction in olfactory sensitivity. However, this inference of derivation and directionality assumes an ancestral state of olfaction, usually by comparison to a group of extant non-primate mammals. Thus, the accuracy of the inference depends on the assumed ancestral state. Here I present a phylogenetic model of continuous trait evolution that reconstructs olfactory bulb volumes for ancestral nodes of primates and mammal outgroups. Parent-daughter comparisons suggest that, relative to the ancestral euarchontan, the crown-primate node is plesiomorphic and that derived reduction in olfactory sensitivity is an attribute of the haplorhine lineage. The model also suggests a derived increase in olfactory sensitivity at the strepsirrhine node. This oppositional diversification of the strepsirrhine and haplorhine lineages from an intermediate and non-derived ancestor is inconsistent with a characterization of graded reduction through primate evolution. PMID:25426851

  5. Pulmonary vascular disease in mice xenografted with human BM progenitors from patients with pulmonary arterial hypertension

    PubMed Central

    Farha, Samar; Lichtin, Alan; Graham, Brian; George, Deepa; Aldred, Micheala; Hazen, Stanley L.; Loyd, James; Tuder, Rubin

    2012-01-01

    Hematopoietic myeloid progenitors released into the circulation are able to promote vascular remodeling through endothelium activation and injury. Endothelial injury is central to the development of pulmonary arterial hypertension (PAH), a proliferative vasculopathy of the pulmonary circulation, but the origin of vascular injury is unknown. In the present study, mice transplanted with BM-derived CD133+ progenitor cells from patients with PAH, but not from healthy controls, exhibited morbidity and/or death due to features of PAH: in situ thrombi and endothelial injury, angioproliferative remodeling, and right ventricular hypertrophy and failure. Myeloid progenitors from patients with heritable and/or idiopathic PAH all produced disease in xenografted mice. Analyses of hematopoietic transcription factors and colony formation revealed underlying abnormalities of progenitors that skewed differentiation toward the myeloid-erythroid lineage. The results of the present study suggest a causal role for hematopoietic stem cell abnormalities in vascular injury, right ventricular hypertrophy, and morbidity associated with PAH. PMID:22745307

  6. Development and rescue of human familial hypercholesterolaemia in a xenograft mouse model

    PubMed Central

    Bissig-Choisat, Beatrice; Wang, Lili; Legras, Xavier; Saha, Pradip K.; Chen, Leon; Bell, Peter; Pankowicz, Francis P.; Hill, Matthew C.; Barzi, Mercedes; Leyton, Claudia Kettlun; Leung, Hon-Chiu Eastwood; Kruse, Robert L.; Himes, Ryan W.; Goss, John A.; Wilson, James M.; Chan, Lawrence; Lagor, William R.; Bissig, Karl-Dimiter

    2015-01-01

    Diseases of lipid metabolism are a major cause of human morbidity, but no animal model entirely recapitulates human lipoprotein metabolism. Here we develop a xenograft mouse model using hepatocytes from a patient with familial hypercholesterolaemia caused by loss-of-function mutations in the low-density lipoprotein receptor (LDLR). Like familial hypercholesterolaemia patients, our familial hypercholesterolaemia liver chimeric mice develop hypercholesterolaemia and a 'humanized‘ serum profile, including expression of the emerging drug targets cholesteryl ester transfer protein and apolipoprotein (a), for which no genes exist in mice. We go on to replace the missing LDLR in familial hypercholesterolaemia liver chimeric mice using an adeno-associated virus 9-based gene therapy and restore normal lipoprotein profiles after administration of a single dose. Our study marks the first time a human metabolic disease is induced in an experimental animal model by human hepatocyte transplantation and treated by gene therapy. Such xenograft platforms offer the ability to validate human experimental therapies and may foster their rapid translation into the clinic. PMID:26081744

  7. Morphological Features of the Porcine Lacrimal Gland and Its Compatibility for Human Lacrimal Gland Xenografting

    PubMed Central

    Gaffling, Simone; Asano, Nagayoshi; Hampel, Ulrike; Garreis, Fabian; Hornegger, Joachim; Paulsen, Friedrich

    2013-01-01

    In this study, we present first data concerning the anatomical structure, blood supply and location of the lacrimal gland of the pig. Our data indicate that the porcine lacrimal gland may serve as a potential xenograft candidate in humans or as an animal model for engineering of a bioartificial lacrimal gland tissue construct for clinical application. For this purpose, we used different macroscopic preparation techniques and digital reconstruction of the histological gland morphology to gain new insights and important information concerning the feasibility of a lacrimal gland transplantation from pig to humans in general. Our results show that the lacrimal gland of the pig reveals a lot of morphological similarities to the analogous human lacrimal gland and thus might be regarded as a xenograft in the future. This is true for a similar anatomical location within the orbit as well as for the feeding artery supply to the organ. Functional differences concerning the composition of the tear fluid, due to a different secretory unit distribution within the gland tissue will, however, be a challenge in future investigations. PMID:24069265

  8. Association of Primate Veterinarians 2014 Nonhuman Primate Housing Survey.

    PubMed

    Bennett, B Taylor

    2016-01-01

    The Board of Directors of the Association of Primate Veterinarians supported conducting a survey to determine how NHP were housed in USDA-registered research facilities. The data generated were to be used to refute allegations in a petition filed with the USDA by the New England Antivivisectionist Society, which alleged that the proportion of NHP housed singly had not improved since the implementation of the standards contained in §3.81 of the Animal Welfare Regulations. The survey gathered housing information on approximately 90% of the NHP housed in research facilities in FY2014. That information documented that the number of NHP housed in groups or pairs has increased by 20 percentage points to 84% since the USDA's survey conducted in 2000 and 2001. This article describes the methodology and approach used to conduct the survey, summarizes the data obtained, and discusses the meaning of those data. PMID:27025809

  9. Uterine transplantation.

    PubMed

    Brännström, Mats; Racho El-Akouri, Randa; Wranning, Caiza Almén

    2003-08-15

    Uterine factor infertility is either due to congenital malformation or acquired. Most women with uterine factor infertility have no chance to become genetic mothers, except by the use of gestational surrogacy. The logical but radical approach for treatment would be replacement of the unfunctional or absent uterus. Uterine transplantation could allow these women to become both genetic and gestational mothers. The present work reviews the existing literature on the history and recent development around this topic. We also briefly describe a newly developed model for heterotopic uterine transplantation in the mouse, in which pregnancies have been accomplished. Some specific issues that are required to be solved prior any further attempts to transplant the uterus in humans are also addressed. PMID:12860325

  10. Special issue: Comparative biogeography of Neotropical primates.

    PubMed

    Lynch Alfaro, Jessica W; Cortés-Ortiz, Liliana; Di Fiore, Anthony; Boubli, Jean P

    2015-01-01

    New research presented in this special issue of Molecular Phylogenetics and Evolution on the "Phylogeny and Biogeography of Neotropical Primates" greatly improves our understanding of the evolutionary history of the New World monkeys and provides insights into the multiple platyrrhine radiations, diversifications, extinctions, and recolonizations that have taken place over time and over space in the Neotropics. Here, we synthesize genetic and biogeographic research from the past several years to construct an overarching hypothesis for platyrrhine evolution. We also highlight continuing controversies in Neotropical primate biogeography, such as whether the location of origin of platyrrhines was Africa or Asia; whether Patagonian fossil primates are stem or crown platyrrhines; and whether cis- and trans-Andean Neotropical primates were subject to vicariance through Andes mountain building, or instead diversified through isolation in mountain valleys after skirting around the Andes on the northwestern coast of South America. We also consider the role of the Amazon River and its major tributaries in shaping platyrrhine biodiversity, and how and when primates from the Amazon reached the Atlantic Forest. A key focus is on primate colonizations and extirpations in Central America, the Andes, and the seasonally dry tropical forests and savannas (such as the Llanos, Caatinga, and Cerrado habitats), all ecosystems that have been understudied up until now for primates. We suggest that most primates currently inhabiting drier open habitats are relatively recent arrivals, having expanded from rainforest habitats in the Pleistocene. We point to the Pitheciidae as the taxonomic group most in need of further phylogenetic and biogeographic research. Additionally, genomic studies on the Platyrrhini are deeply needed and are expected to bring new surprises and insights to the field of Neotropical primate biogeography. PMID:25451803

  11. Primates in 21st century ecosystems: does primate conservation promote ecosystem conservation?

    PubMed

    Norconk, Marilyn A; Boinski, Sue; Forget, Pierre-Michel

    2011-01-01

    Contributors to this issue of the American Journal of Primatology were among the participants in an invited symposium at the 2008 Association for Tropical Biology and Conservation meeting in Paramaribo, Suriname. They were asked to assess how essential primates are to tropical ecosystems and, given their research interests, discuss how primate research contributes to the broader understanding about how ecosystems function. This introduction to the issue is divided into three parts: a review of the roles that nonhuman primates play in tropical ecosystems; the implementation of large-scale landscape methods used to identify primate densities; and concerns about the increasingly porous boundaries between humans, nonhuman primates, and pathogens. Although 20th century primate research created a rich database on individual species, including both theoretical and descriptive approaches, the dual effects of high human population densities and widespread habitat destruction should warn us that creative, interdisciplinary and human-related research is needed to solve 21st century problems. PMID:20677224

  12. Oligocene primates from China reveal divergence between African and Asian primate evolution.

    PubMed

    Ni, Xijun; Li, Qiang; Li, Lüzhou; Beard, K Christopher

    2016-05-01

    Profound environmental and faunal changes are associated with climatic deterioration during the Eocene-Oligocene transition (EOT) roughly 34 million years ago. Reconstructing how Asian primates responded to the EOT has been hindered by a sparse record of Oligocene primates on that continent. Here, we report the discovery of a diverse primate fauna from the early Oligocene of southern China. In marked contrast to Afro-Arabian Oligocene primate faunas, this Asian fauna is dominated by strepsirhines. There appears to be a strong break between Paleogene and Neogene Asian anthropoid assemblages. Asian and Afro-Arabian primate faunas responded differently to EOT climatic deterioration, indicating that the EOT functioned as a critical evolutionary filter constraining the subsequent course of primate evolution across the Old World. PMID:27151861

  13. Kidney transplantation after liver transplantation.

    PubMed

    Wu, Li-Yang; Liu, Hang; Liu, Wei; Li, Han; Zhang, Xiao-Dong

    2016-08-01

    Kidney transplantation after liver transplantation (KALT) offers longer survival and a better quality of life to liver transplantation recipients who develop chronic renal failure. This article aimed to discuss the efficacy and safety of KALT compared with other treatments. The medical records of 5 patients who had undergone KALT were retrospectively studied, together with a literature review of studies. Three of them developed chronic renal failure after liver transplantation because of calcineurin inhibitor (CNI)-induced nephrotoxicity, while the others had lupus nephritis or non-CNI drug-induced nephrotoxicity. No mortality was observed in the 5 patients. Three KALT cases showed good prognoses, maintaining a normal serum creatinine level during entire follow-up period. Chronic rejection occurred in the other two patients, and a kidney graft was removed from one of them. Our data suggested that KALT is a good alternative to dialysis for liver transplantation recipients. The cases also indicate that KALT can be performed with good long-term survival. PMID:27498586

  14. The Automated Primate Research Laboratory (APRL)

    NASA Technical Reports Server (NTRS)

    Pace, N.; Smith, G. D.

    1972-01-01

    A description is given of a self-contained automated primate research laboratory to study the effects of weightlessness on subhuman primates. Physiological parameters such as hemodynamics, respiration, blood constituents, waste, and diet and nutrition are analyzed for abnormalities in the simulated space environment. The Southeast Asian pig-tailed monkey (Macaca nemistrina) was selected for the experiments owing to its relative intelligence and learning capacity. The objective of the program is to demonstrate the feasibility of a man-tended primate space flight experiment.

  15. The isolation and characterization of renal cancer initiating cells from human Wilms' tumour xenografts unveils new therapeutic targets†

    PubMed Central

    Pode-Shakked, Naomi; Shukrun, Rachel; Mark-Danieli, Michal; Tsvetkov, Peter; Bahar, Sarit; Pri-Chen, Sara; Goldstein, Ronald S; Rom-Gross, Eithan; Mor, Yoram; Fridman, Edward; Meir, Karen; Simon, Amos; Magister, Marcus; Kaminski, Naftali; Goldmacher, Victor S; Harari-Steinberg, Orit; Dekel, Benjamin

    2013-01-01

    There are considerable differences in tumour biology between adult and paediatric cancers. The existence of cancer initiating cells/cancer stem cells (CIC/CSC) in paediatric solid tumours is currently unclear. Here, we show the successful propagation of primary human Wilms' tumour (WT), a common paediatric renal malignancy, in immunodeficient mice, demonstrating the presence of a population of highly proliferative CIC/CSCs capable of serial xenograft initiation. Cell sorting and limiting dilution transplantation analysis of xenograft cells identified WT CSCs that harbour a primitive undifferentiated – NCAM1 expressing – “blastema” phenotype, including a capacity to expand and differentiate into the mature renal-like cell types observed in the primary tumour. WT CSCs, which can be further enriched by aldehyde dehydrogenase activity, overexpressed renal stemness and genes linked to poor patient prognosis, showed preferential protein expression of phosphorylated PKB/Akt and strong reduction of the miR-200 family. Complete eradication of WT in multiple xenograft models was achieved with a human NCAM antibody drug conjugate. The existence of CIC/CSCs in WT provides new therapeutic targets. PMID:23239665

  16. Investigation of the origin of stromal and endothelial cells at the desmoplastic interface in xenograft tumor in mice.

    PubMed

    Jung, Minsun; Ryu, Young-joon; Kang, Gu

    2015-12-01

    Carcinoma-associated fibroblasts found at the interface between a tumor and the normal stroma play several roles in the development of cancer, including cancer initiation, growth, and progression, thereby also affecting patient prognosis. Although recent studies have focused on carcinoma-associated fibroblasts as potential treatment targets, the origin of these fibroblasts remains unclear. One theory suggests that these cells arise from tumor cells undergoing the epithelial-mesenchymal transition, i.e., tumor cells transform into carcinoma-associated fibroblasts. Therefore, in this study, we aimed to elucidate the cellular origin of carcinoma-associated fibroblasts in a mouse xenograft model. Mice were transplanted with human lung cancer cells (H226 and A549 cells). After sacrifice, tumor masses and surrounding tissues were excised. Interestingly, the excised xenograft tissues contained a significant proportion of desmoplastic fibroblasts that exhibited strong expression of α-smooth muscle actin (SMA). Immunohistochemical staining with pan-cytokeratin, vimentin, β-catenin, E-cadherin, and CD34 showed no evidence of the epithelial-mesenchymal transition. Additional evaluation using dual-color silver in situ hybridization with dinitrophenyl-labeled human epidermal growth factor receptor 2 (HER2) and digoxigenin-labeled chromosome 17 centromere probes also showed similar results. In conclusion, our results revealed that the epithelial-mesenchymal transition may not occur in tumor xenograft models, regardless of evidence supporting this phenomenon in humans. PMID:26564105

  17. Heart Transplantation

    MedlinePlus

    A heart transplant removes a damaged or diseased heart and replaces it with a healthy one. The healthy heart comes from a donor who has died. It is the last resort for people with heart failure when all other treatments have failed. The ...

  18. Transplant production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    For field pepper (Capsicum spp.) production, plants can be established from direct seed or transplants depending on the location and cultural practices for the specific pepper type grown. Direct seeding can result in slow, variable, and reduced plant stands due to variations in soil temperature, wat...

  19. Lung Transplantation

    MedlinePlus

    ... years. Their conditions are so severe that other treatments, such as medicines or breathing devices, no longer work. Lung transplants most often are used to treat people who have severe COPD Cystic fibrosis Idiopathic pulmonary fibrosis Alpha-1 antitrypsin deficiency Pulmonary ...

  20. Global Conservation of Protein Status between Cell Lines and Xenografts.

    PubMed

    Biau, Julian; Chautard, Emmanuel; Court, Frank; Pereira, Bruno; Verrelle, Pierre; Devun, Flavien; De Koning, Leanne; Dutreix, Marie

    2016-08-01

    Common preclinical models for testing anticancer treatment include cultured human tumor cell lines in monolayer, and xenografts derived from these cell lines in immunodeficient mice. Our goal was to determine how similar the xenografts are compared with their original cell line and to determine whether it is possible to predict the stability of a xenograft model beforehand. We studied a selection of 89 protein markers of interest in 14 human cell cultures and respective subcutaneous xenografts using the reverse-phase protein array technology. We specifically focused on proteins and posttranslational modifications involved in DNA repair, PI3K pathway, apoptosis, tyrosine kinase signaling, stress, cell cycle, MAPK/ERK signaling, SAPK/JNK signaling, NFκB signaling, and adhesion/cytoskeleton. Using hierarchical clustering, most cell culture-xenograft pairs cluster together, suggesting a global conservation of protein signature. Particularly, Akt, NFkB, EGFR, and Vimentin showed very stable protein expression and phosphorylation levels highlighting that 4 of 10 pathways were highly correlated whatever the model. Other proteins were heterogeneously conserved depending on the cell line. Finally, cell line models with low Akt pathway activation and low levels of Vimentin gave rise to more reliable xenograft models. These results may be useful for the extrapolation of cell culture experiments to in vivo models in novel targeted drug discovery. PMID:27567954

  1. Development and characterization of a human orthotopic neuroblastoma xenograft

    PubMed Central

    Stewart, Elizabeth; Shelat, Anang; Bradley, Cori; Chen, Xiang; Federico, Sara; Thiagarajan, Suresh; Shirinifard, Abbas; Bahrami, Armita; Pappo, Alberto; Qu, Chunxu; Finkelstein, David; Sablauer, Andras; Dyer, Michael A.

    2016-01-01

    Neuroblastoma is a pediatric cancer of the developing sympathoadrenal lineage. The tumors are known to develop from the adrenal gland or paraspinal ganglia and have molecular and cellular features of sympathetic neurons such as dense core vesicles and catecholamine production. Here we present the detailed molecular, cellular, genetic and epigenetic characterization of an orthotopic xenograft derived from a high-risk stage 4 neuroblastoma patient. Overall, the xenografted tumor retained the high risk features of the primary tumor and showed aggressive growth and metastasis in the mouse. Also, the genome was preserved with no additional copy number variations, structural variations or aneuploidy. There were 13 missense mutations identified in the xenograft that were not present in the patient’s primary tumor and there were no new nonsense mutations. None of the missense mutations acquired in the xenograft were in known cancer genes. We also demonstrate the feasibility of using the orthotopic neuroblastoma xenograft to test standard of care chemotherapy and molecular targeted therapeutics. Finally, we optimized a new approach to produce primary cultures of the neuroblastoma xenografts for high-throughput drug screening which can be used to test new combinations of therapeutic agents for neuroblastoma. PMID:25863122

  2. Biokinetics of Plutonium in Nonhuman Primates.

    PubMed

    Poudel, Deepesh; Guilmette, Raymond A; Gesell, Thomas F; Harris, Jason T; Brey, Richard R

    2016-10-01

    A major source of data on metabolism, excretion and retention of plutonium comes from experimental animal studies. Although old world monkeys are one of the closest living relatives to humans, certain physiological differences do exist between these nonhuman primates and humans. The objective of this paper was to describe the metabolism of plutonium in nonhuman primates using the bioassay and retention data obtained from macaque monkeys injected with plutonium citrate. A biokinetic model for nonhuman primates was developed by adapting the basic model structure and adapting the transfer rates described for metabolism of plutonium in adult humans. Significant changes to the parameters were necessary to explain the shorter retention of plutonium in liver and skeleton of the nonhuman primates, differences in liver to bone partitioning ratio, and significantly higher excretion of plutonium in feces compared to that in humans. PMID:27575347

  3. The use of nonhuman primates in space

    NASA Technical Reports Server (NTRS)

    Simmonds, R. C. (Editor); Bourne, G. H. (Editor)

    1977-01-01

    Space related biomedical research involving nonhuman primates is reviewed. The scientific assets of various species and the instruments used for monitoring physiological processes during long duration experimentations are described.

  4. A Mitogenomic Phylogeny of Living Primates

    PubMed Central

    Finstermeier, Knut; Zinner, Dietmar; Brameier, Markus; Meyer, Matthias; Kreuz, Eva; Hofreiter, Michael; Roos, Christian

    2013-01-01

    Primates, the mammalian order including our own species, comprise 480 species in 78 genera. Thus, they represent the third largest of the 18 orders of eutherian mammals. Although recent phylogenetic studies on primates are increasingly built on molecular datasets, most of these studies have focused on taxonomic subgroups within the order. Complete mitochondrial (mt) genomes have proven to be extremely useful in deciphering within-order relationships even up to deep nodes. Using 454 sequencing, we sequenced 32 new complete mt genomes adding 20 previously not represented genera to the phylogenetic reconstruction of the primate tree. With 13 new sequences, the number of complete mt genomes within the parvorder Platyrrhini was widely extended, resulting in a largely resolved branching pattern among New World monkey families. We added 10 new Strepsirrhini mt genomes to the 15 previously available ones, thus almost doubling the number of mt genomes within this clade. Our data allow precise date estimates of all nodes and offer new insights into primate evolution. One major result is a relatively young date for the most recent common ancestor of all living primates which was estimated to 66-69 million years ago, suggesting that the divergence of extant primates started close to the K/T-boundary. Although some relationships remain unclear, the large number of mt genomes used allowed us to reconstruct a robust primate phylogeny which is largely in agreement with previous publications. Finally, we show that mt genomes are a useful tool for resolving primate phylogenetic relationships on various taxonomic levels. PMID:23874967

  5. Conversion of monkey fibroblasts to transplantable telencephalic neuroepithelial stem cells.

    PubMed

    Ai, Zongyong; Xiang, Zheng; Li, Yuemin; Liu, Guoku; Wang, Hong; Zheng, Yun; Qiu, Xiaoyan; Zhao, Shumei; Zhu, Xiaoqing; Li, Yanhua; Ji, Weizhi; Li, Tianqing

    2016-01-01

    Non-human primates provide optimal models for the development of stem cell therapies. Although somatic cells have been converted into neural stem/progenitor cells, it is unclear whether telencephalic neuroepithelial stem cells (NESCs) with stable properties can be generated from fibroblasts in primate. Here we report that a combination of transcription factors (Oct4, Sox2, Klf4) with a new culture medium induces rhesus monkey fibroblasts into NESCs, which can develop into miniature neural tube (NT)-like structures at a cell level. Furthermore, single induced NESCs (iNESCs) can generate later-stage 3D-NTs after grown on matrigel in suspension culture. iNESCs express NT cell markers, have a unique gene expression pattern biasing towards telencephalic patterning, and give rise to cortical neurons. Via transplantation, single iNESCs can extensively survive, regenerate myelinated neuron axons and synapse structures in adult monkey striatum and cortex, and differentiate into cortical neurons. Successful transplantation is closely associated with graft regions and grafted cell identities. The ability to generate defined and transplantable iNESCs from primate fibroblasts under a defined condition with predictable fate choices will facilitate disease modeling and cell therapy. PMID:26584346

  6. Contextualising primate origins--an ecomorphological framework.

    PubMed

    Soligo, Christophe; Smaers, Jeroen B

    2016-04-01

    Ecomorphology - the characterisation of the adaptive relationship between an organism's morphology and its ecological role - has long been central to theories of the origin and early evolution of the primate order. This is exemplified by two of the most influential theories of primate origins: Matt Cartmill's Visual Predation Hypothesis, and Bob Sussman's Angiosperm Co-Evolution Hypothesis. However, the study of primate origins is constrained by the absence of data directly documenting the events under investigation, and has to rely instead on a fragmentary fossil record and the methodological assumptions inherent in phylogenetic comparative analyses of extant species. These constraints introduce particular challenges for inferring the ecomorphology of primate origins, as morphology and environmental context must first be inferred before the relationship between the two can be considered. Fossils can be integrated in comparative analyses and observations of extant model species and laboratory experiments of form-function relationships are critical for the functional interpretation of the morphology of extinct species. Recent developments have led to important advancements, including phylogenetic comparative methods based on more realistic models of evolution, and improved methods for the inference of clade divergence times, as well as an improved fossil record. This contribution will review current perspectives on the origin and early evolution of primates, paying particular attention to their phylogenetic (including cladistic relationships and character evolution) and environmental (including chronology, geography, and physical environments) contextualisation, before attempting an up-to-date ecomorphological synthesis of primate origins. PMID:26830706

  7. Islet Transplantation

    PubMed Central

    2003-01-01

    EXECUTIVE SUMMARY Objective The Medical Advisory Secretariat undertook a review of the evidence on the effectiveness and cost-effectiveness of islet transplantation alone (ITA) in non-uremic patients with type 1 DM who have severe hypoglycemia and uncontrolled diabetes (brittle diabetics). Results In a health technology assessment from Alberta, Guo et al. (2003) stated that limited evidence from the Edmonton series suggested that islet cell transplantation (ITA) (using the Edmonton Protocol) is effective in 1) controlling labile diabetes and 2) protecting against unrecognized hypoglycemia in highly selected patients in the short term. This conclusion by Guo et al. (2003) was based on the results of 11/17 insulin independent patients who were followed up for a median of 20.4 months in the trial by Ryan et al. (2002). In contrast, Paty et al. (2002) concluded that glucagon and epinephrine responses and hypoglycemic symptom recognition were not improved by islet transplantation in patients receiving the procedure in Edmonton, despite prolonged insulin independence and near-normal glycemic control. Paty et al. (2002) (a member of the Edmonton team) examined 7 ITA recipients, 7 type 1 DM patients (nonITA), and 7 nondiabetic control patients. The follow-up for most studies was short. It was suggested that the modifications to the conventional ITA approaches, including the steroid free immunosuppressive regimen, islet preparation in xenoproteins free media and transplantation of fresh islets from multiple donors were associated with improved success. The effects of ITA on beta cell function (secretion of insulin) look promising, however, the effects of ITA on pancreatic alpha cell function (secretion of counter-regulatory hormones such as glucagon and epinephrine) in long standing type 1 diabetes remain unclear. The most important barriers to more widespread islet transplantation using the Edmonton protocol are the availability of sufficient donor organs and the

  8. PTEN Loss Does Not Predict for Response to RAD001 (Everolimus) in a Glioblastoma Orthotopic Xenograft Test Panel

    PubMed Central

    Yang, Lin; Clarke, Michelle J.; Carlson, Brett L.; Mladek, Ann C.; Schroeder, Mark A.; Decker, Paul; Wu, Wenting; Kitange, Gaspar J.; Grogan, Patrick T.; Goble, Jennie M.; Uhm, Joon; Galanis, Evanthia; Giannini, Caterina; Lane, Heidi A.; James, C. David; Sarkaria, Jann N.

    2014-01-01

    Purpose Hyperactivation of the phosphatidylinositol 3-kinase/Akt signaling through disruption of PTEN function is common in glioblastoma multiforme, and these genetic changes are predicted to enhance sensitivity to mammalian target of rapamycin (mTOR) inhibitors such as RAD001 (everolimus). Experimental Design To test whether PTEN loss could be used as a predictive marker for mTOR inhibitor sensitivity, the response of 17 serially transplantable glioblastoma multiforme xenografts was evaluated in an orthotopic therapy evaluation model. Of these 17 xenograft lines, 7 have either genomic deletion or mutation of PTEN. Results Consistent with activation of Akt signaling, there was a good correlation between loss of PTEN function and elevated levels of Akt phosphorylation. However, of the 7 lines with disrupted PTEN function, only 1 tumor line (GBM10) was significantly sensitive to RAD001 therapy (25% prolongation in median survival), whereas1 of 10 xenograft lines with wild-type PTEN was significantly sensitive to RAD001 (GS22; 34% prolongation in survival). Relative to placebo, 5 days of RAD001 treatment was associated with a marked 66% reduction in the MIB1 proliferation index in the sensitive GBM10 line (deleted PTEN) compared with a 25% and 7% reduction in MIB1 labeling index in the insensitive GBM14 (mutant PTEN) and GBM15 (wild-type PTEN) lines, respectively. Consistent with a cytostatic antitumor effect, bioluminescent imaging of luciferase-transduced intracranial GBM10 xenografts showed slowed tumor growth without significant tumor regression during RAD001 therapy. Conclusion These data suggest that loss of PTEN function is insufficient to adequately predict responsiveness to mTOR inhibitors in glioblastoma multiforme. PMID:18559622

  9. Perceptions of nonhuman primates in human-wildlife conflict scenarios.

    PubMed

    Hill, Catherine M; Webber, Amanda D

    2010-09-01

    Nonhuman primates (referred to as primates in this study) are sometimes revered as gods, abhorred as evil spirits, killed for food because they damage crops, or butchered for sport. Primates' perceived similarity to humans places them in an anomalous position. While some human groups accept the idea that primates "straddle" the human-nonhuman boundary, for others this resemblance is a violation of the human-animal divide. In this study we use two case studies to explore how people's perceptions of primates are often influenced by these animals' apparent similarity to humans, creating expectations, founded within a "human morality" about how primates should interact with people. When animals transgress these social rules, they are measured against the same moral framework as humans. This has implications for how people view and respond to certain kinds of primate behaviors, their willingness to tolerate co-existence with primates and their likely support for primate conservation initiatives. PMID:20806339

  10. Development of Patient Derived Xenograft Models of Overt Spontaneous Breast Cancer Metastasis: A Cautionary Note

    PubMed Central

    Paez-Ribes, Marta; Man, Shan; Xu, Ping; Kerbel, Robert S.

    2016-01-01

    Several approaches are being evaluated to improve the historically limited value of studying transplanted primary tumors derived by injection of cells from established cell lines for predicting subsequent cancer therapy outcomes in patients and clinical trials. These approaches include use of genetically engineered mouse models (GEMMs) of spontaneous tumors, or patient tumor tissue derived xenografts (PDXs). Almost all such therapy studies utilizing such models involve treatment of established primary tumors. An alternative approach we have developed involves transplanted human tumor xenografts derived from established cell lines to treat mice with overt visceral metastases after primary tumor resection. The rationale is to mimic the more challenging circumstance of treating patients with late stage metastatic disease. These metastatic models entail prior in vivo selection of heritable, phenotypically stable variants with increased aggressiveness for spontaneous metastasis; they were derived by orthotopic injection of tumor cells followed by primary tumor resection and serial selection of distant spontaneous metastases, from which variant cell lines having a more aggressive heritable metastatic phenotype were established. We attempted to adopt this strategy for breast cancer PDXs. We studied five breast cancer PDXs, with the emphasis on two, called HCI-001 and HCI-002, both derived from triple negative breast cancer patients. However significant technical obstacles were encountered. These include the inherent slow growth rates of PDXs, the rarity of overt spontaneous metastases (detected in only 3 of 144 mice), very high rates of tumor regrowths at the primary tumor resection site, the failure of the few human PDX metastases isolated to manifest a more aggressive metastatic phenotype upon re-transplantation into new hosts, and the formation of metastases which were derived from de novo mouse thymomas arising in aged SCID mice that we used for the experiments. We

  11. Molecular profiling of patient-derived breast cancer xenografts

    PubMed Central

    2012-01-01

    Introduction Identification of new therapeutic agents for breast cancer (BC) requires preclinical models that reproduce the molecular characteristics of their respective clinical tumors. In this work, we analyzed the genomic and gene expression profiles of human BC xenografts and the corresponding patient tumors. Methods Eighteen BC xenografts were obtained by grafting tumor fragments from patients into Swiss nude mice. Molecular characterization of patient tumors and xenografts was performed by DNA copy number analysis and gene expression analysis using Affymetrix Microarrays. Results Comparison analysis showed that 14/18 pairs of tumors shared more than 56% of copy number alterations (CNA). Unsupervised hierarchical clustering analysis showed that 16/18 pairs segregated together, confirming the similarity between tumor pairs. Analysis of recurrent CNA changes between patient tumors and xenografts showed losses in 176 chromosomal regions and gains in 202 chromosomal regions. Gene expression profile analysis showed that less than 5% of genes had recurrent variations between patient tumors and their respective xenografts; these genes largely corresponded to human stromal compartment genes. Finally, analysis of different passages of the same tumor showed that sequential mouse-to-mouse tumor grafts did not affect genomic rearrangements or gene expression profiles, suggesting genetic stability of these models over time. Conclusions This panel of human BC xenografts maintains the overall genomic and gene expression profile of the corresponding patient tumors and remains stable throughout sequential in vivo generations. The observed genomic profile and gene expression differences appear to be due to the loss of human stromal genes. These xenografts, therefore, represent a validated model for preclinical investigation of new therapeutic agents. PMID:22247967

  12. Voice discrimination in four primates.

    PubMed

    Candiotti, Agnès; Zuberbühler, Klaus; Lemasson, Alban

    2013-10-01

    One accepted function of vocalisations is to convey information about the signaller, such as its age-sex class, motivation, or relationship with the recipient. Yet, in natural habitats individuals not only interact with conspecifics but also with members of other species. This is well documented for African forest monkeys, which form semi-permanent mixed-species groups that can persist for decades. Although members of such groups interact with each other on a daily basis, both physically and vocally, it is currently unknown whether they can discriminate familiar and unfamiliar voices of heterospecific group members. We addressed this question with playbacks on monkey species known to form polyspecific associations in the wild: red-capped mangabeys, Campbell's monkeys and Guereza colobus monkeys. We tested subjects' discrimination abilities of contact calls of familiar and unfamiliar female De Brazza monkeys. When pooling all species, subjects looked more often towards the speaker when hearing contact calls of unfamiliar than familiar callers. When testing De Brazza monkeys with their own calls, we found the same effect with the longest gaze durations after hearing unfamiliar voices. This suggests that primates can discriminate, not only between familiar and unfamiliar voices of conspecifics, but also between familiar and unfamiliar voices of heterospecifics living within a close proximity. PMID:23800631

  13. Globin gene switching in primates.

    PubMed

    Johnson, Robert M; Gumucio, Deborah; Goodman, Morris

    2002-11-01

    Evolutionary approaches to the identification of DNA sequences required for transcription of the genes of the beta-globin cluster are reviewed. Sequence alignments of non-coding regions from widely divergent species revealed many conserved motifs (phylogenetic footprints) that were putative transcription factor binding sites and candidate binding proteins were identified. The differential timing of the prosimian and simian gamma-globin genes was analyzed by identifying base changes in the vicinity of the phylogenetic footprints. These differential phylogenetic footprints were shown to bind different nuclear factors, and the behavior of constructs with human or galago gamma-promoters in transgenic mice indicated that DNA motifs near the gamma-globin genes are sufficient to determine the developmental stage of expression. Locus control region alignments have identified many conserved sequence differences outside of the hypersensitive sites. Globin protein and mRNA expression profiles during embryological development in a series of catarrhine (Old World monkeys and apes) and platyrrhine (New World monkeys) primates have been determined. While all catarrhines examined to date have globin expression patterns that are highly similar to the well-established human switching behavior, platyrrhines have inactivated their gamma 1 genes by a variety of mechanisms, and have an earlier gamma-beta switch. PMID:12443943

  14. Before the Transplant

    MedlinePlus

    ... Devices About Organ Allocation Getting on the List Financing a Transplant Waiting for your Transplant About the ... Types Being a Living Donor About the Operation Financing Living Donation Home / Before The Transplant Organ Facts ...

  15. International Transplant Nurses Society

    MedlinePlus

    ... Register for the 25th Annual ITNS Symposium The International Transplant Nurses Society (ITNS) cordially invites transplant nurses ... Barriers (PDF) This pocket guide, developed by the International Transplant Nurses Society (ITNS), provides an overview of ...

  16. Pancreatic Islet Transplantation

    MedlinePlus

    ... allo-transplantation?" For each pancreatic islet allo-transplant infusion, researchers use specialized enzymes to remove islets from ... in a lab. Transplant patients typically receive two infusions with an average of 400,000 to 500, ...

  17. Endocrine function after immunosuppression of pancreatic allograft by ionizing irradiation in the primate

    SciTech Connect

    Du Toit, D.F.; Heydenrych, J.J.; Smit, B.; Louw, G.; Zuurmond, T.; Laker, L.; Els, D.; Weideman, A.; Wolfe-Coote, S.; Du Toit, L.B.

    1986-05-01

    The object of this preliminary study was to evaluate the endocrine function after heterotopic intraperitoneal segmental pancreatic allotransplantation with unligated duct in irradiated, totally pancreatectomized primates. All allograft recipients received, pre- and peroperative donor-specific blood transfusions and peroperative external irradiation from a linear accelerator; 200 rads was administered weekly and increased to a total dose of 1,500 rads. Pancreatic transplantation was performed between 2 and 6 weeks after completion of irradiation and preoperative blood transfusions. As previously reported, only minimal pancreatic allograft survival was achieved following preoperative irradiation. One recipient remained normoglycaemic for greater than 100 days after transplantation, the longest surviving pancreatic allograft recipient reported from this laboratory. Intravenous glucose tolerance test results in this recipient revealed normoglycaemia, reduced K-value, hypoinsulinaemia, normal glucagon response, reduced C-peptide values, and moderate glucose intolerance. Aortography and electron-microscopic examination of allograft biopsy tissue confirmed the presence of a functioning allograft.

  18. A human fetal prostate xenograft model of developmental estrogenization.

    PubMed

    Saffarini, Camelia M; McDonnell-Clark, Elizabeth V; Amin, Ali; Boekelheide, Kim

    2015-01-01

    Prostate cancer is a common disease in older men. Rodent models have demonstrated that an early and later-life exposure to estrogen can lead to cancerous lesions and implicated hormonal dysregulation as an avenue for developing future prostate neoplasia. This study utilizes a human fetal prostate xenograft model to study the role of estrogen in the progression of human disease. Histopathological lesions were assessed in 7-, 30-, 90-, 200-, and 400-day human prostate xenografts. Gene expression for cell cycle, tumor suppressors, and apoptosis-related genes (ie, CDKN1A, CASP9, ESR2, PTEN, and TP53) was performed for 200-day estrogen-treated xenografts. Glandular hyperplasia was observed in xenografts given both an initial and secondary exposure to estradiol in both 200- and 400-day xenografts. Persistent estrogenic effects were verified using immunohistochemical markers for cytokeratin 10, p63, and estrogen receptor α. This model provides data on the histopathological state of the human prostate following estrogenic treatment, which can be utilized in understanding the complicated pathology associated with prostatic disease and early and later-life estrogenic exposures. PMID:25633637

  19. Establishment and Characterization of a Human Neuroendocrine Tumor Xenograft.

    PubMed

    Yang, Zhaoying; Zhang, Le; Serra, Stefano; Law, Calvin; Wei, Alice; Stockley, Tracy L; Ezzat, Shereen; Asa, Sylvia L

    2016-06-01

    Neuroendocrine tumors (NETs) are increasing in incidence yet the cause of these tumors remains unknown. Familial associations have shed light on the genetic basis of some of these tumors, but sporadic tumors seem to have primarily epigenetic dysregulation. The rarity of cell lines and animal models has been a barrier to studies of treatment modalities. We set out to develop a xenograft model of gastrointestinal NETs. Primary human NETs were collected at the time of surgery under sterile conditions and xenografted into the flanks of immunodeficient mice. Tumor growth was measured and when tumors reached 1500 mm(3), they were excised and half was re-xenografted through multiple generations. The other half was bisected; a part was frozen and a part was fixed for morphologic and immunohistochemical characterization as well as molecular validation of fidelity of a successful xenograft. Of 106 human NETs, seven were successfully engrafted of which only one tumor was successfully propagated for eight passages. Two years later, the tumor retains its neuroendocrine features and similarity to the original primary human tumor. It has retained expression of keratin as well as chromogranin A reactivity. The establishment of a NET xenograft provides a model for further study of the biological behavior of these tumors and can be used to examine the in vivo effects of various medical and targeted radiotherapeutic agents on tumor growth. PMID:27067082

  20. Ancient single origin for Malagasy primates.

    PubMed Central

    Yoder, A D; Cartmill, M; Ruvolo, M; Smith, K; Vilgalys, R

    1996-01-01

    We report new evidence that bears decisively on a long-standing controversy in primate systematics. DNA sequence data for the complete cytochrome b gene, combined with an expanded morphological data set, confirm the results of a previous study and again indicate that all extant Malagasy lemurs originated from a single common ancestor. These results, as well as those from other genetic studies, call for a revision of primate classifications in which the dwarf and mouse lemurs are placed within the Afro-Asian lorisiforms. The phylogenetic results, in agreement with paleocontinental data, indicate an African origin for the common ancestor of lemurs and lorises (the Strepsirrhini). The molecular data further suggest the surprising conclusion that lemurs began evolving independently by the early Eocene at the latest. This indicates that the Malagasy primate lineage is more ancient than generally thought and places the split between the two strepsirrhine lineages well before the appearance of known Eocene fossil primates. We conclude that primate origins were marked by rapid speciation and diversification sometime before the late Paleocene. Images Fig. 1 Fig. 2 PMID:8643538

  1. Sperm Morphology Assessment in Captive Neotropical Primates.

    PubMed

    Swanson, W F; Valle, R R; Carvalho, F M; Arakaki, P R; Rodas-Martínez, A Z; Muniz, Japc; García-Herreros, M

    2016-08-01

    The main objective of this study was to evaluate sperm morphology in four neotropical primate species to compare the sperm morphological traits and the sperm morphometric parameters as a basis for establishing normative sperm standards for each species. Data from 80 ejaculates collected from four primate species, Callithrix jacchus, Callimico goeldii, Alouatta caraya and Ateles geoffroyi, were analysed for detection of sperm morphological alterations using subjective World Health Organization (WHO-2010) standards and Sperm Deformity Index (SDI) criteria, objective computer-assisted sperm morphometry analysis (CASMA) and subpopulation sperm determination (SSD) methods. There were multiple differences (p < 0.01) observed among primate species in values obtained from WHO-2010, SDI, CASMA and SSD sperm analysis methods. In addition, multiple significant positive and negative correlations were observed between the sperm morphological traits (SDI, Sperm Deformity Index Head Defects, Sperm Deformity Index Midpiece Defects, Sperm Deformity Index Tail Defects, Normal Sperm, Head Defects, Midpiece Defects and Tail Defects) and the sperm morphometric parameters (SSD, Area (A), Perimeter (P), Length (L), Width (W), Ellipticity, Elongation and Rugosity) (p ≤ 0.046). In conclusion, our findings using different evaluation methods indicate that pronounced sperm morphological variation exists among these four neotropical primate species. Because of the strong relationship observed among morphological and morphometric parameters, these results suggest that application of objective analysis methods could substantially improve the reliability of comparative studies and help to establish valid normative sperm values for neotropical primates. PMID:27260333

  2. Neocortex size predicts deception rate in primates.

    PubMed Central

    Byrne, Richard W.; Corp, Nadia

    2004-01-01

    Human brain organization is built upon a more ancient adaptation, the large brain of simian primates: on average, monkeys and apes have brains twice as large as expected for mammals of their size, principally as a result of neocortical enlargement. Testing the adaptive benefit of this evolutionary specialization depends on finding an association between brain size and function in primates. However, most cognitive capacities have been assessed in only a restricted range of species under laboratory conditions. Deception of conspecifics in social circumstances is an exception, because a corpus of field data is available that encompasses all major lines of the primate radiation. We show that the use of deception within the primates is well predicted by the neocortical volume, when observer effort is controlled for; by contrast, neither the size of the rest of the brain nor the group size exert significant effects. These findings are consistent with the hypothesis that neocortical expansion has been driven by social challenges among the primates. Complex social manipulations such as deception are thought to be based upon rapid learning and extensive social knowledge; thus, learning in social contexts may be constrained by neocortical size. PMID:15306289

  3. Operant Nociception in Nonhuman Primates

    PubMed Central

    Kangas, Brian D.; Bergman, Jack

    2014-01-01

    The effective management of pain is a longstanding public health concern. Morphine-like opioids have long been front-line analgesics, but produce undesirable side effects that can limit their application. Slow progress in the introduction of novel improved medications for pain management over the last 5 decades has prompted a call for innovative translational research, including new preclinical assays. Most current in vivo procedures (e.g., tail flick, hot plate, warm water tail withdrawal) assay the effects of nociceptive stimuli on simple spinal reflexes or unconditioned behavioral reactions. However, clinical treatment goals may include the restoration of previous behavioral activities, which can be limited by medication-related side-effects that are not measured in such procedures. The present studies describe an apparatus and procedure to study the disruptive effects of nociceptive stimuli on voluntary behavior in nonhuman primates, and the ability of drugs to restore such behavior through their analgesic actions. Squirrel monkeys were trained to pull a cylindrical thermode for access to a highly palatable food. Next, sessions were conducted in which the temperature of the thermode was increased stepwise until responding stopped, permitting the determination of stable nociceptive thresholds. Tests revealed that several opioid analgesics, but not d-amphetamine or Δ9-THC, produced dose-related increases in threshold that were antagonist-sensitive and efficacy-dependent, consistent with their effects using traditional measures of antinociception. Unlike traditional reflex-based measures, however, the results also permitted the concurrent evaluation of response disruption, providing an index with which to characterize the behavioral selectivity of antinociceptive drugs. PMID:24968803

  4. Patient-derived bladder cancer xenografts: a systematic review.

    PubMed

    Bernardo, Carina; Costa, Céu; Sousa, Nuno; Amado, Francisco; Santos, Lúcio

    2015-10-01

    Patient-derived tumor xenografts (PDTXs) are said to accurately reflect the heterogeneity of human tumors. In the case of human bladder cancer, few studies are available featuring these models. The best methodology to develop and the real value of the model remain unclear. This systematic review aims to elucidate the best methodology to establish and use PDTXs to study the characteristics and behavior of human bladder tumors. The value and potential application of these models are also addressed. A comprehensive literature search was performed to identify published studies using xenograft models directly established from human bladder cancer samples into mice. A total of 12 studies were included in the final analysis. All studies differed in design; the reported take rate varied between 11% and 80%, with the implantation via dorsal incision and with matrigel obtaining the higher take rate. Advanced stage and high-grade tumors were associated with increased take rate. Xenografts preserved the original tumor identity in the establishment phase and after serial passages. Although some studies suggest a correlation between engraftment success and clinical prognosis, evidence about the association between the response of xenografts to treatment and the clinical response of the tumor of origin is still missing. All methodological approaches resulted in the establishment of tumor xenografts with preservation of the original tumor identity but variable take rate. The time needed to establish the model and propagate xenografts to a number suitable for drug testing is the main limitation of the model, along with the success rate and lack of consistency in the early passages. Comparison between tumor response in mice and clinical outcome remains to be assessed. PMID:25742701

  5. The social nature of primate cognition

    PubMed Central

    Barrett, Louise; Henzi, Peter

    2005-01-01

    The hypothesis that the enlarged brain size of the primates was selected for by social, rather than purely ecological, factors has been strongly influential in studies of primate cognition and behaviour over the past two decades. However, the Machiavellian intelligence hypothesis, also known as the social brain hypothesis, tends to emphasize certain traits and behaviours, like exploitation and deception, at the expense of others, such as tolerance and behavioural coordination, and therefore presents only one view of how social life may shape cognition. This review outlines work from other relevant disciplines, including evolutionary economics, cognitive science and neurophysiology, to illustrate how these can be used to build a more general theoretical framework, incorporating notions of embodied and distributed cognition, in which to situate questions concerning the evolution of primate social cognition. PMID:16191591

  6. Genetic correlates of the evolving primate brain

    PubMed Central

    Vallender, Eric J.

    2012-01-01

    The tremendous shifts in the size, structure, and function of the brain during primate evolution are ultimately caused by changes at the genetic level. Understanding what these changes are and how they effect the phenotypic changes observed lies at the heart of understanding evolutionary change. This chapter focuses on understanding the genetic basis of primate brain evolution, considering the substrates and mechanisms through which genetic change occurs. It also discusses the implications that our current understandings and tools have for what we have already discovered and where our studies will head in the future. While genetic and genomic studies have identified many regions undergoing positive selection during primate evolution, the findings are certainly not exhaustive and functional relevance remains to be confirmed. Nevertheless, a strong foundation has been built upon which future studies will emerge. PMID:22230621

  7. The ecology of primate material culture.

    PubMed

    Koops, Kathelijne; Visalberghi, Elisabetta; van Schaik, Carel P

    2014-11-01

    Tool use in extant primates may inform our understanding of the conditions that favoured the expansion of hominin technology and material culture. The 'method of exclusion' has, arguably, confirmed the presence of culture in wild animal populations by excluding ecological and genetic explanations for geographical variation in behaviour. However, this method neglects ecological influences on culture, which, ironically, may be critical for understanding technology and thus material culture. We review all the current evidence for the role of ecology in shaping material culture in three habitual tool-using non-human primates: chimpanzees, orangutans and capuchin monkeys. We show that environmental opportunity, rather than necessity, is the main driver. We argue that a better understanding of primate technology requires explicit investigation of the role of ecological conditions. We propose a model in which three sets of factors, namely environment, sociality and cognition, influence invention, transmission and retention of material culture. PMID:25392310

  8. Convergent evolution in primates and an insectivore

    SciTech Connect

    Boffelli, Dario; Cheng, Jan-Fang; Rubin, Edward M.

    2003-04-16

    The cardiovascular risk factor apolipoprotein(a) (apo(a)) has a puzzling distribution among mammals, its presence being limited to a subset of primates and a member of the insectivore lineage, the hedgehog. To explore the evolutionary history of apo(a), we performed extensive genomic sequence comparisons of multiple species with and without an apo(a) gene product, such as human, baboon, hedgehog, lemurand mouse. This analysis indicated that apo(a) arose independently in a subset of primates, including baboon and human, and an insectivore, the hedgehog, and was not simply lost by species lacking it. The similar structural domains shared by the hedgehog and primate apo(a) indicate that they were formed by a unique molecular mechanism involving the convergent evolution of paralogous genes in these distantspecies.

  9. Patient-Derived Tumor Xenografts Are Susceptible to Formation of Human Lymphocytic Tumors1

    PubMed Central

    Bondarenko, Gennadiy; Ugolkov, Andrey; Rohan, Stephen; Kulesza, Piotr; Dubrovskyi, Oleksii; Gursel, Demirkan; Mathews, Jeremy; O’Halloran, Thomas V.; Wei, Jian J.; Mazar, Andrew P.

    2015-01-01

    Patient-derived xenograft (PDX) tumor models have emerged as a new approach to evaluate the effects of cancer drugs on patients’ personalized tumor grafts enabling to select the best treatment for the cancer patient and providing a new tool for oncology drug developers. Here, we report that human tumors engrafted in immunodeficient mice are susceptible to formation of B-and T-cell PDX tumors. We xenografted human primary and metastatic tumor samples into immunodeficient mice and found that a fraction of PDX tumors generated from patients’ samples of breast, colon, pancreatic, bladder and renal cancer were histologically similar to lymphocytic neoplasms. Moreover, we found that the first passage of breast and pancreatic cancer PDX tumors after initial transplantation of the tumor pieces from the same human tumor graft could grow as a lymphocytic tumor in one mouse and as an adenocarcinoma in another mouse. Whereas subcutaneous PDX tumors resembling human adenocarcinoma histology were slow growing and non-metastatic, we found that subcutaneous PDX lymphocytic tumors were fast growing and formed large metastatic lesions in mouse lymph nodes, liver, lungs, and spleen. PDX lymphocytic tumors were comprised of B-cells which were Epstein-Barr virus positive and expressed CD45 and CD20. Because B-cells are typically present in malignant solid tumors, formation of B-cell tumor may evolve in a wide range of PDX tumor models. Although PDX tumor models show great promise in the development of personalized therapy for cancer patients, our results suggest that confidence in any given PDX tumor model requires careful screening of lymphocytic markers. PMID:26476081

  10. Expression and targeting of human fibroblast activation protein in a human skin/severe combined immunodeficient mouse breast cancer xenograft model.

    PubMed

    Tahtis, Kiki; Lee, Fook-Thean; Wheatley, Jennifer M; Garin-Chesa, Pilar; Park, John E; Smyth, Fiona E; Obata, Yuichi; Stockert, Elisabeth; Hall, Cathrine M; Old, Lloyd J; Rettig, Wolfgang J; Scott, Andrew M

    2003-08-01

    Antigens and receptors that are highly expressed on tumor stromal cells, such as fibroblast activation protein (FAP), are attractive targets for antibody-based therapies because the supporting stroma and vessel network is essential for a solid neoplasm to grow beyond a size of 1-2 mm. The in vivo characterization of antibodies targeting human stromal or vessel antigens is hindered by the lack of an appropriate mouse model system because xenografts in standard mouse models express stromal and vessels elements of murine origin. This limitation may be overcome by the development of a human skin/mouse chimeric model, which is established by transplanting human foreskin on to the lateral flank of severe combined immunodeficient mice. The subsequent inoculation of breast carcinoma MCF-7 cells within the dermis of the transplanted human skin resulted in the production of xenografts expressing stromal and vessel elements of human origin. Widespread expression of human FAP-positive reactive stromal fibroblasts within xenografts was seen up to 2 months posttransplantation and postinjection of cells. Human blood vessel antigen expression also persisted at 2 months posttransplantation and postinjection of cells with murine vessels coexisting with the human vascular supply. The model was subsequently used to evaluate the biodistribution properties of an iodine-131-labeled humanized anti-FAP monoclonal antibody (BIBH-7). The results showed high specific targeting of the stromal compartment of the xenograft, indicating that the model provides a useful and novel approach for the in vivo assessment of the immunotherapeutic potential of molecules targeting human stroma and angiogenic systems. PMID:12939462

  11. Ontogeny of the nasopalatine duct in primates.

    PubMed

    Shimp, Kristin L; Bhatnagar, Kunwar P; Bonar, Christopher J; Smith, Timothy D

    2003-09-01

    Ecological explanations have been put forward to account for the precocious or delayed development of patency in ducts leading to the vomeronasal organ (VNO) in certain mammals. Perinatal function may be related, in part, to the patency or fusion of the vomeronasal and nasopalatine (NPD) ducts. However, few studies have focused on NPD development in primates, which generally have a prolonged period of dependence during infancy. In this study we examined 24 prenatal primates and 13 neonatal primates, and a comparative sample of fetal mice and insectivores. In embryonic and early fetal Microcebus murinus, the NPD was completely fused, whereas in fetuses of later stages the duct was partially fused or completely patent. M. myoxinus of all stages demonstrated some degree of NPD fusion. In all other prenatal primates, the NPD was fused to some extent. Four prenatal insectivores (Tenrec ecaudatus) showed some degree of NPD fusion. In Mus musculus at 19 days gestation, the NPD was patent, although the anatomically separate VNO duct was fused. T. ecaudatus and most of the neonatal primates revealed complete NPD patency. An exception was Saguinus geoffroyi, which exhibited fusion of the NPD near the VNO opening. These observations may relate to differences in perinatal VNO function. The differences noted in our study suggest that M. murinus and M. myoxinus may differ in perinatal VNO functionality and perhaps in related behavior. Observations of neonatal primates suggest that NPD patency may be relatively common at birth and could serve other purposes in addition to being an access route for VNO stimuli. PMID:12923897

  12. Mouse-Based Research on Quiescent Primate Malaria Parasites.

    PubMed

    Markus, Miles B

    2016-04-01

    Mice engrafted with primate tissue make two important plasmodial dormancy-related questions researchable. The first is concerned with whether latent merozoites in the lymphatic system can give rise to relapse-like, recurrent malaria in primates. The second is that genetic evidence of hypnozoite activation as the source of relapsing primate malaria can be looked for. PMID:26961183

  13. Predictive value of primate models for AIDS.

    PubMed

    Haigwood, Nancy L

    2004-01-01

    A number of obstacles remain in the search for an animal model for HIV infection and pathogenesis that can serve to predict efficacy in humans. HIV-1 fails to replicate and cause disease except in humans or chimpanzees, thereby limiting our ability to evaluate compounds or vaccines prior to human testing. Despite this limitation, nonhuman primate lentivirus models have been established that recapitulate the modes of infection, disease course, and antiviral immunity that is seen in HIV infection of humans. These models have been utilized to understand key aspects of disease and to evaluate concepts in therapies and vaccine development. By necessity, animal models can only be validated after successful trials in humans and the determination of correlates of protection. Because the only vaccine product tested in phase III trials in humans failed to achieve the desired protective threshold, we are as yet unable to validate any of the currently used nonhuman primate models for vaccine research. In the absence of a validated model, many experts in the field have concluded that prophylactic vaccines and therapeutic concepts should bypass primate models, and rely solely upon the systematic testing of each individual and combined vaccine element in human phase I or I/II trials to determine their relative merits. Indeed, a large effort is underway to expand efforts to test all products as part of an international effort termed "The HIV Vaccine Enterprise", with major contributions from the Bill and Melinda Gates Foundation. This Herculean task could potentially be reduced if it were possible to utilize even partially validated nonhuman primate models as part of the screening efforts. The purpose of this article is to review the data from nonhuman primate models that have contributed to our understanding of lentivirus infection and pathogenesis, and to critically evaluate how well these models have predicted outcomes in humans. Key features of the models developed to date are

  14. The primate semicircular canal system and locomotion

    PubMed Central

    Spoor, Fred; Garland, Theodore; Krovitz, Gail; Ryan, Timothy M.; Silcox, Mary T.; Walker, Alan

    2007-01-01

    The semicircular canal system of vertebrates helps coordinate body movements, including stabilization of gaze during locomotion. Quantitative phylogenetically informed analysis of the radius of curvature of the three semicircular canals in 91 extant and recently extinct primate species and 119 other mammalian taxa provide support for the hypothesis that canal size varies in relation to the jerkiness of head motion during locomotion. Primate and other mammalian species studied here that are agile and have fast, jerky locomotion have significantly larger canals relative to body mass than those that move more cautiously. PMID:17576932

  15. Learning about primates' learning, language, and cognition

    NASA Technical Reports Server (NTRS)

    Rumbaugh, Duane M.

    1992-01-01

    Results are presented of many years of research on the methods of teaching primates the language and cognitive skills which were long considered to be unteachable to particular species of primates. It was found that chimpanzee subjects could not only learn a number of 'stock sentences' but to use them in variations and several combinations for the purpose of solving various problems. Apes placed in different rooms could be taught to communicate via computer, and collaborate with each other on doing specific tasks. Contrary to expectations, young rhesus monkeys proved to be able to learn as much as the chimpanzee species.

  16. Combined Bone Marrow and Kidney Transplantation for the Induction of Specific Tolerance.

    PubMed

    Chen, Yi-Bin; Kawai, Tatsuo; Spitzer, Thomas R

    2016-01-01

    The induction of specific tolerance, in order to avoid the detrimental effects of lifelong systemic immunosuppressive therapy after organ transplantation, has been considered the "Holy Grail" of transplantation. Experimentally, tolerance has been achieved through clonal deletion, through costimulatory blockade, through the induction or infusion of regulatory T-cells, and through the establishment of hematopoietic chimerism following donor bone marrow transplantation. The focus of this review is how tolerance has been achieved following combined bone marrow and kidney transplantation. Preclinical models of combined bone marrow and kidney transplantation have shown that tolerance can be achieved through either transient or sustained hematopoietic chimerism. Combined transplants for patients with multiple myeloma have shown that organ tolerance and prolonged disease remissions can be accomplished with such an approach. Similarly, multiple clinical strategies for achieving tolerance in patients without an underlying malignancy have been described, in the context of either transient or durable mixed chimerism or sustained full donor hematopoiesis. To expand the chimerism approach to deceased donor transplants, a delayed tolerance approach, which will involve organ transplantation with conventional immunosuppression followed months later by bone marrow transplantation, has been successful in a primate model. As combined bone marrow and organ transplantation become safer and increasingly successful, the achievement of specific tolerance may become more widely applicable. PMID:27239198

  17. Combined Bone Marrow and Kidney Transplantation for the Induction of Specific Tolerance

    PubMed Central

    Chen, Yi-Bin; Kawai, Tatsuo; Spitzer, Thomas R.

    2016-01-01

    The induction of specific tolerance, in order to avoid the detrimental effects of lifelong systemic immunosuppressive therapy after organ transplantation, has been considered the “Holy Grail” of transplantation. Experimentally, tolerance has been achieved through clonal deletion, through costimulatory blockade, through the induction or infusion of regulatory T-cells, and through the establishment of hematopoietic chimerism following donor bone marrow transplantation. The focus of this review is how tolerance has been achieved following combined bone marrow and kidney transplantation. Preclinical models of combined bone marrow and kidney transplantation have shown that tolerance can be achieved through either transient or sustained hematopoietic chimerism. Combined transplants for patients with multiple myeloma have shown that organ tolerance and prolonged disease remissions can be accomplished with such an approach. Similarly, multiple clinical strategies for achieving tolerance in patients without an underlying malignancy have been described, in the context of either transient or durable mixed chimerism or sustained full donor hematopoiesis. To expand the chimerism approach to deceased donor transplants, a delayed tolerance approach, which will involve organ transplantation with conventional immunosuppression followed months later by bone marrow transplantation, has been successful in a primate model. As combined bone marrow and organ transplantation become safer and increasingly successful, the achievement of specific tolerance may become more widely applicable. PMID:27239198

  18. Update on cellular transplantation into the CNS as a novel therapy for chronic pain.

    PubMed

    Czech, K A; Sagen, J

    1995-08-01

    The transplantation of cells that secrete neuroactive substances with analgesic properties into the CNS is a novel method that challenges current approaches in treating chronic pain. This review covers pre-clinical and clinical studies from both allogeneic and xenogeneic sources. One cell source that has been utilized successfully is the adrenal chromaffin cell, since such cells constitutively release catecholamines, opioid peptides, and neurotrophic factors; release can be augmented with nicotine. Other graft sources include AtT-20 and B-16 cell lines which release enkephalins and catecholamines, respectively. For grafting in rodents, adrenal medullary tissue pieces are transplanted to the subarachnoid space. Chromaffin cell transplants can decrease pain sensitivity in normal rats using standard acute pain tests (paw-pinch, hot-plate, and tail-flick). In addition, transplants can restore normal pain thresholds in rodent models of chronic pain (formalin, adjuvant-induced arthritis, and sciatic-nerve tie) which closely similate the pathologies of human chronic pain conditions. Xenografts have been studied due to concerns that future application for human pain may be limited by donor availability. Despite immune privileges of the CNS, xenografts require at least short-term immunosuppression to obtain a viable graft. Cell encapsulation is one method of sustaining a xenograft (in rat and human hosts) while circumventing the need for immunosuppression. Clinical studies have been initiated for terminal cancer patients with promising results as assessed by markedly reduced narcotic intake, visual analog scale ratings, and increased CSF levels of catecholamines and met-enkephalin. PMID:8532850

  19. 184AA3: a xenograft model of ER+ breast adenocarcinoma.

    PubMed

    Hines, William C; Kuhn, Irene; Thi, Kate; Chu, Berbie; Stanford-Moore, Gaelen; Sampayo, Rocío; Garbe, James C; Stampfer, Martha; Borowsky, Alexander D; Bissell, Mina J

    2016-01-01

    Despite the prevalence and significant morbidity resulting from estrogen receptor positive (ER(+)) breast adenocarcinomas, there are only a few models of this cancer subtype available for drug development and arguably none for studying etiology. Those models that do exist have questionable clinical relevance. Given our goal of developing luminal models, we focused on six cell lines derived by minimal mutagenesis from normal human breast cells, and asked if any could generate clinically relevant xenografts, which we then extensively characterized. Xenografts of one cell line, 184AA3, consistently formed ER(+) adenocarcinomas that had a high proliferative rate and other features consistent with "luminal B" intrinsic subtype. Squamous and spindle cell/mesenchymal differentiation was absent, in stark contrast to other cell lines that we examined or others have reported. We explored intratumoral heterogeneity produced by 184AA3 by immunophenotyping xenograft tumors and cultured cells, and characterized marker expression by immunofluorescence and flow cytometry. A CD44(High) subpopulation was discovered, yet their tumor forming ability was far less than CD44(Low) cells. Single cell cloning revealed the phenotypic plasticity of 184AA3, consistent with the intratumoral heterogeneity observed in xenografts. Characterization of ER expression in cultures revealed ER protein and signaling is intact, yet when estrogen was depleted in culture, and in vivo, it did not impact cell or tumor growth, analogous to therapeutically resistant ER(+) cancers. This model is appropriate for studies of the etiology of ovarian hormone independent adenocarcinomas, for identification of therapeutic targets, predictive testing, and drug development. PMID:26661596

  20. Disproportional Representation of Primates in the Ecological Literature

    PubMed Central

    Heymann, Eckhard W.; Zinner, Dietmar; Ganzhorn, Jörg U.

    2013-01-01

    We address the question why papers dealing with the ecology of primates are so sparsely represented in the general ecological literature. A literature analyses based on entries in Web of Science and PrimateLit reveals that despite a large number of papers published on primates in general and on the ecology of primates, only a very small fraction of these papers is published in high-ranking international ecological journals. We discuss a number of potential reasons for the disproportion and highlight the problems associated with experimental research on wild primates and constraints on sample size as major issues. PMID:24339882

  1. Transplantation of islet allografts and xenografts in totally pancreatectomized diabetic dogs using the hybrid artificial pancreas.

    PubMed Central

    Monaco, A P; Maki, T; Ozato, H; Carretta, M; Sullivan, S J; Borland, K M; Mahoney, M D; Chick, W L; Muller, T E; Wolfrum, J

    1991-01-01

    Previously the authors reported on a Hybrid Artificial Pancreas device that maintained patent vascular anastomoses in normal dogs and, when seeded with allogeneic canine islets, maintained normal fasting blood sugars (FBS) in diabetic pancreatectomized dogs. Eventual failure of these devices was believed to be related to loss of islet viability and/or insufficient islet mass. The current study evaluates the effect of increased islet mass produced by implantation of two islet-seeded devices in pancreatectomized dogs and compares the results with those from dogs that received a single device. Twelve of fifteen dogs receiving single devices showed initial function as determined by elimination or reduction of exogenous insulin requirement; four showed initial function and seven showed extended function (100 to 284 days). Excessive weight loss (more than 20%), despite normal FBS and insulin dependence, required that four animals in this latter group be killed. Devices seeded with xenogeneic islets have met with limited success. One dog that received two bovine islet-seeded devices achieved function for more than 100 days; the remaining bovine-seeded devices (n = 8) functioned for only 3 to 16 days. Porcine islet-seeded devices were assessed by intravenous glucose tolerance tests (IVGTT). Recipients of two devices seeded with allogeneic islets demonstrated improved IVGTT results when compared to those from pancreatectomized dogs and recipients of single devices but were abnormal when compared to intact animals. Histologic examination of device and autopsy material from all failed experiments was performed and showed no mononuclear cell infiltration of the islet chamber or vascular graft material, only a few incidence of device thrombosis, and varying degrees of islet viability as judged by morphologic and immunohistochemical evaluation. The authors believe they have demonstrated progress toward the development and clinical applicability of the Hybrid Artificial Pancreas. Images Figs. 1A and B. Figs. 15A and B. Figs. 16A and B. Figs. 17A and B. PMID:1929614

  2. Homeostasis in primates in hyperacceleration fields

    NASA Technical Reports Server (NTRS)

    Fuller, C. A.

    1984-01-01

    Various homeostatic responses of a nonhuman primate, the squirrel monkey (Saimiri sciureus) to acute changes in the acceleration environment were examined. When these animals were exposed to a hyperdynamic field the body temperature was consistently depressed and the animals showed behavioral indications of increased drowsiness. Further, time of day played a significant role in influencing these responses.

  3. Primate Thalamus: More Than Meets an Eye.

    PubMed

    Wallace, Damian J; Fitzpatrick, David; Kerr, Jason N D

    2016-01-25

    A recent study shows conclusively that the koniocellular layers of the marmoset dorsal lateral geniculate nucleus have binocularly responsive neurons. This adds a new twist to the traditional view about binocular processing in the primate visual system and raises questions about the role of dorsal lateral geniculate nucleus in early binocular processing. PMID:26811887

  4. Alu insertion loci and platyrrhine primate phylogeny.

    PubMed

    Ray, David A; Xing, Jinchuan; Hedges, Dale J; Hall, Michael A; Laborde, Meredith E; Anders, Bridget A; White, Brittany R; Stoilova, Nadica; Fowlkes, Justin D; Landry, Kate E; Chemnick, Leona G; Ryder, Oliver A; Batzer, Mark A

    2005-04-01

    Short INterspersed Elements (SINEs) make very useful phylogenetic markers because the integration of a particular element at a location in the genome is irreversible and of known polarity. These attributes make analysis of SINEs as phylogenetic characters an essentially homoplasy-free affair. Alu elements are primate-specific SINEs that make up a large portion of the human genome and are also widespread in other primates. Using a combination wet-bench and computational approach we recovered 190 Alu insertions, 183 of which are specific to the genomes of nine New World primates. We used these loci to investigate branching order and have produced a cladogram that supports a sister relationship between Atelidae (spider, woolly, and howler monkeys) and Cebidae (marmosets, tamarins, and owl monkeys) and then the joining of this two family clade to Pitheciidae (titi and saki monkeys). The data support these relationships with a homoplasy index of 0.00. In this study, we report one of the largest applications of SINE elements to phylogenetic analysis to date, and the results provide a robust molecular phylogeny for platyrrhine primates. PMID:15737586

  5. Remarkable ancient divergences amongst neglected lorisiform primates

    PubMed Central

    Nekaris, K. Anne‐Isola; Perkin, Andrew; Bearder, Simon K.; Pimley, Elizabeth R.; Schulze, Helga; Streicher, Ulrike; Nadler, Tilo; Kitchener, Andrew; Zischler, Hans; Zinner, Dietmar; Roos, Christian

    2015-01-01

    Lorisiform primates (Primates: Strepsirrhini: Lorisiformes) represent almost 10% of the living primate species and are widely distributed in sub‐Saharan Africa and South/South‐East Asia; however, their taxonomy, evolutionary history, and biogeography are still poorly understood. In this study we report the largest molecular phylogeny in terms of the number of represented taxa. We sequenced the complete mitochondrial cytochrome b gene for 86 lorisiform specimens, including ∼80% of all the species currently recognized. Our results support the monophyly of the Galagidae, but a common ancestry of the Lorisinae and Perodicticinae (family Lorisidae) was not recovered. These three lineages have early origins, with the Galagidae and the Lorisinae diverging in the Oligocene at about 30 Mya and the Perodicticinae emerging in the early Miocene. Our mitochondrial phylogeny agrees with recent studies based on nuclear data, and supports Euoticus as the oldest galagid lineage and the polyphyletic status of Galagoides. Moreover, we have elucidated phylogenetic relationships for several species never included before in a molecular phylogeny. The results obtained in this study suggest that lorisiform diversity remains substantially underestimated and that previously unnoticed cryptic diversity might be present within many lineages, thus urgently requiring a comprehensive taxonomic revision of this primate group. © 2015 The Linnean Society of London PMID:26900177

  6. Quantification of neocortical ratios in stem primates.

    PubMed

    Long, Adam; Bloch, Jonathan I; Silcox, Mary T

    2015-07-01

    Extant euprimates (=crown primates) have a characteristically expanded neocortical region of the brain relative to that of other mammals, but the timing of that expansion in their evolutionary history is poorly resolved. Examination of anatomical landmarks on fossil endocasts of Eocene euprimates suggests that significant neocortical expansion relative to contemporaneous mammals was already underway. Here, we provide quantitative estimates of neocorticalization in stem primates (plesiadapiforms) relevant to the question of whether relative neocortical expansion was uniquely characteristic of the crown primate radiation. Ratios of neocortex to endocast surface areas were calculated for plesiadapiforms using measurements from virtual endocasts of the paromomyid Ignacius graybullianus (early Eocene, Wyoming) and the microsyopid Microsyops annectens (middle Eocene, Wyoming). These data are similar to a published estimate for the plesiadapid, Plesiadapis tricuspidens, but contrast with those calculated for early Tertiary euprimates in being within the 95% confidence intervals for archaic mammals generally. Interpretation of these values is complicated by the paucity of sampled endocasts for older stem primates and euarchontogliran outgroups, as well as by a combination of effects related to temporal trends, allometry, and taxon-unique specializations. Regardless, these results are consistent with the hypothesis that a shift in brain organization occurred in the first euprimates, likely in association with elaborations to the visual system. PMID:25693873

  7. Chewing variation in lepidosaurs and primates.

    PubMed

    Ross, C F; Baden, A L; Georgi, J; Herrel, A; Metzger, K A; Reed, D A; Schaerlaeken, V; Wolff, M S

    2010-02-15

    Mammals chew more rhythmically than lepidosaurs. The research presented here evaluated possible reasons for this difference in relation to differences between lepidosaurs and mammals in sensorimotor systems. Variance in the absolute and relative durations of the phases of the gape cycle was calculated from kinematic data from four species of primates and eight species of lepidosaurs. The primates exhibit less variance in the duration of the gape cycle than in the durations of the four phases making up the gape cycle. This suggests that increases in the durations of some gape cycle phases are accompanied by decreases in others. Similar effects are much less pronounced in the lepidosaurs. In addition, the primates show isometric changes in gape cycle phase durations, i.e. the relative durations of the phases of the gape cycle change little with increasing cycle time. In contrast, in the lepidosaurs variance in total gape cycle duration is associated with increases in the proportion of the cycle made up by the slow open phase. We hypothesize that in mammals the central nervous system includes a representation of the optimal chew cycle duration maintained using afferent feedback about the ongoing state of the chew cycle. The differences between lepidosaurs and primates do not lie in the nature of the sensory information collected and its feedback to the feeding system, but rather the processing of that information by the CNS and its use feed-forward for modulating jaw movements and gape cycle phase durations during chewing. PMID:20118308

  8. Processing Of Visual Information In Primate Brains

    NASA Technical Reports Server (NTRS)

    Anderson, Charles H.; Van Essen, David C.

    1991-01-01

    Report reviews and analyzes information-processing strategies and pathways in primate retina and visual cortex. Of interest both in biological fields and in such related computational fields as artificial neural networks. Focuses on data from macaque, which has superb visual system similar to that of humans. Authors stress concept of "good engineering" in understanding visual system.

  9. Chronic Wasting Disease Agents in Nonhuman Primates

    PubMed Central

    Meade-White, Kimberly D.; Phillips, Katie; Striebel, James; Race, Richard; Chesebro, Bruce

    2014-01-01

    Chronic wasting disease is a prion disease of cervids. Assessment of its zoonotic potential is critical. To evaluate primate susceptibility, we tested monkeys from 2 genera. We found that 100% of intracerebrally inoculated and 92% of orally inoculated squirrel monkeys were susceptible, but cynomolgus macaques were not, suggesting possible low risk for humans. PMID:24751215

  10. Olfactory Receptor Patterning in a Higher Primate

    PubMed Central

    Horowitz, Lisa F.; Saraiva, Luis R.; Kuang, Donghui; Yoon, Kyoung-hye

    2014-01-01

    The mammalian olfactory system detects a plethora of environmental chemicals that are perceived as odors or stimulate instinctive behaviors. Studies using odorant receptor (OR) genes have provided insight into the molecular and organizational strategies underlying olfaction in mice. One important unanswered question, however, is whether these strategies are conserved in primates. To explore this question, we examined the macaque, a higher primate phylogenetically close to humans. Here we report that the organization of sensory inputs in the macaque nose resembles that in mouse in some respects, but not others. As in mouse, neurons with different ORs are interspersed in the macaque nose, and there are spatial zones that differ in their complement of ORs and extend axons to different domains in the olfactory bulb of the brain. However, whereas the mouse has multiple discrete band-like zones, the macaque appears to have only two broad zones. It is unclear whether the organization of OR inputs in a rodent/primate common ancestor degenerated in primates or, alternatively became more sophisticated in rodents. The mouse nose has an additional small family of chemosensory receptors, called trace amine-associated receptors (TAARs), which may detect social cues. Here we find that TAARs are also expressed in the macaque nose, suggesting that TAARs may also play a role in human olfactory perception. We further find that one human TAAR responds to rotten fish, suggesting a possible role as a sentinel to discourage ingestion of food harboring pathogenic microorganisms. PMID:25209267

  11. Olfactory receptor patterning in a higher primate.

    PubMed

    Horowitz, Lisa F; Saraiva, Luis R; Kuang, Donghui; Yoon, Kyoung-hye; Buck, Linda B

    2014-09-10

    The mammalian olfactory system detects a plethora of environmental chemicals that are perceived as odors or stimulate instinctive behaviors. Studies using odorant receptor (OR) genes have provided insight into the molecular and organizational strategies underlying olfaction in mice. One important unanswered question, however, is whether these strategies are conserved in primates. To explore this question, we examined the macaque, a higher primate phylogenetically close to humans. Here we report that the organization of sensory inputs in the macaque nose resembles that in mouse in some respects, but not others. As in mouse, neurons with different ORs are interspersed in the macaque nose, and there are spatial zones that differ in their complement of ORs and extend axons to different domains in the olfactory bulb of the brain. However, whereas the mouse has multiple discrete band-like zones, the macaque appears to have only two broad zones. It is unclear whether the organization of OR inputs in a rodent/primate common ancestor degenerated in primates or, alternatively became more sophisticated in rodents. The mouse nose has an additional small family of chemosensory receptors, called trace amine-associated receptors (TAARs), which may detect social cues. Here we find that TAARs are also expressed in the macaque nose, suggesting that TAARs may also play a role in human olfactory perception. We further find that one human TAAR responds to rotten fish, suggesting a possible role as a sentinel to discourage ingestion of food harboring pathogenic microorganisms. PMID:25209267

  12. The Neuroendocrinology of Primate Maternal Behavior

    PubMed Central

    Saltzman, Wendy; Maestripieri, Dario

    2010-01-01

    In nonhuman primates and humans, similar to other mammals, hormones are not strictly necessary for the expression of maternal behavior, but nevertheless influence variation in maternal responsiveness and parental behavior both within and between individuals. A growing number of correlational and experimental studies have indicated that high circulating estrogen concentrations during pregnancy increase maternal motivation and responsiveness to infant stimuli, while effects of prepartum or postpartum estrogens and progestogens on maternal behavior are less clear. Prolactin is thought to play a role in promoting paternal and alloparental care in primates, but little is known about the relationship between this hormone and maternal behavior. High circulating cortisol levels appear to enhance arousal and responsiveness to infant stimuli in young, relatively inexperienced female primates, but interfere with the expression of maternal behavior in older and more experienced mothers. Among neuropeptides and neurotransmitters, preliminary evidence indicates that oxytocin and endogenous opioids affect maternal attachment to infants, including maintenance of contact, grooming, and responses to separation. Brain serotonin affects anxiety and impulsivity, which in turn may affect maternal behaviors such as infant retrieval or rejection of infants’ attempts to make contact with the mother. Although our understanding of the neuroendocrine correlates of primate maternal behavior has grown substantially in the last two decades, very little is known about the mechanisms underlying these effects, e.g., the extent to which these mechanisms may involve changes in perception, emotion, or cognition. PMID:20888383

  13. A Sensitive IHC Method for Monitoring Autophagy-Specific Markers in Human Tumor Xenografts

    PubMed Central

    He, Helen; Yang, Yu; Xiang, Zhongmin; Yu, Lunyin; Chouitar, Jouhara; Yu, Jie; D'Amore, Natalie Roy; Li, Ping; Li, Zhi; Bowman, Douglas; Theisen, Matthew; Brownell, James E.; Tirrell, Stephen

    2016-01-01

    Objective. Use of tyramide signal amplification (TSA) to detect autophagy biomarkers in formalin fixed and paraffin embedded (FFPE) xenograft tissue. Materials and Methods. Autophagy marker regulation was studied in xenograft tissues using Amp HQ IHC and standard IHC methods. Results. The data demonstrate the feasibility of using high sensitivity TSA IHC assays to measure low abundant autophagy markers in FFPE xenograft tissue. PMID:27247826

  14. INTUSSUSCEPTIVE-LIKE ANGIOGENESIS IN HUMAN FETAL LUNG XENOGRAFTS: LINK WITH BRONCHOPULMONARY DYSPLASIA-ASSOCIATED MICROVASCULAR DYSANGIOGENESIS?

    PubMed Central

    De Paepe, Monique E.; Chu, Sharon; Hall, Susan; McDonnell-Clark, Elizabeth; Heger, Nicholas E.; Schorl, Christoph; Mao, Quanfu; Boekelheide, Kim

    2016-01-01

    Background Human fetal lung xenografts display an unusual pattern of non-sprouting, plexus-forming angiogenesis that is reminiscent of the dysmorphic angioarchitecture described in bronchopulmonary dysplasia (BPD). The aim of this study was to determine the clinicopathological correlates, growth characteristics and molecular regulation of this aberrant form of graft angiogenesis. Methods Fetal lung xenografts, derived from 12 previable fetuses (15 to 22 weeks’ gestation) and engrafted in the renal subcapsular space of SCID-beige mice, were analyzed 4 weeks post-transplantation for morphology, vascularization, proliferative activity and gene expression. Results Focal plexus-forming angiogenesis (PFA) was observed in 60/230 (26%) of xenografts. PFA was characterized by a complex network of tortuous non-sprouting vascular structures with low endothelial proliferative activity, suggestive of intussusceptive-type angiogenesis. There was no correlation between the occurrence of PFA and gestational age or time interval between delivery and engraftment. PFA was preferentially localized in the relatively hypoxic central subcapsular area. Microarray analysis suggested altered expression of 15 genes in graft regions with PFA, of which 7 are known angiogenic/lymphangiogenic regulators and 5 are known hypoxia-inducible genes. qRT-PCR analysis confirmed significant upregulation of SULF2, IGF2 and HMOX1 in graft regions with PFA. Conclusion These observations in human fetal lungs ex vivo suggest that postcanalicular lungs can switch from sprouting angiogenesis to an aberrant intussusceptive-type of angiogenesis that is highly reminiscent of BPD-associated dysangiogenesis. While circumstantial evidence suggests hypoxia may be implicated, the exact triggering mechanisms, molecular regulation and clinical implications of this angiogenic switch in preterm lungs in vivo remain to be determined. PMID:26495956

  15. Organ transplantation in Tunisia.

    PubMed

    El Matri, Aziz; Ben Abdallah, Taieb

    2015-04-01

    Kidney transplants were first performed in Tunisia in 1986, and transplants soon extended to other organs including the heart, liver, and pancreas. Live-related donor and deceased-donor kidney transplants were both began in the summer of 1986. An organ procurement and transplant law was passed in March 1991, and the National Centre for Advancement of Organ Transplantation was created in 1995. The number of transplantation units has increased to 7 throughout the country, and the yearly transplant number has progressively increased to 139 in 2010, including 20% from deceased kidney donors. Despite these gains, the need continues to grow. Heart transplants began in January 1993, and Tunisia and Jordan are currently the only Arab countries where it is practiced. However, only 16 patients have received a heart transplant as of 2004, and the number of recipients has decreased in the past 10 years. Liver transplants are rare in other Arab countries, but began in Tunisia in January 1998. Over 10 years, 38 patients benefited from this procedure. After a few years of stagnation, the number of liver transplants is increasing. While all types of transplantation are needed, kidney transplantation is a priority in Tunisia. The target is to perform 400 transplants annually, which would require a long-term strategy to provide full financial coverage using the National Health Insurance Funds in both the public and private sectors. PMID:25894125

  16. Fine-tuning patient-derived xenograft models for precision medicine approaches in leukemia.

    PubMed

    Francis, Olivia L; Milford, Terry-Ann M; Beldiman, Cornelia; Payne, Kimberly J

    2016-03-01

    Many leukemias are characterized by well-known mutations that drive oncogenesis. Mice engineered with these mutations provide a foundation for understanding leukemogenesis and identifying therapies. However, data from whole genome studies provide evidence that malignancies are characterized by multiple genetic alterations that vary between patients, as well as inherited genetic variation that can also contribute to oncogenesis. Improved outcomes will require precision medicine approaches-targeted therapies tailored to malignancies in each patient. Preclinical models that reflect the range of mutations and the genetic background present in patient populations are required to develop and test the combinations of therapies that will be used to provide precision medicine therapeutic strategies. Patient-derived xenografts (PDX) produced by transplanting leukemia cells from patients into immune deficient mice provide preclinical models where disease mechanisms and therapeutic efficacy can be studied in vivo in context of the genetic variability present in patient tumors. PDX models are possible because many elements in the bone marrow microenvironment show cross-species activity between mice and humans. However, several cytokines likely to impact leukemia cells are species-specific with limited activity on transplanted human leukemia cells. In this review we discuss the importance of PDX models for developing precision medicine approaches to leukemia treatment. We illustrate how PDX models can be optimized to overcome a lack of cross-species cytokine activity by reviewing a recent strategy developed for use with a high-risk form of B-cell acute lymphoblastic leukemia (B-ALL) that is characterized by overexpression of CRLF2, a receptor component for the cytokine, TSLP. PMID:26912005

  17. A robust and rapid xenograft model to assess efficacy of chemotherapeutic agents for human acute myeloid leukemia

    PubMed Central

    Saland, E; Boutzen, H; Castellano, R; Pouyet, L; Griessinger, E; Larrue, C; de Toni, F; Scotland, S; David, M; Danet-Desnoyers, G; Vergez, F; Barreira, Y; Collette, Y; Récher, C; Sarry, J-E

    2015-01-01

    Relevant preclinical mouse models are crucial to screen new therapeutic agents for acute myeloid leukemia (AML). Current in vivo models based on the use of patient samples are not easy to establish and manipulate in the laboratory. Our objective was to develop robust xenograft models of human AML using well-characterized cell lines as a more accessible and faster alternative to those incorporating the use of patient-derived AML cells. Five widely used AML cell lines representing various AML subtypes were transplanted and expanded into highly immunodeficient non-obese diabetic/LtSz-severe combined immunodeficiency IL2Rγcnull mice (for example, cell line-derived xenografts). We show here that bone marrow sublethal conditioning with busulfan or irradiation has equal efficiency for the xenotransplantation of AML cell lines. Although higher number of injected AML cells did not change tumor engraftment in bone marrow and spleen, it significantly reduced the overall survival in mice for all tested AML cell lines. On the basis of AML cell characteristics, these models also exhibited a broad range of overall mouse survival, engraftment, tissue infiltration and aggressiveness. Thus, we have established a robust, rapid and straightforward in vivo model based on engraftment behavior of AML cell lines, all vital prerequisites for testing new therapeutic agents in preclinical studies. PMID:25794133

  18. Development and analysis of patient-derived xenograft mouse models in intravascular large B-cell lymphoma.

    PubMed

    Shimada, K; Shimada, S; Sugimoto, K; Nakatochi, M; Suguro, M; Hirakawa, A; Hocking, T D; Takeuchi, I; Tokunaga, T; Takagi, Y; Sakamoto, A; Aoki, T; Naoe, T; Nakamura, S; Hayakawa, F; Seto, M; Tomita, A; Kiyoi, H

    2016-07-01

    Intravascular large B-cell lymphoma (IVLBCL) is a distinct disease entity with the peculiar characteristic that tumor cells proliferate within vessels. Despite recent advances in understanding the disease from clinical aspects, the underlying pathogenesis remains unknown. Here we demonstrate analyses of IVLBCL biology using four xenograft mouse models established from primary IVLBCL samples. In all four models, the main characteristic of IVLBCL tumor cell proliferation within vessels was retained. Time-lapse engraftment analyses revealed that the tumor cells initially engrafted and proliferated in the sinusoids and vessels in the liver and then engrafted and proliferated in multiple organs. Intriguingly, serial passage of tumor cells from the adrenal gland of a transplanted mouse developed from primary patient bone marrow cells into a second mouse showed that the tumor cells mainly distributed into the adrenal gland in the second mouse, implying the existence of clonal selection and/or evolution at engraftment of a specific organ. Gene expression profiling analyses demonstrated that the gene set associated with cell migration was enriched for normal peripheral blood B cells, indicating that inhibition of cell migration might be involved in IVLBCL pathogenesis. In conclusion, the mouse xenograft models described here are essential tools for uncovering IVLBCL biology. PMID:27001523

  19. What Is a Heart Transplant?

    MedlinePlus

    ... from the NHLBI on Twitter. What Is a Heart Transplant? A heart transplant is surgery to remove a ... return to work for many different reasons. The Heart Transplant Process The heart transplant process starts when doctors ...

  20. Who Needs a Heart Transplant?

    MedlinePlus

    ... from the NHLBI on Twitter. Who Needs a Heart Transplant? Most patients referred to heart transplant centers have ... for heart failure. Who Is Eligible for a Heart Transplant? The specialists at the heart transplant center will ...

  1. Who Needs a Lung Transplant?

    MedlinePlus

    ... from the NHLBI on Twitter. Who Needs a Lung Transplant? Your doctor may recommend a lung transplant ... lungs to pick up oxygen. Applying to a Lung Transplant Program Lung transplants are done in medical ...

  2. A Large-Scale Investigation of Hypoxia-Preconditioned Allogeneic Mesenchymal Stem Cells for Myocardial Repair in Nonhuman Primates

    PubMed Central

    Hu, Xinyang; Xu, Yinchuan; Zhong, Zhiwei; Wu, Yan; Zhao, Jing; Wang, Yingchao; Cheng, Haifeng; Kong, Minjian; Zhang, Fengjiang; Chen, Qi; Sun, Jianzhong; Li, Qian; Jin, Jing; Li, Qingju; Chen, Lihong; Wang, Chen; Zhan, Hongwei; Fan, Youqi; Yang, Qian; Yu, Lei; Wu, Rongrong; Liang, Jie; Zhu, Jinyun; Wang, Ya; Jin, Yiping; Lin, Yifan; Yang, Fan; Jia, Liangliang; Zhu, Wei; Chen, Jinghai; Yu, Hong

    2016-01-01

    Rationale: The effectiveness of transplanted bone marrow mesenchymal stem cells (MSCs) for cardiac repair has been limited; thus, strategies for optimizing stem-cell–based myocardial therapy are needed. Objective: The present study was designed to test our central hypothesis that hypoxia-preconditioned MSCs (HP-MSCs) are more effective than MSCs cultured under ambient oxygen levels for the treatment of myocardial injury in a large-scale (N=49), long-term (9 months), nonhuman primate (Cynomolgous monkeys) investigation. Methods and Results: MSCs were engineered to express green fluorescent protein, cultured under ambient oxygen or 0.5% oxygen (HP-MSCs) for 24 hours and then tested in the infarcted hearts of Cynomolgus monkeys (1×107 cells per heart). Hypoxia preconditioning increased the expression of several prosurvival/proangiogenic factors in cultured MSCs, and measurements of infarct size and left-ventricular function at day 90 after myocardial infarction were significantly more improved in monkeys treated with HP-MSCs than in monkeys treated with the control vehicle; functional improvements in normal cultured bone marrow mesenchymal stem cells–treated monkeys were not significant. HP-MSCs transplantation was also associated with increases in cardiomyocyte proliferation, vascular density, myocardial glucose uptake, and engraftment of the transplanted cells and with declines in endogenous cell apoptosis, but did not increase the occurrence of arrhythmogenic complications. Conclusions: Hypoxia preconditioning improved the effectiveness of MSCs transplantation for the treatment of myocardial infarction in nonhuman primates without increasing the occurrence of arrhythmogenic complications, which suggests that future clinical trials of HP-MSCs transplantation are warranted. PMID:26838793

  3. Intra- and inter-tumor heterogeneity in a vemurafenib-resistant melanoma patient and derived xenografts

    PubMed Central

    Kemper, Kristel; Krijgsman, Oscar; Cornelissen-Steijger, Paulien; Shahrabi, Aida; Weeber, Fleur; Song, Ji-Ying; Kuilman, Thomas; Vis, Daniel J; Wessels, Lodewyk F; Voest, Emile E; Schumacher, Ton NM; Blank, Christian U; Adams, David J; Haanen, John B; Peeper, Daniel S

    2015-01-01

    The development of targeted inhibitors, like vemurafenib, has greatly improved the clinical outcome of BRAFV600E metastatic melanoma. However, resistance to such compounds represents a formidable problem. Using whole-exome sequencing and functional analyses, we have investigated the nature and pleiotropy of vemurafenib resistance in a melanoma patient carrying multiple drug-resistant metastases. Resistance was caused by a plethora of mechanisms, all of which reactivated the MAPK pathway. In addition to three independent amplifications and an aberrant form of BRAFV600E, we identified a new activating insertion in MEK1. This MEK1T55delinsRT mutation could be traced back to a fraction of the pre-treatment lesion and not only provided protection against vemurafenib but also promoted local invasion of transplanted melanomas. Analysis of patient-derived xenografts (PDX) from therapy-refractory metastases revealed that multiple resistance mechanisms were present within one metastasis. This heterogeneity, both inter- and intra-tumorally, caused an incomplete capture in the PDX of the resistance mechanisms observed in the patient. In conclusion, vemurafenib resistance in a single patient can be established through distinct events, which may be preexisting. Furthermore, our results indicate that PDX may not harbor the full genetic heterogeneity seen in the patient’s melanoma. PMID:26105199

  4. Improved Method for Ex Ovo-Cultivation of Developing Chicken Embryos for Human Stem Cell Xenografts

    PubMed Central

    Schomann, Timo; Qunneis, Firas; Widera, Darius; Kaltschmidt, Christian; Kaltschmidt, Barbara

    2013-01-01

    The characterization of human stem cells for the usability in regenerative medicine is particularly based on investigations regarding their differentiation potential in vivo. In this regard, the chicken embryo model represents an ideal model organism. However, the access to the chicken embryo is only achievable by windowing the eggshell resulting in limited visibility and accessibility in subsequent experiments. On the contrary, ex ovo-culture systems avoid such negative side effects. Here, we present an improved ex ovo-cultivation method enabling the embryos to survive 13 days in vitro. Optimized cultivation of chicken embryos resulted in a normal development regarding their size and weight. Our ex ovo-approach closely resembles the development of chicken embryos in ovo, as demonstrated by properly developed nervous system, bones, and cartilage at expected time points. Finally, we investigated the usability of our method for trans-species transplantation of adult stem cells by injecting human neural crest-derived stem cells into late Hamburger and Hamilton stages (HH26–HH28/E5—E6) of ex ovo-incubated embryos. We demonstrated the integration of human cells allowing experimentally easy investigation of the differentiation potential in the proper developmental context. Taken together, this ex ovo-method supports the prolonged cultivation of properly developing chicken embryos enabling integration studies of xenografted mammalian stem cells at late developmental stages. PMID:23554818

  5. Application of a Patient Derived Xenograft Model for Predicative Study of Uterine Fibroid Disease.

    PubMed

    Fritsch, Martin; Schmidt, Nicole; Gröticke, Ina; Frisk, Anna-Lena; Keator, Christopher S; Koch, Markus; Slayden, Ov D

    2015-01-01

    Human uterine fibroids, benign tumors derived from the smooth muscle layers of the uterus, impose a major health burden to up to 50% of premenopausal women in their daily life. To improve our understanding of this disease, we developed and characterized a patient-derived xenograft model by subcutaneous transplantation of pieces of human uterine fibroid tissue into three different strains of severe combined immunodeficient mice. Engrafted uterine fibroid tissue preserved the classical morphology with interwoven bundles of smooth muscle cells and an abundant deposition of collagenous matrix, similar to uterine fibroids in situ. The grafts expressed both estrogen receptor 1 and progesterone receptor. Additionally, both receptors were up-regulated by estrogen treatment. Growth of the fibroid grafts was dependent on 17β-estradiol and progesterone supplementation at levels similar to women with the disease and was studied for up to 60 days at maximum. Co-treatment with the antiprogestin mifepristone reduced graft growth (four independent donors, p<0.0001 two-sided t-test), as did treatment with the mTOR inhibitor rapamycin (three independent donors, p<0.0001 two-sided t-test). This in vivo animal model preserves the main histological and functional characteristics of human uterine fibroids, is amenable to intervention by pharmacological treatment, and can thus serve as an adequate model for the development of novel therapies. PMID:26588841

  6. Residual Disease in a Novel Xenograft Model of RUNX1-Mutated, Cytogenetically Normal Acute Myeloid Leukemia

    PubMed Central

    Sivagnanalingam, Umayal; Balys, Marlene; Eberhardt, Allison; Wang, Nancy; Myers, Jason R.; Ashton, John M.; Becker, Michael W.; Calvi, Laura M.; Mendler, Jason H.

    2015-01-01

    Cytogenetically normal acute myeloid leukemia (CN-AML) patients harboring RUNX1 mutations have a dismal prognosis with anthracycline/cytarabine-based chemotherapy. We aimed to develop an in vivo model of RUNX1-mutated, CN-AML in which the nature of residual disease in this molecular disease subset could be explored. We utilized a well-characterized patient-derived, RUNX1-mutated CN-AML line (CG-SH). Tail vein injection of CG-SH into NOD scid gamma mice led to leukemic engraftment in the bone marrow, spleen, and peripheral blood within 6 weeks. Treatment of leukemic mice with anthracycline/cytarabine-based chemotherapy resulted in clearance of disease from the spleen and peripheral blood, but persistence of disease in the bone marrow as assessed by flow cytometry and secondary transplantation. Whole exome sequencing of CG-SH revealed mutations in ASXL1, CEBPA, GATA2, and SETBP1, not previously reported. We conclude that CG-SH xenografts are a robust, reproducible in vivo model of CN-AML in which to explore mechanisms of chemotherapy resistance and novel therapeutic approaches. PMID:26177509

  7. Patient-derived bladder cancer xenografts in the preclinical development of novel targeted therapies.

    PubMed

    Jäger, Wolfgang; Xue, Hui; Hayashi, Tetsutaro; Janssen, Claudia; Awrey, Shannon; Wyatt, Alexander W; Anderson, Shawn; Moskalev, Igor; Haegert, Anne; Alshalalfa, Mohammed; Erho, Nicholas; Davicioni, Elai; Fazli, Ladan; Li, Estelle; Collins, Colin; Wang, Yuzhuo; Black, Peter C

    2015-08-28

    Optimal animal models of muscle invasive bladder cancer (MIBC) are necessary to overcome the current lack of novel targeted therapies for this malignancy. Here we report on the establishment and characterization of patient-derived primary xenografts (PDX). Patient tumors were grafted under the renal capsule of mice and subsequently transplanted over multiple generations. Patient tumor and PDX were processed for analysis of copy number variations by aCGH, gene expression by microarray, and expression of target pathways by immunohistochemistry (IHC). One PDX harbouring an FGFR3 mutation was treated with an inhibitory monoclonal antibody targeting FGFR3. Five PDX were successfully established. Tumor doubling time ranged from 5 to 11 days. Array CGH revealed shared chromosomal aberrations in the patient tumors and PDX. Gene expression microarray and IHC confirmed that PDXs maintain similar patterns to the parental tumors. Tumor growth in the PDX with an FGFR3 mutation was inhibited by the FGFR3 inhibitor. PDXs recapitulate the tumor biology of the patients' primary tumors from which they are derived. Investigations related to tumor biology and drug testing in these models are therefore more likely to be relevant to the disease state in patients. They represent a valuable tool for developing precision therapy in MIBC. PMID:26041878

  8. A Patient-Derived Xenograft Model of Parameningeal Embryonal Rhabdomyosarcoma for Preclinical Studies

    PubMed Central

    Hooper, Jody E.; Cantor, Emma L.; Ehlen, Macgregor S.; Banerjee, Avirup; Malempati, Suman; Stenzel, Peter; Woltjer, Randy L.; Gandour-Edwards, Regina; Goodwin, Neal C.; Yang, Yan; Kaur, Pali; Bult, Carol J.; Airhart, Susan D.; Keller, Charles

    2015-01-01

    Embryonal rhabdomyosarcoma (eRMS) is one of the most common soft tissue sarcomas in children and adolescents. Parameningeal eRMS is a variant that is often more difficult to treat than eRMS occurring at other sites. A 14-year-old female with persistent headaches and rapid weight loss was diagnosed with parameningeal eRMS. She progressed and died despite chemotherapy with vincristine, actinomycin-D, and cyclophosphamide plus 50.4 Gy radiation therapy to the primary tumor site. Tumor specimens were acquired by rapid autopsy and tumor tissue was transplanted into immunodeficient mice to create a patient-derived xenograft (PDX) animal model. As autopsy specimens had an ALK R1181C mutation, PDX tumor bearing animals were treated with the pan-kinase inhibitor lestaurtinib but demonstrated no decrease in tumor growth, suggesting that single agent kinase inhibitor therapy may be insufficient in similar cases. This unique parameningeal eRMS PDX model is publicly available for preclinical study. PMID:26696773

  9. Application of a Patient Derived Xenograft Model for Predicative Study of Uterine Fibroid Disease

    PubMed Central

    Gröticke, Ina; Frisk, Anna-Lena; Keator, Christopher S.; Koch, Markus; Slayden, Ov D.

    2015-01-01

    Human uterine fibroids, benign tumors derived from the smooth muscle layers of the uterus, impose a major health burden to up to 50% of premenopausal women in their daily life. To improve our understanding of this disease, we developed and characterized a patient-derived xenograft model by subcutaneous transplantation of pieces of human uterine fibroid tissue into three different strains of severe combined immunodeficient mice. Engrafted uterine fibroid tissue preserved the classical morphology with interwoven bundles of smooth muscle cells and an abundant deposition of collagenous matrix, similar to uterine fibroids in situ. The grafts expressed both estrogen receptor 1 and progesterone receptor. Additionally, both receptors were up-regulated by estrogen treatment. Growth of the fibroid grafts was dependent on 17β-estradiol and progesterone supplementation at levels similar to women with the disease and was studied for up to 60 days at maximum. Co-treatment with the antiprogestin mifepristone reduced graft growth (four independent donors, p<0.0001 two-sided t-test), as did treatment with the mTOR inhibitor rapamycin (three independent donors, p<0.0001 two-sided t-test). This in vivo animal model preserves the main histological and functional characteristics of human uterine fibroids, is amenable to intervention by pharmacological treatment, and can thus serve as an adequate model for the development of novel therapies. PMID:26588841

  10. Nuclear microprobe study of TiO 2-penetration in the epidermis of human skin xenografts

    NASA Astrophysics Data System (ADS)

    Kertész, Zs.; Szikszai, Z.; Gontier, E.; Moretto, P.; Surlève-Bazeille, J.-E.; Kiss, B.; Juhász, I.; Hunyadi, J.; Kiss, Á. Z.

    2005-04-01

    Titanium-dioxide is a widely used physical photoprotective component of various cosmetic products. However, very few experiments have been carried out on its penetration through the human epidermal barrier and its possible biological effects in vivo and in vitro. In the frame of the NANODERM EU5 project, the penetration of TiO2-nanoparticles through the epidermis of human foreskin grafts transplanted into SCID mice was investigated in the Debrecen and Bordeaux nuclear microprobe laboratories using combined IBA techniques. Transmission electron microscope studies of the same samples were also carried out in the DMPFCS laboratory. The skin grafts were treated with a hydrophobic emulsion containing micronised TiO2-nanoparticles in occlusion, for different time periods. Quantitative elemental concentrations and distributions have been determined in 14-16 μm thick freeze-dried sections obtained from quick frozen punch biopsies using STIM, PIXE and RBS analytical methods. Using both microscopic methods, we have observed nanoparticles having penetrated into the corneocyte layers of stratum corneum by direct visualisation in TEM and via their chemical fingerprint in PIXE. The human skin xenograft has proved to be a model particularly well adapted to such penetration studies.

  11. Taxonomy and conservation of Vietnam's primates: a review.

    PubMed

    Blair, Mary E; Sterling, Eleanor J; Hurley, Martha M

    2011-11-01

    Vietnam has the highest number of primate taxa overall (24-27) and the highest number of globally threatened primate taxa (minimum 20) in Mainland Southeast Asia. Conservation management of these species depends in part on resolving taxonomic uncertainties, which remain numerous among the Asian primates. Recent research on genetic, morphological, and acoustic diversity in Vietnam's primates has clarified some of these uncertainties, although a number of significant classification issues still remain. Herein, we summarize and compare the major current taxonomic classifications of Vietnam's primates, discuss recent advances in the context of these taxonomies, and suggest key areas for additional research to best inform conservation efforts in a region crucial to global primate diversity. Among the most important next steps for the conservation of Vietnam's primates is a new consensus list of Asian primates that resolves current differences between major taxonomies, incorporates recent research advances, and recognizes units of diversity at scales below the species-level, whether termed populations, morphs, or subspecies. Priority should be placed on recognizing distinct populations, regardless of the species concept in use, in order to foster the evolutionary processes necessary for primate populations to cope with inevitable environmental changes. The long-term conservation of Vietnam's primates depends not only on an accepted and accurate taxonomy but also on funding for on-the-ground conservation activities, including training, and the continued dedication and leadership of Vietnamese researchers and managers. PMID:21948330

  12. Pancreas transplantation: review

    PubMed Central

    Meirelles, Roberto Ferreira; Salvalaggio, Paolo; Pacheco-Silva, Alvaro

    2015-01-01

    ABSTRACT Vascularized pancreas transplantation is the only treatment that establishes normal glucose levels and normalizes glycosylated hemoglobin levels in type 1 diabetic patients. The first vascularized pancreas transplant was performed by William Kelly and Richard Lillehei, to treat a type 1 diabetes patient, in December 1966. In Brazil, Edison Teixeira performed the first isolated segmental pancreas transplant in 1968. Until the 1980s, pancreas transplants were restricted to a few centers of the United States and Europe. The introduction of tacrolimus and mycophenolate mofetil in 1994, led to a significant outcome improvement and consequently, an increase in pancreas transplants in several countries. According to the International Pancreas Transplant Registry, until December 31st, 2010, more than 35 thousand pancreas transplants had been performed. The one-year survival of patients and pancreatic grafts exceeds 95 and 83%, respectively. The better survival of pancreatic (86%) and renal (93%) grafts in the first year after transplantation is in the simultaneous pancreas-kidney transplant group of patients. Immunological loss in the first year after transplant for simultaneous pancreas-kidney, pancreas after kidney, and pancreas alone are 1.8, 3.7, and 6%, respectively. Pancreas transplant has 10 to 20% surgical complications requiring laparotomy. Besides enhancing quality of life, pancreatic transplant increases survival of uremic diabetic patient as compared to uremic diabetic patients on dialysis or with kidney transplantation alone. PMID:26154551

  13. An MHC-defined primate model reveals significant rejection of bone marrow after mixed chimerism induction despite full MHC matching.

    PubMed

    Larsen, C P; Page, A; Linzie, K H; Russell, M; Deane, T; Stempora, L; Strobert, E; Penedo, M C T; Ward, T; Wiseman, R; O'Connor, D; Miller, W; Sen, S; Singh, K; Kean, L S

    2010-11-01

    In murine models, mixed hematopoietic chimerism induction leads to robust immune tolerance. However, translation to primates and to patients has been difficult. In this study, we used a novel MHC-defined rhesus macaque model to examine the impact of MHC matching on the stability of costimulation blockade-/sirolimus-mediated chimerism, and to probe possible mechanisms of bone marrow rejection after nonmyeloablative transplant. Using busulfan-based pretransplant preparation and maintenance immunosuppression with sirolimus, as well as CD28 and CD154 blockade, all recipients demonstrated donor engraftment after transplant. However, the mixed chimerism that resulted was compartmentalized, with recipients demonstrating significantly higher whole blood chimerism compared to T cell chimerism. Thus, the vast majority of T cells presenting posttransplant were recipient-rather than donor-derived. Surprisingly, even in MHC-matched transplants, rejection of donor hematopoiesis predominated after immunosuppression withdrawal. Weaning of immunosuppression was associated with a surge of antigen-experienced T cells, and transplant rejection was associated with the acquisition of donor-directed T cell alloreactivity. These results suggest that a reservoir of alloreactive cells was present despite prior costimulation blockade and sirolimus, and that the post-immunosuppression lymphocytic rebound may have lead to a phenotypic shift in these recipient T cells towards an activated, antigen-experienced phenotype, and ultimately, to transplant rejection. PMID:20849552

  14. Diet and Transplantation

    MedlinePlus

    ... Sign up for our FREE magazine, Kidney Living Organ Donation & Transplantation Be an Organ Donor Living Donation Donor ... Giving Primary menu Home Prevention Kidney Disease Patients Organ Donation & Transplantation Professionals Events Advocacy Donate Search Search Header ...

  15. [Promoting Living Kidney Transplantation].

    PubMed

    Lin, Chiu-Chu

    2016-04-01

    Kidney transplantation is the best approach for treating patients with end stage renal disease, offering patients the best chance of returning to normal health. While the techniques used in kidney transplantation surgery are mature and highly successful, there is a severe shortage of donor organs. Statistics show a serious imbalance between organ donations and patients on the waiting list for organ transplantation. Moreover, evidence from empirical studies has shown a better transplantation outcome for patients who receive living donor transplantation than for those who receive organs from cadavers. Although using relatives as donors offers an effective way to reduce the problem of organ shortage, this strategy faces many challenges and many other factors affect the promotion of living donor transplantation. This article elaborates how cultural and psychological factors, kidney transplantation awareness, and ethics and laws impact upon living kidney donations and then proposes coping strategies for promoting living kidney transplantation. PMID:27026555

  16. Pancreatic Islet Transplantation

    MedlinePlus

    ... researchers at the University of Alberta in Edmonton, Canada, reported their findings in the New England Journal ... transplantation as therapeutic. In other countries, such as Canada and Scandinavia, islet allo-transplantation is no longer ...

  17. Pancreatic Islet Transplantation

    MedlinePlus

    ... of immunosuppressive medications?" [ Top ] Collaborative Islet Transplant Registry Data In its 2010 annual report, 1 the Collaborative Islet Transplant Registry presented data on 571 patients who received pancreatic islet allo- ...

  18. Modifying the sugar icing on the transplantation cake.

    PubMed

    Cooper, David K C

    2016-06-01

    As a transplant surgeon, my interest in glycobiology began through my research into ABO-incompatible allotransplantation, and grew when my goal became overcoming the shortage of organs from deceased human donors by the transplantation of pig organs into patients with terminal organ failure (xenotransplantation/cross-species transplantation). The major target for human "natural" (preformed) anti-pig antibodies is galactose-α(1,3)-galactose (the "Gal" epitope), which is expressed on many pig cells, including the vascular endothelium. The binding of human IgM and IgG antibodies to Gal antigens initiates the process of hyperacute rejection, resulting in destruction of the pig graft within minutes or hours. This major barrier has been overcome by the production of pigs in which the gene for the enzyme α(1,3)-galactosyltransferase (GT) has been deleted by genetic engineering, resulting in GT knockout (GTKO) pigs. The two other known carbohydrate antigenic targets on pig cells for human anti-pig antibodies are (i) the product of the cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) gene, i.e., N-glycolylneuraminic acid, and (ii) the product of the β1,4 N-acetylgalactosaminyltransferase gene, i.e., the Sd(a) antigen. Expression of these two has also been deleted in pigs. These genetic manipulations, together with others directed to overcoming primate complement and coagulation activation (the latter of which also relates to glycobiology) have contributed to the prolongation of pig graft survival in nonhuman primate recipients to many months rather than a few minutes. Clinical trials of the transplantation of pig cells are already underway and transplantation of pig organs may be expected within the relatively near future. PMID:26935763

  19. Nonhuman primate dermatology: a literature review

    PubMed Central

    Bernstein, Joseph A.; Didier, Peter J.

    2015-01-01

    In general, veterinary dermatologists do not have extensive clinical experience of nonhuman primate (NHP) dermatoses. The bulk of the published literature does not provide an organized evidence-based approach to the NHP dermatologic case. The veterinary dermatologist is left to extract information from both human and veterinary dermatology, an approach that can be problematic as it forces the clinician to make diagnostic and therapeutic decisions based on two very disparate bodies of literature. A more cohesive approach to NHP dermatology – without relying on assumptions that NHP pathology most commonly behaves similarly to other veterinary and human disease – is required. This review of the dermatology of NHP species includes discussions of primary dermatoses, as well as diseases where dermatologic signs represent a significant secondary component, provides a first step towards encouraging the veterinary community to study and report the dermatologic diseases of nonhuman primates. PMID:19490576

  20. The neurobiology of primate vocal communication

    PubMed Central

    Ghazanfar, Asif A.; Eliades, Steven J.

    2014-01-01

    Recent investigations of non-human primate communication revealed vocal behaviors far more complex than previously appreciated. Understanding the neural basis of these communicative behaviors is important as it has the potential to reveal the basic underpinnings of the still more complex human speech. The latest work revealed vocalization-sensitive regions both within and beyond the traditional boundaries of the central auditory system. The importance and mechanisms of multi-sensory face-voice integration in vocal communication are also increasingly apparent. Finally, studies on the mechanisms of vocal production demonstrated auditory-motor interactions that may allow for self-monitoring and vocal control. We review the current work in these areas of primate communication research. PMID:25062473

  1. Nonhuman primate models of polycystic ovary syndrome

    PubMed Central

    Abbott, David H; Nicol, Lindsey E; Levine, Jon E; Xu, Ning; Goodarzi, Mark O; Dumesic, Daniel A

    2013-01-01

    With close genomic and phenotypic similarity to humans, nonhuman primate models provide comprehensive epigenetic mimics of polycystic ovary syndrome (PCOS), suggesting early life targeting for prevention. Fetal exposure to testosterone (T), of all nonhuman primate emulations, provides the closest PCOS-like phenotypes, with early-to-mid gestation T-exposed female rhesus monkeys exhibiting adult reproductive, endocrinological and metabolic dysfunctional traits that are co-pathologies of PCOS. Late gestational T exposure, while inducing adult ovarian hyperandrogenism and menstrual abnormalities, has less dysfunctional metabolic accompaniment. Fetal exposures to dihydrotestosterone (DHT) or diethylstilbestrol (DES) suggest androgenic and estrogenic aspects of fetal programming. Neonatal exposure to T produces no PCOS-like outcome, while continuous T treatment of juvenile females causes precocious weight gain and early menarche (high T), or high LH and weight gain (moderate T). Acute T exposure of adult females generates polyfollicular ovaries, while chronic T exposure induces subtle menstrual irregularities without metabolic dysfunction. PMID:23370180

  2. Effective primate conservation education: gaps and opportunities.

    PubMed

    Jacobson, Susan K

    2010-05-01

    Conservation education goals generally include influencing people's conservation awareness, attitudes, and behaviors. Effective programs can help foster sustainable behavior, improve public support for conservation, reduce vandalism and poaching in protected areas, improve compliance with conservation regulations, increase recreation carrying capacities, and influence policies and decisions that affect the environment. Primate conservation problems cut across many disciplines, and primate conservation education must likewise address cross-disciplinary issues. Conservation educators must incorporate both theoretical and practical knowledge and skills to develop effective programs, and the skill set must stretch beyond pedagogy. Expertise needed comes from the areas of planning, collaboration, psychology, entertainment, and evaluation. Integration of these elements can lead to greater program success. PMID:20041471

  3. [Ecotourism disturbances to non-human primates].

    PubMed

    Fan, Peng-Lai; Xiang, Zuo-Fu

    2013-02-01

    In tandem with economic growth and rising living conditions, ecotourism has increasingly gained popularity among the Chinese public. Non-human primates, as charismatic animals and the closest relatives of human beings, have shown a strong affinity in attracting the general public and raising money, and for that reason a variety of monkey parks, valleys, and islands are becoming increasingly popular in China. Though successful in raising a substantial sum of money for the managing agency of a nature reserve, there may be negative impacts on monkey groups used in ecotourism. Here, to establish effective guards for non-human primates involved in ecotourism, we present a review on tourism disturbance and summarize the negative impacts on behavioral patterns, reproduction, and health condition of animals. PMID:23389980

  4. Parthenogenetic dopamine neurons from primate embryonic stem cells restore function in experimental Parkinson's disease

    PubMed Central

    Lee, Hyojin; Patterson, Michaela; Reske-Nielsen, Casper; Yoshizaki, Takahito; Sonntag, Kai C.; Studer, Lorenz; Isacson, Ole

    2008-01-01

    The identity and functional potential of dopamine neurons derived in vitro from embryonic stem cells are critical for the development of a stem cell-based replacement therapy for Parkinson's disease. Using a parthenogenetic primate embryonic stem cell line, we have generated dopamine neurons that display persistent expression of midbrain regional and cell-specific transcription factors, which establish their proper identity and allow for their survival. We show here that transplantation of parthenogenetic dopamine neurons restores motor function in hemi-parkinsonian, 6-hydroxy-dopamine-lesioned rats. Exposure to Wnt5a and fibroblast growth factors (FGF) 20 and 2 at the final stage of in vitro differentiation enhanced the survival of dopamine neurons and, correspondingly, the extent of motor recovery of transplanted animals. Importantly for future development of clinical applications, dopamine neurons were post-mitotic at the time of transplantation and there was no tumour formation. These data provide proof for the concept that parthenogenetic stem cells are a suitable source of functional neurons for therapeutic applications. PMID:18669499

  5. Buyer beware transplantation.

    PubMed

    Chapman, Jeremy R; Delmonico, Francis L

    2016-05-01

    Poor long-term outcomes of commercial transplantation of transplant tourists reinforce the need to prevent this form of human trafficking. The development of an International Convention by the Council of Europe is highlighted and the implications for physicians of the criminalizing of organ trafficking are considered. The causes of poor outcomes from transplant tourism are considered, with the actions needed to provide both equity and sufficiency of access to transplantation as critical deterrent measures. PMID:27083275

  6. Molecular evolution of prolactin in primates.

    PubMed

    Wallis, O Caryl; Mac-Kwashie, Akofa O; Makri, Georgia; Wallis, Michael

    2005-05-01

    Pituitary prolactin, like growth hormone (GH) and several other protein hormones, shows an episodic pattern of molecular evolution in which sustained bursts of rapid change contrast with long periods of slow evolution. A period of rapid change occurred in the evolution of prolactin in primates, leading to marked sequence differences between human prolactin and that of nonprimate mammals. We have defined this burst more precisely by sequencing the coding regions of prolactin genes for a prosimian, the slow loris (Nycticebus pygmaeus), and a New World monkey, the marmoset (Callithrix jacchus). Slow loris prolactin is very similar in sequence to pig prolactin, so the episode of rapid change occurred during primate evolution, after the separation of lines leading to prosimians and higher primates. Marmoset prolactin is similar in sequence to human prolactin, so the accelerated evolution occurred before divergence of New World monkeys and Old World monkeys/apes. The burst of change was confined largely to coding sequence (nonsynonymous sites) for mature prolactin and is not marked in other components of the gene sequence. This and the observations that (1) there was no apparent loss of function during the episode of rapid evolution, (2) the rate of evolution slowed toward the basal rate after this burst, and (3) the distribution of substitutions in the prolactin molecule is very uneven support the idea that this episode of rapid change was due to positive adaptive selection. In the slow loris and marmoset there is no evidence for duplication of the prolactin gene, and evidence from another New World monkey (Cebus albifrons) and from the chimpanzee and human genome sequences, suggests that this is the general position in primates, contrasting with the situation for GH genes. The chimpanzee prolactin sequence differs from that of human at two residues and comparison of human and chimpanzee prolactin gene sequences suggests that noncoding regions associated with regulating

  7. [Experimental whooping cough of nonhuman primate].

    PubMed

    Kubrava, D T; Medkova, A Iu; Siniashina, L N; Shevtsova, Z V; Matua, A Z; Kondzharia, I G; Barkaia, V S; Elistratova, Zh V; Karataev, G I; Mikvabia, Z Ia; Gintsburg, A L

    2013-01-01

    Despite considerable success in study of Bordetella pertussis virulence factors, pathogenesis of whooping cough, duration of B. pertussis bacteria persistence, types and mechanisms of immune response are still keep underinvestigated. It can be explained by the absence ofadequate experimental animal model for pertussis study. Our study estimates clinical and laboratory parameters of whooping cough in non-human primates of the Old World in the process of intranasan infection by virulent B. pertussis bacteria. Also the duration of B. pertussis bacteria persistence in animals was investigated. 14 animal units of 4 species of non-human primates of the Old World were used for intranasal infection. The examination of infect animals included: visual exploration of nasopharynx, thermometry, clinical and biochemical blood analyses, identification ofB. pertussis, using microbiologic and molecular genetic analyses, estimation of innate and adoptive immune factors. The development of infectious process was accompanied by generation of B. pertussis bacteria, catarrhal inflammation of nasopharyngeal mucosa, leucocytosis, hypoglycemia specific for pertussis, and activation of innate and adaptive immunity for all primates regardless of specie were seen. While repeated experimental infection in primates single bacterial colonies were registered during only first week after challenge. It occurs like the absence of inflammation of nasopharyngeal mucosa and the lack of laboratory marks of whooping cough, recorded after first challenge. The evident booster effect of humoral immunity was observed. As a model for investigation of B. pertussis bacteria persistence and immune response against whooping cough we suggest the usage of rhesus macaque as more available to experiments. PMID:24340642

  8. Fear generalization in the primate amygdala.

    PubMed

    Resnik, Jennifer; Paz, Rony

    2015-02-01

    Broad generalization of negative memories is a potential etiology for anxiety disorders, yet the underlying mechanisms remain unknown. We developed a non-human primate model that replicates behavioral observations in humans and identifies specific changes in tuning properties of amygdala neurons: the width of auditory tuning increases with the distance of its center from the conditioned stimulus. This center-width relationship can account for better detection and at the same time explain the wide stimulus generalization. PMID:25531573

  9. Classification and automatic transcription of primate calls.

    PubMed

    Versteegh, Maarten; Kuhn, Jeremy; Synnaeve, Gabriel; Ravaux, Lucie; Chemla, Emmanuel; Cäsar, Cristiane; Fuller, James; Murphy, Derek; Schel, Anne; Dunbar, Ewan

    2016-07-01

    This paper reports on an automated and openly available tool for automatic acoustic analysis and transcription of primate calls, which takes raw field recordings and outputs call labels time-aligned with the audio. The system's output predicts a majority of the start times of calls accurately within 200 milliseconds. The tools do not require any manual acoustic analysis or selection of spectral features by the researcher. PMID:27475207

  10. Ecological importance of trichromatic vision to primates.

    PubMed

    Dominy, N J; Lucas, P W

    2001-03-15

    Trichromatic colour vision, characterized by three retinal photopigments tuned to peak wavelengths of approximately 430 nm, approximately 535 nm and approximately 562 nm (refs 1, 2), has evolved convergently in catarrhine primates and one genus of New World monkey, the howlers (genus Alouatta). This uniform capacity to discriminate red-green colours, which is not found in other mammals, has been proposed as advantageous for the long-range detection of either ripe fruits or young leaves (which frequently flush red in the tropics) against a background of mature foliage. Here we show that four trichromatic primate species in Kibale Forest, Uganda, eat leaves that are colour discriminated only by red-greenness, a colour axis correlated with high protein levels and low toughness. Despite their divergent digestive systems, these primates have no significant interspecific differences in leaf colour selection. In contrast, eaten fruits were generally discriminated from mature leaves on both red-green and yellow-blue channels and also by their luminance, with a significant difference between chimpanzees and monkeys in fruit colour choice. Our results implicate leaf consumption, a critical food resource when fruit is scarce, as having unique value in maintaining trichromacy in catarrhines. PMID:11268211