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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. Germ cell transplantation and testis tissue xenografting in mice.

    PubMed

    Tang, Lin; Rodriguez-Sosa, Jose Rafael; Dobrinski, Ina

    2012-01-01

    recipient somatic cell compartment with the germ cells from phylogenetically distant species(12). An alternative approach is transplantation of germ cells from large species together with their surrounding somatic compartment. We first reported in 2002, that small fragments of testis tissue from immature males transplanted under the dorsal skin of immunodeficient mice are able to survive and undergo full development with the production of fertilization competent sperm(13). Since then testis tissue xenografting has been shown to be successful in many species and emerged as a valuable alternative to study testis development and spermatogenesis of large animals in mice(14). PMID:22330955

  4. Transplantation of Tissue-Engineered Cartilage in an Animal Model (Xenograft and Autograft): Construct Validation.

    PubMed

    Nemoto, Hitoshi; Watson, Deborah; Masuda, Koichi

    2015-01-01

    Tissue engineering holds great promise for cartilage repair with minimal donor-site morbidity. The in vivo maturation of a tissue-engineered construct can be tested in the subcutaneous tissues of the same species for autografts or of immunocompromised animals for allografts or xenografts. This section describes detailed protocols for the surgical transplantation of a tissue-engineered construct into an animal model to assess construct validity.

  5. Human cytomegalovirus infection leads to elevated levels of transplant arteriosclerosis in a humanized mouse aortic xenograft model.

    PubMed

    Abele-Ohl, S; Leis, M; Wollin, M; Mahmoudian, S; Hoffmann, J; Müller, R; Heim, C; Spriewald, B M; Weyand, M; Stamminger, T; Ensminger, S M

    2012-07-01

    Recent findings emphasized an important role of human cytomegalovirus (HCMV) infection in the development of transplant arteriosclerosis. Therefore, the aim of this study was to develop a human peripheral blood lymphocyte (hu-PBL)/Rag-2(-/-) γc(-/-) mouse-xenograft-model to investigate both immunological as well as viral effector mechanisms in the progression of transplant arteriosclerosis. For this, sidebranches from the internal mammary artery were recovered during coronary artery bypass graft surgery, tissue-typed and infected with HCMV. Then, size-matched sidebranches were implanted into the infrarenal aorta of Rag-2(-/-) γc(-/-) mice. The animals were reconstituted with human peripheral blood mononuclear cells (PBMCs) 7 days after transplantation. HCMV-infection was confirmed by Taqman-PCR and immunofluorescence analyses. Arterial grafts were analyzed by histology on day 40 after transplantation. PBMC-reconstituted Rag-2(-/-) γc(-/-) animals showed splenic chimerism levels ranging from 1-16% human cells. After reconstitution, Rag-2(-/-) γc(-/-) mice developed human leukocyte infiltrates in their grafts and vascular lesions that were significantly elevated after infection. Cellular infiltration revealed significantly increased ICAM-1 and PDGF-R-β expression after HCMV-infection of the graft. Arterial grafts from unreconstituted Rag-2(-/-) γc(-/-) recipients showed no vascular lesions. These data demonstrate a causative relationship between HCMV-infection as an isolated risk factor and the development of transplant-arteriosclerosis in a humanized mouse arterial-transplant-model possibly by elevated ICAM-1 and PDGF-R-β expression.

  6. Survival of free and encapsulated human and rat islet xenografts transplanted into the mouse bone marrow.

    PubMed

    Meier, Raphael P H; Seebach, Jörg D; Morel, Philippe; Mahou, Redouan; Borot, Sophie; Giovannoni, Laurianne; Parnaud, Geraldine; Montanari, Elisa; Bosco, Domenico; Wandrey, Christine; Berney, Thierry; Bühler, Leo H; Muller, Yannick D

    2014-01-01

    Bone marrow was recently proposed as an alternative and potentially immune-privileged site for pancreatic islet transplantation. The aim of the present study was to assess the survival and rejection mechanisms of free and encapsulated xenogeneic islets transplanted into the medullary cavity of the femur, or under the kidney capsule of streptozotocin-induced diabetic C57BL/6 mice. The median survival of free rat islets transplanted into the bone marrow or under the kidney capsule was 9 and 14 days, respectively, whereas that of free human islets was shorter, 7 days (bone marrow) and 10 days (kidney capsule). Infiltrating CD8+ T cells and redistributed CD4+ T cells, and macrophages were detected around the transplanted islets in bone sections. Recipient mouse splenocytes proliferated in response to donor rat stimulator cells. One month after transplantation under both kidney capsule or into bone marrow, encapsulated rat islets had induced a similar degree of fibrotic reaction and still contained insulin positive cells. In conclusion, we successfully established a small animal model for xenogeneic islet transplantation into the bone marrow. The rejection of xenogeneic islets was associated with local and systemic T cell responses and macrophage recruitment. Although there was no evidence for immune-privilege, the bone marrow may represent a feasible site for encapsulated xenogeneic islet transplantation.

  7. 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

  8. Development of transplantable human chordoma xenograft for preclinical assessment of novel therapeutic strategies

    PubMed Central

    Bozzi, Fabio; Manenti, Giacomo; Conca, Elena; Stacchiotti, Silvia; Messina, Antonella; Dagrada, GianPaolo; Gronchi, Alessandro; Panizza, Pietro; Pierotti, Marco A.; Tamborini, Elena; Pilotti, Silvana

    2014-01-01

    Background Chordomas are rare and indolent bone tumors that arise in the skull base and mobile spine. Distant metastases occur in >20% of cases, but morbidity and mortality are mainly related to local relapses that affect the majority of patients. Standard chemotherapy has modest activity, whereas new targeted therapies (alone or in combination) have some activity in controlling disease progression. However, the scarcity of preclinical models capable of testing in vivo responses to these therapies hampers the development of new medical strategies. Methods In this study, 8 chordoma samples taken from 8 patients were implanted in nude mice. Four engrafted successfully and gave rise to tumor masses that were analyzed histologically, by means of fluorescence in situ hybridization and biochemical techniques. The data relating to each of the mouse tumors were compared with those obtained from the corresponding human tumor. Results All 4 engraftments retained the histological, genetic and biochemical features of the human tumors they came from. In one epidermal growth factor receptor(EGFR)-positive xenograft, responsiveness to lapatinib was evaluated by comparing the pre- and posttreatment findings. The treatment induced a low-level, heterogeneous switching off of EGFR and its downstream signaling effectors. Conclusions Overall, this model is very close to human chordoma and represents a new means of undertaking preclinical investigations and developing tailored therapies. PMID:24366975

  9. Development of transplantable human chordoma xenograft for preclinical assessment of novel therapeutic strategies.

    PubMed

    Bozzi, Fabio; Manenti, Giacomo; Conca, Elena; Stacchiotti, Silvia; Messina, Antonella; Dagrada, Gianpaolo; Gronchi, Alessandro; Panizza, Pietro; Pierotti, Marco A; Tamborini, Elena; Pilotti, Silvana

    2013-12-16

    BackgroundChordomas are rare and indolent bone tumors that arise in the skull base and mobile spine. Distant metastases occur in >20% of cases, but morbidity and mortality are mainly related to local relapses that affect the majority of patients. Standard chemotherapy has modest activity, whereas new targeted therapies (alone or in combination) have some activity in controlling disease progression. However, the scarcity of preclinical models capable of testing in vivo responses to these therapies hampers the development of new medical strategies.MethodsIn this study, 8 chordoma samples taken from 8 patients were implanted in nude mice. Four engrafted successfully and gave rise to tumor masses that were analyzed histologically, by means of fluorescence in situ hybridization and biochemical techniques. The data relating to each of the mouse tumors were compared with those obtained from the corresponding human tumor.ResultsAll 4 engraftments retained the histological, genetic and biochemical features of the human tumors they came from. In one epidermal growth factor receptor(EGFR)-positive xenograft, responsiveness to lapatinib was evaluated by comparing the pre- and posttreatment findings. The treatment induced a low-level, heterogeneous switching off of EGFR and its downstream signaling effectors.ConclusionsOverall, this model is very close to human chordoma and represents a new means of undertaking preclinical investigations and developing tailored therapies. PMID:24343111

  10. 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

  11. Xenograft of microencapsulated Sertoli cells for the cell therapy of type 2 diabetes mellitus in spontaneously diabetic nonhuman primates: preliminary data.

    PubMed

    Luca, G; Cameron, D F; Arato, I; Mancuso, F; Linden, E H; Calvitti, M; Falabella, G; Szekeres, K; Bodo, M; Ricci, G; Hansen, B C; Calafiore, R

    2014-01-01

    Insulin resistance in type 2 diabetes mellitus (T2DM) may be due to a chronic inflammation of the visceral adipose tissue (VAT) leading to local and systemic increases in proinflammatory cytokines. Microencapsulated porcine Sertoli cells (MC-pSC), by provision of immunomodulatory and trophic factors, have been successfully used to reduce such inflammation in rodent animal models of type 1 diabetes with no complications or deleterious side effects. Herein, we have begun to investigate this novel and safe therapeutic approach in the spontaneously obese nonhuman primate with spontaneous, insulin-dependent T2DM. After MC-pSC intraperitoneal injection we have evaluated, throughout a 6-month follow-up period, daily ad libitum fed glucose levels, daily exogenous insulin supplementation, biweekly body weight measurements, periodic fasting blood glucose concentrations, glycated hemoglobin (HbA1c) levels, glucose tolerance tests (GTT), and fluorescence-activated cell sorting cytometry (FACS) assessment of peripheral blood mononuclear cells. Very preliminarily, we have observed a slight reduction in fasting (FPG) and mean nonfasting (NF) plasma glucose levels. We found minimal changes, only in 1 animal, in daily exogenous insulin requirements and HbA1c levels. Flow cytometric analysis was associated with decrease in CD8(+) cells only in 1 recipient with a reduction in mean regulatory T Cells (Treg), whereas interestingly, decrease of B lymphocytes was observed in both animals. These results may suggest that this novel MC-SC-based transplantation protocol might possibly impact the metabolic status of T2DM in higher mammals that are close to humans.

  12. 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.

  13. 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

    2016-04-05

    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.

  14. 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

  15. 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

  16. CTLA4Ig prevents alloantibody formation following nonhuman primate islet transplantation using the CD40-specific antibody 3A8.

    PubMed

    Badell, I R; Russell, M C; Cardona, K; Shaffer, V O; Turner, A P; Avila, J G; Cano, J A; Leopardi, F V; Song, M; Strobert, E A; Ford, M L; Pearson, T C; Kirk, A D; Larsen, C P

    2012-07-01

    Islet transplantation to treat type 1 diabetes has been limited in part by toxicities of current immunosuppression and recipient humoral sensitization. Blockade of the CD28/CD80/86 and CD40/CD154 pathways has shown promise to remedy both these limitations, but translation has been hampered by difficulties in translating CD154-directed therapies. Prior CD40-directed regimens have led to prolonged islet survival, but fail to prevent humoral allosensitization. We therefore evaluated the addition of CTLA4Ig to a CD40 blockade-based regimen in nonhuman primate (NHP) alloislet transplantation. Diabetic rhesus macaques were transplanted allogeneic islets using the CD40-specific antibody 3A8, basiliximab induction, and sirolimus with or without CTLA4Ig maintenance therapy. Allograft survival was determined by fasting blood glucose levels and flow cytometric techniques were used to test for donor-specific antibody (DSA) formation. CTLA4Ig plus 3A8, basiliximab and sirolimus was well tolerated and induced long-term islet allograft survival. The addition of CTLA4Ig prevented DSA formation, but did not facilitate withdrawal of the 3A8-based regimen. Thus, CTLA4Ig combines with a CD40-specific regimen to prevent DSA formation in NHPs, and offers a potentially translatable calcineurin inhibitor-free protocol inclusive of a single investigational agent for use in clinical islet transplantation without relying upon CD154 blockade. PMID:22458552

  17. Antitumor effect of Deoxypodophyllotoxin on human breast cancer xenograft transplanted in BALB/c nude mice model.

    PubMed

    Khaled, Meyada; Belaaloui, Ghania; Jiang, Zhen-Zhou; Zhu, Xiong; Zhang, Lu-Yong

    2016-10-01

    Recently, biologically active compounds isolated from plants used in herbal medicine have been the center of interest. Deoxypodophyllotoxin (DPT), structurally closely related to the lignan podophyllotoxin, was found to be a potent antitumor and antiproliferative agent, in several tumor cells, in vitro. However, DPT has not been used clinically yet because of the lack of in vivo studies. This study is the first report demonstrating the antitumor effect of DPT on MDA-MB-231 human breast cancer xenografts in nude mice. DPT, significantly, inhibited the growth of MDA-MB-231 xenograft in BALB/c nude mice. The T/C value (the value of the relative tumor volume of treatment group compared to the control group) of groups treated with 5, 10, and 20 mg/kg of intravenous DPT-HP-β-CD was 42.87%, 34.04% and 9.63%, respectively, suggesting the positive antitumor activity of DPT. In addition, the antitumor effect of DPT-HP-β-CD (20 mg/kg) in human breast cancer MDA-MB-231 xenograft was more effective than etoposide (VP-16) (20 mg/kg) and docetaxel (20 mg/kg). These findings suggest that this drug is a promising chemotherapy candidate against human breast carcinoma. PMID:27578026

  18. 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.

  19. 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.

  20. 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.

  1. Preclinical safety evaluation of human mesenchymal stem cell transplantation in cerebrum of nonhuman primates.

    PubMed

    Feng, Ming; Li, Yan; Han, Qin; Bao, Xinjie; Yang, Ming; Zhu, Hua; Li, Qin; Wei, Junji; Ma, Wenbin; Gao, Hong; An, Yihua; Zhao, Robert Chunhua; Qin, Chuan; Wang, Renzhi

    2014-01-01

    The efficacy of stem cell transplantation for promoting recovery of patients with neurological diseases, such as stroke, has been reported in several studies. However, the safety of the intracerebral transplantation of human mesenchymal stem cells (hMSCs) remains unclear. The aim of the study was to evaluate the safety of hMSCs transplanted in cerebrum of Macaca fascicularis and to provide evidence for clinical application. A total of 24 M fascicularis were assigned to 3 groups randomly: low dose (3.0 × 10(5) cells/kg), high dose (2.5 × 10(6) cells/kg), and the control (normal saline [NS]). Human mesenchymal stem cells or NS were injected into each monkey for 2 times, with an interval of 3 weeks. The injection point was located outside of the right putamen, according to a stereotactic map and preoperative magnetic resonance imaging of the monkeys. Animal health, behavior, biophysical and biochemical parameters, and brain neurological function were routinely monitored over a 6-month period posttransplantation, and the histopathologic examinations were also performed. The results showed that local pathologic damage including local tissue necrosis and inflammation was induced after the injection. The damage of low-dose and high-dose groups was greater than that of the control group, yet over time, the damage could be repaired gradually. No major hMSCs-associated changes were induced from other indicators, and the transplantation of hMSCs in monkeys did not affect total immunoglobulin (Ig) M, total IgG, CD3, CD4, or CD8 values. We therefore conclude that transplantation of hMSCs to the cerebrum represents a safe alternative for clinical application of neurological disorders.

  2. Future of liver transplantation: Non-human primates for patient-specific organs from induced pluripotent stem cells

    PubMed Central

    Sanal, Madhusudana Girija

    2011-01-01

    Strategies to fill the huge gap in supply versus demand of human organs include bioartificial organs, growing humanized organs in animals, cell therapy, and implantable bioengineered constructs. Reproducing the complex relations between different cell types, generation of adequate vasculature, and immunological complications are road blocks in generation of bioengineered organs, while immunological complications limit the use of humanized organs produced in animals. Recent developments in induced pluripotent stem cell (iPSC) biology offer a possibility of generating human, patient-specific organs in non-human primates (NHP) using patient-derived iPSC and NHP-derived iPSC lacking the critical developmental genes for the organ of interest complementing a NHP tetraploid embryo. The organ derived in this way will have the same human leukocyte antigen (HLA) profile as the patient. This approach can be curative in genetic disorders as this offers the possibility of gene manipulation and correction of the patient’s genome at the iPSC stage before tetraploid complementation. The process of generation of patient-specific organs such as the liver in this way has the great advantage of making use of the natural signaling cascades in the natural milieu probably resulting in organs of great quality for transplantation. However, the inexorable scientific developments in this direction involve several social issues and hence we need to educate and prepare society in advance to accept the revolutionary consequences, good, bad and ugly. PMID:21990949

  3. Transplanted myoblasts can migrate several millimeters to fuse with damaged myofibers in nonhuman primate skeletal muscle.

    PubMed

    Skuk, Daniel; Goulet, Marlyne; Tremblay, Jacques P

    2011-09-01

    A major restriction of the intramuscular transplantation of myoblasts is that the grafted cells fuse mostly with myofibers along the injection trajectories. This has been attributed to a "lack of migration ability" of the grafted myoblasts. It has been assumed that grafted myoblasts remain motionless in the sites of delivery and fuse only with myofibers with which they come into contact. In the present study, we analyzed this phenomenon in 17 cynomolgus monkeys. We found that intramuscularly injected myoblasts within 1 hour after their injection are mainly located in the perimysium and not distributed along the injection trajectories. This suggested that the grafted myoblasts later migrate from the perimysium to fuse with myofibers that are damaged by the injections. Therefore, we analyzed whether β-galactosidase-labeled myoblasts injected subcutaneously over skeletal muscles migrate in needle-damaged and nondamaged muscle regions. We observed that grafted myoblasts migrated up to 1cm in depth from the muscle surface into the muscles, although they seemingly fused mainly with damaged myofibers. Our findings suggest that myoblast transplantation is not necessarily restricted bya "lack of migration ability" of the grafted cells but by the fact that myoblasts fuse with regenerating myofibers and not with undamaged myofibers.

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. The role of additional chemotherapy with oral UFT in intravenous combination chemotherapy with cisplatin and 5-fluorouracil for human gastric cancer xenograft lines of well- and poorly- differentiated adenocarcinomas transplanted in nude mice.

    PubMed

    Tseng, C C; Nio, Y; Tsubono, M; Kawabata, K; Masai, Y; Hayashi, H; Fukumoto, M; Tobe, T

    1992-01-01

    In order to assess the role of maintenance chemotherapy with the oral anticancer agent UFT, a mixture of uracil and futraful, in the intensive intravenous chemotherapy for gastric cancer, nude mice transplanted with human gastric cancer xenografts were treated with intravenous 5-fluorouracil (5-FU) and cisplatin (CDDP), alone or in combination, with or without the oral anticancer agent UFT. UFT was given at its maximal clinical dose of 10 mg/kg of body weight daily for 2 weeks, while 5-FU and/or CDDP was intravenously administered at the dose of 20 mg/kg and 1.8 mg/kg of body weight respectively once a week, alone or in combination, for two weeks. The results revealed that 5-FU or CDDP alone were ineffective for both GC-YN, a well differentiated adenocarcinoma line, and GC-SF, a poorly differentiated adenocarcinoma line; however, UFT was effective for GC-SF. In combinations, only the three-agent combination 5-FU + CDDP + UFT (FPU) was effective for GC-YN; however, all the two-agent combinations and FPU were effective for GC-SF. FPU significantly suppressed the growth of GC-YN much more than all the other treatment groups. In contrast, although all combinations as well as UFT alone were effective for GC-SF, there was no significant difference among these effective groups. Moreover, no side effects were noted in combined use of UFT. This study suggests that oral UFT as a maintenance treatment may be beneficial in the combination chemotherapy for human gastric cancer.

  11. 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.

  12. [Xenograft of human nasopharyngeal mucosa in nude mice].

    PubMed

    Huang, P

    1989-01-01

    Human nasopharyngeal mucosa from 22-cases of chronic nasopharyngitis was transplanted into 26 nude mice. The xenografts were examined on 15, 30, 45 and 60 days after transplantation, and found to have survived in 19 mice. The survival rate was 73.1 per cent. The developed epithelia took the shape of cystic cavities, which gradually enlarged and the thickly laminated columnar epithelia with cells in mitoses or squamous metaplasia changed into thin and flat ones. The epithelium proliferated actively after 15 to 30 days of transplantation. The results afford useful reference to the study of induction of cancer in human nasopharyngeal mucosa transplanted into nude mice.

  13. Primate archaeology.

    PubMed

    Haslam, Michael; Hernandez-Aguilar, Adriana; Ling, Victoria; Carvalho, Susana; de la Torre, Ignacio; DeStefano, April; Du, Andrew; Hardy, Bruce; Harris, Jack; Marchant, Linda; Matsuzawa, Tetsuro; McGrew, William; Mercader, Julio; Mora, Rafael; Petraglia, Michael; Roche, Hélène; Visalberghi, Elisabetta; Warren, Rebecca

    2009-07-16

    All modern humans use tools to overcome limitations of our anatomy and to make difficult tasks easier. However, if tool use is such an advantage, we may ask why it is not evolved to the same degree in other species. To answer this question, we need to bring a long-term perspective to the material record of other members of our own order, the Primates.

  14. 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.

  15. COAGULATION DYSREGULATION AS A BARRIER TO XENOTRANSPLANTATION IN THE PRIMATE

    PubMed Central

    Lin, Chih Che; Cooper, David K.C.; Dorling, Anthony

    2009-01-01

    Purpose of review The ability to generate pigs expressing a human complement regulatory protein (hCRP) and/or pigs in which the α1,3-galactosyltransferase gene has been knocked out (GT-KO) has largely overcome the barrier of hyperacute rejection of a pig organ transplanted into a primate. However, acute humoral xenograft rejection (AHXR), presenting as microvascular thrombosis and/or consumptive coagulopathy, remains a major hurdle to successful xenotransplantation. This review summarizes recent studies of the coagulation problems associated with xenotransplantation, and discusses potential strategies to overcome them. Recent progress Organ transplantation into nonhuman primates from GT-KO pigs that express a hCRP are not susceptible to hyperacute rejection. Nevertheless, most recipients of GT-KO and/or hCRP transgenic pig organs develop a consumptive coagulopathy, even when the graft remains functioning. This is associated with platelet aggregation, thrombocytopenia, anemia, and a tendency to bleed. Whilst this may reflect an ongoing immune response against the graft, (as exposure to anti-nonGal antibodies in vitro induces procoagulant changes in porcine ECs, even in the absence of complement), histological examination of the graft often shows only minimal features of immune injury, unlike grafts undergoing typical AHXR. Importantly, recent in vitro studies have indicated that the coincubation of porcine endothelial cells (ECs) with human platelets activates the platelets to express tissue factor, independent of a humoral immune response. These observations suggest that the use of organs from GT-KO pigs that express a hCRP may not be sufficient to prevent the development of a coagulation disorder following xenotransplantation, even if complete immunological tolerance can be achieved. Summary Both thrombotic microangiopathy and systemic consumptive coagulopathy are increasingly recognized as barriers to successful xenotransplantation. The breeding of transgenic

  16. Future of transplantation medicine.

    PubMed

    Rowiński, Wojciech

    2007-01-01

    Organ transplantation has become very successful method of treatment of end stage organ disease. However the waiting lists of patients aiming such treatment are exponentially growing due to insufficient organ supply. Prognosis of the future for transplantation medicine is truly difficult. Prospects from past years, that "soon induction of tolerance will become possible"(1975), wide xenogenic transplant utilization (in 2000), fetal brain cell transplantation to treat some neurologic disease and transplantation of isolated cells instead of whole organs (1998) proved wrong. The research in the nearest future will be focused on tolerance induction, inhibition of alloreaction in blood-group discordant transplants (in immunized patients) and xenografts. In parallel, studies on hybrid and totally artificial, implantable devices (artificial pancreas and liver) will be carried on. 21st century will belong to regeneration medicine, with therapeutic applications of stem cells.

  17. Ethics in actual surgery. Ethics and organ transplantation.

    PubMed

    Eyskens, E

    1994-01-01

    Actual organ transplantation evokes more and more ethical questions. There is scarcity of donor organs. The waiting lists of potential recipients for organ transplantation are steadily growing as is the number of dead among the waiting patients. In Belgium the mortality rate of traffic victims during the first thirty days of hospital admission has been reduced by half. Among this group the number of potential cadaveric donor candidates is further reduced following complications of sustained intensive care. Shortage of cadaveric organs prompts some to select candidates for transplantation with exclusion of those considered responsible for their illness. Some centres incline to reconsider the definition of cerebral death by extending this notion to the irreversibly unconscious and therefore socially dead. Organ donation by living donors opens the way to commercialism specially in case of unrelated living donation. Living donors are often insufficiently informed about their risks and the final outcome of these transplantations. The use of implantable artificial organs should be the solution to many ethical problems. But some experience with the Jarvik heart as a temporary implant increases so far the shortage of donor heart supply and the number of patients on the waiting lists as well. It also excludes patients who became unsuitable for transplantation after complication of the Jarvik implantation. Xenotransplantation is largely under investigation. However, it is out of question that primates, which are threatened already with extinction should act as organ suppliers for mankind. Xenograft organs should be found in animals for food consumption, sufficient in number and more easily accepted as organ donors on ethical ground. PMID:8067169

  18. Ethics in actual surgery. Ethics and organ transplantation.

    PubMed

    Eyskens, E

    1994-01-01

    Actual organ transplantation evokes more and more ethical questions. There is scarcity of donor organs. The waiting lists of potential recipients for organ transplantation are steadily growing as is the number of dead among the waiting patients. In Belgium the mortality rate of traffic victims during the first thirty days of hospital admission has been reduced by half. Among this group the number of potential cadaveric donor candidates is further reduced following complications of sustained intensive care. Shortage of cadaveric organs prompts some to select candidates for transplantation with exclusion of those considered responsible for their illness. Some centres incline to reconsider the definition of cerebral death by extending this notion to the irreversibly unconscious and therefore socially dead. Organ donation by living donors opens the way to commercialism specially in case of unrelated living donation. Living donors are often insufficiently informed about their risks and the final outcome of these transplantations. The use of implantable artificial organs should be the solution to many ethical problems. But some experience with the Jarvik heart as a temporary implant increases so far the shortage of donor heart supply and the number of patients on the waiting lists as well. It also excludes patients who became unsuitable for transplantation after complication of the Jarvik implantation. Xenotransplantation is largely under investigation. However, it is out of question that primates, which are threatened already with extinction should act as organ suppliers for mankind. Xenograft organs should be found in animals for food consumption, sufficient in number and more easily accepted as organ donors on ethical ground.

  19. Progress with nonhuman primate embryonic stem cells.

    PubMed

    Wolf, Don P; Kuo, Hung-Chih; Pau, K-Y Francis; Lester, Linda

    2004-12-01

    Embryonic stem cells hold potential in the fields of regenerative medicine, developmental biology, tissue regeneration, disease pathogenicity, and drug discovery. Embryonic stem (ES) cell lines are now available in primates, including man, rhesus, and cynomologous monkeys. Monkey ES cells serve as invaluable clinically relevant models for studies that can't be conducted in humans because of practical or ethical limitations, or in rodents because of differences in physiology and anatomy. Here, we review the current status of nonhuman primate research with ES cells, beginning with a description of their isolation, characterization, and availability. Substantial limitations still plague the use of primate ES cells, such as their required growth on feeder layers, poor cloning efficiency, and restricted availability. The ability to produce homogenous populations of both undifferentiated as well as differentiated phenotypes is an important challenge, and genetic approaches to achieving these objectives are discussed. Finally, safety, efficiency, and feasibility issues relating to the transplantation of ES-derived cells are considered.

  20. 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.

  1. Human immunodeficiency virus type 1 infection of neural xenografts.

    PubMed Central

    Cvetkovich, T A; Lazar, E; Blumberg, B M; Saito, Y; Eskin, T A; Reichman, R; Baram, D A; del Cerro, C; Gendelman, H E; del Cerro, M

    1992-01-01

    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. Images PMID:1594627

  2. 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.

  3. Immunohistochemical demonstration of epidermal growth factor in human gastric cancer xenografts of nude mice.

    PubMed

    Yoshiyuki, T; Shimizu, Y; Onda, M; Tokunaga, A; Kiyama, T; Nishi, K; Mizutani, T; Matsukura, N; Tanaka, N; Akimoto, M

    1990-02-15

    Thirty-two surgical specimens and three cell lines of human gastric cancers were used for subcutaneous transplantation into nude mice, resulting in the establishment of eight (25%) xenografts from the surgical specimens and two (67%) from the cell lines. The localization of epidermal growth factor (EGF) in the surgical specimens and cell lines of the gastric cancers and their xenografts in nude mice was then investigated immunohistochemically. Epidermal growth factor was stained in the cytoplasm of the cancer cells, being detected in 16 (50%) of the 32 surgical specimens and in all of the cell lines. Seven (44%) of the sixteen EGF-positive surgical specimens and one (6%) of the 16 EGF-negative ones were tumorigenic in nude mice. All of the xenografts in nude mice were positive for EGF. The tumorigenicity of human gastric cancer xenografts in nude mice may, therefore, be correlated with the presence of EGF in cancer cells.

  4. Primate photopigments and primate color vision.

    PubMed

    Jacobs, G H

    1996-01-23

    The past 15 years have brought much progress in our understanding of several basic features of primate color vision. There has been particular success in cataloging the spectral properties of the cone photopigments found in retinas of a number of primate species and in elucidating the relationship between cone opsin genes and their photopigment products. Direct studies of color vision show that there are several modal patterns of color vision among groupings of primates: (i) Old World monkeys, apes, and humans all enjoy trichromatic color vision, although the former two groups do not seem prone to the polymorphic variations in color vision that are characteristic of people; (ii) most species of New World monkeys are highly polymorphic, with individual animals having any of several types of dichromatic or trichromatic color vision; (iii) less is known about color vision in prosimians, but evidence suggests that at least some diurnal species have dichromatic color vision; and (iv) some nocturnal primates may lack color vision completely. In many cases the photopigments and photopigment gene arrangements underlying these patterns have been revealed and, as a result, hints are emerging about the evolution of color vision among the primates. PMID:8570598

  5. Primate photopigments and primate color vision.

    PubMed Central

    Jacobs, G H

    1996-01-01

    The past 15 years have brought much progress in our understanding of several basic features of primate color vision. There has been particular success in cataloging the spectral properties of the cone photopigments found in retinas of a number of primate species and in elucidating the relationship between cone opsin genes and their photopigment products. Direct studies of color vision show that there are several modal patterns of color vision among groupings of primates: (i) Old World monkeys, apes, and humans all enjoy trichromatic color vision, although the former two groups do not seem prone to the polymorphic variations in color vision that are characteristic of people; (ii) most species of New World monkeys are highly polymorphic, with individual animals having any of several types of dichromatic or trichromatic color vision; (iii) less is known about color vision in prosimians, but evidence suggests that at least some diurnal species have dichromatic color vision; and (iv) some nocturnal primates may lack color vision completely. In many cases the photopigments and photopigment gene arrangements underlying these patterns have been revealed and, as a result, hints are emerging about the evolution of color vision among the primates. PMID:8570598

  6. 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…

  7. Raptors and primate evolution.

    PubMed

    McGraw, W Scott; Berger, Lee R

    2013-01-01

    Most scholars agree that avoiding predators is a central concern of lemurs, monkeys, and apes. However, given uncertainties about the frequency with which primates actually become prey, the selective importance of predation in primate evolution continues to be debated. Some argue that primates are often killed by predators, while others maintain that such events are relatively rare. Some authors have contended that predation's influence on primate sociality has been trivial; others counter that predation need not occur often to be a powerful selective force. Given the challenges of documenting events that can be ephemeral and irregular, we are unlikely ever to amass the volume of systematic, comparative data we have on such topics as feeding, social dynamics, or locomotor behavior. Nevertheless, a steady accumulation of field observations, insight gained from natural experiments, and novel taphonomic analyses have enhanced understanding of how primates interact with several predators, especially raptors, the subject of this review. PMID:24347501

  8. Genetically Engineered Cancer Models, But Not Xenografts, Faithfully Predict Anticancer Drug Exposure in Melanoma Tumors

    PubMed Central

    Combest, Austin J.; Roberts, Patrick J.; Dillon, Patrick M.; Sandison, Katie; Hanna, Suzan K.; Ross, Charlene; Habibi, Sohrab; Zamboni, Beth; Müller, Markus; Brunner, Martin; Sharpless, Norman E.

    2012-01-01

    Background. Rodent studies are a vital step in the development of novel anticancer therapeutics and are used in pharmacokinetic (PK), toxicology, and efficacy studies. Traditionally, anticancer drug development has relied on xenograft implantation of human cancer cell lines in immunocompromised mice for efficacy screening of a candidate compound. The usefulness of xenograft models for efficacy testing, however, has been questioned, whereas genetically engineered mouse models (GEMMs) and orthotopic syngeneic transplants (OSTs) may offer some advantages for efficacy assessment. A critical factor influencing the predictability of rodent tumor models is drug PKs, but a comprehensive comparison of plasma and tumor PK parameters among xenograft models, OSTs, GEMMs, and human patients has not been performed. Methods. In this work, we evaluated the plasma and tumor dispositions of an antimelanoma agent, carboplatin, in patients with cutaneous melanoma compared with four different murine melanoma models (one GEMM, one human cell line xenograft, and two OSTs). Results. Using microdialysis to sample carboplatin tumor disposition, we found that OSTs and xenografts were poor predictors of drug exposure in human tumors, whereas the GEMM model exhibited PK parameters similar to those seen in human tumors. Conclusions. The tumor PKs of carboplatin in a GEMM of melanoma more closely resembles the tumor disposition in patients with melanoma than transplanted tumor models. GEMMs show promise in becoming an improved prediction model for intratumoral PKs and response in patients with solid tumors. PMID:22993143

  9. 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.

  10. Depletion of Mouse Cells from Human Tumor Xenografts Significantly Improves Downstream Analysis of Target Cells.

    PubMed

    Agorku, David J; Tomiuk, Stefan; Klingner, Kerstin; Wild, Stefan; Rüberg, Silvia; Zatrieb, Lisa; Bosio, Andreas; Schueler, Julia; Hardt, Olaf

    2016-01-01

    The use of in vitro cell line models for cancer research has been a useful tool. However, it has been shown that these models fail to reliably mimic patient tumors in different assays(1). Human tumor xenografts represent the gold standard with respect to tumor biology, drug discovery, and metastasis research (2-4). Tumor xenografts can be derived from different types of material like tumor cell lines, tumor tissue from primary patient tumors(4) or serially transplanted tumors. When propagated in vivo, xenografted tissue is infiltrated and vascularized by cells of mouse origin. Multiple factors such as the tumor entity, the origin of xenografted material, growth rate and region of transplantation influence the composition and the amount of mouse cells present in tumor xenografts. However, even when these factors are kept constant, the degree of mouse cell contamination is highly variable. Contaminating mouse cells significantly impair downstream analyses of human tumor xenografts. As mouse fibroblasts show high plating efficacies and proliferation rates, they tend to overgrow cultures of human tumor cells, especially slowly proliferating subpopulations. Mouse cell derived DNA, mRNA, and protein components can bias downstream gene expression analysis, next-generation sequencing, as well as proteome analysis (5). To overcome these limitations, we have developed a fast and easy method to isolate untouched human tumor cells from xenografted tumor tissue. This procedure is based on the comprehensive depletion of cells of mouse origin by combining automated tissue dissociation with the benchtop tissue dissociator and magnetic cell sorting. Here, we demonstrate that human target cells can be can be obtained with purities higher than 96% within less than 20 min independent of the tumor type. PMID:27501218

  11. Pancreatic islet transplantation in cynomolgus monkeys. Initial studies and evidence that cyclosporine impairs glucose tolerance in normal monkeys.

    PubMed

    Stegall, M D; Chabot, J; Weber, C; Reemtsma, K; Hardy, M A

    1989-12-01

    Using a model of streptozotocin-induced, ketosis-prone, insulin-dependent diabetes mellitus (IDDM) in the cynomolgus monkey, we performed 11 intraportal transplants of collagenase-digested, Ficoll-purified pancreatic islets (9 ABO-compatible allografts and 2 concordant baboon xenografts). Islets were pretreated with ultraviolet-B irradiation and recipients received cyclosporine A immunosuppression. Two grafts never functioned, five grafts showed evidence of partial function, and four grafts (three allografts and one xenograft) showed evidence of good function, with the animals independent of exogenous insulin with morning fasting blood glucose levels less than 200 mg/dl. Because two grafts functioned only after CsA was either tapered or discontinued, we performed a related study that showed that therapeutic doses of CsA (morning trough serum level 150-250 ng/ml) impaired intravenous glucose tolerance tests (IVGTT) of normal monkeys and may contributed to graft dysfunction in our islet transplantation model. The results show that there is a decrease in release of serum insulin during an IVGTT leading to impairment of glucose utilization, while serum glucagon remains unaffected. After cessation of CsA, the IVGTT did not return to normal for 28 days. Oral glucose tolerance tests were unaffected in CsA-treated monkeys. These initial studies show that the streptozotocin-diabetic monkey is a valuable model to study IDDM and islet transplantation in nonhuman primates. We also confirm studies in rodents, dogs, and sheep by showing that CsA partially inhibits beta cell function in normal monkeys.

  12. Establishment of Patient-Derived Xenograft (PDX) Models of Human Breast Cancer.

    PubMed

    Zhang, Xiaomei; Lewis, Michael T

    2013-03-01

    Patient-derived xenograft (PDX) models of human breast cancer are proving useful for preclinical evaluation of experimental therapeutics. However, until recently, generation of PDX models reflecting the full spectrum of human breast cancers has been an elusive goal. We recently developed a method for establishing serially transplantable, phenotypically stable, human breast cancer xenograft models in immunocompromised mice with comparatively high efficiency (overall ∼25%). These xenografts represent the major clinically defined subtypes of breast cancer [e.g. estrogen receptor positive (ER+), HER2 positive (HER2+), and "triple negative" (TN) breast cancers]. This method, and methods being developed in other laboratories, may soon allow for conducting "animal clinical trials" once sufficient numbers of clinically relevant models are generated. Curr. Protoc. Mouse Biol. 3:21-29 © 2013 by John Wiley & Sons, Inc.

  13. 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 ...

  14. 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

  15. 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 ...

  16. 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)

  17. [Effects of baicalin on HL-60 cell xenografts in nude mice and its mechanism].

    PubMed

    Zheng, Jing; Hu, Jian-Da; Huang, Yi; Chen, Ying-Yu; Li, Jing; Chen, Bu-Yuan

    2012-10-01

    This study was aimed to investigate the effects of baicalin on HL-60 cell xenografts in nude mice in vivo and explore its mechanism. Xenograft tumor model of HL-60 cells in nude mice was established, which was divided randomly into 6 groups: negative control group (injection of 5% NaHCO(3)), 25, 50 and 100 mg/kg baicalin groups, combination group (50 mg/kg baicalin + 2 mg/kg VP16) and positive control group (VP16 4 mg/kg). The nude mice with HL-60 cell xenografts were treated with drugs via intraperitoneal injection daily. After treatment for 14 days average weigh and inhibitory rate of transplanted tumor stripped from 5 nude mice in each group were calculated, and the ultrastructure change of xenografts cells were tested by transmission electron microscopy. Histopathologic examination was used to observed the change of main organs in nude mice. The expression of signaling molecular PI3K/Akt proteins extracted from xenografts was detected by Western blot. The effects of baicalin on overall survival time in nude mice with HL-60 cell xenografts were evaluated. The results showed that baicalin could inhibit the growth of transplanted tumors in dose-dependent manner. There were more necrotic and apoptotic cells in mice of baicalin-treated groups and combination group than that in mice of negative control group. Baicalin could inhibit the proliferation of HL-60 cells in vivo by down-regulating the PI3K/Akt/mTOR signal pathway, where the expressions of p-Akt, mTOR and p-mTOR proteins decreased compared with negative control group, and no significant difference of Akt expression was found between different groups. Compared with negative control group, the median survival time of mice in combination group was more prolongated (P < 0.05). It is concluded that baicalin can inhibit growth and induce apoptosis of HL-60 cell xenografts in nude mice, and prolong median survival time of nude mice. The possible mechanisms may be related to inhibition of Akt activity and down

  18. Hypoxia-regulated gene expression explains differences between melanoma cell line-derived xenografts and patient-derived xenografts

    PubMed Central

    Bhadury, Joydeep; Einarsdottir, Berglind O.; Podraza, Agnieszka; Bagge, Roger Olofsson; Stierner, Ulrika; Ny, Lars; López, Marcela Dávila; Nilsson, Jonas A.

    2016-01-01

    Cell line-derived xenografts (CDXs) are an integral part of drug efficacy testing during development of new pharmaceuticals against cancer but their accuracy in predicting clinical responses in patients have been debated. Patient-derived xenografts (PDXs) are thought to be more useful for predictive biomarker identification for targeted therapies, including in metastatic melanoma, due to their similarities to human disease. Here, tumor biopsies from fifteen patients and ten widely-used melanoma cell lines were transplanted into immunocompromised mice to generate PDXs and CDXs, respectively. Gene expression profiles generated from the tumors of these PDXs and CDXs clustered into distinct groups, despite similar mutational signatures. Hypoxia-induced gene signatures and overexpression of the hypoxia-regulated miRNA hsa-miR-210 characterized CDXs. Inhibition of hsa-miR-210 with decoys had little phenotypic effect in vitro but reduced sensitivity to MEK1/2 inhibition in vivo, suggesting down-regulation of this miRNA could result in development of resistance to MEK inhibitors. PMID:27009863

  19. Preventing T cell rejection of pig xenografts.

    PubMed

    Higginbotham, Laura; Ford, Mandy L; Newell, Kenneth A; Adams, Andrew B

    2015-11-01

    Xenotransplantation is a potential solution to the limited supply of donor organs. While early barriers to xenograft acceptance, such as hyperacute rejection, are now largely avoided through genetic engineering, the next frontier in successful xenograft survival will require prevention of T cell-mediated rejection. Most successful immunosuppressive regimens in xenotransplantation utilize T cell depletion with antibody therapy. Additionally, the use of T cell costimulatory blockade - specifically blockade of the CD40-CD154 pathway - shows promise with several reports of long-term xenograft survival. Additional therapies, such as transgenic expression of T cell coinhibitory molecules or transfer of immunomodulatory cells to promote tolerance, may be necessary to achieve reliable long-term xenograft acceptance. Further studies in pre-clinical models are essential in order to optimize these regimens prior to trials in patients.

  20. 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 - ...

  1. 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

  2. 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.

  3. Patient-derived orthotopic xenografts: better mimic of metastasis than subcutaneous xenografts.

    PubMed

    Hoffman, Robert M

    2015-08-01

    The majority of human solid tumours do not metastasize when grown subcutaneously in immunocompromised mice; this includes patient-derived xenograft (PDX) models. However, orthotopic implantation of intact tumour tissue can lead to metastasis that mimics that seen in patients. These patient-derived orthotopic xenograft (PDOX) models have a long history and might better recapitulate human tumours than PDX models.

  4. 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

  5. Kidney transplant

    MedlinePlus

    Renal transplant; Transplant - kidney ... Barry JM, Conlin MJ. In: Renal transplantation. Wein AJ, ed. Campbell-Walsh Urology . 10th ed. Philadelphia, PA: Elsevier Saunders; 2011:chap 44. Kidney Disease: Improving Global Outcomes ( ...

  6. 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

  7. Bone graft substitute: allograft and xenograft.

    PubMed

    Shibuya, Naohiro; Jupiter, Daniel C

    2015-01-01

    Rapid bone graft incorporation for structural rigidity is essential. Early range of motion, exercise, and weight-bearing are keys to rehabilitation. Structural and nonstructural bone grafts add length, height, and volume to alter alignment, function, and appearance. Bone graft types include: corticocancellous autograft, allograft, xenograft, and synthetic graft. Autogenic grafts are harvested from the patient, less likely to be rejected, and more likely to be incorporated; however, harvesting adds a procedure and donor site complication is common. Allografts, xenografts, and synthetic grafts eliminate secondary procedures and donor site complications; however, rejection and slower incorporation can occur.

  8. Modeling of Chronic Myeloid Leukemia: An Overview of In Vivo Murine and Human Xenograft Models.

    PubMed

    Sontakke, Pallavi; Jaques, Jenny; Vellenga, Edo; Schuringa, Jan Jacob

    2016-01-01

    Over the past years, a wide variety of in vivo mouse models have been generated in order to unravel the molecular pathology of Chronic Myeloid Leukemia (CML) and to develop and improve therapeutic approaches. These models range from (conditional) transgenic models, knock-in models, and murine bone marrow retroviral transduction models followed by transplantation. With the advancement of immunodeficient xenograft models, it has become possible to use human stem/progenitor cells for in vivo studies as well as cells directly derived from CML patients. These models not only mimic CML but also have been instrumental in uncovering various fundamental mechanisms of CML disease progression and tyrosine kinase inhibitor (TKI) resistance. With the availability of iPSC technology, it has become feasible to derive, maintain, and expand CML subclones that are at least genetically identical to those in patients. The following review provides an overview of all murine as well as human xenograft models for CML established till date. PMID:27642303

  9. Modeling of Chronic Myeloid Leukemia: An Overview of In Vivo Murine and Human Xenograft Models

    PubMed Central

    Vellenga, Edo

    2016-01-01

    Over the past years, a wide variety of in vivo mouse models have been generated in order to unravel the molecular pathology of Chronic Myeloid Leukemia (CML) and to develop and improve therapeutic approaches. These models range from (conditional) transgenic models, knock-in models, and murine bone marrow retroviral transduction models followed by transplantation. With the advancement of immunodeficient xenograft models, it has become possible to use human stem/progenitor cells for in vivo studies as well as cells directly derived from CML patients. These models not only mimic CML but also have been instrumental in uncovering various fundamental mechanisms of CML disease progression and tyrosine kinase inhibitor (TKI) resistance. With the availability of iPSC technology, it has become feasible to derive, maintain, and expand CML subclones that are at least genetically identical to those in patients. The following review provides an overview of all murine as well as human xenograft models for CML established till date.

  10. Modeling of Chronic Myeloid Leukemia: An Overview of In Vivo Murine and Human Xenograft Models

    PubMed Central

    Vellenga, Edo

    2016-01-01

    Over the past years, a wide variety of in vivo mouse models have been generated in order to unravel the molecular pathology of Chronic Myeloid Leukemia (CML) and to develop and improve therapeutic approaches. These models range from (conditional) transgenic models, knock-in models, and murine bone marrow retroviral transduction models followed by transplantation. With the advancement of immunodeficient xenograft models, it has become possible to use human stem/progenitor cells for in vivo studies as well as cells directly derived from CML patients. These models not only mimic CML but also have been instrumental in uncovering various fundamental mechanisms of CML disease progression and tyrosine kinase inhibitor (TKI) resistance. With the availability of iPSC technology, it has become feasible to derive, maintain, and expand CML subclones that are at least genetically identical to those in patients. The following review provides an overview of all murine as well as human xenograft models for CML established till date. PMID:27642303

  11. Lymphoid neogenesis in skin of human hand, nonhuman primate, and rat vascularized composite allografts.

    PubMed

    Hautz, Theresa; Zelger, Bettina G; Nasr, Isam W; Mundinger, Gerhard S; Barth, Rolf N; Rodriguez, Eduardo D; Brandacher, Gerald; Weissenbacher, Annemarie; Zelger, Bernhard; Cavadas, Pedro; Margreiter, Raimund; Lee, W P Andrew; Pratschke, Johann; Lakkis, Fadi G; Schneeberger, Stefan

    2014-09-01

    The mechanisms of skin rejection in vascularized composite allotransplantation (VCA) remain incompletely understood. The formation of tertiary lymphoid organs (TLO) in hand transplantation has been recently described. We assess this phenomenon in experimental and clinical VCA rejection. Skin biopsies of human (n = 187), nonhuman primate (n = 11), and rat (n = 15) VCAs were analyzed for presence of TLO. A comprehensive immunohistochemical assessment (characterization of the cell infiltrate, expression of adhesion molecules) including staining for peripheral node addressin (PNAd) was performed and correlated with rejection and time post-transplantation. TLO were identified in human, nonhuman primate, and rat skin samples. Expression of PNAd was increased in the endothelium of vessels upon rejection in human skin (P = 0.003) and correlated with B- and T-lymphocyte numbers and LFA-1 expression. PNAd expression was observed at all time-points after transplantation and increased significantly after year 5. In nonhuman primate skin, PNAd expression was found during inflammatory conditions early and late after transplantation. In rat skin, PNAd expression was strongly associated with acute rejection and time post-transplantation. Lymphoid neogenesis and TLO formation can be uniformly found in experimental and human VCA. PNAd expression in vascular endothelium correlates with skin rejection and T- and B-cell infiltration.

  12. 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

  13. 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.

  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. 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.

  16. Captivity humanizes the primate microbiome

    PubMed Central

    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

    2016-01-01

    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

  17. 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

  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.

  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.

  20. A Novel Chordoma Xenograft Allows In Vivo Drug Testing and Reveals the Importance of NF-κB Signaling in Chordoma Biology

    PubMed Central

    Trucco, Matteo M.; Awad, Ola; Wilky, Breelyn A.; Goldstein, Seth D.; Huang, Ruili; Walker, Robert L.; Shah, Preeti; Katuri, Varalakshmi; Gul, Naheed; Zhu, Yuelin J.; McCarthy, Edward F.; Paz-Priel, Ido; Meltzer, Paul S.; Austin, Christopher P.; Xia, Menghang; Loeb, David M.

    2013-01-01

    Chordoma is a rare primary bone malignancy that arises in the skull base, spine and sacrum and originates from remnants of the notochord. These tumors are typically resistant to conventional chemotherapy, and to date there are no FDA-approved agents to treat chordoma. The lack of in vivo models of chordoma has impeded the development of new therapies for this tumor. Primary tumor from a sacral chordoma was xenografted into NOD/SCID/IL-2R γ-null mice. The xenograft is serially transplantable and was characterized by both gene expression analysis and whole genome SNP genotyping. The NIH Chemical Genomics Center performed high-throughput screening of 2,816 compounds using two established chordoma cell lines, U-CH1 and U-CH2B. The screen yielded several compounds that showed activity and two, sunitinib and bortezomib, were tested in the xenograft. Both agents slowed the growth of the xenograft tumor. Sensitivity to an inhibitor of IκB, as well as inhibition of an NF-κB gene expression signature demonstrated the importance of NF-κB signaling for chordoma growth. This serially transplantable chordoma xenograft is thus a practical model to study chordomas and perform in vivo preclinical drug testing. PMID:24223206

  1. Transplant services

    MedlinePlus

    ... diseased body part with a healthy one. SOLID ORGAN TRANSPLANTS Auto islet cell transplant is done after a ... selected experts, including: Surgeons who specialize in performing ... doctors Radiologists and medical imaging technologists Nurses ...

  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. 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

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

    PubMed Central

    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.

    2014-01-01

    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-Rag1null IL2rγnull 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

  5. 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

  6. Cardiac transplantation.

    PubMed

    Shanewise, Jack

    2004-12-01

    Cardiac transplantation is a proven, accepted mode of therapy for selected patients with end-stage heart failure, but the inadequate number of suitable donor hearts available ultimately limits its application. This chapter reviews adult cardiac transplantation, with an emphasis on the anesthetic considerations of the heart transplant operation itself.

  7. Hepatocyte innervation in primates

    PubMed Central

    1977-01-01

    The efferent innervation and some characteristics of nerve fibers of the liver lobule in the tree shrew, a primate, are described. Nerve endings on hepatocytes were encountered regularly and were determined to be efferent adrenergic nerves. Transmission electron microscopy revealed nerve endings and varicosities in close apposition to the hepatocytes adjacent to the connective tissue of the triads as well as within the liver lobule in the space of Disse. Fluorescence microscopy indicated the existence of adrenergic nerves with a similar distribution. Autoradiography of the avid uptake of exogenous [3H]norepinephrine indicated that all intralobular nerves are potentially norepinephrinergic (adrenergic). Chemical sympathectomy with 6-OH-dopamine resulted in the degeneration of all intralobular liver nerve fibers as revealed by fluorescence microscopy and electron microscopy. Substantial regeneration occurred after 60-90 days but was not completed by that time. Some nerves were also observed in close association with von Kupffer cells and endothelial cells. The functional significance of the efferent liver innervation is discussed. PMID:406265

  8. 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

  9. A simple PCR-based strategy for estimating species-specific contributions in chimeras and xenografts

    PubMed Central

    Ealba, Erin L.; Schneider, Richard A.

    2013-01-01

    Many tissue-engineering approaches for repair and regeneration involve transplants between species. Yet a challenge is distinguishing donor versus host effects on gene expression. This study provides a simple molecular strategy to quantify species-specific contributions in chimeras and xenografts. Species-specific primers for reverse transcription quantitative real-time PCR (RT-qPCR) were designed by identifying silent mutations in quail, duck, chicken, mouse and human ribosomal protein L19 (RPL19). cDNA from different pairs of species was mixed in a dilution series and species-specific RPL19 primers were used to generate standard curves. Then quail cells were transplanted into transgenic-GFP chick and resulting chimeras were analyzed with species-specific primers. Fluorescence-activated cell sorting (FACS) confirmed that donor- and host-specific levels of RPL19 expression represent actual proportions of cells. To apply the RPL19 strategy, we measured Runx2 expression in quail-duck chimeras. Elevated Runx2 levels correlated with higher percentages of donor cells. Finally, RPL19 primers also discriminated mouse from human and chick. Thus, this strategy enables chimeras and/or xenografts to be screened rapidly at the molecular level. PMID:23785056

  10. Orthotopic xenografts of RCC retain histological, immunophenotypic and genetic features of tumors in patients

    PubMed Central

    Grisanzio, Chiara; Seeley, Apryle; Chang, Michelle; Collins, Michael; Di Napoli, Arianna; Cheng, Su-Chun; Percy, Andrew; Beroukhim, Rameen; Signoretti, Sabina

    2013-01-01

    Renal cell carcinoma (RCC) is an aggressive malignancy with limited responsiveness to existing treatments. In vivo models of human cancer, including RCC, are critical for developing more effective therapies. Unfortunately, current RCC models do not accurately represent relevant properties of the human disease. The goal of this study was to develop clinically relevant animal models of RCC for preclinical investigations. We transplanted intact human tumor tissue fragments orthotopically in immunodeficient mice. The xenografts were validated by comparing the morphologic, phenotypic, and genetic characteristics of the kidney tumor tissues before and after implantation. Twenty kidney tumors were transplanted into mice. Successful tumor growth was detected in 19 cases (95%). The histopathologic and immunophenotypic features of the xenografts and those of the original tumors largely overlapped in all the cases. Evaluation of genetic alterations in a subset of 10 cases demonstrated that the grafts largely retained the genetic features of the pre-implantation RCC tissues. Indeed, primary tumors and corresponding grafts displayed identical VHL mutations. Moreover, an identical pattern of DNA copy amplification or loss was observed in 6 of 10 cases (60%). In summary, orthotopic engrafting of RCC tissue fragments can be successfully used to generate animal models that closely resemble RCC in patients. These models will be invaluable for in vivo preclinical drug testing, and for deeper understanding of kidney carcinogenesis. PMID:21710693

  11. 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.

  12. Hair transplantation.

    PubMed

    Al-Khair, Y M

    2000-09-01

    Hair transplantation is a technique in which hair follicles are harvested from the occipital area and re-transplanted in the frontal bald area. Hair transplantation is the most common cosmetic procedure in the United States nowadays despite the fact that it is expensive. Usually, patients need more than one session to receive a cosmetically acceptable result and patients need to be understanding and have realistic expectations. Although most of our patients are males, females represent about 10-15% of our new patients. This article reviews the basic principals of hair transplantation and describes new and improved techniques of hair transplantation. PMID:11376357

  13. Simultaneous transplantation.

    PubMed

    Sala, P

    1993-01-01

    1. Thoracic organ transplantation requires extensive preparation with little advance notice. 2. A single organ transplant requires a team of various staff members, and may include one or two circulating nurses, two scrub technologists or nurses, one perfusionist, one surgeon's assistant, two surgeons, and one anesthesiologist. 3. Timing is important in organ transplantation because thoracic organs ideally should be transplanted within four hours after cross-clamping the aorta of the donor. 4. The dedication, expertise, and thorough follow-up care provided by transplant surgeons, nurse transplant coordinators, organ procurement coordinators, and the CICU and coronary care nurses/departments directly relate to the success of a thoracic organ transplant program. PMID:8493710

  14. Inhibition of erythropoietin signalling destroys xenografts of ovarian and uterine cancers in nude mice

    PubMed Central

    Yasuda, Y; Musha, T; Tanaka, H; Fujita, Y; Fujita, H; Utsumi, H; Matsuo, T; Masuda, S; Nagao, M; Sasaki, R; Nakamura, Y

    2001-01-01

    We have recently shown that malignant tumours from the ovary and uterus expressed erythropoietin (Epo) and its receptor (EpoR), and that deprivation of Epo signal in tumour blocks induced death of malignant cells and capillary endothelial cells in vitro (Yasuda et al, submitted). These in vitro results prompted us to examine the effect of Epo-signal withdrawal on tumours in vivo. RT-PCR analysis demonstrated the expression of mRNAs for Epo and EpoR in the transplants of uterine and ovarian tumours in nude mice. Then we injected locally anti-Epo antibody or soluble form of EpoR into the transplants. At 12 h, 1, 7 or 14 days after the injection, all transplants were resected and examined macro- and microscopically. Tumour size was reduced in Epo signal-deprived transplants. Immunohistochemical examinations revealed destruction of Epo-responding malignant and capillary endothelial cells through apoptotic death. The degree of tumour regression correlated well with the dose and frequency of the injections. Control xenografts with saline injection or needle insertion showed well-developed tumour masses. This Epo response pathway will have profound implications for our understanding of the development and progression of malignant tumours and for the use of Epo-signal deprivation as an effective therapy. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11259101

  15. The malignant primate?

    PubMed

    de Grouchy, J

    1991-01-01

    Speciation and carcinogenesis result from genomic instability at the gametic or at the somatic levels. After an infinity of trials they occur, by chromosome rearrangements, in single individuals or in single cells and evolve by similar chromosomal or clonal evolutions. Loss of heterozygosity for the first event is essential in both processes: in evolution, a chromosomal rearrangement, a pericentric inversion or a Robertsonian fusion, must become homozygous to ensure a reproductive barrier for a new species; Knudson's two-event sequence is a similar situation in cancer. Position effect is equally important: we have shown overexpression of the SOD1 gene in the orangutan phylum probably by an intrachromosomal rearrangement; the t(9;22) in CML acts by typical position effect. Parental imprinting underlies the evolution of genome function and the unset of certain cancers. Evolution and malignancy are interweaved by viruses and oncogenes since the dawn of life. Cancer uses its intelligence to expand and to destroy the other tissues, using subtle metabolic pathways and a variety of tricks to metastasize other cells. It always wins but saws the branch on which it sits. Mankind also grows exponentially, killing thousands of other species, poisoning the oceans and soft waters, polluting the atmosphere, all for his egoistic needs. Man also travels and metastasizes other Earths. He modifies his genome or that of other species, and develops new technologies for his reproduction. He can destroy the planet in an eyeblink. To be or not to be the malignant primate, that will be the dilemma for the 21st Century. PMID:1809219

  16. 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

  17. 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

  18. 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

  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.

  20. Assessing anxiety in nonhuman primates.

    PubMed

    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.

  1. Enrichment and aggression in primates.

    PubMed

    Honess, P E; Marin, C M

    2006-01-01

    There is considerable evidence that primates housed under impoverished conditions develop behavioural abnormalities, including, in the most extreme example, self-harming behaviour. This has implications for all contexts in which primates are maintained in captivity from laboratories to zoos since by compromising the animals' psychological well-being and allowing them to develop behavioural abnormalities their value as appropriate educational and research models is diminished. This review examines the extensive body of literature documenting attempts to improve living conditions with a view to correcting behavioural abnormalities and housing primates in such a way that they are encouraged to exhibit a more natural range and proportion of behaviours, including less self-directed and social aggression. The results of housing, feeding, physical, sensory and social enrichment efforts are examined with specific focus on their effect on aggressive behaviour and variation in their use and efficacy. It is concluded that while inappropriate or poorly distributed enrichment may encourage aggressive competition, enrichment that is species, sex, age and background appropriate can dramatically reduce aggression, can eliminate abnormal behaviour and substantially improve the welfare of primates maintained in captivity.

  2. 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

  3. Neuroethology of primate social behavior.

    PubMed

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

    2013-06-18

    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.

  4. Organ Transplantation

    MedlinePlus

    ... 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 life to help keep your body from rejecting the new organ.

  5. 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. ...

  6. 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 ...

  7. 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.

  8. 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

  9. Underground hibernation in a primate.

    PubMed

    Blanco, Marina B; Dausmann, Kathrin H; Ranaivoarisoa, Jean F; Yoder, Anne D

    2013-01-01

    Hibernation in mammals is a remarkable state of heterothermy wherein metabolic rates are reduced, core body temperatures reach ambient levels, and key physiological functions are suspended. Typically, hibernation is observed in cold-adapted mammals, though it has also been documented in tropical species and even primates, such as the dwarf lemurs of Madagascar. Western fat-tailed dwarf lemurs are known to hibernate for seven months per year inside tree holes. Here, we report for the first time the observation that eastern dwarf lemurs also hibernate, though in self-made underground hibernacula. Hence, we show evidence that a clawless primate is able to bury itself below ground. Our findings that dwarf lemurs can hibernate underground in tropical forests draw unforeseen parallels to mammalian temperate hibernation. We expect that this work will illuminate fundamental information about the influence of temperature, resource limitation and use of insulated hibernacula on the evolution of hibernation.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. Serendipitous insights involving nonhuman primates.

    PubMed

    Morton, William R; Swindler, Kathryn

    2005-01-01

    Serendipity is discussed as a form of controlled chaos, a phenomenon in a class with synchronicity and other actions affecting research in terms of theory versus observation (e.g., "optional stopping"). Serendipity is a fundamental aspect of basic research, a profitable and normal outcome in the context of "informed observation." The serendipitous finding fits into the following pattern: it is unanticipated, anomalous, and strategic. All observations that have meaning must fit into some context in the observer's mind or suggest a revolutionary new context. It is critically important to maintain access to the resources provided by established primate centers and similar laboratories to capitalize in a timely way on serendipitous findings and to benefit from valuable discoveries made in more directly targeted development investments. Examples are given of serendipitous insights gained in experimentation and observation relative to nonhuman primate research, including both broad and narrow topics. Genomics, which uses comparison-based strategies and capitalizes on the DNA sequences of genetic information, presents what might seem the basis for endless serendipity because nonhuman primates are likely to share most genes present in the human genome. Other topics discussed include infant behavior, birth periodicity, leprosy, cystic fibrosis, environmental enrichment, endocrinology, drug development, and the rapidly expanding study of infectious diseases and pathogen-based bioterrorism. PMID:16179742

  15. 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

  16. The Zebrafish Xenograft Platform: Evolution of a Novel Cancer Model and Preclinical Screening Tool.

    PubMed

    Wertman, Jaime; Veinotte, Chansey J; Dellaire, Graham; Berman, Jason N

    2016-01-01

    Animal xenografts of human cancers represent a key preclinical tool in the field of cancer research. While mouse xenografts have long been the gold standard, investigators have begun to use zebrafish (Danio rerio) xenotransplantation as a relatively rapid, robust and cost-effective in vivo model of human cancers. There are several important methodological considerations in the design of an informative and efficient zebrafish xenotransplantation experiment. Various transgenic fish strains have been created that facilitate microscopic observation, ranging from the completely transparent casper fish to the Tg(fli1:eGFP) fish that expresses fluorescent GFP protein in its vascular tissue. While human cancer cell lines have been used extensively in zebrafish xenotransplantation studies, several reports have also used primary patient samples as the donor material. The zebrafish is ideally suited for transplanting primary patient material by virtue of the relatively low number of cells required for each embryo (between 50 and 300 cells), the absence of an adaptive immune system in the early zebrafish embryo, and the short experimental timeframe (5-7 days). Following xenotransplantation into the fish, cells can be tracked using in vivo or ex vivo measures of cell proliferation and migration, facilitated by fluorescence or human-specific protein expression. Importantly, assays have been developed that allow for the reliable detection of in vivo human cancer cell growth or inhibition following administration of drugs of interest. The zebrafish xenotransplantation model is a unique and effective tool for the study of cancer cell biology.

  17. 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

  18. 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

  19. The Zebrafish Xenograft Platform: Evolution of a Novel Cancer Model and Preclinical Screening Tool.

    PubMed

    Wertman, Jaime; Veinotte, Chansey J; Dellaire, Graham; Berman, Jason N

    2016-01-01

    Animal xenografts of human cancers represent a key preclinical tool in the field of cancer research. While mouse xenografts have long been the gold standard, investigators have begun to use zebrafish (Danio rerio) xenotransplantation as a relatively rapid, robust and cost-effective in vivo model of human cancers. There are several important methodological considerations in the design of an informative and efficient zebrafish xenotransplantation experiment. Various transgenic fish strains have been created that facilitate microscopic observation, ranging from the completely transparent casper fish to the Tg(fli1:eGFP) fish that expresses fluorescent GFP protein in its vascular tissue. While human cancer cell lines have been used extensively in zebrafish xenotransplantation studies, several reports have also used primary patient samples as the donor material. The zebrafish is ideally suited for transplanting primary patient material by virtue of the relatively low number of cells required for each embryo (between 50 and 300 cells), the absence of an adaptive immune system in the early zebrafish embryo, and the short experimental timeframe (5-7 days). Following xenotransplantation into the fish, cells can be tracked using in vivo or ex vivo measures of cell proliferation and migration, facilitated by fluorescence or human-specific protein expression. Importantly, assays have been developed that allow for the reliable detection of in vivo human cancer cell growth or inhibition following administration of drugs of interest. The zebrafish xenotransplantation model is a unique and effective tool for the study of cancer cell biology. PMID:27165359

  20. Establishment of patient-derived cancer xenografts in immunodeficient NOG mice.

    PubMed

    Chijiwa, Tsuyoshi; Kawai, Kenji; Noguchi, Akira; Sato, Hidemitsu; Hayashi, Akimune; Cho, Haruhiko; Shiozawa, Manabu; Kishida, Takeshi; Morinaga, Soichiro; Yokose, Tomoyuki; Katayama, Makoto; Takenaka, Nobuo; Suemizu, Hiroshi; Yamada, Roppei; Nakamura, Yoshiyasu; Ohtsu, Takashi; Takano, Yasuo; Imai, Kohzoh; Miyagi, Yohei; Nakamura, Masato

    2015-07-01

    Viable and stable human cancer cell lines and animal models combined with adequate clinical information are essential for future advances in cancer research and patient care. Conventional in vitro cancer cell lines are commonly available; however, they lack detailed information on the patient from which they originate, including disease phenotype and drug sensitivity. Patient-derived xenografts (PDX) with clinical information (so-called 'cancer xenopatients') are a promising advance that may accelerate the development of anticancer therapies. We established 61 PDX lines from 116 surgically removed tumor tissues inoculated subcutaneously into NOG mice (53% success rate). PDX lines were established from various types of epithelial tumors and also from sarcomas, including gastrointestinal stromal tumors and Ewing/PNET sarcomas. The metastatic tumors yielded PDX lines more effectively (65%) than the primary tumors (27%, P<0.001). In our PDX models, morphological characteristics, gene expression profiles, and genetic alteration patterns were all well preserved. In eight cases (7%), the transplantable xenografts for several generations were composed of large monotonous nonepithelial cells of human origin, revealed to be Epstein-Barr virus infection-associated lympho-proliferative lesions. Despite this, PDX linked with clinical information offer many advantages for preclinical studies investigating new anticancer drugs. The fast and efficient establishment of individual PDX may also contribute to future personalized anticancer therapies.

  1. 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

  2. Human polyethylene granuloma tissues inhibit bone healing in a novel xenograft animal model.

    PubMed

    Esposito, Christina I; Oliver, Rema A; Campbell, Patricia A; Yu, Yan; Walter, William L; Walter, William K; Walsh, William R

    2014-06-01

    During revision of a conventional polyethylene joint replacement, surgeons usually remove the source of osteolysis (polyethylene) but cannot always remove all of the polyethylene granuloma tissues. We developed a human/rat xenograft model to investigate the effects of polyethylene granuloma tissues on bone healing. Human osteoarthritic and periprosthetic tissues collected during primary and revision hip arthroplasty surgeries were transplanted into the distal femora of athymic nude rats. After 3 weeks in vivo, there was a significant difference in the bone volume fraction (Vf ) between empty, primary, and revision defects (p = 0.02), with a lower Vf in defects with revision granuloma tissues compared to defects with primary osteoarthritic tissues. Polyethylene granuloma tissues in trabecular bone defects inhibited bone healing. Therefore, debridement around a metal-on-polyethylene hip replacement may shorten the time it takes to achieve secondary stability around a revision hip replacement.

  3. Lung transplant

    MedlinePlus

    Solid organ transplant - lung ... the new lung Have severe disease of other organs Cannot reliably take their medicines Are unable to ... medicines Damage to your kidneys, liver, or other organs from anti-rejection medicines Future risk of certain ...

  4. Corneal transplant

    MedlinePlus

    ... transplant are: Bleeding Cataracts Infection of the eye Glaucoma (high pressure in the eye that can cause ... clot (blood thinners) for 10 days before the surgery. Some of these are aspirin, ibuprofen (Advil, Motrin), ...

  5. 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 ...

  6. Liver transplant

    MedlinePlus

    ... toxins in the blood Storing sugars, fats, iron, copper, and vitamins The most common reason for a ... cirrhosis or primary sclerosing cholangitis Metabolic disorders of copper or iron ( Wilson's disease and hemochromatosis ) Liver transplant ...

  7. Heart transplant

    MedlinePlus

    ... PA: Elsevier Saunders; 2014:chap 28. Bernstein D. Pediatric heart and heart-lung transplantation. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbook of Pediatrics . 19th ed. Philadelphia, PA: Elsevier Saunders; 2011:chap ...

  8. Antral follicles develop in xenografted cryopreserved African elephant (Loxodonta africana) ovarian tissue.

    PubMed

    Gunasena, K T; Lakey, J R; Villines, P M; Bush, M; Raath, C; Critser, E S; McGann, L E; Critser, J K

    1998-10-01

    The preservation of germ plasm from endangered species could augment captive breeding programs aimed at maintaining genetic diversity. Mammalian female germ plasm (oocytes) is extremely difficult to collect and cryopreserve; however, a promising alternative is the cryopreservation of ovarian tissue. In the present study, athymic nude (nu/nu) Balb/C mice were used to evaluate in vivo viability of cryopreserved ovarian tissue from Institute of Cancer Research genotype (ICR) mice or elephants. Female mice were ovariectomized prior to transplant of cryopreserved-thawed ovarian tissue from ICR mice (n=4) or elephants (n=6). Control mice were sham operated (n=4) or ovariectomized (n=5). Transplants were in the ovarian bursa, enabling in vivo ovulation and pregnancies from allografts. Vaginal cytology was monitored daily, and the intervals between and duration of epithelial cells present in smears were evaluated. Appearance of epithelial cells in sham-operated and allografted mice were at intervals of 4.3+/-0.6 and 3.3+/-0.5 days, lasting for 1.4+/-0.1 and 1.6+/-0.2 days, respectively. Sporadic incidence of epithelial cells in ovariectomized animals occurred at longer intervals (8.6+/-3.8 days). Females with xenografted elephant ovarian tissue demonstrated epithelial cells in vaginal smears at intervals of 4.5+/-1.0 days, for 2.5+/-0.5 days duration, which was significantly longer than the other groups (P < 0.05). Histological evaluation of tissues at the time of epithelial cells in smears demonstrated well-developed antral follicles, although oocytes were of poor morphological appearance or only cumulus-like complexes were seen. The nude mouse model is effective for assessing cryopreserved ovarian tissue xenograft function which can support the development of antral follicles.

  9. Ecology and evolution of primate colour vision.

    PubMed

    Vorobyev, Misha

    2004-07-01

    More than one hundred years ago, Grant Allen suggested that colour vision in primates, birds and insects evolved as an adaptation for foraging on colourful advertisements of plants--fruits and flowers. Recent studies have shown that well developed colour vision appeared long before fruits and flowers evolved. Thus, colour vision is generally beneficial for many animals, not only for those eating colourful food. Primates are the only placental mammals that have trichromatic colour vision. This may indicate either that trichromacy is particularly useful for primates or that primates are unique among placental mammals in their ability to utilise the signals of three spectrally distinct types of cones or both. Because fruits are an important component of the primate diet, primate trichromacy could have evolved as a specific adaptation for foraging on fruits. Alternatively, primate trichromacy could have evolved as an adaptation for many visual tasks. Comparative studies of mammalian eyes indicate that primates are the only placental mammals that have in their retina a pre-existing neural machinery capable of utilising the signals of an additional spectral type of cone. Thus, the failure of non-primate placental mammals to evolve trichromacy can be explained by constraints imposed on the wiring of retinal neurones. PMID:15312027

  10. Ecology and evolution of primate colour vision.

    PubMed

    Vorobyev, Misha

    2004-07-01

    More than one hundred years ago, Grant Allen suggested that colour vision in primates, birds and insects evolved as an adaptation for foraging on colourful advertisements of plants--fruits and flowers. Recent studies have shown that well developed colour vision appeared long before fruits and flowers evolved. Thus, colour vision is generally beneficial for many animals, not only for those eating colourful food. Primates are the only placental mammals that have trichromatic colour vision. This may indicate either that trichromacy is particularly useful for primates or that primates are unique among placental mammals in their ability to utilise the signals of three spectrally distinct types of cones or both. Because fruits are an important component of the primate diet, primate trichromacy could have evolved as a specific adaptation for foraging on fruits. Alternatively, primate trichromacy could have evolved as an adaptation for many visual tasks. Comparative studies of mammalian eyes indicate that primates are the only placental mammals that have in their retina a pre-existing neural machinery capable of utilising the signals of an additional spectral type of cone. Thus, the failure of non-primate placental mammals to evolve trichromacy can be explained by constraints imposed on the wiring of retinal neurones.

  11. 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

  12. Comprehensive analysis of leukocytes, vascularization and matrix metalloproteinases in human menstrual xenograft model.

    PubMed

    Guo, Yong; He, Bin; Xu, Xiangbo; Wang, Jiedong

    2011-02-17

    In our previous study, menstrual-like changes in mouse were provoked through the pharmacologic withdrawal of progesterone with mifepristone following induction of decidualization. However, mouse is not a natural menstruation animal, and the menstruation model using external stimuli may not truly reflect the occurrence and development of the human menstrual process. Therefore, we established a model of menstruation based on human endometrial xenotransplantation. In this model, human endometrial tissues were transplanted subcutaneously into SCID mice that were ovarectomized and supplemented with estrogen and progestogen by silastic implants with a scheme imitating the endocrinological milieu of human menstrual cycle. Morphology, hormone levels, and expression of vimentin and cytokeratin markers were evaluated to confirm the menstrual-like changes in this model. With 28 days of hormone treatment, transplanted human endometrium survived and underwent proliferation, differentiation and disintegration, similar to human endometrium in vivo. Human CD45+ cells showed a peak of increase 28 days post-transplantation. Three days after progesterone withdrawal, mouse CD45+ cells increased rapidly in number and were significantly greater than human CD45+ cell counts. Mouse CD31+ blood vascular-like structures were detected in both transplanted and host tissues. After progesterone withdrawal, the expression levels of matrix metalloproteinases (MMP) 1, 2, and 9 were increased. In summary, we successfully established a human endometrial xenotransplantation model in SCID mice, based on the results of menstrual-like changes in which MMP-1, 2 and 9 are involved. We showed that leukocytes are originated from in situ proliferation in human xenografts and involved in the occurrence of menstruation. This model will help to further understand the occurrence, growth, and differentiation of the endometrium and the underlying mechanisms of menstruation.

  13. Clonidine inhibits anti-non-Gal IgM xenoantibody elicited in multiple pig-to-primate models

    PubMed Central

    Stewart, John M.; Tarantal, Alice F.; Hawthorne, Wayne J.; Salvaris, Evelyn J.; O’Connell, Philip J.; Nottle, Mark B.; d’Apice, Anthony J. F.; Cowan, Peter J.; Kearns-Jonker, Mary

    2016-01-01

    Background Survival of vascularized xenografts is dependent on pre-emptive inhibition of the xenoantibody response against galactosyltransferase knockout (GTKO) porcine organs. Our analysis in multiple GTKO pig-to-primate models of xenotransplantation has demonstrated that the anti-non-gal-α-1,3-gal (anti-non-Gal) xenoanti-body response displays limited structural diversity. This allowed our group to identify an experimental compound which selectively inhibited induced anti-non-Gal IgM xenoantibodies. However, because this compound had an unknown safety profile, we extended this line of research to include screening small molecules with known safety profiles allowing rapid advancement to large animal models. Methods The NIH clinical collections of small molecules were screened by ELISA for their ability to inhibit xenoantibody binding to GTKO pig endothelial cells. Serum collected from non-immunosuppressed rhesus monkeys at day 14 post-injection with GTKO pig endothelial cells was utilized as a source of elicited xenoantibody for initial screening. Virtual small molecule screening based on xenoanti-body structure was used to assess the likelihood that the identified small molecules bound xenoantibody directly. As a proxy for selectivity, ELISAs against tetanus toxoid and the natural antigens laminin, thyroglobulin, and single-stranded DNA (ssDNA) were utilized to assess the ability of the identified reagents to inhibit additional antibody responses. The identified inhibitory small molecules were further tested for their ability to inhibit xenoantibody elicited in multiple settings, including rhesus monkeys pre-treated with an anti-non-Gal selective anti-idiotypic antibody, non-immunosuppressed rhesus monkeys immunized with wild-type fetal pig isletlike cell clusters, and non-immunosuppressed baboons transplanted with GTKO multiple transgenic pig kidneys. Results Four clinically relevant small molecules inhibited anti-non-Gal IgM binding to GTKO pig endothelial

  14. Transplant nephrectomy

    PubMed Central

    Akoh, Jacob A

    2011-01-01

    About 10% of all renal allografts fail during the first year of transplantation and thereafter approximately 3%-5% yearly. Given that approximately 69 400 renal transplants are performed worldwide annually, the number of patients returning to dialysis following allograft failure is increasing. A failed transplant kidney, whether maintained by low dose immunosuppression or not, elicits an inflammatory response and is associated with increased morbidity and mortality. The risk for transplant nephrectomy (TN) is increased in patients who experienced multiple acute rejections prior to graft failure, develop chronic graft intolerance, sepsis, vascular complications and early graft failure. TN for late graft failure is associated with greater morbidity and mortality, bleeding being the leading cause of morbidity and infection the main cause of mortality. TN appears to be beneficial for survival on dialysis but detrimental to the outcome of subsequent transplantation by virtue of increased level of antibodies to mismatched antigens, increased rate of primary non function and delayed graft function. Many of the studies are characterized by a retrospective and univariate analysis of small numbers of patients. The lack of randomization in many studies introduced a selection bias and conclusions drawn from such studies should be applied with caution. Pending a randomised controlled trial on the role of TN in the management of transplant failure patients, it is prudent to remove failed symptomatic allografts and all grafts failing within 3 mo of transplantation, monitor inflammatory markers in patients with retained failed allografts and remove the allograft in the event of a significant increase in levels. PMID:24175187

  15. 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

  16. 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

  17. Bion 11 mission: primate experiments

    NASA Technical Reports Server (NTRS)

    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.

  18. 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.

  19. 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

  20. Combined PCR and Q-RT-PCR technique for detecting chimerism in a non-human Primate vascularized osteomyocutaneous allografts model.

    PubMed

    Jiang, J; Wang, J; Zhong, F; Chen, G; Li, Y; Zheng, X X

    2016-01-01

    Face transplantation and other composite tissue transplantation (CTA) are permissive to transplantation tolerance. The real reason, that composite tissue containing bone achieves transplantation immune tolerance more easily than the composite tissue without the bone is not clear. The chimerism may be the main mechanism in the progress of inducing the transplantation tolerance by CTA. We currently have established a non-human Primate Vascularized Osteomyocutaneous Allografts Model. To test the chimerism which comes from donor after the transplantation, we developed a method which combined reverse transcription polymerase chain reaction (RT-PCR) and real-time quantitative PCR (qRT-PCR) technique using primers specific for Macaca fascicularis sex determination region on the Y chromosome (SRY) gene. With the method, we estimated the level of the chimerism. PMID:27453269

  1. Establishment and characterization of esophageal squamous cell carcinoma patient-derived xenograft mouse models for preclinical drug discovery.

    PubMed

    Zhang, Jingchuan; Jiang, Dongxian; Li, Xiaojing; Lv, Jing; Xie, Liang; Zheng, Li; Gavine, Paul R; Hu, Qin; Shi, Yuan; Tan, Lijie; Ge, Di; Xu, Songtao; Li, Leon; Zhu, Lifang; Hou, Yingyong; Wang, Qun

    2014-08-01

    The purpose of this study was to establish and characterize patient-derived esophageal squamous cell carcinoma xenograft (PDECX) mice for utilization in antitumor drug discovery. A total of 96 esophageal squamous cell carcinoma (ESCC) tissues from Chinese patients were transplanted subcutaneously into immunodeficient mice. Histology, EGFR, K-ras, B-raf, and PIK3CA mutations, and HER2 gene amplifications were analyzed in both patient tumors and mouse xenograft tissues using immunohistochemistry, mutant-enriched liquid chip sequencing and fluorescence in situ hybridization assays, respectively. Furthermore, in vivo efficacy studies using five PDECX mice harboring a variety of genetic aberrations were performed using the chemotherapy agents 5-fluorouracil (5-FU) and cisplatin. Thirty-seven PDECX mouse models were successfully established in immunodeficient mice. Pathological analysis revealed similar histological architecture and degrees of differentiation between patient ESCC and xenografted tumors. No mutations were identified in EGFR, K-ras, and B-raf genes in either xenograft models or patient ESCC tissues. In contrast, PIK3CA gene mutations were detected in 12.5% (12/96) ESCC patients and 18.9% (7/37) PDECX models. Interestingly, patient ESCC tissues exhibiting HER2 overexpression or gene amplification were unable to survive in immunodeficient mice. Further analysis showed that PDECX models carrying HER2 2+ expression had no response to 5-FU/cisplatin, compared with HER2-negative models. In conclusion, a panel of PDECX mouse models, which include PIK3CA mutant and HER2-positive models, was established and characterized thus mimicking the current clinical genetic setting of esophageal carcinoma. The sensitivity of HER2-negative ESCC models to chemotherapy supports stratification approaches in the treatment of esophageal carcinoma patients and warrants further investigation of the impact of PI3KCA on treatment response.

  2. 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

  3. 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...

  4. Transplantation tolerance

    PubMed Central

    Muller, Yannick D; Seebach, Jörg D; Bühler, Leo H; Pascual, Manuel

    2011-01-01

    The major challenge in transplantation medicine remains long-term allograft acceptance, with preserved allograft function under minimal chronic immunosuppression. To safely achieve the goal of sustained donor-specific T and B cell non-responsiveness, research efforts are now focusing on therapies based on cell subsets with regulatory properties. In particular the transfusion of human regulatory T cells (Treg) is currently being evaluated in phase I/II clinical trials for the treatment of graft versus host disease following hematopoietic stem cell transplantation, and is also under consideration for solid organ transplantation. The purpose of this review is to recapitulate current knowledge on naturally occurring as well as induced human Treg, with emphasis on their specific phenotype, suppressive function and how these cells can be manipulated in vitro and/or in vivo for therapeutic purposes in transplantation medicine. We highlight the potential but also possible limitations of Treg-based strategies to promote long-term allograft survival. It is evident that the bench-to-beside translation of these protocols still requires further understanding of Treg biology. Nevertheless, current data already suggest that Treg therapy alone will not be sufficient and needs to be combined with other immunomodulatory approaches in order to induce allograft tolerance. PMID:21776332

  5. 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 ...

  6. Pancreas transplant

    MedlinePlus

    ... evidence that the complications of diabetes, such as diabetic retinopathy, may not get worse and may even improve after a pancreas-kidney transplant. More than 95% of people survive ... of the donated pancreas and kidney for the rest of your life.

  7. A human fetal prostate xenograft model of developmental estrogenization

    PubMed Central

    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 (i.e. CDKN1A, CASP9, ESR2, PTEN, and TP53) were 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

  8. A brief history of corneal transplantation: From ancient to modern.

    PubMed

    Crawford, Alexandra Z; Patel, Dipika V; McGhee, Charles Nj

    2013-09-01

    This review highlights many of the fundamental concepts and events in the development of corneal transplantation - from ancient times to modern. Tales of eye, limb, and even heart transplantation appear in ancient and medieval texts; however, in the scientific sense, the original concepts of corneal surgery date back to the Greek physician Galen (130-200 AD). Although proposals to provide improved corneal clarity by surgical interventions, including keratoprostheses, were better developed by the 17(th) and 18(th) centuries, true scientific and surgical experimentation in this field did not begin until the 19(th) century. Indeed, the success of contemporary corneal transplantation is largely the result of a culmination of pivotal ideas, experimentation, and perseverance by inspired individuals over the last 200 years. Franz Reisinger initiated experimental animal corneal transplantation in 1818, coining the term "keratoplasty". Subsequently, Wilhelmus Thorne created the term corneal transplant and 3 years later Samuel Bigger, 1837, reported successful corneal transplantation in a gazelle. The first recorded therapeutic corneal xenograft on a human was reported shortly thereafter in 1838-unsurprisingly this was unsuccessful. Further progress in corneal transplantation was significantly hindered by limited understanding of antiseptic principles, anesthesiology, surgical technique, and immunology. There ensued an extremely prolonged period of debate and experimentation upon the utility of animal compared to human tissue, and lamellar versus penetrating keratoplasty. Indeed, the first successful human corneal transplant was not performed by Eduard Zirm until 1905. Since that first successful corneal transplant, innumerable ophthalmologists have contributed to the development and refinement of corneal transplantation aided by the development of surgical microscopes, refined suture materials, the development of eye banks, and the introduction of corticosteroids. Recent

  9. A brief history of corneal transplantation: From ancient to modern

    PubMed Central

    Crawford, Alexandra Z; Patel, Dipika V; McGhee, Charles NJ

    2013-01-01

    This review highlights many of the fundamental concepts and events in the development of corneal transplantation – from ancient times to modern. Tales of eye, limb, and even heart transplantation appear in ancient and medieval texts; however, in the scientific sense, the original concepts of corneal surgery date back to the Greek physician Galen (130-200 AD). Although proposals to provide improved corneal clarity by surgical interventions, including keratoprostheses, were better developed by the 17th and 18th centuries, true scientific and surgical experimentation in this field did not begin until the 19th century. Indeed, the success of contemporary corneal transplantation is largely the result of a culmination of pivotal ideas, experimentation, and perseverance by inspired individuals over the last 200 years. Franz Reisinger initiated experimental animal corneal transplantation in 1818, coining the term “keratoplasty”. Subsequently, Wilhelmus Thorne created the term corneal transplant and 3 years later Samuel Bigger, 1837, reported successful corneal transplantation in a gazelle. The first recorded therapeutic corneal xenograft on a human was reported shortly thereafter in 1838—unsurprisingly this was unsuccessful. Further progress in corneal transplantation was significantly hindered by limited understanding of antiseptic principles, anesthesiology, surgical technique, and immunology. There ensued an extremely prolonged period of debate and experimentation upon the utility of animal compared to human tissue, and lamellar versus penetrating keratoplasty. Indeed, the first successful human corneal transplant was not performed by Eduard Zirm until 1905. Since that first successful corneal transplant, innumerable ophthalmologists have contributed to the development and refinement of corneal transplantation aided by the development of surgical microscopes, refined suture materials, the development of eye banks, and the introduction of corticosteroids. Recent

  10. A brief history of corneal transplantation: From ancient to modern.

    PubMed

    Crawford, Alexandra Z; Patel, Dipika V; McGhee, Charles Nj

    2013-09-01

    This review highlights many of the fundamental concepts and events in the development of corneal transplantation - from ancient times to modern. Tales of eye, limb, and even heart transplantation appear in ancient and medieval texts; however, in the scientific sense, the original concepts of corneal surgery date back to the Greek physician Galen (130-200 AD). Although proposals to provide improved corneal clarity by surgical interventions, including keratoprostheses, were better developed by the 17(th) and 18(th) centuries, true scientific and surgical experimentation in this field did not begin until the 19(th) century. Indeed, the success of contemporary corneal transplantation is largely the result of a culmination of pivotal ideas, experimentation, and perseverance by inspired individuals over the last 200 years. Franz Reisinger initiated experimental animal corneal transplantation in 1818, coining the term "keratoplasty". Subsequently, Wilhelmus Thorne created the term corneal transplant and 3 years later Samuel Bigger, 1837, reported successful corneal transplantation in a gazelle. The first recorded therapeutic corneal xenograft on a human was reported shortly thereafter in 1838-unsurprisingly this was unsuccessful. Further progress in corneal transplantation was significantly hindered by limited understanding of antiseptic principles, anesthesiology, surgical technique, and immunology. There ensued an extremely prolonged period of debate and experimentation upon the utility of animal compared to human tissue, and lamellar versus penetrating keratoplasty. Indeed, the first successful human corneal transplant was not performed by Eduard Zirm until 1905. Since that first successful corneal transplant, innumerable ophthalmologists have contributed to the development and refinement of corneal transplantation aided by the development of surgical microscopes, refined suture materials, the development of eye banks, and the introduction of corticosteroids. Recent

  11. 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

  12. 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.

  13. Role of complement in graft rejection after organ transplantation.

    PubMed

    Bos, Ineke G A; Ten Berge, Ineke J M; Hack, C Erik

    2002-07-01

    Activation of the complement system may significantly contribute to the inflammatory reaction after solid organ transplantation. In allotransplantation, the complement system may be activated by ischemia/reperfusion and, possibly, by antibodies directed against the graft. In xenotransplantation from nonprimates to primates, the major activators for complement are preexisting antibodies. Studies in animal models have shown that the use of complement inhibitors may significantly prolong graft survival. This review describes the role of the complement system in organ injury after organ transplantation and the use of complement inhibitors to prevent damage to the graft after allo- or xenotransplantation.

  14. Systemic therapy of myeloma xenografts by an attenuated measles virus.

    PubMed

    Peng, K W; Ahmann, G J; Pham, L; Greipp, P R; Cattaneo, R; Russell, S J

    2001-10-01

    Conditionally replicating viruses are promising agents for the treatment of malignancy. Here it is shown that the live attenuated Edmonston-B vaccine strain of measles virus (MV-Edm) replicates selectively in human myeloma cells and has potent antitumor activity. In vitro, replication of MV-Edm was restricted in phytohemagglutinin (PHA)-stimulated peripheral blood lymphocytes (PBLs) but proceeded efficiently in a panel of 6 myeloma cell lines-ARH-77, RPMI 8226, JJN-3, MM1, KAS-6/1, and KMS-11-and in primary myeloma cells isolated by CD138 sorting from the bone marrow aspirates of 6 patients. MV-Edm infection induced potent cytopathic effects in these myeloma cells, resulting in the formation of multinucleated syncytia that eventually became nonviable. In contrast, syncytial formation in PHA-stimulated PBLs was minimal after MV-Edm infection. In vivo, MV-Edm was antitumorigenic and inhibited the establishment of myeloma cells as xenografts in immunocompromised mice. When injected directly into ARH-77 myeloma xenografts in the mice, MV-Edm caused complete regression of these xenografts. MV-Edm administered intravenously into the tail veins of mice also showed significant antineoplastic activity against established RPMI 8226 and ARH-77 xenografts. In particular, the ARH-77 myeloma xenografts were exquisitely sensitive to MV-Edm therapy, and tumors in all mice regressed completely. In light of its selectivity for myeloma cells and its potent antineoplastic activity against myeloma xenografts in vivo, MV-Edm merits further development for the treatment of multiple myeloma.

  15. 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.

  16. 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

  17. Polyomaviruses of Nonhuman Primates: Implications for Research

    PubMed Central

    Simon, Meredith A

    2008-01-01

    Polyomaviruses are a family of small nonenveloped DNA viruses that infect birds and mammals. At least 7 nonhuman primate polyomaviruses that occur in macaques, African green monkeys, marmosets baboons, and chimpanzees have been described, as well as 4 polyomaviruses that occur in humans. Simian virus 40 (SV40), which infects macaques, was the first nonhuman primate polyomavirus identified as a contaminant of early polio vaccines. Primate polyomaviruses cause inapparent primary infections but persist in the host and can cause severe disease in situations of immunocompromise. This review describes the primate polyomaviruses, and the diseases associated with the viruses of macaques. In macaques, the greatest current concerns are the potential confounding of study results by polyomavirus infections and the zoonotic potential of SV40. PMID:19793457

  18. Exposure to Nonhuman Primates in Rural Cameroon

    PubMed Central

    Prosser, A. Tassy; Carr, Jean K.; Tamoufe, Ubald; Mpoudi-Ngole, Eitel; Torimiro, J. Ndongo; LeBreton, Matthew; McCutchan, Francine E.; Birx, Deborah L.; Burke, Donald S.

    2004-01-01

    Exposure to nonhuman primates has led to the emergence of important diseases, including Ebola hemorrhagic fever, AIDS, and adult T-cell leukemia. To determine the extent of exposure to nonhuman primates, persons were examined in 17 remote villages in Cameroon that represented three habitats (savanna, gallery forest, and lowland forest). Questionnaire data were collected to assess whether persons kept wild animal pets; hunted and butchered wild game; had experienced bites, scratches, or injuries from live animals; or had been injured during hunting or butchering. While all villages had substantial exposure to nonhuman primates, higher rates of exposure were seen in lowland forest sites. The study demonstrates that exposure is not limited to small groups of hunters. A high percentage of rural villagers report exposure to nonhuman primate blood and body fluids and risk acquiring infectious diseases. PMID:15663844

  19. 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.

  20. 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.

  1. Patient-Derived Tumor Xenografts Are Susceptible to Formation of Human Lymphocytic Tumors.

    PubMed

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

    2015-09-01

    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

  2. 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

  3. Follicular development in cryopreserved Common Wombat ovarian tissue xenografted to Nude rats.

    PubMed

    Wolvekamp, M C; Cleary, M L; Cox, S L; Shaw, J M; Jenkin, G; Trounson, A O

    2001-01-31

    The Northern Hairy-nosed Wombat (Lasiorhinus krefftii) is a highly endangered marsupial species and every possible option for sustaining the species needs to be explored. One important approach may be the development of assisted reproductive technologies in the non-endangered Common Wombat (Vombatus ursinus) and Southern Hairy-nosed Wombat (Lasiorhinus latifrons) for application in breeding the Northern Hairy-nosed Wombat. In this study, it was examined whether cryopreserved Wombat ovarian tissue would develop following xenografting to immunologically deficient rats. Ovarian tissue was collected from Common Wombats (n = 3) and cryopreserved as small cortical pieces. After thawing the cortical pieces were grafted underneath the kidney capsule of Nude rats (n = 16). The grafts were recovered at 2, 4, and 10 weeks after transplantation and their gross and histological appearance investigated. Two weeks after grafting (n = 2), the tissue was revascularized and healthy primordial follicles were present. At week 4 (n = 2), some follicular development was present. At week 10, six rats received human chorionic gonadotrophin (hCG) to trigger follicle and oocyte maturation while another six rats were not given any treatment. The administration of hCG did not induce preovulatory follicles and oocyte maturation although type 5 follicles were present in ovarian tissue collected 10 weeks posttransplantation in both treated and untreated groups. This study demonstrates for the first time that Wombat ovarian tissue can survive and function when grafted into immunocompromized rats and that Wombat ovarian follicles can be recruited to growth and development in an ovarian xenograft. This model system has the potential to produce mature oocytes from endangered species for use in assisted reproductive technologies such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and mature oocytes from non-endangered species for nuclear transfer which may be necessary for

  4. Patient-Derived Tumor Xenografts Are Susceptible to Formation of Human Lymphocytic Tumors.

    PubMed

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

    2015-09-01

    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.

  5. Follicular development in cryopreserved Common Wombat ovarian tissue xenografted to Nude rats.

    PubMed

    Wolvekamp, M C; Cleary, M L; Cox, S L; Shaw, J M; Jenkin, G; Trounson, A O

    2001-01-31

    The Northern Hairy-nosed Wombat (Lasiorhinus krefftii) is a highly endangered marsupial species and every possible option for sustaining the species needs to be explored. One important approach may be the development of assisted reproductive technologies in the non-endangered Common Wombat (Vombatus ursinus) and Southern Hairy-nosed Wombat (Lasiorhinus latifrons) for application in breeding the Northern Hairy-nosed Wombat. In this study, it was examined whether cryopreserved Wombat ovarian tissue would develop following xenografting to immunologically deficient rats. Ovarian tissue was collected from Common Wombats (n = 3) and cryopreserved as small cortical pieces. After thawing the cortical pieces were grafted underneath the kidney capsule of Nude rats (n = 16). The grafts were recovered at 2, 4, and 10 weeks after transplantation and their gross and histological appearance investigated. Two weeks after grafting (n = 2), the tissue was revascularized and healthy primordial follicles were present. At week 4 (n = 2), some follicular development was present. At week 10, six rats received human chorionic gonadotrophin (hCG) to trigger follicle and oocyte maturation while another six rats were not given any treatment. The administration of hCG did not induce preovulatory follicles and oocyte maturation although type 5 follicles were present in ovarian tissue collected 10 weeks posttransplantation in both treated and untreated groups. This study demonstrates for the first time that Wombat ovarian tissue can survive and function when grafted into immunocompromized rats and that Wombat ovarian follicles can be recruited to growth and development in an ovarian xenograft. This model system has the potential to produce mature oocytes from endangered species for use in assisted reproductive technologies such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and mature oocytes from non-endangered species for nuclear transfer which may be necessary for

  6. Meniscal allograft transplantation

    MedlinePlus

    Meniscus transplant; Surgery - knee - meniscus transplant; Surgery - knee - cartilage; Arthroscopy - knee - meniscus transplant ... the lab for any diseases and infection. Other surgeries, such as ligament or cartilage repairs, may be ...

  7. 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, ...

  8. Correlates of body mass evolution in primates.

    PubMed

    Soligo, Christophe

    2006-07-01

    Body mass is undoubtedly central to the overall adaptive profile of any organism. Despite this, very little is known of what forces drive evolutionary changes in body mass and, consequently, shape patterns of body mass distribution exhibited by animal radiations. The search for factors that may influence evolutionary processes in general frequently focuses on environmental parameters such as climate change or interspecific competition. With respect to body mass, there is also the suggestion that evolutionary lineages may follow an inherent trend toward increased body mass, known as Cope's rule. The present paper investigates whether overall directional trends of body mass change, or correlations between patterns of body mass evolution and environmental factors have influenced the evolution of body mass in plesiadapiforms and primates. Analyses of the global fossil record of plesiadapiforms and primates suggest that the former did indeed follow an overall trend toward increased body mass compatible with the predictions of Cope's rule. In contrast, neither primates as a whole, nor a number of individual primate radiations (Adapiformes, Omomyiformes, and Anthropoidea), show any indication of overall directional patterns of body mass change. No correlations of primate body mass change with either the latitudinal distribution of fossil species, or with estimates of global temperature trends, were found. There is evidence, however, that direct competition between omomyiforms and adapiforms (the two main primate radiations known from the Paleogene) influenced processes of body mass evolution in omomyiforms.

  9. 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.

  10. Forest structure drives global diversity of primates.

    PubMed

    Gouveia, Sidney F; Villalobos, Fabricio; Dobrovolski, Ricardo; Beltrão-Mendes, Raone; Ferrari, Stephen F

    2014-11-01

    Geographic gradients in the species richness of non-human primates have traditionally been attributed to the variation in forest productivity (related to precipitation levels), although an all-inclusive, global-scale analysis has never been conducted. We perform a more comprehensive test on the role of precipitation and biomass production and propose an alternative hypothesis - the variation in vertical structure of forest habitats as measured by forest canopy height - in determining primate species richness on a global scale. Considering the potential causal relationships among precipitation, productivity and forest structure, we arranged these variables within a path framework to assess their direct and indirect associations with the pattern of primate species richness using structural equation modelling. The analysis also accounted for the influence of spatial autocorrelation in the relationships and assessed possible historical differences among biogeographical regions. The path coefficients indicate that forest canopy height (used as a proxy for vertical forest structure) is a better predictor of primate species richness than either precipitation or productivity on both global and continental scales. The only exception was Asia, where precipitation prevailed, albeit independently from productivity or forest structure. The influence of spatially structured processes varied markedly among biogeographical regions. Our results challenge the traditional rainfall-based viewpoint in favour of forest distribution and structure as primary drivers of primate species richness, which aggregate potential effects from both climatic factors and habitat complexity. These findings may support predictions of the impact of forest removal on primate species richness.

  11. Modeling Leukemogenesis in the Zebrafish Using Genetic and Xenograft Models.

    PubMed

    Rajan, Vinothkumar; Dellaire, Graham; Berman, Jason N

    2016-01-01

    The zebrafish is a widely accepted model to study leukemia. The major advantage of studying leukemogenesis in zebrafish is attributed to its short life cycle and superior imaging capacity. This chapter highlights using transgenic- and xenograft-based models in zebrafish to study a specific leukemogenic mutation and analyze therapeutic responses in vivo. PMID:27464808

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

    PubMed

    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

  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. Heart transplantation.

    PubMed

    Nakatani, Takeshi

    2009-06-01

    A total of 59 heart transplantations (HTx) have been performed in Japan as of September, 2008, since the Organ Transplantation Law was settled in October 1997. The majority of recipients were suffered from dilated cardiomyopathy and waiting condition of all recipients were status 1. The mean waiting time was 777 day; 50 patients (85%) were supported by several types of left ventricular assist systems (LVAS) and the mean duration of support was 780 days. The majority of patients underwent operation by modified bicaval method with Celsior solution for cardiac preservation, and 64% of recipients were administered triple therapy with cyclosporine, mycophenolate mofetil, and steroid as the initial immunosuppressive regimen. The 9-year survival rate was 94%, which was superior to that of the international registry. HTx in Japan has been very limited by a severe shortage of donors, but the results have been excellent even though the majority of recipients were waiting for long-term with a LVAS as a bridge to HTx.

  15. 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

  16. 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

  17. Primate energy expenditure and life history

    PubMed Central

    Pontzer, Herman; Raichlen, David A.; Gordon, Adam D.; Schroepfer-Walker, Kara K.; Hare, Brian; O’Neill, Matthew C.; Muldoon, Kathleen M.; Dunsworth, Holly M.; Wood, Brian M.; Isler, Karin; Burkart, Judith; Irwin, Mitchell; Shumaker, Robert W.; Lonsdorf, Elizabeth V.; Ross, Stephen R.

    2014-01-01

    Humans and other primates are distinct among placental mammals in having exceptionally slow rates of growth, reproduction, and aging. Primates’ slow life history schedules are generally thought to reflect an evolved strategy of allocating energy away from growth and reproduction and toward somatic investment, particularly to the development and maintenance of large brains. Here we examine an alternative explanation: that primates’ slow life histories reflect low total energy expenditure (TEE) (kilocalories per day) relative to other placental mammals. We compared doubly labeled water measurements of TEE among 17 primate species with similar measures for other placental mammals. We found that primates use remarkably little energy each day, expending on average only 50% of the energy expected for a placental mammal of similar mass. Such large differences in TEE are not easily explained by differences in physical activity, and instead appear to reflect systemic metabolic adaptation for low energy expenditures in primates. Indeed, comparisons of wild and captive primate populations indicate similar levels of energy expenditure. Broad interspecific comparisons of growth, reproduction, and maximum life span indicate that primates’ slow metabolic rates contribute to their characteristically slow life histories. PMID:24474770

  18. 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.

  19. 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

  20. 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.

  1. Molecular correlates of platinum response in human high-grade serous ovarian cancer patient-derived xenografts

    PubMed Central

    Topp, M; Hartley, L; Cook, M; Heong, V; Boehm, E; McShane, L; Pyman, J; McNally, O; Ananda, S; Harrell, M; Etemadmoghadam, D; Galletta, L; Alsop, K; Mitchell, G; Fox, SB; Kerr, JB; Hutt, KJ; Kaufmann, SH; Swisher, EM; Bowtell, DD; Wakefield, M; Scott, CL

    2015-01-01

    Introduction Improvement in the ability to target underlying drivers and vulnerabilities of high-grade serous ovarian cancer (HG-SOC) requires the development of molecularly annotated pre-clinical models reflective of clinical responses. Methods We generated patient-derived xenografts (PDXs) from consecutive, chemotherapy-naïve, human HG-SOC by transplanting fresh human HG-SOC fragments into subcutaneous and intra-ovarian bursal sites of NOD/SCID IL2Rγnull recipient mice, completed molecular annotation and assessed platinum sensitivity. Results The success rate of xenografting was 83%. Of ten HG-SOC PDXs, all contained mutations in TP53, two were mutated for BRCA1, three for BRCA2, and in two, BRCA1 was methylated. In vivo cisplatin response, determined as platinum sensitive (progression-free interval ≥100 d, n=4), resistant (progression-free interval <100 d, n=3) or refractory (n=3), was largely consistent with patient outcome. Three of four platinum sensitive HG-SOC PDXs contained DNA repair gene mutations, and the fourth was methylated for BRCA1. In contrast, all three platinum refractory PDXs overexpressed dominant oncogenes (CCNE1, LIN28B and/or BCL2). Conclusions Because PDX platinum response reflected clinical outcome, these annotated PDXs will provide a unique model system for preclinical testing of novel therapies for HG-SOC. PMID:24560445

  2. 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.

  3. 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.

  4. Protopithecus: rediscovering the first fossil primate.

    PubMed

    Hartwig, W C

    1995-01-01

    The earliest discoveries of extinct primates and humans profoundly affected the course of evolutionary theory as a scientific model for explaining life and its diversity through time. The absence of such fossils in the early nineteenth century provided important negative evidence to the competing French intellectual schools of Lamarckian evolutionism and Cuvierian catastrophism. Indeed, the first recognition of extinct primates fell serendipitously between the death of Cuvier in 1832 and the revolutionary writings of Darwin in 1859. Largely unknown to history, however, is that four different European scholars, working on three continents, independently discovered and recognized extinct primates within a few months of each other in 1836. The first of these to be formally named, Protopithecus, is ironically the least well known despite being the largest monkey ever discovered in the western hemisphere. The reasons for this forgotten first discovery reflect a general unawareness of South American mammals, and propagation of misinterpretation at a critical time in the history of primatology.

  5. Primate color vision: a comparative perspective.

    PubMed

    Jacobs, Gerald H

    2008-01-01

    Thirty years ago virtually everything known about primate color vision derived from psychophysical studies of normal and color-defective humans and from physiological investigations of the visual system of the macaque monkey, the most popular of human surrogates for this purpose. The years since have witnessed much progress toward the goal of understanding this remarkable feature of primate vision. Among many advances, investigations focused on naturally occurring variations in color vision in a wide range of nonhuman primate species have proven to be particularly valuable. Results from such studies have been central to our expanding understanding of the interrelationships between opsin genes, cone photopigments, neural organization, and color vision. This work is also yielding valuable insights into the evolution of color vision.

  6. 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.

  7. 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

  8. Lipoprotein(a): nonhuman primate models.

    PubMed

    Makino, K; Scanu, A M

    1991-09-01

    Lipoprotein(a) [Lp(a)] is a low density lipoprotein which has apo(a) disulfide-linked to apoB100. Apo(a) has recently been shown to have a striking homology with plasminogen, a knowledge that has stimulated a lot of interest in the mechanism of atherogenicity and thrombogenicity of this lipoprotein particle. Several studies have documented the presence of Lp(a) in nonhuman primates with particular reference to the rhesus monkeys and baboons. The Lp(a) of rhesus monkey is structurally very similar to that of humans, except for the absence of kringle V and the amino acid composition of the catalytic region. The Lp(a) of nonhuman primates, like their human counterparts, exhibit a wide range of interindividual plasma levels and also a wide size polymorphism of apo(a). Nonhuman primates appear to represent a good model for the study of the structure and biology of Lp(a).

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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

  16. The use of medicinal plants by primates: A missing link?

    PubMed

    Newton, P

    1991-09-01

    There is growing evidence that some species of wild nonhuman primate, especially chimpanzees, take herbal and clay medicines to treat and prevent disease. Such a primate pharmacopoeia may be a missing link in our understanding of the relationship between primate foraging and ranging strategies and plant chemistry; not all plant secondary compounds may be deleterious to the consumer. Just as study of traditional herbal medicines has yielded powerful drugs, so primate medicines may hint at drugs useful in treating human disease.

  17. Body weight, diet and home range area in primates.

    PubMed

    Milton, K; May, M L

    1976-02-12

    Primates show a strong positive relationship between body weight and home range area. Dietary habits also influence home range area. Folivorous primates occupy smaller home range areas for their body weight than do frugivores and omnivores. Primates generally require smaller home range area per individual than solitary terrestrial mammals, but primates living in social groups have much larger total home range than individual solitary mammals. This trend may necessitate higher expenditures of energy in food-gathering or modifications in movement patterns.

  18. Biosafety in Ex Vivo Gene Therapy and Conditional Ablation of Lentivirally Transduced Hepatocytes in Nonhuman Primates

    PubMed Central

    Menzel, Olivier; Birraux, Jacques; Wildhaber, Barbara E; Jond, Caty; Lasne, Françoise; Habre, Walid; Trono, Didier; Nguyen, Tuan H; Chardot, Christophe

    2009-01-01

    Ex vivo gene therapy is an interesting alternative to orthotopic liver transplantation (OLT) for treating metabolic liver diseases. In this study, we investigated its efficacy and biosafety in nonhuman primates. Hepatocytes isolated from liver lobectomy were transduced in suspension with a bicistronic liver-specific lentiviral vector and immediately autotransplanted (SLIT) into three cynomolgus monkeys. The vector encoded cynomolgus erythropoietin (EPO) and the conditional suicide gene herpes simplex virus-thymidine kinase (HSV-TK). Survival of transduced hepatocytes and vector dissemination were evaluated by detecting transgene expression and vector DNA. SLIT was safely performed within a day in all three subjects. Serum EPO and hematocrit rapidly increased post-SLIT and their values returned to baseline within about 1 month. Isoforms of EPO detected in monkeys' sera differed from the physiological renal EPO. In liver biopsies at months 8 and 15, we detected EPO protein, vector mRNA and DNA, demonstrating long-term survival and functionality of transplanted lentivirally transduced hepatocytes. Valganciclovir administration resulted in complete ablation of the transduced hepatocytes. We demonstrated the feasibility and biosafety of SLIT, and the long term (>1 year) functionality of lentivirally transduced hepatocytes in nonhuman primates. The HSV-TK/valganciclovir suicide strategy can increase the biosafety of liver gene therapy protocols by safely and completely ablating transduced hepatocytes on demand. PMID:19568222

  19. 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

  20. Exclusion of Complex Paraannular Aortic Abscess With the Freestyle Xenograft.

    PubMed

    Guihaire, Julien; Kloeckner, Martin; Deleuze, Philippe

    2016-10-01

    Destructive aortic valve endocarditis is a serious condition that can result in aortoventricular disjunction. The appropriate surgical approach for severe excavating lesions remains a matter of debate. Homografts, prosthetic valves associated with a pericardial patch for annulus repair, and prosthetic valve conduits can be used. We report the technical issue of subcoronary inclusion of the full root Freestyle xenograft for complicated aortic endocarditis extending to the left ventricular outflow tract. PMID:27645988

  1. 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.

  2. 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.

  3. Erlotinib Inhibits Growth of a Patient-Derived Chordoma Xenograft

    PubMed Central

    Siu, I-Mei; Ruzevick, Jacob; Zhao, Qi; Connis, Nick; Jiao, Yuchen; Bettegowda, Chetan; Xia, Xuewei; Burger, Peter C.; Hann, Christine L.; Gallia, Gary L.

    2013-01-01

    Chordomas are rare primary bone tumors that occur along the neuraxis. Primary treatment is surgery, often followed by radiotherapy. Treatment options for patients with recurrence are limited and, notably, there are no FDA approved therapeutic agents. Development of therapeutic options has been limited by the paucity of preclinical model systems. We have established and previously reported the initial characterization of the first patient-derived chordoma xenograft model. In this study, we further characterize this model and demonstrate that it continues to resemble the original patient tumor histologically and immunohistochemically, maintains nuclear expression of brachyury, and is highly concordant with the original patient tumor by whole genome genotyping. Pathway analysis of this xenograft demonstrates activation of epidermal growth factor receptor (EGFR). In vitro studies demonstrate that two small molecule inhibitors of EGFR, erlotinib and gefitinib, inhibit proliferation of the chordoma cell line U-CH 1. We further demonstrate that erlotinib significantly inhibits chordoma growth in vivo. Evaluation of tumors post-treatment reveals that erlotinib reduces phosphorylation of EGFR. This is the first demonstration of antitumor activity in a patient-derived chordoma xenograft model and these findings support further evaluation of EGFR inhibitors in this disease. PMID:24260133

  4. Genomic profiling of patient-derived colon cancer xenograft models.

    PubMed

    Lee, Won-Suk; Kim, Hye-Youn; Seok, Jae Yeon; Jang, Ho Hee; Park, Yeon Ho; Kim, So-Young; Shin, Dong Bok; Hong, Suntaek

    2014-12-01

    Recent evidence suggests that patient derived xenograft (PDX) models can maintain certain pathological and molecular features of the original disease. However, these characterizations are limited to immunohistochemistry or by tissue microarray analysis. We conducted a high-throughput sequencing of primary colon tumor and PDX has not been reported yet. Fresh primary colon cancer tissues that originate from surgery were implanted into the subcutaneous space of 6- to 8-week-old female BALB/c nu/nu or NOD/SCID mice and serially passaged in vivo. Ion AmpliSeq Cancer Hotspot Panel v2 (Ion Torrent) was used to detect frequent somatic mutations and similarity of molecular characteristics between the 10 patient tumors and matched PDX. Histologic and immunohistochemical analyses revealed a high degree of pathologic similarity including histologic architecture and expression of CEA, CK7, and CD20 between the patient and xenograft tumors. In 80% cases, all of the somatic mutations detected in primary tumor were concordantly detected in PDX models. However, 2 PDX models showed gained mutations such as PIK3CA or FBWX7 mutation. Ten patient-derived advanced colon cancer xenograft models were established. These models maintained the key characteristic features of the original tumors, suggesting useful tool for preclinical personalized medicine platform.

  5. Erlotinib inhibits growth of a patient-derived chordoma xenograft.

    PubMed

    Siu, I-Mei; Ruzevick, Jacob; Zhao, Qi; Connis, Nick; Jiao, Yuchen; Bettegowda, Chetan; Xia, Xuewei; Burger, Peter C; Hann, Christine L; Gallia, Gary L

    2013-01-01

    Chordomas are rare primary bone tumors that occur along the neuraxis. Primary treatment is surgery, often followed by radiotherapy. Treatment options for patients with recurrence are limited and, notably, there are no FDA approved therapeutic agents. Development of therapeutic options has been limited by the paucity of preclinical model systems. We have established and previously reported the initial characterization of the first patient-derived chordoma xenograft model. In this study, we further characterize this model and demonstrate that it continues to resemble the original patient tumor histologically and immunohistochemically, maintains nuclear expression of brachyury, and is highly concordant with the original patient tumor by whole genome genotyping. Pathway analysis of this xenograft demonstrates activation of epidermal growth factor receptor (EGFR). In vitro studies demonstrate that two small molecule inhibitors of EGFR, erlotinib and gefitinib, inhibit proliferation of the chordoma cell line U-CH 1. We further demonstrate that erlotinib significantly inhibits chordoma growth in vivo. Evaluation of tumors post-treatment reveals that erlotinib reduces phosphorylation of EGFR. This is the first demonstration of antitumor activity in a patient-derived chordoma xenograft model and these findings support further evaluation of EGFR inhibitors in this disease.

  6. 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.

  7. Nutritional contributions of insects to primate diets: implications for primate evolution.

    PubMed

    Rothman, Jessica M; Raubenheimer, David; Bryer, Margaret A H; Takahashi, Maressa; Gilbert, Christopher C

    2014-06-01

    Insects and other invertebrates form a portion of many living and extinct primate diets. We review the nutritional profiles of insects in comparison with other dietary items, and discuss insect nutrients in relation to the nutritional needs of living primates. We find that insects are incorporated into some primate diets as staple foods whereby they are the majority of food intake. They can also be incorporated as complements to other foods in the diet, providing protein in a diet otherwise dominated by gums and/or fruits, or be incorporated as supplements to likely provide an essential nutrient that is not available in the typical diet. During times when they are very abundant, such as in insect outbreaks, insects can serve as replacements to the usual foods eaten by primates. Nutritionally, insects are high in protein and fat compared with typical dietary items like fruit and vegetation. However, insects are small in size and for larger primates (>1 kg) it is usually nutritionally profitable only to consume insects when they are available in large quantities. In small quantities, they may serve to provide important vitamins and fatty acids typically unavailable in primate diets. In a brief analysis, we found that soft-bodied insects are higher in fat though similar in chitin and protein than hard-bodied insects. In the fossil record, primates can be defined as soft- or hard-bodied insect feeders based on dental morphology. The differences in the nutritional composition of insects may have implications for understanding early primate evolution and ecology.

  8. 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

  9. 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

  10. Primacy and recency effects in nonhuman primates.

    PubMed

    Castro, C A; Larsen, T

    1992-10-01

    The reports of primacy and recency memory effects in nonhuman primates have been criticized because they have all used an initiating response. That is, the presentation of the to-be-remembered list of items was always contingent on a response being initiated by the nonhuman primate. It has been argued that this initiating response improves performance for early items in the list, resulting in the occurrence of the primacy effect, independent of any memory processing mechanism. This criticism was addressed in the present study by not using an initiating response prior to the presentation of the list. Nevertheless, both a primacy and a recency effect were observed in all 6 rhesus monkeys evaluated using a serial probe recognition task. Thus, the results are similar to those for humans, in that both primacy and recency effects can be obtained in nonhuman primates. A brief literature review is included, and it is proposed that the primacy and recency effects observed in humans, nonhuman primates, and infraprimates can be explained within the context of the configural-association theory.

  11. Nonhuman primate quarantine: its evolution and practice.

    PubMed

    Roberts, Jeffrey A; Andrews, Kirk

    2008-01-01

    Nonhuman primates (NHPs) are imported to the United States for use in research, domestic breeding, and propagation of endangered populations in zoological gardens. During the past 60 years, individuals responsible for NHP importation programs have observed morbidity and mortality typically associated with infectious disease outbreaks. These outbreaks have included infectious agents such as tuberculosis, Herpesvirus sp., simian hemorrhagic fever, and filovirus infections such as the Ebola and Marburg viruses. Some outbreaks have affected both animal and human populations. These epizootics are attributable to a variety of factors, including increased population density, exposure of naïve populations to new infectious agents, and stress. The practice of quarantining animals arriving in the United States was first applied by individual research programs to improve animal health and ensure the quality of animals entering research programs. The development of government regulations for nonhuman primate quarantine accompanied the recognition that imported NHPs could pose a risk to public health. This article briefly reviews the history of US NHP importation and the factors behind the development of NHP quarantine regulations. The focus is on regulations concerned with infectious disease, public health, and the health of domestic primate colonies. These regulations have had the dual benefit of protecting public health as well as reducing animal morbidity and mortality during importation and quarantine. We review current practices and facilities for nonhuman primate quarantine and identify challenges for the future. PMID:18323577

  12. 42 CFR 71.53 - Nonhuman primates.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... nonhuman primates that is suspected of being yellow fever, monkeypox, or Marburg/Ebola disease. (3... disease that may constitute a threat to public health, the Director may provide for or require examination... be required under other Federal regulations (50 CFR parts 17 and 23) protecting such...

  13. 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

  14. Chronic wasting disease agents in nonhuman primates.

    PubMed

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

    2014-05-01

    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.

  15. 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

  16. [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.

  17. 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.

  18. 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.

  19. 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 ...

  20. Establishment of a patient-derived orthotopic Xenograft (PDOX) model of HER-2-positive cervical cancer expressing the clinical metastatic pattern.

    PubMed

    Hiroshima, Yukihiko; Zhang, Yong; Zhang, Nan; Maawy, Ali; Mii, Sumiyuki; Yamamoto, Mako; Uehara, Fuminari; Miwa, Shinji; Yano, Shuya; Murakami, Takashi; Momiyama, Masashi; Chishima, Takashi; Tanaka, Kuniya; Ichikawa, Yasushi; Bouvet, Michael; Murata, Takuya; Endo, Itaru; Hoffman, Robert M

    2015-01-01

    Squamous cell carcinoma of the cervix, highly prevalent in the developing world, is often metastatic and treatment resistant with no standard treatment protocol. Our laboratory pioneered the patient-derived orthotopic xenograft (PDOX) nude mouse model with the technique of surgical orthotopic implantation (SOI). Unlike subcutaneous transplant patient-derived xenograft (PDX) models, PDOX models metastasize. Most importantly, the metastasis pattern correlates to the patient. In the present report, we describe the development of a PDOX model of HER-2-positive cervical cancer. Metastasis after SOI in nude mice included peritoneal dissemination, liver metastasis, lung metastasis as well as lymph node metastasis reflecting the metastatic pattern in the donor patient. Metastasis was detected in 4 of 6 nude mice with primary tumors. Primary tumors and metastases in the nude mice had histological structures similar to the original tumor and were stained by an anti-HER-2 antibody in the same pattern as the patient's cancer. The metastatic pattern, histology and HER-2 tumor expression of the patient were thus preserved in the PDOX model. In contrast, subcutaneous transplantation of the patient's cervical tumors resulted in primary growth but not metastasis.

  1. Predictors of orbital convergence in primates: a test of the snake detection hypothesis of primate evolution.

    PubMed

    Wheeler, Brandon C; Bradley, Brenda J; Kamilar, Jason M

    2011-09-01

    Traditional explanations for the evolution of high orbital convergence and stereoscopic vision in primates have focused on how stereopsis might have aided early primates in foraging or locomoting in an arboreal environment. It has recently been suggested that predation risk by constricting snakes was the selective force that favored the evolution of orbital convergence in early primates, and that later exposure to venomous snakes favored further degrees of convergence in anthropoid primates. Our study tests this snake detection hypothesis (SDH) by examining whether orbital convergence among extant primates is indeed associated with the shared evolutionary history with snakes or the risk that snakes pose for a given species. We predicted that orbital convergence would be higher in species that: 1) have a longer history of sympatry with venomous snakes, 2) are likely to encounter snakes more frequently, 3) are less able to detect or deter snakes due to group size effects, and 4) are more likely to be preyed upon by snakes. Results based on phylogenetically independent contrasts do not support the SDH. Orbital convergence shows no relationship to the shared history with venomous snakes, likelihood of encountering snakes, or group size. Moreover, those species less likely to be targeted as prey by snakes show significantly higher values of orbital convergence. Although an improved ability to detect camouflaged snakes, along with other cryptic stimuli, is likely a consequence of increased orbital convergence, this was unlikely to have been the primary selective force favoring the evolution of stereoscopic vision in primates.

  2. Preservation of KIT genotype in a novel pair of patient-derived orthotopic xenograft mouse models of metastatic pediatric CNS germinoma.

    PubMed

    Lindsay, Holly; Huang, Yulun; Du, Yuchen; Braun, Frank K; Teo, Wan Yee; Kogiso, Mari; Qi, Lin; Zhang, Huiyuan; Zhao, Sibo; Mao, Hua; Lin, Frank; Baxter, Patricia; Su, Jack M; Terashima, Keita; Perlaky, Laszlo; Chintagumpala, Murali; Adesina, Adekunle; Lau, Ching C; Williams Parsons, D; Li, Xiao-Nan

    2016-05-01

    Metastatic intracranial germinoma is difficult to treat. Although the proto-oncogene KIT is recognized as one of the most frequent genetic abnormalities in CNS germinoma, the development of new target therapeutic agents for CNS germinoma is hampered by the lack of clinically-relevant animal models that replicate the mutated or over-expressed KIT. CNS germinoma tumor cells from five pediatric patients were directly implanted into the brains of Rag2/severe combined immune deficiency mice. Once established, the xenograft tumors were sub-transplanted in vivo in mouse brains. Characterization of xenograft tumors were performed through histologic and immunohistochemical staining, and KIT mutation analysed with quantitative pyro-sequencing. Expression of putative cancer stem cell markers (CD133, CD15, CD24, CD44, CD49f) was analyzed through flow cytometry. Two patient-derived orthotopic xenograft (PDOX) models (IC-6999GCT and IC-9302GCT) were established from metastatic germinoma and serially sub-transplanted five times in mouse brains. Similar to the original patient tumors, they both exhibited faint expression (+) of PLAP, no expression (-) of β-HCG and strong (+++) expression of KIT. KIT mutation (D816H), however, was only found in IC-9320GCT. This mutation was maintained during the five in vivo tumor passages with an increased mutant allele frequency compared to the patient tumor. Expression of putative cancer stem cell markers CD49f and CD15 was also detected in a small population of tumor cells in both models. This new pair of PDOX models replicated the key biological features of pediatric intracranial germinoma and should facilitate the biological and pre-clinical studies for metastatic intracranial germinomas.

  3. Variation in the molecular clock of primates

    PubMed Central

    Moorjani, Priya; Amorim, Carlos Eduardo G.; Arndt, Peter F.; Przeworski, Molly

    2016-01-01

    Events in primate evolution are often dated by assuming a constant rate of substitution per unit time, but the validity of this assumption remains unclear. Among mammals, it is well known that there exists substantial variation in yearly substitution rates. Such variation is to be expected from differences in life history traits, suggesting it should also be found among primates. Motivated by these considerations, we analyze whole genomes from 10 primate species, including Old World Monkeys (OWMs), New World Monkeys (NWMs), and apes, focusing on putatively neutral autosomal sites and controlling for possible effects of biased gene conversion and methylation at CpG sites. We find that substitution rates are up to 64% higher in lineages leading from the hominoid–NWM ancestor to NWMs than to apes. Within apes, rates are ∼2% higher in chimpanzees and ∼7% higher in the gorilla than in humans. Substitution types subject to biased gene conversion show no more variation among species than those not subject to it. Not all mutation types behave similarly, however; in particular, transitions at CpG sites exhibit a more clocklike behavior than do other types, presumably because of their nonreplicative origin. Thus, not only the total rate, but also the mutational spectrum, varies among primates. This finding suggests that events in primate evolution are most reliably dated using CpG transitions. Taking this approach, we estimate the human and chimpanzee divergence time is 12.1 million years,​ and the human and gorilla divergence time is 15.1 million years​. PMID:27601674

  4. Variation in the molecular clock of primates.

    PubMed

    Moorjani, Priya; Amorim, Carlos Eduardo G; Arndt, Peter F; Przeworski, Molly

    2016-09-20

    Events in primate evolution are often dated by assuming a constant rate of substitution per unit time, but the validity of this assumption remains unclear. Among mammals, it is well known that there exists substantial variation in yearly substitution rates. Such variation is to be expected from differences in life history traits, suggesting it should also be found among primates. Motivated by these considerations, we analyze whole genomes from 10 primate species, including Old World Monkeys (OWMs), New World Monkeys (NWMs), and apes, focusing on putatively neutral autosomal sites and controlling for possible effects of biased gene conversion and methylation at CpG sites. We find that substitution rates are up to 64% higher in lineages leading from the hominoid-NWM ancestor to NWMs than to apes. Within apes, rates are ∼2% higher in chimpanzees and ∼7% higher in the gorilla than in humans. Substitution types subject to biased gene conversion show no more variation among species than those not subject to it. Not all mutation types behave similarly, however; in particular, transitions at CpG sites exhibit a more clocklike behavior than do other types, presumably because of their nonreplicative origin. Thus, not only the total rate, but also the mutational spectrum, varies among primates. This finding suggests that events in primate evolution are most reliably dated using CpG transitions. Taking this approach, we estimate the human and chimpanzee divergence time is 12.1 million years,​ and the human and gorilla divergence time is 15.1 million years​. PMID:27601674

  5. Variation in the molecular clock of primates.

    PubMed

    Moorjani, Priya; Amorim, Carlos Eduardo G; Arndt, Peter F; Przeworski, Molly

    2016-09-20

    Events in primate evolution are often dated by assuming a constant rate of substitution per unit time, but the validity of this assumption remains unclear. Among mammals, it is well known that there exists substantial variation in yearly substitution rates. Such variation is to be expected from differences in life history traits, suggesting it should also be found among primates. Motivated by these considerations, we analyze whole genomes from 10 primate species, including Old World Monkeys (OWMs), New World Monkeys (NWMs), and apes, focusing on putatively neutral autosomal sites and controlling for possible effects of biased gene conversion and methylation at CpG sites. We find that substitution rates are up to 64% higher in lineages leading from the hominoid-NWM ancestor to NWMs than to apes. Within apes, rates are ∼2% higher in chimpanzees and ∼7% higher in the gorilla than in humans. Substitution types subject to biased gene conversion show no more variation among species than those not subject to it. Not all mutation types behave similarly, however; in particular, transitions at CpG sites exhibit a more clocklike behavior than do other types, presumably because of their nonreplicative origin. Thus, not only the total rate, but also the mutational spectrum, varies among primates. This finding suggests that events in primate evolution are most reliably dated using CpG transitions. Taking this approach, we estimate the human and chimpanzee divergence time is 12.1 million years,​ and the human and gorilla divergence time is 15.1 million years​.

  6. Occurrence and distribution of Indian primates

    USGS Publications Warehouse

    Karanth, K.K.; Nichols, J.D.; Hines, J.E.

    2010-01-01

    Global and regional species conservation efforts are hindered by poor distribution data and range maps. Many Indian primates face extinction, but assessments of population status are hindered by lack of reliable distribution data. We estimated the current occurrence and distribution of 15 Indian primates by applying occupancy models to field data from a country-wide survey of local experts. We modeled species occurrence in relation to ecological and social covariates (protected areas, landscape characteristics, and human influences), which we believe are critical to determining species occurrence in India. We found evidence that protected areas positively influence occurrence of seven species and for some species are their only refuge. We found evergreen forests to be more critical for some primates along with temperate and deciduous forests. Elevation negatively influenced occurrence of three species. Lower human population density was positively associated with occurrence of five species, and higher cultural tolerance was positively associated with occurrence of three species. We find that 11 primates occupy less than 15% of the total land area of India. Vulnerable primates with restricted ranges are Golden langur, Arunachal macaque, Pig-tailed macaque, stump-tailed macaque, Phayre's leaf monkey, Nilgiri langur and Lion-tailed macaque. Only Hanuman langur and rhesus macaque are widely distributed. We find occupancy modeling to be useful in determining species ranges, and in agreement with current species ranking and IUCN status. In landscapes where monitoring efforts require optimizing cost, effort and time, we used ecological and social covariates to reliably estimate species occurrence and focus species conservation efforts. ?? Elsevier Ltd.

  7. Pancreas transplantation: review.

    PubMed

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

    2015-01-01

    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.

  8. 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

  9. Analysis of the Lipidome of Xenografts Using MALDI-IMS and UHPLC-ESI-QTOF

    NASA Astrophysics Data System (ADS)

    Fernández, Roberto; Lage, Sergio; Abad-García, Beatriz; Barceló-Coblijn, Gwendolyn; Terés, Silvia; López, Daniel H.; Guardiola-Serrano, Francisca; Martín, M. Laura; Escribá, Pablo V.; Fernández, José A.

    2014-07-01

    Human tumor xenografts in immunodeficient mice are a very popular model to study the development of cancer and to test new drug candidates. Among the parameters analyzed are the variations in the lipid composition, as they are good indicators of changes in the cellular metabolism. Here, we present a study on the distribution of lipids in xenografts of NCI-H1975 human lung cancer cells, using MALDI imaging mass spectrometry and UHPLC-ESI-QTOF. The identification of lipids directly from the tissue by MALDI was aided by the comparison with identification using ESI ionization in lipid extracts from the same xenografts. Lipids belonging to PCs, PIs, SMs, DAG, TAG, PS, PA, and PG classes were identified and their distribution over the xenograft was determined. Three areas were identified in the xenograft, corresponding to cells in different metabolic stages and to a layer of adipose tissue that covers the xenograft.

  10. Islet Cell Transplantation

    MedlinePlus

    ... the body use glucose for energy. Islet cell transplantation transfers cells from an organ donor into the ... to make and release insulin. Researchers hope islet transplantation will help people with type 1 diabetes live ...

  11. Transplantation for stroke.

    PubMed

    Roitberg, Ben

    2004-04-01

    have been suggested and tried. Methods and controversies abound, and include: local delivery of cells to the area of the stroke versus grafting to an area of the brain far removed form the stroke; cell therapy for reconstitution of structure and function versus use of cell grafts to support intrinsic repair and recovery mechanisms; intravascular administration of bone marrow or other stem cells; and combination grafts, or co-grafting of several cell types or cells and other substances. The various strategies address the issue of restorative treatments form different perspectives. Some interventions occur early after stroke, or are intended to preserve existing neural structures. For example, treatment strategies that aim to provide trophic support may demonstrate early beneficial results. Other strategies aim for growth and integration of new neurons to replace those lost after stroke. In this case, early beneficial results are not likely. Functional integration of grafted neurons, if it can ever happen, is likely to require training and exercise of the appropriate capacities. Further advances in preclinical studies of neural transplantation will require improved animal models with increased sensitivity to subtle behavioral and imaging changes. Non-human primate models have been established and may increase in importance as a phase before clinical trials. The future of brain repair for stroke is likely to require some form of combination therapy designed to replace the lost cells and supporting structure, attract new blood supply, support and enhance intrinsic repair and plasticity mechanisms. PMID:15142317

  12. 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

  13. 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

  14. Organ Transplants in Kazakhstan.

    PubMed

    Baigenzhin, Abay; Doskaliyev, Zhaksylyk; Tuganbekova, Saltanat; Zharikov, Serik; Altynova, Sholpan; Gaipov, Abduzhappar

    2015-11-01

    The Republic of Kazakhstan is one of the fastest developing countries in the world and has a health care system that is unique in Central Asia. Its organ transplant services are also developing rapidly. We aimed to analyze and briefly report on the current status of organ transplant in the Republic of Kazakhstan. We analyzed organ transplant activities in that country for the period 2012 to 2014. All data were collected from the official database of the National Transplant Coordinating Center of the Republic of Kazakhstan. At the end of 2014, the number of transplant centers had increased to 10, three of which could perform multiorgan transplants; during the same period, the number of deceased-donor organ-donating hospitals increased up to 37. By 2013, the transplant activity rate for all centers had reached 9.22 per million population. During the previous 3 years (2012-2014), there was a 3-fold increase in the number of living donors and an 18-fold increase in the number of kidney transplants. Between 2012 and 2014, the number of living-donor liver transplants increased from 17 to 25, and the number of deceased-donor transplants increased from 3 to 7. During the last 3 years (2012-2014), the number of heart transplants increased to 7 cases. During the last 3 years (2012-2014), Kazakhstan achieved a significant improvement in the organization of its transplant services, and a noticeable upward trend in the system continues.

  15. 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.

  16. Canine size, shape, and bending strength in primates and carnivores.

    PubMed

    Plavcan, J Michael; Ruff, Christopher B

    2008-05-01

    Anthropoid primates are well known for their highly sexually dimorphic canine teeth, with males possessing canines that are up to 400% taller than those of females. Primate canine dimorphism has been extensively documented, with a consensus that large male primate canines serve as weapons for intrasexual competition, and some evidence that large female canines in some species may likewise function as weapons. However, apart from speculation that very tall male canines may be relatively weak and that seed predators have strong canines, the functional significance of primate canine shape has not been explored. Because carnivore canine shape and size are associated with killing style, this group provides a useful comparative baseline for primates. We evaluate primate maxillary canine tooth size, shape and relative bending strength against body size, skull size, and behavioral and demographic measures of male competition and sexual selection, and compare them to those of carnivores. We demonstrate that, relative to skull length and body mass, primate male canines are on average as large as or larger than those of similar sized carnivores. The range of primate female canine sizes embraces that of carnivores. Male and female primate canines are generally as strong as or stronger than those of carnivores. Although we find that seed-eating primates have relatively strong canines, we find no clear relationship between male primate canine strength and demographic or behavioral estimates of male competition or sexual selection, in spite of a strong relationship between these measures and canine crown height. This suggests either that most primate canines are selected to be very strong regardless of variation in behavior, or that primate canine shape is inherently strong enough to accommodate changes in crown height without compromising canine function.

  17. Alefacept promotes immunosuppression-free renal allograft survival in nonhuman primates via depletion of recipient memory T cells.

    PubMed

    Lee, S; Yamada, Y; Tonsho, M; Boskovic, S; Nadazdin, O; Schoenfeld, D; Cappetta, K; Atif, M; Smith, R-N; Cosimi, A B; Benichou, G; Kawai, T

    2013-12-01

    Renal allograft tolerance has been achieved in MHC-mismatched primates via nonmyeloablative conditioning beginning 6 days prior to planned kidney and donor bone marrow transplantation (DBMT). To extend the applicability of this approach to deceased donor transplantation, we recently developed a novel-conditioning regimen, the "delayed protocol" in which donor bone marrow (DBM) is transplanted several months after kidney transplantation. However, activation/expansion of donor-reactive CD8(+) memory T cells (TMEM) occurring during the interval between kidney and DBM transplantation impaired tolerance induction using this strategy. In the current study, we tested whether, Alefacept, a fusion protein which targets LFA-3/CD2 interactions and selectively depletes CD2(high) CD8(+) effector memory T cells (TEM) could similarly induce long-term immunosuppression-free renal allograft survival but avoid the deleterious effects of anti-CD8 mAb treatment. We found that Alefacept significantly delayed the expansion of CD2(high) cells including CD8(+) TEM while sparing naïve CD8(+) T and NK cells and achieved mixed chimerism and long-term immunosuppression-free renal allograft survival. In conclusion, elimination of CD2(high) T cells represents a promising approach to prevent electively the expansion/activation of donor-reactive TEM and promotes tolerance induction via the delayed protocol mixed chimerism approach.

  18. 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

  19. 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

  20. Nonhuman primate models of polycystic ovary syndrome.

    PubMed

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

    2013-07-01

    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.

  1. 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

  2. Optogenetics in primates: a shining future?

    PubMed

    Gerits, Annelies; Vanduffel, Wim

    2013-07-01

    To understand the functional role of specific neurons in micro- and macro-brain circuitry, health, and disease, it is critical to control their activity precisely. This ambitious goal was first achieved by optogenetics, allowing researchers to increase or decrease neural activity artificially with high temporal and spatial precision. In contrast to the revolution optogenetics engendered in invertebrate and rodent research, only a few studies have reported optogenetic-induced neuronal and behavioral effects in primates. Such studies are nonetheless critical before optogenetics can be applied in a clinical setting. Here, we review the state-of-the-art tools for performing optogenetics in mammals, emphasizing recent neuronal and behavioral results obtained in nonhuman primates.

  3. Induced Pluripotent Stem Cells from Nonhuman Primates.

    PubMed

    Mishra, Anuja; Qiu, Zhifang; Farnsworth, Steven L; Hemmi, Jacob J; Li, Miao; Pickering, Alexander V; Hornsby, Peter J

    2016-01-01

    Induced pluripotent stem cells from nonhuman primates (NHPs) have unique roles in cell biology and regenerative medicine. Because of the relatedness of NHPs to humans, NHP iPS cells can serve as a source of differentiated derivatives that can be used to address important questions in the comparative biology of primates. Additionally, when used as a source of cells for regenerative medicine, NHP iPS cells serve an invaluable role in translational experiments in cell therapy. Reprogramming of NHP somatic cells requires the same conditions as previously established for human cells. However, throughout the process, a variety of modifications to the human cell protocols must be made to accommodate significant species differences.

  4. [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

  5. [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.

  6. Regression of prostate cancer xenografts by RLIP76 depletion

    PubMed Central

    Singhal, Sharad S.; Roth, Cherice; Leake, Kathryn; Singhal, Jyotsana; Yadav, Sushma; Awasthi, Sanjay

    2009-01-01

    RLIP76 plays a central role in radiation and chemotherapy resistance through its activity as a multi-specific ATP-dependent transporter which is over-expressed in a number of types of cancers. RLIP76 appears to be necessary for cancer cell survival because both in vitro cell culture and in vivo animal tumor studies show that depletion or inhibition of RLIP76 causes selective toxicity in malignant cells. RLIP76 induces apoptosis in cancer cells through the accumulation of endogenously formed GS-E. The results of our in vivo studies demonstrate that administration of RLIP76 antibodies, siRNA or anti-sense to mice bearing xenografts of PC-3 prostate cancer cells leads to near complete regression of established subcutaneous xenografts with no apparent toxic effects. Since anti-RLIP76 IgG (which inhibit RLIP76- mediated transport), siRNA and antisense (which deplete RLIP76) showed similar tumor regressing activities, our results indicate that the inhibition of RLIP76 transport activity at the cell surface is sufficient for observed anti-tumor activity. These studies indicate that RLIP76 serves a key effector function for the survival of prostate cancer cells and that it is a valid target for cancer therapy. PMID:19073149

  7. Integrated Analysis of Transcriptome in Cancer Patient-Derived Xenografts

    PubMed Central

    Li, Hong; Zhu, Yinjie; Tang, Xiaoyan; Li, Junyi; Li, Yuanyuan; Zhong, Zhaomin; Ding, Guohui; Li, Yixue

    2015-01-01

    Patient-derived xenograft (PDX) tumor model is a powerful technology in evaluating anti-cancer drugs and facilitating personalized medicines. Multiple research centers and commercial companies have put huge efforts into building PDX mouse models. However, PDX models have not been widely available and their molecular features have not been systematically characterized. In this study, we provided a comprehensive survey of PDX transcriptome by integrating analysis of 58 patients involving 8 different tumors. The median correlation coefficient between patients and xenografts is 0.94, which is higher than that between patients and cell line panel or between patients with the same tumor. Major differential gene expressions in PDX occur in the engraftment of human tumor tissue into mice, while gene expressions are relatively stable over passages. 48 genes are frequently differentially expressed in PDX mice of multiple cancers. They are enriched in extracellular matrix and immune response, and some are reported as targets for anticancer drugs. A simulation study showed that expression change between PDX and patient tumor (6%) would result in acceptable change in drug sensitivity (3%). Our findings demonstrate that PDX mice represent the gene-expression and drug-response features of primary tumors effectively, and it is recommended to monitoring the overall expression profiles and drug target genes in clinical application. PMID:25951608

  8. Reproducibility of Differential Proteomic Technologies in CPTAC Fractionated Xenografts

    PubMed Central

    2015-01-01

    The NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC) employed a pair of reference xenograft proteomes for initial platform validation and ongoing quality control of its data collection for The Cancer Genome Atlas (TCGA) tumors. These two xenografts, representing basal and luminal-B human breast cancer, were fractionated and analyzed on six mass spectrometers in a total of 46 replicates divided between iTRAQ and label-free technologies, spanning a total of 1095 LC–MS/MS experiments. These data represent a unique opportunity to evaluate the stability of proteomic differentiation by mass spectrometry over many months of time for individual instruments or across instruments running dissimilar workflows. We evaluated iTRAQ reporter ions, label-free spectral counts, and label-free extracted ion chromatograms as strategies for data interpretation (source code is available from http://homepages.uc.edu/~wang2x7/Research.htm). From these assessments, we found that differential genes from a single replicate were confirmed by other replicates on the same instrument from 61 to 93% of the time. When comparing across different instruments and quantitative technologies, using multiple replicates, differential genes were reproduced by other data sets from 67 to 99% of the time. Projecting gene differences to biological pathways and networks increased the degree of similarity. These overlaps send an encouraging message about the maturity of technologies for proteomic differentiation. PMID:26653538

  9. Integrated analysis of transcriptome in cancer patient-derived xenografts.

    PubMed

    Li, Hong; Zhu, Yinjie; Tang, Xiaoyan; Li, Junyi; Li, Yuanyuan; Zhong, Zhaomin; Ding, Guohui; Li, Yixue

    2015-01-01

    Patient-derived xenograft (PDX) tumor model is a powerful technology in evaluating anti-cancer drugs and facilitating personalized medicines. Multiple research centers and commercial companies have put huge efforts into building PDX mouse models. However, PDX models have not been widely available and their molecular features have not been systematically characterized. In this study, we provided a comprehensive survey of PDX transcriptome by integrating analysis of 58 patients involving 8 different tumors. The median correlation coefficient between patients and xenografts is 0.94, which is higher than that between patients and cell line panel or between patients with the same tumor. Major differential gene expressions in PDX occur in the engraftment of human tumor tissue into mice, while gene expressions are relatively stable over passages. 48 genes are frequently differentially expressed in PDX mice of multiple cancers. They are enriched in extracellular matrix and immune response, and some are reported as targets for anticancer drugs. A simulation study showed that expression change between PDX and patient tumor (6%) would result in acceptable change in drug sensitivity (3%). Our findings demonstrate that PDX mice represent the gene-expression and drug-response features of primary tumors effectively, and it is recommended to monitoring the overall expression profiles and drug target genes in clinical application.

  10. Mifepristone improves chemo-radiation response in glioblastoma xenografts

    PubMed Central

    2013-01-01

    Background We have investigated the ability of Mifepristone, an anti-progestin and anti-glucocorticoid drug, to modulate the antitumor effect of current standard clinical treatment in glioblastoma xenografts. Methods The effect of radiation alone or combined with Mifepristone and Temozolamide was evaluated on tumor growth in glioblastoma xenografts, both in terms of preferentially triggering tumor cell death and inhibiting angiogenesis. Tumor size was measured once a week using a caliper and tumor metabolic-activity was carried out by molecular imaging using a microPET/CT scanner. The effect of Mifepristone on the expression of angiogenic factors after concomitant radio-chemotherapy was determined using a quantitative real-time PCR analysis of VEGF gene expression. Results The analysis of the data shows a significant antitumoral effect by the simultaneous administration of radiation-Mifepristone-Temozolamide in comparison with radiation alone or radiation-Temozolamide. Conclusion Our results suggest that Mifepristone could improve the efficacy of chemo-radiotherapy in Glioblastoma. The addition of Mifepristone to standard radiation-Temozolamide therapy represents a potential approach as a chemo-radio-sensitizer in treating GBMs, which have very limited treatment options. PMID:23530939

  11. 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

  12. Macroporous Three Dimensional PDMS Scaffolds for Extrahepatic Islet Transplantation

    PubMed Central

    Pedraza, Eileen; Brady, Ann-Christina; Fraker, Christopher A.; Molano, R. Damaris; Sukert, Steven; Berman, Dora M.; Kenyon, Norma S.; Pileggi, Antonello; Ricordi, Camillo; Stabler, Cherie L.

    2015-01-01

    Clinical islet transplantation has demonstrated success in treating type 1 diabetes. A current limitation is the intrahepatic portal vein transplant site, which is prone to mechanical stress and inflammation. Transplantation of pancreatic islets into alternative sites is preferable, but challenging, as it may require a three-dimensional vehicle to confer mechanical protection and to confine islets to a well-defined, retrievable space where islet neovascularization can occur. We have fabricated biostable, macroporous scaffolds from poly(dimethylsiloxane) (PDMS) and investigated islet retention and distribution, metabolic function, and glucose-dependent insulin secretion within these materials. Islets from multiple sources, including rodents, non-human primates, and humans, were tested in vitro. We observed high islet retention and distribution within PDMS scaffolds, with retention of small islets (< 100 µm) improved through the post-loading addition of fibrin gel. Islets loaded within PDMS scaffolds exhibited viability and function comparable to standard culture conditions when incubated under normal oxygen tensions, but displayed improved viability compared to standard two-dimensional culture controls under low oxygen tensions. In vivo efficacy of scaffolds to support islet grafts was evaluated after transplantation in the omental pouch of chemically-induced diabetic syngeneic rats, which promptly achieved normoglycemia. Collectively, these results are promising in that they indicate the potential for transplanting islets into a clinically relevant, extrahepatic site that provides spatial distribution of islets, as well as intra-device vascularization. PMID:23031502

  13. Prospective Clinical Testing of Regulatory Dendritic Cells in Organ Transplantation

    PubMed Central

    Thomson, Angus W.; Zahorchak, Alan F.; Ezzelarab, Mohamed B.; Butterfield, Lisa H.; Lakkis, Fadi G.; Metes, Diana M.

    2016-01-01

    Dendritic cells (DC) are rare, professional antigen-presenting cells with ability to induce or regulate alloimmune responses. Regulatory DC (DCreg) with potential to down-modulate acute and chronic inflammatory conditions that occur in organ transplantation can be generated in vitro under a variety of conditions. Here, we provide a rationale for evaluation of DCreg therapy in clinical organ transplantation with the goal of promoting sustained, donor-specific hyporesponsiveness, while lowering the incidence and severity of rejection and reducing patients’ dependence on anti-rejection drugs. Generation of donor- or recipient-derived DCreg that suppress T cell responses and prolong transplant survival in rodents or non-human primates has been well-described. Recently, good manufacturing practice (GMP)-grade DCreg have been produced at our Institution for prospective use in human organ transplantation. We briefly review experience of regulatory immune therapy in organ transplantation and describe our experience generating and characterizing human monocyte-derived DCreg. We propose a phase I/II safety study in which the influence of donor-derived DCreg combined with conventional immunosuppression on subclinical and clinical rejection and host alloimmune responses will be examined in detail. PMID:26858719

  14. Efficient and Targeted Transduction of Nonhuman Primate Liver With Systemically Delivered Optimized AAV3B Vectors.

    PubMed

    Li, Shaoyong; Ling, Chen; Zhong, Li; Li, Mengxin; Su, Qin; He, Ran; Tang, Qiushi; Greiner, Dale L; Shultz, Leonard D; Brehm, Michael A; Flotte, Terence R; Mueller, Christian; Srivastava, Arun; Gao, Guangping

    2015-12-01

    Recombinant adeno-associated virus serotype 3B (rAAV3B) can transduce cultured human liver cancer cells and primary human hepatocytes efficiently. Serine (S)- and threonine (T)-directed capsid modifications further augment its transduction efficiency. Systemically delivered capsid-optimized rAAV3B vectors can specifically target cancer cells in a human liver cancer xenograft model, suggesting their potential use for human liver-directed gene therapy. Here, we compared transduction efficiencies of AAV3B and AAV8 vectors in cultured primary human hepatocytes and cancer cells as well as in human and mouse hepatocytes in a human liver xenograft NSG-PiZ mouse model. We also examined the safety and transduction efficacy of wild-type (WT) and capsid-optimized rAAV3B in the livers of nonhuman primates (NHPs). Intravenously delivered S663V+T492V (ST)-modified self-complementary (sc) AAV3B-EGFP vectors led to liver-targeted robust enhanced green fluorescence protein (EGFP) expression in NHPs without apparent hepatotoxicity. Intravenous injections of both WT and ST-modified rAAV3B.ST-rhCG vectors also generated stable super-physiological levels of rhesus chorionic gonadotropin (rhCG) in NHPs. The vector genome predominantly targeted the liver. Clinical chemistry and histopathology examinations showed no apparent vector-related toxicity. Our studies should be important and informative for clinical development of optimized AAV3B vectors for human liver-directed gene therapy.

  15. Relaxin and the control of primate parturition.

    PubMed

    Weiss, Gerson

    2013-01-01

    In primate pregnancy, circulating relaxin, solely a product of the corpus luteum, peaks in the first trimester of pregnancy then declines and levels off for the remainder of pregnancy. Relaxin actions in pregnancy include increasing cervical pro-MMP-1 and pro-MMP-3 and decreasing TIMP-1, changes which soften the cervix. Relaxin, from early pregnancy, increases endometrial natural killer cells, macrophages and neutrophils, blood flow and arterial number. Hyperrelaxinemia correlates with preterm birth.

  16. 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

  17. 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.

  18. Argentine hemorrhagic fever: a primate model.

    PubMed

    Weissenbacher, M C; Calello, M A; Colillas, O J; Rondinone, S N; Frigerio, M J

    1979-01-01

    Experimental Junin virus infection of a New World primate, Callithrix jacchus, was evaluated. The virus produced anorexia, loss of weight, thrombocytopenia, leukopenia, and hemorrhagic and neurological symptoms and terminated in death. Virus was recovered from urine, blood samples and all tissues taken at autopsy. These preliminary observations show that several aspects of the experimental disease in C. jacchus are quite similar to severe natural Argentine hemorrhagic fever of man.

  19. 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

  20. Human amniotic membrane-derived epithelial stem cells display anticancer activity in BALB/c female nude mice bearing disseminated breast cancer xenografts.

    PubMed

    Kang, Nam-Hee; Yi, Bo-Rim; Lim, So Yoon; Hwang, Kyung-A; Baek, Young Seok; Kang, Kyung-Sun; Choi, Kyung-Chul

    2012-06-01

    Breast cancer is one of the most common malignant tumors and the leading cause of mortality among women. In this study, we propose a human stem cell transplantation strategy, an important method for treating various cancers, as a potential breast cancer therapy. To this end, we used human amniotic membrane-derived epithelial stem cells (hAECs) as a cell source for performing human stem cell transplantation. hAECs have multipotent differentiation abilities and possess high proliferative potential. We transplanted hAECs into female BALB/c nude mice bearing tumors originating from MDA-MB-231 breast cancer cells. Co-culturred hAECs and MDA-MB-231 cells at a ratio of 1:4 or 1:8 (tumor cells to stem cells) inhibited breast cancer cell growth by 67.29 and 67.33%, respectively. In the xenograft mouse model, tumor volumes were significantly decreased by 5-flurouracil (5-FU) treatment and two different ratios of hAECs (1:4 and 1:8) by 84.33, 73.88 and 56.89%, respectively. Treatment of nude mice with hAECs (1:4) produced remarkable antitumor effects without any side-effects (e.g., weight loss, death and bruising) compared to the mice that received only 5-FU treatment. Tumor progression was significantly reduced by hAEC treatment compared to the xenograft model. On the other hand, breast tissues (e.g., the epidermis, dermis and reticular layer) appeared to be well-maintained following treatment with hAECs. Taken together, these results provide strong evidence that hAECs can be used as a safe and effective cancer-targeting cytotherapy for treating breast cancer.

  1. [Transplantation and outcome quality].

    PubMed

    Bechstein, W O; Wullstein, C

    2002-06-01

    Organ transplants are procedures which require intensive personal and material resources. The results of organ transplants have continuously improved during recent decades. International data bases (registries) have documented the continuous evolution of organ transplantation. On the basis of the German Transplant Law guidelines for "Requirements regarding quality control for procedures related to organ procurement and transplantation" have been formulated by the German Medical Chamber. Thus, monitoring of outcome quality will become a requirement for all German transplant centers. In this paper, the guidelines for the different organ transplants (kidney, pancreas, liver, heart, lung) are discussed as well as quality control for living donor transplantation. Studies from the USA and Europe demonstrated volume-outcome relationships in organ transplantation. In addition, in kidney transplantation a centre-effect could be demonstrated which influences outcome more than the immunological match between donor and recipient. The introduction of required quality control may have far reaching consequences for the future structure of organ transplantation in Germany. PMID:12149941

  2. THE KINEMATICS OF PRIMATE MIDFOOT FLEXIBILITY

    PubMed Central

    Greiner, Thomas M.; Ball, Kevin A.

    2015-01-01

    This study describes a unique assessment of primate intrinsic foot joint kinematics based upon bone pin rigid cluster tracking. It challenges the assumption that human evolution resulted in a reduction of midfoot flexibility, which has been identified in other primates as the “midtarsal break.” Rigid cluster pins were inserted into the foot bones of human, chimpanzee, baboon and macaque cadavers. The positions of these bone pins were monitored during a plantarflexion-dorsiflexion movement cycle. Analysis resolved flexion-extension movement patterns and the associated orientation of rotational axes for the talonavicular, calcaneocuboid and lateral cubometatarsal joints. Results show that midfoot flexibility occurs primarily at the talonavicular and cubometatarsal joints. The rotational magnitudes are roughly similar between humans and chimps. There is also a similarity among evaluated primates in the observed rotations of the lateral cubometatarsal joint, but there was much greater rotation observed for the talonavicular joint, which may serve to differentiate monkeys from the hominines. It appears that the capability for a midtarsal break is present within the human foot. A consideration of the joint axes shows that the medial and lateral joints have opposing orientations, which has been associated with a rigid locking mechanism in the human foot. However, the potential for this same mechanism also appears in the chimpanzee foot. These findings demonstrate a functional similarity within the midfoot of the hominines. Therefore, the kinematic capabilities and restrictions for the skeletal linkages of the human foot may not be as unique as has been previously suggested. PMID:25234343

  3. 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

  4. Behavioral abnormalities in captive nonhuman primates.

    PubMed

    Mallapur, Avanti; Choudhury, B C

    2003-01-01

    In this study, we dealt with 11 species of nonhuman primates across 10 zoos in India. We recorded behavior as instantaneous scans between 9 a.m. and 5 p.m. In the study, we segregated behaviors for analyses into abnormal, undesirable, active, and resting. The 4 types of abnormal behavior exhibited included floating limb, self-biting, self-clasping, and stereotypic pacing. In the study, we recorded 2 types of undesirable behavior: autoerotic stimulation and begging. Langurs and group-housed macaques did not exhibit undesirable behaviors. A male lion-tailed macaque and a male gibbon exhibited begging behavior. autoerotic stimulation and self-biting occurred rarely. Males exhibited higher levels of undesirable behavior than did females. Animals confiscated from touring zoos, circuses, and animal traders exhibited higher levels of abnormal behaviors than did animals reared in larger, recognized zoos. The stump-tailed macaque was the only species to exhibit floating limb, autoerotic stimulation, self-biting, and self-clasping. Our results show that rearing experience and group composition influence the proportions of abnormal behavior exhibited by nonhuman primates in captivity. The history of early social and environmental deprivation in these species of captive nonhuman primates probably is critical in the development of behavioral pathologies. Establishing this will require further research.

  5. Emotions, stress, and maternal motivation in primates.

    PubMed

    Maestripieri, Dario

    2011-06-01

    Recent research conducted with nonhuman primates confirms that adaptive emotional processes, such as maternal attraction arousability and maternal anxiety arousability, enhance and sustain female motivation to interact with infants, invest in them, and protect them during the postpartum period. Changes in these emotional processes, and concomitant changes in maternal motivation, facilitate the reduction and eventual termination of maternal investment associated with infant weaning. Although laboratory studies of rodents and socially deprived rhesus monkeys have suggested that nulliparous females are neophobic and find infant stimuli aversive, recent primate research indicates that neophobia or aversion to infant stimuli do not occur in females with normal developmental experience. Furthermore, although some rodent and human studies have shown that lactation is accompanied by physiological hyporesponsiveness to stress, other studies of rodents, nonhuman primates, and humans indicate that mothers are highly vulnerable to stress and that stress-induced dysregulation of emotions can interfere with maternal motivation and parenting behavior. It is possible that some aspects of the emotional and experiential regulation of maternal motivation and parental behavior are different in different mammalian species. However, variation in the environments in which subjects are tested and in their developmental experience may also be responsible for the some discrepancies between the results of different studies.

  6. Phylogenomics of primates and their ancestral populations

    PubMed Central

    Siepel, Adam

    2009-01-01

    Genome assemblies are now available for nine primate species, and large-scale sequencing projects are underway or approved for six others. An explicitly evolutionary and phylogenetic approach to comparative genomics, called phylogenomics, will be essential in unlocking the valuable information about evolutionary history and genomic function that is contained within these genomes. However, most phylogenomic analyses so far have ignored the effects of variation in ancestral populations on patterns of sequence divergence. These effects can be pronounced in the primates, owing to large ancestral effective population sizes relative to the intervals between speciation events. In particular, local genealogies can vary considerably across loci, which can produce biases and diminished power in many phylogenomic analyses of interest, including phylogeny reconstruction, the identification of functional elements, and the detection of natural selection. At the same time, this variation in genealogies can be exploited to gain insight into the nature of ancestral populations. In this Perspective, I explore this area of intersection between phylogenetics and population genetics, and its implications for primate phylogenomics. I begin by “lifting the hood” on the conventional tree-like representation of the phylogenetic relationships between species, to expose the population-genetic processes that operate along its branches. Next, I briefly review an emerging literature that makes use of the complex relationships among coalescence, recombination, and speciation to produce inferences about evolutionary histories, ancestral populations, and natural selection. Finally, I discuss remaining challenges and future prospects at this nexus of phylogenetics, population genetics, and genomics. PMID:19801602

  7. Advances in pancreas transplantation.

    PubMed

    Dholakia, Shamik; Oskrochi, Youssof; Easton, Graham; Papalois, Vassilios

    2016-04-01

    The potential to reverse diabetes has to be balanced against the morbidity of long-term immunosuppression associated with transplantation. For a patient with renal failure, the treatment of choice is often a simultaneous transplant of the pancreas and kidney or pancreas after kidney. For a patient with glycaemic instability, choices between a solid organ or islet transplant have to be weighed against benefits and risks of remaining on insulin. Results of simultaneous transplant of the pancreas and kidney transplantation are comparable to other solid-organ transplants, and there is evidence of improved quality of life and life expectancy. There is some evidence of benefit with respect to the progression of secondary diabetic complications in patients with functioning transplants for several years.

  8. Infection Prevention in Transplantation.

    PubMed

    Pergam, Steven A

    2016-01-01

    The number of patients undergoing hematopoietic cell and solid organ transplantation are increasing every year, as are the number of centers both transplanting and caring for these patients. Improvements in transplant procedures, immunosuppressive regimens, and prevention of transplant-associated complications have led to marked improvements in survival in both populations. Infections remain one of the most important sources of excess morbidity and mortality in transplant, and therefore, infection prevention strategies are a critical element for avoiding these complications in centers caring for high-risk patients. This manuscript aims to provide an update of recent data on prevention of major healthcare-associated infections unique to transplantation, reviews the emergence of antimicrobial resistant infections, and discusses updated strategies to both identify and prevent transmission of these pathogens in transplant recipients.

  9. The oldest known primate skeleton and early haplorhine evolution.

    PubMed

    Ni, Xijun; Gebo, Daniel L; Dagosto, Marian; Meng, Jin; Tafforeau, Paul; Flynn, John J; Beard, K Christopher

    2013-06-01

    Reconstructing the earliest phases of primate evolution has been impeded by gaps in the fossil record, so that disagreements persist regarding the palaeobiology and phylogenetic relationships of the earliest primates. Here we report the discovery of a nearly complete and partly articulated skeleton of a primitive haplorhine primate from the early Eocene of China, about 55 million years ago, the oldest fossil primate of this quality ever recovered. Coupled with detailed morphological examination using propagation phase contrast X-ray synchrotron microtomography, our phylogenetic analysis based on total available evidence indicates that this fossil is the most basal known member of the tarsiiform clade. In addition to providing further support for an early dichotomy between the strepsirrhine and haplorhine clades, this new primate further constrains the age of divergence between tarsiiforms and anthropoids. It also strengthens the hypothesis that the earliest primates were probably diurnal, arboreal and primarily insectivorous mammals the size of modern pygmy mouse lemurs.

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

    PubMed Central

    Larsen, Christian P.; Page, Andrew; Linzie, Kelly Hamby; Russell, Maria; Deane, Taylor; Stempora, Linda; Strobert, Elizabeth; Penedo, Maria Cecilia T.; Ward, Thea; Wiseman, Roger; O'Connor, David; Miller, Weston; Sen, Sharon; Singh, Karnail; Kean, Leslie S.

    2010-01-01

    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 non-myeloablative transplant. Using busulfan-based pre-transplant 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 present post-transplant 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

  11. Therapeutic efficacy evaluation of 111in-VNB-liposome on human colorectal adenocarcinoma HT-29/ luc mouse xenografts

    NASA Astrophysics Data System (ADS)

    Lee, Wan-Chi; Hwang, Jeng-Jong; Tseng, Yun-Long; Wang, Hsin-Ell; Chang, Ya-Fang; Lu, Yi-Ching; Ting, Gann; Whang-Peng, Jaqueline; Wang, Shyh-Jen

    2006-12-01

    The purpose of this study is to evaluate the therapeutic efficacy of the liposome encaged with vinorelbine (VNB) and 111In-oxine on human colorectal adenocarcinoma (HT-29) using HT-29/ luc mouse xenografts. HT-29 cells stably transfected with plasmid vectors containing luciferase gene ( luc) were transplanted subcutaneously into the male NOD/SCID mice. Biodistribution of the drug was performed when tumor size reached 500-600 mm 3. The uptakes of 111In-VNB-liposome in tumor and normal tissues/organs at various time points postinjection were assayed. Multimodalities, including gamma scintigraphy, bioluminescence imaging (BLI) and whole-body autoradiography (WBAR), were applied for evaluating the therapeutic efficacy when tumor size was about 100 mm 3. The tumor/blood ratios of 111In-VNB-liposome were 0.044, 0.058, 2.690, 20.628 and 24.327, respectively, at 1, 4, 24, 48 and 72 h postinjection. Gamma scinitigraphy showed that the tumor/muscle ratios were 2.04, 2.25 and 4.39, respectively, at 0, 5 and 10 mg/kg VNB. BLI showed that significant tumor control was achieved in the group of 10 mg/kg VNB ( 111In-VNB-liposome). WBAR also confirmed this result. In this study, we have demonstrated a non-invasive imaging technique with a luciferase reporter gene and BLI for evaluation of tumor treatment efficacy in vivo. The SCID mice bearing HT-29/ luc xenografts treated with 111In-VNB-liposome were shown with tumor reduction by this technique.

  12. The adaptive value of primate color vision for predator detection.

    PubMed

    Pessoa, Daniel Marques Almeida; Maia, Rafael; de Albuquerque Ajuz, Rafael Cavalcanti; De Moraes, Pedro Zurvaino Palmeira Melo Rosa; Spyrides, Maria Helena Constantino; Pessoa, Valdir Filgueiras

    2014-08-01

    The complex evolution of primate color vision has puzzled biologists for decades. Primates are the only eutherian mammals that evolved an enhanced capacity for discriminating colors in the green-red part of the spectrum (trichromatism). However, while Old World primates present three types of cone pigments and are routinely trichromatic, most New World primates exhibit a color vision polymorphism, characterized by the occurrence of trichromatic and dichromatic females and obligatory dichromatic males. Even though this has stimulated a prolific line of inquiry, the selective forces and relative benefits influencing color vision evolution in primates are still under debate, with current explanations focusing almost exclusively at the advantages in finding food and detecting socio-sexual signals. Here, we evaluate a previously untested possibility, the adaptive value of primate color vision for predator detection. By combining color vision modeling data on New World and Old World primates, as well as behavioral information from human subjects, we demonstrate that primates exhibiting better color discrimination (trichromats) excel those displaying poorer color visions (dichromats) at detecting carnivoran predators against the green foliage background. The distribution of color vision found in extant anthropoid primates agrees with our results, and may be explained by the advantages of trichromats and dichromats in detecting predators and insects, respectively. PMID:24535839

  13. Comparative primate genomics: emerging patterns of genome content and dynamics.

    PubMed

    Rogers, Jeffrey; Gibbs, Richard A

    2014-05-01

    Advances in genome sequencing technologies have created new opportunities for comparative primate genomics. Genome assemblies have been published for various primate species, and analyses of several others are underway. Whole-genome assemblies for the great apes provide remarkable new information about the evolutionary origins of the human genome and the processes involved. Genomic data for macaques and other non-human primates offer valuable insights into genetic similarities and differences among species that are used as models for disease-related research. This Review summarizes current knowledge regarding primate genome content and dynamics, and proposes a series of goals for the near future.

  14. Comparative primate genomics: emerging patterns of genome content and dynamics.

    PubMed

    Rogers, Jeffrey; Gibbs, Richard A

    2014-05-01

    Advances in genome sequencing technologies have created new opportunities for comparative primate genomics. Genome assemblies have been published for various primate species, and analyses of several others are underway. Whole-genome assemblies for the great apes provide remarkable new information about the evolutionary origins of the human genome and the processes involved. Genomic data for macaques and other non-human primates offer valuable insights into genetic similarities and differences among species that are used as models for disease-related research. This Review summarizes current knowledge regarding primate genome content and dynamics, and proposes a series of goals for the near future. PMID:24709753

  15. Comparative primate genomics: emerging patterns of genome content and dynamics

    PubMed Central

    Rogers, Jeffrey; Gibbs, Richard A.

    2014-01-01

    Preface Advances in genome sequencing technologies have created new opportunities for comparative primate genomics. Genome assemblies have been published for several primates, with analyses of several others underway. Whole genome assemblies for the great apes provide remarkable new information about the evolutionary origins of the human genome and the processes involved. Genomic data for macaques and other nonhuman primates provide valuable insight into genetic similarities and differences among species used as models for disease-related research. This review summarizes current knowledge regarding primate genome content and dynamics and offers a series of goals for the near future. PMID:24709753

  16. Why is a landscape perspective important in studies of primates?

    PubMed

    Arroyo-Rodríguez, Víctor; Fahrig, Lenore

    2014-10-01

    With accelerated deforestation and fragmentation through the tropics, assessing the impact that landscape spatial changes may have on biodiversity is paramount, as this information is required to design and implement effective management and conservation plans. Primates are expected to be particularly dependent on the landscape context; yet, our understanding on this topic is limited as the majority of primate studies are at the local scale, meaning that landscape-scale inferences are not possible. To encourage primatologists to assess the impact of landscape changes on primates, and help future studies on the topic, we describe the meaning of a "landscape perspective" and evaluate important assumptions of using such a methodological approach. We also summarize a number of important, but unanswered, questions that can be addressed using a landscape-scale study design. For example, it is still unclear if habitat loss has larger consistent negative effects on primates than habitat fragmentation per se. Furthermore, interaction effects between habitat area and other landscape effects (e.g., fragmentation) are unknown for primates. We also do not know if primates are affected by synergistic interactions among factors at the landscape scale (e.g., habitat loss and diseases, habitat loss and climate change, hunting, and land-use change), or whether landscape complexity (or landscape heterogeneity) is important for primate conservation. Testing for patterns in the responses of primates to landscape change will facilitate the development of new guidelines and principles for improving primate conservation.

  17. The adaptive value of primate color vision for predator detection.

    PubMed

    Pessoa, Daniel Marques Almeida; Maia, Rafael; de Albuquerque Ajuz, Rafael Cavalcanti; De Moraes, Pedro Zurvaino Palmeira Melo Rosa; Spyrides, Maria Helena Constantino; Pessoa, Valdir Filgueiras

    2014-08-01

    The complex evolution of primate color vision has puzzled biologists for decades. Primates are the only eutherian mammals that evolved an enhanced capacity for discriminating colors in the green-red part of the spectrum (trichromatism). However, while Old World primates present three types of cone pigments and are routinely trichromatic, most New World primates exhibit a color vision polymorphism, characterized by the occurrence of trichromatic and dichromatic females and obligatory dichromatic males. Even though this has stimulated a prolific line of inquiry, the selective forces and relative benefits influencing color vision evolution in primates are still under debate, with current explanations focusing almost exclusively at the advantages in finding food and detecting socio-sexual signals. Here, we evaluate a previously untested possibility, the adaptive value of primate color vision for predator detection. By combining color vision modeling data on New World and Old World primates, as well as behavioral information from human subjects, we demonstrate that primates exhibiting better color discrimination (trichromats) excel those displaying poorer color visions (dichromats) at detecting carnivoran predators against the green foliage background. The distribution of color vision found in extant anthropoid primates agrees with our results, and may be explained by the advantages of trichromats and dichromats in detecting predators and insects, respectively.

  18. Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates

    NASA Astrophysics Data System (ADS)

    Veiseh, Omid; Doloff, Joshua C.; Ma, Minglin; Vegas, Arturo J.; Tam, Hok Hei; Bader, Andrew R.; Li, Jie; Langan, Erin; Wyckoff, Jeffrey; Loo, Whitney S.; Jhunjhunwala, Siddharth; Chiu, Alan; Siebert, Sean; Tang, Katherine; Hollister-Lock, Jennifer; Aresta-Dasilva, Stephanie; Bochenek, Matthew; Mendoza-Elias, Joshua; Wang, Yong; Qi, Merigeng; Lavin, Danya M.; Chen, Michael; Dholakia, Nimit; Thakrar, Raj; Lacík, Igor; Weir, Gordon C.; Oberholzer, Jose; Greiner, Dale L.; Langer, Robert; Anderson, Daniel G.

    2015-06-01

    The efficacy of implanted biomedical devices is often compromised by host recognition and subsequent foreign body responses. Here, we demonstrate the role of the geometry of implanted materials on their biocompatibility in vivo. In rodent and non-human primate animal models, implanted spheres 1.5 mm and above in diameter across a broad spectrum of materials, including hydrogels, ceramics, metals and plastics, significantly abrogated foreign body reactions and fibrosis when compared with smaller spheres. We also show that for encapsulated rat pancreatic islet cells transplanted into streptozotocin-treated diabetic C57BL/6 mice, islets prepared in 1.5-mm alginate capsules were able to restore blood-glucose control for up to 180 days, a period more than five times longer than for transplanted grafts encapsulated within conventionally sized 0.5-mm alginate capsules. Our findings suggest that the in vivo biocompatibility of biomedical devices can be significantly improved simply by tuning their spherical dimensions.

  19. Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates

    PubMed Central

    Veiseh, Omid; Doloff, Joshua C.; Ma, Minglin; Vegas, Arturo J.; Tam, Hok Hei; Bader, Andrew R.; Li, Jie; Langan, Erin; Wyckoff, Jeffrey; Loo, Whitney S.; Jhunjhunwala, Siddharth; Chiu, Alan; Siebert, Sean; Tang, Katherine; Hollister-Lock, Jennifer; Aresta-Dasilva, Stephanie; Bochenek, Matthew; Mendoza-Elias, Joshua; Wang, Yong; Qi, Merigeng; Lavin, Danya M.; Chen, Michael; Dholakia, Nimit; Thakrar, Raj; Lacík, Igor; Weir, Gordon C.; Oberholzer, Jose; Greiner, Dale L.; Langer, Robert; Anderson, Daniel G.

    2015-01-01

    The efficacy of implanted biomedical devices is often compromised by host recognition and subsequent foreign body responses. Here, we demonstrate the role of the geometry of implanted materials on their biocompatibility in vivo. In rodent and non-human primate animal models, implanted spheres 1.5 mm and above in diameter across a broad spectrum of materials, including hydrogels, ceramics, metals, and plastics, significantly abrogated foreign body reactions and fibrosis when compared to smaller spheres. We also show that for encapsulated rat pancreatic islet cells transplanted into streptozotocin-treated diabetic C57BL/6 mice, islets prepared in 1.5 mm alginate capsules were able to restore blood-glucose control for up to 180 days, a period more than 5-fold longer than for transplanted grafts encapsulated within conventionally sized 0.5-mm alginate capsules. Our findings suggest that the in vivo biocompatibility of biomedical devices can be significantly improved by simply tuning their spherical dimensions. PMID:25985456

  20. Transplantation of Simian Mesenchymal Stem Cells to Baboons with Experimentally Induced Myocardial Infarction.

    PubMed

    Agrba, V Z; Porkhanov, V A; Karal-Ogly, D D; Leontyuk, A V; Kovalenko, A L; Sholin, I Yu; Gvozdik, T E; Ignatova, I E; Agumava, A A; Chuguev, Yu P; Gvaramiya, I A; Lapin, B A

    2016-02-01

    Culture of mesenchymal stem cells isolated from the bone marrow of primates by their characteristics met the requirements of stem cells. It was shown that transplantation of allogeneic mesenchymal stem cells (2 million cells per 1 kg body weight) immediately after ligation of the left anterior descending coronary artery between the middle and upper thirds led to neovascularization and capillarization of the ischemic myocardium. PMID:26906203

  1. Imaging Axl expression in pancreatic and prostate cancer xenografts

    SciTech Connect

    Nimmagadda, Sridhar; Pullambhatla, Mrudula; Lisok, Ala; Hu, Chaoxin; Maitra, Anirban; Pomper, Martin G

    2014-01-10

    Highlights: •Axl is overexpressed in a variety of cancers. •Axl overexpression confers invasive phenotype. •Axl imaging would be useful for therapeutic guidance and monitoring. •Axl expression imaging is demonstrated in pancreatic and prostate cancer xenografts. •Graded levels of Axl expression imaging is feasible. -- Abstract: The receptor tyrosine kinase Axl is overexpressed in and leads to patient morbidity and mortality in a variety of cancers. Axl–Gas6 interactions are critical for tumor growth, angiogenesis and metastasis. The goal of this study was to investigate the feasibility of imaging graded levels of Axl expression in tumors using a radiolabeled antibody. We radiolabeled anti-human Axl (Axl mAb) and control IgG1 antibodies with {sup 125}I with high specific radioactivity and radiochemical purity, resulting in an immunoreactive fraction suitable for in vivo studies. Radiolabeled antibodies were investigated in severe combined immunodeficient mice harboring subcutaneous CFPAC (Axl{sup high}) and Panc1 (Axl{sup low}) pancreatic cancer xenografts by ex vivo biodistribution and imaging. Based on these results, the specificity of [{sup 125}I]Axl mAb was also validated in mice harboring orthotopic Panc1 or CFPAC tumors and in mice harboring subcutaneous 22Rv1 (Axl{sup low}) or DU145 (Axl{sup high}) prostate tumors by ex vivo biodistribution and imaging studies at 72 h post-injection of the antibody. Both imaging and biodistribution studies demonstrated specific and persistent accumulation of [{sup 125}I]Axl mAb in Axl{sup high} (CFPAC and DU145) expression tumors compared to the Axl{sup low} (Panc1 and 22Rv1) expression tumors. Axl expression in these tumors was further confirmed by immunohistochemical studies. No difference in the uptake of radioactivity was observed between the control [{sup 125}I]IgG1 antibody in the Axl{sup high} and Axl{sup low} expression tumors. These data demonstrate the feasibility of imaging Axl expression in pancreatic

  2. Comparative analysis of the primate X-inactivation center region and reconstruction of the ancestral primate XIST locus

    PubMed Central

    Horvath, Julie E.; Sheedy, Christina B.; Merrett, Stephanie L.; Diallo, Abdoulaye Banire; Swofford, David L.; NISC Comparative Sequencing Program; Green, Eric D.; Willard, Huntington F.

    2011-01-01

    Here we provide a detailed comparative analysis across the candidate X-Inactivation Center (XIC) region and the XIST locus in the genomes of six primates and three mammalian outgroup species. Since lemurs and other strepsirrhine primates represent the sister lineage to all other primates, this analysis focuses on lemurs to reconstruct the ancestral primate sequences and to gain insight into the evolution of this region and the genes within it. This comparative evolutionary genomics approach reveals significant expansion in genomic size across the XIC region in higher primates, with minimal size alterations across the XIST locus itself. Reconstructed primate ancestral XIC sequences show that the most dramatic changes during the past 80 million years occurred between the ancestral primate and the lineage leading to Old World monkeys. In contrast, the XIST locus compared between human and the primate ancestor does not indicate any dramatic changes to exons or XIST-specific repeats; rather, evolution of this locus reflects small incremental changes in overall sequence identity and short repeat insertions. While this comparative analysis reinforces that the region around XIST has been subject to significant genomic change, even among primates, our data suggest that evolution of the XIST sequences themselves represents only small lineage-specific changes across the past 80 million years. PMID:21518738

  3. Prioritizing therapeutic targets using patient-derived xenograft models.

    PubMed

    Lodhia, K A; Hadley, A M; Haluska, P; Scott, C L

    2015-04-01

    Effective systemic treatment of cancer relies on the delivery of agents with optimal therapeutic potential. The molecular age of medicine has provided genomic tools that can identify a large number of potential therapeutic targets in individual patients, heralding the promise of personalized treatment. However, determining which potential targets actually drive tumor growth and should be prioritized for therapy is challenging. Indeed, reliable molecular matches of target and therapeutic agent have been stringently validated in the clinic for only a small number of targets. Patient-derived xenografts (PDXs) are tumor models developed in immunocompromised mice using tumor procured directly from the patient. As patient surrogates, PDX models represent a powerful tool for addressing individualized therapy. Challenges include humanizing the immune system of PDX models and ensuring high quality molecular annotation, in order to maximize insights for the clinic. Importantly, PDX can be sampled repeatedly and in parallel, to reveal clonal evolution, which may predict mechanisms of drug resistance and inform therapeutic strategy design.

  4. Transplantation psychoneuroimmunology: building hypotheses.

    PubMed

    Klapheke, M M

    2000-06-01

    The research findings of psychoneuroimmunology have not yet been fully applied to the field of transplantation psychiatry. Though much study has been devoted to the impact of psychiatric disease on the immunosuppressed state and disease progression in HIV-related illness, little has yet been written on the immunology implications of psychiatric disturbances in the immunosuppressed post-transplant patient. Utilizing Medline literature searches to review relevant research data in psychoneuroimmunology and transplantation immunology, the author formulates and examines four transplantation psychoneuroimmunology hypotheses involving the potential impact of depression on post-transplant organ rejection, cancer, coronary artery disease, and infections. The author concludes that though major questions remain, it appears reasonable to include the impact of depression, and possibly other psychological states, among factors that may affect the net state of immunosuppression in transplant patients.

  5. Lung transplantation at Duke

    PubMed Central

    Gray, Alice L.; Hartwig, Matthew G.

    2016-01-01

    Lung transplantation represents the gold-standard therapy for patients with end-stage lung disease. Utilization of this therapy continues to rise. The Lung Transplant Program at Duke University Medical Center was established in 1992, and since that time has grown to one of the highest volume centers in the world. The program to date has performed over 1,600 lung transplants. This report represents an up-to-date review of the practice and management strategies employed for safe and effective lung transplantation at our center. Specific attention is paid to the evaluation of candidacy for lung transplantation, donor selection, surgical approach, and postoperative management. These evidence-based strategies form the foundation of the clinical transplantation program at Duke. PMID:27076968

  6. Cuba's kidney transplantation program.

    PubMed

    Mármol, Alexander; Pérez, Alexis; Pérez de Prado, Juan C; Fernández-Vega, Silvia; Gutiérrez, Francisco; Arce, Sergio

    2010-10-01

    The first kidney transplant in Cuba was performed on 24 February 1970, using a cadaveric donor. In 1979, living donor kidney transplantation began between first-degree relatives. A total of 2775 patients are enrolled in renal replacement therapy in 47 hospitals across the country, 1440 of whom are awaiting kidney transplantation. Organs for the kidney program are procured in 63 accredited hospitals equipped for multidisciplinary management of brain death. Accordingly, over 90% of transplanted kidneys are from cadaveric donors. Identification of potential recipients is carried out through a national, computerized program that affords all patients the same opportunity regardless of distance from a transplant center, and selection of the most suitable candidate is based primarily on HLA compatibility. KEYWORDS Chronic renal failure, kidney transplantation.

  7. Effect of ionizing radiation on the primate pancreas: an endocrine and morphologic study

    SciTech Connect

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

    1987-01-01

    In this study we evaluated the endocrine, biochemical, and haematological derangements as well as pancreatic and histological changes of the bonemarrow in the primate following external fractionated subtotal marrow irradiation without bonemarrow reconstitution. The irradiation was administered in preparation for pancreatic transplantation. Two groups of animals (ten in each group) received 800 rad (8 Gy) and 1000 rad (10 Gy) respectively over 4 to 5 weeks. A maximum of 200 rads (2 Gy) were administered weekly as photons from a 6 MV linear accelerator. During irradiation the animals remained normoglycaemic in the presence of transiently elevated liver enzymes and serum amylase values, which returned to normal on completion of the irradiation. Insulin release was significantly reduced in both groups during irradiation and was associated with minimally decreased K-values in the presence of mild glucose intolerance. Pancreatic light morphologic changes included structural changes of both exocrine and endocrine elements and included necrosis of the islet cells and acinar tissue. Islet histology demonstrated striking cytocavitary network changes of alpha and beta cells, including degranulation, vacuolization, mitochondrial destruction, and an increase in lysosomes. A hypoplastic bonemarrow ranging from moderate to severe was observed in all irradiated recipients. Near total fractionated body irradiation in the primate is therefore associated with elevated liver enzymes, pancytopenia, transient hyperamylasaemia, hypoinsulinaemia, a varying degree of pancreatitis, and bonemarrow hypoplasia.

  8. Human Embryonic Stem Cell-Derived Cardiomyocytes Regenerate Non-Human Primate Hearts

    PubMed Central

    Chong, James J.H.; Yang, Xiulan; Don, Creighton W.; Minami, Elina; Liu, Yen-Wen; Weyers, Jill J; Mahoney, William M.; Van Biber, Benjamin; Cook, Savannah M.; Palpant, Nathan J; Gantz, Jay; Fugate, James A.; Muskheli, Veronica; Gough, G. Michael; Vogel, Keith W.; Astley, Cliff A.; Hotchkiss, Charlotte E.; Baldessari, Audrey; Pabon, Lil; Reinecke, Hans; Gill, Edward A.; Nelson, Veronica; Kiem, Hans-Peter; Laflamme, Michael A.; Murry, Charles E.

    2014-01-01

    Pluripotent stem cells provide a potential solution to current epidemic rates of heart failure 1 by providing human cardiomyocytes to support heart regeneration 2. Studies of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) in small animal models have shown favorable effects of this treatment 3–7. It remains unknown, however, whether clinical scale hESC-CMs transplantation is feasible, safe or can provide large-scale myocardial regeneration. Here we show that hESC-CMs can be produced at a clinical scale (>1 billion cells/batch) and cryopreserved with good viability. Using a non-human primate (NHP) model of myocardial ischemia-reperfusion, we show that that cryopreservation and intra-myocardial delivery of 1 billion hESC-CMs generates significant remuscularization of the infarcted heart. The hESC-CMs showed progressive but incomplete maturation over a three-month period. Grafts were perfused by host vasculature, and electromechanical junctions between graft and host myocytes were present within 2 weeks of engraftment. Importantly, grafts showed regular calcium transients that were synchronized to the host electrocardiogram, indicating electromechanical coupling. In contrast to small animal models 7, non-fatal ventricular arrhythmias were observed in hESC-CM engrafted primates. Thus, hESC-CMs can remuscularize substantial amounts of the infarcted monkey heart. Comparable remuscularization of a human heart should be possible, but potential arrhythmic complications need to be overcome. PMID:24776797

  9. Why Primates? The Importance of Nonhuman Primates for Understanding Human Infancy

    ERIC Educational Resources Information Center

    Weiss, Daniel J.; Santos, Laurie R.

    2006-01-01

    We introduce the thematic collection by noting some striking similarities in the cognitive abilities of human infants and nonhuman primates. What are the implications of these similarities for our comprehension of human infant cognition? After providing a brief historical and conceptual background on comparative behavioral research, we discuss how…

  10. The Ethics of Infection Challenges in Primates.

    PubMed

    Barnhill, Anne; Joffe, Steven; Miller, Franklin G

    2016-07-01

    In the midst of the recent Ebola outbreak, scientific developments involving infection challenge experiments on nonhuman primates (NHPs) sparked hope that successful treatments and vaccines may soon become available. Yet these studies pose a stark ethical quandary. On the one hand, they represent an important step in developing novel therapies and vaccines for Ebola and the Marburg virus, with the potential to save thousands of human lives and to protect whole communities from devastation; on the other hand, they intentionally expose sophisticated animals to severe suffering and a high risk of death. Other studies that infect NHPs with a lethal disease in order to test interventions that may prove beneficial for humans pose the same ethical difficulty. Some advocates have argued that all research on primates should be phased out, and ethicists have questioned whether a moral justification of primate research is possible. A 2010 European Union directive banned virtually all research on great apes, and 2013 guidelines from the National Institutes of Health (NIH), based upon recommendations in an influential 2011 Institute of Medicine (IOM) report, eliminated most biomedical research with chimpanzees in the United States. But studies involving other NHPs face no comparable restrictions. Should research on NHPs other than great apes be subject to tighter restrictions than it currently is? In this article, we explore this general question in the context of one particular type of biomedical research: infection challenge studies. We advocate a presumptive prohibition on infection challenge experiments in NHPs, but we also argue that exceptions to this prohibition are permissible, subject to strict substantive and procedural safeguards, when necessary to avert substantial loss of human life or severe morbidity for a substantial number of people. PMID:27417865

  11. The Ethics of Infection Challenges in Primates.

    PubMed

    Barnhill, Anne; Joffe, Steven; Miller, Franklin G

    2016-07-01

    In the midst of the recent Ebola outbreak, scientific developments involving infection challenge experiments on nonhuman primates (NHPs) sparked hope that successful treatments and vaccines may soon become available. Yet these studies pose a stark ethical quandary. On the one hand, they represent an important step in developing novel therapies and vaccines for Ebola and the Marburg virus, with the potential to save thousands of human lives and to protect whole communities from devastation; on the other hand, they intentionally expose sophisticated animals to severe suffering and a high risk of death. Other studies that infect NHPs with a lethal disease in order to test interventions that may prove beneficial for humans pose the same ethical difficulty. Some advocates have argued that all research on primates should be phased out, and ethicists have questioned whether a moral justification of primate research is possible. A 2010 European Union directive banned virtually all research on great apes, and 2013 guidelines from the National Institutes of Health (NIH), based upon recommendations in an influential 2011 Institute of Medicine (IOM) report, eliminated most biomedical research with chimpanzees in the United States. But studies involving other NHPs face no comparable restrictions. Should research on NHPs other than great apes be subject to tighter restrictions than it currently is? In this article, we explore this general question in the context of one particular type of biomedical research: infection challenge studies. We advocate a presumptive prohibition on infection challenge experiments in NHPs, but we also argue that exceptions to this prohibition are permissible, subject to strict substantive and procedural safeguards, when necessary to avert substantial loss of human life or severe morbidity for a substantial number of people.

  12. Trabecular bone structure in the primate wrist.

    PubMed

    Schilling, Ann-Marie; Tofanelli, Sergio; Hublin, Jean-Jacques; Kivell, Tracy L

    2014-05-01

    Trabecular (or cancellous) bone has been shown to respond to mechanical loading throughout ontogeny and thus can provide unique insight into skeletal function and locomotion in comparative studies of living and fossil mammalian morphology. Trabecular bone of the hand may be particularly functionally informative because the hand has more direct contact with the substrate compared with the remainder of the forelimb during locomotion in quadrupedal mammals. This study investigates the trabecular structure within the wrist across a sample of haplorhine primates that vary in locomotor behaviour (and thus hand use) and body size. High-resolution microtomographic scans were collected of the lunate, scaphoid, and capitate in 41 individuals and eight genera (Homo, Gorilla, Pan, Papio, Pongo, Symphalangus, Hylobates, and Ateles). We predicted that particular trabecular parameters would 1) vary across suspensory, quadrupedal, and bipedal primates based on differences in hand use and load, and 2) scale with carpal size following similar allometric patterns found previously in other skeletal elements across a larger sample of mammals and primates. Analyses of variance (trabecular parameters analysed separately) and principal component analyses (trabecular parameters analysed together) revealed no clear functional signal in the trabecular structure of any of the three wrist bones. Instead, there was a large degree of variation within suspensory and quadrupedal locomotor groups, as well as high intrageneric variation within some taxa, particularly Pongo and Gorilla. However, as predicted, Homo sapiens, which rarely use their hands for locomotion and weight support, were unique in showing lower relative bone volume (BV/TV) compared with all other taxa. Furthermore, parameters used to quantify trabecular structure within the wrist scale with size generally following similar allometric patterns found in trabeculae of other mammalian skeletal elements. We discuss the challenges

  13. Stepwise evolution of stable sociality in primates.

    PubMed

    Shultz, Susanne; Opie, Christopher; Atkinson, Quentin D

    2011-11-09

    Although much attention has been focused on explaining and describing the diversity of social grouping patterns among primates, less effort has been devoted to understanding the evolutionary history of social living. This is partly because social behaviours do not fossilize, making it difficult to infer changes over evolutionary time. However, primate social behaviour shows strong evidence for phylogenetic inertia, permitting the use of Bayesian comparative methods to infer changes in social behaviour through time, thereby allowing us to evaluate alternative models of social evolution. Here we present a model of primate social evolution, whereby sociality progresses from solitary foraging individuals directly to large multi-male/multi-female aggregations (approximately 52 million years (Myr) ago), with pair-living (approximately 16 Myr ago) or single-male harem systems (approximately 16 Myr ago) derivative from this second stage. This model fits the data significantly better than the two widely accepted alternatives (an unstructured model implied by the socioecological hypothesis or a model that allows linear stepwise changes in social complexity through time). We also find strong support for the co-evolution of social living with a change from nocturnal to diurnal activity patterns, but not with sex-biased dispersal. This supports suggestions that social living may arise because of increased predation risk associated with diurnal activity. Sociality based on loose aggregation is followed by a second shift to stable or bonded groups. This structuring facilitates the evolution of cooperative behaviours and may provide the scaffold for other distinctive anthropoid traits including coalition formation, cooperative resource defence and large brains.

  14. Intestinal transplantation: a review.

    PubMed

    Desai, Chirag Sureshchandra; Khan, Khalid Mahmood; Girlanda, Raffaele; Fishbein, Thomas M

    2012-09-01

    Parenteral nutrition is a life-saving therapy for patients with intestinal failure. Intestinal transplantation is now recognized as a treatment for patients who develop complications of parenteral nutrition and in whom attempts at intestinal rehabilitation have failed. Patients with parenteral nutrition related liver disease will require a liver graft typically part of a multivisceral transplant. Isolated intestinal transplants are more commonly performed in adults while multivisceral transplants are most commonly performed in infants. Isolated intestinal transplants have the best short-term outcome, with over 80 % survival at 1 year. Patients requiring multivisceral transplants have a high rate of attrition with a 1 year survival less than 70 %. Prognostic factors for a poor outcome include patient hospitalization at the time of transplant and donor age greater than 40 years while systemic sepsis and acute rejection are the major determinant of early postoperative outcome. For patients surviving the first year the outcome of transplantation of the liver in addition to intestine affords some survival advantage though long-term outcome does not yet match other abdominal organs. Outcomes for intestinal retransplantation are poor as a result of immunology and patient debility. Overall intestinal transplantation continues to develop and is a clear indication with cost and quality of life advantages in patients with intestinal failure that do not remain stable on parenteral nutrition.

  15. [Infertility and kidney transplantation].

    PubMed

    Atallah, David; Salameh, Charbel; El Kassis, Nadine; Safi, Joelle; Lutfallah, Fouad; Bejjani, Lina; Ghaname, Wadih; Moukarzel, Maroun

    2015-01-01

    Renal failure impairs the endocrine system, especially in women, due to hyperprolactinemia, altering fertility, ovulatory cycles, libido and growth in adolescents. Renal transplantation is considered the best solution to the problems of renal failure and and of dialysis, as evidenced by comparing the rate of hyperprolactinemia (100% in chronic renal failure, 60% in patients on dialysis and 35% in post-transplantation). Kidney transplant is less efficient for restoring perfect function of the hypothalamic-pituitary-gonadal axis due in part to the immunosuppressant regimens prescribed. When these drugs are properly managed, transplantation will restore near normal sexual function.

  16. Split liver transplantation.

    PubMed

    Yersiz, H; Cameron, A M; Carmody, I; Zimmerman, M A; Kelly, B S; Ghobrial, R M; Farmer, D G; Busuttil, R W

    2006-03-01

    Seventy-five thousand Americans develop organ failure each year. Fifteen percent of those on the list for transplantation die while waiting. Several possible mechanisms to expand the organ pool are being pursued including the use of extended criteria donors, living donation, and split deceased donor transplants. Cadaveric organ splitting results from improved understanding of the surgical anatomy of the liver derived from Couinaud. Early efforts focused on reduced-liver transplantation (RLT) reported by both Bismuth and Broelsch in the mid-1980s. These techniques were soon modified to create both a left lateral segment graft appropriate for a pediatric recipient and a right trisegment for an appropriately sized adult. Techniques of split liver transplantation (SLT) were also modified to create living donor liver transplantation. Pichlmayr and Bismuth reported successful split liver transplantation in 1989 and Emond reported a larger series of nine split procedures in 1990. Broelsch and Busuttil described a technical modification in which the split was performed in situ at the donor institution with surgical division completed in the heart beating cadaveric donor. In situ splitting reduces cold ischemia, simplifies identification of biliary and vascular structures, and reduces reperfusion hemorrhage. However, in situ splits require specialized skills, prolonged operating room time, and increased logistical coordination at the donor institution. At UCLA over 120 in situ splits have been performed and this technique is the default when an optimal donor is available. Split liver transplantation now accounts for 10% of adult transplantations at UCLA and 40% of pediatric transplantations.

  17. Two Influential Primate Classifications Logically Aligned

    PubMed Central

    Franz, Nico M.; Pier, Naomi M.; Reeder, Deeann M.; Chen, Mingmin; Yu, Shizhuo; Kianmajd, Parisa; Bowers, Shawn; Ludäscher, Bertram

    2016-01-01

    Classifications and phylogenies of perceived natural entities change in the light of new evidence. Taxonomic changes, translated into Code-compliant names, frequently lead to name:meaning dissociations across succeeding treatments. Classification standards such as the Mammal Species of the World (MSW) may experience significant levels of taxonomic change from one edition to the next, with potential costs to long-term, large-scale information integration. This circumstance challenges the biodiversity and phylogenetic data communities to express taxonomic congruence and incongruence in ways that both humans and machines can process, that is, to logically represent taxonomic alignments across multiple classifications. We demonstrate that such alignments are feasible for two classifications of primates corresponding to the second and third MSW editions. Our approach has three main components: (i) use of taxonomic concept labels, that is name sec. author (where sec. means according to), to assemble each concept hierarchy separately via parent/child relationships; (ii) articulation of select concepts across the two hierarchies with user-provided Region Connection Calculus (RCC-5) relationships; and (iii) the use of an Answer Set Programming toolkit to infer and visualize logically consistent alignments of these input constraints. Our use case entails the Primates sec. Groves (1993; MSW2–317 taxonomic concepts; 233 at the species level) and Primates sec. Groves (2005; MSW3–483 taxonomic concepts; 376 at the species level). Using 402 RCC-5 input articulations, the reasoning process yields a single, consistent alignment and 153,111 Maximally Informative Relations that constitute a comprehensive meaning resolution map for every concept pair in the Primates sec. MSW2/MSW3. The complete alignment, and various partitions thereof, facilitate quantitative analyses of name:meaning dissociation, revealing that nearly one in three taxonomic names are not reliable across

  18. Biorhythms and space experiments with nonhuman primates

    NASA Technical Reports Server (NTRS)

    Winget, C. M.

    1977-01-01

    Man's response to exposure to spaceflight and weightlessness is expressed in physiological adjustments which involve his health and ability to function. The amplitude and periodicity of fluctuations in biological processes affect various functions and responses to provocative stimuli. Primates and other species are subjected to tests to determine the consequences of an altered biorhythm on work and performance, emotional stability, biomedical evaluation in space, the ability to cope with the unexpected, and susceptibility to infection, toxicity, radiation, drugs, and stress. Factors in the environment or operational setup which can change the physiological baseline must be determined and controlled.

  19. Two Influential Primate Classifications Logically Aligned.

    PubMed

    Franz, Nico M; Pier, Naomi M; Reeder, Deeann M; Chen, Mingmin; Yu, Shizhuo; Kianmajd, Parisa; Bowers, Shawn; Ludäscher, Bertram

    2016-07-01

    Classifications and phylogenies of perceived natural entities change in the light of new evidence. Taxonomic changes, translated into Code-compliant names, frequently lead to name:meaning dissociations across succeeding treatments. Classification standards such as the Mammal Species of the World (MSW) may experience significant levels of taxonomic change from one edition to the next, with potential costs to long-term, large-scale information integration. This circumstance challenges the biodiversity and phylogenetic data communities to express taxonomic congruence and incongruence in ways that both humans and machines can process, that is, to logically represent taxonomic alignments across multiple classifications. We demonstrate that such alignments are feasible for two classifications of primates corresponding to the second and third MSW editions. Our approach has three main components: (i) use of taxonomic concept labels, that is name sec. author (where sec. means according to), to assemble each concept hierarchy separately via parent/child relationships; (ii) articulation of select concepts across the two hierarchies with user-provided Region Connection Calculus (RCC-5) relationships; and (iii) the use of an Answer Set Programming toolkit to infer and visualize logically consistent alignments of these input constraints. Our use case entails the Primates sec. Groves (1993; MSW2-317 taxonomic concepts; 233 at the species level) and Primates sec. Groves (2005; MSW3-483 taxonomic concepts; 376 at the species level). Using 402 RCC-5 input articulations, the reasoning process yields a single, consistent alignment and 153,111 Maximally Informative Relations that constitute a comprehensive meaning resolution map for every concept pair in the Primates sec. MSW2/MSW3. The complete alignment, and various partitions thereof, facilitate quantitative analyses of name:meaning dissociation, revealing that nearly one in three taxonomic names are not reliable across treatments

  20. Primates, Provisioning and Plants: Impacts of Human Cultural Behaviours on Primate Ecological Functions

    PubMed Central

    Sengupta, Asmita; McConkey, Kim R.; Radhakrishna, Sindhu

    2015-01-01

    Human provisioning of wildlife with food is a widespread global practice that occurs in multiple socio-cultural circumstances. Provisioning may indirectly alter ecosystem functioning through changes in the eco-ethology of animals, but few studies have quantified this aspect. Provisioning of primates by humans is known to impact their activity budgets, diets and ranging patterns. Primates are also keystone species in tropical forests through their role as seed dispersers; yet there is no information on how provisioning might affect primate ecological functions. The rhesus macaque is a major human-commensal species but is also an important seed disperser in the wild. In this study, we investigated the potential impacts of provisioning on the role of rhesus macaques as seed dispersers in the Buxa Tiger Reserve, India. We studied a troop of macaques which were provisioned for a part of the year and were dependent on natural resources for the rest. We observed feeding behaviour, seed handling techniques and ranging patterns of the macaques and monitored availability of wild fruits. Irrespective of fruit availability, frugivory and seed dispersal activities decreased when the macaques were provisioned. Provisioned macaques also had shortened daily ranges implying shorter dispersal distances. Finally, during provisioning periods, seeds were deposited on tarmac roads that were unconducive for germination. Provisioning promotes human-primate conflict, as commensal primates are often involved in aggressive encounters with humans over resources, leading to negative consequences for both parties involved. Preventing or curbing provisioning is not an easy task as feeding wild animals is a socio-cultural tradition across much of South and South-East Asia, including India. We recommend the initiation of literacy programmes that educate lay citizens about the ill-effects of provisioning and strongly caution them against the practice. PMID:26536365

  1. Primates, Provisioning and Plants: Impacts of Human Cultural Behaviours on Primate Ecological Functions.

    PubMed

    Sengupta, Asmita; McConkey, Kim R; Radhakrishna, Sindhu

    2015-01-01

    Human provisioning of wildlife with food is a widespread global practice that occurs in multiple socio-cultural circumstances. Provisioning may indirectly alter ecosystem functioning through changes in the eco-ethology of animals, but few studies have quantified this aspect. Provisioning of primates by humans is known to impact their activity budgets, diets and ranging patterns. Primates are also keystone species in tropical forests through their role as seed dispersers; yet there is no information on how provisioning might affect primate ecological functions. The rhesus macaque is a major human-commensal species but is also an important seed disperser in the wild. In this study, we investigated the potential impacts of provisioning on the role of rhesus macaques as seed dispersers in the Buxa Tiger Reserve, India. We studied a troop of macaques which were provisioned for a part of the year and were dependent on natural resources for the rest. We observed feeding behaviour, seed handling techniques and ranging patterns of the macaques and monitored availability of wild fruits. Irrespective of fruit availability, frugivory and seed dispersal activities decreased when the macaques were provisioned. Provisioned macaques also had shortened daily ranges implying shorter dispersal distances. Finally, during provisioning periods, seeds were deposited on tarmac roads that were unconducive for germination. Provisioning promotes human-primate conflict, as commensal primates are often involved in aggressive encounters with humans over resources, leading to negative consequences for both parties involved. Preventing or curbing provisioning is not an easy task as feeding wild animals is a socio-cultural tradition across much of South and South-East Asia, including India. We recommend the initiation of literacy programmes that educate lay citizens about the ill-effects of provisioning and strongly caution them against the practice. PMID:26536365

  2. The unique value of primate models in translational research. Nonhuman primate models of women's health: introduction and overview.

    PubMed

    Shively, Carol A; Clarkson, Thomas B

    2009-09-01

    This special issue of AJP is focused on research using nonhuman primates as models to further the understanding of women's health. Nonhuman primates play a unique role in translational science by bridging the gap between basic and clinical investigations. The use of nonhuman primates in biomedical research challenges our resolve to treat all life as sacred. The scientific community has responded by developing ethical guidelines for the care and the use of primates and clarifying the responsibility of investigators to insure the physical and psychological well-being of nonhuman primates used in research. Preclinical investigations often involve the use of animal models. Rodent models have been the mainstay of biomedical science and have provided enormous insight into the workings of many mammalian systems that have proved applicable to human biological systems. Rodent models are dissimilar to primates in numerous ways, which may limit the generalizability to human biological systems. These limitations are much less likely in nonhuman primates and in Old World primates, in particular, Macaques are useful models for investigations involving the reproductive system, bioenergetics, obesity and diabetes, cardiovascular health, central nervous system function, cognitive and social behavior, the musculoskeletal system, and diseases of aging. This issue considers primate models of polycystic ovary syndrome; diet effects on glycemic control, breast and endometrium; estrogen, reproductive life stage and atherosclerosis; estrogen and diet effects on inflammation in atherogenesis; the neuroprotective effects of estrogen therapy; social stress and visceral obesity; and sex differences in the role of social status in atherogenesis. Unmet research needs in women's health include the use of diets in nonhuman primate studies that are similar to those consumed by human beings, primate models of natural menopause, dementia, hypertension, colon cancer, and frailty in old age, and

  3. Bone marrow transplant – children - discharge

    MedlinePlus

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

  4. Development of payload subsystem-primate mission-Biosatellite program

    NASA Technical Reports Server (NTRS)

    Hall, J. F., Jr.

    1971-01-01

    Design and operation of the primate life support subsystem for the Biosatellite Program as used during the flight of Biosatellite 3 are discussed. Included are preflight changes necessitated by the primate's (a Macaca nemistrina monkey) influence on the initial equipment design.

  5. What Cognitive Representations Support Primate Theory of Mind?

    PubMed

    Martin, Alia; Santos, Laurie R

    2016-05-01

    Much recent work has examined the evolutionary origins of human mental state representations. This work has yielded strikingly consistent results: primates show a sophisticated ability to track the current and past perceptions of others, but they fail to represent the beliefs of others. We offer a new account of the nuanced performance of primates in theory of mind (ToM) tasks. We argue that primates form awareness relations tracking the aspects of reality that other agents are aware of. We contend that these awareness relations allow primates to make accurate predictions in social situations, but that this capacity falls short of our human-like representational ToM. We end by explaining how this new account makes important new empirical predictions about primate ToM.

  6. In Transition: Primate Genomics at a Time of Rapid Change

    PubMed Central

    Rogers, Jeffrey

    2013-01-01

    The field of nonhuman primate genomics is undergoing rapid change and making impressive progress. Exploiting new technologies for DNA sequencing, researchers have generated new whole-genome sequence assemblies for multiple primate species over the past 6 years. In addition, investigations of within-species genetic variation, gene expression and RNA sequences, conservation of non-protein-coding regions of the genome, and other aspects of comparative genomics are moving at an accelerating speed. This progress is opening a wide array of new research opportunities in the analysis of comparative primate genome content and evolution. It also creates new possibilities for the use of nonhuman primates as model organisms in biomedical research. This transition, based on both new technology and the new information being generated in regard to human genetics, provides an important justification for reevaluating the research goals, strategies, and study designs used in primate genetics and genomics. PMID:24174444

  7. Derivation of sperm from xenografted testis cells and tissues of the peccary (Tayassu tajacu).

    PubMed

    Campos-Junior, Paulo Henrique Almeida; Costa, Guilherme Mattos Jardim; Avelar, Gleide Fernandes; Lacerda, Samyra Maria Santos Nassif; da Costa, Nathália Nogueira; Ohashi, Otávio Mitio; Miranda, Moysés dos Santos; Barcelos, Lucíola Silva; Jorge, Erika Cristina; Guimarães, Diva Anelie; de França, Luiz Renato

    2014-03-01

    Because the collared peccary (Tayassu tajacu) has a peculiar Leydig cell cytoarchitecture, this species represents a unique mammalian model for investigating testis function. Taking advantage of the well-established and very useful testis xenograft technique, in the present study, testis tissue and testis cell suspensions from immature collared peccaries (n=4; 3 months old) were xenografted in SCID mice (n=48) and evaluated at 2, 4, 6, and 8 months after grafting. Complete spermatogenesis was observed at 6 and 8 months after testis tissue xenografting. However, probably due to de novo testis morphogenesis and low androgen secretion, functionally evaluated by the seminal vesicle weight, a delay in spermatogenesis progression was observed in the testis cell suspension xenografts, with the production of fertile sperm only at 8 months after grafting. Importantly, demonstrating that the peculiar testicular cytoarchitecture of the collared peccary is intrinsically programmed, the unique Leydig cell arrangement observed in this species was re-established after de novo testis morphogenesis. The sperm collected from the xenografts resulted in diploid embryos that expressed the paternally imprinted gene NNAT after ICSI. The present study is the first to demonstrate complete spermatogenesis with the production of fertile sperm from testis cell suspension xenografts in a wild mammalian species. Therefore, due to its unique testicular cytoarchitecture, xenograft techniques, particularly testis cell suspensions, may represent a new and very promising approach to evaluate testis morphogenesis and to investigate spermatogonial stem cell physiology and niche in the collared peccary.

  8. Vorinostat, an HDAC inhibitor attenuates epidermoid squamous cell carcinoma growth by dampening mTOR signaling pathway in a human xenograft murine model

    SciTech Connect

    Kurundkar, Deepali; Srivastava, Ritesh K.; Chaudhary, Sandeep C.; Ballestas, Mary E.; Kopelovich, Levy; Elmets, Craig A.; Athar, Mohammad

    2013-01-15

    Histone deacetylase (HDAC) inhibitors are potent anticancer agents and show efficacy against various human neoplasms. Vorinostat is a potent HDAC inhibitor and has shown potential to inhibit growth of human xenograft tumors. However, its effect on the growth of skin neoplasm remains undefined. In this study, we show that vorinostat (2 μM) reduced expression of HDAC1, 2, 3, and 7 in epidermoid carcinoma A431 cells. Consistently, it increased acetylation of histone H3 and p53. Vorinostat (100 mg/kg body weight, IP) treatment reduced human xenograft tumor growth in highly immunosuppressed nu/nu mice. Histologically, the vorinostat-treated tumor showed features of well-differentiation with large necrotic areas. Based on proliferating cell nuclear antigen (PCNA) staining and expression of cyclins D1, D2, E, and A, vorinostat seems to impair proliferation by down-regulating the expression of these proteins. However, it also induced apoptosis. The mechanism by which vorinostat blocks proliferation and makes tumor cells prone to apoptosis, involved inhibition of mTOR signaling which was accompanied by reduction in cell survival AKT and extracellular-signal regulated kinase (ERK) signaling pathways. Our data provide a novel mechanism-based therapeutic intervention for cutaneous squamous cell carcinoma (SCC). Vorinostat may be utilized to cure skin neoplasms in organ transplant recipient (OTR). These patients have high morbidity and surgical removal of these lesions which frequently develop in these patients, is difficult. -- Highlights: ► Vorinostat reduces SCC growth in a xenograft murine model. ► Vorinostat dampens proliferation and induces apoptosis in tumor cells. ► Diminution in mTOR, Akt and ERK signaling underlies inhibition in proliferation. ► Vorinostat by inhibiting HDACs inhibits epithelial–mesenchymal transition.

  9. Primate vaginal microbiomes exhibit species specificity without universal Lactobacillus dominance

    PubMed Central

    Yildirim, Suleyman; Yeoman, Carl J; Janga, Sarath Chandra; Thomas, Susan M; Ho, Mengfei; Leigh, Steven R; Consortium, Primate Microbiome; White, Bryan A; Wilson, Brenda A; Stumpf, Rebecca M

    2014-01-01

    Bacterial communities colonizing the reproductive tracts of primates (including humans) impact the health, survival and fitness of the host, and thereby the evolution of the host species. Despite their importance, we currently have a poor understanding of primate microbiomes. The composition and structure of microbial communities vary considerably depending on the host and environmental factors. We conducted comparative analyses of the primate vaginal microbiome using pyrosequencing of the 16S rRNA genes of a phylogenetically broad range of primates to test for factors affecting the diversity of primate vaginal ecosystems. The nine primate species included: humans (Homo sapiens), yellow baboons (Papio cynocephalus), olive baboons (Papio anubis), lemurs (Propithecus diadema), howler monkeys (Alouatta pigra), red colobus (Piliocolobus rufomitratus), vervets (Chlorocebus aethiops), mangabeys (Cercocebus atys) and chimpanzees (Pan troglodytes). Our results indicated that all primates exhibited host-specific vaginal microbiota and that humans were distinct from other primates in both microbiome composition and diversity. In contrast to the gut microbiome, the vaginal microbiome showed limited congruence with host phylogeny, and neither captivity nor diet elicited substantial effects on the vaginal microbiomes of primates. Permutational multivariate analysis of variance and Wilcoxon tests revealed correlations among vaginal microbiota and host species-specific socioecological factors, particularly related to sexuality, including: female promiscuity, baculum length, gestation time, mating group size and neonatal birth weight. The proportion of unclassified taxa observed in nonhuman primate samples increased with phylogenetic distance from humans, indicative of the existence of previously unrecognized microbial taxa. These findings contribute to our understanding of host–microbe variation and coevolution, microbial biogeography, and disease risk, and have important

  10. Fallback foods, preferred foods, adaptive zones, and primate origins.

    PubMed

    Rosenberger, Alfred L

    2013-09-01

    Appreciation has grown for the impact of tropical forest seasonality and fallback foods on primate diets, behaviors, and morphology. As critically important resources in times of shortage, seasonal fallback foods may have an outsized role in selecting for form and function while the diversity of preferred plant foods has played an equally prominent role in shaping primate evolution. Here, hypotheses of primate origins are examined in the context of food choice models developed by Marshall and Wrangham [2007] and related to the broader concepts of adaptive zones and radiations. The integrated evolution of primate diet and positional behavior is consistent with a growing reliance on angiosperm products--not prey--as preferred and seasonal fallback foods, temporally and phylogenetically coordinated with evolutionary phases of the angiosperm adaptive radiation. Selection for an incisor oriented but non-specialized heterodont dentition, in contrast with most other orders, attests to the universal role of a highly varied vegetation diet as the primates' primary food resource, with diverse physical properties, phenology and high seasonality. A preference by plesiadapiforms for eating small protein- and lipid-rich seeds may have predisposed the primates and advanced angiosperms to diversify their evolving ecological interdependence, which established the primate adaptive zone and became realized more fully with the rise of the modern euprimate and angiosperm phenotypes. The "narrow niche" hypothesis, a recent challenge to the angiosperm co-evolution hypothesis, is evaluated further. Finally, I note support for visual predation as a core adaptive breakthrough for primates or euprimates remains elusive and problematic, especially considering the theoretical framework provided by the Marshall-Wrangham model, updated evidence of primate feeding habits and the counterpoint lessons of the most successful primate predators, the tarsiiforms.

  11. Transplantation activities in Iran.

    PubMed

    Broumand, Behrooz

    2005-06-01

    Iran is a tropical country with a land area of 1,648,000 square kilometers and a population of 68,100,000. Iran has a recorded history that dates back 2553 years. Its earliest medical school was Pasargad. Jondi Chapour University was founded 1753 years ago during the Sassanid dynasty as a center for higher education in medicine, philosophy, and pharmacology. Indeed, the idea of xenotransplantation dates back to days of Achaemenidae (Achaemenian dynasty), as evidenced by engravings of many mythologic chimeras still present in Persepolis. Avicenna (980-1037 AD), the great Iranian physician, performed the first nerve repair. Transplantation progress in Iran follows roughly the same pattern as that of the rest of the world, with some 10-20 years' delay. Modern organ transplantation dates back to 1935, when the first cornea transplant was performed at Farabi Hospital in Tehran, Iran. The first living-related kidney transplantation performed at Shiraz University Hospital dates back to 1968. The first bone marrow transplant was performed at Dr. Shariaati's Hospital in Tehran. The first heart transplant was performed 1993 in Tabriz, Iran. The first liver transplant was performed in 1993 in Shiraz. The first lung transplant was performed in 2001, and the first heart and lung transplants were performed in 2002, both at Tehran. In late 1985, the renal transplantation program was officially started in a major university hospital in Tehran and was poised to carry out 2 to 4 transplantations each week. Soon, another large center initiated a similar program. Both of these centers accepted surgical, medical, and nursing teams from other academic medical centers for training in kidney transplantation. Since 2002, Iran has grown to include 23 active renal, 68 cornea, 2 liver, 4 heart, 2 lung, and 2 bone marrow transplantation centers in different cities. In June 2000, the Organ Transplantation Brain Death Act was approved by the Parliament, followed by the establishment of the

  12. Primate Socioecology: New Insights from Males

    NASA Astrophysics Data System (ADS)

    Kappeler, Peter M.

    Primate males have only recently returned to the center stage of socioecological research. This review surveys new studies that examine variation in the behavior of adult males and their role in social evolution. It is shown that group size, composition, and social behavior are determined not only by resource distribution, predation risk, and other ecological factors, but that life history traits and social factors, especially those related to sexual coercion, can have equally profound consequences for social systems. This general point is illustrated by examining male behavior at three levels: the evolution of permanent associations between males and females, the causes and consequences of variation in the number of males between group-living species, and the determinants of social relationships within and between the sexes. Direct and indirect evidence reviewed in connection with all three questions indicates that the risk of infanticide has been a pervasive force in primate social evolution. Several areas are identified for future research on male life histories that should contribute to a better understanding of male reproductive strategies and corresponding female counterstrategies.

  13. Short hyperdynamic profiles influence primate temperature regulation

    NASA Technical Reports Server (NTRS)

    Fuller, C. A.; Williams, B. A.

    1982-01-01

    Primates have been shown to be sensitive to hyperdynamic fields. That is, when exposed to + 2Gz, body temperature falls. The purpose of this study was to examine the relative sensitivity of these animals to short centrifugation profiles which mimic the gravitational envelope seen on the Space Shuttle during launch (8 minutes, 2.9 Gz max) and re-entry (19 min, 1.7 Gz max). Four loosely restrained squirrel monkeys, isolated from additional external stimuli, were exposed to these profiles. During launch simulation, the temperatures never fell markedly below control levels. However, subsequent to return to 1G, the recovery phase showed decreases in body temperature in all four animals averaging 0.4 C over the next 10 to 15 minutes. The two animals exposed to the reentry profile showed decreases in body temperature within five minutes of the onset of centrifugation. Maximum fall in body temperature was reached by the end of the centrifugation phase and averaged 0.7 C. Thus, the temperature regulation system of this primate is sensitive to short hyperdynamic field exposures.

  14. Primate pelvic anatomy and implications for birth

    PubMed Central

    Trevathan, Wenda

    2015-01-01

    The pelvis performs two major functions for terrestrial mammals. It provides somewhat rigid support for muscles engaged in locomotion and, for females, it serves as the birth canal. The result for many species, and especially for encephalized primates, is an ‘obstetric dilemma’ whereby the neonate often has to negotiate a tight squeeze in order to be born. On top of what was probably a baseline of challenging birth, locomotor changes in the evolution of bipedalism in the human lineage resulted in an even more complex birth process. Negotiation of the bipedal pelvis requires a series of rotations, the end of which has the infant emerging from the birth canal facing the opposite direction from the mother. This pattern, strikingly different from what is typically seen in monkeys and apes, places a premium on having assistance at delivery. Recently reported observations of births in monkeys and apes are used to compare the process in human and non-human primates, highlighting similarities and differences. These include presentation (face, occiput anterior or posterior), internal and external rotation, use of the hands by mothers and infants, reliance on assistance, and the developmental state of the neonate. PMID:25602069

  15. Hunting, law enforcement, and African primate conservation.

    PubMed

    N'Goran, Paul K; Boesch, Christophe; Mundry, Roger; N'Goran, Eliezer K; Herbinger, Ilka; Yapi, Fabrice A; Kühl, Hjalmar S

    2012-06-01

    Primates are regularly hunted for bushmeat in tropical forests, and systematic ecological monitoring can help determine the effect hunting has on these and other hunted species. Monitoring can also be used to inform law enforcement and managers of where hunting is concentrated. We evaluated the effects of law enforcement informed by monitoring data on density and spatial distribution of 8 monkey species in Taï National Park, Côte d'Ivoire. We conducted intensive surveys of monkeys and looked for signs of human activity throughout the park. We also gathered information on the activities of law-enforcement personnel related to hunting and evaluated the relative effects of hunting, forest cover and proximity to rivers, and conservation effort on primate distribution and density. The effects of hunting on monkeys varied among species. Red colobus monkeys (Procolobus badius) were most affected and Campbell's monkeys (Cercopithecus campbelli) were least affected by hunting. Density of monkeys irrespective of species was up to 100 times higher near a research station and tourism site in the southwestern section of the park, where there is little hunting, than in the southeastern part of the park. The results of our monitoring guided law-enforcement patrols toward zones with the most hunting activity. Such systematic coordination of ecological monitoring and law enforcement may be applicable at other sites.

  16. Social inequalities in health in nonhuman primates.

    PubMed

    Shively, Carol A; Day, Stephen M

    2015-01-01

    Overall health has been linked to socioeconomic status, with the gap between social strata increasing each year. Studying the impact of social position on health and biological functioning in nonhuman primates has allowed researchers to model the human condition while avoiding ethical complexities or other difficulties characteristic of human studies. Using female cynomolgus macaques (Macaca fascicularis), our lab has examined the link between social status and stress for 30 years. Female nonhuman primates are especially sensitive to social stressors which can deleteriously affect reproductive health, leading to harmful consequences to their overall health. Subordinates have lower progesterone concentrations during the luteal phase of menstrual cycle, which is indicative of absence or impairment of ovulation. Subordinate animals receive more aggression, less affiliative attention, and are more likely to exhibit depressive behaviors. They also express higher stress-related biomarkers such as increased heart rates and lower mean cortisol. While no differences in body weight between dominant and subordinate animals are observed, subordinates have lower bone density and more visceral fat than their dominant counterparts. The latter increases risk for developing inflammatory diseases. Differences are also observed in neurological and autonomic function. A growing body of data suggests that diet composition may amplify or diminish physiological stress responses which have deleterious effects on health. More experimental investigation of the health effects of diet pattern is needed to further elucidate these differences in an ongoing search to find realistic and long-term solutions to the declining health of individuals living across the ever widening socioeconomic spectrum.

  17. Social inequalities in health in nonhuman primates

    PubMed Central

    Shively, Carol A.; Day, Stephen M.

    2014-01-01

    Overall health has been linked to socioeconomic status, with the gap between social strata increasing each year. Studying the impact of social position on health and biological functioning in nonhuman primates has allowed researchers to model the human condition while avoiding ethical complexities or other difficulties characteristic of human studies. Using female cynomolgus macaques (Macaca fascicularis), our lab has examined the link between social status and stress for 30 years. Female nonhuman primates are especially sensitive to social stressors which can deleteriously affect reproductive health, leading to harmful consequences to their overall health. Subordinates have lower progesterone concentrations during the luteal phase of menstrual cycle, which is indicative of absence or impairment of ovulation. Subordinate animals receive more aggression, less affiliative attention, and are more likely to exhibit depressive behaviors. They also express higher stress-related biomarkers such as increased heart rates and lower mean cortisol. While no differences in body weight between dominant and subordinate animals are observed, subordinates have lower bone density and more visceral fat than their dominant counterparts. The latter increases risk for developing inflammatory diseases. Differences are also observed in neurological and autonomic function. A growing body of data suggests that diet composition may amplify or diminish physiological stress responses which have deleterious effects on health. More experimental investigation of the health effects of diet pattern is needed to further elucidate these differences in an ongoing search to find realistic and long-term solutions to the declining health of individuals living across the ever widening socioeconomic spectrum. PMID:27589665

  18. Voice cells in the primate temporal lobe.

    PubMed

    Perrodin, Catherine; Kayser, Christoph; Logothetis, Nikos K; Petkov, Christopher I

    2011-08-23

    Communication signals are important for social interactions and survival and are thought to receive specialized processing in the visual and auditory systems. Whereas the neural processing of faces by face clusters and face cells has been repeatedly studied [1-5], less is known about the neural representation of voice content. Recent functional magnetic resonance imaging (fMRI) studies have localized voice-preferring regions in the primate temporal lobe [6, 7], but the hemodynamic response cannot directly assess neurophysiological properties. We investigated the responses of neurons in an fMRI-identified voice cluster in awake monkeys, and here we provide the first systematic evidence for voice cells. "Voice cells" were identified, in analogy to "face cells," as neurons responding at least 2-fold stronger to conspecific voices than to "nonvoice" sounds or heterospecific voices. Importantly, whereas face clusters are thought to contain high proportions of face cells [4] responding broadly to many faces [1, 2, 4, 5, 8-10], we found that voice clusters contain moderate proportions of voice cells. Furthermore, individual voice cells exhibit high stimulus selectivity. The results reveal the neurophysiological bases for fMRI-defined voice clusters in the primate brain and highlight potential differences in how the auditory and visual systems generate selective representations of communication signals. PMID:21835625

  19. Fish cognition: a primate's eye view.

    PubMed

    Bshary, Redouan; Wickler, Wolfgang; Fricke, Hans

    2002-03-01

    We provide selected examples from the fish literature of phenomena found in fish that are currently being examined in discussions of cognitive abilities and evolution of neocortex size in primates. In the context of social intelligence, we looked at living in individualized groups and corresponding social strategies, social learning and tradition, and co-operative hunting. Regarding environmental intelligence, we searched for examples concerning special foraging skills, tool use, cognitive maps, memory, anti-predator behaviour, and the manipulation of the environment. Most phenomena of interest for primatologists are found in fish as well. We therefore conclude that more detailed studies on decision rules and mechanisms are necessary to test for differences between the cognitive abilities of primates and other taxa. Cognitive research can benefit from future fish studies in three ways: first, as fish are highly variable in their ecology, they can be used to determine the specific ecological factors that select for the evolution of specific cognitive abilities. Second, for the same reason they can be used to investigate the link between cognitive abilities and the enlargement of specific brain areas. Third, decision rules used by fish could be used as 'null-hypotheses' for primatologists looking at how monkeys might make their decisions. Finally, we propose a variety of fish species that we think are most promising as study objects.

  20. Primate pelvic anatomy and implications for birth.

    PubMed

    Trevathan, Wenda

    2015-03-01

    The pelvis performs two major functions for terrestrial mammals. It provides somewhat rigid support for muscles engaged in locomotion and, for females, it serves as the birth canal. The result for many species, and especially for encephalized primates, is an 'obstetric dilemma' whereby the neonate often has to negotiate a tight squeeze in order to be born. On top of what was probably a baseline of challenging birth, locomotor changes in the evolution of bipedalism in the human lineage resulted in an even more complex birth process. Negotiation of the bipedal pelvis requires a series of rotations, the end of which has the infant emerging from the birth canal facing the opposite direction from the mother. This pattern, strikingly different from what is typically seen in monkeys and apes, places a premium on having assistance at delivery. Recently reported observations of births in monkeys and apes are used to compare the process in human and non-human primates, highlighting similarities and differences. These include presentation (face, occiput anterior or posterior), internal and external rotation, use of the hands by mothers and infants, reliance on assistance, and the developmental state of the neonate.

  1. Conditioned Sexual Arousal in a Nonhuman Primate

    PubMed Central

    Snowdon, Charles T.; Tannenbaum, Pamela L.; Schultz-Darken, Nancy J.; Ziegler, Toni E.; Ferris, Craig F.

    2010-01-01

    Conditioning of sexual arousal has been demonstrated in several species from fish to humans, but has not been demonstrated in nonhuman primates. Controversy exists over whether nonhuman primates produce pheromones that arouse sexual behavior. Although common marmosets copulate throughout the ovarian cycle and during pregnancy, males exhibit behavioral signs of arousal, demonstrate increased neural activation of anterior hypothalamus and medial preoptic area and have an increase in serum testosterone after exposure to odors of novel ovulating females suggestive of a sexually arousing pheromone. Males also have increased androgens prior to their mate’s ovulation. However, males presented with odors of ovulating females demonstrate activation of many other brain areas associated with motivation, memory and decision making. In this study we demonstrate that male marmosets can be conditioned to a novel, arbitrary odor (lemon) with observation of erections, and increased exploration of the location where they previously experienced a receptive female, and increased scratching in postconditioning test without a female present. This conditioned response was demonstrated up to a week after the end of conditioning trials, a much longer lasting effect of conditioning than reported in studies of other species. These results further suggest that odors of ovulating females are not pheromones, strictly speaking, and that marmoset males may learn specific characteristics of odors of females providing a possible basis for mate identification. PMID:21029736

  2. Social inequalities in health in nonhuman primates.

    PubMed

    Shively, Carol A; Day, Stephen M

    2015-01-01

    Overall health has been linked to socioeconomic status, with the gap between social strata increasing each year. Studying the impact of social position on health and biological functioning in nonhuman primates has allowed researchers to model the human condition while avoiding ethical complexities or other difficulties characteristic of human studies. Using female cynomolgus macaques (Macaca fascicularis), our lab has examined the link between social status and stress for 30 years. Female nonhuman primates are especially sensitive to social stressors which can deleteriously affect reproductive health, leading to harmful consequences to their overall health. Subordinates have lower progesterone concentrations during the luteal phase of menstrual cycle, which is indicative of absence or impairment of ovulation. Subordinate animals receive more aggression, less affiliative attention, and are more likely to exhibit depressive behaviors. They also express higher stress-related biomarkers such as increased heart rates and lower mean cortisol. While no differences in body weight between dominant and subordinate animals are observed, subordinates have lower bone density and more visceral fat than their dominant counterparts. The latter increases risk for developing inflammatory diseases. Differences are also observed in neurological and autonomic function. A growing body of data suggests that diet composition may amplify or diminish physiological stress responses which have deleterious effects on health. More experimental investigation of the health effects of diet pattern is needed to further elucidate these differences in an ongoing search to find realistic and long-term solutions to the declining health of individuals living across the ever widening socioeconomic spectrum. PMID:27589665

  3. Tomato paste alters NF-κB and cancer-related mRNA expression in prostate cancer cells, xenografts, and xenograft microenvironment.

    PubMed

    Kolberg, Marit; Pedersen, Sigrid; Bastani, Nasser E; Carlsen, Harald; Blomhoff, Rune; Paur, Ingvild

    2015-01-01

    Tomatoes may protect against prostate cancer development, possibly through targeting signaling pathways such as nuclear factor-κB (NF-κB). We investigated whether tomato paste could modulate NF-κB activity and cancer-related gene expression in human derived prostate cancer cells (PC3) and PC3 xenografts. PC3-cells were stably transduced with an NF-κB-luciferase construct, and treated with tomato extracts or vehicle control. Nude mice bearing PC3 xenografts were fed a Western-like diet with or without 10% tomato paste for 6.5 wk. The tomato diet significantly inhibited TNFα stimulated NF-κB activity in cultured PC3 cells, and modulated the expression of genes associated with inflammation, apoptosis, and cancer progression. Accumulation of lycopene occurred in liver, xenografts, and serum of mice fed tomato diet. Tomato paste in the diet did not affect tumor size in mice; however, there was a trend toward inhibition of NF-κB activity in the xenografts. The effect of tomato on gene expression was most prominent in the xenograft microenvironment, where among others NFKB2, STAT3, and STAT6 showed higher expression levels after tomato treatment. Our findings support biological activity of tomatoes in cancer-related inflammation. PMID:25664890

  4. XactMice: humanizing mouse bone marrow enables microenvironment reconstitution in a patient-derived xenograft model of head and neck cancer.

    PubMed

    Morton, J J; Bird, G; Keysar, S B; Astling, D P; Lyons, T R; Anderson, R T; Glogowska, M J; Estes, P; Eagles, J R; Le, P N; Gan, G; McGettigan, B; Fernandez, P; Padilla-Just, N; Varella-Garcia, M; Song, J I; Bowles, D W; Schedin, P; Tan, A-C; Roop, D R; Wang, X-J; Refaeli, Y; Jimeno, A

    2016-01-21

    The limitations of cancer cell lines have led to the development of direct patient-derived xenograft models. However, the interplay between the implanted human cancer cells and recruited mouse stromal and immune cells alters the tumor microenvironment and limits the value of these models. To overcome these constraints, we have developed a technique to expand human hematopoietic stem and progenitor cells (HSPCs) and use them to reconstitute the radiation-depleted bone marrow of a NOD/SCID/IL2rg(-/-) (NSG) mouse on which a patient's tumor is then transplanted (XactMice). The human HSPCs produce immune cells that home into the tumor and help replicate its natural microenvironment. Despite previous passage on nude mice, the expression of epithelial, stromal and immune genes in XactMice tumors aligns more closely to that of the patient tumor than to those grown in non-humanized mice-an effect partially facilitated by human cytokines expressed by both the HSPC progeny and the tumor cells. The human immune and stromal cells produced in the XactMice can help recapitulate the microenvironment of an implanted xenograft, reverse the initial genetic drift seen after passage on non-humanized mice and provide a more accurate tumor model to guide patient treatment.

  5. Porcine xenograft aortic root replacement in a three month old with severe truncal insufficiency.

    PubMed

    Chancellor, William; DiBardino, Daniel J; Gupta, Bhawna; Knudson, Jarrod D; Eddine, Ahmad Charaf; Salazar, Jorge D

    2014-07-01

    Outcomes for truncus arteriosus repair are impacted significantly by the severity of truncal valve dysfunction. When satisfactory repair of the regurgitant truncal valve is unattainable, replacement is required. Given our experience in children with stentless porcine xenografts in the aortic position and the incidence of early valve failure for aortic homografts in infants, we replaced a severely regurgitant truncal valve with a full-root porcine xenograft in a 3-month-old infant. The initial and early result are encouraging, suggesting that the stentless porcine xenograft may be considered an option in cases where primary repair of the truncal (or aortic) valve is not possible.

  6. Hepatitis C: liver transplantation.

    PubMed

    Metts, Julius; Carmichael, Lesley; Kokor, Winfred; Scharffenberg, Robert

    2014-12-01

    Hepatitis C virus (HCV)-related cirrhosis and hepatocellular carcinoma account for approximately 40% of the 6,000 adult liver transplantations performed each year in the United States. Survival rates are 76% to 83% at 2 years and 69% to 72% at 5 years. If eligible for surgery and in the absence of contraindications, any patient with HCV infection who develops decompensated liver disease or hepatocellular carcinoma is a candidate for liver transplantation. Most transplantation programs require that a patient with a history of alcohol or drug abuse be abstinent for at least 6 months and active in a substance abuse rehabilitation program. Prioritization for transplantation is based primarily on a patient's model for end-stage liver disease score, though other factors are considered. Complications after liver transplantation include recurrence of HCV infection, rejection of the transplanted liver, and an increased rate of infection because of immunosuppression. Various drugs are used to prevent infection and organ rejection. Liver transplant recipients also develop diabetes, hypertension, hyperlipidemia, renal dysfunction, osteopenia, and cancers at high rates, likely because of the effects of immunosuppressive drugs, particularly steroids and calcineurin inhibitors. The family physician's role in caring for liver transplant recipients often involves detection and management of these conditions. PMID:25478647

  7. Organ transplantation and replacement

    SciTech Connect

    Cerilli, G.J.

    1988-01-01

    This book contains 49 chapters. Some of the titles are: Molecular, Genetic, and Clinical Aspects of the HLA System; The Normal Immune Response; Significance of the ABO Antigen System; The Role of Dialysis in the Management of End-Stage Renal Disease; Access for Dialysis; Patient Selection for Renal Transplantation; The Living Donor in Kidney Transplantation; and Kidney Preservation by Cold Storage.

  8. Islet cell transplantation.

    PubMed

    Srinivasan, P; Huang, G C; Amiel, S A; Heaton, N D

    2007-04-01

    People with type 1 diabetes have normal exocrine pancreatic function, making islet cell rather than whole organ transplantation an attractive option. Achieving insulin independence in type 1 diabetes was the perceived goal of islet cell transplantation. The success of the Edmonton group in achieving this in a selected group of type 1 patients has led to renewed optimism that this treatment could eventually replace whole organ pancreas transplantation. However the long-term results of this treatment indicate that insulin independence is lost with time in a significant proportion of patients, although they may retain glycaemic stability. In this context, the indications for islet cell transplantation, which have evolved over the last 5 years, indicate that the patients who benefit most are those who experience severe hypoglycaemic reactions despite optimal insulin therapy. This review will summarise the history of islet cell transplantation, islet isolation techniques, the transplant procedure, immunosuppressive therapy, indications for islet cell transplantation, current clinical trials, the early UK islet cell transplant experience using the Edmonton protocol, and some of the challenges that lie ahead. PMID:17403947

  9. Heart transplantation: review

    PubMed Central

    Mangini, Sandrigo; Alves, Bárbara Rubim; Silvestre, Odílson Marcos; Pires, Philippe Vieira; Pires, Lucas José Tachotti; Curiati, Milena Novaes Cardoso; Bacal, Fernando

    2015-01-01

    ABSTRACT Heart transplantation is currently the definitive gold standard surgical approach in the treatment of refractory heart failure. However, the shortage of donors limits the achievement of a greater number of heart transplants, in which the use of mechanical circulatory support devices is increasing. With well-established indications and contraindications, as well as diagnosis and treatment of rejection through defined protocols of immunosuppression, the outcomes of heart transplantation are very favorable. Among early complications that can impact survival are primary graft failure, right ventricular dysfunction, rejection, and infections, whereas late complications include cardiac allograft vasculopathy and neoplasms. Despite the difficulties for heart transplantation, in particular, the shortage of donors and high mortality while on the waiting list, in Brazil, there is a great potential for both increasing effective donors and using circulatory assist devices, which can positively impact the number and outcomes of heart transplants. PMID:26154552

  10. Bioethics of Organ Transplantation

    PubMed Central

    Caplan, Arthur

    2014-01-01

    As the ability to transplant organs and tissues has grown, the demand for these procedures has increased as well—to the point at which it far exceeds the available supply creating the core ethical challenge for transplantation—rationing. The gap between supply and demand, although large, is worse than it appears to be. There are two key steps to gaining access to a transplant. First, one must gain access to a transplant center. Then, those waiting need to be selected for a transplant. Many potential recipients do not get admitted to a program. They are deemed too old, not of the right nationality, not appropriate for transplant as a result of severe mental impairment, criminal history, drug abuse, or simply because they do not have access to a competent primary care physician who can refer them to a transplant program. There are also financial obstacles to access to transplant waiting lists in the United States and other nations. In many poor nations, those needing transplants simply die because there is no capacity or a very limited capacity to perform transplants. Although the demand for organs now exceeds the supply, resulting in rationing, the size of waiting lists would quickly expand were there to suddenly be an equally large expansion in the number of organs available for transplantation. Still, even with the reality of unavoidable rationing, saving more lives by increasing organ supply is a moral good. Current public policies for obtaining organs from cadavers are not adequate in that they do not produce the number of organs that public polls of persons in the United States indicate people are willing to donate. PMID:24478386

  11. Survival and growth of human preantral follicles after cryopreservation of ovarian tissue, follicle isolation and short-term xenografting.

    PubMed

    Paulini, Fernanda; Vilela, Janice M V; Chiti, Maria Costanza; Donnez, Jacques; Jadoul, Pascale; Dolmans, Marie-Madeleine; Amorim, Christiani A

    2016-09-01

    In women, chemotherapy and radiotherapy can be harmful to the ovaries, causing loss of endocrine and reproductive functions. When gonadotoxic treatment cannot be delayed, ovarian tissue cryobanking is the only way of preserving fertility. This technique, however, is not advisable for patients with certain types of cancer, because of the risk of reintroducing malignant cells present in the cryopreserved tissue. Our objective is therefore to develop a transplantable artificial ovary. To this end, cryopreserved human preantral follicles were isolated and embedded in fibrin formulations prepared with 50 mg/ml fibrinogen and 10 IU/ml thrombin supplemented or not with 3% hyaluronic acid, and respectively xenografted to specially created right and left peritoneal pockets in eight nude mice. On days 0 and 7, the animals were killed and the matrices retrieved. On day 7, no difference was observed in the recovery rate of follicles embedded in fibrin alone (23.4%) or fibrin-hyaluronic acid (20.5%). Ki67 staining confirmed growth of the grafted follicles and terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labelling assay revealed 100% of the follicles to be viable in both groups on day 7. In conclusion, fibrin seems to be a promising material for creation of an artificial ovary, supporting follicle survival and development. PMID:27210771

  12. 5-Fluorouracil + cisplatin + mitomycin C is a relatively most effective combination against xenograft lines of human colorectal cancer.

    PubMed

    Kawabata, K; Nio, Y; Imamura, M

    1997-09-01

    5-Fluorouracil (5-FU) has been an accepted effective against colorectal cancer, but combination regimens resulted in a lesser effect than 5-FU alone. The present study was designed to evaluate the efficiency of various combination chemotherapies, including 5-FU, on human colorectal cancer xenograft lines (CC-KK and RC-TK), which had been passed by transplantation in nude mice. Eight anticancer agents [5-FU, mitomycin C (MMC), adriamycin (ADR), 4'-epirubicin (EPIR), carboquone (CQ), cisplatin, carboplatin and etoposide (VP-16)] and their combinations were evaluated at 2-4 times the clinical dose. When the agents were administered singly, 5-FU, EPIR and CQ were effective against CC-KK, and 5-FU, MMC, EPIR, ADR, CQ and carboplatin were effective against RC-TK. Of the two-agent combinations including 5-FU, cisplatin + 5-FU was the most effective against both CC-KK and RC-TK. However, of the three-agent combinations, only cisplatin + 5-FU + MMC was more effective against both lines than cisplatin + 5-FU. These results suggest that cisplatin + 5-FU + MMC may be the most useful regimen against colorectal cancers in clinical application.

  13. Patient-derived xenograft models in gynecologic malignancies.

    PubMed

    Scott, Clare L; Mackay, Helen J; Haluska, Paul

    2014-01-01

    In the era of targeted therapies, patients with gynecologic malignancies have not yet been major beneficiaries of this new class of agents. This may reflect the fact that the main tumor types-ovarian, uterine, and cervical--are a highly heterogeneous group of cancers with variable response to standard chemotherapies and the lack of models in which to study the diversity of these cancers. Cancer-derived cell lines fail to adequately recapitulate molecular hallmarks of specific cancer subsets and complex microenvironments, which may be critical for sensitivity to targeted therapies. Patient-derived xenografts (PDX) generated from fresh human tumor without prior in vitro culture, combined with whole genome expression, gene copy number, and sequencing analyses, could dramatically aid the development of novel therapies for gynecologic malignancies. Gynecologic tumors can be engrafted in immunodeficient mice with a high rate of success and within a reasonable time frame. The resulting PDX accurately recapitulates the patient's tumor with respect to histologic, molecular, and in vivo treatment response characteristics. Orthotopic PDX develop complications relevant to the clinic, such as ascites and bowel obstruction, providing opportunities to understand the biology of these clinical problems. Thus, PDX have great promise for improved understanding of gynecologic malignancies, serve as better models for designing novel therapies and clinical trials, and could underpin individualized, directed therapy for patients from whom such models have been established.

  14. Maintaining Tumor Heterogeneity in Patient-Derived Tumor Xenografts.

    PubMed

    Cassidy, John W; Caldas, Carlos; Bruna, Alejandra

    2015-08-01

    Preclinical models often fail to capture the diverse heterogeneity of human malignancies and as such lack clinical predictive power. Patient-derived tumor xenografts (PDX) have emerged as a powerful technology: capable of retaining the molecular heterogeneity of their originating sample. However, heterogeneity within a tumor is governed by both cell-autonomous (e.g., genetic and epigenetic heterogeneity) and non-cell-autonomous (e.g., stromal heterogeneity) drivers. Although PDXs can largely recapitulate the polygenomic architecture of human tumors, they do not fully account for heterogeneity in the tumor microenvironment. Hence, these models have substantial utility in basic and translational research in cancer biology; however, study of stromal or immune drivers of malignant progression may be limited. Similarly, PDX models offer the ability to conduct patient-specific in vivo and ex vivo drug screens, but stromal contributions to treatment responses may be under-represented. This review discusses the sources and consequences of intratumor heterogeneity and how these are recapitulated in the PDX model. Limitations of the current generation of PDXs are discussed and strategies to improve several aspects of the model with respect to preserving heterogeneity are proposed.

  15. Hyperthermic radiosensitization of cells from a human melanoma xenograft

    SciTech Connect

    Rofstad, E.K.; Brustad, T.

    1984-07-01

    Cells derived directly from a human melanoma xenograft were exposed to radiation and/or hyperthermia under aerobic conditions in vitro. Single cell survival was assayed in soft agar. The activation energies for heat treatment alone were 420 +/- 40 kcal/mole (41.5-42.5/sup 0/C) and 170 +/- 10 kcal/mole (43.0-45.5/sup 0/C). Heat doses of 41.5/sup 0/C (30 min) or 43.5/sup 0/C (30 min) did not cause a reduction in the shoulder of the X-ray survival curve of the cells, but the D/sub 0/ value was reduced. The thermal enhancement ratios (the ratio of the D/sub 0/ values) were in the ranges 1.0-1.3 (41.5/sup 0/C, 30 min) and 1.1-1.7 (43.5/sup 0/C, 30 min), depending on the sequence and the time between the treatments. Repair of sublethal radiation damage was not significantly inhibited when treatments with 41.5/sup 0/C (30 min) or 43.5/sup 0/C (30 min) preceded irradiation, but was inhibited when 44.5/sup 0/C (30 min) was given immediately before radiation and when 4l.5/sup 0/C (120 min) was given immediately after radiation. Implications of the results for clinical treatment of malignant melanomas are discussed.

  16. Prolongation of segmental and pancreaticoduodenal allografts in the primate with total-lymphoid irradiation and cyclosporine

    SciTech Connect

    Du Toit, D.F.; Heydenrych, J.J.; Smit, B.; Louw, G.; Zuurmond, T.; Els, D.; Du Toit, L.B.; Weideman, A.; Davids, H.; van der Merwe, E.

    1987-09-01

    The prolongation of segmental and pancreaticoduodenal allografts (PDA) by total lymphoid irradiation (TLI) and in combination with cyclosporine (CsA) was assessed in a well established total pancreatectomy, diabetic, primate transplantation model. Pancreatic transplantation was performed in 119 pancreatectomized baboons (Papio ursinus). Of a total of 109 allografts performed, 71 were segmental allografts (open duct drainage) and 38 PDA. Of 119 graft recipients, 10 received segmental pancreatic autografts. TLI and CsA administered separately to segmental allograft recipients resulted in modest allograft survival and indefinite graft survival was not observed. 8 of 17 (47%) segmental allograft recipients that received TLI and CsA had graft survival beyond 100 days, indicating highly significant pancreatic allograft survival. All long-term segmental allograft recipients were rendered normoglycemic (plasma glucose less than 8 mmol/L) by this immunosuppressive regimen. In contrast, poor results were observed in PDA recipients treated with TLI and CsA. Mean survival in 18 treated PDA recipients was 23.8 days, 8 survived longer than 20 days (44.4%), and 1 greater than 100 days (5.5%). Despite treatment, early rejection of the duodenum in PDA recipients frequently resulted in necrosis and perforation and contributed to a high morbidity and mortality. This study indicates that, in contrast to the significant prolongation of segmental allografts by TLI and CsA, poor immunosuppression was achieved by this regimen in PDA recipients and was associated with a high morbidity and mortality caused by early rejection of the duodenum.

  17. Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model.

    PubMed

    Takagi, Yasushi; Takahashi, Jun; Saiki, Hidemoto; Morizane, Asuka; Hayashi, Takuya; Kishi, Yo; Fukuda, Hitoshi; Okamoto, Yo; Koyanagi, Masaomi; Ideguchi, Makoto; Hayashi, Hideki; Imazato, Takayuki; Kawasaki, Hiroshi; Suemori, Hirofumi; Omachi, Shigeki; Iida, Hidehiko; Itoh, Nobuyuki; Nakatsuji, Norio; Sasai, Yoshiki; Hashimoto, Nobuo

    2005-01-01

    Parkinson disease (PD) is a neurodegenerative disorder characterized by loss of midbrain dopaminergic (DA) neurons. ES cells are currently the most promising donor cell source for cell-replacement therapy in PD. We previously described a strong neuralizing activity present on the surface of stromal cells, named stromal cell-derived inducing activity (SDIA). In this study, we generated neurospheres composed of neural progenitors from monkey ES cells, which are capable of producing large numbers of DA neurons. We demonstrated that FGF20, preferentially expressed in the substantia nigra, acts synergistically with FGF2 to increase the number of DA neurons in ES cell-derived neurospheres. We also analyzed the effect of transplantation of DA neurons generated from monkey ES cells into 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated (MPTP-treated) monkeys, a primate model for PD. Behavioral studies and functional imaging revealed that the transplanted cells functioned as DA neurons and attenuated MPTP-induced neurological symptoms.

  18. Contributions of Nonhuman Primates to Research on Aging

    PubMed Central

    Didier, E. S.; MacLean, A. G.; Mohan, M.; Didier, P. J.; Lackner, A. A.; Kuroda, M. J.

    2016-01-01

    Aging is the biological process of declining physiologic function associated with increasing mortality rate during advancing age. Humans and higher nonhuman primates exhibit unusually longer average life spans as compared with mammals of similar body mass. Furthermore, the population of humans worldwide is growing older as a result of improvements in public health, social services, and health care systems. Comparative studies among a wide range of organisms that include nonhuman primates contribute greatly to our understanding about the basic mechanisms of aging. Based on their genetic and physiologic relatedness to humans, nonhuman primates are especially important for better understanding processes of aging unique to primates, as well as for testing intervention strategies to improve healthy aging and to treat diseases and disabilities in older people. Rhesus and cynomolgus macaques are the predominant monkeys used in studies on aging, but research with lower nonhuman primate species is increasing. One of the priority topics of research about aging in nonhuman primates involves neurologic changes associated with cognitive decline and neurodegenerative diseases. Additional areas of research include osteoporosis, reproductive decline, caloric restriction, and their mimetics, as well as immune senescence and chronic inflammation that affect vaccine efficacy and resistance to infections and cancer. The purpose of this review is to highlight the findings from nonhuman primate research that contribute to our understanding about aging and health span in humans. PMID:26869153

  19. Historical contingency in the evolution of primate color vision.

    PubMed

    Dominy, Nathaniel J; Svenning, Jens Christian; Li, Wen Hsiung

    2003-01-01

    Primates are unique among eutherian mammals for possessing three types of retinal cone. Curiously, catarrhines, platyrrhines, and strepsirhines share this anatomy to different extents, and no hypothesis has hitherto accounted for this variability. Here we propose that the historical biogeography of figs and arborescent palms accounts for the global variation in primate color vision. Specifically, we suggest that primates invaded Paleogene forests characterized by figs and palms, the fruits of which played a keystone function. Primates not only relied on such resources, but also provided high-quality seed dispersal. In turn, figs and palms lost or simply did not evolve conspicuous coloration, as this conferred little advantage for attracting mammals. We suggest that the abundance and coloration of figs and palms offered a selective advantage to foraging groups with mixed capabilities for chromatic distinction. Climatic cooling at the end of the Eocene and into the Neogene resulted in widespread regional extinction or decimation of palms and (probably) figs. In regions where figs and palms became scarce, we suggest primates evolved routine trichromatic vision in order to exploit proteinaceous young leaves as a replacement resource. A survey of the hue and biogeography of extant figs and palms provides some empirical support. Where these resources are infrequent, primates are routinely trichromatic and consume young leaves during seasonal periods of fruit dearth. These results imply a link between the differential evolution of primate color vision and climatic changes during the Eocene-Oligocene transition.

  20. Fruits, foliage and the evolution of primate colour vision.

    PubMed

    Regan, B C; Julliot, C; Simmen, B; Viénot, F; Charles-Dominique, P; Mollon, J D

    2001-03-29

    Primates are apparently unique amongst the mammals in possessing trichromatic colour vision. However, not all primates are trichromatic. Amongst the haplorhine (higher) primates, the catarrhines possess uniformly trichromatic colour vision, whereas most of the platyrrhine species exhibit polymorphic colour vision, with a variety of dichromatic and trichromatic phenotypes within the population. It has been suggested that trichromacy in primates and the reflectance functions of certain tropical fruits are aspects of a coevolved seed-dispersal system: primate colour vision has been shaped by the need to find coloured fruits amongst foliage, and the fruits themselves have evolved to be salient to primates and so secure dissemination of their seeds. We review the evidence for and against this hypothesis and we report an empirical test: we show that the spectral positioning of the cone pigments found in trichromatic South American primates is well matched to the task of detecting fruits against a background of leaves. We further report that particular trichromatic platyrrhine phenotypes may be better suited than others to foraging for particular fruits under particular conditions of illumination; and we discuss possible explanations for the maintenance of polymorphic colour vision amongst the platyrrhines.

  1. The welfare and suitability of primates kept as pets.

    PubMed

    Soulsbury, Carl D; Iossa, Graziella; Kennell, Sarah; Harris, Stephen

    2009-01-01

    Amid growing concern about keeping exotic species as companion animals, nonhuman primates have been highlighted as inappropriate for private ownership. However, there has been no comprehensive review of the suitability of primates as pets, using a framework such as Schuppli and Fraser's (2000). Schuppli and Fraser incorporate welfare of the individual, of others, and of the environment. This article (a) examines the numbers, origins, ages, and ownership trends of primates kept as pets in the United Kingdom and (b) identifies a number of welfare, health, and environmental concerns. Overall, strong evidence supports the argument that primates are not suitable pets; it is unlikely that the welfare of pet primates can be adequately addressed in normal households. Finally, using unpublished data on complaints and inquiries received by the Royal Society for the Prevention of Cruelty to Animals, the study assesses the degree of public concern about the welfare of primates kept as pets in England and Wales. The article identifies a wide range of concerns about keeping pet primates and concludes that this practice should end.

  2. Evolution of the primate cytochrome c oxidase subunit II gene.

    PubMed

    Adkins, R M; Honeycutt, R L

    1994-03-01

    We examined the nucleotide and amino acid sequence variation of the cytochrome c oxidase subunit II (COII) gene from 25 primates (4 hominoids, 8 Old World monkeys, 2 New World monkeys, 2 tarsiers, 7 lemuriforms, 2 lorisiforms). Marginal support was found for three phylogenetic conclusions: (1) sister-group relationship between tarsiers and a monkey/ape clade, (2) placement of the aye-aye (Daubentonia) sister to all other strepsirhine primates, and (3) rejection of a sister-group relationship of dwarf lemurs (i.e., Cheirogaleus) with lorisiform primates. Stronger support was found for a sister-group relationship between the ring-tail lemur (Lemur catta) and the gentle lemurs (Hapalemur). In congruence with previous studies on COII, we found that the monkeys and apes have undergone a nearly two-fold increase in the rate of amino acid replacement relative to other primates. Although functionally important amino acids are generally conserved among all primates, the acceleration in amino acid replacements in higher primates is associated with increased variation in the amino terminal end of the protein. Additionally, the replacement of two carboxyl-bearing residues (glutamate and aspartate) at positions 114 and 115 may provide a partial explanation for the poor enzyme kinetics in cross-reactions between the cytochromes c and cytochrome c oxidases of higher primates and other mammals. PMID:8006990

  3. Fruits, foliage and the evolution of primate colour vision.

    PubMed

    Regan, B C; Julliot, C; Simmen, B; Viénot, F; Charles-Dominique, P; Mollon, J D

    2001-03-29

    Primates are apparently unique amongst the mammals in possessing trichromatic colour vision. However, not all primates are trichromatic. Amongst the haplorhine (higher) primates, the catarrhines possess uniformly trichromatic colour vision, whereas most of the platyrrhine species exhibit polymorphic colour vision, with a variety of dichromatic and trichromatic phenotypes within the population. It has been suggested that trichromacy in primates and the reflectance functions of certain tropical fruits are aspects of a coevolved seed-dispersal system: primate colour vision has been shaped by the need to find coloured fruits amongst foliage, and the fruits themselves have evolved to be salient to primates and so secure dissemination of their seeds. We review the evidence for and against this hypothesis and we report an empirical test: we show that the spectral positioning of the cone pigments found in trichromatic South American primates is well matched to the task of detecting fruits against a background of leaves. We further report that particular trichromatic platyrrhine phenotypes may be better suited than others to foraging for particular fruits under particular conditions of illumination; and we discuss possible explanations for the maintenance of polymorphic colour vision amongst the platyrrhines. PMID:11316480

  4. Fruits, foliage and the evolution of primate colour vision.

    PubMed Central

    Regan, B C; Julliot, C; Simmen, B; Viénot, F; Charles-Dominique, P; Mollon, J D

    2001-01-01

    Primates are apparently unique amongst the mammals in possessing trichromatic colour vision. However, not all primates are trichromatic. Amongst the haplorhine (higher) primates, the catarrhines possess uniformly trichromatic colour vision, whereas most of the platyrrhine species exhibit polymorphic colour vision, with a variety of dichromatic and trichromatic phenotypes within the population. It has been suggested that trichromacy in primates and the reflectance functions of certain tropical fruits are aspects of a coevolved seed-dispersal system: primate colour vision has been shaped by the need to find coloured fruits amongst foliage, and the fruits themselves have evolved to be salient to primates and so secure dissemination of their seeds. We review the evidence for and against this hypothesis and we report an empirical test: we show that the spectral positioning of the cone pigments found in trichromatic South American primates is well matched to the task of detecting fruits against a background of leaves. We further report that particular trichromatic platyrrhine phenotypes may be better suited than others to foraging for particular fruits under particular conditions of illumination; and we discuss possible explanations for the maintenance of polymorphic colour vision amongst the platyrrhines. PMID:11316480

  5. Small Bowel Transplant

    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 small bowel transplant in the treatment of intestinal failure. Small Bowel Transplantation Intestinal failure is the loss of absorptive capacity of the small intestine that results in an inability to meet the nutrient and fluid requirements of the body via the enteral route. Patients with intestinal failure usually receive nutrients intravenously, a procedure known as parenteral nutrition. However, long-term parenteral nutrition is associated with complications including liver failure and loss of venous access due to recurrent infections. Small bowel transplant is the transplantation of a cadaveric intestinal allograft for the purpose of restoring intestinal function in patients with irreversible intestinal failure. The transplant may involve the small intestine alone (isolated small bowel ISB), the small intestine and the liver (SB-L) when there is irreversible liver failure, or multiple organs including the small bowel (multivisceral MV or cluster). Although living related donor transplant is being investigated at a limited number of centres, cadaveric donors have been used in most small bowel transplants. The actual transplant procedure takes approximately 12-18 hours. After intestinal transplant, the patient is generally placed on prophylactic antibiotic medication and immunosuppressive regimen that, in the majority of cases, would include tacrolimus, corticosteroids and an induction agent. Close monitoring for infection and rejection are essential for early treatment. Medical Advisory Secretariat Review The Medical Advisory Secretariat undertook a review of 35 reports from 9 case series and 1 international registry. Sample size of the individual studies ranged from 9 to 155. As of May 2001, 651 patients had received small bowel transplant procedures worldwide. According to information from the Canadian Organ Replacement

  6. Drug testing using a soft agar stem cell assay on patient and xenograft tumor material

    SciTech Connect

    Hanson, J.; Coombs, A.; Moore, J.L.

    1984-09-01

    Since 1981 the authors have received 50 tumor samples from 10 different sites; over half were breast or ovary. Of the 27 that were considered suitable for cloning, 11 produced colony formation and 6 of these were drug tested. One ovarian granulosa cell tumor and its xenograft (V7) were tested against several cytotoxic agents. During a period of 16 months, sensitivity to cisplatin was relatively stable but sensitivity to vinblastine was markedly changed when the original tumor cells and original cells stored in liquid nitrogen were compared with xenograft cells. Gross histology of original tumor and xenograft were similar. Chemosensitization in vivo of a breast xenograft (Hx99) to melphalan by misonidazole was investigated. Misonidazole at a total dose of 0.5 g/kg given prior to melphalan (14 mg/kg) was an effective chemosensitizer.

  7. Pediatric heart transplantation

    PubMed Central

    Stiasny, Brian; Dave, Hitendu; Cavigelli-Brunner, Anna; Balmer, Christian; Kretschmar, Oliver; Bürki, Christoph; Klauwer, Dietrich; Hübler, Michael

    2015-01-01

    Pediatric heart transplantation (pHTx) represents a small (14%) but very important and particular part in the field of cardiac transplantation. This treatment has lifelong impact on children. To achieve the best short and especially long-term survival with adequate quality of life, which is of crucial importance for this young patient population, one has to realize and understand the differences with adult HTx. Indication for transplantation, waitlist management including ABO incompatible (ABOi) transplantation and immunosuppression differ. Although young transplant recipients are ultimately likely to be considered for re-transplantation. One has to distinguish between myopathy and complex congenital heart disease (CHD). The differences in anatomy and physiology make the surgical procedure much more complex and create unique challenges. These recipients need a well-organized and educated team with pediatric cardiologists and intensivists, including a high skilled surgeon, which is dedicated to pHTx. Therefore, these types of transplants are best concentrated in specialized centers to achieve promising outcome. PMID:25922739

  8. Pediatric heart transplantation.

    PubMed

    Schweiger, Martin; Stiasny, Brian; Dave, Hitendu; Cavigelli-Brunner, Anna; Balmer, Christian; Kretschmar, Oliver; Bürki, Christoph; Klauwer, Dietrich; Hübler, Michael

    2015-03-01

    Pediatric heart transplantation (pHTx) represents a small (14%) but very important and particular part in the field of cardiac transplantation. This treatment has lifelong impact on children. To achieve the best short and especially long-term survival with adequate quality of life, which is of crucial importance for this young patient population, one has to realize and understand the differences with adult HTx. Indication for transplantation, waitlist management including ABO incompatible (ABOi) transplantation and immunosuppression differ. Although young transplant recipients are ultimately likely to be considered for re-transplantation. One has to distinguish between myopathy and complex congenital heart disease (CHD). The differences in anatomy and physiology make the surgical procedure much more complex and create unique challenges. These recipients need a well-organized and educated team with pediatric cardiologists and intensivists, including a high skilled surgeon, which is dedicated to pHTx. Therefore, these types of transplants are best concentrated in specialized centers to achieve promising outcome.

  9. Intestinal and multivisceral transplantation

    PubMed Central

    Meira, Sérgio Paiva; Guardia, Bianca Della; Evangelista, Andréia Silva; Matielo, Celso Eduardo Lourenço; Neves, Douglas Bastos; Pandullo, Fernando Luis; Felga, Guilherme Eduardo Gonçalves; Alves, Jefferson André da Silva; Curvelo, Lilian Amorim; Diaz, Luiz Gustavo Guedes; Rusi, Marcela Balbo; Viveiros, Marcelo de Melo; de Almeida, Marcio Dias; Epstein, Marina Gabrielle; Pedroso, Pamella Tung; Salvalaggio, Paolo; Meirelles, Roberto Ferreira; Rocco, Rodrigo Andrey; de Almeida, Samira Scalso; de Rezende, Marcelo Bruno

    2015-01-01

    Intestinal transplantation has shown exceptional growth over the past 10 years. At the end of the 1990’s, intestinal transplantation moved out of the experimental realm to become a routine practice in treating patients with severe complications related to total parenteral nutrition and intestinal failure. In the last years, several centers reported an increasing improvement in survival outcomes (about 80%), during the first 12 months after surgery, but long-term survival is still a challenge. Several advances led to clinical application of transplants. Immunosuppression involved in intestinal and multivisceral transplantation was the biggest gain for this procedure in the past decade due to tacrolimus, and new inducing drugs, mono- and polyclonal anti-lymphocyte antibodies. Despite the advancement of rigid immunosuppression protocols, rejection is still very frequent in the first 12 months, and can result in long-term graft loss. The future of intestinal transplantation and multivisceral transplantation appears promising. The major challenge is early recognition of acute rejection in order to prevent graft loss, opportunistic infections associated to complications, post-transplant lymphoproliferative disease and graft versus host disease; and consequently, improve results in the long run. PMID:25993080

  10. Coffee inhibits nuclear factor-kappa B in prostate cancer cells and xenografts.

    PubMed

    Kolberg, Marit; Pedersen, Sigrid; Mitake, Maiko; Holm, Kristine Lillebø; Bøhn, Siv Kjølsrud; Blomhoff, Heidi Kiil; Carlsen, Harald; Blomhoff, Rune; Paur, Ingvild

    2016-01-01

    Chronic inflammation contributes to prostate cancer and the transcription factor Nuclear Factor-kappa B (NF-κB) is constitutively active in most such cancers. We examine the effects of coffee on NF-κB and on the regulation of selected genes in human-derived prostate cancer cells (PC3) and in PC3 xenografts in athymic nude mice. PC3 cells stably transduced with an NF-κB-luciferase reporter were used both in vitro and for xenografts. NF-κB activity was measured by reporter assays, DNA binding and in vivo imaging. Gene expression was measured in PC3 cells, xenografts and tumor microenvironment by low-density arrays. Western blotting of activated caspases was used to quantify apoptosis. Coffee inhibited TNFα-induced NF-κB activity and DNA-binding in PC3 cells. Furthermore, coffee increased apoptosis and modulated expression of a number of inflammation- and cancer-related genes in TNFα-treated PC3 cells. In vivo imaging revealed a 31% lower NF-κB-luciferase activation in the xenografts of the mice receiving 5% coffee compared to control mice. Interestingly, we observed major changes in gene expression in the PC3 cells in xenografts as compared to PC3 cells in vitro. In PC3 xenografts, genes related to inflammation, apoptosis and cytoprotection were down-regulated in mice receiving coffee, and coffee also affected the gene expression in the xenograft microenvironment. Our data demonstrate that coffee inhibits NF-κB activity in PC3 cells in vitro and in xenografts. Furthermore, coffee modulates transcription of genes related to prostate cancer and inflammation. Our results are the first to suggest mechanistic links between coffee consumption and prostate cancer in an experimental mouse model.

  11. Coffee inhibits nuclear factor-kappa B in prostate cancer cells and xenografts.

    PubMed

    Kolberg, Marit; Pedersen, Sigrid; Mitake, Maiko; Holm, Kristine Lillebø; Bøhn, Siv Kjølsrud; Blomhoff, Heidi Kiil; Carlsen, Harald; Blomhoff, Rune; Paur, Ingvild

    2016-01-01

    Chronic inflammation contributes to prostate cancer and the transcription factor Nuclear Factor-kappa B (NF-κB) is constitutively active in most such cancers. We examine the effects of coffee on NF-κB and on the regulation of selected genes in human-derived prostate cancer cells (PC3) and in PC3 xenografts in athymic nude mice. PC3 cells stably transduced with an NF-κB-luciferase reporter were used both in vitro and for xenografts. NF-κB activity was measured by reporter assays, DNA binding and in vivo imaging. Gene expression was measured in PC3 cells, xenografts and tumor microenvironment by low-density arrays. Western blotting of activated caspases was used to quantify apoptosis. Coffee inhibited TNFα-induced NF-κB activity and DNA-binding in PC3 cells. Furthermore, coffee increased apoptosis and modulated expression of a number of inflammation- and cancer-related genes in TNFα-treated PC3 cells. In vivo imaging revealed a 31% lower NF-κB-luciferase activation in the xenografts of the mice receiving 5% coffee compared to control mice. Interestingly, we observed major changes in gene expression in the PC3 cells in xenografts as compared to PC3 cells in vitro. In PC3 xenografts, genes related to inflammation, apoptosis and cytoprotection were down-regulated in mice receiving coffee, and coffee also affected the gene expression in the xenograft microenvironment. Our data demonstrate that coffee inhibits NF-κB activity in PC3 cells in vitro and in xenografts. Furthermore, coffee modulates transcription of genes related to prostate cancer and inflammation. Our results are the first to suggest mechanistic links between coffee consumption and prostate cancer in an experimental mouse model. PMID:26419686

  12. [Surgical techniques of organ transplants].

    PubMed

    Froněk, Jiří

    2015-01-01

    The list of surgical procedures of solid organ transplantations appears very interesting and colorful, even with overlap among techniques. Liver transplantation is a life-saving procedure in a majority of cases, the liver can be transplanted as a full or partial graft. The liver graft can be split for two recipients; it can also be reduced for a small recipient if splitting is not indicated. Kidney transplantation is the most common solid organ transplant procedure, the majority of kidney grafts come from brain-dead donors whereas the number of live donor transplants is increasing, also thanks to paired donation and blood group incompatible transplantation methods. The small bowel and multivisceral transplantation are rare procedures; they serve selected patients with short bowel syndrome, some patients with retroperitoneal tumors or with extensive visceral thrombosis. Solid organ transplants are well established treatment methods with good and proven outcomes. A majority of patients can return to a normal life after their transplants.

  13. Transplant tourism: understanding the risks.

    PubMed

    Babik, Jennifer M; Chin-Hong, Peter

    2015-04-01

    Transplant tourism is commonly defined as travel abroad for the purpose of transplantation, but the term evokes ethical and legal concerns about commercial transplantation. Due to the mismatch in supply and demand for organs, transplant tourism has increased over the last several decades and now accounts for 10 % of transplants worldwide. Patients from the USA who pursue transplantation abroad do so most commonly for renal transplantation, and travel mostly to China, the Philippines, and India. Transplant tourism puts the organ recipient at risk for surgical complications, poor graft outcome, increased mortality, and a variety of infectious complications. Bacterial, viral, fungal, and parasitic infections have all been described, and most concerning are the high rates of blood-borne viral infections and invasive, often fatal, fungal infections. Transplant and infectious diseases physicians should have a high degree of suspicion for infectious complications in patients returning from transplantation abroad.

  14. [Surgical techniques of organ transplants].

    PubMed

    Froněk, Jiří

    2015-01-01

    The list of surgical procedures of solid organ transplantations appears very interesting and colorful, even with overlap among techniques. Liver transplantation is a life-saving procedure in a majority of cases, the liver can be transplanted as a full or partial graft. The liver graft can be split for two recipients; it can also be reduced for a small recipient if splitting is not indicated. Kidney transplantation is the most common solid organ transplant procedure, the majority of kidney grafts come from brain-dead donors whereas the number of live donor transplants is increasing, also thanks to paired donation and blood group incompatible transplantation methods. The small bowel and multivisceral transplantation are rare procedures; they serve selected patients with short bowel syndrome, some patients with retroperitoneal tumors or with extensive visceral thrombosis. Solid organ transplants are well established treatment methods with good and proven outcomes. A majority of patients can return to a normal life after their transplants. PMID:26585110

  15. Biomechanical research of joints: IV. the biohinge of primates

    NASA Astrophysics Data System (ADS)

    Zhang, Renxiang; Yu, Jie; Lan, Zu-yun; Qu, Wen-ji; Zhang, Hong-zi; Zhang, Kui; Zhang, Liang

    1991-04-01

    In this paper moire topography is applied to study the femoral articular facies of the knee of Primates. For compari son with each other of different families of Primates we suggest the comparative targets a y and the grade G of the moire contour fringes on two condyles of knee of Primates and comparative study of the articulation of knee between the Macaca assamensis M cellaud Presbytis phayrei Rhinopithecus roxellanae Hylobates concolor leucogenys Nycticebus concany Gorilla gorilla Anthropopithecus troglodytes Sirnia satyrus and human being are given. The results may be useful reference in the study of Biomechanics Zoology and Anthropology.

  16. Neurobiological roots of language in primate audition: common computational properties.

    PubMed

    Bornkessel-Schlesewsky, Ina; Schlesewsky, Matthias; Small, Steven L; Rauschecker, Josef P

    2015-03-01

    Here, we present a new perspective on an old question: how does the neurobiology of human language relate to brain systems in nonhuman primates? We argue that higher-order language combinatorics, including sentence and discourse processing, can be situated in a unified, cross-species dorsal-ventral streams architecture for higher auditory processing, and that the functions of the dorsal and ventral streams in higher-order language processing can be grounded in their respective computational properties in primate audition. This view challenges an assumption, common in the cognitive sciences, that a nonhuman primate model forms an inherently inadequate basis for modeling higher-level language functions.

  17. The Evolution of Primate Communication and Metacommunication

    PubMed Central

    2016-01-01

    Abstract Against the prior view that primate communication is based only on signal decoding, comparative evidence suggests that primates are able, no less than humans, to intentionally perform or understand impulsive or habitual communicational actions with a structured evaluative nonconceptual content. These signals convey an affordance‐sensing that immediately motivates conspecifics to act. Although humans have access to a strategic form of propositional communication adapted to teaching and persuasion, they share with nonhuman primates the capacity to communicate in impulsive or habitual ways. They are also similarly able to monitor fluency, informativeness and relevance of messages or signals through nonconceptual cues. PMID:27134332

  18. Neurobiological roots of language in primate audition: common computational properties

    PubMed Central

    Bornkessel-Schlesewsky, Ina; Schlesewsky, Matthias; Small, Steven L.; Rauschecker, Josef P.

    2015-01-01

    This paper presents a new perspective on an old question: how does the neurobiology of human language relate to brain systems in nonhuman primates? We argue that higher-order language combinatorics – including sentence and discourse processing – can be situated in a unified, cross-species dorsal-ventral streams architecture for higher auditory processing, and that the functions of the dorsal and ventral streams in higher-order language processing can be grounded in their respective computational properties in primate audition. This view challenges an assumption, common in the cognitive sciences, that a nonhuman primate model forms an inherently inadequate basis for modeling higher-level language functions. PMID:25600585

  19. Neurobiological roots of language in primate audition: common computational properties.

    PubMed

    Bornkessel-Schlesewsky, Ina; Schlesewsky, Matthias; Small, Steven L; Rauschecker, Josef P

    2015-03-01

    Here, we present a new perspective on an old question: how does the neurobiology of human language relate to brain systems in nonhuman primates? We argue that higher-order language combinatorics, including sentence and discourse processing, can be situated in a unified, cross-species dorsal-ventral streams architecture for higher auditory processing, and that the functions of the dorsal and ventral streams in higher-order language processing can be grounded in their respective computational properties in primate audition. This view challenges an assumption, common in the cognitive sciences, that a nonhuman primate model forms an inherently inadequate basis for modeling higher-level language functions. PMID:25600585

  20. Character displacement of Cercopithecini primate visual signals

    PubMed Central

    Allen, William L.; Stevens, Martin; Higham, James P.

    2014-01-01

    Animal visual signals have the potential to act as an isolating barrier to prevent interbreeding of populations through a role in species recognition. Within communities of competing species, species recognition signals are predicted to undergo character displacement, becoming more visually distinctive from each other, however this pattern has rarely been identified. Using computational face recognition algorithms to model primate face processing, we demonstrate that the face patterns of guenons (tribe: Cercopithecini) have evolved under selection to become more visually distinctive from those of other guenon species with whom they are sympatric. The relationship between the appearances of sympatric species suggests that distinguishing conspecifics from other guenon species has been a major driver of diversification in guenon face appearance. Visual signals that have undergone character displacement may have had an important role in the tribe’s radiation, keeping populations that became geographically separated reproductively isolated on secondary contact. PMID:24967517

  1. Isolation of Pancreatic Islets from Nonhuman Primates.

    PubMed

    Berman, Dora M

    2016-01-01

    Nonhuman primates (NHP) constitute a highly relevant pre-clinical animal model to develop strategies for beta cell replacement. The close phylogenetic and immunologic relationship between NHP and humans results in cross-reactivity of various biological agents with NHP cells, as well as a very similar cytoarchitecture between islets from human and NHP that is strikingly different from that observed in rodent islets. The composition and location of endocrine cells in human or NHP islets, randomly distributed and associated with blood vessels, have functional consequences and a predisposition for paracrine interactions. Furthermore, translation of approaches that proved successful in rodent models to the clinic has been limited. Consequently, data collected from NHP studies can form the basis for an IND submission to the FDA. This chapter describes in detail the key aspects for isolation of islets from NHP, from organ procurement up to assessment of islet function, comparing and emphasizing the similarities between isolation procedures for human and NHP islets. PMID:27586422

  2. IACUC Review of Nonhuman Primate Research

    PubMed Central

    Tardif, Suzette D.; Coleman, Kristine; Hobbs, Theodore R.; Lutz, Corrine

    2013-01-01

    This article will detail some of the issues that must be considered as institutional animal care and use committees (IACUCs) review the use of nonhuman primates (NHPs) in research. As large, intelligent, social, long-lived, and non-domesticated animals, monkeys are amongst the most challenging species used in biomedical research and the duties of the IACUC in relation to reviewing research use of these species can also be challenging. Issues of specific concern for review of NHP research protocols that are discussed in this article include scientific justification, reuse, social housing requirements, amelioration of distress, surgical procedures, and humane endpoints. Clear institutional policies and procedures as regards NHP in these areas are critical, and the discussion of these issues presented here can serve as a basis for the informed establishment of such policies and procedures. PMID:24174445

  3. Living related liver transplantation.

    PubMed

    Makuuchi, M; Kawarazaki, H; Iwanaka, T; Kamada, N; Takayama, T; Kumon, M

    1992-01-01

    Liver transplantation from a brain death donor has not yet been accepted in Japan. The only alternative method at present is transplantation from a living donor. After the first successful living related liver transplantation was performed by Strong in Brisbane, Australia, Japanese hepatic and transplant surgeons also began to perform such operations. As of February 1991, 16 living related liver transplantations had already been performed in Japan, mainly for children with biliary atresia. Five of these patients subsequently died, however, our patient has survived more than 1 year, and she is presently leading a normal school life. The most important issue regarding living related liver transplantation is to ensure the donor's safety. For this purpose, we conducted a preoperative banking of the donor's own blood and plasma. In addition, a selective vascular occlusion was carried out to reduce blood loss during the resection of the liver. Intraoperative color Doppler ultrasonography was introduced for evaluating the circulation of the graft. By using this modality, the following three points were able to be accurately estimated in order to obtain optimal graft perfusion: 1) The most suitable position for the graft to be fixed to the abdominal wall, 2) whether or not the abdominal wall could be closed and 3) the indication for a ligation of the collateral veins to form a porto-systemic shunt. Thanks to these procedures, living related liver transplantations have now become an acceptable transplant method, however, a transplantation from a cadaver that is brain dead but still has a beating heart is still absolutely necessary for adult recipients. Therefore, in the future, both methods should be performed.

  4. First virtual endocasts of adapiform primates.

    PubMed

    Harrington, Arianna R; Silcox, Mary T; Yapuncich, Gabriel S; Boyer, Doug M; Bloch, Jonathan I

    2016-10-01

    Well-preserved crania of notharctine adapiforms from the Eocene of North America provide the best direct evidence available for inferring neuroanatomy and encephalization in early euprimates (crown primates). Virtual endocasts of the notharctines Notharctus tenebrosus (n = 3) and Smilodectes gracilis (n = 4) from the middle Eocene Bridger formation of Wyoming, and the late Eocene European adapid adapiform Adapis parisiensis (n = 1), were reconstructed from high-resolution X-ray computed tomography (CT) data. While the three species share many neuroanatomical similarities differentiating them from plesiadapiforms (stem primates) and extant euprimates, our sample of N. tenebrosus displays more variation than that of S. gracilis, possibly related to differences in the patterns of cranial sexual dimorphism or within-lineage evolution. Body masses predicted from associated teeth suggest that N. tenebrosus was larger and had a lower encephalization quotient (EQ) than S. gracilis, despite their close relationship and similar inferred ecologies. Meanwhile, body masses predicted from cranial length of the same specimens suggest that the two species were more similar, with overlapping body mass and EQ, although S. gracilis exhibits a range of EQs shifted upwards relative to that of N. tenebrosus. While associated data from other parts of the skeleton are mostly lacking for specimens included in this study, measurements for unassociated postcrania attributed to these species yield body mass and EQ estimates that are also more similar to each other than those based on teeth. Regardless of the body mass prediction method used, results suggest that the average EQ of adapiforms was similar to that of plesiadapiforms, only overlapped the lower quadrant for the range of extant strepsirrhines, and did not overlap with the range of extant haplorhines. However, structural changes evident in these endocasts suggest that early euprimates relied more on vision than olfaction

  5. First virtual endocasts of adapiform primates.

    PubMed

    Harrington, Arianna R; Silcox, Mary T; Yapuncich, Gabriel S; Boyer, Doug M; Bloch, Jonathan I

    2016-10-01

    Well-preserved crania of notharctine adapiforms from the Eocene of North America provide the best direct evidence available for inferring neuroanatomy and encephalization in early euprimates (crown primates). Virtual endocasts of the notharctines Notharctus tenebrosus (n = 3) and Smilodectes gracilis (n = 4) from the middle Eocene Bridger formation of Wyoming, and the late Eocene European adapid adapiform Adapis parisiensis (n = 1), were reconstructed from high-resolution X-ray computed tomography (CT) data. While the three species share many neuroanatomical similarities differentiating them from plesiadapiforms (stem primates) and extant euprimates, our sample of N. tenebrosus displays more variation than that of S. gracilis, possibly related to differences in the patterns of cranial sexual dimorphism or within-lineage evolution. Body masses predicted from associated teeth suggest that N. tenebrosus was larger and had a lower encephalization quotient (EQ) than S. gracilis, despite their close relationship and similar inferred ecologies. Meanwhile, body masses predicted from cranial length of the same specimens suggest that the two species were more similar, with overlapping body mass and EQ, although S. gracilis exhibits a range of EQs shifted upwards relative to that of N. tenebrosus. While associated data from other parts of the skeleton are mostly lacking for specimens included in this study, measurements for unassociated postcrania attributed to these species yield body mass and EQ estimates that are also more similar to each other than those based on teeth. Regardless of the body mass prediction method used, results suggest that the average EQ of adapiforms was similar to that of plesiadapiforms, only overlapped the lower quadrant for the range of extant strepsirrhines, and did not overlap with the range of extant haplorhines. However, structural changes evident in these endocasts suggest that early euprimates relied more on vision than olfaction

  6. Prosocial primates: selfish and unselfish motivations

    PubMed Central

    de Waal, Frans B. M.; Suchak, Malini

    2010-01-01

    Non-human primates are marked by well-developed prosocial and cooperative tendencies as reflected in the way they support each other in fights, hunt together, share food and console victims of aggression. The proximate motivation behind such behaviour is not to be confused with the ultimate reasons for its evolution. Even if a behaviour is ultimately self-serving, the motivation behind it may be genuinely unselfish. A sharp distinction needs to be drawn, therefore, between (i) altruistic and cooperative behaviour with knowable benefits to the actor, which may lead actors aware of these benefits to seek them by acting cooperatively or altruistically and (ii) altruistic behaviour that offers the actor no knowable rewards. The latter is the case if return benefits occur too unpredictably, too distantly in time or are of an indirect nature, such as increased inclusive fitness. The second category of behaviour can be explained only by assuming an altruistic impulse, which—as in humans—may be born from empathy with the recipient's need, pain or distress. Empathy, a proximate mechanism for prosocial behaviour that makes one individual share another's emotional state, is biased the way one would predict from evolutionary theories of cooperation (i.e. by kinship, social closeness and reciprocation). There is increasing evidence in non-human primates (and other mammals) for this proximate mechanism as well as for the unselfish, spontaneous nature of the resulting prosocial tendencies. This paper further reviews observational and experimental evidence for the reciprocity mechanisms that underlie cooperation among non-relatives, for inequity aversion as a constraint on cooperation and on the way defection is dealt with. PMID:20679114

  7. Comparative primate energetics and hominid evolution.

    PubMed

    Leonard, W R; Robertson, M L

    1997-02-01

    There is currently great interest in developing ecological models for investigating human evolution. Yet little attention has been given to energetics, one of the cornerstones of modern ecosystem ecology. This paper examines the ecological correlates of variation in metabolic requirements among extant primate species, and uses this information to draw inferences about the changes in energy demands over the course of human evolution. Data on body size, resting metabolism, and activity budgets for selected anthropoid species and human hunter-gatherers are used to estimate total energy expenditure (TEE). Analyses indicate that relative energy expenditure levels and day ranges are positively correlated with diet quality; that is, more active species tend to consume more energy-rich diets. Human foragers fall at the positive extremes for modern primates in having high expenditure levels, large ranges, and very high quality diets. During hominid evolution, it appears that TEE increased substantially with the emergence of Homo erectus. This increase is partly attributable to larger body size as well as likely increases in day range and activity level. Assuming similar activity budgets for all early hominid species, estimated TEE for H. erectus is 40-45% greater than for the australopithecines. If, however, it is assumed that the evolution of early Homo was also associated with a shift to a more "human-like" foraging strategy, estimated expenditure levels for H. erectus are 80-85% greater than in the australopithecines. Changing patterns of resource distribution associated with the expansion of African savannas between 2.5 and 1.5 mya may been the impetus for a shift in foraging behavior among early members of the genus Homo. Such ecological changes likely would have made animal foods a more attractive resource. Moreover, greater use of animal foods and the resulting higher quality diet would have been important for supporting the larger day ranges and greater energy

  8. Early primate evolution in Afro-Arabia.

    PubMed

    Seiffert, Erik R

    2012-11-01

    The peculiar mammalian fauna that inhabited Afro-Arabia during the Paleogene first came to the attention of the scientific community in the early part of the twentieth century, when Andrews1 and Schlosser2 published their landmark descriptions of fossil mammals from the Fayum Depression in northern Egypt. Their studies revealed a highly endemic assemblage of land mammals that included the first known Paleogene records of hyraxes, proboscideans, and anthropoid primates, but which lacked ancestors of many iconic mammalian lineages that are found in Africa today, such as rhinos, zebras, bovids, giraffes, and cats. Over the course of the last century, the Afro-Arabian Paleogene has yielded fossil remains of several other endemic mammalian lineages,3 as well as a diversity of prosimian primates,4 but we are only just beginning to understand how the continent's faunal composition came to be, through ancient processes such as the movement of tectonic plates, changes in climate and sea level, and early phylogenetic splits among the major groups of placental mammals. These processes, in turn, made possible chance dispersal events that were critical in determining the competitive landscape--and, indeed, the survival--of our earliest anthropoid ancestors. Newly discovered fossils indicate that the persistence and later diversification of Anthropoidea was not an inevitable result of the clade's competitive isolation or adaptive superiority, as has often been assumed, but rather was as much due to the combined influences of serendipitous geographic conditions, global cooling, and competition with a group of distantly related extinct strepsirrhines with anthropoid-like adaptations known as adapiforms. Many of the important details of this story would not be known, and could never have been predicted, without the fossil evidence that has recently been unearthed by field paleontologists. PMID:23280921

  9. Microgravity Flight - Accommodating Non-Human Primates

    NASA Technical Reports Server (NTRS)

    Dalton, Bonnie P.; Searby, Nancy; Ostrach, Louis

    1994-01-01

    Spacelab Life Sciences-3 (SLS-3) was scheduled to be the first United States man-tended microgravity flight containing Rhesus monkeys. The goal of this flight as in the five untended Russian COSMOS Bion flights and an earlier American Biosatellite flight, was to understand the biomedical and biological effects of a microgravity environment using the non-human primate as human surrogate. The SLS-3/Rhesus Project and COSMOS Primate-BIOS flights all utilized the rhesus monkey, Macaca mulatta. The ultimate objective of all flights with an animal surrogate has been to evaluate and understand biological mechanisms at both the system and cellular level, thus enabling rational effective countermeasures for future long duration human activity under microgravity conditions and enabling technical application to correction of common human physiological problems within earth's gravity, e.g., muscle strength and reloading, osteoporosis, immune deficiency diseases. Hardware developed for the SLS-3/Rhesus Project was the result of a joint effort with the French Centre National d'Etudes Spatiales (CNES) and the United States National Aeronautics and Space Administration (NASA) extending over the last decade. The flight hardware design and development required implementation of sufficient automation to insure flight crew and animal bio-isolation and maintenance with minimal impact to crew activities. A variety of hardware of varying functional capabilities was developed to support the scientific objectives of the original 22 combined French and American experiments, along with 5 Russian co-investigations, including musculoskeletal, metabolic, and behavioral studies. Unique elements of the Rhesus Research Facility (RRF) included separation of waste for daily delivery of urine and fecal samples for metabolic studies and a psychomotor test system for behavioral studies along with monitored food measurement. As in untended flights, telemetry measurements would allow monitoring of

  10. Mutational Landscapes of Sequential Prostate Metastases and Matched Patient Derived Xenografts during Enzalutamide Therapy.

    PubMed

    Kohli, Manish; Wang, Liguo; Xie, Fang; Sicotte, Hugues; Yin, Ping; Dehm, Scott M; Hart, Steven N; Vedell, Peter T; Barman, Poulami; Qin, Rui; Mahoney, Douglas W; Carlson, Rachel E; Eckel-Passow, Jeanette E; Atwell, Thomas D; Eiken, Patrick W; McMenomy, Brendan P; Wieben, Eric D; Jha, Gautam; Jimenez, Rafael E; Weinshilboum, Richard; Wang, Liewei

    2015-01-01

    Developing patient derived models from individual tumors that capture the biological heterogeneity and mutation landscape in advanced prostate cancer is challenging, but essential for understanding tumor progression and delivery of personalized therapy in metastatic castrate resistant prostate cancer stage. To demonstrate the feasibility of developing patient derived xenograft models in this stage, we present a case study wherein xenografts were derived from cancer metastases in a patient progressing on androgen deprivation therapy and prior to initiating pre-chemotherapy enzalutamide treatment. Tissue biopsies from a metastatic rib lesion were obtained for sequencing before and after initiating enzalutamide treatment over a twelve-week period and also implanted subcutaneously as well as under the renal capsule in immuno-deficient mice. The genome and transcriptome landscapes of xenografts and the original patient tumor tissues were compared by performing whole exome and transcriptome sequencing of the metastatic tumor tissues and the xenografts at both time points. After comparing the somatic mutations, copy number variations, gene fusions and gene expression we found that the patient's genomic and transcriptomic alterations were preserved in the patient derived xenografts with high fidelity. These xenograft models provide an opportunity for predicting efficacy of existing and potentially novel drugs that is based on individual metastatic tumor expression signature and molecular pharmacology for delivery of precision medicine.

  11. Patient-derived xenografts recapitulate molecular features of human uveal melanomas.

    PubMed

    Laurent, Cécile; Gentien, David; Piperno-Neumann, Sophie; Némati, Fariba; Nicolas, André; Tesson, Bruno; Desjardins, Laurence; Mariani, Pascale; Rapinat, Audrey; Sastre-Garau, Xavier; Couturier, Jérôme; Hupé, Philippe; de Koning, Leanne; Dubois, Thierry; Roman-Roman, Sergio; Stern, Marc-Henri; Barillot, Emmanuel; Harbour, J William; Saule, Simon; Decaudin, Didier

    2013-06-01

    We have previously developed a new method for the development and maintenance of uveal melanoma (UM) xenografts in immunodeficient mice. Here, we compare the genetic profiles of the primary tumors to their corresponding xenografts that have been passaged over time. The study included sixteen primary UMs and corresponding xenografts at very early (P1), early (P4), and late (P9) in vivo passages. The tumors were analyzed for mutation status of GNAQ, GNA11, GNAS, GNA15, BAP1, and BRAF, chromosomal copy number alterations using Affymetrix GeneChip(®) Genome-Wide Human SNP6.0 arrays, gene expression profiles using GeneChip(®) Human Exon 1.0 ST arrays, BAP1 mRNA and protein expression, and MAPK pathway status using Reverse Phase Protein Arrays (RPPA). The UM xenografts accurately recapitulated the genetic features of primary human UMs and they exhibited genetic stability over the course of their in vivo maintenance. Our technique for establishing and maintaining primary UMs as xenograft tumors in immunodeficient mice exhibit a high degree of genetic conservation between the primary tumors and the xenograft tumors over multiple passages in vivo. These models therefore constitute valuable preclinical tool for drug screening in UM.

  12. Frequent Infection of Human Cancer Xenografts with Murine Endogenous Retroviruses in Vivo

    PubMed Central

    Naseer, Asif; Terry, Anne; Gilroy, Kathryn; Kilbey, Anna; Watts, Ciorsdaidh; Mackay, Nancy; Bell, Margaret; Mason, Susan; Blyth, Karen; Cameron, Ewan; Neil, James C.

    2015-01-01

    Infection of human cancer xenografts in mice with murine leukemia viruses (MLVs) is a long-standing observation, but the likelihood of infection in vivo and its biological consequences are poorly understood. We therefore conducted a prospective study in commonly used xenograft recipient strains. From BALB/c nude mice engrafted with MCF7 human mammary carcinoma cells, we isolated a virus that was virtually identical to Bxv1, a locus encoding replication-competent xenotropic MLV (XMLV). XMLV was detected in 9/17 (53%) independently isolated explants. XMLV was not found in primary leukemias or in THP1 leukemia cells grown in Bxv1-negative NSG (NOD/SCID/γCnull) mice, although MCF7 explants harbored replication-defective MLV proviruses. To assess the significance of infection for xenograft behavior in vivo, we examined changes in growth and global transcription in MCF7 and the highly susceptible Raji Burkitt lymphoma cell line chronically infected with XMLV. Raji cells showed a stronger transcriptional response that included up-regulation of chemokines and effectors of innate antiviral immunity. In conclusion, the risk of de novo XMLV infection of xenografts is high in Bxv1 positive mice, while infection can have positive or negative effects on xenograft growth potential with significant consequences for interpretation of many xenograft studies. PMID:25912714

  13. Pediatric transplantation: preventing thrombosis.

    PubMed

    Robertson, J D

    2015-06-01

    Due to progressive advances in surgical techniques, immunosuppressive therapies, and supportive care, outcomes from both solid organ transplantation and hematopoietic stem cell transplantation continue to improve. Thrombosis remains a challenging management issue in this context, with implications for both graft survival and long-term quality of life. Unfortunately, there remains a general paucity of pediatric-specific data regarding thrombosis incidence, risk stratification, and the safety or efficacy of preventative strategies with which to guide treatment algorithms. This review summarizes the available evidence and rationale underlying the spectrum of current practices aimed at preventing thrombosis in the transplant recipient, with a particular focus on risk factors, pathophysiology, and described antithrombotic regimens.

  14. Bone Marrow Transplantation

    MedlinePlus

    Bone marrow is the spongy tissue inside some of your bones, such as your hip and thigh bones. ... platelets, which help the blood to clot. A bone marrow transplant is a procedure that replaces a person's ...

  15. Liver transplant - series (image)

    MedlinePlus

    Liver failure causes many problems, including malnutrition, problems with blood clotting, bleeding form the gastrointestinal tract, and jaundice. Frequently, patients who undergo liver transplantation are quite ill, and require ...

  16. Textbooks, Transitions, and Transplants

    ERIC Educational Resources Information Center

    Callahan, Leroy G.; Passi, Sneh Lata

    1972-01-01

    Three popular textbooks were analyzed for level of cognitive processes used, and implications were drawn regarding supplementary activities if the English primary school model is to be transplanted" in America. (MM)

  17. Corneal transplant - series (image)

    MedlinePlus

    Corneal transplantation is recommended for: severe corneal infection, injury, damage, or scarring corneas that no longer allow light to pass through (opaque), often secondary to lens surgery (see cataract surgery), infections, and inherited diseases ...

  18. Kidney transplant - slideshow

    MedlinePlus

    ... M. Editorial team. Related MedlinePlus Health Topics Kidney Transplantation A.D.A.M., Inc. is accredited by ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  19. Talking about Kidney Transplants.

    ERIC Educational Resources Information Center

    Solomon, Joan; Swift, Julia

    1990-01-01

    Described is a project in which information about the moral issues surrounding tissue transplants was obtained and videotaped for classroom use. Moral positions and possible educational strategies are discussed. Examples of student statements are presented. (CW)

  20. Parkinson's disease and primate research: past, present, and future

    PubMed Central

    Pereira, E A C; Aziz, T Z

    2006-01-01

    Scientific research involving non‐human primates has contributed towards many advances in medicine and surgery. This review discusses its role in the progress made towards our understanding of Parkinson's disease and its treatment. Established medical treatments like dopamine agonists continue to need primate models to assess their efficacy, safety, and mechanism of action. The recently developed treatment of deep brain stimulation of the subthalamic nucleus required validation in primates before entering the clinic. Controversies surrounding future treatments such as gene therapy show the need for properly evaluated preclinical research using appropriate animal models before progression to clinical trials. Research on primates has played—and continues to play—a crucial part in deepening our understanding of Parkinson's disease, improving current therapies, and developing new treatments that are both safe and effective. In animal research, the “three Rs” of humane technique—reduction, refinement, and replacement—should be adhered to. PMID:16679465

  1. The earliest fossil evidence for sexual dimorphism in primates

    NASA Technical Reports Server (NTRS)

    Krishtalka, Leonard; Stucky, Richard K.; Beard, K. C.

    1990-01-01

    Recently obtained material of the early Eocene primate Notharctus venticolus, including two partial skulls from a single stratigraphic horizon, provides the geologically earliest evidence of sexual dimorphism in canine size and shape in primates and the only unequivocal evidence for such dimorphism in strepsirhines. By analogy with living platyrrhines, these data suggest that Notharctus venticolus may have lived in polygynous social groups characterized by a relatively high level of intermale competition for mates and other limited resources. The anatomy of the upper incisors and related evidence imply that Notharctus is not as closely related to extant lemuriform primates as has been recently proposed. The early Eocene evidence for canine sexual dimorphism reported here, and its occurrence in a nonanthropoid, indicates that in the order Primates such a condition is either primitive or evolved independently more than once.

  2. Comparative Triceps Surae Morphology in Primates: A Review

    PubMed Central

    Hanna, Jandy B.; Schmitt, Daniel

    2011-01-01

    Primate locomotor evolution, particularly the evolution of bipedalism, is often examined through morphological studies. Many of these studies have examined the uniqueness of the primate forelimb, and others have examined the primate hip and thigh. Few data exist, however, regarding the myology and function of the leg muscles, even though the ankle plantar flexors are highly important during human bipedalism. In this paper, we draw together data on the fiber type and muscle mass variation in the ankle plantar flexors of primates and make comparisons to other mammals. The data suggest that great apes, atelines, and lorisines exhibit similarity in the mass distribution of the triceps surae. We conclude that variation in triceps surae may be related to the shared locomotor mode exhibited by these groups and that triceps surae morphology, which approaches that of humans, may be related to frequent use of semiplantigrade locomotion and vertical climbing. PMID:22567288

  3. Light responses of primate and other mammalian cones

    PubMed Central

    Cao, Li-Hui; Luo, Dong-Gen; Yau, King-Wai

    2014-01-01

    Retinal cones are photoreceptors for daylight vision. For lower vertebrates, cones are known to give monophasic, hyperpolarizing responses to light flashes. For primate cones, however, they have been reported to give strongly biphasic flash responses, with an initial hyperpolarization followed by a depolarization beyond the dark level, now a textbook dogma. We have reexamined this primate-cone observation and, surprisingly, found predominantly monophasic cone responses. Correspondingly, we found that primate cones began to adapt to steady light at much lower intensities than previously reported, explainable by a larger steady response to background light for a monophasic than for a biphasic response. Similarly, we have found a monophasic cone response for several other mammalian species. Thus, a monophasic flash response may in fact be the norm for primate and other mammalian cones as for lower-vertebrate cones. This revised information is important for ultimately understanding human retinal signal processing and correlating with psychophysical data. PMID:24550304

  4. The scaling of frontal cortex in primates and carnivores

    PubMed Central

    Bush, Eliot C.; Allman, John M.

    2004-01-01

    Size has a profound effect on the structure of the brain. Many brain structures scale allometrically, that is, their relative size changes systematically as a function of brain size. Here we use independent contrasts analysis to examine the scaling of frontal cortex in 43 species of mammals including 25 primates and 15 carnivores. We find evidence for significant differences in scaling between primates and carnivores. Primate frontal cortex hyperscales relative to the rest of neocortex and the rest of the brain. The slope of frontal cortex contrasts on rest of cortex contrasts is 1.18 (95% confidence interval, 1.06-1.30) for primates, which is significantly greater than isometric. It is also significantly greater than the carnivore value of 0.94 (95% confidence interval, 0.82-1.07). This finding supports the idea that there are substantial differences in frontal cortex structure and development between the two groups. PMID:15007170

  5. Bat hepadnaviruses and the origins of primate hepatitis B viruses.

    PubMed

    Rasche, Andrea; Souza, Breno Frederico de Carvalho Dominguez; Drexler, Jan Felix

    2016-02-01

    The origin of primate HBV (family Hepadnaviridae) is unknown. Hepadnaviruses are ancient pathogens and may have been associated with old mammalian lineages like bats for prolonged time. Indeed, the genetic diversity of bat hepadnaviruses exceeds that of extant hepadnaviruses in other host orders, suggesting a long evolution of hepadnaviruses in bats. Strikingly, a recently detected New World bat hepadnavirus is antigenically related to HBV and can infect human hepatocytes. Together with genetically diverse hepadnaviruses from New World rodents and a non-human primate, these viruses argue for a New World origin of ancestral orthohepadnaviruses. Multiple host switches of bat and primate viruses are evident and bats are likely sources of ancestral hepadnaviruses acquired by primates. PMID:26897577

  6. Light responses of primate and other mammalian cones.

    PubMed

    Cao, Li-Hui; Luo, Dong-Gen; Yau, King-Wai

    2014-02-18

    Retinal cones are photoreceptors for daylight vision. For lower vertebrates, cones are known to give monophasic, hyperpolarizing responses to light flashes. For primate cones, however, they have been reported to give strongly biphasic flash responses, with an initial hyperpolarization followed by a depolarization beyond the dark level, now a textbook dogma. We have reexamined this primate-cone observation and, surprisingly, found predominantly monophasic cone responses. Correspondingly, we found that primate cones began to adapt to steady light at much lower intensities than previously reported, explainable by a larger steady response to background light for a monophasic than for a biphasic response. Similarly, we have found a monophasic cone response for several other mammalian species. Thus, a monophasic flash response may in fact be the norm for primate and other mammalian cones as for lower-vertebrate cones. This revised information is important for ultimately understanding human retinal signal processing and correlating with psychophysical data. PMID:24550304

  7. Burnout in transplant nurses.

    PubMed

    Jesse, Michelle T; Abouljoud, Marwan S; Hogan, Kathy; Eshelman, Anne

    2015-09-01

    Context-Burnout is a response to chronic strain within the workplace and is common across nursing professions. Little has been published about burnout in organ transplant nurses. Objective-To report the prevalence of the 3 main components of burnout (emotional exhaustion, depersonalization, and reduced personal accomplishment) in organ transplant nurses and to examine factors that contribute to the development of burnout in transplant nurses. Design-Cross-sectional survey of transplant nurses (recruited via listservs) on professional and personal demographics, decisional authority, psychological job demands, supervisor and coworker support, frequency and comfort with difficult patient interactions, and burnout. Participants-369 transplant nurses. Results-About half reported high levels of emotional exhaustion, 15.7% reported high levels of depersonalization, and 51.8% reported low levels of personal accomplishment. Working more hours per week, lower decisional authority, greater psychological job demands, lower perceived supervisor support, and greater frequency and discomfort with difficult patient interactions were significant predictors of emotional exhaustion. Greater frequency and discomfort with difficult patient interactions were significant predictors of depersonalization. Younger age, lower decisional authority, and greater discomfort with difficult patient interactions were predictors of low personal accomplishment. Conclusions-The study provides strong evidence of the presence of burnout in transplant nurses and opportunities for focused and potentially very effective interventions aimed at reducing burnout. PMID:26308777

  8. Burnout in transplant nurses.

    PubMed

    Jesse, Michelle T; Abouljoud, Marwan S; Hogan, Kathy; Eshelman, Anne

    2015-09-01

    Context-Burnout is a response to chronic strain within the workplace and is common across nursing professions. Little has been published about burnout in organ transplant nurses. Objective-To report the prevalence of the 3 main components of burnout (emotional exhaustion, depersonalization, and reduced personal accomplishment) in organ transplant nurses and to examine factors that contribute to the development of burnout in transplant nurses. Design-Cross-sectional survey of transplant nurses (recruited via listservs) on professional and personal demographics, decisional authority, psychological job demands, supervisor and coworker support, frequency and comfort with difficult patient interactions, and burnout. Participants-369 transplant nurses. Results-About half reported high levels of emotional exhaustion, 15.7% reported high levels of depersonalization, and 51.8% reported low levels of personal accomplishment. Working more hours per week, lower decisional authority, greater psychological job demands, lower perceived supervisor support, and greater frequency and discomfort with difficult patient interactions were significant predictors of emotional exhaustion. Greater frequency and discomfort with difficult patient interactions were significant predictors of depersonalization. Younger age, lower decisional authority, and greater discomfort with difficult patient interactions were predictors of low personal accomplishment. Conclusions-The study provides strong evidence of the presence of burnout in transplant nurses and opportunities for focused and potentially very effective interventions aimed at reducing burnout.

  9. Patient-Derived Tumor Xenograft Models of Breast Cancer.

    PubMed

    Suarez, Christopher D; Littlepage, Laurie E

    2016-01-01

    The need for model systems that more accurately predict patient outcome has led to a renewed interest and a rapid development of orthotopic transplantation models designed to grow, expand, and study patient-derived human breast tumor tissue in mice. After implanting a human breast tumor piece into a mouse mammary fat pad and allowing the tumor to grow in vivo, the tumor tissue can be either harvested and immediately implanted into mice or can be stored as tissue pieces in liquid nitrogen for surgical implantation at a later time. Here, we describe the process of surgically implanting patient-derived breast tumor tissue into the mammary gland of nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice and harvesting tumor tissue for long-term storage in liquid nitrogen.

  10. Primate postcrania from the late middle Eocene of Myanmar

    PubMed Central

    Ciochon, Russell L.; Gingerich, Philip D.; Gunnell, Gregg F.; Simons, Elwyn L.

    2001-01-01

    Fossil primates have been known from the late middle to late Eocene Pondaung Formation of Myanmar since the description of Pondaungia cotteri in 1927. Three additional primate taxa, Amphipithecus mogaungensis, Bahinia pondaungensis and Myanmarpithecus yarshensis, were subsequently described. These primates are represented mostly by fragmentary dental and cranial remains. Here we describe the first primate postcrania from Myanmar, including a complete left humerus, a fragmentary right humerus, parts of left and right ulnae, and the distal half of a left calcaneum, all representing one individual. We assign this specimen to a large species of Pondaungia based on body size and the known geographic distribution and diversity of Myanmar primates. Body weight estimates of Pondaungia range from 4,000 to 9,000 g, based on humeral length, humeral midshaft diameter, and tooth area by using extant primate regressions. The humerus and ulna indicate that Pondaungia was capable of a wide variety of forelimb movements, with great mobility at the shoulder joint. Morphology of the distal calcaneus indicates that the hind feet were mobile at the transverse tarsal joint. Postcrania of Pondaungia present a mosaic of features, some shared in common with notharctine and adapine adapiforms, some shared with extant lorises and cebids, some shared with fossil anthropoids, and some unique. Overall, Pondaungia humeral and calcaneal morphology is most consistent with that of other known adapiforms. It does not support the inclusion of Pondaungia in Anthropoidea. PMID:11438722

  11. The evolution of primate general and cultural intelligence.

    PubMed

    Reader, Simon M; Hager, Yfke; Laland, Kevin N

    2011-04-12

    There are consistent individual differences in human intelligence, attributable to a single 'general intelligence' factor, g. The evolutionary basis of g and its links to social learning and culture remain controversial. Conflicting hypotheses regard primate cognition as divided into specialized, independently evolving modules versus a single general process. To assess how processes underlying culture relate to one another and other cognitive capacities, we compiled ecologically relevant cognitive measures from multiple domains, namely reported incidences of behavioural innovation, social learning, tool use, extractive foraging and tactical deception, in 62 primate species. All exhibited strong positive associations in principal component and factor analyses, after statistically controlling for multiple potential confounds. This highly correlated composite of cognitive traits suggests social, technical and ecological abilities have coevolved in primates, indicative of an across-species general intelligence that includes elements of cultural intelligence. Our composite species-level measure of general intelligence, 'primate g(S)', covaried with both brain volume and captive learning performance measures. Our findings question the independence of cognitive traits and do not support 'massive modularity' in primate cognition, nor an exclusively social model of primate intelligence. High general intelligence has independently evolved at least four times, with convergent evolution in capuchins, baboons, macaques and great apes.

  12. Euarchontan Opsin Variation Brings New Focus to Primate Origins.

    PubMed

    Melin, Amanda D; Wells, Konstans; Moritz, Gillian L; Kistler, Logan; Orkin, Joseph D; Timm, Robert M; Bernard, Henry; Lakim, Maklarin B; Perry, George H; Kawamura, Shoji; Dominy, Nathaniel J

    2016-04-01

    Debate on the adaptive origins of primates has long focused on the functional ecology of the primate visual system. For example, it is hypothesized that variable expression of short- (SWS1) and middle-to-long-wavelength sensitive (M/LWS) opsins, which confer color vision, can be used to infer ancestral activity patterns and therefore selective ecological pressures. A problem with this approach is that opsin gene variation is incompletely known in the grandorder Euarchonta, that is, the orders Scandentia (treeshrews), Dermoptera (colugos), and Primates. The ancestral state of primate color vision is therefore uncertain. Here, we report on the genes (OPN1SW and OPN1LW) that encode SWS1 and M/LWS opsins in seven species of treeshrew, including the sole nocturnal scandentian Ptilocercus lowii. In addition, we examined the opsin genes of the Central American woolly opossum (Caluromys derbianus), an enduring ecological analogue in the debate on primate origins. Our results indicate: 1) retention of ultraviolet (UV) visual sensitivity in C. derbianus and a shift from UV to blue spectral sensitivities at the base of Euarchonta; 2) ancient pseudogenization of OPN1SW in the ancestors of P. lowii, but a signature of purifying selection in those of C. derbianus; and, 3) the absence of OPN1LW polymorphism among diurnal treeshrews. These findings suggest functional variation in the color vision of nocturnal mammals and a distinctive visual ecology of early primates, perhaps one that demanded greater spatial resolution under light levels that could support cone-mediated color discrimination.

  13. Stable carbon and nitrogen isotope enrichment in primate tissues

    PubMed Central

    Carter, Melinda L.; Karpanty, Sarah M.; Zihlman, Adrienne L.; Koch, Paul L.; Dominy, Nathaniel J.

    2010-01-01

    Isotopic studies of wild primates have used a wide range of tissues to infer diet and model the foraging ecologies of extinct species. The use of mismatched tissues for such comparisons can be problematic because differences in amino acid compositions can lead to small isotopic differences between tissues. Additionally, physiological and dietary differences among primate species could lead to variable offsets between apatite carbonate and collagen. To improve our understanding of the isotopic chemistry of primates, we explored the apparent enrichment (ε*) between bone collagen and muscle, collagen and fur or hair keratin, muscle and keratin, and collagen and bone carbonate across the primate order. We found that the mean ε* values of proteinaceous tissues were small (≤1‰), and uncorrelated with body size or phylogenetic relatedness. Additionally, ε* values did not vary by habitat, sex, age, or manner of death. The mean ε* value between bone carbonate and collagen (5.6 ± 1.2‰) was consistent with values reported for omnivorous mammals consuming monoisotopic diets. These primate-specific apparent enrichment values will be a valuable tool for cross-species comparisons. Additionally, they will facilitate dietary comparisons between living and fossil primates. Electronic supplementary material The online version of this article (doi:10.1007/s00442-010-1701-6) contains supplementary material, which is available to authorized users. PMID:20628886

  14. Primate spatial strategies and cognition: introduction to this special issue.

    PubMed

    Garber, Paul A; Dolins, Francine L

    2014-05-01

    Wild primates face significant challenges associated with locating resources that involve learning through exploration, encoding, and recalling travel routes, orienting to single landmarks or landmark arrays, monitoring food availability, and applying spatial strategies that reduce effort and increase efficiency. These foraging decisions are likely to involve tradeoffs between traveling to nearby or distant feeding sites based on expectations of resource productivity, predation risk, the availability of other nearby feeding sites, and individual requirements associated with nutrient balancing. Socioecological factors that affect primate foraging decisions include feeding competition, intergroup encounters, mate defense, and opportunities for food sharing. The nine research papers in this Special Issue, "Primate Spatial Strategies and Cognition," address a series of related questions examining how monkeys, apes, and humans encode, internally represent, and integrate spatial, temporal, and quantity information in efficiently locating and relocating productive feeding sites in both small-scale and large-scale space. The authors use a range of methods and approaches to study wild and captive primates, including computer and mathematical modeling, virtual reality, and detailed examinations of animal movement using GPS and GIS analyses to better understand primate cognitive ecology and species differences in decision-making. We conclude this Introduction by identifying a series of critical questions for future research designed to document species-specific differences in primate spatial cognition.

  15. Eye-Blink Behaviors in 71 Species of Primates

    PubMed Central

    Tada, Hideoki; Omori, Yasuko; Hirokawa, Kumi; Ohira, Hideki; Tomonaga, Masaki

    2013-01-01

    The present study was performed to investigate the associations between eye-blink behaviors and various other factors in primates. We video-recorded 141 individuals across 71 primate species and analyzed the blink rate, blink duration, and “isolated” blink ratio (i.e., blinks without eye or head movement) in relation to activity rhythms, habitat types, group size, and body size factors. The results showed close relationships between three types of eye-blink measures and body size factors. All of these measures increased as a function of body weight. In addition, diurnal primates showed more blinks than nocturnal species even after controlling for body size factors. The most important findings were the relationships between eye-blink behaviors and social factors, e.g., group size. Among diurnal primates, only the blink rate was significantly correlated even after controlling for body size factors. The blink rate increased as the group size increased. Enlargement of the neocortex is strongly correlated with group size in primate species and considered strong evidence for the social brain hypothesis. Our results suggest that spontaneous eye-blinks have acquired a role in social communication, similar to grooming, to adapt to complex social living during primate evolution. PMID:23741522

  16. Nonhuman Primate Models in the Genomic Era: A Paradigm Shift

    PubMed Central

    Vallender, Eric J.; Miller, Gregory M.

    2013-01-01

    Because of their strong similarities to humans across physiologic, developmental, behavioral, immunologic, and genetic levels, nonhuman primates are essential models for a wide spectrum of biomedical research. But unlike other animal models, nonhuman primates possess substantial outbred genetic variation, reducing statistical power and potentially confounding interpretation of results in research studies. Although unknown genetic variation is a hindrance in studies that allocate animals randomly, taking genetic variation into account in study design affords an opportunity to transform the way that nonhuman primates are used in biomedical research. New understandings of how the function of individual genes in rhesus macaques mimics that seen in humans are greatly advancing the rhesus macaques utility as research models, but epistatic interaction, epigenetic regulatory mechanisms, and the intricacies of gene networks limit model development. We are now entering a new era of nonhuman primate research, brought on by the proliferation and rapid expansion of genomic data. Already the cost of a rhesus macaque genome is dwarfed by its purchase and husbandry costs, and complete genomic datasets will inevitably encompass each rhesus macaque used in biomedical research. Advancing this outcome is paramount. It represents an opportunity to transform the way animals are assigned and used in biomedical research and to develop new models of human disease. The genetic and genomic revolution brings with it a paradigm shift for nonhuman primates and new mandates on how nonhuman primates are used in biomedical research. PMID:24174439

  17. A Genome-Wide Landscape of Retrocopies in Primate Genomes.

    PubMed

    Navarro, Fábio C P; Galante, Pedro A F

    2015-08-01

    Gene duplication is a key factor contributing to phenotype diversity across and within species. Although the availability of complete genomes has led to the extensive study of genomic duplications, the dynamics and variability of gene duplications mediated by retrotransposition are not well understood. Here, we predict mRNA retrotransposition and use comparative genomics to investigate their origin and variability across primates. Analyzing seven anthropoid primate genomes, we found a similar number of mRNA retrotranspositions (∼7,500 retrocopies) in Catarrhini (Old Word Monkeys, including humans), but a surprising large number of retrocopies (∼10,000) in Platyrrhini (New World Monkeys), which may be a by-product of higher long interspersed nuclear element 1 activity in these genomes. By inferring retrocopy orthology, we dated most of the primate retrocopy origins, and estimated a decrease in the fixation rate in recent primate history, implying a smaller number of species-specific retrocopies. Moreover, using RNA-Seq data, we identified approximately 3,600 expressed retrocopies. As expected, most of these retrocopies are located near or within known genes, present tissue-specific and even species-specific expression patterns, and no expression correlation to their parental genes. Taken together, our results provide further evidence that mRNA retrotransposition is an active mechanism in primate evolution and suggest that retrocopies may not only introduce great genetic variability between lineages but also create a large reservoir of potentially functional new genomic loci in primate genomes. PMID:26224704

  18. The evolution of primate general and cultural intelligence

    PubMed Central

    Reader, Simon M.; Hager, Yfke; Laland, Kevin N.

    2011-01-01

    There are consistent individual differences in human intelligence, attributable to a single ‘general intelligence’ factor, g. The evolutionary basis of g and its links to social learning and culture remain controversial. Conflicting hypotheses regard primate cognition as divided into specialized, independently evolving modules versus a single general process. To assess how processes underlying culture relate to one another and other cognitive capacities, we compiled ecologically relevant cognitive measures from multiple domains, namely reported incidences of behavioural innovation, social learning, tool use, extractive foraging and tactical deception, in 62 primate species. All exhibited strong positive associations in principal component and factor analyses, after statistically controlling for multiple potential confounds. This highly correlated composite of cognitive traits suggests social, technical and ecological abilities have coevolved in primates, indicative of an across-species general intelligence that includes elements of cultural intelligence. Our composite species-level measure of general intelligence, ‘primate gS’, covaried with both brain volume and captive learning performance measures. Our findings question the independence of cognitive traits and do not support ‘massive modularity’ in primate cognition, nor an exclusively social model of primate intelligence. High general intelligence has independently evolved at least four times, with convergent evolution in capuchins, baboons, macaques and great apes. PMID:21357224

  19. Afrotarsius chatrathi, first tarsiiform primate (? Tarsiidae) from Africa

    USGS Publications Warehouse

    Simons, E.L.; Bown, T.M.

    1985-01-01

    Tarsiiform primates have long been regarded as a Laurasian group, with an extensive fossil record in the Eocene of North America and Europe1-4 and two important but less well-known records from Asia5,6. The only living genus is Tarsius (Tarsiidae), whereas all of the fossil tarsier-like primates are usually placed in the extinct family Omomyidae3. We now report the discovery of Afrotarsius chatrathi from early Oligocene rocks of Fayum Province, Egypt. This is the first known tarsiiform primate from Africa. Compared with fossil primates, the molar tooth morphology of this diminutive prosimian is most similar to that of the European Eocene microchoerine Pseudoloris; however, the closest similarity is to the molars of Tarsius. Because the phylogenetic relationships among living Tarsius and the omomyids remain unclear7,8 and because of the fragmentary nature of the only known specimen of this new primate, allocation of Afrotarsius to either Omomyidae or Tarsiidae is necessarily provisional. As we believe that its molar teeth are more like those of Tarsius than of any omomyids (including Pseudoloris), we tentatively assign the new genus to the extant family Tarsiidae as its only known fossil representative. Recovery of a Tarsius-like primate from Africa suggests that it or its ancestors might have been immigrants from Europe, may have been derived from an unknown Asian stock related to the ancestry of Tarsius, or may have originated in Africa. ?? 1985 Nature Publishing Group.

  20. Systemic shRNA mediated knock-down of S100A4 in colorectal cancer xenografted mice reduces metastasis formation

    PubMed Central

    Dahlmann, Mathias; Sack, Ulrike; Herrmann, Pia; Lemm, Margit; Fichtner, Iduna; Schlag, Peter M.; Stein, Ulrike

    2012-01-01

    The metastasis-inducing protein S100A4 was found to be a prognostic indicator for the development of metachronous metastases. S100A4 expression levels correlate with the formation of human colorectal cancer metastases and shorter patients’ survival. Inhibition of S100A4 expression in patients might therefore result in decreased metastasis formation and prolonged survival. In the present study, we used shRNA expression plasmids to inhibit S100A4 expression in the colorectal cancer cell lines HCT116, SW620 and DLD-1. Cell lines with reduced S100A4 expression showed reduced cell migration and invasion in vitro. The knock-down of S100A4 expression also led to significantly diminished formation of liver metastases when intrasplenically transplanted in mice (P = 0.004). We then focused on the therapeutic potential of systemically applied shRNA expression plasmids acting on S100A4 via repeated hydrodynamics-based tail vein injection of plasmid DNA. Mice, intrasplenically transplanted with HCT116 cells and treated systemically with S100A4-shRNA plasmids, showed a decrease of S100A4 and MMP9 expression levels, resulting in significantly reduced liver metastases (P = 0.005). In summary, we show for the first time the intratumoral knock-down of S100A4 via systemic application of S100A4-shRNA plasmid DNA, which restricts metastasis formation in a xenografted mouse model of colorectal cancer. PMID:22878175

  1. MR imaging of human pancreatic cancer xenograft labeled with superparamagnetic iron oxide in nude mice.

    PubMed

    Wu, Chao Ying; Pu, Yu; Liu, Gang; Shao, Yang; Ma, Qing Song; Zhang, Xiao Ming

    2012-01-01

    The aim of this work was to investigate the MRI findings on tumor xenografts induced in nude mice by the inoculation of human pancreatic cancer cells labeled with superparamagnetic iron oxide (SPIO), and to monitor the kinetics of SPIO distribution in tumor xenografts. The labeled cancer cells were subcutaneously inoculated into 11 nude mice to induce tumor xenograft. The unlabeled cancer cells served as a control inoculated into nine nude mice. MR imaging was performed with a 1.5 T MR scanner for the tumor xenograft at the first, second and third week after the inoculation. We found that the tumor xenograft was induced in 100% nude mice on MR imaging for both groups in the first week after the inoculation. In the SPIO group, the tumors showed homogeneous hypointensity on T₁ - and T₂ -weighted and FIESTA images 1 week after inoculation. Two and 3 weeks after inoculation, the center of the tumors was still hypointense on all the above sequences. The tumor periphery was isointense on T₁ -weighted, and hyperintense on T₂ -weighted and FIESTA images. The tumors in control group were homogeneously hypointense or isointense on T₁ -weighted, and hyperintense on T₂ -weighted and FIESTA images in the first, second and third week after the inoculation. The size and signal-to-noise ratio of the tumor center in the SPIO group had decreased subsequent to the inoculation in all T₁ - and T₂ -weighted images and FIESTA. Our results showed the human pancreatic cancer cells labeled with SPIO can induce tumor xenograft in nude mice and MRI can monitor the kinetics of SPIO distribution in tumor xenografts.

  2. Transplant Outcomes (Bone Marrow and Cord Blood)

    MedlinePlus

    ... reports show patient survival and transplant data of bone marrow and umbilical cord blood transplants in the transplant ... Data by Center Report —View the number of bone marrow and cord blood transplants performed at a specific ...

  3. Comparative primate energetics and hominid evolution.

    PubMed

    Leonard, W R; Robertson, M L

    1997-02-01

    There is currently great interest in developing ecological models for investigating human evolution. Yet little attention has been given to energetics, one of the cornerstones of modern ecosystem ecology. This paper examines the ecological correlates of variation in metabolic requirements among extant primate species, and uses this information to draw inferences about the changes in energy demands over the course of human evolution. Data on body size, resting metabolism, and activity budgets for selected anthropoid species and human hunter-gatherers are used to estimate total energy expenditure (TEE). Analyses indicate that relative energy expenditure levels and day ranges are positively correlated with diet quality; that is, more active species tend to consume more energy-rich diets. Human foragers fall at the positive extremes for modern primates in having high expenditure levels, large ranges, and very high quality diets. During hominid evolution, it appears that TEE increased substantially with the emergence of Homo erectus. This increase is partly attributable to larger body size as well as likely increases in day range and activity level. Assuming similar activity budgets for all early hominid species, estimated TEE for H. erectus is 40-45% greater than for the australopithecines. If, however, it is assumed that the evolution of early Homo was also associated with a shift to a more "human-like" foraging strategy, estimated expenditure levels for H. erectus are 80-85% greater than in the australopithecines. Changing patterns of resource distribution associated with the expansion of African savannas between 2.5 and 1.5 mya may been the impetus for a shift in foraging behavior among early members of the genus Homo. Such ecological changes likely would have made animal foods a more attractive resource. Moreover, greater use of animal foods and the resulting higher quality diet would have been important for supporting the larger day ranges and greater energy

  4. Functional Analysis of the Primate Shoulder

    PubMed Central

    Hohn, Bianca; Scherf, Heike; Schmidt, Manuela; Krause, Cornelia; Witzel, Ulrich

    2010-01-01

    Studies of the shoulder girdle are in most cases restricted to morphological comparisons and rarely aim at elucidating function in a strictly biomechanical sense. To fill this gap, we investigated the basic functional conditions that occur in the shoulder joint and shoulder girdle of primates by means of mechanics. Because most of nonhuman primate locomotion is essentially quadrupedal walking—although on very variable substrates—our analysis started with quadrupedal postures. We identified the mechanical situation at the beginning, middle, and end of the load-bearing stance phase by constructing force parallelograms in the shoulder joint and the scapulo-thoracal connection. The resulting postulates concerning muscle activities are in agreement with electromyographical data in the literature. We determined the magnitude and directions of the internal forces and explored mechanically optimal shapes of proximal humerus, scapula, and clavicula using the Finite Element Method. Next we considered mechanical functions other than quadrupedal walking, such as suspension and brachiation. Quadrupedal walking entails muscle activities and joint forces that require a long scapula, the cranial margin of which has about the same length as the axillary margin. Loading of the hand in positions above the head and suspensory behaviors lead to force flows along the axillary margin and so necessitate a scapula with an extended axillary and a shorter cranial margin. In all cases, the facies glenoidalis is nearly normal to the calculated joint forces. In anterior view, terrestrial monkeys chose a direction of the ground reaction force requiring (moderate) activity of the abductors of the shoulder joint, whereas more arboreal monkeys prefer postures that necessitate activity of the adductors of the forelimb even when walking along branches. The same adducting and retracting muscles are recruited in various forms of suspension. As a mechanical consequence, the scapula is in a more

  5. The global alliance for transplantation.

    PubMed

    Groth, C G; Chapman, J R

    2006-03-01

    In 2002, The Transplantation Society proposed the creation of a Global Alliance for Transplantation, with the purpose of reducing the existing disparity regarding transplantation activities across the globe. This alliance should include major international scientific societies, international governmental organizations, and pharmaceutical companies. Consultations with each of these parties have taken place during the past 18 months and three Strategic Programs have been initiated: (1) the collection of information on transplantation; (2) the expansion of education in transplantation; and (3) the development of professional guidelines for organ donation and transplantation. PMID:16549119

  6. RNAi-mediated silencing of HLA A2 suppressed acute rejection against human fibroblast xenografts in the striatum of 6-OHDA lesioned rats.

    PubMed

    Liang, Caixia; Xu, Yunzhi; Zheng, Deyu; Sun, Xiaohong; Xu, Qunyuan; Duan, Deyi

    2016-08-15

    Major histocompatibility complex class l (MHC I) molecules play a role in determining whether transplanted cells will be accepted or rejected, and masking of MHC I on donor cells has been found useful for immunoprotection of neural xenografts. In the present study, primary human embryonic lung fibroblasts (HELF), HELF treated with lentivirus-mediated small interfering RNAs (siRNAs) targeting human leukocyte antigen A2 (HLA A2, MHC I in humans) (siHELF), and rat embryonic lung fibroblasts (RELF) were stereotaxically grafted into the striatum of 6-hydroxydopamine lesioned rats to explore whether knockdown of HLA A2 could reduce host immune responses against xenografts. Before lentiviral infection, the cells were transduced with retroviruses harboring tyrosine hydroxylase cDNA. Knockdown of HLA A2 protein was examined by Western blotting. The immune responses (the number of CD4 and CD8 T-cells in the brain and peripheral blood), glial reaction, and survival of human fibroblasts were quantitatively evaluated by flow cytometry and immunohistochemistry at 4d, 2w, and 6w post-graft. Animal behaviors were assessed by counting apomorphine-induced rotations pre- and post-grafts. It was shown that a lower level of HLA A2 was observed in siHELF grafts than in HELF grafts, and knockdown of HLA A2 decreased rat immune responses, as indicated by less remarkable increases in the number of CD8 and CD4 T-cells in the brain and the ratio of CD4:CD8 T-cells in the peripheral blood in rats grafted with siHELF. Rats grafted with siHELF exhibited a significant improvement in motor asymmetry post-transplantation and a better survival of human fibroblasts at 2w. The increasing number of activated microglia and the decreasing number of astrocytes were found in three groups of rats post-implantation. These data suggested that RNAi-mediated knockdown of HLA A2 could suppress acute rejection against xenogeneic human cell transplants in the rat brain. PMID:27397073

  7. Survival of primates following orthotopic cardiac transplantation treated with total lymphoid irradiation and chemical immune suppression

    SciTech Connect

    Pennock, J.L.; Reitz, B.A.; Beiber, C.P.; Aziz, S.; Oyer, P.E.; Strober, S.; Hoppe, R.; Kaplan, H.S.; Stinson, E.B.; Shumway, N.E.

    1981-12-01

    Fractionated total lymphoid irradiation (TLI) has been used for attempts at induction of a donor-specific tolerant-like state in allograft recipients and for immunosuppressive effects. Cyclosporin A (Cy A) has been shown to suppress rejection of organ grafts in many species including man. The present study was designed to test the effectiveness of TLI in combination with either Cy A or rabbit anticynomolgus thymocyte globulin (ATG) and azathioprine. Thirty-one orthotopic cardiac allografts were performed using surface cooling and total circulatory arrest in outbred cynomolgus monkeys. TLI was administered preoperatively in fractions of 100 rad until a total of 600 or 1800 rad was achieved. Cy A was administered 17 mg/kg/day. All treatment groups demonstrated extended survival. Myocardial biopsies as early as 4 weeks were consistent with mild rejection in all treatment groups. No significant synergistic effect upon survival could be demonstrated utilizing TLI (1800 rad) plus ATG and azathioprine was associated with a high incidence of early death attributable to leukopenia and infection. Cy A alone or in combination with TLI was associated with the development of lymphoid malignancy.

  8. Survival of primates following orthotopic cardiac transplantation treated with total lymphoid irradiation and chemical immune suppression

    SciTech Connect

    Pennock, J.L.; Reitz, B.A.; Bieber, C.P.; Aziz, S.; Oyer, P.E.; Strober, S.; Hoppe, R.; Kaplan, H.S.; Stinson, E.B.; Shumway, N.E.

    1981-12-01

    Fractionated total lymphoid irradiation (TLI) has been used for attempts at induction of a donor-specific tolerant-like state in allograft recipients and for immunosuppressive effects. Cyclosporin A (Cy A) has been shown to suppress rejection of organ grafts in many species including man. The present study was designed to test the effectiveness of TLI in combination with either CY A or rabbit anticynomolgus thymocyte globulin (ATG) and azathioprine. Thirty-one orthotopic cardiac allografts were performed using surface cooling and total circulatory arrest in outbred cynomolgus monkeys. TLI was administered preoperatively in fractions of 100 rad until a total of 600 or 1800 rad was achieved. Cy A was administered 17 mg/kg/day. All treatment groups demonstrated extended survival. Myocardial biopsies as early as 4 weeks were consistent with mild rejection in all treatment groups. No significant synergistic effect upon survival could be demonstrated utilizing TLI plus Cy A when compared with using Cy A alone. TLI (1800 rad) plus ATG and azathioprine was associated with a high incidence of early death attributable to leukopenia and infection. Cy A alone or in combination with TLI was associated with the development of lymphoid malignancy.

  9. Liver transplantation in Germany.

    PubMed

    Tacke, Frank; Kroy, Daniela C; Barreiros, Ana Paula; Neumann, Ulf P

    2016-08-01

    Liver transplantation (LT) is a well-accepted procedure for end-stage liver disease in Germany. In 2015, 1489 patients were admitted to the waiting list (including 1308 new admissions), with the leading etiologies being fibrosis and cirrhosis (n = 349), alcoholic liver disease (n = 302), and hepatobiliary malignancies (n = 220). Organ allocation in Germany is regulated within the Eurotransplant system based on urgency as expressed by the Model for End-Stage Liver Disease score. In 2015, only 894 LTs (n = 48 from living donors) were performed at 23 German transplant centers, reflecting a shortage of organs. Several factors may contribute to the low number of organ donations. The German transplant legislation only accepts donation after brain death (not cardiac death), whereas advances in neurosurgery and a more frequently requested "palliative care" approach render fewer patients suitable as potential donors. The legislation further requires the active consent of the donor or first-degree relatives before donation. Ongoing debates within the German transplant field address the optimal management of patients with alcoholic liver cirrhosis, hepatocellular carcinoma (HCC), and cholangiocarcinoma and measures to increase living donor transplantations. As a result of irregularities at mainly 4 German transplant centers that were exposed in 2012, guiding principles updated by the German authorities have since implemented strict rules (including internal and external auditing, the 8-eyes principle, mandatory repeated testing for alcohol consumption) to prohibit any manipulations in organ allocation. In conclusion, we will summarize important aspects on the management of LT in Germany, discuss legal and organizational aspects, and highlight challenges mainly related to the relative lack of organ donations, increasing numbers of extended criteria donors, and the peculiarities of the recipient patients. Liver Transplantation 22 1136-1142 2016 AASLD.

  10. Liver transplantation in Germany.

    PubMed

    Tacke, Frank; Kroy, Daniela C; Barreiros, Ana Paula; Neumann, Ulf P

    2016-08-01

    Liver transplantation (LT) is a well-accepted procedure for end-stage liver disease in Germany. In 2015, 1489 patients were admitted to the waiting list (including 1308 new admissions), with the leading etiologies being fibrosis and cirrhosis (n = 349), alcoholic liver disease (n = 302), and hepatobiliary malignancies (n = 220). Organ allocation in Germany is regulated within the Eurotransplant system based on urgency as expressed by the Model for End-Stage Liver Disease score. In 2015, only 894 LTs (n = 48 from living donors) were performed at 23 German transplant centers, reflecting a shortage of organs. Several factors may contribute to the low number of organ donations. The German transplant legislation only accepts donation after brain death (not cardiac death), whereas advances in neurosurgery and a more frequently requested "palliative care" approach render fewer patients suitable as potential donors. The legislation further requires the active consent of the donor or first-degree relatives before donation. Ongoing debates within the German transplant field address the optimal management of patients with alcoholic liver cirrhosis, hepatocellular carcinoma (HCC), and cholangiocarcinoma and measures to increase living donor transplantations. As a result of irregularities at mainly 4 German transplant centers that were exposed in 2012, guiding principles updated by the German authorities have since implemented strict rules (including internal and external auditing, the 8-eyes principle, mandatory repeated testing for alcohol consumption) to prohibit any manipulations in organ allocation. In conclusion, we will summarize important aspects on the management of LT in Germany, discuss legal and organizational aspects, and highlight challenges mainly related to the relative lack of organ donations, increasing numbers of extended criteria donors, and the peculiarities of the recipient patients. Liver Transplantation 22 1136-1142 2016 AASLD. PMID:27082951

  11. Liver transplantation in Spain.

    PubMed

    de la Rosa, Gloria; Fondevila, Constantino; Navasa, Miquel

    2016-09-01

    Liver transplantation (LT) activity started in Spain in 1984 and has exceeded 23,700 interventions, with more than 1000 transplants performed yearly. Every hospital needs official authorization to perform a LT, which implies the obligation to register all patients on the national waiting list. The Spanish National Transplant Organization (ONT) provides essential support for organ procurement, allocation, and management of the waiting list at a national level. Liver allocation is center-oriented as all available organs are referred to the ONT for the whole country. The allocation rules for LT are made according to disease severity after consensus among professionals from every transplant center and ratified by representatives of the regional health authorities. Authorization and location/distribution of transplant centers are regulated by the country (Spain) and by the different regions according to the Real Decreto 1723/2012. For a total population of 47,850,795 inhabitants, there are 24 centers for LT for adults (1 team/2 million people) and 5 for LT for children (1 team/9.5 million people). Nonbiliary cirrhosis, particularly alcohol- and hepatitis C virus-related cirrhosis (60%), and tumors, mainly hepatocellular carcinoma (19%), are the most common indications for LT in Spain. Unusual causes of LT include metabolic diseases like Wilson's disease, familial amyloid polyneuropathy and hyperoxaluria type I, polycystic kidney and liver disease, and some tumors (epithelioid hemangioendothelioma and neuroendocrine tumors). Important efforts are now being undertaken to improve the quality and transplantability of extended criteria livers, in particular those arising from DCD, which represent the greatest opportunity to expand the donor pool. These efforts have to be addressed to adapt the organ preservation procedures, be it through the application of regional perfusion in situ or the use of machine perfusion preservation ex situ. Liver Transplantation 22 1259-1264 2016

  12. European Transplant Registry of Senior Renal Transplant Recipients on Advagraf

    ClinicalTrials.gov

    2016-08-11

    Graft Failure; Death; Acute Rejection of Renal Transplant; Infections; Bone Disease; Post Transplant Diabetes Mellitus; Quality of Life; HLA Antibody Production; Cardiovascular Risk Factors; Non-HLA Antibody Production

  13. Microrefined microfollicular hair transplant: a new modification in hair transplant.

    PubMed

    Gupta, Amit

    2014-09-01

    : Hair transplant is the most common cosmetic surgery procedure in men; at our center, we perform nearly 40 transplants a month, with nearly 450 procedures in a year. Current techniques of hair transplant are well established and several authors have had remarkable results using the current techniques of microfollicular hair transplant. Orentreich described hair transplant, Shiell has reviewed current techniques in his paper, whereas Rose reviews the latest innovations in hair transplant including Neograft and robotic procedures. We present our modifications to the process based on our experience of more than 1000 cases in the last 3 years.Microrefined microfollicular hair transplant is a procedure with innovations at each step of the standard microfollicular hair transplant procedure to improve results.The steps of the procedure are as follows: PMID:24374401

  14. Successful Xenograft of Endoscopic Ultrasound-Guided Fine-Needle Aspiration Specimen from Human Extrahepatic Cholangiocarcinoma into an Immunodeficient Mouse.

    PubMed

    Jang, Se Young; Bae, Han Ik; Lee, In Kyu; Park, Hwan Ki; Cho, Chang-Min

    2015-11-23

    Patient-derived tumor xenograft is the transfer of primary human tumors directly into an immunodeficient mouse. Patient-derived tumor xenograft plays an important role in the development and evaluation of new chemotherapeutic agents. We succeeded in generating a patient-derived tumor xenograft of a biliary tumor obtained by endoscopic ultrasound-guided fine-needle aspiration from a patient who had an inoperable extrahepatic cholangiocarcinoma. This patient-derived tumor xenograft will be a promising tool for individualized cancer therapy and can be used in developing new chemotherapeutic agents for the treatment of biliary cancer in the future.

  15. Experimental schistosomiasis in primates in Tanzania

    PubMed Central

    Jordan, P.; von Lichtenberg, F.; Goatly, K. D.

    1967-01-01

    Laboratory infection of animals with Schistosoma haematobium is generally unsatisfactory as adult worms invariably inhabit the portal venous system rather than the vesical plexus as in man. However, it was thought that certain primates might prove more valuable for experimental studies of schistosomiasis than the usual laboratory animals. Baboons, Papio anubis, were therefore exposed to cercariae of S. haematobium and the pattern of egg excretion in stools and urine was followed quantitatively. Histological studies of various organs were made and it was found that although eggs were excreted in the faeces, they were also passed in the urine and that tissue changes in the bladder were similar to those found in human infections. It is suggested that the sequelae of S. haematobium infection found in man might develop in baboons and that the animal may be useful for studying their development in the laboratory. ImagesFIG. 3FIG. 8FIG. 11FIG. 4FIG. 10FIG. 9FIG. 6FIG. 7FIG. 5 PMID:4968348

  16. Neurobiological mechanisms of puberty in higher primates.

    PubMed

    Plant, Tony M; Barker-Gibb, Mandi L

    2004-01-01

    Puberty in humans is comprised of two developmental processes; namely, gonadarche and adrenarche. Of the two, gonadarche is fundamentally the most important, and this review examines the neurobiological mechanisms that first prevent, and later trigger, progression into this critically important phase of human development when the ability to first reproduce is established. The review draws extensively upon results obtained by studies of the rhesus monkey (Macaca mulatta), a representative higher primate which, like man, exhibits a postnatal pattern in activity of the hypothalamic-pituitary-gonadal axis that is characterized by a prolonged period of relative quiescence from late infancy until the initiation of the pubertal process. The proximate cause of the prepubertal quiescence in this neuroendocrine axis is the arrest or restraint of the pulsatile mode of hypothalamic GnRH release by a neurobiological brake that holds in check release of this decapeptide, without seeming to down-regulate the transcriptional activity of the gene encoding GnRH (GnRH-I). Thus, if neurogenomes control the onset of gonadarche, they must reside upstream from that of the GnRH neuron. The genetic and physiological factors (with a particular emphasis on leptin) that time the application and duration of the prepubertal brake on GnRH release are also considered.

  17. Computer retina that models the primate retina

    NASA Astrophysics Data System (ADS)

    Shah, Samir; Levine, Martin D.

    1994-06-01

    At the retinal level, the strategies utilized by biological visual systems allow them to outperform machine vision systems, serving to motivate the design of electronic or `smart' sensors based on similar principles. Design of such sensors in silicon first requires a model of retinal information processing which captures the essential features exhibited by biological retinas. In this paper, a simple retinal model is presented, which qualitatively accounts for the achromatic information processing in the primate cone system. The model exhibits many of the properties found in biological retina such as data reduction through nonuniform sampling, adaptation to a large dynamic range of illumination levels, variation of visual acuity with illumination level, and enhancement of spatio temporal contrast information. The model is validated by replicating experiments commonly performed by electrophysiologists on biological retinas and comparing the response of the computer retina to data from experiments in monkeys. In addition, the response of the model to synthetic images is shown. The experiments demonstrate that the model behaves in a manner qualitatively similar to biological retinas and thus may serve as a basis for the development of an `artificial retina.'

  18. Stereometrics In Primate Taxonomy And Phylogeny

    NASA Astrophysics Data System (ADS)

    Creel, Norman

    1980-07-01

    Studies of the systematic relationships within the primate taxa Homo, Hylobatidae (lesser apes), Hominoidea (apes and man) and Colobinae (Asian and African leaf monkeys) are described. All are based in large part on multivariate statistical analyses of cranial morphology. Adequate quantification of the frequently complex and subtle differences in the morphology of the animals being compared, as well as the inclusion of statistically adequate samples of as many presumed species or other groups of interest as possible, are essential to the success of such analyses. Two methods of stereometric measurement have been developed to make this possible. In initial studies of the Hylobatidae and the Hominoidea, a simple mechanical device was designed which determines the tri-dimensional coordinates of an anatomical point by measuring an angle and two distances. An improved version was used in an investigation of Subsaharan human crania. In a taxonomic revision of the Colobinae now in progress, crania are photographed in several views with a pair of metric cameras; point coordinates are then measured in a modified stereoplotter and the views rotated mathematically into a single coordinate system. Although stereometrics is only one component in a complex system of analysis, it is an extremely important one. Taxonomic revisions of the described scope and depth could not be carried out with conventional methods of measurement without a much greater commitment of resources, if at all.

  19. Context modulates signal meaning in primate communication

    PubMed Central

    Flack, Jessica C.; de Waal, Frans

    2007-01-01

    A central issue in the evolution of social complexity and the evolution of communication concerns the capacity to communicate about increasingly abstract objects and concepts. Many animals can communicate about immediate behavior, but to date, none have been reported to communicate about behavior during future interactions. In this study, we show that a special, unidirectional, cost-free dominance-related signal used by monkeys (pigtailed macaques: Macaca nemestrina) means submission (immediate behavior) or subordination (pattern of behavior) depending on the context of usage. We hypothesize that to decrease receiver uncertainty that the signal object is subordination, senders shift contextual usage from the conflict context, where the signal evolved, to a peaceful one, in which submission is unwarranted. We predict and find that deceasing receiver uncertainty through peaceful signal exchange facilitates the development of higher quality social relationships: Individuals exchanging the peaceful variant groom and reconcile more frequently and fight less frequently than individuals exchanging signals only in the conflict context or no signals. We rule out alternative hypotheses, including an underlying reciprocity rule, temperament, and proximity effects. Our results suggest that primates can communicate about behavioral patterns when these concern relationship rules. The invention of signals decreasing uncertainty about relationship state is likely to have been critical for the evolution of social complexity and to the emergence of robust power structures that feed down to influence rapidly changing individual behavior. PMID:17244712

  20. Evolutionary pressures on primate intertemporal choice.

    PubMed

    Stevens, Jeffrey R

    2014-07-01

    From finding food to choosing mates, animals must make intertemporal choices that involve fitness benefits available at different times. Species vary dramatically in their willingness to wait for delayed rewards. Why does this variation across species exist? An adaptive approach to intertemporal choice suggests that time preferences should reflect the temporal problems faced in a species's environment. Here, I use phylogenetic regression to test whether allometric factors relating to body size, relative brain size and social group size predict how long 13 primate species will wait in laboratory intertemporal choice tasks. Controlling for phylogeny, a composite allometric factor that includes body mass, absolute brain size, lifespan and home range size predicted waiting times, but relative brain size and social group size did not. These findings support the notion that selective pressures have sculpted intertemporal choices to solve adaptive problems faced by animals. Collecting these types of data across a large number of species can provide key insights into the evolution of decision making and cognition. PMID:24827445

  1. FTIR study of primate color visual pigments

    PubMed Central

    Katayama, Kota; Kandori, Hideki

    2015-01-01

    How do we distinguish colors? Humans possess three color pigments; red-, green-, and blue-sensitive proteins, which have maximum absorbance (λmax) at 560, 530, and 420 nm, respectively, and contribute to normal human trichromatic vision (RGB). Each color pigments consists of a different opsin protein bound to a common chromophore molecule, 11-cis-retinal, whereas different chromophore-protein interactions allow preferential absorption of different colors. However, detailed experimental structural data to explain the molecular basis of spectral tuning of color pigments are lacking, mainly because of the difficulty in sample preparation. We thus started structural studies of primate color visual pigments using low-temperature Fourier-transform infrared (FTIR) spectroscopy, which needs only 0.3 mg protein for a single measurement. Here we report the first structural data of monkey red- (MR) and green- (MG) sensitive pigments, in which the information about the protein, retinal chromophore, and internal water molecules is contained. Molecular mechanism of color discrimination between red and green pigments will be discussed based on the structural data by FTIR spectroscopy. PMID:27493516

  2. FTIR study of primate color visual pigments.

    PubMed

    Katayama, Kota; Kandori, Hideki

    2015-01-01

    How do we distinguish colors? Humans possess three color pigments; red-, green-, and blue-sensitive proteins, which have maximum absorbance (λmax) at 560, 530, and 420 nm, respectively, and contribute to normal human trichromatic vision (RGB). Each color pigments consists of a different opsin protein bound to a common chromophore molecule, 11-cis-retinal, whereas different chromophore-protein interactions allow preferential absorption of different colors. However, detailed experimental structural data to explain the molecular basis of spectral tuning of color pigments are lacking, mainly because of the difficulty in sample preparation. We thus started structural studies of primate color visual pigments using low-temperature Fourier-transform infrared (FTIR) spectroscopy, which needs only 0.3 mg protein for a single measurement. Here we report the first structural data of monkey red- (MR) and green- (MG) sensitive pigments, in which the information about the protein, retinal chromophore, and internal water molecules is contained. Molecular mechanism of color discrimination between red and green pigments will be discussed based on the structural data by FTIR spectroscopy.

  3. Anthocyanin Induces Apoptosis of DU-145 Cells In Vitro and Inhibits Xenograft Growth of Prostate Cancer

    PubMed Central

    Ha, U-Syn; Bae, Woong Jin; Kim, Su Jin; Yoon, Byung Il; Hong, Sung Hoo; Lee, Ji Youl; Hwang, Tae-Kon; Hwang, Sung Yeoun; Wang, Zhiping

    2015-01-01

    Purpose To investigate the effects of anthocyanins extracted from black soybean, which have antioxidant activity, on apoptosis in vitro (in hormone refractory prostate cancer cells) and on tumor growth in vivo (in athymic nude mouse xenograft model). Materials and Methods The growth and viability of DU-145 cells treated with anthocyanins were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and apoptosis was assessed by DNA laddering. Immunoblotting was conducted to evaluate differences in the expressions of p53, Bax, Bcl, androgen receptor (AR), and prostate specific antigen (PSA). To study the inhibitory effects of anthocyanins on tumor growth in vivo, DU-145 tumor xenografts were established in athymic nude mice. The anthocyanin group was treated with daily oral anthocyanin (8 mg/kg) for 14 weeks. After 2 weeks of treatment, DU-145 cells (2×106) were inoculated subcutaneously into the right flank to establish tumor xenografts. Tumor dimensions were measured twice a week using calipers and volumes were calculated. Results Anthocyanin treatment of DU-145 cells resulted in 1) significant increase in apoptosis in a dose-dependent manner, 2) significant decrease in p53 and Bcl-2 expressions (with increased Bax expression), and 3) significant decrease in PSA and AR expressions. In the xenograft model, anthocyanin treatment significantly inhibit tumor growth. Conclusion This study suggests that anthocyanins from black soybean inhibit the progression of prostate cancer in vitro and in a xenograft model. PMID:25510742

  4. [Renal transplantation: ethical issues].

    PubMed

    Mamzer-Bruneel, Marie-France; Laforêt, Emmanuelle Grand; Kreis, Henri; Thervet, Éric; Martinez, Frank; Snanoudj, Renaud; Hervé, Christian; Legendre, Christophe

    2012-12-01

    One of the most significant advances in medicine during the last 50 years is the development of organ transplantation. In the context of chronic kidney diseases, renal transplantation offers patients a better clinical outcome than other treatment options. However, the benefits of organ transplantation have not been maximized due to an inadequate supply of organs for transplantation. Despite the establishment of elaborate legal rules for organs procurement, both on deceased and living donors in numerous countries, ethical concerns remain. Most of them are consequences of the strategies implemented or proposed to address the so-called organ shortage. The involvement of society in these complex problems is crucial as numerous questions emerge: could actual state of organ procurement change? Is it possible and/or realistic to increase the number of organs, with respects to living donors or deceased persons? Is the shortage an indicator to limit the use of kidney transplantation? How do we maintain efficiency and justice, in this context. PMID:23168353

  5. Stem Cell Transplants (For Teens)

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Stem Cell Transplants KidsHealth > For Teens > Stem Cell Transplants Print ... Does it Take to Recover? Coping What Are Stem Cells? As you probably remember from biology class, every ...

  6. Intraocular retinal transplantation: a review.

    PubMed

    Hammer, R M; Yinon, U

    1991-01-01

    This review covers intraocular transplantation of retinal tissue. This has importance both for theoretical understanding of retinal and neural development and for possible future clinical application. Transplantation sites have ranged from the anterior chamber through the retina to the subretinal space. Transplanted tissue has ranged from whole retina to specific retinal layers or specific types of retinal cells. Both within-species and inter-species transplants have been performed, and donor age has ranged from embryonic to adult. The ability of transplanted tissue to be accepted and to differentiate in host eyes has been studied. The conditions under which successful transplants are obtained, host-graft interactions, and transplantation methodologies have been explored. Morphological, and to a small extent, also functional characteristics of the transplants have been studied. PMID:1747393

  7. About the Operation: Liver Transplant

    MedlinePlus

    ... Heart/Lung Kidney Pancreas Kidney/Pancreas Liver Intestine Liver Transplant There are two very different surgical approaches to liver transplantation: the orthotopic and the heterotopic approach, both ...

  8. No need to replace an "anomalous" primate (Primates) with an "anomalous" bear (Carnivora, Ursidae).

    PubMed

    Gutiérrez, Eliécer E; Pine, Ronald H

    2015-01-01

    By means of mitochondrial 12S rRNA sequencing of putative "yeti", "bigfoot", and other "anomalous primate" hair samples, a recent study concluded that two samples, presented as from the Himalayas, do not belong to an "anomalous primate", but to an unknown, anomalous type of ursid. That is, that they match 12S rRNA sequences of a fossil Polar Bear (Ursusmaritimus), but neither of modern Polar Bears, nor of Brown Bears (Ursusarctos), the closest relative of Polar Bears, and one that occurs today in the Himalayas. We have undertaken direct comparison of sequences; replication of the original comparative study; inference of phylogenetic relationships of the two samples with respect to those from all extant species of Ursidae (except for the Giant Panda, Ailuropodamelanoleuca) and two extinct Pleistocene species; and application of a non-tree-based population aggregation approach for species diagnosis and identification. Our results demonstrate that the very short fragment of the 12S rRNA gene sequenced by Sykes et al. is not sufficiently informative to support the hypotheses provided by these authors with respect to the taxonomic identity of the individuals from which these sequences were obtained. We have concluded that there is no reason to believe that the two samples came from anything other than Brown Bears. These analyses afforded an opportunity to test the monophyly of morphologically defined species and to comment on both their phylogenetic relationships and future efforts necessary to advance our understanding of ursid systematics.

  9. LOGISMOS-B for primates: primate cortical surface reconstruction and thickness measurement

    NASA Astrophysics Data System (ADS)

    Oguz, Ipek; Styner, Martin; Sanchez, Mar; Shi, Yundi; Sonka, Milan

    2015-03-01

    Cortical thickness and surface area are important morphological measures with implications for many psychiatric and neurological conditions. Automated segmentation and reconstruction of the cortical surface from 3D MRI scans is challenging due to the variable anatomy of the cortex and its highly complex geometry. While many methods exist for this task in the context of the human brain, these methods are typically not readily applicable to the primate brain. We propose an innovative approach based on our recently proposed human cortical reconstruction algorithm, LOGISMOS-B, and the Laplace-based thickness measurement method. Quantitative evaluation of our approach was performed based on a dataset of T1- and T2-weighted MRI scans from 12-month-old macaques where labeling by our anatomical experts was used as independent standard. In this dataset, LOGISMOS-B has an average signed surface error of 0.01 +/- 0.03mm and an unsigned surface error of 0.42 +/- 0.03mm over the whole brain. Excluding the rather problematic temporal pole region further improves unsigned surface distance to 0.34 +/- 0.03mm. This high level of accuracy reached by our algorithm even in this challenging developmental dataset illustrates its robustness and its potential for primate brain studies.

  10. No need to replace an "anomalous" primate (Primates) with an "anomalous" bear (Carnivora, Ursidae).

    PubMed

    Gutiérrez, Eliécer E; Pine, Ronald H

    2015-01-01

    By means of mitochondrial 12S rRNA sequencing of putative "yeti", "bigfoot", and other "anomalous primate" hair samples, a recent study concluded that two samples, presented as from the Himalayas, do not belong to an "anomalous primate", but to an unknown, anomalous type of ursid. That is, that they match 12S rRNA sequences of a fossil Polar Bear (Ursusmaritimus), but neither of modern Polar Bears, nor of Brown Bears (Ursusarctos), the closest relative of Polar Bears, and one that occurs today in the Himalayas. We have undertaken direct comparison of sequences; replication of the original comparative study; inference of phylogenetic relationships of the two samples with respect to those from all extant species of Ursidae (except for the Giant Panda, Ailuropodamelanoleuca) and two extinct Pleistocene species; and application of a non-tree-based population aggregation approach for species diagnosis and identification. Our results demonstrate that the very short fragment of the 12S rRNA gene sequenced by Sykes et al. is not sufficiently informative to support the hypotheses provided by these authors with respect to the taxonomic identity of the individuals from which these sequences were obtained. We have concluded that there is no reason to believe that the two samples came from anything other than Brown Bears. These analyses afforded an opportunity to test the monophyly of morphologically defined species and to comment on both their phylogenetic relationships and future efforts necessary to advance our understanding of ursid systematics. PMID:25829853

  11. Gut microbiota and allogeneic transplantation.

    PubMed

    Wang, Weilin; Xu, Shaoyan; Ren, Zhigang; Jiang, Jianwen; Zheng, Shusen

    2015-08-23

    The latest high-throughput sequencing technologies show that there are more than 1000 types of microbiota in the human gut. These microbes are not only important to maintain human health, but also closely related to the occurrence and development of various diseases. With the development of transplantation technologies, allogeneic transplantation has become an effective therapy for a variety of end-stage diseases. However, complications after transplantation still restrict its further development. Post-transplantation complications are closely associated with a host's immune system. There is also an interaction between a person's gut microbiota and immune system. Recently, animal and human studies have shown that gut microbial populations and diversity are altered after allogeneic transplantations, such as liver transplantation (LT), small bowel transplantation (SBT), kidney transplantation (KT) and hematopoietic stem cell transplantation (HTCT). Moreover, when complications, such as infection, rejection and graft versus host disease (GVHD) occur, gut microbial populations and diversity present a significant dysbiosis. Several animal and clinical studies have demonstrated that taking probiotics and prebiotics can effectively regulate gut microbiota and reduce the incidence of complications after transplantation. However, the role of intestinal decontamination in allogeneic transplantation is controversial. This paper reviews gut microbial status after transplantation and its relationship with complications. The role of intervention methods, including antibiotics, probiotics and prebiotics, in complications after transplantation are also discussed. Further research in this new field needs to determine the definite relationship between gut microbial dysbiosis and complications after transplantation. Additionally, further research examining gut microbial intervention methods to ameliorate complications after transplantation is warranted. A better understanding of the

  12. Donor selection in heart transplantation

    PubMed Central

    Emani, Sitaramesh; Sai-Sudhakar, Chittoor B.; Higgins, Robert S. D.; Whitson, Bryan A.

    2014-01-01

    There is increased scrutiny on the quality in health care with particular emphasis on institutional heart transplant survival outcomes. An important aspect of successful transplantation is appropriate donor selection. We review the current guidelines as well as areas of controversy in the selection of appropriate hearts as donor organs to ensure optimal outcomes. This decision is paramount to the success of a transplant program as well as recipient survival and graft function post-transplant. PMID:25132976

  13. Neurological complications of transplantation.

    PubMed

    Pustavoitau, Aliaksei; Bhardwaj, Anish; Stevens, Robert

    2011-01-01

    Recipients of solid organ or hematopoietic cell transplants are at risk of life-threatening neurological disorders including encephalopathy, seizures, infections and tumors of the central nervous system, stroke, central pontine myelinolysis, and neuromuscular disorders-often requiring admission to, or occurring in, the intensive care unit (ICU). Many of these complications are linked directly or indirectly to immunosuppressive therapy. However, neurological disorders may also result from graft versus host disease, or be an expression of the underlying disease which prompted transplantation, as well as injury induced during radiation, chemotherapy, surgery, and ICU stay. In rare cases, neuroinfectious pathogens may be transmitted with the transplanted tissue or organ. Diagnosis may be a challenge because clinical symptoms and findings on neuroimaging lack specificity, and a biological specimen or tissue diagnosis is often needed for definitive diagnosis. Management is centered on preventing further neurological injury, etiology-targeted therapy, and balancing the benefits and toxicities of specific immunosuppressive agents. PMID:21764765

  14. Liver transplantation: current concepts.

    PubMed Central

    Wall, W J

    1988-01-01

    In this decade liver transplantation has been established as the preferred treatment for children and adults with irreversible end-stage liver disease. Biliary atresia in children and nonalcoholic cirrhosis in adults are the most common indications for the procedure. Transplantation currently plays only a minor role in the treatment of hepatic malignant disease. Blood group compatibility between donor and recipient is preferred, but histocompatibility matching (tissue typing) currently has no significant role in the selection of recipients. Approximately 70% of recipients survive for 1 year, and these patients have an excellent prospect of long-term survival. The emerging evidence indicates that the quality of life and rehabilitation of most liver recipients are good. The current success of liver transplantation can be attributed to critical selection of recipients, modern anesthetic and surgical techniques, improved perioperative care, accurate diagnosis of rejection and superior immunosuppression with cyclosporine. PMID:3289710

  15. Pediatric liver transplantation

    PubMed Central

    Spada, Marco; Riva, Silvia; Maggiore, Giuseppe; Cintorino, Davide; Gridelli, Bruno

    2009-01-01

    In previous decades, pediatric liver transplantation has become a state-of-the-art operation with excellent success and limited mortality. Graft and patient survival have continued to improve as a result of improvements in medical, surgical and anesthetic management, organ availability, immunosuppression, and identification and treatment of postoperative complications. The utilization of split-liver grafts and living-related donors has provided more organs for pediatric patients. Newer immunosuppression regimens, including induction therapy, have had a significant impact on graft and patient survival. Future developments of pediatric liver transplantation will deal with long-term follow-up, with prevention of immunosuppression-related complications and promotion of as normal growth as possible. This review describes the state-of-the-art in pediatric liver transplantation. PMID:19222089

  16. Establishment and characterization of a canine xenograft model of inflammatory mammary carcinoma.

    PubMed

    Camacho, L; Peña, L; González Gil, A; Cáceres, S; Díez, L; Illera, J C

    2013-12-01

    Canine inflammatory mammary cancer (IMC) and human inflammatory breast cancer (IBC) are the most aggressive form of mammary/breast cancer. Both species naturally develop it, sharing epidemiological, clinical and histological characteristics. Thus, IMC has been suggested as a model to study the human disease. We have developed the first IMC xenograft model in SCID mice. Xenografts reproduced the histological features from the primary tumor, were highly aggressive and showed dermal tumor emboli, distinctive hallmarks of IMC/IBC. This model was hormone receptors positive and HER2 negative. Our findings showed that estrogens and androgens are locally produced in tissues. Factors related to tumor vascularization showed positive expression and xenografts with the highest expression of all analyzed vascular factors had the highest rate of tumor proliferation. The role of steroid hormones and the angio/lymphangiogenic properties found in this model, provide additional knowledge for future interventions in the diagnosis, treatment and prevention of the disease.

  17. Successful implementation of cooperative handling eliminates the need for restraint in a complex nonhuman primate disease model

    PubMed Central

    Graham, Melanie L; Rieke, Eric F; Mutch, Lucas A; Zolondek, Elizabeth K; Faig, Aaron W; DuFour, Theresa A; Munson, James W; Kittredge, Jessica A; Schuurman, Henk-Jan

    2011-01-01

    Introduction Streptozotocin-induced diabetic nonhuman primates are used to study efficacy and safety of innovative immunosuppression after islet transplantation. We implemented a training program for medical management of a chronic disease state. Methods Cooperation with hand feeding and drinking; shifting; and limb presentation were trained utilizing predominately positive but also negative reinforcement in 52 animals compared with 28 macaques subjected to conventional physical and/or chemical restraint. The success of and timing of behavior acquisition was evaluated in a representative subset of 14 animals. Results Over 90% of animals were successful in behavior acquisition. Programmatically this resulted in complete elimination of chair restraint and negligible requirement for sedation. About half of trained animals had no to moderate thymic involution, indicative of a substantial reduction in stress. Conclusion Cooperative handling enhances animal well-being. This contributes to validity of scientific results and eliminates model-induced confounding that can obstruct interpretation of safety and efficacy data. PMID:22150842

  18. THEMES OF LIVER TRANSPLANTATION

    PubMed Central

    Starzl, Thomas E.; Fung, John J.

    2010-01-01

    Liver transplantation was the product of 5 interlocking themes. These began in 1958-59 with canine studies of then theoretical hepatotrophic molecules in portal venous blood (Theme I) and with the contemporaneous parallel development of liver and multivisceral transplant models (Theme II). Further Theme I investigations showed that insulin was the principal, although not the only, portal hepatotrophic factor. In addition to resolving long-standing controversies about the pathophysiology of portacaval shunt, the hepatotrophic studies blazed new trails in the regulation of liver size, function, and regeneration. They also targeted inborn metabolic errors (e.g. familial hyperlipoproteinemia) whose palliation by portal diversion presaged definitive correction with liver replacement. Clinical use of the Theme II transplant models depended on multiple drug immunosuppression (Theme III, Immunology), guided by an empirical algorithm of pattern recognition and therapeutic response. Successful liver replacement was first accomplished in 1967 with azathioprine, prednisone, and ALG. With this regimen, the world’s longest surviving liver recipient is now 40 years postoperative. Incremental improvements in survival outcome occurred (Theme IV) when azathioprine was replaced by cyclosporine (1979) which was replaced in turn by tacrolimus (1989). However, the biologic meaning of alloengraftment remained enigmatic until multilineage donor leukocyte microchimerism was discovered in 1992 in long surviving organ recipients. Seminal mechanisms were then identified (clonal exhaustion-deletion and immune ignorance) that linked organ engraftment and the acquired tolerance of bone marrow transplantation and eventually clarified the relationship of transplantation immunology to the immunology of infections, neoplasms, and autoimmune disorders. With this insight, better strategies of immunosuppression have evolved. As liver and other kinds of organ transplantation became accepted as

  19. Germ cell differentiation in cryopreserved, immature, Indian spotted mouse deer (Moschiola indica) testes xenografted onto mice.

    PubMed

    Pothana, Lavanya; Makala, Himesh; Devi, Lalitha; Varma, Vivek Phani; Goel, Sandeep

    2015-03-01

    Death of immature animals is one of the reasons for the loss of genetic diversity of rare and endangered species. Because sperm cannot be collected from immature males, cryobanking of testicular tissue combined with testis xenografting is a potential option for conservation. The objective of this study was to evaluate the establishment of spermatogenesis in cryopreserved immature testicular tissues from Indian spotted mouse deer (Moschiola indica) after ectopic xenografting onto immunodeficient nude mice. Results showed that testis tissues that were frozen in cryomedia containing either 10% DMSO with 80% fetal bovine serum (D10S80) or 20% DMSO with 20% fetal bovine serum (D20S20) had significantly more (P < 0.01) terminal deoxynucleotidyl transferase-mediated dUTP nick end labeled positive interstitial cells when compared with fresh testis tissues (46.3 ± 3.4 and 51.9 ± 4.0 vs. 22.8 ± 2.0). Xenografted testicular tissues showed degenerated seminiferous tubules 24 weeks after grafting in testes that had been cryopreserved in D20S20; alternatively, pachytene spermatocytes were the most advanced germ cells in testes that were cryopreserved in D10S80. Proliferating cell nuclear antigen staining confirmed the proliferative status of spermatocytes, and the increases in tubular and lumen diameters indicated testicular maturation in xenografts. However, persistent anti-Müllerian hormone staining in Sertoli cells of xenografts revealed incomplete testicular maturation. This study reports that cryopreserved testis tissue that had been xenografted from endangered animals onto mice resulted in the establishment of spermatogenesis with initiation of meiosis. These findings are encouraging for cryobanking of testicular tissues from immature endangered animals to conserve their germplasm. PMID:25467768

  20. Multimodality Imaging Methods for Assessing Retinoblastoma Orthotopic Xenograft Growth and Development

    PubMed Central

    Corson, Timothy W.; Samuels, Brian C.; Wenzel, Andrea A.; Geary, Anna J.; Riley, Amanda A.; McCarthy, Brian P.; Hanenberg, Helmut; Bailey, Barbara J.; Rogers, Pamela I.; Pollok, Karen E.; Rajashekhar, Gangaraju; Territo, Paul R.

    2014-01-01

    Genomic studies of the pediatric ocular tumor retinoblastoma are paving the way for development of targeted therapies. Robust model systems such as orthotopic xenografts are necessary for testing such therapeutics. One system involves bioluminescence imaging of luciferase-expressing human retinoblastoma cells injected into the vitreous of newborn rat eyes. Although used for several drug studies, the spatial and temporal development of tumors in this model has not been documented. Here, we present a new model to allow analysis of average luciferin flux () through the tumor, a more biologically relevant parameter than peak bioluminescence as traditionally measured. Moreover, we monitored the spatial development of xenografts in the living eye. We engineered Y79 retinoblastoma cells to express a lentivirally-delivered enhanced green fluorescent protein-luciferase fusion protein. In intravitreal xenografts, we assayed bioluminescence and computed , as well as documented tumor growth by intraocular optical coherence tomography (OCT), brightfield, and fluorescence imaging. In vivo bioluminescence, ex vivo tumor size, and ex vivo fluorescent signal were all highly correlated in orthotopic xenografts. By OCT, xenografts were dense and highly vascularized, with well-defined edges. Small tumors preferentially sat atop the optic nerve head; this morphology was confirmed on histological examination. In vivo, in xenografts showed a plateau effect as tumors became bounded by the dimensions of the eye. The combination of modeling and in vivo intraocular imaging allows both quantitative and high-resolution, non-invasive spatial analysis of this retinoblastoma model. This technique will be applied to other cell lines and experimental therapeutic trials in the future. PMID:24901248

  1. Multimodality imaging methods for assessing retinoblastoma orthotopic xenograft growth and development.

    PubMed

    Corson, Timothy W; Samuels, Brian C; Wenzel, Andrea A; Geary, Anna J; Riley, Amanda A; McCarthy, Brian P; Hanenberg, Helmut; Bailey, Barbara J; Rogers, Pamela I; Pollok, Karen E; Rajashekhar, Gangaraju; Territo, Paul R

    2014-01-01

    Genomic studies of the pediatric ocular tumor retinoblastoma are paving the way for development of targeted therapies. Robust model systems such as orthotopic xenografts are necessary for testing such therapeutics. One system involves bioluminescence imaging of luciferase-expressing human retinoblastoma cells injected into the vitreous of newborn rat eyes. Although used for several drug studies, the spatial and temporal development of tumors in this model has not been documented. Here, we present a new model to allow analysis of average luciferin flux ([Formula: see text]) through the tumor, a more biologically relevant parameter than peak bioluminescence as traditionally measured. Moreover, we monitored the spatial development of xenografts in the living eye. We engineered Y79 retinoblastoma cells to express a lentivirally-delivered enhanced green fluorescent protein-luciferase fusion protein. In intravitreal xenografts, we assayed bioluminescence and computed [Formula: see text], as well as documented tumor growth by intraocular optical coherence tomography (OCT), brightfield, and fluorescence imaging. In vivo bioluminescence, ex vivo tumor size, and ex vivo fluorescent signal were all highly correlated in orthotopic xenografts. By OCT, xenografts were dense and highly vascularized, with well-defined edges. Small tumors preferentially sat atop the optic nerve head; this morphology was confirmed on histological examination. In vivo, [Formula: see text] in xenografts showed a plateau effect as tumors became bounded by the dimensions of the eye. The combination of [Formula: see text] modeling and in vivo intraocular imaging allows both quantitative and high-resolution, non-invasive spatial analysis of this retinoblastoma model. This technique will be applied to other cell lines and experimental therapeutic trials in the future. PMID:24901248

  2. Immunosuppressive Therapy in Transplantation.

    PubMed

    Allison, Terri L

    2016-03-01

    This article discusses immunosuppressive medications used in organ and hematopoietic stem cell transplantation. Induction, maintenance, and rescue therapy are administered throughout different periods during and after transplantation to modulate the immune system response in the recipient to prevent or treat rejection or graft-versus-host disease. Indications, dosing strategies, required monitoring, complications, adverse events, and concomitant drug interactions associated with immunosuppressive medications are presented. Classes of medications discussed include polyclonal and monoclonal antibodies, calcineurin inhibitors, antiproliferative agents, mammalian target of rapamycin inhibitors, and corticosteroids. Medications having significant interactions with immunosuppression are also examined.

  3. Obesity and liver transplantation

    PubMed Central

    Ayloo, Subhashini; Armstrong, John; Hurton, Scott; Molinari, Michele

    2015-01-01

    The percentage of overweight and obese patients (OPs) waiting for a liver transplant continues to increase. Despite the significant advances occurred in bariatric medicine, obesity is still considered a relative contraindication to liver transplantation (LT). The main aim of this review is to appraise the literature on the outcomes of OPs undergoing LT, treatments that might reduce their weight before, during or after surgery, and discuss some of the controversies and limitations of the current knowledge with the intent of highlighting areas where future research is needed. PMID:26421262

  4. Led by the nose: Olfaction in primate feeding ecology.

    PubMed

    Nevo, Omer; Heymann, Eckhard W

    2015-01-01

    Olfaction, the sense of smell, was a latecomer to the systematic investigation of primate sensory ecology after long years in which it was considered to be of minor importance. This view shifted with the growing understanding of its role in social behavior and the accumulation of physiological studies demonstrating that the olfactory abilities of some primates are on a par with those of olfactory-dependent mammals such as dogs and rodents. Recent years have seen a proliferation of physiological, behavioral, anatomical, and genetic investigations of primate olfaction. These investigations have begun to shed light on the importance of olfaction in the process of food acquisition. However, integration of these works has been limited. It is therefore still difficult to pinpoint large-scale evolutionary scenarios, namely the functions that the sense of smell fulfills in primates' feeding ecology and the ecological niches that favor heavier reliance on olfaction. Here, we review available behavioral and physiological studies of primates in the field or captivity and try to elucidate how and when the sense of smell can help them acquire food. PMID:26267435

  5. Primate Anatomy, Kinematics, and Principles for Humanoid Design

    NASA Technical Reports Server (NTRS)

    Ambrose, Robert O.; Ambrose, Catherine G.

    2004-01-01

    The primate order of animals is investigated for clues in the design of Humanoid Robots. The pursuit is directed with a theory that kinematics, musculature, perception, and cognition can be optimized for specific tasks by varying the proportions of limbs, and in particular, the points of branching in kinematic trees such as the primate skeleton. Called the Bifurcated Chain Hypothesis, the theory is that the branching proportions found in humans may be superior to other animals and primates for the tasks of dexterous manipulation and other human specialties. The primate taxa are defined, contemporary primate evolution hypotheses are critiqued, and variations within the order are noted. The kinematic branching points of the torso, limbs and fingers are studied for differences in proportions across the order, and associated with family and genus capabilities and behaviors. The human configuration of a long waist, long neck, and short arms is graded using a kinematic workspace analysis and a set of design axioms for mobile manipulation robots. It scores well. The re emergence of the human waist, seen in early Prosimians and Monkeys for arboreal balance, but lost in the terrestrial Pongidae, is postulated as benefiting human dexterity. The human combination of an articulated waist and neck will be shown to enable the use of smaller arms, achieving greater regions of workspace dexterity than the larger limbs of Gorillas and other Hominoidea.

  6. Male infanticide leads to social monogamy in primates.

    PubMed

    Opie, Christopher; Atkinson, Quentin D; Dunbar, Robin I M; Shultz, Susanne

    2013-08-13

    Although common in birds, social monogamy, or pair-living, is rare among mammals because internal gestation and lactation in mammals makes it advantageous for males to seek additional mating opportunities. A number of hypotheses have been proposed to explain the evolution of social monogamy among mammals: as a male mate-guarding strategy, because of the benefits of biparental care, or as a defense against infanticidal males. However, comparative analyses have been unable to resolve the root causes of monogamy. Primates are unusual among mammals because monogamy has evolved independently in all of the major clades. Here we combine trait data across 230 primate species with a Bayesian likelihood framework to test for correlated evolution between monogamy and a range of traits to evaluate the competing hypotheses. We find evidence of correlated evolution between social monogamy and both female ranging patterns and biparental care, but the most compelling explanation for the appearance of monogamy is male infanticide. It is only the presence of infanticide that reliably increases the probability of a shift to social monogamy, whereas monogamy allows the secondary adoption of paternal care and is associated with a shift to discrete ranges. The origin of social monogamy in primates is best explained by long lactation periods caused by altriciality, making primate infants particularly vulnerable to infanticidal males. We show that biparental care shortens relative lactation length, thereby reducing infanticide risk and increasing reproductive rates. These phylogenetic analyses support a key role for infanticide in the social evolution of primates, and potentially, humans.

  7. Female reproductive synchrony predicts skewed paternity across primates

    PubMed Central

    Nunn, Charles L.; Schülke, Oliver

    2008-01-01

    Recent studies have uncovered remarkable variation in paternity within primate groups. To date, however, we lack a general understanding of the factors that drive variation in paternity skew among primate groups and across species. Our study focused on hypotheses from reproductive skew theory involving limited control and the use of paternity “concessions” by investigating how paternity covaries with the number of males, female estrous synchrony, and rates of extragroup paternity. In multivariate and phylogenetically controlled analyses of data from 27 studies on 19 species, we found strong support for a limited control skew model, with reproductive skew within groups declining as female reproductive synchrony and the number of males per group increase. Of these 2 variables, female reproductive synchrony explained more of the variation in paternity distributions. To test whether dominant males provide incentives to subordinates to resist matings by extragroup males, that is, whether dominants make concessions of paternity, we derived a novel prediction that skew is lower within groups when threat from outside the group exists. This prediction was not supported as a primary factor underlying patterns of reproductive skew among primate species. However, our approach revealed that if concessions occur in primates, they are most likely when female synchrony is low, as these conditions provide alpha male control of paternity that is assumed by concessions models. Collectively, our analyses demonstrate that aspects of male reproductive competition are the primary drivers of reproductive skew in primates. PMID:19018288

  8. Reproductive aging patterns in primates reveal that humans are distinct

    PubMed Central

    Alberts, Susan C.; Altmann, Jeanne; Brockman, Diane K.; Cords, Marina; Fedigan, Linda M.; Pusey, Anne; Stoinski, Tara S.; Strier, Karen B.; Morris, William F.; Bronikowski, Anne M.

    2013-01-01

    Women rarely give birth after ∼45 y of age, and they experience the cessation of reproductive cycles, menopause, at ∼50 y of age after a fertility decline lasting almost two decades. Such reproductive senescence in mid-lifespan is an evolutionary puzzle of enduring interest because it should be inherently disadvantageous. Furthermore, comparative data on reproductive senescence from other primates, or indeed other mammals, remains relatively rare. Here we carried out a unique detailed comparative study of reproductive senescence in seven species of nonhuman primates in natural populations, using long-term, individual-based data, and compared them to a population of humans experiencing natural fertility and mortality. In four of seven primate species we found that reproductive senescence occurred before death only in a small minority of individuals. In three primate species we found evidence of reproductive senescence that accelerated throughout adulthood; however, its initial rate was much lower than mortality, so that relatively few individuals experienced reproductive senescence before death. In contrast, the human population showed the predicted and well-known pattern in which reproductive senescence occurred before death for many women and its rate accelerated throughout adulthood. These results provide strong support for the hypothesis that reproductive senescence in midlife, although apparent in natural-fertility, natural-mortality populations of humans, is generally absent in other primates living in such populations. PMID:23898189

  9. Male infanticide leads to social monogamy in primates

    PubMed Central

    Opie, Christopher; Atkinson, Quentin D.; Dunbar, Robin I. M.; Shultz, Susanne

    2013-01-01

    Although common in birds, social monogamy, or pair-living, is rare among mammals because internal gestation and lactation in mammals makes it advantageous for males to seek additional mating opportunities. A number of hypotheses have been proposed to explain the evolution of social monogamy among mammals: as a male mate-guarding strategy, because of the benefits of biparental care, or as a defense against infanticidal males. However, comparative analyses have been unable to resolve the root causes of monogamy. Primates are unusual among mammals because monogamy has evolved independently in all of the major clades. Here we combine trait data across 230 primate species with a Bayesian likelihood framework to test for correlated evolution between monogamy and a range of traits to evaluate the competing hypotheses. We find evidence of correlated evolution between social monogamy and both female ranging patterns and biparental care, but the most compelling explanation for the appearance of monogamy is male infanticide. It is only the presence of infanticide that reliably increases the probability of a shift to social monogamy, whereas monogamy allows the secondary adoption of paternal care and is associated with a shift to discrete ranges. The origin of social monogamy in primates is best explained by long lactation periods caused by altriciality, making primate infants particularly vulnerable to infanticidal males. We show that biparental care shortens relative lactation length, thereby reducing infanticide risk and increasing reproductive rates. These phylogenetic analyses support a key role for infanticide in the social evolution of primates, and potentially, humans. PMID:23898180

  10. Grooming reciprocation among female primates: a meta-analysis.

    PubMed

    Schino, Gabriele; Aureli, Filippo

    2008-02-23

    The theory of reciprocal altruism offers an explanation for the evolution of altruistic behaviours among unrelated animals. Among primates, grooming is one of the most common altruistic behaviours. Primates have been suggested to exchange grooming both for itself and for rank-related benefits. While previous meta-analyses have shown that they direct their grooming up the hierarchy and exchange it for agonistic support, no comprehensive evaluation of grooming reciprocation has been made. Here we report on a meta-analysis of grooming reciprocation among female primates based on 48 social groups belonging to 22 different species and 12 genera. The results of this meta-analysis showed that female primates groom preferentially those group mates that groom them most. To the extent allowed by the availability of kinship data, this result holds true when controlling for maternal kinship. These results, together with previous findings, suggest that primates are indeed able to exchange grooming both for itself and for different rank-related benefits.

  11. Led by the nose: Olfaction in primate feeding ecology.

    PubMed

    Nevo, Omer; Heymann, Eckhard W

    2015-01-01

    Olfaction, the sense of smell, was a latecomer to the systematic investigation of primate sensory ecology after long years in which it was considered to be of minor importance. This view shifted with the growing understanding of its role in social behavior and the accumulation of physiological studies demonstrating that the olfactory abilities of some primates are on a par with those of olfactory-dependent mammals such as dogs and rodents. Recent years have seen a proliferation of physiological, behavioral, anatomical, and genetic investigations of primate olfaction. These investigations have begun to shed light on the importance of olfaction in the process of food acquisition. However, integration of these works has been limited. It is therefore still difficult to pinpoint large-scale evolutionary scenarios, namely the functions that the sense of smell fulfills in primates' feeding ecology and the ecological niches that favor heavier reliance on olfaction. Here, we review available behavioral and physiological studies of primates in the field or captivity and try to elucidate how and when the sense of smell can help them acquire food.

  12. Microgravity Flight - Accommodating Non-Human Primates

    NASA Technical Reports Server (NTRS)

    Dalton, Bonnie P.; Searby, Nancy; Ostrach, Louis

    1994-01-01

    Spacelab Life Sciences-3 (SLS-3) was scheduled to be the first United States man-tended microgravity flight containing Rhesus monkeys. The goal of this flight as in the five untended Russian COSMOS Bion flights and an earlier American Biosatellite flight, was to understand the biomedical and biological effects of a microgravity environment using the non-human primate as human surrogate. The SLS-3/Rhesus Project and COSMOS Primate-BIOS flights all utilized the rhesus monkey Macaca mulatta. The ultimate objective of all flights with an animal surrogate has been to evaluate and understand biological mechanisms at both the system and cellular level, thus enabling rational effective countermeasures for future long duration human activity under microgravity conditions and enabling technical application to correction of common human physiological problems within earth's gravity, e.g., muscle strength and reloading, osteoporosis, immune deficiency diseases. Hardware developed for the SLS-3/Rhesus Project was the result of a joint effort with the French Centre National d'Etudes Spatiales (CNES) and the United States National Aeronautics and Space Administration (NASA) extending over the last decade. The flight hardware design and development required implementation of sufficient automation to insure flight crew and animal bio-isolation and maintenance with minimal impact to crew activities. A variety of hardware of varying functional capabilities was developed to support the scientific objectives of the original 22 combined French and American experiments, along with 5 Russian co-investigations, including musculoskeletal, metabolic, and behavioral studies. Unique elements of the Rhesus Research Facility (RRF) included separation of waste for daily delivery of urine and fecal samples for metabolic studies and a psychomotor test system for behavioral studies along with monitored food measurement. As in untended flights, telemetry measurements would allow monitoring of

  13. Microgravity Flight: Accommodating Non-Human Primates

    NASA Technical Reports Server (NTRS)

    Dalton, Bonnie P.; Searby, Nancy; Ostrach, Louis

    1995-01-01

    Spacelab Life Sciences-3 (SLS-3) was scheduled to be the first United States man-tended microgravity flight containing Rhesus monkeys. The goal of this flight as in the five untended Russian COSMOS Bion flights and an earlier American Biosatellite flight, was to understand the biomedical and biological effects of a microgravity environment using the non-human primate as human surrogate. The SLS-3/Rhesus Project and COSMOS Primate-BIOS flights all utilized the rhesus monkey, Macaca mulatta. The ultimate objective of all flights with an animal surrogate has been to evaluate and understand biological mechanisms at both the system and cellular level, thus enabling rational effective countermeasures for future long duration human activity under microgravity conditions and enabling technical application to correction of common human physiological problems within earth's gravity, e.g., muscle strength and reloading, osteoporosis, immune deficiency diseases. Hardware developed for the SLS-3/Rhesus Project was the result of a joint effort with the French Centre National d'Etudes Spatiales (CNES) and the United States National Aeronautics and Space Administration (NASA) extending over the last decade. The flight hardware design and development required implementation of sufficient automation to insure flight crew and animal bio-isolation and maintenance with minimal impact to crew activities. A variety of hardware of varying functional capabilities was developed to support the scientific objectives of the original 22 combined French and American experiments, along with 5 Russian co-investigations, including musculoskeletal, metabolic, and behavioral studies. Unique elements of the Rhesus Research Facility (RRF) included separation of waste for daily delivery of urine and fecal samples for metabolic studies and a psychomotor test system for behavioral studies along with monitored food measurement. As in untended flights, telemetry measurements would allow monitoring of

  14. Evolution of coding microsatellites in primate genomes.

    PubMed

    Loire, Etienne; Higuet, Dominique; Netter, Pierre; Achaz, Guillaume

    2013-01-01

    Microsatellites (SSRs) are highly susceptible to expansions and contractions. When located in a coding sequence, the insertion or the deletion of a single unit for a mono-, di-, tetra-, or penta(nucleotide)-SSR creates a frameshift. As a consequence, one would expect to find only very few of these SSRs in coding sequences because of their strong deleterious potential. Unexpectedly, genomes contain many coding SSRs of all types. Here, we report on a study of their evolution in a phylogenetic context using the genomes of four primates: human, chimpanzee, orangutan, and macaque. In a set of 5,015 orthologous genes unambiguously aligned among the four species, we show that, except for tri- and hexa-SSRs, for which insertions and deletions are frequently observed, SSRs in coding regions evolve mainly by substitutions. We show that the rate of substitution in all types of coding SSRs is typically two times higher than in the rest of coding sequences. Additionally, we observe that although numerous coding SSRs are created and lost by substitutions in the lineages, their numbers remain constant. This last observation suggests that the coding SSRs have reached equilibrium. We hypothesize that this equilibrium involves a combination of mutation, drift, and selection. We thus estimated the fitness cost of mono-SSRs and show that it increases with the number of units. We finally show that the cost of coding mono-SSRs greatly varies from function to function, suggesting that the strength of the selection that acts against them can be correlated to gene functions.

  15. Anti-tumor effect of bevacizumab on a xenograft model of feline mammary carcinoma

    PubMed Central

    MICHISHITA, Masaki; OHTSUKA, Aya; NAKAHIRA, Rei; TAJIMA, Tsuyoshi; NAKAGAWA, Takayuki; SASAKI, Nobuo; ARAI, Toshiro; TAKAHASHI, Kimimasa

    2015-01-01

    Feline mammary carcinomas are characterized by rapid progression and metastases. Vascular endothelial growth factor (VEGF) is a key regulator of tumor angiogenesis, proliferation and metastasis. The present study aimed to investigate the effects of a single drug therapy of bevacizumab on a xenograft model of feline mammary carcinoma expressing VEGF protein. Bevacizumab treatment suppressed tumor growth by inhibiting angiogenesis and enhancing apoptosis; however, it did not affect the tumor proliferation index. Thus, bevacizumab had anti-tumor effects on a xenograft model, and this may be useful for the treatment of feline mammary carcinoma. PMID:26616000

  16. Vascular permeability in a human tumour xenograft: molecular charge dependence

    PubMed Central

    Dellian, M; Yuan, F; Trubetskoy, V S; Torchilin, V P; Jain, R K

    2000-01-01

    Molecular charge is one of the main determinants of transvascular transport. There are, however, no data available on the effect of molecular charge on microvascular permeability of macromolecules in solid tumours. To this end, we measured tumour microvascular permeability to different proteins having similar size but different charge. Measurements were performed in the human colon adenocarcinoma LS174T transplanted in transparent dorsal skinfold chambers in severe combined immunodeficient (SCID) mice. Bovine serum albumin (BSA) and IgG were fluorescently labelled and were either cationized by conjugation with hexamethylenediamine or anionized by succinylation. The molecules were injected i.v. and the fluorescence in tumour tissue was quantified by intravital fluorescence microscopy. The fluorescence intensity and pharmacokinetic data were used to calculate the microvascular permeability. We found that tumour vascular permeability of cationized BSA (pI-range: 8.6–9.1) and IgG (pI: 8.6–9.3) was more than two-fold higher (4.25 and 4.65 × 10−7cm s−1) than that of the anionized BSA (pI ≈ 2.0) and IgG (pI: 3.0–3.9; 1.11 and 1.93 × 10−7cm s−1, respectively). Our results indicate that positively charged molecules extravasate faster in solid tumours compared to the similar-sized compounds with neutral or negative charges. However, the plasma clearance of cationic molecules was ∼2 × faster than that of anionic ones, indicating that the modification of proteins enhances drug delivery to normal organs as well. Therefore, caution should be exercised when such a strategy is used to improve drug and gene delivery to solid tumours. © 2000 Cancer Research Campaign PMID:10789717

  17. Vascular permeability in a human tumour xenograft: molecular charge dependence.

    PubMed

    Dellian, M; Yuan, F; Trubetskoy, V S; Torchilin, V P; Jain, R K

    2000-05-01

    Molecular charge is one of the main determinants of transvascular transport. There are, however, no data available on the effect of molecular charge on microvascular permeability of macromolecules in solid tumours. To this end, we measured tumour microvascular permeability to different proteins having similar size but different charge. Measurements were performed in the human colon adenocarcinoma LS174T transplanted in transparent dorsal skinfold chambers in severe combined immunodeficient (SCID) mice. Bovine serum albumin (BSA) and IgG were fluorescently labelled and were either cationized by conjugation with hexamethylenediamine or anionized by succinylation. The molecules were injected i.v. and the fluorescence in tumour tissue was quantified by intravital fluorescence microscopy. The fluorescence intensity and pharmacokinetic data were used to calculate the microvascular permeability. We found that tumour vascular permeability of cationized BSA (pI-range: 8.6-9.1) and IgG (pI: 8.6-9.3) was more than two-fold higher (4.25 and 4.65x10(-7) cm s(-1)) than that of the anionized BSA (pI approximately 2.0) and IgG (pI: 3.0-3.9; 1.11 and 1.93x10(-7) cm s(-1), respectively). Our results indicate that positively charged molecules extravasate faster in solid tumours compared to the similar-sized compounds with neutral or negative charges. However, the plasma clearance of cationic molecules was approximately 2x faster than that of anionic ones, indicating that the modification of proteins enhances drug delivery to normal organs as well. Therefore, caution should be exercised when such a strategy is used to improve drug and gene delivery to solid tumours.

  18. In Silico cancer cell versus stroma cellularity index computed from species-specific human and mouse transcriptome of xenograft models: towards accurate stroma targeting therapy assessment

    PubMed Central

    2014-01-01

    Background The current state of the art for measuring stromal response to targeted therapy requires burdensome and rate limiting quantitative histology. Transcriptome measures are increasingly affordable and provide an opportunity for developing a stromal versus cancer ratio in xenograft models. In these models, human cancer cells are transplanted into mouse host tissues (stroma) and together coevolve into a tumour microenvironment. However, profiling the mouse or human component separately remains problematic. Indeed, laser capture microdissection is labour intensive. Moreover, gene expression using commercial microarrays introduces significant and underreported cross-species hybridization errors that are commonly overlooked by biologists. Method We developed a customized dual-species array, H&M array, and performed cross-species and species-specific hybridization measurements. We validated a new methodology for establishing the stroma vs cancer ratio using transcriptomic data. Results In the biological validation of the H&M array, cross-species hybridization of human and mouse probes was significantly reduced (4.5 and 9.4 fold reduction, respectively; p < 2x10-16 for both, Mann-Whitney test). We confirmed the capability of the H&M array to determine the stromal to cancer cells ratio based on the estimation of cellularity index of mouse/human mRNA content in vitro. This new metrics enable to investigate more efficiently the stroma-cancer cell interactions (e.g. cellularity) bypassing labour intensive requirement and biases of laser capture microdissection. Conclusion These results provide the initial evidence of improved and cost-efficient analytics for the investigation of cancer cell microenvironment, using species-specificity arrays specifically designed for xenografts models. PMID:25079962

  19. Changing Role of Heart Transplantation.

    PubMed

    Kittleson, Michelle M

    2016-07-01

    Heart transplantation has become standard of care for end-stage heart failure. Challenges include the limited supply of donor organs and the increased complexity of heart transplant candidates who are at higher risk for poor outcomes. Recent advances may address these challenges, including proposed changes in heart transplant allocation policy, a better understanding of the definition and management of primary graft dysfunction, and advances in the management of sensitized heart transplant candidates. Developments in these areas may result in more equitable distribution and expansion of the donor pool and improved quality of life and survival for heart transplant recipients. PMID:27371517

  20. [Running through the liver transplantation].

    PubMed

    Grecu, F

    2003-01-01

    An overview of the organization, timing and developing of the liver transplantation is difficult to be made in terms of multiple sequences and a great variety of activities during the developing of such activity. A well-trained transplant team must carry out the potential donor, the liver grafts manipulation and the graft receptor, in the condition of a competitive medical system. A summary presentation, showing the essentials of the proceedings in liver transplantation could be assimilated as a guide of multidisciplinary sequences that leads to the completion of the liver grafting. The common feature of all that means the liver transplantation and generally in organ transplantation is the performance and exactingness.

  1. Tarsier-like locomotor specializations in the Oligocene primate Afrotarsius

    PubMed Central

    Rasmussen, D. Tab; Conroy, Glenn C.; Simons, Elwyn L.

    1998-01-01

    Tarsiers and extinct tarsier-like primates have played a central role in views of primate phylogeny and evolution for more than a century. Because of the importance of tarsiers in so many primatological problems, there has been particular interest in questions about the origin of tarsier specializations and the biogeography of early tarsioid radiations. We report on a new fossil of rare Afrotarsius that shows near identity to modern Tarsius in unique specializations of the leg, which provides information about the locomotor behavior and clarifies the phylogenetic position of this previously controversial primate. These specializations constitute evidence that Afrotarsius is a tarsiid, closely related to extant Tarsius; hence, it is now excluded from being a generalized sister taxon to Anthropoidea. PMID:9843978

  2. Convergence of complex cognitive abilities in cetaceans and primates.

    PubMed

    Marino, Lori

    2002-01-01

    What examples of convergence in higher-level complex cognitive characteristics exist in the animal kingdom? In this paper I will provide evidence that convergent intelligence has occurred in two distantly related mammalian taxa. One of these is the order Cetacea (dolphins, whales and porpoises) and the other is our own order Primates, and in particular the suborder anthropoid primates (monkeys, apes, and humans). Despite a deep evolutionary divergence, adaptation to physically dissimilar environments, and very different neuroanatomical organization, some primates and cetaceans show striking convergence in social behavior, artificial 'language' comprehension, and self-recognition ability. Taken together, these findings have important implications for understanding the generality and specificity of those processes that underlie cognition in different species and the nature of the evolution of intelligence.

  3. Primate evolution of the recombination regulator PRDM9.

    PubMed

    Schwartz, Jerrod J; Roach, David J; Thomas, James H; Shendure, Jay

    2014-07-08

    The PRDM9 gene encodes a protein with a highly variable tandem-repeat zinc finger (ZF) DNA-binding domain that plays a key role in determining sequence-specific hotspots of meiotic recombination genome wide. Here we survey the diversity of the PRDM9 ZF domain by sequencing this region in 64 primates from 18 species, revealing 68 unique alleles across all groups. We report ubiquitous positive selection at nucleotide positions corresponding to DNA contact residues and the expansion of ZFs within clades, which confirms the rapid evolution of the ZF domain throughout the primate lineage. Alignment of Neandertal and Denisovan sequences suggests that PRDM9 in archaic hominins was closely related to present-day human alleles that are rare and specific to African populations. In the context of its role in reproduction, our results are consistent with variation in PRDM9 contributing to speciation events in primates.

  4. Primate-specific evolution of an LDLR enhancer

    SciTech Connect

    Wang, Qian-Fei; Prabhakar, Shyam; Wang, Qianben; Moses, Alan M.; Chanan, Sumita; Brown, Myles; Eisen, Michael B.; Cheng, Jan-Fang; Rubin,Edward M.; Boffelli, Dario

    2005-12-01

    Sequence changes in regulatory regions have often been invoked to explain phenotypic divergence among species, but molecular examples of this have been difficult to obtain. In this study we identified an anthropoid primate-specific sequence element that contributed to the regulatory evolution of the low-density lipoprotein receptor. Using a combination of close and distant species genomic sequence comparisons coupled with in vivo and in vitro studies, we found that a functional cholesterol-sensing sequence motif arose and was fixed within a pre-existing enhancer in the common ancestor of anthropoid primates. Our study demonstrates one molecular mechanism by which ancestral mammalian regulatory elements can evolve to perform new functions in the primate lineage leading to human.

  5. Xenografting of testis tissue from bison calf donors into recipient mice as a strategy for salvaging genetic material.

    PubMed

    Abbasi, Sepideh; Honaramooz, Ali

    2011-09-01

    The objective was to evaluate the long-term outcome of testis tissue xenografting from neonatal bison calves as a model for closely related rare or endangered ungulates. Testis tissue was collected postmortem from two newborn bison calves (Bison bison bison) and small fragments of the tissue were grafted under the back skin of immunodeficient recipient mice (n = 15 mice; eight fragments/mouse). Single xenograft samples were removed from representative recipient mice every 2 mo after grafting (for up to 16 mo). The retrieved xenografts were evaluated for seminiferous tubular density, tubular diameter, seminiferous tubular morphology, and identification of the most advanced germ cell type. Overall, 69% of the grafted testis fragments were recovered as xenografts. Xenografts weight increased (P < 0.02) approximately four-fold by 2 mo and 10-fold by 16 mo post-grafting. In testis xenografts, gradual maturational changes were evident, manifested as the first detection of the following at the times specified: seminiferous tubule expansion, 2 mo; spermatocytes, 6 mo; round spermatids, 12 mo; and elongated spermatids, 16 mo. Furthermore, there were differences between the two donor calves regarding the efficiency of spermatogenesis in xenografts. The timing of complete spermatogenesis approximately corresponded to the reported timing of sexual maturation in bison. This study demonstrated, apparently for the first time, that testis tissue xenografting from neonatal bison donors into recipient mice resulted in testicular maturation and complete development of spermatogenesis in the grafts.

  6. Lung Transplantation for Cystic Fibrosis

    PubMed Central

    Adler, Frederick R.; Aurora, Paul; Barker, David H.; Barr, Mark L.; Blackwell, Laura S.; Bosma, Otto H.; Brown, Samuel; Cox, D. R.; Jensen, Judy L.; Kurland, Geoffrey; Nossent, George D.; Quittner, Alexandra L.; Robinson, Walter M.; Romero, Sandy L.; Spencer, Helen; Sweet, Stuart C.; van der Bij, Wim; Vermeulen, J.; Verschuuren, Erik A. M.; Vrijlandt, Elianne J. L. E.; Walsh, William; Woo, Marlyn S.; Liou, Theodore G.

    2009-01-01

    Lung transplantation is a complex, high-risk, potentially life-saving therapy for the end-stage lung disease of cystic fibrosis (CF). The decision to pursue transplantation involves comparing the likelihood of survival with and without transplantation as well as assessing the effect of wait-listing and transplantation on the patient's quality of life. Although recent population-based analyses of the US lung allocation system for the CF population have raised controversies about the survival benefits of transplantation, studies from the United Kingdom and Canada have suggested a definite survival advantage for those receiving transplants. In response to these and other controversies, leaders in transplantation and CF met together in Lansdowne, Virginia, to consider the state of the art in lung transplantation for CF in an international context, focusing on advances in surgical technique, measurement of outcomes, use of prognostic criteria, variations in local control over listing, and prioritization among the United States, Canada, the United Kingdom, and The Netherlands, patient adherence before and after transplantation and other issues in the broader context of lung transplantation. Finally, the conference members carefully considered how efforts to improve outcomes for lung transplantation for CF lung disease might best be studied. This Roundtable seeks to communicate the substance of our discussions. PMID:20008865

  7. Facial transplantation: A concise update

    PubMed Central

    Barrera-Pulido, Fernando; Gomez-Cia, Tomas; Sicilia-Castro, Domingo; Garcia-Perla-Garcia, Alberto; Gacto-Sanchez, Purificacion; Hernandez-Guisado, Jose-Maria; Lagares-Borrego, Araceli; Narros-Gimenez, Rocio; Gonzalez-Padilla, Juan D.

    2013-01-01

    Objectives: Update on clinical results obtained by the first worldwide facial transplantation teams as well as review of the literature concerning the main surgical, immunological, ethical, and follow-up aspects described on facial transplanted patients. Study design: MEDLINE search of articles published on “face transplantation” until March 2012. Results: Eighteen clinical cases were studied. The mean patient age was 37.5 years, with a higher prevalence of men. Main surgical indication was gunshot injuries (6 patients). All patients had previously undergone multiple conventional surgical reconstructive procedures which had failed. Altogether 8 transplant teams belonging to 4 countries participated. Thirteen partial face transplantations and 5 full face transplantations have been performed. Allografts are varied according to face anatomical components and the amount of skin, muscle, bone, and other tissues included, though all were grafted successfully and remained viable without significant postoperative surgical complications. The patient with the longest follow-up was 5 years. Two patients died 2 and 27 months after transplantation. Conclusions: Clinical experience has demonstrated the feasibility of facial transplantation as a valuable reconstructive option, but it still remains considered as an experimental procedure with unresolved issues to settle down. Results show that from a clinical, technical, and immunological standpoint, facial transplantation has achieved functional, aesthetic, and social rehabilitation in severely facial disfigured patients. Key words:Face transplantation, composite tissue transplantation, face allograft, facial reconstruction, outcomes and complications of face transplantation. PMID:23229268

  8. Imaging in liver transplantation

    PubMed Central

    Caruso, Settimo; Miraglia, Roberto; Maruzzelli, Luigi; Gruttadauria, Salvatore; Luca, Angelo; Gridelli, Bruno

    2009-01-01

    The aim of this study was to illustrate the role of non-invasive imaging tools such as ultrasonography, multi-detector row computed tomography, and magnetic resonance imaging in the evaluation of pediatric and adult liver recipients and potential liver donors, and in the detection of potential complications arising from liver transplantation. PMID:19222090

  9. Organ Harvesting and Transplants

    ERIC Educational Resources Information Center

    Baskette, Kimberly G.; Ritz, John M.

    2010-01-01

    Humans and animals need healthy organs to live. Due to medical conditions and accidents, some organs fail to function properly. For these reasons, the medical community has experimented and can now perform successful organ transplants, allowing patients to continue to live their lives. Many countries have medical programs where individuals can…

  10. [Glaucoma and corneal transplantation].

    PubMed

    Geerling, G; Müller, M; Zierhut, M; Klink, T

    2010-05-01

    Glaucoma and corneal disorders are often associated and are of diagnostic, therapeutic and prognostic relevance for each other. Glaucoma is already present in approximately 15% of eyes prior to keratoplasty, whereas in addition approximately 15% of cases are diagnosed following corneal transplantation. Corneal opacities, surface irregularities and pachymetric deviations from the norm can have a negative impact on tonometry, perimetry and morphological glaucoma diagnosis. Digital and intracameral tonometry as well as flash VEP to determine the visual potential can be helpful in this setting. Increased intraocular pressure (IOP), long-term application of antiglaucomatous medication or the use of antimetabolites in glaucoma surgery can all induce keratopathy. Therefore, intraocular pressure should be regulated prior to corneal transplantation. Risk factors for the evolution of glaucoma following corneal transplantation are the specific indication and surgical technique (e. g. combined corneal and cataract/vitreoretinal surgery), as well as postoperative steroid application and chamber angle synechiae. Unpreserved glaucoma medication without pro-inflammatory effects should be preferred following keratoplasty. In the long term surgery to control IOP is required in approximately 25% of eyes. The wider use of lamellar techniques for corneal transplantation is likely to reduce the incidence of secondary glaucoma.

  11. After the Transplant

    MedlinePlus

    ... you from post-surgical pain for a short time. Follow your team's pain management instructions to make the overall experience as comfortable as possible. Transplant is major surgery. It may take time to get back to eating normally, moving around, ...

  12. Hair transplantation update.

    PubMed

    Rogers, Nicole E

    2015-06-01

    Contemporary hair transplant surgery offers results that are natural and undetectable. It is an excellent treatment option for male and female pattern hair loss. Patients are encouraged to also use medical therapy to help protect their surgical results and prevent ongoing thinning of the surrounding hairs. The two major techniques of donor elliptical harvesting and follicular unit extraction are discussed here. PMID:26176286

  13. Ovary and uterus transplantation.

    PubMed

    Gosden, Roger G

    2008-12-01

    Ovarian and uterine transplantation are procedures gaining more attention again because of potential applications in respectively fertility preservation for cancer and other patients and, more tentatively, women with uterine agenesis or hysterectomy. Cryopreservation of tissue slices, and possibly whole organs, is providing opportunities for banking ovaries for indefinite periods before transplanting them back to restore fertility. The natural plasticity of this organ facilitates grafting to different sites where they can be revascularized and rapidly restore the normal physiology of secretion and ovulation. Ischemic damage is a chief limitation because many follicles are lost, at least in avascular grafts, and functional longevity is reduced. Nevertheless, grafts of young ovarian tissue, even after cryopreservation, can be highly fertile in laboratory rodents and, in humans, autografts have functioned for up to 3 years before needing replacement. Transplantation by vascular anastomosis provides potentially longer function but it is technically much more demanding and riskier for the recipient. It is the only practicable method with the uterus, and has enabled successful pregnancies in several species, but not yet in humans. Contrary to claims made many years ago, neither organ is privileged immunologically, and allografts become rapidly rejected except in hosts whose immune system is deficient or suppressed pharmacologically. All in all, transplantation of these organs, especially the ovary, provides a broad platform of opportunities for research and new applications in reproductive medicine and conservation biology.

  14. Cancer in the Transplant Recipient

    PubMed Central

    Chapman, Jeremy R.; Webster, Angela C.; Wong, Germaine

    2013-01-01

    Malignancy has become one of the three major causes of death after transplantation in the past decade and is thus increasingly important in all organ transplant programs. Death from cardiovascular disease and infection are both decreasing in frequency from a combination of screening, prophylaxis, aggressive risk factor management, and interventional therapies. Cancer, on the other hand, is poorly and expensively screened for; risk factors are mostly elusive and/or hard to impact on except for the use of immunosuppression itself; and finally therapeutic approaches to the transplant recipient with cancer are often nihilistic. This article provides a review of each of the issues as they come to affect transplantation: cancer before wait-listing, cancer transmission from the donor, cancer after transplantation, outcomes of transplant recipients after a diagnosis of cancer, and the role of screening and therapy in reducing the impact of cancer in transplant recipients. PMID:23818517

  15. Hypercoagulability in Kidney Transplant Recipients.

    PubMed

    Parajuli, Sandesh; Lockridge, Joseph B; Langewisch, Eric D; Norman, Douglas J; Kujovich, Jody L

    2016-04-01

    Thrombosis remains an important complication after kidney transplantation. Outcomes for graft and deep vein thrombosis are not favorable. The majority of early kidney transplant failure in adults is due to allograft thrombosis. Risk stratification, early diagnosis, and appropriate intervention are critical to the management of thrombotic complications of transplant. In patients with end-stage renal disease, the prevalence of acquired risk factors for thrombosis is significantly high. Because of hereditary and acquired risk factors, renal transplant recipients manifest features of a chronic prothrombotic state. Identification of hereditary thrombotic risk factors before transplantation may be a useful tool for selecting appropriate candidates for thrombosis prophylaxis immediately after transplantation. Short-term anticoagulation may be appropriate for all patients after kidney transplantation.

  16. Transplant tourism: a growing phenomenon.

    PubMed

    Cohen, David J

    2009-03-01

    Medical tourism is increasing owing to high costs of care, lack of availability or long waits for procedures, and improvements in technology and standards of care in many countries. Transplant tourism is one example of medical tourism that has been attracting increasing attention because of concerns over poor treatment and outcomes of both donors and recipients. Most such cases involve vended kidneys obtained from vulnerable populations, and both donors and recipients receive inferior care by US standards. This commentary discusses a paper by Gill et al. that compared outcomes of 33 transplant tourists with those of patients transplanted at a US center. Fewer complications and better outcomes were seen in patients transplanted in the US center than among transplant tourists. Large transplant centers with long waiting times are increasingly likely to see patients return newly transplanted from overseas; such patients require urgent attention, with particular consideration to infectious complications.

  17. Will Regenerative Medicine Replace Transplantation?

    PubMed Central

    Orlando, Giuseppe; Soker, Shay; Stratta, Robert J.; Atala, Anthony

    2013-01-01

    Recent groundbreaking advances in organ bioengineering and regeneration have provided evidence that regenerative medicine holds promise to dramatically improve the approach to organ transplantation. The two fields, however, share a common heritage. Alexis Carrel can be considered the father of both regenerative medicine and organ transplantation, and it is now clear that his legacy is equally applicable for the present and future generations of transplant and regenerative medicine investigators. In this review, we will briefly illustrate the interplay that should be established between these two complementary disciplines of health sciences. Although regenerative medicine has shown to the transplant field its potential, transplantation is destined to align with regenerative medicine and foster further progress probably more than either discipline alone. Organ bioengineering and regeneration technologies hold the promise to meet at the same time the two most urgent needs in organ transplantation, namely, the identification of a new, potentially inexhaustible source of organs and immunosuppression-free transplantation of tissues and organs. PMID:23906883

  18. Will regenerative medicine replace transplantation?

    PubMed

    Orlando, Giuseppe; Soker, Shay; Stratta, Robert J; Atala, Anthony

    2013-08-01

    Recent groundbreaking advances in organ bioengineering and regeneration have provided evidence that regenerative medicine holds promise to dramatically improve the approach to organ transplantation. The two fields, however, share a common heritage. Alexis Carrel can be considered the father of both regenerative medicine and organ transplantation, and it is now clear that his legacy is equally applicable for the present and future generations of transplant and regenerative medicine investigators. In this review, we will briefly illustrate the interplay that should be established between these two complementary disciplines of health sciences. Although regenerative medicine has shown to the transplant field its potential, transplantation is destined to align with regenerative medicine and foster further progress probably more than either discipline alone. Organ bioengineering and regeneration technologies hold the promise to meet at the same time the two most urgent needs in organ transplantation, namely, the identification of a new, potentially inexhaustible source of organs and immunosuppression-free transplantation of tissues and organs.

  19. Kidney Transplantation in the Elderly

    PubMed Central

    Huang, Edmund; Segev, Dorry L.; Rabb, Hamid

    2010-01-01

    Summary There is an increase in the older incident end-stage renal disease population that is associated with an increasing prevalence of end-stage renal disease in the United States. This trend is paralleled by an increasing rate of kidney transplantation in the elderly. Although patient survival is lower in older versus younger kidney recipients, the elderly benefit from a reduction in mortality rate and improved quality of life with transplantation compared with dialysis. Immunologic, physiologic, and psychosocial factors influence transplant outcomes and should be recognized in the care of the elderly transplant patient. In this review, we discuss transplantation in the elderly patient, particularly the topics of access to transplantation, patient and graft survival, the impact of donor quality on transplant outcomes, immunology and immunosuppression of aging, and ethical considerations in the development of an equitable organ allocation scheme. PMID:20006794

  20. Will regenerative medicine replace transplantation?

    PubMed

    Orlando, Giuseppe; Soker, Shay; Stratta, Robert J; Atala, Anthony

    2013-08-01

    Recent groundbreaking advances in organ bioengineering and regeneration have provided evidence that regenerative medicine holds promise to dramatically improve the approach to organ transplantation. The two fields, however, share a common heritage. Alexis Carrel can be considered the father of both regenerative medicine and organ transplantation, and it is now clear that his legacy is equally applicable for the present and future generations of transplant and regenerative medicine investigators. In this review, we will briefly illustrate the interplay that should be established between these two complementary disciplines of health sciences. Although regenerative medicine has shown to the transplant field its potential, transplantation is destined to align with regenerative medicine and foster further progress probably more than either discipline alone. Organ bioengineering and regeneration technologies hold the promise to meet at the same time the two most urgent needs in organ transplantation, namely, the identification of a new, potentially inexhaustible source of organs and immunosuppression-free transplantation of tissues and organs. PMID:23906883

  1. Euarchontan Opsin Variation Brings New Focus to Primate Origins.

    PubMed

    Melin, Amanda D; Wells, Konstans; Moritz, Gillian L; Kistler, Logan; Orkin, Joseph D; Timm, Robert M; Bernard, Henry; Lakim, Maklarin B; Perry, George H; Kawamura, Shoji; Dominy, Nathaniel J

    2016-04-01

    Debate on the adaptive origins of primates has long focused on the functional ecology of the primate visual system. For example, it is hypothesized that variable expression of short- (SWS1) and middle-to-long-wavelength sensitive (M/LWS) opsins, which confer color vision, can be used to infer ancestral activity patterns and therefore selective ecological pressures. A problem with this approach is that opsin gene variation is incompletely known in the grandorder Euarchonta, that is, the orders Scandentia (treeshrews), Dermoptera (colugos), and Primates. The ancestral state of primate color vision is therefore uncertain. Here, we report on the genes (OPN1SW and OPN1LW) that encode SWS1 and M/LWS opsins in seven species of treeshrew, including the sole nocturnal scandentian Ptilocercus lowii. In addition, we examined the opsin genes of the Central American woolly opossum (Caluromys derbianus), an enduring ecological analogue in the debate on primate origins. Our results indicate: 1) retention of ultraviolet (UV) visual sensitivity in C. derbianus and a shift from UV to blue spectral sensitivities at the base of Euarchonta; 2) ancient pseudogenization of OPN1SW in the ancestors of P. lowii, but a signature of purifying selection in those of C. derbianus; and, 3) the absence of OPN1LW polymorphism among diurnal treeshrews. These findings suggest functional variation in the color vision of nocturnal mammals and a distinctive visual ecology of early primates, perhaps one that demanded greater spatial resolution under light levels that could support cone-mediated color discrimination. PMID:26739880

  2. Primate dietary ecology in the context of food mechanical properties.

    PubMed

    Coiner-Collier, Susan; Scott, Robert S; Chalk-Wilayto, Janine; Cheyne, Susan M; Constantino, Paul; Dominy, Nathaniel J; Elgart, Alison A; Glowacka, Halszka; Loyola, Laura C; Ossi-Lupo, Kerry; Raguet-Schofield, Melissa; Talebi, Mauricio G; Sala, Enrico A; Sieradzy, Pawel; Taylor, Andrea B; Vinyard, Christopher J; Wright, Barth W; Yamashita, Nayuta; Lucas, Peter W; Vogel, Erin R

    2016-09-01

    Substantial variation exists in the mechanical properties of foods consumed by primate species. This variation is known to influence food selection and ingestion among non-human primates, yet no large-scale comparative study has examined the relationships between food mechanical properties and feeding strategies. Here, we present comparative data on the Young's modulus and fracture toughness of natural foods in the diets of 31 primate species. We use these data to examine the relationships between food mechanical properties and dietary quality, body mass, and feeding time. We also examine the relationship between food mechanical properties and categorical concepts of diet that are often used to infer food mechanical properties. We found that traditional dietary categories, such as folivory and frugivory, did not faithfully track food mechanical properties. Additionally, our estimate of dietary quality was not significantly correlated with either toughness or Young's modulus. We found a complex relationship among food mechanical properties, body mass, and feeding time, with a potential interaction between median toughness and body mass. The relationship between mean toughness and feeding time is straightforward: feeding time increases as toughness increases. However, when considering median toughness, the relationship with feeding time may depend upon body mass, such that smaller primates increase their feeding time in response to an increase in median dietary toughness, whereas larger primates may feed for shorter periods of time as toughness increases. Our results emphasize the need for additional studies quantifying the mechanical and chemical properties of primate diets so that they may be meaningfully compared to research on feeding behavior and jaw morphology.

  3. Primate dental ecology: How teeth respond to the environment.

    PubMed

    Cuozzo, Frank P; Ungar, Peter S; Sauther, Michelle L

    2012-06-01

    Teeth are central for the study of ecology, as teeth are at the direct interface between an organism and its environment. Recent years have witnessed a rapid growth in the use of teeth to understand a broad range of topics in living and fossil primate biology. This in part reflects new techniques for assessing ways in which teeth respond to, and interact with, an organism's environment. Long-term studies of wild primate populations that integrate dental analyses have also provided a new context for understanding primate interactions with their environments. These new techniques and long-term field studies have allowed the development of a new perspective-dental ecology. We define dental ecology as the broad study of how teeth respond to, or interact with, the environment. This includes identifying patterns of dental pathology and tooth use-wear, as they reflect feeding ecology, behavior, and habitat variation, including areas impacted by anthropogenic disturbance, and how dental development can reflect environmental change and/or stress. The dental ecology approach, built on collaboration between dental experts and ecologists, holds the potential to provide an important theoretical and practical framework for inferring ecology and behavior of fossil forms, for assessing environmental change in living populations, and for understanding ways in which habitat impacts primate growth and development. This symposium issue brings together experts on dental morphology, growth and development, tooth wear and health, primate ecology, and paleontology, to explore the broad application of dental ecology to questions of how living and fossil primates interact with their environments.

  4. Euarchontan Opsin Variation Brings New Focus to Primate Origins

    PubMed Central

    Melin, Amanda D.; Wells, Konstans; Moritz, Gillian L.; Kistler, Logan; Orkin, Joseph D.; Timm, Robert M.; Bernard, Henry; Lakim, Maklarin B.; Perry, George H.; Kawamura, Shoji; Dominy, Nathaniel J.

    2016-01-01

    Debate on the adaptive origins of primates has long focused on the functional ecology of the primate visual system. For example, it is hypothesized that variable expression of short- (SWS1) and middle-to-long-wavelength sensitive (M/LWS) opsins, which confer color vision, can be used to infer ancestral activity patterns and therefore selective ecological pressures. A problem with this approach is that opsin gene variation is incompletely known in the grandorder Euarchonta, that is, the orders Scandentia (treeshrews), Dermoptera (colugos), and Primates. The ancestral state of primate color vision is therefore uncertain. Here, we report on the genes (OPN1SW and OPN1LW) that encode SWS1 and M/LWS opsins in seven species of treeshrew, including the sole nocturnal scandentian Ptilocercus lowii. In addition, we examined the opsin genes of the Central American woolly opossum (Caluromys derbianus), an enduring ecological analogue in the debate on primate origins. Our results indicate: 1) retention of ultraviolet (UV) visual sensitivity in C. derbianus and a shift from UV to blue spectral sensitivities at the base of Euarchonta; 2) ancient pseudogenization of OPN1SW in the ancestors of P. lowii, but a signature of purifying selection in those of C. derbianus; and, 3) the absence of OPN1LW polymorphism among diurnal treeshrews. These findings suggest functional variation in the color vision of nocturnal mammals and a distinctive visual ecology of early primates, perhaps one that demanded greater spatial resolution under light levels that could support cone-mediated color discrimination. PMID:26739880

  5. Primate dental ecology: How teeth respond to the environment.

    PubMed

    Cuozzo, Frank P; Ungar, Peter S; Sauther, Michelle L

    2012-06-01

    Teeth are central for the study of ecology, as teeth are at the direct interface between an organism and its environment. Recent years have witnessed a rapid growth in the use of teeth to understand a broad range of topics in living and fossil primate biology. This in part reflects new techniques for assessing ways in which teeth respond to, and interact with, an organism's environment. Long-term studies of wild primate populations that integrate dental analyses have also provided a new context for understanding primate interactions with their environments. These new techniques and long-term field studies have allowed the development of a new perspective-dental ecology. We define dental ecology as the broad study of how teeth respond to, or interact with, the environment. This includes identifying patterns of dental pathology and tooth use-wear, as they reflect feeding ecology, behavior, and habitat variation, including areas impacted by anthropogenic disturbance, and how dental development can reflect environmental change and/or stress. The dental ecology approach, built on collaboration between dental experts and ecologists, holds the potential to provide an important theoretical and practical framework for inferring ecology and behavior of fossil forms, for assessing environmental change in living populations, and for understanding ways in which habitat impacts primate growth and development. This symposium issue brings together experts on dental morphology, growth and development, tooth wear and health, primate ecology, and paleontology, to explore the broad application of dental ecology to questions of how living and fossil primates interact with their environments. PMID:22610891

  6. Primate dietary ecology in the context of food mechanical properties.

    PubMed

    Coiner-Collier, Susan; Scott, Robert S; Chalk-Wilayto, Janine; Cheyne, Susan M; Constantino, Paul; Dominy, Nathaniel J; Elgart, Alison A; Glowacka, Halszka; Loyola, Laura C; Ossi-Lupo, Kerry; Raguet-Schofield, Melissa; Talebi, Mauricio G; Sala, Enrico A; Sieradzy, Pawel; Taylor, Andrea B; Vinyard, Christopher J; Wright, Barth W; Yamashita, Nayuta; Lucas, Peter W; Vogel, Erin R

    2016-09-01

    Substantial variation exists in the mechanical properties of foods consumed by primate species. This variation is known to influence food selection and ingestion among non-human primates, yet no large-scale comparative study has examined the relationships between food mechanical properties and feeding strategies. Here, we present comparative data on the Young's modulus and fracture toughness of natural foods in the diets of 31 primate species. We use these data to examine the relationships between food mechanical properties and dietary quality, body mass, and feeding time. We also examine the relationship between food mechanical properties and categorical concepts of diet that are often used to infer food mechanical properties. We found that traditional dietary categories, such as folivory and frugivory, did not faithfully track food mechanical properties. Additionally, our estimate of dietary quality was not significantly correlated with either toughness or Young's modulus. We found a complex relationship among food mechanical properties, body mass, and feeding time, with a potential interaction between median toughness and body mass. The relationship between mean toughness and feeding time is straightforward: feeding time increases as toughness increases. However, when considering median toughness, the relationship with feeding time may depend upon body mass, such that smaller primates increase their feeding time in response to an increase in median dietary toughness, whereas larger primates may feed for shorter periods of time as toughness increases. Our results emphasize the need for additional studies quantifying the mechanical and chemical properties of primate diets so that they may be meaningfully compared to research on feeding behavior and jaw morphology. PMID:27542555

  7. Comparative RNA sequencing reveals substantial genetic variation in endangered primates

    PubMed Central

    Perry, George H.; Melsted, Páll; Marioni, John C.; Wang, Ying; Bainer, Russell; Pickrell, Joseph K.; Michelini, Katelyn; Zehr, Sarah; Yoder, Anne D.; Stephens, Matthew; Pritchard, Jonathan K.; Gilad, Yoav

    2012-01-01

    Comparative genomic studies in primates have yielded important insights into the evolutionary forces that shape genetic diversity and revealed the likely genetic basis for certain species-specific adaptations. To date, however, these studies have focused on only a small number of species. For the majority of nonhuman primates, including some of the most critically endangered, genome-level data are not yet available. In this study, we have taken the first steps toward addressing this gap by sequencing RNA from the livers of multiple individuals from each of 16 mammalian species, including humans and 11 nonhuman primates. Of the nonhuman primate species, five are lemurs and two are lorisoids, for which little or no genomic data were previously available. To analyze these data, we developed a method for de novo assembly and alignment of orthologous gene sequences across species. We assembled an average of 5721 gene sequences per species and characterized diversity and divergence of both gene sequences and gene expression levels. We identified patterns of variation that are consistent with the action of positive or directional selection, including an 18-fold enrichment of peroxisomal genes among genes whose regulation likely evolved under directional selection in the ancestral primate lineage. Importantly, we found no relationship between genetic diversity and endangered status, with the two most endangered species in our study, the black and white ruffed lemur and the Coquerel's sifaka, having the highest genetic diversity among all primates. Our observations imply that many endangered lemur populations still harbor considerable genetic variation. Timely efforts to conserve these species alongside their habitats have, therefore, strong potential to achieve long-term success. PMID:22207615

  8. Bare skin, blood and the evolution of primate colour vision.

    PubMed

    Changizi, Mark A; Zhang, Qiong; Shimojo, Shinsuke

    2006-06-22

    We investigate the hypothesis that colour vision in primates was selected for discriminating the spectral modulations on the skin of conspecifics, presumably for the purpose of discriminating emotional states, socio-sexual signals and threat displays. Here we show that, consistent with this hypothesis, there are two dimensions of skin spectral modulations, and trichromats but not dichromats are sensitive to each. Furthermore, the M and L cone maximum sensitivities for routine trichromats are optimized for discriminating variations in blood oxygen saturation, one of the two blood-related dimensions determining skin reflectance. We also show that, consistent with the hypothesis, trichromat primates tend to be bare faced.

  9. Primate-Specific Evolution of an LDLR Enhancer

    SciTech Connect

    Wang, Qian-fei; Prabhakar, Shyam; Wang, Qianben; Moses, Alan M.; Chanan, Sumita; Brown, Myles; Eisen, Michael B.; Cheng, Jan-Fang; Rubin,Edward M.; Boffelli, Dario

    2006-06-28

    Sequence changes in regulatory regions have often beeninvoked to explain phenotypic divergence among species, but molecularexamples of this have been difficult to obtain. In this study, weidentified an anthropoid primate specific sequence element thatcontributed to the regulatory evolution of the LDL receptor. Using acombination of close and distant species genomic sequence comparisonscoupled with in vivo and in vitro studies, we show that a functionalcholesterol-sensing sequence motif arose and was fixed within apre-existing enhancer in the common ancestor of anthropoid primates. Ourstudy demonstrates one molecular mechanism by which ancestral mammalianregulatory elements can evolve to perform new functions in the primatelineage leading to human.

  10. Key issues in transplant tourism.

    PubMed

    Akoh, Jacob A

    2012-02-24

    Access to organ transplantation depends on national circumstances, and is partly determined by the cost of health care, availability of transplant services, the level of technical capacity and the availability of organs. Commercial transplantation is estimated to account for 5%-10% (3500-7000) of kidney transplants performed annually throughout the world. This review is to determine the state and outcome of renal transplantation associated with transplant tourism (TT) and the key challenges with such transplantation. The stakeholders of commercial transplantation include: patients on the waiting lists in developed countries or not on any list in developing countries; dialysis funding bodies; middlemen, hosting transplant centres; organ-exporting countries; and organ vendors. TT and commercial kidney transplants are associated with a high incidence of surgical complications, acute rejection and invasive infection which cause major morbidity and mortality. There are ethical and medical concerns regarding the management of recipients of organs from vendors. The growing demand for transplantation, the perceived failure of altruistic donation in providing enough organs has led to calls for a legalised market in organ procurement or regulated trial in incentives for donation. Developing transplant services worldwide has many benefits - improving results of transplantation as they would be performed legally, increasing the donor pool and making TT unnecessary. Meanwhile there is a need to re-examine intrinsic attitudes to TT bearing in mind the cultural and economic realities of globalisation. Perhaps the World Health Organization in conjunction with The Transplantation Society would set up a working party of stakeholders to study this matter in greater detail and make recommendations. PMID:24175191

  11. Key issues in transplant tourism.

    PubMed

    Akoh, Jacob A

    2012-02-24

    Access to organ transplantation depends on national circumstances, and is partly determined by the cost of health care, availability of transplant services, the level of technical capacity and the availability of organs. Commercial transplantation is estimated to account for 5%-10% (3500-7000) of kidney transplants performed annually throughout the world. This review is to determine the state and outcome of renal transplantation associated with transplant tourism (TT) and the key challenges with such transplantation. The stakeholders of commercial transplantation include: patients on the waiting lists in developed countries or not on any list in developing countries; dialysis funding bodies; middlemen, hosting transplant centres; organ-exporting countries; and organ vendors. TT and commercial kidney transplants are associated with a high incidence of surgical complications, acute rejection and invasive infection which cause major morbidity and mortality. There are ethical and medical concerns regarding the management of recipients of organs from vendors. The growing demand for transplantation, the perceived failure of altruistic donation in providing enough organs has led to calls for a legalised market in organ procurement or regulated trial in incentives for donation. Developing transplant services worldwide has many benefits - improving results of transplantation as they would be performed legally, increasing the donor pool and making TT unnecessary. Meanwhile there is a need to re-examine intrinsic attitudes to TT bearing in mind the cultural and economic realities of globalisation. Perhaps the World Health Organization in conjunction with The Transplantation Society would set up a working party of stakeholders to study this matter in greater detail and make recommendations.

  12. Key issues in transplant tourism

    PubMed Central

    Akoh, Jacob A

    2012-01-01

    Access to organ transplantation depends on national circumstances, and is partly determined by the cost of health care, availability of transplant services, the level of technical capacity and the availability of organs. Commercial transplantation is estimated to account for 5%-10% (3500-7000) of kidney transplants performed annually throughout the world. This review is to determine the state and outcome of renal transplantation associated with transplant tourism (TT) and the key challenges with such transplantation. The stakeholders of commercial transplantation include: patients on the waiting lists in developed countries or not on any list in developing countries; dialysis funding bodies; middlemen, hosting transplant centres; organ-exporting countries; and organ vendors. TT and commercial kidney transplants are associated with a high incidence of surgical complications, acute rejection and invasive infection which cause major morbidity and mortality. There are ethical and medical concerns regarding the management of recipients of organs from vendors. The growing demand for transplantation, the perceived failure of altruistic donation in providing enough organs has led to calls for a legalised market in organ procurement or regulated trial in incentives for donation. Developing transplant services worldwide has many benefits - improving results of transplantation as they would be performed legally, increasing the donor pool and making TT unnecessary. Meanwhile there is a need to re-examine intrinsic attitudes to TT bearing in mind the cultural and economic realities of globalisation. Perhaps the World Health Organization in conjunction with The Transplantation Society would set up a working party of stakeholders to study this matter in greater detail and make recommendations. PMID:24175191

  13. Uterus transplantation: From animal models through the first heart beating pregnancy to the first human live birth.

    PubMed

    Ozkan, Omer; Dogan, Nasuh Utku; Ozkan, Ozlenen; Mendilcioglu, Inanc; Dogan, Selen; Aydinuraz, Batu; Simsek, Mehmet

    2016-07-01

    Absolute uterine factor infertility affects 3-5% of the general population, and unfortunately this condition is untreatable. There are some available options, including surrogacy or adoption, but neither of these suits each and every woman who desires to have her own genetic child. With recent advances in surgery and transplant immunology, uterus transplantation may be a source of hope for these women with uterine infertility. In the last decade, a number of animal species including rats, mice, rabbits, pigs, sheep, and primates have been used as experimental models, and pregnancies were achieved in some of these. Human data consist of 11 subjects yielding positive pregnancy results with no live births in the second trial from Turkey and, more fortunately, live births from the latest trial from Sweden. In the light of all these studies, uterus transplantation has been proven to be a viable option for women with uterine factor infertility. PMID:27638900

  14. The inhibitory efficacy of methylseleninic acid against colon cancer xenografts in C57BL/6 mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Data indicate that methylselenol is a critical selenium (Se) metabolite for anticancer activity in vivo. We tested the hypoththesis that oral dosing methylseleninic acid (MSeA), a methylselenol precursor, inhibits the growth of colon cancer xenografts in C57BL/6 mice fed a Se adequate diet. In this...

  15. Xenografting of canine ovarian tissue to ovariectomized severe combined immunodeficient (SCID) mice.

    PubMed

    Metcalfe, S S; Shaw, J M; Gunn, I M

    2001-01-01

    Xenografting of ovarian tissue salvaged from valuable dogs to an immunologically incompetent recipient is a possible mechanism to allow the ovarian tissue to be used for recovery of fertilizable oocytes. In this study, follicular development was assessed after xenotransplantation of fresh canine ovarian tissue into immunodeficient mice. Fresh prepubertal canine ovarian tissue was grafted beneath the kidney capsule of 7-week-old ovariectomized severe combined immunodeficient mice. At intervals after grafting, the recipient mice were killed, necropsied and the xenografts were recovered. The number and stage of development of follicles were assessed quantitatively by histological examination of serial sections of the xenografts. By day 56 after grafting, recruitment of primordial follicles had occurred but follicular development to the antral stage was not observed. The recipients showed persistent vaginal cornification and uterine dilation, which indicates that the grafts were producing hormones. However, these changes are not consistent with the oestrous cycle of either bitches or mice, indicating that inappropriate communication may occur between the recipient hypothalamic-pituitary glands and the axis of the xenograft gonad.

  16. A Nonhuman Primate Model of Human Radiation-Induced Venocclusive Liver Disease and Hepatocyte Injury

    SciTech Connect

    Yannam, Govardhana Rao; Han, Bing; Setoyama, Kentaro; Yamamoto, Toshiyuki; Ito, Ryotaro; Brooks, Jenna M.; Guzman-Lepe, Jorge; Galambos, Csaba; Fong, Jason V.; Deutsch, Melvin; Quader, Mubina A.; Yamanouchi, Kosho; Kabarriti, Rafi; Mehta, Keyur; Soto-Gutierrez, Alejandro; and others

    2014-02-01

    Background: Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease. Methods and Materials: We performed a dose-escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals. Results: At doses ≥40 Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses in which radiation-induced liver disease was mild or nonexistent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis. Conclusions: The cynomolgus monkey, as the first animal model of human veno-occlusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury.

  17. Mesenchymal stem cell-based NK4 gene therapy in nude mice bearing gastric cancer xenografts.

    PubMed

    Zhu, Yin; Cheng, Ming; Yang, Zhen; Zeng, Chun-Yan; Chen, Jiang; Xie, Yong; Luo, Shi-Wen; Zhang, Kun-He; Zhou, Shu-Feng; Lu, Nong-Hua

    2014-01-01

    Mesenchymal stem cells (MSCs) have been recognized as promising delivery vehicles for gene therapy of tumors. Gastric cancer is the third leading cause of worldwide cancer mortality, and novel treatment modalities are urgently needed. NK4 is an antagonist of hepatocyte growth factor receptors (Met) which are often aberrantly activated in gastric cancer and thus represent a useful candidate for targeted therapies. This study investigated MSC-delivered NK4 gene therapy in nude mice bearing gastric cancer xenografts. MSCs were transduced with lentiviral vectors carrying NK4 complementary DNA or enhanced green fluorescent protein (GFP). Such transduction did not change the phenotype of MSCs. Gastric cancer xenografts were established in BALB/C nude mice, and the mice were treated with phosphate-buffered saline (PBS), MSCs-GFP, Lenti-NK4, or MSCs-NK4. The tropism of MSCs toward gastric cancer cells was determined by an in vitro migration assay using MKN45 cells, GES-1 cells and human fibroblasts and their presence in tumor xenografts. Tumor growth, tumor cell apoptosis and intratumoral microvessel density of tumor tissue were measured in nude mice bearing gastric cancer xenografts treated with PBS, MSCs-GFP, Lenti-NK4, or MSCs-NK4 via tail vein injection. The results showed that MSCs migrated preferably to gastric cancer cells in vitro. Systemic MSCs-NK4 injection significantly suppressed the growth of gastric cancer xenografts. MSCs-NK4 migrated and accumulated in tumor tissues after systemic injection. The microvessel density of tumor xenografts was decreased, and tumor cellular apoptosis was significantly induced in the mice treated with MSCs-NK4 compared to control mice. These findings demonstrate that MSC-based NK4 gene therapy can obviously inhibit the growth of gastric cancer xenografts, and MSCs are a better vehicle for NK4 gene therapy than lentiviral vectors. Further studies are warranted to explore the efficacy and safety of the MSC-based NK4 gene therapy in

  18. Mesenchymal stem cell-based NK4 gene therapy in nude mice bearing gastric cancer xenografts.

    PubMed

    Zhu, Yin; Cheng, Ming; Yang, Zhen; Zeng, Chun-Yan; Chen, Jiang; Xie, Yong; Luo, Shi-Wen; Zhang, Kun-He; Zhou, Shu-Feng; Lu, Nong-Hua

    2014-01-01

    Mesenchymal stem cells (MSCs) have been recognized as promising delivery vehicles for gene therapy of tumors. Gastric cancer is the third leading cause of worldwide cancer mortality, and novel treatment modalities are urgently needed. NK4 is an antagonist of hepatocyte growth factor receptors (Met) which are often aberrantly activated in gastric cancer and thus represent a useful candidate for targeted therapies. This study investigated MSC-delivered NK4 gene therapy in nude mice bearing gastric cancer xenografts. MSCs were transduced with lentiviral vectors carrying NK4 complementary DNA or enhanced green fluorescent protein (GFP). Such transduction did not change the phenotype of MSCs. Gastric cancer xenografts were established in BALB/C nude mice, and the mice were treated with phosphate-buffered saline (PBS), MSCs-GFP, Lenti-NK4, or MSCs-NK4. The tropism of MSCs toward gastric cancer cells was determined by an in vitro migration assay using MKN45 cells, GES-1 cells and human fibroblasts and their presence in tumor xenografts. Tumor growth, tumor cell apoptosis and intratumoral microvessel density of tumor tissue were measured in nude mice bearing gastric cancer xenografts treated with PBS, MSCs-GFP, Lenti-NK4, or MSCs-NK4 via tail vein injection. The results showed that MSCs migrated preferably to gastric cancer cells in vitro. Systemic MSCs-NK4 injection significantly suppressed the growth of gastric cancer xenografts. MSCs-NK4 migrated and accumulated in tumor tissues after systemic injection. The microvessel density of tumor xenografts was decreased, and tumor cellular apoptosis was significantly induced in the mice treated with MSCs-NK4 compared to control mice. These findings demonstrate that MSC-based NK4 gene therapy can obviously inhibit the growth of gastric cancer xenografts, and MSCs are a better vehicle for NK4 gene therapy than lentiviral vectors. Further studies are warranted to explore the efficacy and safety of the MSC-based NK4 gene therapy in

  19. Associations of Pre-Transplant Serum Albumin with Post-Transplant Outcomes in Kidney Transplant Recipients

    PubMed Central

    Molnar, Miklos Z; Kovesdy, Csaba P; Bunnapradist, Suphamai; Streja, Elani; Mehrotra, Rajnish; Krishnan, Mahesh; Nissenson, Allen R; Kalantar-Zadeh, Kamyar

    2011-01-01

    The association between pre-transplant serum albumin concentration and post-transplant outcomes in kidney transplant recipients is unclear. We hypothesized that in transplant-waitlisted hemodialysis patients, lower serum albumin concentrations are associated with worse post-transplant outcomes. Linking the 5-year patient data of a large dialysis organization (DaVita) to the Scientific Registry of Transplant Recipients, we identified 8961 hemodialysis patients who underwent first kidney transplantation. Mortality or graft failure and delayed graft function (DGF) risks were estimated by Cox regression (hazard ratio [HR]) and logistic regression (Odds ratio [OR]), respectively. Patients were 48±13 years old and included 37% women and 27% diabetics. The higher pre-transplant serum albumin was associated with lower mortality, graft failure and DGF risk even after multivariate adjustment for case-mix, malnutrition-inflammation complex and transplant related variable. Every 0.2 g/dL higher pre-transplant serum albumin concentration was associated with 13% lower all-cause mortality (HR=0.87 [95% confidence interval: 0.82-0.93]), 17% lower cardiovascular mortality (HR=0.83[0.74-0.93]), 7% lower combined risk of death or graft failure (HR=0.93[0.89-0.97]), and 4% lower DGF risk (OR=0.96[0.93-0.99]). Hence, lower pre-transplant serum albumin level is associated with worse post-transplant outcomes. Clinical trials to examine interventions to improve nutritional status in transplant-wait-listed hemodialysis patients and their impacts on post-transplant outcomes are indicated. PMID:21449945

  20. Evolution of activity patterns and chromatic vision in primates: morphometrics, genetics and cladistics.

    PubMed

    Heesy, C P; Ross, C F

    2001-02-01

    Hypotheses for the adaptive origin of primates have reconstructed nocturnality as the primitive activity pattern for the entire order based on functional/adaptive interpretations of the relative size and orientation of the orbits, body size and dietary reconstruction. Based on comparative data from extant taxa this reconstruction implies that basal primates were also solitary, faunivorous, and arboreal. Recently, primates have been hypothesized to be primitively diurnal, based in part on the distribution of color-sensitive photoreceptor opsin genes and active trichromatic color vision in several extant strepsirrhines, as well as anthropoid primates (Tan & Li, 1999 Nature402, 36; Li, 2000 Am. J. phys. Anthrop. Supple.30, 318). If diurnality is primitive for all primates then the functional and adaptive significance of aspects of strepsirrhine retinal morphology and other adaptations of the primate visual system such as high acuity stereopsis, have been misinterpreted for decades. This hypothesis also implies that nocturnality evolved numerous times in primates. However, the hypothesis that primates are primitively diurnal has not been analyzed in a phylogenetic context, nor have the activity patterns of several fossil primates been considered. This study investigated the evolution of activity patterns and trichromacy in primates using a new method for reconstructing activity patterns in fragmentary fossils and by reconstructing visual system character evolution at key ancestral nodes of primate higher taxa. Results support previous studies that reconstruct omomyiform primates as nocturnal. The larger body sizes of adapiform primates confound inferences regarding activity pattern evolution in this group. The hypothesis of diurnality and trichromacy as primitive for primates is not supported by the phylogenetic data. On the contrary, nocturnality and dichromatic vision are not only primitive for all primates, but also for extant strepsirrhines. Diurnality, and