221 research outputs found

    Carpal tunnel pressure measurement during two-portal endoscopic carpal tunnel release

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    Background: Although there remain concerns of median nerve damage during endoscopic carpal tunnel release for carpal tunnel syndrome, carpal tunnel pressure variations during Chow's two-portal techinique have not been well investigated. Methods: We performed a modified two-portal endoscopic carpal tunnel release on 30 patients by inserting a catheter pressure transducer into the carpal tunnel for continuous pressure measurement during the procedure. Grip and pinch strengths, Semmes-Weinstein monofilament test, and nerve conduction studies were examined preoperatively and at postoperative 1, 3, and 6 months. Numbness and the Disabilities of the Arm, Shoulder and Hand score were also evaluated pre and postoperatively. Findings: Subjective symptoms and nerve conduction study findings improved uneventfully. The pressure was always observed to be maximum pressure immediately before the cannula was withdrawn from the exit portal, and carpal tunnel pressure >300 mm Hg was recorded in most of the patients. Interpretation: A transient increase in the carpal tunnel pressure occurred in all the patients; however, it did not correlate with their clinical outcome or with increased risk of pen-operative complications. Since time-pressure threshold of the median nerve during endoscopic carpal tunnel release is still unknown, our results did not guarantee its safety.ArticleCLINICAL BIOMECHANICS. 25(9):893-898 (2010)journal articl

    A New Light on the Evolution and Propagation of Prehistoric Grain Pests: The World's Oldest Maize Weevils Found in Jomon Potteries, Japan

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    Three Sitophilus species (S. granarius L., S. oryzae L., and S. zeamais Mots.) are closely related based on DNA analysis of their endosymbionts. All are seed parasites of cereal crops and important economic pest species in stored grain. The Sitophilus species that currently exist, including these three species, are generally believed to be endemic to Asia's forested areas, suggesting that the first infestations of stored grain must have taken place near the forested mountains of southwestern Asia. Previous archaeological data and historical records suggest that the three species may have been diffused by the spread of Neolithic agriculture, but this hypothesis has only been established for granary weevils in European and southwestern Asian archaeological records. There was little archeological evidence for grain pests in East Asia before the discovery of maize weevil impressions in Jomon pottery in 2004 using the “impression replica” method. Our research on Jomon agriculture based on seed and insect impressions in pottery continued to seek additional evidence. In 2010, we discovered older weevil impressions in Jomon pottery dating to ca. 10 500 BP. These specimens are the oldest harmful insects in the world discovered at archaeological sites. Our results provide evidence of harmful insects living in the villages from the Earliest Jomon, when no cereals were cultivated. This suggests we must reconsider previous scenarios for the evolution and propagation of grain pest weevils, especially in eastern Asia. Although details of their biology or the foods they infested remain unclear, we hope future interdisciplinary collaborations among geneticists, entomologists, and archaeologists will provide the missing details

    Intercomparison of global river discharge simulations focusing on dam operation --- Part II: Multiple models analysis in two case-study river basins, Missouri-Mississippi and Green-Colorado

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    We performed a twofold intercomparison of river discharge regulated by dams under multiple meteorological forcings among multiple global hydrological models for a historical period by simulation. Paper II provides an intercomparison of river discharge simulated by five hydrological models under four meteorological forcings. This is the first global multimodel intercomparison study on dam-regulated river flow. Although the simulations were conducted globally, the Missouri-Mississippi and Green-Colorado Rivers were chosen as case-study sites in this study. The hydrological models incorporate generic schemes of dam operation, not specific to a certain dam. We examined river discharge on a longitudinal section of river channels to investigate the effects of dams on simulated discharge, especially at the seasonal time scale. We found that the magnitude of dam regulation differed considerably among the hydrological models. The difference was attributable not only to dam operation schemes but also to the magnitude of simulated river discharge flowing into dams. That is, although a similar algorithm of dam operation schemes was incorporated in different hydrological models, the magnitude of dam regulation substantially differed among the models. Intermodel discrepancies tended to decrease toward the lower reaches of these river basins, which means model dependence is less significant toward lower reaches. These case-study results imply that, intermodel comparisons of river discharge should be made at different locations along the river’s course to critically examine the performance of hydrological models because the performance can vary with the locations

    Contributions of Mamu-A*01 Status and TRIM5 Allele Expression, But Not CCL3L Copy Number Variation, to the Control of SIVmac251 Replication in Indian-Origin Rhesus Monkeys

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    CCL3 is a ligand for the HIV-1 co-receptor CCR5. There have recently been conflicting reports in the literature concerning whether CCL3-like gene (CCL3L) copy number variation (CNV) is associated with resistance to HIV-1 acquisition and with both viral load and disease progression following infection with HIV-1. An association has also been reported between CCL3L CNV and clinical sequelae of the simian immunodeficiency virus (SIV) infection in vivo in rhesus monkeys. The present study was initiated to explore the possibility of an association of CCL3L CNV with the control of virus replication and AIDS progression in a carefully defined cohort of SIVmac251-infected, Indian-origin rhesus monkeys. Although we demonstrated extensive variation in copy number of CCL3L in this cohort of monkeys, CCL3L CNV was not significantly associated with either peak or set-point plasma SIV RNA levels in these monkeys when MHC class I allele Mamu-A*01 was included in the models or progression to AIDS in these monkeys. With 66 monkeys in the study, there was adequate power for these tests if the correlation of CCL3L and either peak or set-point plasma SIV RNA levels was 0.34 or 0.36, respectively. These findings call into question the premise that CCL3L CNV is important in HIV/SIV pathogenesis

    Immunization with Cocktail of HIV-Derived Peptides in Montanide ISA-51 Is Immunogenic, but Causes Sterile Abscesses and Unacceptable Reactogenicity

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    BACKGROUND: A peptide vaccine was produced containing B and T cell epitopes from the V3 and C4 Envelope domains of 4 subtype B HIV-1 isolates (MN, RF, CanO, & Ev91). The peptide mixture was formulated as an emulsion in incomplete Freund's adjuvant (IFA). METHODS: Low-risk, healthy adult subjects were enrolled in a randomized, placebo-controlled dose-escalation study, and selected using criteria specifying that 50% in each study group would be HLA-B7+. Immunizations were scheduled at 0, 1, and 6 months using a total peptide dose of 1 or 4 mg. Adaptive immune responses in16 vaccine recipients and two placebo recipients after the 2nd immunization were evaluated using neutralization assays of sera, as well as ELISpot and ICS assays of cryopreserved PBMCs to assess CD4 and CD8 T-cell responses. In addition, (51)Cr release assays were performed on fresh PBMCs following 14-day stimulation with individual vaccine peptide antigens. RESULTS: 24 subjects were enrolled; 18 completed 2 injections. The study was prematurely terminated because 4 vaccinees developed prolonged pain and sterile abscess formation at the injection site-2 after dose 1, and 2 after dose 2. Two other subjects experienced severe systemic reactions consisting of headache, chills, nausea, and myalgia. Both reactions occurred after the second 4 mg dose. The immunogenicity assessments showed that 6/8 vaccinees at each dose level had detectable MN-specific neutralizing (NT) activity, and 2/7 HLA-B7+ vaccinees had classical CD8 CTL activity detected. However, using both ELISpot and ICS, 8/16 vaccinees (5/7 HLA-B7+) and 0/2 controls had detectable vaccine-specific CD8 T-cell responses. Subjects with moderate or severe systemic or local reactions tended to have more frequent T cell responses and higher antibody responses than those with mild or no reactions. CONCLUSIONS: The severity of local responses related to the formulation of these four peptides in IFA is clinically unacceptable for continued development. Both HIV-specific antibody and T cell responses were induced and the magnitude of response correlated with the severity of local and systemic reactions. If potent adjuvants are necessary for subunit vaccines to induce broad and durable immune responses, careful, incremental clinical evaluation is warranted to minimize the risk of adverse events. TRIAL REGISTRATION: ClinicalTrials.gov NCT00000886

    Association of Activating KIR Copy Number Variation of NK Cells with Containment of SIV Replication in Rhesus Monkeys

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    While the contribution of CD8+ cytotoxic T lymphocytes to early containment of HIV-1 spread is well established, a role for NK cells in controlling HIV-1 replication during primary infection has been uncertain. The highly polymorphic family of KIR molecules expressed on NK cells can inhibit or activate these effector cells and might therefore modulate their activity against HIV-1-infected cells. In the present study, we investigated copy number variation in KIR3DH loci encoding the only activating KIR receptor family in rhesus monkeys and its effect on simian immunodeficiency virus (SIV) replication during primary infection in rhesus monkeys. We observed an association between copy numbers of KIR3DH genes and control of SIV replication in Mamu-A*01– rhesus monkeys that express restrictive TRIM5 alleles. These findings provide further evidence for an association between NK cells and the early containment of SIV replication, and underscore the potential importance of activating KIRs in stimulating NK cell responses to control SIV spread

    Current Bioengineering and Regenerative Strategies for the Generation of Kidney Grafts on Demand

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    [EN] Currently in the USA, one name is added to the organ transplant waiting list every 15 min. As this list grows rapidly, fewer than one-third of waiting patients can receive matched organs from donors. Unfortunately, many patients who require a transplant have to wait for long periods of time, and many of them die before receiving the desired organ. In the USA alone, over 100,000 patients are waiting for a kidney transplant. However, it is a problem that affects around 6% of the word population. Therefore, seeking alternative solutions to this problem is an urgent work. Here, we review the current promising regenerative technologies for kidney function replacement. Despite many approaches being applied in the different ways outlined in this work, obtaining an organ capable of performing complex functions such as osmoregulation, excretion or hormone synthesis is still a long-term goal. However, in the future, the efforts in these areas may eliminate the long waiting list for kidney transplants, providing a definitive solution for patients with end-stage renal disease.This study was supported by a grant from ALCER-TURIA, ASTELLAS and PRECIPITA CROWDFUNDING.Garcia-Dominguez, X.; Vicente Antón, JS.; Vera Donoso, CD.; Marco-Jiménez, F. (2017). Current Bioengineering and Regenerative Strategies for the Generation of Kidney Grafts on Demand. Current Urology Reports. 18(1):1-8. https://doi.org/10.1007/s11934-017-0650-6S18181Ott HC, Mathisen DJ. Bioartificial tissues and organs: are we ready to translate? Lancet. 2011;378:1977–8.Salvatori M, Peloso A, Katari R, Orlando G. Regeneration and bioengineering of the kidney: current status and future challenges. Curr Urol Rep. 2014;15:379.D’Agati VD. Growing new kidneys from embryonic cell suspensions: fantasy or reality? J Am Soc Nephrol. 2002;11:1763–6.Abouna GM. Organ shortage crisis: problems and possible solutions. Transplant Proc. 2008;40:34–8.Ozbolat IT, Yu Y. Bioprinting toward organ fabrication: challenges and future trends. IEEE Trans Biomed Eng. 2013;60:691–9.Badylak SF, Taylor D, Uygun K. Whole-organ tissue engineering: decellularization and recellularization of three-dimensional matrix scaffolds. Annu Rev Biomed Eng. 2011;13:27–53.Meeus F, Kourilsky O, Guerin AP, Gaudry C, Marchais SJ, London GM. Pathophysiology of cardiovascular disease in hemodialysis patients. Kidney Int Suppl. 2000;76:140–7.Jofré R. Factores que afectan a la calidad de vida en pacientes en prediálisis, diálisis y trasplante renal. Nefrologia. 1999;19:84–90.Villa G, Rodríguez-Carmona A, Fernández-Ortiz L, Cuervo J, Rebollo P, Otero A, et al. Cost analysis of the Spanish renal replacement therapy programme. Nephrol Dial Transplant. 2011;26:3709–14.MJ C, Marshall D, Dilworth M, Bottomley M, Ashton N, Brenchley P. Immunosuppression is essential for successful allogeneic transplantation of the metanephroi. Transplantation. 2009;88:151–9.Xinaris C, Yokoo T. Reforming the kidney starting from a single-cell suspension. Nephron Exp Nephrol. 2014;126:107.Nguyen DM, El-Serag HB. The epidemiology of obesity. Gastroenterol Clin N Am. 2010;39:1–7.Song JJ, Guyette JP, Gilpin SE, Gonzalez G, Vacanti JP, Ott HC. Regeneration and experimental orthotopic transplantation of a bioengineered kidney. Nat Med. 2013;19:646–51.Hariharan K, Kurtz A, Schmidt-Ott KM. Assembling kidney tissues from cells: the long road from organoids to organs. Front Cell Dev Biol. 2015;3:70.Montserrat N, Garreta E, Izpisua Belmonte JC. Regenerative strategies for kidney engineering, FEBS J. 2016; in press. doi: 10.1111/febs.13704 .Hammerman MR. Transplantation of renal primordia: renal organogenesis. Pediatr Nephrol. 2007;22:1991–8.Basma H, Soto-Gutiérrez A, Yannam GR, Liu L, Ito R, Yamamoto T, et al. Differentiation and transplantation of human embryonic stem cell-derived hepatocytes. Gastroenterology. 2009;136:990–9.Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol. 2009;27:275–80.Takahashi T, Lord B, Schulze PC, Fryer RM, Sarang SS, Gullans SR, et al. Ascorbic acid enhances differentiation of embryonic stem cells into cardiac myocytes. Circulation. 2003;107:1912–6.Zhang D, Jiang W, Liu M, Sui X, Yin X, Chen S, et al. Highly efficient differentiation of human ES cells and iPS cells into mature pancreatic insulin-producing cells. Cell Res. 2009;19:429–38.Ledran MH, Krassowska A, Armstrong L, Dimmick I, Renström J, Lang R, et al. Efficient hematopoietic differentiation of human embryonic stem cells on stromal cells derived from hematopoietic niches. Cell Stem Cell. 2008;3:85–98.Yamanaka S, Yokoo T. Current bioengineering methods for whole kidney regeneration. Stem Cells Int. 2015;2015:724047.Xia Y, Nivet E, Sancho-Martinez I, Gallegos T, Suzuki K, Okamura D, et al. Directed differentiation of human pluripotent cells to ureteric bud kidney progenitor-like cells. Nat Cell Biol. 2013;15:1507–15.Taguchi A, Kaku Y, Ohmori T, Sharmin S, Ogawa M, Sasaki H, et al. Redefining the in vivo origin of metanephric nephron progenitors enables generation of complex kidney structures from pluripotent stem cells. Cell Stem Cell. 2014;14:53–67.Simerman AA, Dumesic DA, Chazenbalk GD. Pluripotent muse cells derived from human adipose tissue: a new perspective on regenerative medicine and cell therapy. Clin Transl Med. 2014;3:12.Verdi J, Tan A, Shoae-Hassani A, Seifalian AM. Endometrial stem cells in regenerative medicine. J Biol Eng. 2014;8:20.Maeshima A, Yamashita S, Nojima Y. Identification of renal progenitor-like tubular cells that participate in the regeneration processes of the kidney. J Am Soc Nephrol. 2003;14:3138–46.Sagrinati C, Netti GS, Mazzinghi B, Lazzeri E, Liotta F, Frosali F, et al. Isolation and characterization of multipotent progenitor cells from the Bowman’s capsule of adult human kidneys. J Am Soc Nephrol. 2006;17:2443–56.Oliver JA, Maarouf O, Cheema FH, Martens TP, Al-Awqati Q. The renal papilla is a niche for adult kidney stem cells. J Clin Invest. 2004;114:795–804.Kitamura S, Yamasaki Y, Kinomura M, Sugaya T, Sugiyama H, Maeshima Y, et al. Establishment and characterization of renal progenitor like cells from S3 segment of nephron in rat adult kidney. FASEB J. 2005;19:1789–97.Kitamura S, Sakurai H, Makino H. Single adult kidney stem/progenitor cells reconstitute three-dimensional nephron structures in vitro. Stem Cells. 2015;33:774–84.Li M, Suzuki K, Kim NY, Liu GH, Izpisua Belmonte JC. A cut above the rest: targeted genome editing technologies in human pluripotent stem cells. J Biol Chem. 2014;289:4594–9.Freedman BS, Brooks CR, Lam AQ, Fu H, Morizane R, Agrawal V, et al. Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids. Nat Commun. 2015;6:8715.Hu J, Lei Y, Wong WK, Liu S, Lee KC, He X, et al. Direct activation of human and mouse Oct4 genes using engineered TALE and Cas9 transcription factors. Nucleic Acids Res. 2014;42:4375–90.Den Hartogh SC, Schreurs C, Monshouwer-Kloots JJ, Davis RP, Elliott DA, Mummery CL, et al. Dual reporter MESP1 mCherry/w-NKX2-5 eGFP/w hESCs enable studying early human cardiac differentiation. Stem Cells. 2015;33:56–67.Fukui A, Yokoo T. Kidney regeneration using developing xenoembryo. Curr Opin Organ Transplant. 2015;20:160–4.Chen J, Lansford R, Stewart V, Young F, Alt FW. RAG-2-deficient blastocyst complementation: an assay of gene function in lymphocyte development. Proc Natl Acad Sci U S A. 1993;90:4528–32.Ueno H, Turnbull BB, Weissman IL. Two-step oligoclonal development of male germ cells. Proc Natl Acad Sci U S A. 2009;106:175–80.Fraidenraich D, Stillwell E, Romero E, Wilkes D, Manova K, Basson CT, et al. Rescue of cardiac defects in id knockout embryos by injection of embryonic stem cells. Science. 2004;306:247–52.Kobayashi T, Yamaguchi T, Hamanaka S, Kato-Itoh M, Yamazaki Y, Ibata M, et al. Generation of rat pancreas in mouse by interspecific blastocyst injection of pluripotent stem cells. Cell. 2010;142:787–99.Matsunari H, Nagashima H, Watanabe M, Umeyama K, Nakano K, Nagaya M, et al. Blastocyst complementation generates exogenic pancreas in vivo in apancreatic cloned pigs. Proc Natl Acad Sci U S A. 2013;110:4557–62.Espejel S, Roll GR, McLaughlin KJ, Lee AY, Zhang JY, Laird DJ, et al. Induced pluripotent stem cell-derived hepatocytes have the functional and proliferative capabilities needed for liver regeneration in mice. J Clin Invest. 2010;120:3120–6.Usui J, Kobayashi T, Yamaguchi T, Knisely AS, Nishinakamura R, Nakauchi H. Generation of kidney from pluripotent stem cells via blastocyst complementation. Am J Pathol. 2012;180:2417–26.Aggarwal S, Moggio A, Bussolati B. Concise review: stem/progenitor cells for renal tissue repair: current knowledge and perspectives. Stem Cells Transl Med. 2013;2:1011–9.Yokote S, Yokoo T. Organogenesis for kidney regeneration. Curr Opin Organ Transplant. 2013;18:186–90.Crapo PM, Gilbert TW, Badylak SF. An overview of tissue and whole organ decellularization processes. Biomaterials. 2011;32:3233–43.Berthiaume F, Maguire TJ, Yarmush ML. Tissue engineering and regenerative medicine: history, progress, and challenges. Annu Rev Chem Biomol Eng. 2011;2:403–30.Badylak SF. Xenogeneic extracellular matrix as a scaffold for tissue reconstruction. Transpl Immunol. 2004;12:367–77.Badylak SF. The extracellular matrix as a biologic scaffold material. Biomaterials. 2007;28:3587–93.Ott HC, Matthiesen TS, Goh SK, Black LD, Kren SM, Netoff TI, et al. Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat Med. 2008;14:213–21.Yokoo T. Kidney regeneration with stem cells: an overview. Nephron Exp Nephrol. 2014;126(2):54.Uygun BE, Soto-Gutierrez A, Yagi H, Izamis ML, Guzzardi MA, Shulman C, et al. Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat Med. 2010;16:814–20.Ott HC, Clippinger B, Conrad C, Schuetz C, Pomerantseva I, Ikonomou L, et al. Regeneration and orthotopic transplantation of a bioartificial lung. Nat Med. 2010;16:927–33.Montserrat N, Garreta E, Izpisua Belmonte JC. Regenerative strategies for kidney engineering. FEBS J. 2016. doi: 10.1111/febs.13704 .Murphy SV, Atala A. 3D bioprinting of tissues and organs. Nat Biotechnol. 2014;32:773–85.Groll J, Boland T, Blunk T, Burdick JA, Cho DW, Dalton PD, et al. Biofabrication: reappraising the definition of an evolving field. Biofabrication. 2016;8:013001.Mandrycky C, Wang Z, Kim K, Kim DH. 3D bioprinting for engineering complex tissues. Biotechnol Adv. 2016;34:422–34.Uzarski JS, Xia Y, Belmonte JC, Wertheim JA. New strategies in kidney regeneration and tissue engineering. Curr Opin Nephrol Hypertens. 2014;23:399–405.Humes HD, Buffington DA, MacKay SM, Funke AJ, Weitzel WF. Replacement of renal function in uremic animals with a tissue-engineered kidney. Nat Biotechnol. 1999;17:451–5.Chevtchik NV, Fedecostante M, Jansen J, Mihajlovic M, Wilmer M, Rüth M, Masereeuw R, Stamatialis D. Upscaling of a living membrane for bioartificial kidney device. Eur J Pharmacol. 2016.Humes HD, Sobota JT, Ding F, Song JH. A selective cytopheretic inhibitory device to treat the immunological dysregulation of acute and chronic renal failure. Blood Purif. 2010;29:183–90.Tumlin J, Wali R, Williams W, Murray P, Tolwani AJ, Vinnikova AK, et al. Efficacy and safety of renal tubule cell therapy for acute renal failure. J Am Soc Nephrol. 2008;19:1034–40.Yokoo T, Ohashi T, Shen JS, Sakurai K, Miyazaki Y, Utsunomiya Y, et al. Human mesenchymal stem cells in rodent whole-embryo culture are reprogrammed to contribute to kidney tissues. Proc Natl Acad Sci U S A. 2005;102(9):3296–300.Yokoo T, Fukui A, Ohashi T, Miyazaki Y, Utsunomiya Y, Kawamura T, et al. Xenobiotic kidney organogenesis from human mesenchymal stem cells using a growing rodent embryo. J Am Soc Nephrol. 2006;17:1026–34.Cooper DK. A brief history of cross-species organ transplantation. Proc (Bayl Univ Med Cent). 2012;25:49–57.Costa MR, Fischer N, Gulich B, Tönjes RR. Comparison of porcine endogenous retroviruses infectious potential in supernatants of producer cells and in cocultures. Xenotransplantation. 2014;21:162–73.Takeda S, Rogers SA, Hammerman MR. Differential origin for endothelial and mesangial cells after transplantation of pig fetal renal primordia into rats. Transpl Immunol. 2006;15:211–5.Yasutomi Y. Establishment of specific pathogen-free macaque colonies in Tsukuba Primate Research Center of Japan for AIDS research. Vaccine. 2010;28:75–7.Dekel B, Burakova T, Arditti FD, Reich-Zeliger S, Milstein O, Aviel-Ronen S, et al. Human and porcine early kidney precursors as a new source for transplantation. Nat Med. 2003;9:53–60.Hammerman MR. Classic and current opinion in embryonic organ transplantation. Curr Opin Organ Transplant. 2014;19:133–9.Rogers SA, Hammerman MR. Prolongation of life in anephric rats following de novo renal organogenesis. Organogenesis. 2004;1:22–5.•• Yokote S, Matsunari H, Iwai S, Yamanaka S, Uchikura A, Fujimoto E, et al. Urine excretion strategy for stem cell-generated embryonic kidneys. Proc Natl Acad Sci U S A. 2015;112:12980–5. This manuscript describes the developed-metanephros ability to produce urine when it was connected to the excretory system of the recipient organism. They demonstrated the potential of this technique as a possible solution to the kidneys shortage.Yokote S, Yokoo T, Matsumoto K, Utsunomiya Y, Kawamura T, Hosoya T. The effect of metanephroi transplantation on blood pressure in anephric rats with induced acute hypotension. Nephrol Dial Transplant. 2012;27:3449–55.Matsumoto K, Yokoo T, Yokote S, Utsunomiya Y, Ohashi T, Hosoya T. Functional development of a transplanted embryonic kidney: effect of transplantation site. J Nephrol. 2012;25:50–5.Yokote S, Yokoo T, Matsumoto K, Ohkido I, Utsunomiya Y, Kawamura T, et al. Metanephroi transplantation inhibits the progression of vascular calcification in rats with adenine-induced renal failure. Nephron Exp Nephrol. 2012;120:e32–40.Matsumoto K, Yokoo T, Matsunari H, Iwai S, Yokote S, Teratani T, et al. Xeno‐transplanted embryonic kidney provides a niche for endogenous mesenchymal stem cell differentiation into erythropoietin-producing tissue. Stem Cells. 2012;30:1228–35.Abrahamson DR. Glomerular development in intraocular and intrarenal graft of fetal kidney. Lab Investig. 1991;64:629–39.Woolf AS, Palmer SJ, Snow ML, Fine LG. Creation of functioning chimeric mammalian kidney. Kidney Int. 1990;38:991–7.Robert B, St John PL, Hyink DP, Abrahamson DR. Evidence that embryonic kidney cells expressing flk-1 are intrinsic, vasculogenic angioblasts. Am J Physiol. 1996;271:F744–53.Koseki C, Herzlinger D, Al-Awqati Q. Integration of embryonic nephrogenic cells carrying a reporter gene into functioning nephrons. Am J Physiol. 1991;261:C550–4.Rogers SA, Lowell JA, Hammerman NA, Hammerman MR. Transplantation of developing metanephroi into adult rats. Kidney Int. 1998;54:27–37.Barakat TL, Harrison RG. The capacity of fetal and neonatal renal tissues to regenerate and differentiate in a heterotropic allogenic subcutaneous tissue site in the rat. J Anat. 1971;110:393–407.Rogers SA, Liapis H, Hammerman MR. Transplantation of metanephroi across the major histocompatibility complex in rats. Am J Physiol Regul Integr Comp Physiol. 2001;280:R132–6.Vera-Donoso CD, García-Dominguez X, Jiménez-Trigos E, García-Valero L, Vicente JS, Marco-Jiménez F. Laparoscopic transplantation of metanephroi: a first step to kidney xenotransplantation. Actas Urol Esp. 2015;39:527–34.•• Marco-Jiménez F, Garcia-Dominguez X, Jimenez-Trigos E, Vera-Donoso CD, Vicente JS. Vitrification of kidney precursors as a new source for organ transplantation. Cryobiology. 2015;70:278–82. This study found that it is possible to create a long-term biobank of kidney precursors as an unlimited source of organs for transplantation and open new therapeutic possibilities for the patients with chronic renal failure.Garcia-Dominguez X, Vicente JS, Vera-Donoso C, Jimenez-Trigos E, Marco-Jiménez F. First steps towards organ banks: vitrification of renal primordia. CryoLetters. 2016;37:47–52.•• García-Domínguez X, Vera-Donoso CD, García-Valero L, Vicente JS, Marco-Jiménez F. Embryonic organ transplantation: the new era of xenotransplantation. In: Abdeldayem H, El-Kased AF, El-Shaarawy A, editors. Frontiers in transplantology. 2016. pp. 26–46. This manuscript describes for the first time the protocol for transplantation of embryonic kidneys as an organ replacement therapy using laparoscopic surgery.Bottomley MJ, Baicu S, Boggs JM, Marshall DP, Clancy M, Brockbank KG, et al. Preservation of embryonic kidneys for transplantation. Transplant Proc. 2005;37:280–4.Hara J, Tottori J, Anders M, Dadhwal S, Asuri P, Mobed-Miremadi M. Trehalose effectiveness as a cryoprotectant in 2D and 3D cell cultures of human embryonic kidney cells. Artif Cells Nanomed Biotechnol. 2016. doi: 10.3109/21691401.2016.1167698 .Xu Y, Zhao G, Zhou X, Ding W, Shu Z, Gao D. Biotransport and intracellular ice formation phenomena in freezing human embryonic kidney cells (HEK293T). Cryobiology. 2014;68:294–302

    Dual Neonate Vaccine Platform against HIV-1 and M. tuberculosis

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    Acquired immunodeficiency syndrome and tuberculosis (TB) are two of the world's most devastating diseases. The first vaccine the majority of infants born in Africa receive is Mycobacterium bovis bacillus Calmette-Guérin (BCG) as a prevention against TB. BCG protects against disseminated disease in the first 10 years of life, but provides a variable protection against pulmonary TB and enhancing boost delivered by recombinant modified vaccinia virus Ankara (rMVA) expressing antigen 85A (Ag85A) of M. tuberculosis is currently in phase IIb evaluation in African neonates. If the newborn's mother is positive for human immunodeficiency virus type 1 (HIV-1), the baby is at high risk of acquiring HIV-1 through breastfeeding. We suggested that a vaccination consisting of recombinant BCG expressing HIV-1 immunogen administered at birth followed by a boost with rMVA sharing the same immunogen could serve as a strategy for prevention of mother-to-child transmission of HIV-1 and rMVA expressing an African HIV-1-derived immunogen HIVA is currently in phase I trials in African neonates. Here, we aim to develop a dual neonate vaccine platform against HIV-1 and TB consisting of BCG.HIVA administered at birth followed by a boost with MVA.HIVA.85A. Thus, mMVA.HIVA.85A and sMVA.HIVA.85A vaccines were constructed, in which the transgene transcription is driven by either modified H5 or short synthetic promoters, respectively, and tested for immunogenicity alone and in combination with BCG.HIVA222. mMVA.HIVA.85A was produced markerless and thus suitable for clinical manufacture. While sMVA.HIVA.85A expressed higher levels of the immunogens, it was less immunogenic than mMVA.HIVA.85A in BALB/c mice. A BCG.HIVA222–mMVA.HIVA.85A prime-boost regimen induced robust T cell responses to both HIV-1 and M. tuberculosis. Therefore, proof-of-principle for a dual anti-HIV-1/M. tuberculosis infant vaccine platform is established. Induction of immune responses against these pathogens soon after birth is highly desirable and may provide a basis for lifetime protection maintained by boosts later in life
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