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  1. Article ; Online: Induced regulatory T cells: mechanisms of conversion and suppressive potential.

    Dons, Eefje M / Raimondi, Giorgio / Cooper, David K C / Thomson, Angus W

    Human immunology

    2012  Volume 73, Issue 4, Page(s) 328–334

    Abstract: Thymus-derived, naturally occurring CD4(+) Forkhead Box P3(+) regulatory T cells (nTreg) have suppressive activity that is important for the establishment and maintenance of immune homeostasis in the healthy state. Abundant reports have demonstrated that ...

    Abstract Thymus-derived, naturally occurring CD4(+) Forkhead Box P3(+) regulatory T cells (nTreg) have suppressive activity that is important for the establishment and maintenance of immune homeostasis in the healthy state. Abundant reports have demonstrated that they can suppress pathogenic processes in autoimmune diseases and inhibit transplant rejection and graft-versus-host disease. Far less is known about induced regulatory T cells (iTreg) that are generated from naive T cells in the periphery or in vitro by directing naive T cells to acquire suppressive function under the influence of transforming growth factor-β and other factors. In this review, we describe mechanisms by which naive T cells are thought to be converted into iTreg. We also discuss the suppressive potential of iTreg, particularly in comparison with their naturally occurring counterparts, focusing on those reports in which direct comparisons have been made. Based on current knowledge, we consider the rationale for using iTreg versus nTreg in clinical trials.
    MeSH term(s) Animals ; Cell Differentiation/drug effects ; Cell Differentiation/immunology ; Costimulatory and Inhibitory T-Cell Receptors/metabolism ; Drug Synergism ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/metabolism ; Humans ; Interleukin-2/metabolism ; Interleukin-2/pharmacology ; Sirolimus/pharmacology ; T-Lymphocytes/drug effects ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; T-Lymphocytes, Regulatory/drug effects ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; Th17 Cells/immunology ; Th17 Cells/metabolism ; Transforming Growth Factor beta/metabolism ; Transforming Growth Factor beta/pharmacology ; Tretinoin/pharmacology
    Chemical Substances Costimulatory and Inhibitory T-Cell Receptors ; Forkhead Transcription Factors ; Interleukin-2 ; Transforming Growth Factor beta ; Tretinoin (5688UTC01R) ; Sirolimus (W36ZG6FT64)
    Language English
    Publishing date 2012-01-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 801524-7
    ISSN 1879-1166 ; 0198-8859
    ISSN (online) 1879-1166
    ISSN 0198-8859
    DOI 10.1016/j.humimm.2011.12.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Non-human primate regulatory T cells: current biology and implications for transplantation.

    Dons, Eefje M / Raimondi, Giorgio / Cooper, David K C / Thomson, Angus W

    Transplantation

    2010  Volume 90, Issue 8, Page(s) 811–816

    Abstract: Regulatory T cells (Treg) offer potential for improving long-term outcomes in cell and organ transplantation. The non-human primate model is a valuable resource for addressing issues concerning the transfer of Treg therapy to the clinic. Herein, we ... ...

    Abstract Regulatory T cells (Treg) offer potential for improving long-term outcomes in cell and organ transplantation. The non-human primate model is a valuable resource for addressing issues concerning the transfer of Treg therapy to the clinic. Herein, we discuss the properties of non-human primate Treg and prospects for their evaluation in allotransplantation and xenotransplantation.
    MeSH term(s) Adoptive Transfer/methods ; Animals ; Antigens, CD/analysis ; Cell Division ; Flow Cytometry ; Humans ; Immunologic Memory ; Immunosuppressive Agents/therapeutic use ; Lymphocyte Activation ; Lymphocyte Depletion ; Macaca fascicularis ; Primates ; Rodentia ; T-Lymphocytes, Regulatory/cytology ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/physiology ; T-Lymphocytes, Regulatory/transplantation ; Transplantation, Heterologous/immunology
    Chemical Substances Antigens, CD ; Immunosuppressive Agents
    Language English
    Publishing date 2010-06-01
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 208424-7
    ISSN 1534-6080 ; 0041-1337
    ISSN (online) 1534-6080
    ISSN 0041-1337
    DOI 10.1097/TP.0b013e3181ebf782
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Platelet aggregation in humans and nonhuman primates: relevance to xenotransplantation.

    Iwase, Hayato / Ekser, Burcin / Zhou, Hao / Dons, Eefje M / Cooper, David K C / Ezzelarab, Mohamed B

    Xenotransplantation

    2012  Volume 19, Issue 4, Page(s) 233–243

    Abstract: Introduction: Platelet activation/aggregation plays a key role in the dysregulation of coagulation and the development of thrombotic microangiopathy in nonhuman primate recipients of pig xenografts. As a preliminary to the study of anti-platelet therapy ...

    Abstract Introduction: Platelet activation/aggregation plays a key role in the dysregulation of coagulation and the development of thrombotic microangiopathy in nonhuman primate recipients of pig xenografts. As a preliminary to the study of anti-platelet therapy in vitro and in vivo, the present study aimed to compare platelet aggregation in whole blood from humans, baboons, and cynomolgus monkeys.
    Methods: Using "Chrono-log" technology (two-sample four-channel Chrono-log Whole Blood Aggregometer), we studied aggregation of platelets in healthy humans (n = 8), baboons (n = 5), and monkeys (n = 8). Whole blood (WB) samples were collected, and platelet aggregation was assessed using three different volumes of blood (1, 0.5, and 0.25 ml). Platelet activation was induced using collagen (at 3 and 5 μg/ml), ristocetin (at 0.5 and 1.0 mg/ml), adenosine diphosphate (ADP; at 10, 20, and 40 μm), or thrombin (at 1 and 5 IU/ml). Inhibition of agonist-induced platelet aggregation by heparin and low molecular weight heparin (LMWH) (at 1, 10, and 100 IU/ml) was evaluated.
    Results: Mean platelet counts were 222.1, 263.2, and 276.1 (×10(3) /μl) in humans, baboons, and monkeys, respectively. In all three species, platelet aggregation was induced by collagen, ristocetin, ADP, or thrombin in a dose-dependent manner. A blood volume of 0.5 ml provided the most consistent results with all agonists in all three species. Dilution studies indicated that there was a significant positive correlation between platelet count and percent aggregation of platelets (P < 0.05). Collagen (3 and 5 μg/ml), ADP (10, 20, and 40 μm), and thrombin (1 and 5 IU/ml) induced significantly greater platelet aggregation in humans than in baboons. ADP (20 and 40 μm) and thrombin (1 and 5 IU/ml) induced significantly greater platelet aggregation in monkeys than in baboons. There was no species difference with ristocetin (0.5 or 1.0 mg/ml). In all species, thrombin (1 or 5 IU) induced greater platelet aggregation than any of the other reagents. Heparin at 1 IU/ml and LMWH at 10 IU/ml in all species almost completely abrogated thrombin-induced platelet aggregation. Heparin at 100 IU/ml effectively inhibited platelet aggregation induced by collagen, but only partially inhibited aggregation induced by ADP or ristocetin. LMWH only partially inhibited aggregation induced by collagen, ristocetin, and ADP.
    Conclusions: The "Chrono-log" technology proved to be a reliable method of evaluating platelet activation and aggregation in vitro in primates. Species differences may play a role in platelet aggregation, with the monkey being more comparable to the human than the baboon, although overall trends were similar. In all species, thrombin induced greater platelet aggregation than other agonists. Even a concentration of heparin of 1 IU/ml, which is probably the maximal concentration that is clinically-applicable, prevented platelet aggregation induced by thrombin, but was less effective in preventing aggregation induced by collagen, ADP, or, particularly, ristocetin.
    MeSH term(s) Adenosine Diphosphate/pharmacology ; Animals ; Collagen/pharmacology ; Heparin/pharmacology ; Heparin, Low-Molecular-Weight/pharmacology ; Humans ; In Vitro Techniques ; Macaca fascicularis ; Papio anubis ; Platelet Aggregation/drug effects ; Platelet Aggregation/physiology ; Platelet Aggregation Inhibitors/pharmacology ; Ristocetin/pharmacology ; Species Specificity ; Thrombin/pharmacology ; Transplantation, Heterologous/adverse effects
    Chemical Substances Heparin, Low-Molecular-Weight ; Platelet Aggregation Inhibitors ; Ristocetin (1404-55-3) ; Adenosine Diphosphate (61D2G4IYVH) ; Heparin (9005-49-6) ; Collagen (9007-34-5) ; Thrombin (EC 3.4.21.5)
    Language English
    Publishing date 2012-07-20
    Publishing country Denmark
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1236298-0
    ISSN 1399-3089 ; 0908-665X
    ISSN (online) 1399-3089
    ISSN 0908-665X
    DOI 10.1111/j.1399-3089.2012.00712.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Parental fever attitude and management: influence of parental ethnicity and child's age.

    Nijman, Ruud G / Oostenbrink, Rianne / Dons, Eefje M / Bouwhuis, Carola B / Moll, Henriëtte A

    Pediatric emergency care

    2010  Volume 26, Issue 5, Page(s) 339–342

    Abstract: Objective: The objective was to study parental fever management and attitude toward fever from the perspective of the child's ethnicity and age.: Patients and setting: Children with fever presenting at the pediatric emergency department (PED) of the ... ...

    Abstract Objective: The objective was to study parental fever management and attitude toward fever from the perspective of the child's ethnicity and age.
    Patients and setting: Children with fever presenting at the pediatric emergency department (PED) of the Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands, in the period from February 2002 to March 2004.
    Design: Prospective observational.
    Main outcome measures: Parental fever attitude and management assessed by a questionnaire.
    Results: Two hundred eleven children with fever (median age, 1.2 years; interquartile range, 0.7-2.0 years) were included, of whom 108 (55%) were boys. One hundred fourteen children (54%) were self-referrals at the PED. Accompanying symptoms were reported in 95% (50% had > or = 3); median temperature measured at PED was 39.5 degrees C (interquartile range, 38.9 degrees C-40.8 degrees C). One hundred fifty-five parents (74%) had used antipyretics to reduce fever, and 155 parents (74%) were worried about fever and its possible complications. Differences between Dutch and non-Dutch ethnicities were seen in temperature-reducing techniques, self-referral, and parental anxiety of fever and its complications. Age did not influence parental fever attitude and management.
    Conclusions: For most children in our population, the use of antipyretics was justified, as the majority of our children visiting the PED for an acute febrile episode are young infants, in particular with a high degree of fever and accompanying symptoms. We confirm and extend previous findings of ethnicity influencing parental fever management.
    MeSH term(s) Age Factors ; Analgesics, Non-Narcotic/therapeutic use ; Anxiety/ethnology ; Anxiety/psychology ; Attitude to Health ; Body Temperature ; Child, Preschool ; Ethnic Groups ; Female ; Fever/drug therapy ; Fever/ethnology ; Fever/psychology ; Follow-Up Studies ; Humans ; Infant ; Male ; Netherlands/epidemiology ; Parent-Child Relations ; Parents/psychology ; Retrospective Studies ; Surveys and Questionnaires ; Thermometers
    Chemical Substances Analgesics, Non-Narcotic
    Language English
    Publishing date 2010-05
    Publishing country United States
    Document type Comparative Study ; Journal Article
    ZDB-ID 632588-9
    ISSN 1535-1815 ; 0749-5161
    ISSN (online) 1535-1815
    ISSN 0749-5161
    DOI 10.1097/PEC.0b013e3181db1dce
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Technique of endoscopic biopsy of islet allografts transplanted into the gastric submucosal space in pigs.

    Fujita, Minoru / McGrath, Kevin M / Bottino, Rita / Dons, Eefje M / Long, Cassandra / Kumar, Goutham / Ekser, Burcin / Echeverri, Gabriel J / Hata, Jiro / Haruma, Ken / Cooper, David K C / Hara, Hidetaka

    Cell transplantation

    2013  Volume 22, Issue 12, Page(s) 2335–2344

    Abstract: Currently, islet cells are transplanted into the liver via portal vein infusion. One disadvantage of this approach is that it is not possible to adequately biopsy the islets in the liver to assess for rejection. Islet transplantation (Tx) into the ... ...

    Abstract Currently, islet cells are transplanted into the liver via portal vein infusion. One disadvantage of this approach is that it is not possible to adequately biopsy the islets in the liver to assess for rejection. Islet transplantation (Tx) into the gastric submucosal space (GSMS) can be performed endoscopically and has the potential advantage of histological evaluation by endoscopic biopsy. The aim of this study was to determine whether a representative allograft sample could be obtained endoscopically. We performed islet Tx into the GSMS in nonimmunosuppressed pigs using simple endoscopic submucosal injection. Islets were transplanted at four sites. Endoscopic ultrasonography and biopsy of the transplanted islets at two sites by modified endoscopic submucosal dissection were carried out successfully in all pigs 5 days after islet Tx. Tissue obtained at both biopsy and necropsy (including full-thickness sections of the gastric wall around the sites of the remaining islets and biopsies) were examined by histology and immunohistochemistry to confirm the presence of the islet grafts and any features of rejection. Representative allograft sampling was successfully obtained from all biopsy sites. All biopsies included islets with insulin-positive staining. There was significant CD3(+) and CD68(+) cell infiltration in the islet masses obtained at biopsy and from sections taken at necropsy, with similar histopathological features. Endoscopic biopsy of islet allografts in the GSMS is feasible, provides accurate histopathological data, and would provide a significant advance if translated into clinical practice.
    MeSH term(s) Animals ; Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; CD3 Complex/metabolism ; Endoscopy, Digestive System ; Endosonography ; Female ; Gastric Mucosa/surgery ; Graft Survival ; Islets of Langerhans/diagnostic imaging ; Islets of Langerhans/metabolism ; Islets of Langerhans/pathology ; Islets of Langerhans Transplantation ; Necrosis/metabolism ; Necrosis/pathology ; Swine ; Transplantation, Homologous
    Chemical Substances Antigens, CD ; Antigens, Differentiation, Myelomonocytic ; CD3 Complex ; CD68 antigen, human
    Language English
    Publishing date 2013-01-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1135816-6
    ISSN 1555-3892 ; 0963-6897
    ISSN (online) 1555-3892
    ISSN 0963-6897
    DOI 10.3727/096368912X662381
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Is there a correlation between anti-pig antibody levels in humans and geographic location during childhood?

    Kumar, Goutham / Satyananda, Vikas / Fang, Jason / Zhou, Hao / Fujita, Minoru / Ekser, Burcin / Long, Cassandra / Dons, Eefje / Sun, Qing / Ayares, David / Hara, Hidetaka / Cooper, David K C

    Transplantation

    2013  Volume 96, Issue 4, Page(s) 387–393

    Abstract: Background: An initial observation suggested high levels of anti-pig antibodies in healthy humans who had spent their childhood in the Middle East. We tested larger cohorts to determine whether anti-pig antibody levels correlated with the geographic ... ...

    Abstract Background: An initial observation suggested high levels of anti-pig antibodies in healthy humans who had spent their childhood in the Middle East. We tested larger cohorts to determine whether anti-pig antibody levels correlated with the geographic location in which the subject spent his/her childhood, because this might have implications for clinical trials of xenotransplantation.
    Methods: Anti-pig IgM and IgG levels (by flow cytometry using peripheral blood mononuclear cells from wild-type and α1,3-galactosyltransferase gene-knockout pigs) and anti-Gal IgM and IgG levels (by enzyme-linked immunosorbent assay) were measured in 75 volunteers. Comparisons of antibody levels were also made based on subject age, gender, ABO blood group, diet, and history of vaccination.
    Results: Antibody binding to α1,3-galactosyltransferase gene-knockout pig cells was less than to wild-type cells. There was a reduction in anti-pig IgM and anti-Gal IgM, but a slight increase in anti-nonGal IgG, with age. Women had higher levels of anti-Gal IgM than men. Blood group A subjects had higher levels of anti-pig IgM and IgG than those of group AB. Diet had no influence on antibody levels. Typhoid or measles-mumps-rubella vaccination was associated with lower anti-nonGal IgG or anti-Gal IgG, respectively, whereas influenza vaccination was associated with higher anti-nonGal IgG. There were some significant variations in antibody levels associated with location during childhood, with subjects from the Middle East demonstrating higher anti-nonGal IgG and anti-Gal IgG.
    Conclusion: Clinical trials of xenotransplantation may be influenced by various factors, including the geographic location of the recipient during childhood, possibly associated with exposure to different microorganisms.
    MeSH term(s) ABO Blood-Group System ; Adult ; Aged ; Animals ; Antibodies, Heterophile/blood ; Child ; Cohort Studies ; Female ; Galactose/immunology ; Galactosyltransferases/deficiency ; Galactosyltransferases/genetics ; Gene Knockout Techniques ; Humans ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; Leukocytes, Mononuclear/enzymology ; Leukocytes, Mononuclear/immunology ; Male ; Middle Aged ; Middle East/ethnology ; Sus scrofa/genetics ; Sus scrofa/immunology ; Sus scrofa/metabolism ; United States ; Young Adult
    Chemical Substances ABO Blood-Group System ; Antibodies, Heterophile ; Immunoglobulin G ; Immunoglobulin M ; Galactosyltransferases (EC 2.4.1.-) ; N-acetyllactosaminide alpha-1,3-galactosyltransferase (EC 2.4.1.87) ; Galactose (X2RN3Q8DNE)
    Language English
    Publishing date 2013-01-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 208424-7
    ISSN 1534-6080 ; 0041-1337
    ISSN (online) 1534-6080
    ISSN 0041-1337
    DOI 10.1097/TP.0b013e3182992a84
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: A syndrome of severe hypoglycemia and acidosis in young immunosuppressed diabetic monkeys and pigs-association with sepsis.

    Zhou, Hao / van der Windt, Dirk J / Dons, Eefje M / Rigatti, Lora H / Echeverri, Gabriel J / Bottino, Rita / Wijkstrom, Martin / Wagner, Robert / Cooper, David K C

    Transplantation

    2012  Volume 94, Issue 12, Page(s) 1187–1191

    Abstract: Background: Large animals treated with immunosuppressive drugs for preclinical experiments of transplantation have increased risks of infection, which can be compounded by the induction of diabetes if islet transplantation is planned.: Methods: We ... ...

    Abstract Background: Large animals treated with immunosuppressive drugs for preclinical experiments of transplantation have increased risks of infection, which can be compounded by the induction of diabetes if islet transplantation is planned.
    Methods: We report our experience with severe sepsis in two young cynomolgus monkeys and five pigs that were subjected to diabetes induction, immunosuppressive therapy, or islet allotransplantation.
    Results: In two monkeys and five pigs, infection was associated with a syndrome of profound hypoglycemia accompanied by severe acidosis, which was resistant to treatment. We do not believe that this syndrome has been reported previously by others.
    Conclusions: Despite treatment, this syndrome complicated the interpretation of blood glucose readings as a measure of islet graft function and resulted in death or the need for euthanasia in all seven animals. We tentatively suggest that the syndrome may be related to the presence of microorganisms that metabolize glucose and produce lactate.
    MeSH term(s) Acidosis/immunology ; Acidosis/metabolism ; Animals ; Bacteria/metabolism ; Blood Glucose/metabolism ; Diabetes Mellitus, Experimental/immunology ; Diabetes Mellitus, Experimental/metabolism ; Diabetes Mellitus, Experimental/surgery ; Disease Models, Animal ; Graft Rejection/drug therapy ; Graft Rejection/immunology ; Hypoglycemia/immunology ; Hypoglycemia/metabolism ; Immunosuppressive Agents/pharmacology ; Islets of Langerhans Transplantation/adverse effects ; Islets of Langerhans Transplantation/immunology ; Lactic Acid/blood ; Macaca fascicularis ; Sepsis/immunology ; Sepsis/metabolism ; Severity of Illness Index ; Swine ; Syndrome ; Transplantation, Homologous
    Chemical Substances Blood Glucose ; Immunosuppressive Agents ; Lactic Acid (33X04XA5AT)
    Language English
    Publishing date 2012-11-06
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 208424-7
    ISSN 1534-6080 ; 0041-1337
    ISSN (online) 1534-6080
    ISSN 0041-1337
    DOI 10.1097/TP.0b013e318272210c
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Collagenous colitis-like condition in immunosuppressed infant baboons.

    Dons, Eefje M / Echeverri, Gabriel J / Rigatti, Lora H / Klein, Edwin / Montoya, Claudia / Wolf, Roman F / Ijzermans, Jan N M / Cooper, David K C / Wagner, Robert

    Inflammatory bowel diseases

    2012  Volume 18, Issue 7, Page(s) 1325–1332

    Abstract: Background: Collagenous colitis is a chronic inflammatory bowel disease of unknown etiology. It is fairly common in adult humans, but rare in infants, and has been associated with autoimmune disorders.: Methods: We report four infant baboons (age 7- ... ...

    Abstract Background: Collagenous colitis is a chronic inflammatory bowel disease of unknown etiology. It is fairly common in adult humans, but rare in infants, and has been associated with autoimmune disorders.
    Methods: We report four infant baboons (age 7-12 months) that had received a transplant at 3 months of age and subsequent immunosuppressive therapy for periods of 4-10 months. All presented identical symptoms within a period of 4 weeks, including weight loss associated with chronic watery diarrhea that was unresponsive to standard antimicrobial treatment.
    Results: Clinical chemistry evaluations were within normal ranges, viral causes were ruled out, and fecal and blood cultures were repeatedly negative. At necropsy, two infant baboons were found to have a form of collagenous colitis. In the remaining two baboons that had identical clinical features, immunosuppressive therapy was discontinued and treatment with budesonide was initiated. Both baboons recovered and remained well on no medication until the end of follow-up (24 months).
    Conclusions: Collagenous colitis has occasionally been reported in patients with organ transplants. It has been reported only once previously in baboons. The four cases reported here strongly suggest that 1) clinical features as well as histopathological findings of collagenous colitis in baboons are very similar to those in human patients; 2) it was associated with the immunocompromised state of the baboons, as two nonimmunosuppressed age-matched baboons in close proximity did not develop the condition; and 3) it may have had an infectious origin, as all four cases developed within a 4-week period of time.
    MeSH term(s) Animals ; Animals, Newborn ; Anti-Inflammatory Agents/therapeutic use ; Budesonide/therapeutic use ; Colitis, Collagenous/etiology ; Colitis, Collagenous/immunology ; Colitis, Collagenous/pathology ; Diarrhea/drug therapy ; Diarrhea/etiology ; Diarrhea/pathology ; Female ; Humans ; Immunosuppression ; Immunosuppressive Agents/adverse effects ; Male ; Papio ; Weight Loss
    Chemical Substances Anti-Inflammatory Agents ; Immunosuppressive Agents ; Budesonide (51333-22-3)
    Language English
    Publishing date 2012-01-31
    Publishing country England
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1340971-2
    ISSN 1536-4844 ; 1078-0998
    ISSN (online) 1536-4844
    ISSN 1078-0998
    DOI 10.1002/ibd.21900
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: T-lymphocyte homeostasis and function in infant baboons: implications for transplantation.

    van der Windt, Dirk J / Dons, Eefje M / Montoya, Claudia L / Ezzelarab, Mohamed / Long, Cassandra / Wolf, Roman F / Ijzermans, Jan N M / Lakkis, Fadi G / Cooper, David K C

    Transplant international : official journal of the European Society for Organ Transplantation

    2011  Volume 25, Issue 2, Page(s) 218–228

    Abstract: Laboratory mice are born lymphopenic and demonstrate lymphopenia-induced proliferation that generates memory T cells, yet they are prone to immunologic tolerance. Here we tested whether these fundamental immunologic observations apply to higher animals ... ...

    Abstract Laboratory mice are born lymphopenic and demonstrate lymphopenia-induced proliferation that generates memory T cells, yet they are prone to immunologic tolerance. Here we tested whether these fundamental immunologic observations apply to higher animals by studying the immune system of infant baboons. Using flow cytometry of the peripheral blood cells, it was found that baboons are born relatively lymphopenic and subsequently expand their initially naïve T cell pool with increasing numbers of memory T cells. After transplantation of an artery patch allograft or xenograft, non-immunosuppressed recipients readily mounted an immune response against donor-type antigens, as evidenced by mixed lymphocyte reaction. Immunosuppression with anti-thymocyte globulin (ATG), anti-CD154 mAb, and mycophenolate mofetil prevented T cell-mediated rejection. After lymphocyte depletion with ATG, homeostatic T cell proliferation was observed. In conclusion, the baboon proved a suitable model to investigate the infant immune system. In this study, neonatal lymphopenia and expansion of the memory T cell population were observed but, unlike mice, there were no indications that infant baboons are prone to T cell tolerance. The expansion of memory T cells during the neonatal period or after induction therapy may actually form an obstacle to tapering immunosuppressive therapy, or ultimately achieving immunologic tolerance.
    MeSH term(s) Animals ; Animals, Newborn/immunology ; Carotid Arteries/transplantation ; Homeostasis ; Immune Tolerance ; Immunologic Memory ; Lymphocyte Activation ; Papio/immunology ; Swine ; T-Lymphocytes/immunology
    Language English
    Publishing date 2011-11-17
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 639435-8
    ISSN 1432-2277 ; 0934-0874
    ISSN (online) 1432-2277
    ISSN 0934-0874
    DOI 10.1111/j.1432-2277.2011.01384.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Technique of Endoscopic Biopsy of Islet Allografts Transplanted into the Gastric Submucosal Space in Pigs

    Minoru Fujita / Kevin M. McGrath / Rita Bottino / Eefje M. Dons / Cassandra Long / Goutham Kumar / Burcin Ekser / Gabriel J. Echeverri / Jiro Hata, ‡‡ / Ken Haruma / David K. C. Cooper / Hidetaka Hara M.D., Ph.D.

    Cell Transplantation, Vol

    2013  Volume 22

    Abstract: Currently, islet cells are transplanted into the liver via portal vein infusion. One disadvantage of this approach is that it is not possible to adequately biopsy the islets in the liver to assess for rejection. Islet transplantation (Tx) into the ... ...

    Abstract Currently, islet cells are transplanted into the liver via portal vein infusion. One disadvantage of this approach is that it is not possible to adequately biopsy the islets in the liver to assess for rejection. Islet transplantation (Tx) into the gastric submucosal space (GSMS) can be performed endoscopically and has the potential advantage of histological evaluation by endoscopic biopsy. The aim of this study was to determine whether a representative allograft sample could be obtained endoscopically. We performed islet Tx into the GSMS in nonimmunosup-pressed pigs using simple endoscopic submucosal injection. Islets were transplanted at four sites. Endoscopic ultrasonography and biopsy of the transplanted islets at two sites by modified endoscopic submucosal dissection were carried out successfully in all pigs 5 days after islet Tx. Tissue obtained at both biopsy and necropsy (including full-thickness sections of the gastric wall around the sites of the remaining islets and biopsies) were examined by histology and immunohistochemistry to confirm the presence of the islet grafts and any features of rejection. Representative allograft sampling was successfully obtained from all biopsy sites. All biopsies included islets with insulin-positive staining. There was significant CD3 + and CD68 + cell infiltration in the islet masses obtained at biopsy and from sections taken at necropsy, with similar histopathological features. Endoscopic biopsy of islet allografts in the GSMS is feasible, provides accurate histopathological data, and would provide a significant advance if translated into clinical practice.
    Keywords Medicine ; R
    Subject code 610
    Language English
    Publishing date 2013-12-01T00:00:00Z
    Publisher SAGE Publishing
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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