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Genomes and Genes | D A ClarkSummaryAffiliation: McMaster University Country: Canada Publications
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Publications
Regulatory T cells and reproduction: how do they do it?David A Clark
Departments of Medicine, Molecular Medicine and Pathology, Obstetrics and Gynecology, McMaster University, Health Sciences Centre Rm 3H1E, Hamilton, Ontario, Canada L8S 4K1
J Reprod Immunol 96:1-7. 2012..The relevance of findings in mice to human pregnancy problems is also discussed...- The end of evidence-based medicine?David A Clark
Department of Medicine, Molecular Medicine and Pathology, Ob Gyn, Faculty of Graduate Studies, McMaster University, Health Sciences Centre, West, Hamilton, ON L8S 4K1, Canada
Inflammopharmacology 20:187-93. 2012..Advantages of observational studies are outlined, and the importance of assessing one's actual results when applying a treatment based on controlled trial evidence is set out... 
TH1/TH2,3 imbalance due to cytokine-producing NK, gammadelta T and NK-gammadelta T cells in murine pregnancy decidua in success or failure of pregnancyD A Clark
Department of Molecular Medicine and Pathology, Obstetrics Gynecology, McMaster University, Hamilton, Ont, Canada
Am J Reprod Immunol 45:257-65. 2001..However, TGF-beta2-producing cells are present in the decidua of pregnant severe combined immune deficient (SCID) mice, which lack gammadelta T cells...- Anti-TNFalpha therapy in immune-mediated subfertility: state of the artDavid A Clark
McMaster University Room 3V39, 1200 Main St West, Hamilton, Ontario L8N 3Z5, Canada
J Reprod Immunol 85:15-24. 2010..Potential side effects and key issues in informed consent are set out. Anti-TNFalpha drugs may offer a new safe and effective approach to treating patients with Th1-cytokine-dependent infertility and recurrent miscarriages... - The fgl2 prothrombinase/fibroleukin gene is required for lipopolysaccharide-triggered abortions and for normal mouse reproductionDavid A Clark
Department of Medicine, McMaster University Medical Center, Hamilton, Ontario, Canada
Mol Hum Reprod 10:99-108. 2004..Physiological expression of fgl2 in fetal trophoblast may prevent occult loss in early pregnancy, along with other coagulation factors, but fgl2 expression is required for LPS to induce abortion pathology... - Prevention of spontaneous abortion in the CBA x DBA/2 mouse model by intravaginal TGF-beta and local recruitment of CD4+8+ FOXP3+ cellsDavid A Clark
Department of Medicine, McMaster University, Hamilton, ON, Canada
Am J Reprod Immunol 59:525-34. 2008..Seminal plasma contains many factors besides TGF-beta, and a critical test of the hypothesis was required. The purpose of the present study was to directly test the effect of pure TGF-beta... - Tolerance mechanisms in pregnancy: a reappraisal of the role of class I paternal MHC antigensDavid A Clark
Department of Medicine, McMaster University Rm 3V39, Hamilton, ON, Canada
Am J Reprod Immunol 63:93-103. 2010..The alphabeta T-cell receptor recognizes peptide bound to the groove in Class I MHC, and peptides have profound effects on the interaction of KIR receptors on T and NK cells with Class I MHC... - Cell-surface CD200 may predict efficacy of paternal mononuclear leukocyte immunotherapy in treatment of human recurrent pregnancy lossDavid A Clark
Department of Medicine, Molecular Medicine and Pathology, Obstetrics and Gynecology, McMaster University, Hamilton, ON, Canada
Am J Reprod Immunol 61:75-84. 2009..Recent data emphasize an important role of expression of the CD200 tolerance-signaling molecule on cells used to prevent abortions both in mice and humans... - Ecology of danger-dependent cytokine-boosted spontaneous abortion in the CBA x DBA/2 mouse model: II. Fecal LPS levels in colonies with different basal abortion ratesDavid A Clark
Department of Medicine, McMaster University, Hamilton, ON, Canada
Am J Reprod Immunol 60:529-33. 2008..It was predicted that intestinal availability of LPS was a major factor in the endogenous and cytokine-boosted resorption rates... - How should data on murine spontaneous abortion rates be expressed and analyzed?David A Clark
McMaster University Rm 3V39, Hamilton, ON, Canada
Am J Reprod Immunol 60:192-6. 2008..Recently, it has been argued that medians with box plots should replace the accepted standard, but this deprives readers of data needed to verify P-values, and leads to inferences incompatible with biological and statistical reality... - MD-1 is a critical part of the mechanism causing Th1-cytokine-triggered murine fetal loss syndromeDavid A Clark
Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Am J Reprod Immunol 49:297-307. 2003..5 depends on endogenous rate of loss, and appears to depend on microbial flora. Is cytokine-triggered abortion dependent upon a third signaling pathway that senses 'danger'?.. - Placental trophoblast from successful human pregnancies expresses the tolerance signaling molecule, CD200 (OX-2)David A Clark
Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Am J Reprod Immunol 50:187-95. 2003..Abortions could be prevented by administration of a soluble CD200. Is CD200 expressed on trophoblast in successful human pregnancy?.. - Immunological factors in pregnancy wastage: fact or fictionDavid A Clark
Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Am J Reprod Immunol 59:277-300. 2008..In order to select patients most likely to benefit from known treatments, more extensive immunological testing is required. It is also important to determine the karyotype of all failing embryos... - Shall we properly re-examine the status of allogeneic lymphocyte therapy for recurrent early pregnancy failure?David A Clark
Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Am J Reprod Immunol 51:7-15. 2004..How to evaluate immunological therapy advocated for recurrent spontaneous abortion and implantation failure. I was invited to comment on the opinion article of Chaouat (AJRI December 2003)... - The power of observationDavid A Clark
Departments of Medicine, Molecular Medicine and Pathology, and Ob Gyn, McMaster University, 1200 Main Street West, Hamilton, ON, Canada
Am J Reprod Immunol 66:71-5. 2011..In the golden age of evidence-based medicine, how should one view the cohort-controlled study of IVIG + anti-TNF-α (Humira) in recurrent in vitro fertilization (IVF) failure patients with an elevated Th1/Th2 cytokine production ratio... 
Introduction to special issue on implantationDavid A Clark
Department of Medicine, McMaster University, Hamilton, Ontario, Canada
J Assist Reprod Genet 24:282-3. 2007- CD200-dependent and nonCD200-dependent pathways of NK cell suppression by human IVIGDavid A Clark
Department of Medicine, McMaster University, 1200 Main St West, Hamilton, ON L8N 3Z5, Canada
J Assist Reprod Genet 25:67-72. 2008..CD200 acts by binding to CD200 receptors (C200R). The objective of this study was to determine if CD200-dependent NK suppression by IVIG involved direct binding of IVIG-associated CD200 molecules to CD200R on NK cells... - Reduced uterine indoleamine 2,3-dioxygenase versus increased Th1/Th2 cytokine ratios as a basis for occult and clinical pregnancy failure in mice and humansDavid A Clark
Biomedical Research Center, Charite, University Medicine of Berlin, Berlin, Germany
Am J Reprod Immunol 54:203-16. 2005..Could stress act by reducing IDO expression?.. - Is intravenous immunoglobulins (IVIG) efficacious in early pregnancy failure? A critical review and meta-analysis for patients who fail in vitro fertilization and embryo transfer (IVF)David A Clark
Department of Medicine, McMaster University, Hamilton, Ontario, Canada
J Assist Reprod Genet 23:1-13. 2006..Systematic reviews generating inconclusive results have focused on methodological rigor to the exclusion of biological plausibility... - Tolerance signaling moleculesDavid A Clark
McMaster University, Hamilton, Ont, Canada
Chem Immunol Allergy 89:36-48. 2005..This chapter will critically review current data concerning the mechanisms and relevance of the various proposed mechanisms... - Loss of surface CD200 on stored allogeneic leukocytes may impair anti-abortive effect in vivoDavid A Clark
Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Am J Reprod Immunol 53:13-20. 2005..The mechanism and generality of the phenomenon has not been elucidated... - Procoagulants in fetus rejection: the role of the OX-2 (CD200) tolerance signalD A Clark
Departments of Medicine, Molecular Medicine and Pathology, Obstetrics and Gynecology, Mucosal Immunology Group, Immunology and Inflammation Program, McMaster University, Rm 3V39, 1200 Main Street West, Hamilton, Ontario, L8N 3Z5, Canada
Semin Immunol 13:255-63. 2001..Similarities and differences between findings in the mouse and human, and the potential evolutionary significance of mechanisms affecting reproductive success are reviewed... - Fgl2 prothrombinase expression in mouse trophoblast and decidua triggers abortion but may be countered by OX-2D A Clark
Department of Medicine, Pathology and Molecular Medicine, and Department of Obstetrics and Gynecology, McMaster University, 1200 Main St West, Room 3V39, Hamilton, Ontario, Canada L8N 3Z5
Mol Hum Reprod 7:185-94. 2001..Fgl2 prothrombinase may provide a mechanism explaining pregnancy loss, and conversely, successful pregnancy may be due in part to OX-2-dependent activation of maternal tolerance mechanisms at the feto-maternal interface... - Activation of the novel prothrombinase, fg12, as a basis for the pregnancy complications spontaneous abortion and pre-eclampsiaM Knackstedt
Toronto General Hospital Research Institute, University of Toronto, Ontario, Canada
Am J Reprod Immunol 46:196-210. 2001..CONCLUSIONS: Activation of fg12 prothrombinase by Th1-type cytokines in pregnancy may lead to spontaneous abortion, or in ongoing pregnancy, to pre-eclampsia and/or IUGR... - Defining the roles of perforin, Fas/FasL, and tumour necrosis factor alpha in T cell induced mucosal damage in the mouse intestineM Merger
Intestinal Disease Research Program, McMaster University, Hamilton, Ontario L8N 3Z5, Canada
Gut 51:155-63. 2002..The redundancy of the mechanisms of tissue damage will have significant impact on therapeutic strategies aimed at specific and targeted inhibition of inflammatory processes... - Cytokine-dependent abortion in CBA x DBA/2 mice is mediated by the procoagulant fgl2 prothrombinase [correction of prothombinase]D A Clark
McMaster University, Hamilton, Ontario, Canada
J Immunol 160:545-9. 1998..Cytokine-triggered thrombotic/inflammatory processes in maternal uteroplacental blood vessels causes abortion... - Regulation of gene expression of murine MD-1 regulates subsequent T cell activation and cytokine productionR M Gorczynski
Medical Research Council Group on Organ Injury, Transplant Research Division, The Toronto Hospital, Toronto, Canada
J Immunol 165:1925-32. 2000..MD-1 is linked to CD14, a "danger receptor complex," and activation of this complex can regulate cell surface expression of CD80/CD86, which signal T cells... - Unexplained sporadic and recurrent miscarrage in the new millennium: a critical analysis of immune mechanisms and treatmentsD A Clark
Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Hum Reprod Update 7:501-11. 2001.... - Stress triggered abortions are associated with alterations of granulated cells into the deciduaU R Markert
McMaster University, Hamilton, Ontario, Canada
Am J Reprod Immunol 37:94-100. 1997..Substance P release by nerves in endometrium/decidua has been found to be the key neurotransmitter in this pathway. It is still unclear which cells are stimulated by substance P to produce the increased TNF-alpha level... - Th1 cytokines and the prothrombinase fgl2 in stress-triggered and inflammatory abortionM K Knackstedt
Department of Internal Medicine, Charit, Charit, Humboldt University, Berlin, Germany
Am J Reprod Immunol 49:210-20. 2003..A physiological cascade associated with up-regulation of TNF-alpha, and an IL-12-triggered cascade characterized by persistent up-regulation of TNF-alpha and IFN-gamma as well as a persistent increase in fgl2... - Decidua-associated suppressor cells in abortion-prone DBA/2-mated CBA/J mice that release bioactive transforming growth factor beta2-related immunosuppressive molecules express a bone marrow-derived natural suppressor cell marker and gamma delta T-cell reD A Clark
Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Biol Reprod 56:1351-60. 1997.... - The same immunoregulatory molecules contribute to successful pregnancy and transplantationReginald M Gorczynski
Transplant Research Division, The Toronto Hospital, Ontario, Canada
Am J Reprod Immunol 48:18-26. 2002.... - Critical analysis of intravenous immunoglobulin therapy for recurrent miscarriageS Daya
Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada
Hum Reprod Update 5:475-82. 1999..The collective evidence thus far indicates that IVIG does not have a therapeutic effect that is clinically meaningful... - A novel suppressor cell develops in uterine decidua in response to fetal trophoblast-type cellsR M Slapsys
Molecular Virology and Immunology Program, McMaster University, Hamilton, Ontario, Canada
Reg Immunol 1:182-9. 1988..Possible mechanisms of this induction and the importance of trophoblast-decidual interaction in generating localized immunosuppressive buffer zone (chemical barrier) about the implanted conceptus are discussed... - The prothrombinase activity of FGL2 contributes to the pathogenesis of experimental arthritisM C Melnyk
Multi Organ Transplant Program, University of Toronto and Toronto General Hospital, Toronto, ON, Canada
Scand J Rheumatol 40:269-78. 2011..We hypothesized that expression of mFGL2 in inflamed synovium contributes to the fibrin deposition and subsequent inflammation in arthritis... - LPS-induced murine abortions require C5 but not C3, and are prevented by upregulating expression of the CD200 tolerance signaling moleculeGary Yu
Toronto General Research Institute and CIHR Group on Cellular and Molecular Mechanisms of Organ Injury, Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada
Am J Reprod Immunol 60:135-40. 2008..CD200Fc can prevent abortions in the CBA x DBA/2 model, but an action through Fc could not be excluded... - LPS-induced occult loss in mice requires FGL2Katharina Foerster
Toronto General Research Institute and CIHR Group on Cellular and Molecular Mechanisms of Organ Injury, Toronto Hospital, Toronto, ON, Canada
Am J Reprod Immunol 58:524-9. 2007..However, the frequency of such losses appears to vary among breeding periods and between laboratories... - Cytokine-induced hepatic apoptosis is dependent on FGL2/fibroleukin: the role of Sp1/Sp3 and STAT1/PU.1 composite cis elementsMingfeng Liu
Multi Organ Transplant Program, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
J Immunol 176:7028-38. 2006..Overall, this study demonstrates that IFN-gamma and TNF-alpha induce hepatocyte apoptosis in vivo, which is dependent on induction of fgl2, and defines the molecular basis of transcription of fgl2 in vitro... - Ecology of danger-dependent cytokine-boosted spontaneous abortion in the CBA x DBA/2 mouse model. I. Synergistic effect of LPS and (TNF-alpha + IFN-gamma) on pregnancy lossDavid A Clark
Department of Medicine, McMaster University, 1200 Main Street West, Room 3V39, Hamilton, Ontario, Canada L8N 3Z5
Am J Reprod Immunol 52:370-8. 2004..Increased rates of loss triggered by cytokines later in pregnancy may depend on increased absorption of LPS from intestinal flora... - Thinking outside the box: mechanisms of environmental selective pressures on the outcome of the materno-fetal relationshipDavid A Clark
Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Am J Reprod Immunol 47:275-82. 2002..Furthermore, there is a poor correlation between Th1/Th2.3 cytokine ratios and abortion rates. Could there be a third factor involved, and if so, what might this mean?.. - The FGL2-FcgammaRIIB pathway: a novel mechanism leading to immunosuppressionHao Liu
Multi Organ Transplant Program, Toronto General Research Institute, University Health Network, University of Toronto, Toronto, ON, Canada
Eur J Immunol 38:3114-26. 2008..The identification of specific receptor binding has important implications for the pathogenesis of immune-mediated disease and suggests a potential for targeted FGL2 therapy... - Decline in number of elevated blood CD3(+) CD56(+) NKT cells in response to intravenous immunoglobulin treatment correlates with successful pregnancyMarianne J van den Heuvel
Department of Pediatrics, University of Western Ontario, London, ON, Canada
Am J Reprod Immunol 58:447-59. 2007..In mouse models of pregnant failure, NKT cells appear to be important. However, a mouse model may only be pertinent to a subset of patients, as recurrent pregnancy failure is a heterogenous group... - Is there any evidence for immunologically mediated or immunologically modifiable early pregnancy failure?David A Clark
Department of Medicine, 3V39 McMaster Universitty Medical Center, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5
J Assist Reprod Genet 20:63-72. 2003..Genetic abnormalities can explain much of the wastage, but can it explain all of the failures? As embryos bear paternal and embryonic antigens foreign to the maternal immune system, could some otherwise normal embryos be "rejected"?.. - The novel CD4+CD25+ regulatory T cell effector molecule fibrinogen-like protein 2 contributes to the outcome of murine fulminant viral hepatitisItay Shalev
Multi Organ Transplant Program, University of Toronto, Toronto, Ontario, Canada
Hepatology 49:387-97. 2009..The results further suggest that targeting FGL2 may lead to the development of novel treatment approaches for acute viral hepatitis infection... - Transforming growth factor-beta (TGF-beta)D A Clark
Department of Medicine, Pathology, Obstetrics and Gynecology, McMaster University, Hamilton, Ont, Canada
Int J Biochem Cell Biol 30:293-8. 1998..The role of TGF-beta in homeostatic and pathogenic processes suggests numerous applications in the diagnosis and treatment of various diseases characterised by inflammation and fibrosis... - Human ovarian carcinoma: evidence for patient-related differences in susceptibility to cytotoxic effectors that attack different cellular subpopulations within a tumourD A Clark
Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Br J Cancer 58:415-8. 1988..Apparent heterogeneity between patients and stem cell susceptibility to effector cells may be important determinants of the efficacy of treatment of patients with biologic response modifiers such as interferon and interleukin 2... - The Fgl2/fibroleukin prothrombinase contributes to immunologically mediated thrombosis in experimental and human viral hepatitisPhilip A Marsden
CIHR Group on Cellular and Molecular Mechanisms of Organ Injury, Toronto, Ontario, Canada
J Clin Invest 112:58-66. 2003..Fibrin deposition was strongly associated with Fgl2/fibroleukin expression. Collectively, these data indicate a critical role for Fgl2/fibroleukin in the pathophysiology of experimental and human viral hepatitis... - Transfusion-related immunomodulation due to peripheral blood dendritic cells expressing the CD200 tolerance signaling molecule and alloantigenDavid A Clark
Department of Medicine, Immunology and Inflammation Program, McMaster University, Hamilton, Ontario, Canada
Transfusion 48:814-21. 2008.... - Fgl2 deficiency causes neonatal death and cardiac dysfunction during embryonic and postnatal development in miceJunwu Mu
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
Physiol Genomics 31:53-62. 2007.... - Characterization of murine pregnancy decidua transforming growth factor beta. I. Transforming growth factor beta 2-like molecules of unusual molecular size released in bioactive formD A Clark
Molecular Virology Immunology Program, McMaster University, Hamilton, Ontario, Canada
Biol Reprod 52:1380-8. 1995..abstract truncated at 250 words).. - Targeted deletion of fgl2 leads to impaired regulatory T cell activity and development of autoimmune glomerulonephritisItay Shalev
Multi Organ Transplant Program, Department of Immunology, University of Toronto, Ontario, Canada
J Immunol 180:249-60. 2008..Collectively, these data suggest that FGL2 contributes to Treg cell activity and inhibits the development of autoimmune disease... - CD56+ cells are recruited to the uterus in two waves: at ovulation and during the first 2 weeks after missed mensesMarianne J van den Heuvel
Department of Pediatrics, Children s Health Research Institute, University of Western Ontario, London, ON, Canada
Am J Reprod Immunol 59:90-8. 2008..To support a hypothesis that precursors of uNK cells are recruited from blood, adhesive function of blood CD56+ subsets were assessed during one cycle and during pregnancy... - Structural and functional heterogeneity in the CD200R family of immunoregulatory molecules and their expression at the feto-maternal interfaceReginald M Gorczynski
Transplant Research Division, The Toronto Hospital, Ontario, Canada
Am J Reprod Immunol 52:147-63. 2004..CD200 is expressed on a subpopulation of uterine decidua cells and on trophoblast, both in the mouse and human. The receptor(s) for CD200, CD200R(s), was not previously well-characterized... - Kinetic analysis of a unique direct prothrombinase, fgl2, and identification of a serine residue critical for the prothrombinase activityCamie W Y Chan
Multi Organ Transplant Program, Toronto General Hospital and University of Toronto, 621 University Avenue 10th Floor, Room 116, Toronto, Ontario M5G 2C4, Canada
J Immunol 168:5170-7. 2002..In this work we provide direct evidence that fgl2 cleaves prothrombin to thrombin consistent with serine protease activity and requires calcium, phospholipids, and factor Va for its full activity... - Assessing human alloimmunization as a strategy for inducing HIV type 1 neutralizing anti-HLA responsesJonathan G Leith
Department of Immunology, University of Toronto, Toronto, Canada
AIDS Res Hum Retroviruses 19:957-65. 2003.... - Gene transcription of fgl2 in endothelial cells is controlled by Ets-1 and Oct-1 and requires the presence of both Sp1 and Sp3Mingfeng Liu
Multi Organ Transplant Program, Toronto General Hospital and the University of Toronto, Canada
Eur J Biochem 270:2274-86. 2003.... - Fine needle aspiration cytology of a primary amyloid tumor of the breastIbrahim M Zardawi
Acta Cytol 48:286-8. 2004 - The Ronald McDonald House as an alternative to antepartum hospitalizationScott C Dexter
Department of Obstetrics and Gynecology, Albany Medical College, Albany, NY, USA
J Perinatol 24:623-5. 2004..CONCLUSIONS: Outpatient management at the RMH is a cost-effective alternative for selected high-risk pregnancies. No adverse outcomes in the study population were attributable to the utilization of the RMH... - ANCA-positive vasculitis of the breastIbrahim M Zardawi
Pathology 36:370-3. 2004 - Recognizing the clinical features of Trisomy 13 syndromeAngel Rios
Department of Pediatrics, The Children's Hospital at Albany Medical Center, Albany, NY 12208, USA
Adv Neonatal Care 4:332-43. 2004..The diagnosis of Trisomy 13 is confirmed antenatally or after delivery with genetic testing. Prognosis of infants with Trisomy 13 and implications for the infants development are described... - Combined donor leucocyte administration and immunosuppressive drug treatment for survival of rat heart allograftsMarcel den Dulk
AW Morrow Liver Immunobiology Laboratory, Centenary Institute of Cancer Medicine and Cell Biology, Royal Prince Alfred Hospital, Locked Bag #6, Newtown, Sydney NSW 2042, Australia
Transpl Immunol 13:177-84. 2004..Early and extensive inhibition of rejection by MTX was less effective than delayed and partial inhibition of the response by CsA for induction of transplant tolerance... - Tolerance signaling molecules and pregnancy: IDO, galectins, and the renaissance of regulatory T cellsPeter Terness
Institute of Immunology, University of Heidelberg, Heidelberg, Germany
Am J Reprod Immunol 58:238-54. 2007..Is the concept of maternal tolerance preventing rejection of the semi-allogeneic 'fetal allograft' still valid?..