Reginald Gorczynski

University of Toronto | U of T · Department of Surgery

The primary global response to the SARS-CoV-2 pandemic has been to bring to the clinic as rapidly as possible a number of vaccines that are predicted to enhance immunity to this viral infection. While the rapidity with which these vaccines have been developed and tested (at least for short-term efficacy and safety) is commendable, it should be ackn...

The evidence for the cometary origin then rapid global spread of COVID-19 through 2020 is critically reviewed. We outline why it is an alternative plausible scientific explanation to the current bat/pangolin animal jump theories. In our view this explanation is consistent with all the available temporal unfolding scientific data (genomic, immunolog...

Rapid Response to BMJ Editorial, supporting the BMJ's position re. COVID-19, concerning the selective suppression of science

We argue that the new coronavirus COVID-19 was probably linked to the arrival of a pure culture of the virus in cometary debris that was deposited in the stratosphere, and first came down in the Hubei province of China. The subsequent worldwide spread of the virus has taken place by a combination of two effects: the deposition of further large quan...

The pattern of the SARS-CoV-2 incidence concentrated in the 30-50N latitude zone suggests dust carrying the virus is spread by a circum-global jet-stream, specifically the northern subtropical jet-stream that blows in the high-altitude troposphere over northern China in early springtime. It is known that the agent of the Kawasaki disease is carried...

When analysed in patients at epicentres of outbreaks over the first three months of the 2020 pandemic, the virus responsible for COVID-19 cannot be classed as a rapidly mutating virus. It employs a haplotype-switching strategy most likely driven by APOBEC and ADAR cytosine and adenosine deamination events (C>U, A>I) at key selected sites in the ~ 3...

The origins and global spread of two recent, yet quite different, pandemic diseases is discussed and reviewed in depth: Candida auris, a eukaryotic fungal disease, and COVID-19 (SARS-CoV-2), a positive strand RNA viral respiratory disease. Both these diseases display highly distinctive patterns of sudden emergence and global spread, which are not e...

In this Chapter we discuss the various mechanisms that are available for the possible transfer of cosmic microbial living systems from one cosmic habitat to another. With the 100 or so habitable planets that are now known to exist in our galaxy alone transfers of cometary dust carrying life including fragments of icy planetoids/asteroids would be e...

Inflammation is recognized as representing a double-edged sword in terms of tumor growth, in some instances contributing to attenuation of growth and in others to enhanced progression and metastasis. Extracellular signals, released by cells within the tumor microenvironment (TME), including cancer cells themselves, as well as infiltrating immune ce...

We previously reported that CD200 overexpression in the host decreases progression and metastasis of the highly aggressive metastatic 4THM breast carcinoma. We have explored a possible synergistic interaction between the CD200 mimetic PEG-M49 and pegylated liposomal doxorubicin (Peg-Dox) in wild-type CD200 knockout (CD200-/-) and CD200 Receptor 1 k...

We review the main lines of evidence (molecular, cellular and whole organism) published since the 1970s demonstrating Lamarckian Inheritance in animals, plants and microorganisms viz. the transgenerational inheritance of environmentally-induced acquired characteristics. The studies in animals demonstrate the genetic permeability of the soma-germlin...

Functional aptamers displaying agonistic or antagonistic properties are showing great promise as modulators of immune responses. Here, we report the development of a polyethylene glycol-modified (PEGylated) DNA aptamer as a cross-species (murine and human) CD200R1 agonist that modulates inflammatory responses in vivo. Specifically, DNA aptamers wer...

Injections of a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH) reversed cytokine changes in aged mice. To investigate the role of fetal hemoglobin we derived mice with homzygous deletions for either of the two major βchains, HgbβmaKO or HgbβmiKO. Hgbβmi is the most prominent fetal Hgbβ chain, with H...

In previous studies we had reported that the immunosuppressive cell membrane bound molecule CD200 is released from the cell following cleavage by matrix metalloproteases, with the released soluble CD200 acting as an immunosuppressant following binding to, and signaling through, its cognate receptor CD200R expressed on target cells. We now show that...

We review the salient evidence consistent with or predicted by the Hoyle-Wickramasinghe (H- W) thesis of Cometary (Cosmic) Biology. Much of this physical and biological evidence is multifactorial. One particular focus are the recent studies which date the emergence of the complex retroviruses of vertebrate lines at or just before the Cambrian Explo...

Background and purposeIn BALB/c mice with transplantable breast tumors, we showed that CD200R1KO mice were cured of local and metastatic growth of EMT6 cells following surgical resection of localized tumor and immunization with irradiated cells along with CpG as adjuvant. On the other hand, wild-type (WT) animals treated in the same fashion develop...

We review the salient evidence consistent with or predicted by the Hoyle-Wickramasinghe (H- W) thesis of Cometary (Cosmic) Biology. Much of this physical and biological evidence is multifactorial. One particular focus are the recent studies which date the emergence of the complex retroviruses of vertebrate lines at or just before the Cambrian Explo...

Chronic Lymphocytic Leukemia B cells (CLL) are malignant cells which retain at least some functions of normal B cells. Paramount amongst the latter is that when such cells are appropriately stimulated, they are able to present antigens, including any potential tumor antigens, making them excellent choices as a candidate tumor vaccine. We show that...

The tumor microenvironment (TME) is critical to the longevity of tumor B cells in chronic lymphocytic leukemia (CLL). Bone marrow mesenchymal stem cells (BMMSCs) and the cytokines they produce including IL-6 are important components of the TME in CLL. We found BMMSCs supported the survival of CLL cells in vitro through an IL-6 dependent mechanism....

We previously showed that congenic bone marrow transplantation (BMTx) post myeloablation augmented tissue allograft survival in association with increased Tregs of both host and bone marrow donor origin. Regulatory B cells (Bregs) can also modulate T cell immunity and B cells may be implicated in the development of Tregs. Accordingly, we explored t...

Reginald M Gorczynski,1 Fang Zhu2 1Department of Surgical Research, University Health Network, 2Department of Surgical Research, Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada Abstract: In the ontogeny of a normal immune response, a series of checkpoints must be overcome to ensure that unwanted and/or harmful self-directe...

Background The symmetrical immune network theory, developed in 1975, is based on the existence of specific T cell factors and hypothesizes that normal IgG immune responses comprise the production of 2 kinds of antibodies, namely antigen-specific antibodies and anti-idiotypic antibodies. Objective The aim of this study was to confirm the existence...

Functional aptamers displaying agonistic or antagonistic properties are showing great promise in terms of modulating immune responses. Our group has recently developed pegylated DNA aptamers that can either block inflammatory responses (CD200R1agonist) or restore tumor-directed immune responses (PD-1 antagonist) in vivo. Here, we report the derivat...

AIM To determine the effect of overexpression of fibrinogen-like protein 2 (FGL2) on regulatory T cell (Treg) and effector T (Teff) cell function on T cell-induced colitis in Rag1-/- mice. METHODS Treg and Teff cells from fgl2-/-, fgl2+/+, and fgl2Tg mice were purified by FACS. They were studied in vitro for immunosuppressive activity and cell pro...

Phenotypic analysis of CD200-/- mice. A) Levels of sCD200 in the peripheral blood of WT mice and CD200-/- mice as assessed by ELISA. Data show mean (±SD) of 3 mice/group. B) Flow cytometric analysis of cell-surface expression of CD200 by cells in spleen, thymus, and lymph nodes in WT (n = 3) and CD200-/- (n = 6) mice. Shaded curves show tissue stai...

We present new data showing that normal IgG immune responses comprise the production of two kinds of antibodies, namely anti-foreign and anti-anti-self antibodies. For example, immunization of C3H mice by two rounds of BL/6 skin grafting results in the production of anti-BL/6 antibodies plus antiidiotypic antibodies (C3H anti-anti-C3H) with the lat...

The symmetrical immune network theory has been developed since 1975 and is based on the existence of specific T cell factors. The existence of specific T cell factors is controversial. We confirm the existence of these specific immune system components by demonstrating that a rigorous 1975 experiment by Takemori and Tada can be reproduced. We also...

Significant barriers to transplantation exist for individuals who are pre-sensitized to donor Ag and have high titres of donor-reactive Ab. We report the effect of autologous BMTx after myeloablation in pre-sensitized mice along with the use of mAbs to TNFRSF25, expressed on Tregs. C57BL/6 mice, which had been sensitized earlier with BALB/c skin al...

Expression of the nuclear receptor peroxisome proliferator activated receptor delta (PPARδ) in breast cancer cells is negatively associated with patient survival, but the underlying mechanisms are not clear. High PPARδ protein levels in rat breast adenocarcinomas were found to be associated with increased growth in soft agar and mice. Transgenic ex...

Altered interaction between CD200 and CD200R, represents an example of “checkpoint blockade” disrupting an effective, tumor-directed, host response in murine breast cancer cells. In CD200R1KO mice, long-term cure of EMT6 breast cancer, including metastatic spread to lung and liver, was achieved in BALB/c mice. The reverse was observed with 4THM tum...

CD200:CD200 receptor (CD200R) interactions lead to potent immunosuppression and inhibition of autoimmune inflammation. We investigated the effect of “knockout” of CD200 or CD200R, or over-expression of CD200, on susceptibility to dextran sodium sulfate (DSS) - induced colitis, a mouse model of inflammatory bowel disease (IBD). Acute or chronic coli...

PMA-induced CD200 shedding is reflected as a loss of CD200 expression from the surface of CLL cells. (TIF)

PMA induced CD200 shedding in B cells from healthy donor. (TIF)

Background and aim: CD200:CD200 receptor (CD200R) interactions lead to potent immunosuppression and inhibition of autoimmune inflammation. We investigated the effect of "knockout"of CD200 or CD200R, or over-expression of CD200, on susceptibility to dextran sodium sulfate (DSS)-induced colitis, a mouse model of inflammatory bowel disease (IBD). Me...

Effect of CD200 on expression of ILC related transcription factors in DSS-induced chronic colitis. mRNAs for transcription factors were analyzed in colonic tissue harvested 8 days after initiation of the third cycle of DSS-induced chronic colitis. from CD200tg, WT, CD200R1KO and CD200KO mice. Real-time RT-PCR was performed using total RNA extracted...

Effect of CD200 on expression of ILC related transcription factors in DSS-induced acute colitis. Real-time RT-PCR was performed using total RNA extracted from colonic tissue (5 samples/group) or LP cells (3 samples/group), with data normalized to the expression of GAPDH and HPRT in the same organ. Relative expression levels of ILC related transcrip...

Altered interaction between CD200 and CD200R represents an example of "checkpoint blockade" disrupting an effective, tumor-directed, host response in murine breast cancer cells. In CD200R1KO mice, long-term cure of EMT6 breast cancer, including metastatic spread to lung and liver, was achieved in BALB/c mice. The reverse was observed with 4THM tumo...

Attenuated expression of CD200 decreases local tumor growth and metastasis in immunocompetent animals. We explored the ability to cure BALB/c CD200KO or CD200R1KO mice of tumors ≤1cm3 in size by surgical resection of localized tumor, followed by immunization with irradiated EMT6 cells using Monophosphoryl Lipid A (MPLA:25υg/mouse) as adjuvant. Cont...

We have compared cure from local/metastatic tumor growth in BALB/c mice receiving EMT6 or the poorly immunogenic, highly metastatic 4THM, breast cancer cells following manipulation of immunosuppressive CD200:CD200R interactions or conventional chemotherapy. We reported previously that EMT6 tumors are cured in CD200R1KO mice following surgical resec...

Background: CD200 overexpression in transgenic recipients, or by tissue allografts, increases skin and cardiac graft survival in mice receiving rapamycin, in association with increased Foxp3(+)Treg graft infiltration. However, less than 50% of skin grafts persist beyond 25 days. We investigated whether immune ablation using busulphan and cyclophos...

CD200R1 expressed on the surface of myeloid and lymphoid cells delivers immune inhibitory signals to modulate inflammation when engaged with its ligand CD200. Signalling through CD200/CD200R1 has been implicated in a number of immune-related diseases including allergy, infection, cancer and transplantation, as well as several autoimmune disorders i...

In previous studies, we observed that regulation of expression of CD200, both on cells of a transplantable breast cancer, EMT6, and of the host, as well as of the receptor, CD200R in host mice, regulated local tumor growth and metastasis in immunocompetent animals. This in turn led to an improved ability to document immunity to EMT6 in CD200R1KO mi...

Rejection is associated with early degranulation (≥80%) of graft-infiltrating CD200R1 receptor-positive mast cells (MCs). Survival is increased, and MC degranulation is decreased, in CD200 mice but not in CD200R1KO mice. CD200 engagement of CD200R2 (not present on MCs) alters dendritic cell differentiation and enhances induction of Foxp3 regulatory...

CD200:CD200R interactions have been shown to lead to potent immunosuppression, resulting in enhanced allograft survival; reduced collagen-induced arthritis; and increased growth of leukemic, lymphoma cells and breast cancer cells. We have investigated the effect of "knockout"of CD200R, or over-expression of CD200 in transgenic mice (CD200tg), on su...

SUMMARY: Background: Omalizumab, a recombinant humanized monoclonal antibody to IgE, is recommended as a new option for the treatment of severe persistent allergic asthma .The purpose of this study is to assess the effects omalizumab treatment on life quality and its side effects in the severe persistent asthma patients. Methods: In this study, w...

Background. Allergic asthma is showed an increase in Th2-cytokine and IgE levels and an accumulation activation of Th2 cells, eosinophils and mast cells. However, recent studies focused on cell-based mechanisms for the pathogenesis of allergic asthma. Objectives. In this study, we compare the anti-IgE treatment modality in the dynamics of immune sy...

CD200 overexpression in transgenic mice increases skin, cardiac, and renal allograft survival. Elevated levels of soluble CD200 (sCD200) are found in the serum of cancer individuals. We investigated whether sCD200 levels increase in mice with prolonged graft survival. Control or CD200 BL/6 recipients of BALB/c cardiac or skin grafts received low-do...

Background: Allergic asthma is showed an increase in Th2-cytokine and IgE levels and an accumulation activation of Th2 cells, eosinophils and mast cells. However, recent studies focused on cell-based mechanisms for the pathogenesis of allergic asthma. Objectives. In this study, we compare the anti-IgE treatment modality in the dynamics of immune s...

In transgenic mice over-expressing CD200 (CD200(tg)) graft survival is associated with increased intra-graft expression of mRNAs for genes associated with altered T cell subset differentiation (Foxp3; TGFβ; IL-10). Grafts are rejected in recipients lacking the inhibitory receptor for CD200, CD200R1. We compared grafts of C57BL/6 skin taken from con...

Colorectal cancer is the third most common human cancer and the third leading cause of cancer related death. BevacizumAb is a humanized monoclonal antibody developed against vascular endothelial growth factor (VEGF) for the treatment of metastatic cancers. Our goal was to evaluate the possibility of using serum sTRAIL and IL8 as markers of treatmen...

Chronic lymphocytic leukemia (CLL) cells with aggressive clinical properties express Lipoprotein Lipase (LPL), which generates activating ligands for the nuclear receptor Peroxisome Proliferator Activated receptor (PPAR)α and allows fatty acids to be used as fuel. However, the role of PPARα in CLL is unclear. PPARα was found to be expressed by circ...

Previous studies reported that CD200 expression on cells of the transplantable EMT6 mouse breast cancer line was increased during growth in immunocompetent mice. Low levels of expression persisted in NOD-SCID.IL-2(γr-/-) mice or mice with generalized over-expression of a CD200 transgene (CD200(tg) mice), despite the faster tumor growth in both of t...

CD200 is a transmembrane molecule with an important immunoregulatory role that is overexpressed on most chronic lymphocytic leukemia (CLL) cells. In this study, we characterized a previously unknown soluble form of this molecule in human plasma termed sCD200. Levels of sCD200 were elevated in the plasma of patients with CLL as compared with healthy...

Colorectal cancer is the third most common human cancer and the third leading cause of cancer related death. BevacizumAb is a humanized monoclonal antibody developed against vascular endothelial growth factor (VEGF) for the treatment of metastatic cancers. Our goal was to evaluate the possibility of using serum sTRAIL and IL8 as markers of treatmen...

Expression of CD200 increases allograft survival by suppressing inflammation and acquired immunity. Increased allograft survival in transgenic mice overexpressing CD200 (CD200) occurs in association with increased intragraft expression of messenger RNAs (mRNAs) for genes associated with altered T-cell differentiation. We investigated whether donor...

In this study we compare the Omalizumab treatment modality in the dynamics of cell apoptosis regulating molecules in both severe persistent asthma patients who had no other any allergic disease, newly diagnosed patients with allergic asthma, and healthy volunteers. Severe persistent allergic asthma patients were subjected to measurement of serum so...

Background To evaluate the therapeutic efficacy of omalizumab and specific subcutaneous immunotherapy (SCIT) as a treatment modality in patients with more than one allergic-type condition. Methods In the first group (Group A), 2 males and 7 females with severe persistent asthma and a mean age of 34.2 years received omalizumab and SCIT. In the seco...

Background The pathogenesis of allergic asthma and other allergic conditions are believed to be closely interrelated because of the similar dynamics of allergy-inducing cells and molecules, and the independent evidence for their clinical overlap. In this study we compare the diseases and the effect of Omalizumab treatment on the dynamics of cell ap...

Background In this study, the socio-demographic characteristics, skin prick test were evaluated in treated patients diagnosed with Food allergies. Methods The study was conducted in Antalya between 10 November 2009 and 20 September 2010. A questionnaire made by the investigators taking the latest literature data into consideration were used during...

Background Allergen immunotherapy has been used in the management of allergic diseases for nearly 100 years. It is the only specific treatment for hymenoptera venom anaphylaxis. Various venom immunotherapy schedules have been designed to treat anaphylaxis. Although the effect of venom immunotherapy is well documented, there is also an increased ris...

Background The immune system changes with the age. In this study we characterized immune changes by performing immunologic screening profiles on aging individuals (graduation thesis). Methods This study was performed at Akdeniz University, in the Faculty of Medicine, Dept. of Immunology. Healthy volunteers consisted of a young group (22 donors) an...

A 50 year old male patient who was watched because of penicillin and venom allergy in the allergy unit had been admitted to the medical oncology polyclinic with cough, expectoration and hemoptysis 10 years ago. His symptoms had first begun 1 month prior to that admission, and he was then diagnosed with stage IV adeno carcinoma. The first allergic r...

CD200:CD200R interactions regulate immune responses. Since CD200Rs show extensive ho-mology in their extracellular region, generating anti-CD200R specific antibodies is a challenge. We report below on the generation of mAbs spe-cific for murine (m)R1/R2 and evidence that mR2 is expressed on the cell surface in the absence of the adaptor protein Dap...

Objective: Patients with low natural killer (NK) cell activity were shown to have a higher risk of cancer development. Increased cancer risk in rheumatoid arthritis (RA) patients treated with anti-tumor necrosis factor (anti-TNF) agents is still being debated. Therefore, we think it is important to show whether anti-TNF therapy has any effects on t...