“Professor Lechin showed through 30 years of research that the chemicals coming from the brain dramatically affect the immune system and thus cancer”

Chapter 14 therapeutic results

Prof. F. Lechin

The following paper highlights the role of lymphocytes in cancer:

Natural Killer Cells Activity and Neuroimmunological Treatment of Cancer

1. Fuad Lechin and
2. Bertha van der Dijs

1. Alex E. Lechin

We read with great interest the article by Krause et al. (1) . They report on the role played by activated natural killer cells in the treatment of colon and lung cancer patients. With respect to the above, we would like to inform readers of our experience with this issue.
In 1987, we found that neuropharmacological therapy was able to improve different types of cancer patients (2) . In addition, we showed that the clinical improvement was paralleled by an increase in the cytoxicity activity of natural killer cells against the K-562 target cells (3) . This first report was confirmed by further research published in 1989 (4) and 1990 (5) . All our patients were submitted to neuroautonomic and immunological investigations. Neuroautonomic research included the assessment of circulating neurotransmitters: noradrenaline, adrenaline, dopamine, platelet serotonin, and plasma serotonin. We showed that clinical severity correlated negatively with the noradrenaline/adrenaline ratio, which in our experience is associated with “uncoping stress” situation (6 , 7) . Conversely, clinical improvement correlated positively with the noradrenaline/adrenaline ratio. According to the above, the neuropharmacological manipulations we prescribed were addressed to enhance central noradrenergic activity (8, 9, 10) .
The above findings were also the subject of lectures in many cancer hospitals and departments (M. D. Anderson, Ohio State University, University of South Florida, Rosewell Hospital, Hospital de Buenos Aires, and others).
Up to the present, we have treated more than 2,000 advanced cancer patients, which include many types. Prostate, gastric, mammary cancer, and non-Hodgkin’s lymphoma patients were shown to obtain maximal improvement by our neuropharmacological therapy. Our long experience dealing with this issue has been summarized in our recently published book (11) .

References

Krause SW, Gastpar R, Andreesen R, et al Treatment of colon and lung cancer patients with ex vivo heat shock protein 70-peptide-activated, autologous natural killer cells: a clinical phase I trial. Clin Cancer Res 2004;10:3699-707.
Lechin F, van der Dijs B, Azocar J, et al Stress, immunology and cancer: effect of psychoactive drugs. Arch Ven Farm Clin Terap 1987;6:28-43.
Lechin F, van der Dijs B, Jakubowicz D, et al Role of stress in the exacerbation of chronic illness. Effects of clonidine administration on blood pressure, nor-epinephrine, cortisol, growth hormone and prolactin plasma levels. Psychoneuroendocrinology 1987;12:117-29.
Lechin F, van der Dijs B, Lechin S, Vitelli G, Lechin ME, Cabrera A. Neurochemical, hormonal and immunological views of stress: clinical and therapeutic implications in Crohn’s disease and cancer Velazco M eds. . Recent advances in pharmacology and therapeutics. International Congress Series 1989;volume 839:p. 57-70. Excerpta Medica Amsterdam
Lechin F, van der Dijs B, Vitelli G, et al Psychoneuroendocrinological and immunological parameters in cancer patients: involvement of stress and depression. Psychoneuroendocrinology 1990;15:435-51.
Lechin F, van der Dijs B, Lechin AE, et al Plasma neurotransmitters and cortisol in chronic illness: role of stress. J Med 1994;25:181-92.
Lechin F, van der Dijs B, Lechin M. Plasma neurotransmitters and functional illness (review). Psychother Psychosom 1996;65:293-318.
Lechin F, van der Dijs B, Orozco B, et al Plasma neurotransmitters, blood pressure and heart rate during supine-resting, orthostasis and moderate exercise stress test in healthy humans before and after parasympathetic blockade with atropine. Res Comm Biol Psychol Psychiatry 1996;21:55-72.
Lechin F, van der Dijs B, Orozco B, Jahn E, Rodriguez S, Baez S. Neuropharmacological treatment of refractory idiopathic thrombocytopenic purpura: roles of circulating catecholamines and serotonin. Thromb Haemost 2004;91:1254-6.
Lechin F, van der Dijs B, Pardey-Maldonado B, et al Enhancement of noradrenergic neural transmission: an effective therapy of myasthenia gravis. Report of 52 consecutive patients. J Med 2000;31:333-61.
Lechin F, van der Dijs B, Lechin ME. Illustrations of some therapeutic results Lechin F van der Dijs B Lechin ME eds. . Neurocircuitry and neuroautonomic disorders: reviews and strategies of therapy 2002p. 75-94. S. Karger AG Basel

In Response:

We want to thank Dr. Fuad Lechin for his comments about the impact of natural killer (NK) cells in different tumor types including prostate, gastric, mammary and non-Hodgkin lymphoma. His finding that clinical improvement correlated with an increased cytotoxicity against K562 cells, a classical NK target cell line, is of major interest and further confirmed our hypothesis that Hsp70 plasma membrane expression serves as a tumor-specific, stress-inducible recognition site for NK cells. Screening of more than 800 different tumor samples and corresponding normal tissues including lung, colorectal, stomach, pancreas, mammary, head and neck cancers, and leukemic blasts revealed that Hsp70 membrane localization was frequently detected on human tumors (50–80% of the cases) but never on normal tissues (refs. 1 and 2 ; Gabriele Multhoff, Lydia Rossbacher, Mathias Gelermann unpublished observation). Also K562 cells present Hsp70 on their plasma membrane (3) . This Hsp70 membrane expression could be further enhanced by exogenous stress induced by chemotherapy (4 , 5) . High Hsp70 levels have been found to exert dual functions: i.e., on the one hand, they mediate protection against chemotherapy-induced effects (6) ; on the other hand, they serve as a danger signal for NK cells (7) . Incubation of NK cells with the Hsp70-derived peptide “TKD” (TKDNNLLGRFELSG, amino acid 450–463), mimicking the danger signal, was able to enhance the cytolytic and migratory capacity of NK cells toward Hsp70 membrane-positive tumor cells (8) . Granzyme B could be identified as the effector protease inducing programmed cell death in Hsp70 membrane-positive tumor cells (9) . After reinfusion of ex vivo Hsp70-activated autologous NK cells in tumor patients, granzyme B serum levels were found to be elevated (10) . Furthermore, Hsp70 but neither Hsp60 nor Hsp65 antibody levels in the serum also seemed to be affected. The prognostic value of these serum parameters and the clinical efficacy of “TKD”-activated NK cells will be addressed in a multicenter clinical phase II trial in the near future.  

References

Multhoff G, Botzler C, Wiesnet M, et al A stress-inducible 72 kDa heat shock protein is expressed on the cell surface of human tumor cells but not on normal cells. Int J Cancer 1995;61:272-9.
Hantschel M, Pfister K, Jordan A, et al Hsp70 plasma membrane expression on primary tumor biopsy material and bone marrow of leukemic patients. Cell Stress Chaperones 2000;5:438-42.
Gehrmann M, Pfister K, Hutzler P, et al Effects of anti-neoplastic agents on cytoplasmic and membrane-bound Hsp70 levels. Biol Chem 2002;383:1715-25.
Gehrmann M, Brunner M, Pfister K, et al Differential up-regulation of cytosolic and membrane-bound Hsp70 in tumors by anti-inflammatory drugs. Clin Cancer Res 2004;10:3354-64.
Botzler C, Ellwart J, Günther W, et al Synergistic effects of ET-18-OCH3 on membrane expression of Hsp70 and lysis of leukemic K562 cells. Exp Hematol 1999;27:470-8.
Nylandsted J, Gyrd-Hansen M, Danielewicz A, et al Heat shock protein 70 promotes cell survival by inhibiting lysosomal membrane permeabilization. J Exp Med 2004;200:425-35.
Gastpar R, Gross C, Rossbacher L, et al Soluble Hsp70-peptide induces both, migration and cytolytic activity in

CD3-CD94+CD56+ NK cells. J Immunol 2004;172:972-80.
Multhoff G, Pfister K, Gehrmann M, et al A 14-mer Hsp70 peptide stimulates NK cell activity. Cell Stress Chaperones 2001;6:337-44.
Gross C, Koelch W, Arispe N, et al Cell surface-bound Hsp70 mediates perforin-independent apoptosis by specific binding and uptake of granzyme B. J Biol Chem 2003;17:41173-81.
Krause S, Gastpar R, Andreesen R, et al Treatment of cancer patients with autologous ex vivo Hsp70-peptide activated NK cells. A clinical phase I trial. Clin Cancer Res 2004;10:3699-707.
Conclusions: See Volume 4 pages 163 to 176 for papers published by Prof. Lasalvia-Prisco . The concluding remarks from his text book Neurocircuitry and Neuroautonomic Disorders, Karger 2002, are: ' The data and points of view presented in this book arise from the routine neurochemical and immunological investigation of more than 25,000 healthy and diseased subjects. We understand that we have the only laboratory of plasma neurotransmitters are routinely assessed both in basal and stimulated conditions. From their results we design specific neuropharmacological treatments. It is our earnest hope that other research groups will test this procedure. We are sure they will be gratified by the therapeutic results. In addition patients will also be thankful, and indeed grateful, as attested by thousands of successfully treated cases of cancer and autoimmune diseases including multiple sclerosis myositis our arm are Sjogren disease and myasthenia gravis. Dr Lechin's laboratory was not available at any hospital and exists only at high level neurochemistry research institutes.

Neuroimmunology

Neuroimmunology is a field combining neuroscience, the study of the nervous system, and immunology, the study of the immune system. Neuroimmunologists seek to better understand the interactions of these two complex systems during development, homeostasis, and response to injuries. The long-term goal vested in this new field of research is to bridge the gaps of knowledge of how and why different diseases affect people and more important, to attain pharmacological treatments that are not currently available for those who need them. Many types of interactions involve both the nervous and immune systems including but not limited to the physiological functioning of the two systems in both health and disease, malfunction of either and or both systems that leads to disorders, and the physical, chemical, and environmental stressors that affect the two systems on a daily basis.
Contents [hide]
1 Background
2 Epigenetics of neuroimmunology
2.1 Overview
2.2 Neural stem cell fate
2.3 Neurodevelopmental disorders
2.4 Neurodegenerative disorders
2.5 Neuroimmunological disorders
3 Major themes of research
4 Future directions
5 See also
6 Further reading
7 References
8 External links
[edit]Background

Neural targets that control thermogenesis, behavior, sleep, and mood can be affected by pro-inflammatory cytokines which are released by activated macrophages and monocytes during infection. Within the central nervous system production of cytokines has been detected as a result of brain injury, during viral and bacterial infections, and in neurodegenerative processes.
From the US National Institute of Health:[1]
"Despite the brain's status as an immune privileged site, an extensive bi-directional communication takes place between the nervous and the immune system in both health and disease. Immune cells and neuroimmune molecules such as cytokines, chemokines, and growth factors modulate brain function through multiple signaling pathways throughout the lifespan. Immunological, physiological and psychological stressors engage cytokines and other immune molecules as mediators of interactions with neuroendocrine, neuropeptide, and neurotransmitter systems. For example, brain cytokine levels increase following stress exposure, while treatments designed to alleviate stress reverse this effect.
"Neuroinflammation and neuroimmune activation have been shown to play a role in the etiology of a variety of neurological disorders such as stroke, Parkinson's and Alzheimer's disease, multiple sclerosis, pain, and AIDS-associated dementia. However, cytokines and chemokines also modulate CNS function in the absence of overt immunological, physiological, or psychological challenges. For example, cytokines and cytokine receptor inhibitors affect cognitive and emotional processes. Recent evidence suggests that immune molecules modulate brain systems differently across the lifespan. Cytokines and chemokines regulate neurotrophins and other molecules critical to neurodevelopmental processes, and exposure to certain neuroimmune challenges early in life affects brain development. In adults, cytokines and chemokines affect synaptic plasticity and other ongoing neural processes, which may change in aging brains. Finally, interactions of immune molecules with the hypothalamic-pituitary-gonadal system indicate that sex differences are a significant factor determining the impact of neuroimmune influences on brain function and behavior."
Recent research demonstrates that reduction of lymphocyte populations can impair cognition in mice, and that restoration of lymphocytes restores cognitive abilities. [2]
[edit]Epigenetics of neuroimmunology

[edit]Overview
Epigenetic medicine encompasses a new branch of neuroimmunology that studies the brain and behavior. This new branch has already provided unique insights into the mechanisms underlying brain development, evolution, neuronal and network plasticity and homeostasis, senescence, the etiology of diverse neurological diseases and neural regenerative processes. This new study is leading to the discovery of environmental stressors that dictate initiation of specific neurological disorders and specific disease biomarkers. The goal of this is to “promote accelerated recovery of impaired and seemingly irrevocably lost cognitive, behavioral, sensorimotor functions through epigenetic reprogramming of endogenous regional neural stem cells [3].” Understanding epigenetic medicine is important to understanding possible future pharmacological treatments. Many of the immediate gaps in knowledge are attributed to basic lack of understanding of gene expression and regulation and are thus the limiting factors for creating advanced treatments or cures to many diseases. To better understand these processes, neuroimmunological experiments are being created and tested to once and for all amass a more complete anthology of knowledge pertaining to the complex interactions between the nervous and immune systems along with that of gene expression. While some disorders may affect the nervous and immune systems independently of one another, it is impossible to truly understand neuroimmnulogical science without a complex understanding of how each system works independently and also how they work together.
[edit]Neural stem cell fate
Several studies have shown that regulation of stem cell maintenance and the subsequent fate determinations are quite complex. The complexity of determining the fate of a stem cell can be best understood by knowing the “circuitry employed to orchestrate stem cell maintenance and progressive neural fate decisions [4].” Neural fate decisions include the utilization of multiple neurotransmitter signal pathways along with the use of epigenetic regulators. The advancement of neuronal stem cell differentiation and glial fate decisions must be orchestrated timely to determine subtype specification and subsequent maturation processes including myelination [5].
[edit]Neurodevelopmental disorders
Neurodevelopmental disorders result from impairments of growth and development of the brain and nervous system and lead to many disorders. Examples of these disorders include Asperger syndrome, traumatic brain injury, communication, speech and language disorders, genetic disorders such as fragile-X syndrome, Down syndrome, epilepsy, and fetal alcohol syndrome. Studies have shown that autism spectrum disorders (ASDs) may in fact be due to basic disorders of epigenetic regulation [6]. Other neuroimmunological research has shown that deregulation of correlated epigenetic processes in ASDs can alter gene expression and brain function without causing classical genetic lesions which are more easily attributable to a cause and effect relationship [7]. These findings are some of the numerous recent discoveries in previously unknown areas of gene misexpression.
[edit]Neurodegenerative disorders
Increasing evidence suggests that neurodegenerative diseases are mediated by erroneous epigenetic mechanisms. Neurodegenerative diseases include Huntington’s disease and Alzheimer’s disease. Neuroimmunological research into these diseases has yielded evidence including the absence of simple Mendelian inheritance patterns, global transcriptional dysregulation, multiple types of pathogenic RNA alterations, and many more [8]. In one of the experiments, a treatment of Huntington’s disease with histone deacetylases (HDAC), an enzyme that removes acetyl groups from lysine, and DNA/RNA binding anthracylines that affect nucleosome positioning, showed positive effects on behavioral measures, neuroprotection, nuclesome remodeling, and associated chromatin dynamics [9]. Another new finding on neurodegenerative diseases involves the overexpression of HDAC6 suppresses the neurodegenerative phenotype associated with Alzheimer’s disease pathology in associated animal models [10]. Other findings show that additional mechanisms are responsible for the “underlying transcriptional and post-transcriptional dysregulation and complex chromatin abnormalities in Huntington’s disease [11].”
[edit]Neuroimmunological disorders
The nervous and immune systems have many interactions that dictate overall body health. The nervous system is under constant monitoring from both the adaptive and innate immune system. Throughout development and adult life, the immune system detects and responds to changes in cell identity and neural connectivity [12]. Deregulation of both adaptive and acquired immune responses, impairment of crosstalk between these two systems, as well as alterations in the deployment of innate immune mechanisms can predispose the central nervous system (CNS) to autoimmunity and neurodegeneration [13]. Other evidence has shown that development and deployment of the innate and acquired immune systems in response to stressors on functional integrity of cellular and systemic level and the evolution of autoimmunity are mediated by epigenetic mechanisms [14]. Autoimmunity has been increasingly linked to targeted deregulation of epigenetic mechanisms, and therefore, use of epigenetic therapeutic agents may help reverse complex pathogenic processes [15]. Multiple sclerosis (MS) is one type of neuroimmunological disorder that affects many people. MS features CNS inflammation, immune-mediated demyelination and neurodegeneration, and may represent an emerging class of epigenetic disorders [16].
[edit]Major themes of research

The interaction of the CNS and immune system are fairly well known. Burn-induced organ dysfunction using vagus nerve stimulation has been found to attenuate organ and serum cytokine levels. Burns generally induce abacterial cytokine generation and perhaps parasympathetic stimulation after burns would decrease cardiodepressive mediator generation. Multiple groups have produced experimental evidence that support proinflammatory cytokine production being the central element of the burn-induced stress response [17]. Still other groups have shown that vagus nerve signaling has a prominent impact on various inflammatory pathologies. These studies have laid the groundwork for inquiries that vagus nerve stimulation may influence postburn immunological responses and thus can ultimately be used to limit organ damage and failure from burn induced stress.
Basic understanding of neuroimmunological diseases has changed significantly during the last ten years. New data broadening the understanding of new treatment concepts has been obtained for a large number of neuroimmunological diseases, none more so than multiple sclerosis, since many efforts have been undertaken recently to clarify the complexity of pathomechanisms of this disease. Accumulating evidence from animal studies suggests that some aspects of depression and fatigue in MS may be linked to inflammatory markers [18].
Research into the link between smell, depressive behavior, and autoimmunity has turned up interesting findings including the facts that inflammation is common in all of the diseases analyzed, depressive symptoms appear early in the course of most diseases, smell impairment is also apparent early in the development of neurological conditions, and all of the diseases involved the amygdale and hippocampus. Better understanding of how the immune system functions and what factors contribute to responses are being heavily investigated along with the aforementioned coincidences.
[edit]Future directions

The nervous system and immune system require the appropriate degrees of cellular differentiation, organizational integrity, and neural network connectivity. These operational features of the brain and nervous system may make signaling difficult to duplicate in severely diseased scenarios. There are currently three classes of therapies that have been utilized in both animal models of disease and in human clinical trials. These three classes include DNA methylation inhibitors, HDAC inhibitors, and RNA-based approaches. DNA methylation inhibitors are used to activate previously silenced genes. HDACs are a class of enzymes that have a broad set of biochemical modifications and can affect DNA demethylation and synergy with other therapeutic agents. The final therapy includes using RNA-based approaches to enhance stability, specificity, and efficacy, especially in diseases that are caused by RNA alterations. Emerging concepts concerning the complexity and versatility of the epigenome may suggest ways to target genomewide cellular processes. Other studies suggest that eventual seminal regulator targets may be identified allowing with alterations to the massive epigenetic reprogramming during gametogenesis. Many future treatments may extend beyond being purely therapeutic and may in fact be determined to be preventative perhaps in the form of a vaccine. Newer high throughput technologies when combined with advances in imaging modalities such as in vivo optical nanotechnologies may give rise to even greater knowledge of genomic architecture, nuclear organization, and the interplay between the immune and nervous systems. [19]
[edit]See also

Immune system
Immunology
Neural top down control of physiology
Neuroimmune System
Neurology
Psychosomatic illness
[edit]Further reading

Szentivanyi A, Berczi I (2003). The Immune-Neuroendocrine Circuitry, Volume 3 : History and Progress (NeuroImmune Biology). Amsterdam: Elsevier Science. ISBN 0-444-50851-1.
(Written for the highly technical reader)
Mind-Body Medicine: An Overview, US National Institutes of Health, Center for Complementary and Alternative Medicine
Cohen N, Ader R, Felton D (2001). Psychoneuroimmunology (3rd ed.). Boston: Academic Press. ISBN 0-12-044314-7.
Visser A, Goodkin K (eds) (2000). Psychoneuroimmunology: stress, mental disorders, and health. Washington, DC: American Psychiatric Press. ISBN 0-88048-171-4.
technical.
Ransohoff RM (ed) (2002). Universes in delicate balance: chemokines and the nervous system. Amsterdam: Elsevier. ISBN 0-444-51002-8.
Sternberg EM. The Balance Within : The Science Connecting Health and Emotions. San Francisco: W. H. Freeman. ISBN 0-7167-4445-7.
(Written for the general public)
Millington G, Buckingham JC (May 1992). "Thymic peptides and neuroendocrine-immune communication". J Endocrinol. 133 (2): 163–8. doi:10.1677/joe.0.1330163. PMID 1613418.
[edit]References

^ Functional Links between the Immune System, Brain Function and Behavior
^ Kipnis J, Derecki NC, Yang C, Scrable H (October 2008). "Immunity and cognition: what do age-related dementia, HIV-dementia and 'chemo-brain' have in common?". Trends Immunol. 29 (10): 455–63. doi:10.1016/j.it.2008.07.007. PMID 18789764.
^ Abdolmaleky, H.M., Thiagalingam, S., Wilcox, M., 2005. Genetics and epigenetics in major psychiatric disorders: dilemmas, achievements, applications, and future scope. American Journal of Pharmacogenomics 5, 149–160.
^ Diamandis, P., Wildenhain, J., Clarke, I.D., Sacher, A.G., Graham, J., Bellows, D.S., Ling, E.K., Ward, R.J., Jamieson, L.G., Tyers, M., Dirks, P.B., 2007. Chemical genetics reveals a complex functional ground state of neural stem cells. Nat. Chem. Biol. 3, 268–273.
^ Shen, S., Casaccia-Bonnefil, P., 2007. Post-translational modifications of nucleosomal histones in oligodendrocyte lineage cells in development and disease. Journal of Molecular Neuroscience. 35, 13–22.
^ Herbert, M.R., Russo, J.P., Yang, S., Roohi, J., Blaxill, M., Kahler, S.G., Cremer, L., Hatchwell, E., 2006. Autism and environmental genomics. Neurotoxicology 27, 671–684.
^ Badcock, C., Crespi, B., 2006. Imbalanced genomic imprinting in brain development: an evolutionary basis for the aetiology of autism. Journal of Evolutionary Biology. 19, 1007–1032.
^ Greene, L.A., Liu, D.X., Troy, C.M., Biswas, S.C., 2007. Cell cycle molecules define a pathway required for neuron death in development and disease. Biochimica et Biophysica Acta. 1772, 392–401.
^ Abel, T., Zukin, R.S., 2008. Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders. Current Opinion in Pharmacology. 8, 57–64.
^ Pandey, U.B., Nie, Z., Batlevi, Y., McCray, B.A., Ritson, G.P., Nedelsky, N.B., Schwartz, S.L., DiProspero, N.A., Knight, M.A., Schuldiner, O., Padmanabhan, R., Hild, M., Berry, D.L., Garza, D., Hubbert, C.C., Yao, T.P., Baehrecke, E.H., Taylor, J.P., 2007. HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature 447, 859–863.
^ Ballas, N., Mandel, G., 2005. The many faces of REST oversee epigenetic programming of neuronal genes. Curr. Opin. Neurobiol. 15, 500–506.
^ Bailey, S.L., Carpentier, P.A., McMahon, E.J., Begolka, W.S., Miller, S.D., 2006. Innate and adaptive immune responses of the central nervous system. Critical Reviews in Immunology. 26, 149–188.
^ Hauser, S.L., Oksenberg, J.R., 2006. The neurobiology of multiple sclerosis: genes, inflammation, and neurodegeneration. Neuron 52, 61–76.
^ Sawalha, A.H., 2008. Epigenetics and T-cell immunity. Autoimmunity 41, 245–252.
^ Gray, S.G., Dangond, F., 2006. Rationale for the use of histone deacetylase inhibitors as a dual therapeutic modality in multiple sclerosis. Epigenetics 1, 67–75.
^ Brooks, W.H., 2005. Autoimmune disorders result from loss of epigenetic control following chromosome damage. Medical Hypotheses 64, 590–598.
^ S.L. Oke and K.J. Tracey, 2008. From CNI-1493 to the immunological homunculus: physiology of the inflammatory reflex, Journal of Leukocyte Biology 83, 512–517.
^ Gold, Stefan M, Irwin, Michael R, 2009. Depression and Immunity: Inflammation and Depressive Symptoms in Multiple Sclerosis. 29, 309.
^ Rauch, J., Knoch, T.A., Solovei, I., Teller, K., Stein, S., Buiting, K., Horsthemke, B., Langowski, J., Cremer, T., Hausmann, M., Cremer, C., 2008. Light optical precision measurements of the active and inactive Prader-Willi syndrome imprinted regions in human cell nuclei. Differentiation 76, 66–82.
[edit]External links

Neuroimmunology, The Medical School, Birmingham University - Dr Abid Karim
Neuroimmunolgy, McGill University
Online Resources Psychoneuroimmunology, Neuroimmunomodulation
Weetman AP, Pender MP, McCombe PA, Oliveira D (1995). Autoimmune neurological disease. Cambridge, UK: Cambridge University Press. ISBN 0-521-46113-8.
(6 chapters from this Cambridge UP book are freely available)]
More than 100, freely available, published research articles on neuroimmunology and related topics by Professor Michael P. Pender, Neuroimmunology Research Unit, The University of Queensland