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Mikael Pihl, Hugo Barcenilla, Stina Axelsson, Mikael Chéramy, Linda Åkerman, Ingela Johansson, Johnny Ludvigsson, Rosaura Casas
Administration of Glutamic Acid Decarboxylase (GAD)65 formulated in aluminium hydroxide preserved insulin secretion in a phase II trial in recent onset Type 1 Diabetes. A subsequent European phase III trial was closed at 15months after failing to reach primary endpoint, but the majority of the Swedish patients completed the 21months follow-up. We studied the frequencies and phenotype of T cells, suppressive capacity of Tregs, GAD65-induced proliferation, and frequencies of T cells with a GAD65-specific TCR in Swedes participating in the trial...
January 26, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Maren Engelhardt, Graziella di Cristo, Jochen Grabert, Silke Patz, Lamberto Maffei, Nicoletta Berardi, Petra Wahle
Minipump infusions into visual cortex in vivo at the onset of the critical period have revealed that the proinflammatory cytokine leukemia inhibitory factor (LIF) delays the maturation of thalamocortical projection neurons of the lateral geniculate nucleus, and tecto-thalamic projection neurons of the superior colliculus, and cortical layer IV spiny stellates and layer VI pyramidal neurons. Here, we report that P12-20 LIF infusion inhibits somatic maturation of pyramidal neurons and of all interneuron types in vivo...
January 11, 2017: Molecular and Cellular Neurosciences
Tamara Vorobjova, Helerin Raikkerus, Lumme Kadaja, Ija Talja, Oivi Uibo, Kaire Heilman, Raivo Uibo
BACKGROUND: Impaired intestinal integrity, including increased permeability of the small bowel mucosa, has been shown in patients with celiac disease (CD) as well as with type 1 diabetes (T1D). Zonulin (ZO, pre-haptoglobin), a tight junction regulator, plays a particular role in the regulation of intestinal barrier function and in the pathogenesis of the above-mentioned diseases. AIM: To investigate whether enteroviruses (EVs) and immunoregulatory cells are associated with intestinal permeability in patients with CD alone and with coexistent T1D...
December 19, 2016: Digestive Diseases and Sciences
María Lola Evia-Viscarra, Rodolfo Guardado-Mendoza, Edel Rafael Rodea-Montero
BACKGROUND: Current classification of diabetes mellitus (DM) is based on etiology and includes type 1 (T1DM), type 2 (T2DM), gestational, and other. Clinical and pathophysiological characteristics of T1DM and T2DM in the same patient have been designated as type 1.5 DM (T1.5DM). OBJECTIVES: The aim of this study was to classify pediatric patients with DM based on pancreatic autoimmunity and the presence or absence of overweight/obesity, and to compare the clinical, anthropometric, and biochemical characteristics between children in the different classes of DM...
2016: PloS One
Klára Dáňová, Anna Grohová, Pavla Strnadová, David P Funda, Zdeněk Šumník, Jan Lebl, Ondřej Cinek, Štěpánka Průhová, Stanislava Koloušková, Barbora Obermannová, Lenka Petruželková, Anna Šedivá, Petra Fundová, Karsten Buschard, Radek Špíšek, Lenka Palová-Jelínková
Tolerogenic dendritic cells (tolDCs) may offer an interesting intervention strategy to re-establish Ag-specific tolerance in autoimmune diseases, including type 1 diabetes (T1D). T1D results from selective destruction of insulin-producing β cells leading to hyperglycemia that, in turn, specifically affects a patient's immune system. In this study, we prepared monocyte-derived tolDCs modulated by dexamethasone and vitamin D2 from 31 T1D patients with optimal glycemic control and 60 T1D patients with suboptimal glycemic control and assessed their tolerogenic properties in correlation with metabolic state of patients...
December 7, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Steffen U Thorsen, Christian B Pipper, Henrik B Mortensen, Flemming Pociot, Jesper Johannesen, Jannet Svensson
Aims. A new perspective on autoantibodies as pivotal players in the pathogenesis of type 1 diabetes (T1D) has recently emerged. Our key objective was to examine whether increased levels of autoantibodies against the β-cell autoantigens glutamic acid decarboxylase (isoform 65) (GADA) and insulinoma associated antigen-2A (IA-2A) mirrored the 3.4% annual increase in incidence of T1D. Methods. From the Danish Childhood Diabetes Register, we randomly selected 500 patients and 500 siblings for GADA and IA-2A analysis (1997 through 2005)...
2016: International Journal of Endocrinology
Mariana Urrutia, Sebastián Fernández, Marisol González, Rodrigo Vilches, Pablo Rojas, Manuel Vásquez, Mónica Kurte, Ana María Vega-Letter, Flavio Carrión, Fernando Figueroa, Patricio Rojas, Carlos Irarrázabal, Rodrigo A Fuentealba
The neurotransmitter GABA has been recently identified as a potent immunosuppressive agent that targets both innate and adaptive immune systems and prevents disease progression of several autoimmunity models. Mesenchymal stem cells (MSCs) are self-renewing progenitor cells that differentiate into various cell types under specific conditions, including neurons. In addition, MSC possess strong immunosuppressive capabilities. Upon cytokine priming, undifferentiated MSC suppress T-cell proliferation via cell-to-cell contact mechanisms and the secretion of soluble factors like nitric oxide, prostaglandin E2 and IDO...
2016: PloS One
I M Talaat, A Nasr, A A Alsulaimani, H Alghamdi, K A Alswat, D M Almalki, A Abushouk, A M Saleh, G Allam
PURPOSE: Vitamin D may play a role in the pathogenesis of type 1 diabetes (T1D). The aim of the current study was to determine the possible association between 25-hydroxyvitamin D [25(OH)D] levels and circulating levels of type 1 and type 2 cytokines, as well as the pathophysiology of T1D in children. METHODS: A total of 250 T1D patients and 250 sex- and age-matched T1D-free controls were screened for 25(OH)D, hemoglobin A1c (HbA1c), type 1 and type 2 cytokines, C-reactive protein (CRP) and bone mineral metabolism, as well as antibodies against insulin, glutamic acid decarboxylase (anti-GAD 65) and islet cells...
December 2016: Journal of Endocrinological Investigation
Maki Moritani, Ichiro Yokota, Reiko Horikawa, Tatsuhiko Urakami, Aki Nishii, Tomoyuki Kawamura, Nobuyuki Kikuchi, Touru Kikuchi, Tsutomu Ogata, Shigetaka Sugihara, Shin Amemiya
BACKGROUND: Monogenic mutations, such as those in the potassium inwardly-rectifying channel, subfamily J, member 11 (KCNJ11) and insulin (INS) genes, are identified in young patients with type 1B diabetes (non-autoimmune-mediated). We recently reported the results of a test for monogenic forms of diabetes in Japanese children who were diagnosed with type 1B diabetes at <5 years of age. In this study, we tested for monogenic forms of diabetes in Japanese children aged >5 to ≤15...
September 1, 2016: Journal of Pediatric Endocrinology & Metabolism: JPEM
O Hadad-Ophir, Z Ardi, N Brande-Eilat, O Kehat, R Anunu, G Richter-Levin
The degree of behavioral control that an individual has over a stressor can critically determine its behavioral and neurochemical outcomes. Exposure to uncontrollable stress was previously shown to have detrimental effects on behavior, whereas exposure to equivalent controllable stress prevented these negative outcomes and even improved later stress coping. As many lines of evidence show, stress exposure can have maladaptive changes on inhibitory circuitry, and these effects were largely shown in the hippocampus and amygdala...
June 14, 2016: Neurobiology of Learning and Memory
Valentina Medici, Laura Rossini, Francesco Deleo, Giovanni Tringali, Laura Tassi, Francesco Cardinale, Manuela Bramerio, Marco de Curtis, Rita Garbelli, Roberto Spreafico
OBJECTIVE: Several studies have reported that inhibitory networks are altered in dysplastic tissue obtained from epilepsy surgery specimens. A consistent decrease in the number of inhibitory interneuronal subpopulation that expresses parvalbumin (PV) was reported in postsurgical tissue from patients with focal cortical dysplasia (FCD). We tested if the decrease in PV protein expression observed in epileptic tissue corresponds to a parallel impairment in the γ-aminobutyric acid (GABA)ergic compartment...
July 2016: Epilepsia
Chandra Mohan Sharma, Rajendra Kumar Pandey, Banshi Lal Kumawat, Dinesh Khandelwal, Pankaj Gandhi
Antibodies to GAD-65 have been implicated in the pathogenesis of type 1 diabetes, limbic encephalitis and Stiff person syndrome, however these diseases rarely occur concurrently. We intend to present a rare case of 35 year old female who was recently diagnosed as having type 1 diabetes presented with 1½ month history of recurrent seizures, subacute onset gait ataxia, dysathria, psychiatric disturbance and cognitive decline. No tumor was found on imaging and the classic paraneoplastic panel was negative. Cerebrospinal fluid and blood was positive for GAD-65 antibodies...
January 2016: Annals of Indian Academy of Neurology
Anna Konermann, Alpdogan Kantarci, Steven Wilbert, Thomas Van Dyke, Andreas Jäger
CNS key neurotransmitter γ-amino-butyric acid (GABA) and its signaling components are likewise detectable in non-neuronal tissues displaying inter alia immunomodulatory functions. This study aimed at identifying potential glutamate decarboxylase (GAD)65 and GABA receptor expression in periodontal ligament (PDL) cells in vivo and in vitro, with particular regard to inflammation and mechanical loading. Gene expression was analyzed in human PDL cells at rest or in response to IL-1ß (5 ng/ml) or TNFα (5 ng/ml) challenge via qRT-PCR...
November 2016: Cellular and Molecular Neurobiology
Ganesh Jevalikar, Chhavi Kohli, Beena Bansal, Sunil Kumar Mishra, Jasjeet Singh Wasir, Shweta Singh, Jasmine Kaur Ahuja, Parjeet Kaur, Khalid J Farooqui, Ambrish Mithal
OBJECTIVES: To identify proportion of various types of diabetes and differences between type 1 and type 2 diabetes in patients with youth onset diabetes (onset below 25 completed years of age). In addition, concurrent autoimmune diseases in type 1 diabetes were studied in a subset of patients. METHODS: A total of 577 patients (192 girls) with diabetes onset at median age of 14 y (range 1 mo-25 y) with median duration of 1 y (range day of diagnosis- 43 y) were included...
August 2016: Indian Journal of Pediatrics
N Bansal, C S Hampe, L Rodriguez, E O'Brian Smith, J Kushner, A Balasubramanyam, M J Redondo
AIM: To study whether DPD epitope-specific glutamate decarboxylase autoantibodies are found more frequently in children with milder forms of Type 1 diabetes. METHODS: We prospectively evaluated 75 children with new-onset autoimmune Type 1 diabetes, in whom we collected demographic, anthropometric and clinical data and measured islet autoantibodies. Glutamate decarboxylase 65 autoantibody-positive samples were analysed for epitope specificities using recombinant Fab against the DPD-defined epitope of glutamate decarboxylase 65...
January 23, 2016: Diabetic Medicine: a Journal of the British Diabetic Association
Charles A Chang, Waqas Z Haque, Gumpei Yoshimatsu, Prathab S Balajii, Michael C Lawrence, Bashoo Naziruddin
Pancreatic islet transplantation is a promising beta cell replacement treatment for patients with "brittle" type 1 diabetes (T1D) or intractable chronic pancreatitis to restore or preserve pancreatic endocrine function. Early after transplant, a significant islet mass is lost due to an innate inflammatory response, and further loss of the islet graft occurs over time due to immune response, drug toxicity, or metabolic exhaustion. Thus, clinically feasible techniques are essential to monitor islet graft function and survival to maintain appropriate therapy...
March 2016: Panminerva Medica
Susanne Fauser, Ingo Uttner, Helena Ariño, Werner A Scherbaum, Albert Saiz, Jan Lewerenz
BACKGROUND: In the pathogenesis of limbic encephalitis other promoting factors besides the pure existence of autoantibodies are increasingly discussed to play a significant role. This is to our knowledge the first described patient in whom the presence of autoantibodies precedes the manifestation of limbic encephalitis for many years. CASE PRESENTATION: At the age of 38 years, in the serum of a patient with polyendocrine autoimmunity high titers of cytoplasmic islet cell antibodies and of anti-glutamate decarboxylase (GAD) 65 antibodies were observed as an incidential finding, GAD67 antibodies were negative at that time...
2015: BMC Neurology
Christine M Ulbricht, Anthony J Rothschild, Kate L Lapane
BACKGROUND: The objectives were to characterize latent depression subtypes by symptoms, evaluate sex differences in and examine correlates of these subtypes, and examine the association between subtype and symptom remission after citalopram treatment. METHODS: Latent class analysis was applied to baseline data from 2772 participants in the Sequenced Treatment Alternatives to Relieve Depression trial. Indicators were from the Quick Inventory of Depressive Symptomatology...
December 1, 2015: Journal of Affective Disorders
Moinuddin, Nadeem A Ansari, Uzma Shahab, Safia Habeeb, Saheem Ahmad
The repertoire of known auto-antigens is limited to a very small proportion of all human proteins, and the reason why only some proteins become auto-antigens is unclear. The 65 kDa isoform of the enzyme glutamic acid decarboxylase (GAD-65) is a major auto-antigen in type I diabetes, and in various neurological diseases. Most patients with type I diabetes (70-80%) have auto-antibodies against GAD-65, which often appear years before clinical onset of the autoimmune diabetes. Thus, the aim of the study is to focus on the immunogenicity of GAD65 and its reactive oxygen species (ROS) conformer in STZ-induced diabetic rats and on human diabetic patients...
October 2015: IUBMB Life
Yoko Hanno-Iijima, Masami Tanaka, Takatoshi Iijima
Homeostatic synaptic plasticity, or synaptic scaling, is a mechanism that tunes neuronal transmission to compensate for prolonged, excessive changes in neuronal activity. Both excitatory and inhibitory neurons undergo homeostatic changes based on synaptic transmission strength, which could effectively contribute to a fine-tuning of circuit activity. However, gene regulation that underlies homeostatic synaptic plasticity in GABAergic (GABA, gamma aminobutyric) neurons is still poorly understood. The present study demonstrated activity-dependent dynamic scaling in which NMDA-R (N-methyl-D-aspartic acid receptor) activity regulated the expression of GABA synthetic enzymes: glutamic acid decarboxylase 65 and 67 (GAD65 and GAD67)...
2015: PloS One
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