Introduction: Canine diabetes mellitus (CDM) is a relatively common endocrine disease in dogs. Many CDM clinical features resemble human type 1 diabetes mellitus (T1DM), but lack of autoimmune biomarkers makes calling the disease autoimmune controversial. Autoimmune biomarkers linking CDM and T1DM would create an alternative model for drug development impacting both human and canine disease.
View Article and Find Full Text PDFPlantar taping has been used in clinical settings as a short-term conservative treatment for plantar heel pain and related pathologies. The rise of at-home taping methods may offer patients more independence, but effectiveness has not been established. The purpose of this study was to evaluate the effects of plantar taping on foot mechanics during gait.
View Article and Find Full Text PDFTreating MS has been difficult. One successful drug is Ocrelizumab (anti-CD20), used for the chronic relapsing MS (RMS) and the progressive MS (PMS) forms. TH40 cells are pathogenic effector T cells that increase in percentage and numbers during chronic inflammation.
View Article and Find Full Text PDFJ Clin Endocrinol Metab
September 2019
Context: The incidence of type 1 diabetes (T1D) is increasing worldwide. The quest to understand T1D etiology and how to predict diabetes is ongoing; and, in many ways, those goals intertwine. Although genetic components associate with T1D, not all individuals with T1D have those components, and T1D does not develop in all subjects with those components.
View Article and Find Full Text PDFCD40 plays a critical role in the pathogenesis of type 1 diabetes (T1D). The mechanism of action, however, is undetermined, probably because CD40 expression has been grossly underestimated. CD40 is expressed on numerous cell types that now include T cells and pancreatic β cells.
View Article and Find Full Text PDFCD40-CD154 interaction is critically involved in autoimmune diseases, and CD4 T cells play a dominant role in the Experimental Autoimmune Encephalomyelitis (EAE) model of Multiple Sclerosis (MS). CD4 T cells expressing CD40 (Th40) are pathogenic in type I diabetes but have not been evaluated in EAE. We demonstrate here that Th40 cells drive a rapid, more severe EAE disease course than conventional CD4 T cells.
View Article and Find Full Text PDFAims/hypothesis: The CD40-CD154 interaction directs autoimmune inflammation. Therefore, a long-standing goal in the treatment of autoimmune disease has been to control the formation of that interaction and thereby prevent destructive inflammation. Antibodies blocking CD154 are successful in mouse models of autoimmune disease but, while promising when used in humans, unfortunate thrombotic events have occurred, forcing the termination of those studies.
View Article and Find Full Text PDFMultiple Sclerosis (MS) is a chronic inflammatory, neurodegenerative disease. Diagnosis is very difficult requiring defined symptoms and multiple CNS imaging. A complicating issue is that almost all symptoms are not disease specific for MS.
View Article and Find Full Text PDFThis is the first study to examine how both structural and functional components of individuals' social networks may moderate the association between biological sex and experimental pain sensitivity. One hundred and fifty-two healthy adults (mean age = 22yrs., 53% males) were measured for cold pressor task (CPT) pain sensitivity (i.
View Article and Find Full Text PDFThe BDC2.5 T cell clone is highly diabetogenic, but the transgenic mouse generated from that clone is surprisingly slow in diabetes development. Although defining pathogenic effector T cells in autoimmunity has been inconsistent, CD4(+) cells expressing the CD40 receptor (Th40 cells) are highly diabetogenic in NOD mice, and NOD.
View Article and Find Full Text PDFBiomarkers defining pathogenic effector T (Teff) cells slowly have been forthcoming and towards this we identified CD4(+) T cells that express CD40 (CD4(+) CD40(+) ) as pathogenic in the NOD type 1 diabetes (T1D) model. CD4(+) CD40(+) T cells rapidly and efficiently transfer T1D to NOD.scid recipients.
View Article and Find Full Text PDFAlthough regulatory T cells (Tregs) are well described, identifying autoaggressive effector T cells has proven more difficult. However, we identified CD4loCD40+ (Th40) cells as being necessary and sufficient for diabetes in the NOD mouse model. Importantly, these cells are present in pancreata of prediabetic and diabetic NOD mice, and Th40 cells but not CD4+CD40(-) T cells transfer progressive insulitis and diabetes to NOD.
View Article and Find Full Text PDFUnderstanding cytokine profiles of disease states has provided researchers with great insight into immunologic signaling associated with disease onset and progression, affording opportunities for advancement in diagnostics and therapeutic intervention. Multiparameter flow cytometric assays support identification of specific cytokine secreting subpopulations. Bead-based assays provide simultaneous measurement for the production of ever-growing numbers of cytokines.
View Article and Find Full Text PDFHuman T1D pancreatic lymph nodes contain diabetes-autoantigen responsive T cells but identification of such T cells in the periphery has proven difficult. Here we describe a unique T cell subset defined by CD4(lo) and CD40 expression (T(CD40)) that is significantly expanded in peripheral blood of T1D but not control or T2D subjects. The HLA-DR3 and DR4 alleles are considered high risk factors for T1D and T(CD40) expansion occurs in T1D subjects carrying HLA DR3 or DR4 haplotypes but, T1D subjects who do not carry either DR3 or DR4 haplotypes still have an expanded percentage of T(CD40) cells.
View Article and Find Full Text PDFThe generation of auto-aggressive T cells involves failure of central or peripheral tolerance. We previously demonstrated that peripheral CD4(lo)CD40(+) T cells give rise to pathogenic T cells in the non-obese diabetic (NOD) model. Here we show that peripheral CD4(+)CD40(+) T cells from diabetic or pre-diabetic NOD mice induce insulin-dependent diabetes mellitus.
View Article and Find Full Text PDFIn this report we studied coupling of M(2) and M(4) muscarinic acetylcholine receptors to activation of endothelial nitric oxide synthase (eNOS). Chinese hamster ovary cells that co-express the individual receptor subtypes and eNOS in a stable fashion were used as a model. Activation of eNOS was assayed by measuring increasing levels of cyclic GMP in admixed cells that contain guanylate cyclase.
View Article and Find Full Text PDFThe mass attenuation coefficients, mu/rho, for Clear-Pb for photon energies ranging from 10 keV to 10 MeV were determined using Monte Carlo methods and simple equations used to manipulate elemental mass attenuation coefficients. It was determined that the effectiveness of Clear-Pb as a radiation shielding material was greater than plain acrylic for all photon energies, especially those less than 150 keV, and for deep penetration problems where the differences in mu/rho between Clear-Pb and acrylic became more significant. Finally, the usefulness of Clear-Pb as a shielding material when compared with acrylic was determined for the following commonly used radionuclides: 125I, 103Pd, 99mTc, 192Ir, 137Cs, and 60Co.
View Article and Find Full Text PDFThis study examined the relationship between three instruments used in measuring tympanic, axillary, and rectal temperatures in infants less than 1 year of age. Temperatures were measured by Oto-temp Pedi Q tympanic thermometers, Becton Dickinson axillary thermometer, and rectal thermometers. A convenience sample of 5 infants less than 90 day and 54 greater than 90 days with fever, as well as 34 infants less than 90 days and 27 infants greater than 90 days without fever were studied.
View Article and Find Full Text PDFBasic dosimetric parameters as recommended by the AAPM Task Group No. 43 (TG-43) have been determined for recently available IoGold 125I brachytherapy seeds. Monte Carlo methods (MCNP) were used in the calculation of these parameters in water, and results compared with soon to be published experimental parameters also for 125I IoGold seeds as well with parameters for model 6702 and 6711 125I seeds.
View Article and Find Full Text PDFThe different retinal cell types arise during vertebrate development from a common pool of progenitor cells. The mechanisms responsible for determining the fate of individual retinal cells are, as yet, poorly understood. Ganglion cells are one of the first cell types to be produced in the developing vertebrate retina and few ganglion cells are produced late in development.
View Article and Find Full Text PDFClinical observations have revealed that diode readings from 15 MV photon beams with small field sizes and small SSD values were consistently 5%-10% higher than doses calculated at the maximum depth. Dose at depth depends on the collimator scattering factor and the phantom scattering factor--both field size dependent. Diodes are placed on the skin surface, and therefore the phantom scatter factor is different than at depth.
View Article and Find Full Text PDFLoss of the wild-type p53 activity and/or overexpression of the proto-oncogene bcl-2 are frequently detected in breast cancer and suggested to be related to chemotherapy and radiation therapy resistance. To identify the downstream signaling molecules for anti-proliferative and apoptotic activities of p53 and to investigate the interaction of bcl-2 with p53 in human breast epithelial cells, we have used the MCF10A cell line. We previously showed that overexpression of bcl-2 downregulates expression of p21(WAF1/CIP1) (a cyclin dependent kinase inhibitor which mediates p53 dependent G(1) arrest) and suppresses DNA damage-induced apoptosis in MCF10A cells.
View Article and Find Full Text PDFThe aim of this study is to gain insight into the time during the life history of a retinal neuron that it becomes committed to a particular phenotype. At this point, it is not possible to identify the time of commitment, but the time that differentiation begins can be identified. Bromodeoxyuridine labeling coupled with immunohistochemistry with a ganglion cell-specific antibody was used to fix the time of the beginning of ganglion cell differentiation relative to the time of mitosis in the developing chick retina.
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