Center for Chronic Disorders of Aging

Philadelphia, PA, United States

Center for Chronic Disorders of Aging

Philadelphia, PA, United States

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Balin B.J.,Center for Chronic Disorders of Aging | Hammond C.J.,Center for Chronic Disorders of Aging | Little C.S.,Center for Chronic Disorders of Aging | Hingley S.T.,Center for Chronic Disorders of Aging | And 4 more authors.
Advances in Alzheimer's Disease | Year: 2017

Sporadic, late-onset Alzheimer's disease (LOAD) is a progressive neurodegenerative disease that is now the most common and severe form of dementia in the elderly. That dementia is thought to be a direct result of neuronal damage and loss associated with accumulations of abnormal protein deposits in the brain. Great strides have been made in the past 20 years with regard to understanding the pathological entities that arise in the AD brain, both for familial AD (~5% of all cases) and LOAD (~95% of all cases). The neuropathology observed includes: neuritic senile plaques (NSPs), neurofibrillary tangles (NFTs), neuropil threads (NPs), and often deposits of cerebrovascular amyloid. Genetic, biochemical, and immunological analyses have provided a relatively detailed knowledge of these entities, but our understanding of the 'trigger' events leading to the biological processes resulting in this pathology and neurodegeneration remains limited. For this reason, the etiology of AD, in particular LOAD, has remained elusive. However, a number of recent and ongoing studies have implicated infection in the etiology and pathogenesis of LOAD. This review focuses specifically on infection with Chlamydophila (Chlamydia) pneumoniae in LOAD and how this infection may function as a 'trigger or initiator' in the pathogenesis of this disease. © 2017 The authors and IOS Press. All rights reserved.


Little C.S.,Center for Chronic Disorders of Aging | Joyce T.A.,Center for Chronic Disorders of Aging | Matta H.,Center for Chronic Disorders of Aging | Cahn D.,Center for Chronic Disorders of Aging | And 2 more authors.
Frontiers in Aging Neuroscience | Year: 2014

Pathology consistent with that observed in Alzheimer's disease (AD) has previously been documented following intranasal infection of normal wild-type mice with Chlamydia pneumoniae (Cpn) isolated from an AD brain (96-41). In the current study, BALB/c mice were intranasally infected with a laboratory strain of Cpn, AR-39, and brain and olfactory bulbs were obtained at 1-4 months post-infection (pi). Immunohistochemistry for amyloid beta or Cpn antigens was performed on sections from brains of infected or mock-infected mice. Chlamydia-specific immunolabeling was identified in olfactory bulb tissues and in cerebrum of AR-39 infected mice. The Cpn specific labeling was most prominent at 1 month pi and the greatest burden of amyloid deposition was noted at 2 months pi, whereas both decreased at 3 and 4 months. Viable Cpn was recovered from olfactory bulbs of 3 of 3 experimentally infected mice at 1 and 3 months pi, and in 2 of 3 mice at 4 months pi. In contrast, in cortical tissues of infected mice at 1 and 4 months pi no viable organism was obtained. At 3 months pi, only 1 of 3 mice had a measurable burden of viable Cpn from the cortical tissues. Mock-infected mice (0 of 3) had no detectable Cpn in either olfactory bulbs or cortical tissues. These data indicate that the AR-39 isolate of Cpn establishes a limited infection predominantly in the olfactory bulbs of BALB/c mice. Although infection with the laboratory strain of Cpn promotes deposition of amyloid beta, this appears to resolve following reduction of the Cpn antigen burden over time. Our data suggest that infection with the AR-39 laboratory isolate of Cpn results in a different course of amyloid beta deposition and ultimate resolution than that observed following infection with the human AD-brain Cpn isolate, 96-41. These data further support that there may be differences, possibly in virulence factors, between Cpn isolates in the generation of sustainable AD pathology. © 2014 Little, Joyce, Hammond, Matta, Appelt, Balin and Cahn.


Huang F.-M.,University of South China | Huang F.-M.,Central South University | Chen H.-C.,University of South China | Khan M.A.,University of South China | And 6 more authors.
Medical Oncology | Year: 2013

Lung cancer is a common cause of cancer-related death. The link between risk of lung cancer susceptibility and genetic polymorphisms in metabolic enzymes is well documented. In this study, the relationships between lung cancer susceptibility and polymorphisms in the phase I metabolic enzyme genes CYP1A1, CYP2D6, and CYP2A6 were investigated. Genomic DNA was isolated from the peripheral blood of 201 healthy controls and 168 lung carcinoma patients from the Han ethnic group of Hunan Province in Central South China. Polymorphisms of the investigated genes were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and two-step allelic-specific PCR assays. No significant differences were found between the frequencies in cases and controls for the genotypes wild-type (WW), heterozygous mutant, or homozygous mutant; for CYP1A1 or CYP2D6; or for the genotypes WW, heterozygous deletion, or null genotype for CYP2A6. The three-locus model (CYP2A6/CYP1A1/CYP2D6) had a maximum test sample accuracy that was significant (P < 0.001) with a cross-validation consistency of 10. These results indicated that the three-order interaction of CYP2A6, CYP1A1, and CYP2D6 polymorphisms might increase genetic susceptibility to lung cancer. We report the involvement of a three-order interaction between CYP1A1, CYP2A6, and CYP2D6 polymorphisms in lung cancer risk in people in Central South China, although no relationship between lung cancer risk and individual gene polymorphisms was found. © 2013 Springer Science+Business Media New York.


Khan M.A.,University of South China | Tania M.,University of South China | Zhang D.-Z.,University of South China | Zhang D.-Z.,Center for Chronic Disorders of Aging | Chen H.-C.,University of South China
Chinese Journal of Cancer Research | Year: 2010

Although oxidation is the most common biological and energy producing reaction, oxidative stress is harmful to cell, because the products of oxidation such as free radicals and peroxides damage the cellular components, causing several diseases. Damage in DNA is responsible for cancer formation and progression. However, several enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase etc. act as antioxidants to influence oxidative stress. Polymorphisms in these enzymes are supposed to be associated with DNA damage and subsequently the individual's risk of cancer susceptibility. This review article aims to further elucidate the relationship between antioxidant enzymes and cancers by summarizing the findings of some of the important study concerning expression levels and genetic polymorphisms of antioxidant enzymes in cancer patients. © Chinese Anti-Cancer Association and Springer-Verlag Berlin Heidelberg 2010.


Ouyang F.-D.,Central South University | Ouyang F.-D.,Teaching Research Office of Biochemistry | Yang F.-L.,Central South University | Chen H.-C.,Central South University | And 9 more authors.
Tumor Biology | Year: 2013

Lung adenocarcinoma (ADC) is one of the major histological types of lung cancer. Genetic polymorphism in DNA repair genes and lung ADC susceptibility is well documented. In this case-control study, the association between the polymorphic sites of DNA repair genes XPD-751, XRCC1-399, and OGG1-326, and lung ADC susceptibility in ethnic Han Chinese population has been investigated. Genomic DNA was isolated from the peripheral blood of 201 healthy controls and 82 lung ADC patients from the people of Hunan Province, China. Polymorphisms of the investigated genes were analyzed by using polymerase chain reaction-restriction fragment length polymorphism. There was no significant difference between the samples from lung ADC patients and healthy controls about the genotype frequencies of XPD-751, XRCC1-399, and OGG1-326 sites. However, multifactor dimensionality reduction analysis showed that the genetic polymorphisms of the three-loci models of DNA repair genes (XPD-751/XRCC1-399/ OGG1-326) are associated with lung ADC. Thus, this study reveals that a three-order interaction among the polymorphic sites of XPD-751, XRCC1-399, and OGG1-326 is associated with lung ADC risk in the studied population, although polymorphism in individual gene was not associated. © 2013 International Society of Oncology and BioMarkers (ISOBM).


Balin B.J.,Center for Chronic Disorders of Aging | Hammond C.J.,Center for Chronic Disorders of Aging
Neurobehavioral HIV Medicine | Year: 2012

This review focuses on emerging viral and bacterial infections in the human central nervous system (CNS) that are responsible for significant global morbidity and mortality. These infections include those responsible for acute neurological disease such as meningitis and encephalitis as well those associated with chronic neurodegenerative conditions. Recent changes in climate conditions and pollution have been precipitating factors leading to the emergence of many of these pathogenic organisms. In addition, increased urbanization, global travel, life span, and exposure to new vectors have promoted the organisms' spread across the globe. Categorization of many of these organisms includes identification of new species, recognition of new tropism to the CNS, spread into naïve demographic areas, increased human contact with zoonotic repositories including insect vectors, and reemergence of well-known organisms. These mechanisms are highlighted for the different organisms included in this review. Other mechanisms for CNS emergence such as genetic mutation of the organisms and immunosuppression and/or immunosenescence of the host are addressed. Viral and bacterial infections in chronic neurodegenerative diseases traditionally not thought to be infectious are considered. Although this review cannot be all-inclusive, the organisms included represent a sampling of extremely important microbes and their role in CNS pathogenesis in the twenty-first century. © 2012 Balin and Hammond.


Barnes P.L.,Center for Chronic Disorders of Aging | Laboy F.,Center for Chronic Disorders of Aging | Noto-Bell L.,Center for Chronic Disorders of Aging | Ferencz V.,Center for Chronic Disorders of Aging | And 2 more authors.
Journal of Bodywork and Movement Therapies | Year: 2013

Background: Few objective measures have been used to document change in myofascial tissues after OMT. Hypothesis: Paraspinal tissues associated with cervical somatic dysfunction (SD) will demonstrate quantifiable change in myofascial hysteresis characteristics after a given OMT technique but not after a Sham intervention. Materials & methods: 240 subjects were palpated for cervical articular SD. A randomly selected intervention (5 OMT techniques or a Sham) was applied to the cervical SD clinically considered to be most severe. A durometer (SA201®; Sigma Instruments, Cranberry, PA, USA) objectively measured myofascial structures overlying each cervical spinal segment pre- and post- intervention. Using a single consistent piezoelectric impulse, this durometer quantified four hysteresis (tissue texture) characteristics - fixation, mobility, frequency, and motoricity. Results: Baseline changes in median hysteresis values were noted for each OMT technique but not for Sham interventions. Notably, segmental counterstrain OMT resulted in significant motoricity change compared to adjacent segmental myofascial measures (p-value 0.04) along with a suggestive trend in the mobility component (p-value 0.12). Conclusion: When comparing treated to untreated cervical segments, the most significant change occurred post-counterstrain OMT with no overall change following Sham. Overall, quantifiable objective change occurs in myofascial tissues post-OMT, in addition to the noted clinical palpable change. © 2012 Elsevier Ltd.


Palmer G.D.,New York University | Piton A.H.,Center for Chronic Disorders of Aging | Thant L.M.,Center for Chronic Disorders of Aging | Oliveira S.M.,Center for Chronic Disorders of Aging | And 5 more authors.
Journal of Orthopaedic Research | Year: 2010

This study examines the role of F-spondin, an extracellular matrix protein of osteoarthritic cartilage, during chondrocyte maturation in embryonic growth plate cartilage. In chick tibia, F-spondin expression localized to the hypertrophic and calcified zones of the growth plate. Functional studies using tibial organ cultures indicated that F-spondin inhibited (∼35%, p=0.02), and antibodies to F-spondin increased (∼30%, p<0.1) longitudinal limb growth relative to untreated controls. In cell cultures, induction of chondrocyte maturation, by retinoic acid (RA) or transforming growth factor (TGF)-β treatment led to a significant upregulation of F-spondin (p<0.05). F-spondin transfection increased mineral deposition, alkaline phosphatase (AP) and matrix metalloproteinase (MMP)-13 mRNA levels (p<0.05), and AP activity following RA stimulation, compared to mock transfected controls. Using AP as a differentiation marker we then investigated the mechanism of F-spondin promaturation effects. Blocking endogenous F-spondin via its thrombospondin (TSR) domain inhibited RA induced AP activity 40% compared to controls (p<0.05). The stimulatory effect of F-spondin on AP expression was also inhibited following depletion of TGF-β from culture supernatants. Our findings indicate that F-spondin is expressed in embryonic cartilage, where it has the capacity to enhance chondrocyte terminal differentiation and mineralization via interactions in its TSR domain and TGF-β dependent pathways. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

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