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Medical Biochemistry

2012

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Full-Text Articles in Medicine and Health Sciences

Alterations In Glutathione Levels And Apoptotic Regulators Are Associated With Acquisition Of Arsenic Trioxide Resistance In Multiple Myeloma, Shannon M. Matulis, Alejo A. Morales, Lucy Yehiayan, Kelvin P. Lee, Yong Cai, Lawrence H. Boise Dec 2012

Alterations In Glutathione Levels And Apoptotic Regulators Are Associated With Acquisition Of Arsenic Trioxide Resistance In Multiple Myeloma, Shannon M. Matulis, Alejo A. Morales, Lucy Yehiayan, Kelvin P. Lee, Yong Cai, Lawrence H. Boise

Department of Chemistry and Biochemistry

Arsenic trioxide (ATO) has been tested in relapsed/refractory multiple myeloma with limited success. In order to better understand drug mechanism and resistance pathways in myeloma we generated an ATO-resistant cell line, 8226/S-ATOR05, with an IC50 that is 2–3-fold higher than control cell lines and significantly higher than clinically achievable concentrations. Interestingly we found two parallel pathways governing resistance to ATO in 8226/S-ATOR05, and the relevance of these pathways appears to be linked to the concentration of ATO used. We found changes in the expression of Bcl-2 family proteins Bfl-1 and Noxa as well as an increase in cellular glutathione (GSH) …


Targeting Astrocytes Ameliorates Neurologic Changes In A Mouse Model Of Alzheimer's Disease, Jennifer L. Furman, Diana M. Sama, John C. Gant, Tina L. Beckett, M. Paul Murphy, Adam D. Bachstetter, Linda J. Van Eldik, Christopher M. Norris Nov 2012

Targeting Astrocytes Ameliorates Neurologic Changes In A Mouse Model Of Alzheimer's Disease, Jennifer L. Furman, Diana M. Sama, John C. Gant, Tina L. Beckett, M. Paul Murphy, Adam D. Bachstetter, Linda J. Van Eldik, Christopher M. Norris

Pharmacology and Nutritional Sciences Faculty Publications

Astrocytes are the most abundant cell type in the brain and play a critical role in maintaining healthy nervous tissue. In Alzheimer's disease (AD) and most other neurodegenerative disorders, many astrocytes convert to a chronically "activated" phenotype characterized by morphologic and biochemical changes that appear to compromise protective properties and/or promote harmful neuroinflammatory processes. Activated astrocytes emerge early in the course of AD and become increasingly prominent as clinical and pathological symptoms progress, but few studies have tested the potential of astrocyte-targeted therapeutics in an intact animal model of AD. Here, we used adeno-associated virus (AAV) vectors containing the astrocyte-specific …


Muc4 And Muc1 Expression In Adenocarcinoma Of The Stomach Correlates With Vessel Invasion And Lymph Node Metastasis: An Immunohistochemical Study Of Early Gastric Cancer., Yukihiro Tamura, Michiyo Higashi, Sho Kitamoto, Seiya Yokoyama, Masahiko Osako, Michiko Horinouchi, Takeshi Shimizu, Mineo Tabata, Surinder K. Batra, Masamichi Goto, Suguru Yonezawa Nov 2012

Muc4 And Muc1 Expression In Adenocarcinoma Of The Stomach Correlates With Vessel Invasion And Lymph Node Metastasis: An Immunohistochemical Study Of Early Gastric Cancer., Yukihiro Tamura, Michiyo Higashi, Sho Kitamoto, Seiya Yokoyama, Masahiko Osako, Michiko Horinouchi, Takeshi Shimizu, Mineo Tabata, Surinder K. Batra, Masamichi Goto, Suguru Yonezawa

Journal Articles: Biochemistry & Molecular Biology

We have previously reported that MUC4 expression is a poor prognostic factor in various carcinomas. Our previous study also showed that MUC1 expression in gastric cancers, including the early and advanced stages is a poor prognostic factor. In the present study, the expression profiles of MUC4 and MUC1 were examined by immunohistochemistry (IHC) using two anti-MUC4 monoclonal antibodies (MAbs), 8G7 and 1G8, and anti-MUC1 MAb DF3 in 104 gastrectomy specimens of early gastric adenocarcinoma with submucosal invasion (pT1b2), including 197 histological subtype lesions. Before the IHC study of the human specimens, we evaluated the specificity of the two MAbs by …


Aging-Associated Dysfunction Of Akt/Protein Kinase B: S-Nitrosylation And Acetaminophen Intervention, Miaozong Wu, Anjaiah Katta, Murali Gadde, Hua Liu, Sunil Kakarla, Jacqueline Fannin, Satyanarayana Paturi, Ravi Arvapalli, Kevin Rice, Yeling Wang, Eric Blough Nov 2012

Aging-Associated Dysfunction Of Akt/Protein Kinase B: S-Nitrosylation And Acetaminophen Intervention, Miaozong Wu, Anjaiah Katta, Murali Gadde, Hua Liu, Sunil Kakarla, Jacqueline Fannin, Satyanarayana Paturi, Ravi Arvapalli, Kevin Rice, Yeling Wang, Eric Blough

Ravi K. Arvapalli

Background: Aged skeletal muscle is characterized by an increased incidence of metabolic and functional disorders, which if allowed to proceed unchecked can lead to increased morbidity and mortality. The mechanism(s) underlying the development of these disorders in aging skeletal muscle are not well understood. Protein kinase B (Akt/PKB) is an important regulator of cellular metabolism and survival, but it is unclear if aged muscle exhibits alterations in Akt function. Here we report a novel dysfunction of Akt in aging muscle, which may relate to S-nitrosylation and can be prevented by acetaminophen intervention. Principal Findings: Compared to 6- and 27-month rats, …


Stem Cell Transplantation Increases Antioxidant Effects In Diabetic Mice, Ming Li, Luca Vanella, Yuming Zhang, Ming Shi, Takashi Takaki, Joseph I. Shapiro M.D., Susuma Ikehera Oct 2012

Stem Cell Transplantation Increases Antioxidant Effects In Diabetic Mice, Ming Li, Luca Vanella, Yuming Zhang, Ming Shi, Takashi Takaki, Joseph I. Shapiro M.D., Susuma Ikehera

Biochemistry and Microbiology

Intra bone marrow-bone marrow transplantation (IBM- BMT) + thymus transplantation (TT) has been shown to reduce the incidence of graft versus host disease (GVHD) and restore donor-derived T cell function. In addition, an increase in insulin sensitivity occurred in db/db mice after IBM-BMT+TT treatment. Heme oxygenase (HO)-1 is a stress inducible enzyme which exert antioxidant, antiapoptotic, and immune-modulating properties. We examined whether IBM-BMT+TT could modulate the expression of HO-1 in the kidneys of db/db mice. Six-week-old db/db mice with blood glucose levels higher than 250 mg/dl were treated with IBM-BMT+TT. Six weeks later, the db/db mice showed decreased body weight, …


Mucin (Muc) Expression During Pancreatic Cancer Progression In Spontaneous Mouse Model: Potential Implications For Diagnosis And Therapy., Satyanarayana Rachagani, María P Torres, Sushil Kumar, Dhanya Haridas, Michael J. Baine, Muzafar A. Macha, Sukhwinder Kaur, Moorthy P. Ponnusamy, Parama Dey, Parthasarathy Seshacharyulu, Sonny L. Johansson, Maneesh Jain, Kay-Uwe Wagner, Surinder K. Batra Oct 2012

Mucin (Muc) Expression During Pancreatic Cancer Progression In Spontaneous Mouse Model: Potential Implications For Diagnosis And Therapy., Satyanarayana Rachagani, María P Torres, Sushil Kumar, Dhanya Haridas, Michael J. Baine, Muzafar A. Macha, Sukhwinder Kaur, Moorthy P. Ponnusamy, Parama Dey, Parthasarathy Seshacharyulu, Sonny L. Johansson, Maneesh Jain, Kay-Uwe Wagner, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Pancreatic cancer (PC) is a lethal malignancy primarily driven by activated Kras mutations and characterized by the deregulation of several genes including mucins. Previous studies on mucins have identified their significant role in both benign and malignant human diseases including PC progression and metastasis. However, the initiation of MUC expression during PC remains unknown because of lack of early stage tumor tissues from PC patients.

METHODS: In the present study, we have evaluated stage specific expression patterns of mucins during mouse PC progression in (Kras(G12D);Pdx1-Cre (KC)) murine PC model from pancreatic intraepithelial neoplasia (PanIN) to pancreatic ductal adenocarcinoma (PDAC) …


Effects Of Canola And Corn Oil Mimetic On Jurkat Cells, Gabriela Ion, Kayla Fazio, Juliana A. Akinsete, W. Elaine Hardman Oct 2012

Effects Of Canola And Corn Oil Mimetic On Jurkat Cells, Gabriela Ion, Kayla Fazio, Juliana A. Akinsete, W. Elaine Hardman

Gabriela Ion

BACKGROUND: The Western diet is high in omega-6 fatty acids and low in omega-3 fatty acids. Canola oil contains a healthier omega 3 to omega 6 ratio than corn oil. Jurkat T leukemia cells were treated with free fatty acids mixtures in ratios mimicking that found in commercially available canola oil (7% α-linolenic, 30% linoleic, 54% oleic) or corn oil (59% linoleic, 24% oleic) to determine the cell survival or cell death and changes in expression levels of inflammatory cytokines and receptors following oil treatment. METHODS: Fatty acid uptake was assessed by gas chromatography. Cell survival and cell death were …


Mg624, An A7-Nachr Antagonist, Inhibits Angiogenesis Via The Egr-1/Fgf2 Pathway, Kathleen Brown, Jamie Lau, Aaron Dom, Theodore Witte, Haitao Luo, Clayton Crabtree, Yashoni Shah, Brandon Shiflett, Aileen Marcelo, Nancy Proper, W. Hardman, Richard Egleton, Yi Chen, Elsa Mangiarua, Piyali Dasgupta Oct 2012

Mg624, An A7-Nachr Antagonist, Inhibits Angiogenesis Via The Egr-1/Fgf2 Pathway, Kathleen Brown, Jamie Lau, Aaron Dom, Theodore Witte, Haitao Luo, Clayton Crabtree, Yashoni Shah, Brandon Shiflett, Aileen Marcelo, Nancy Proper, W. Hardman, Richard Egleton, Yi Chen, Elsa Mangiarua, Piyali Dasgupta

Nancy A. Proper

Small cell lung cancer (SCLC) demonstrates a strong etiological association with smoking. Although cigarette smoke is a mixture of about 4,000 compounds, nicotine is the addictive component of cigarette smoke. Several convergent studies have shown that nicotine promotes angiogenesis in lung cancers via the α7-nicotinic acetylcholine receptor (α7-nAChR) on endothelial cells. Therefore, we conjectured that α7-nAChR antagonists may attenuate nicotine-induced angiogenesis and be useful for the treatment of human SCLC. For the first time, our study explores the anti-angiogenic activity of MG624, a small-molecule α7-nAChR antagonist, in several experimental models of angiogenesis. We observed that MG624 potently suppressed the proliferation …


Maternal Consumption Of Canola Oil Suppressed Mammary Gland Tumorigenesis In C3(1) Tag Mice Offspring, Gabriela Ion, Juliana A. Akinsete, W. Elaine Hardman Oct 2012

Maternal Consumption Of Canola Oil Suppressed Mammary Gland Tumorigenesis In C3(1) Tag Mice Offspring, Gabriela Ion, Juliana A. Akinsete, W. Elaine Hardman

Gabriela Ion

Background: Maternal consumption of a diet high in omega 6 polyunsaturated fats (n-6 PUFA) has been shown to increase risk whereas a diet high in omega 3 polyunsaturated fats (n-3 PUFA) from fish oil has been shown to decrease risk for mammary gland cancer in female offspring of rats. The aim of this study was to determine whether increasing n-3 PUFA and reducing n-6 PUFA by using canola oil instead of corn oil in the maternal diet might reduce the risk for breast cancer in female offspring. Methods: Female SV 129 mice were divided into two groups and placed on …


Mg624, An A7-Nachr Antagonist, Inhibits Angiogenesis Via The Egr-1/Fgf2 Pathway, Kathleen Brown, Jamie Lau, Aaron Dom, Theodore Witte, Haitao Luo, Clayton Crabtree, Yashoni Shah, Brandon Shiflett, Aileen Marcelo, Nancy Proper, W. Hardman, Richard Egleton, Yi Chen, Elsa Mangiarua, Piyali Dasgupta Oct 2012

Mg624, An A7-Nachr Antagonist, Inhibits Angiogenesis Via The Egr-1/Fgf2 Pathway, Kathleen Brown, Jamie Lau, Aaron Dom, Theodore Witte, Haitao Luo, Clayton Crabtree, Yashoni Shah, Brandon Shiflett, Aileen Marcelo, Nancy Proper, W. Hardman, Richard Egleton, Yi Chen, Elsa Mangiarua, Piyali Dasgupta

Jamie K. Lau

Small cell lung cancer (SCLC) demonstrates a strong etiological association with smoking. Although cigarette smoke is a mixture of about 4,000 compounds, nicotine is the addictive component of cigarette smoke. Several convergent studies have shown that nicotine promotes angiogenesis in lung cancers via the α7-nicotinic acetylcholine receptor (α7-nAChR) on endothelial cells. Therefore, we conjectured that α7-nAChR antagonists may attenuate nicotine-induced angiogenesis and be useful for the treatment of human SCLC. For the first time, our study explores the anti-angiogenic activity of MG624, a small-molecule α7-nAChR antagonist, in several experimental models of angiogenesis. We observed that MG624 potently suppressed the proliferation …


Resveratrol Is Rapidly Metabolized In Athymic (Nu/Nu) Mice And Does Not Inhibit Human Melanoma Xenograft Tumor Growth, Richard Niles, Carla Cook, Gary Meadows, Ya-Min Fu, Jerry Mclaughlin, Gary Rankin Oct 2012

Resveratrol Is Rapidly Metabolized In Athymic (Nu/Nu) Mice And Does Not Inhibit Human Melanoma Xenograft Tumor Growth, Richard Niles, Carla Cook, Gary Meadows, Ya-Min Fu, Jerry Mclaughlin, Gary Rankin

Carla R. Cook

Resveratrol has been shown to have anticarcinogenic activity. We previously found that resveratrol inhibited growth and induced apoptosis in 2 human melanoma cell lines. In this study we determined whether resveratrol would inhibit human melanoma xenograft growth. Athymic mice received control diets or diets containing 110 μmol/L or 263 μmol/L resveratrol, 2 wk prior to subcutaneous injection of the tumor cells. Tumor growth was measured during a 3-wk period. Metabolism of resveratrol was assayed by bolus gavage of 75 mg/kg resveratrol in tumor-bearing and nontumor-bearing mice. Pellets containing 10–100 mg resveratrol were implanted into the mice, next to newly palpated …


Consumption Of High Ω-3 Fatty Acid Diet Suppressed Prostate Tumorigenesis In C3(1) Tag Mice, Juliana Akinsete, Gabriela Ion, Theodore Witte, W. Hardman Oct 2012

Consumption Of High Ω-3 Fatty Acid Diet Suppressed Prostate Tumorigenesis In C3(1) Tag Mice, Juliana Akinsete, Gabriela Ion, Theodore Witte, W. Hardman

Gabriela Ion

Prostate cancer incidence and mortality are high in the Western world and high ω-6/ω-3 PUFA in the Western diet may be a contributing factor. We investigated whether changing from a diet that approximates ω-6 fat content of the Western diet to a high ω-3 fat diet at adulthood might reduce prostate cancer risk. Female SV 129 mice that had consumed a high ω-6 diet containing corn oil for 2 weeks were bred with homozygous C3(1)Tag transgenic male mice. All male offspring were weaned to the corn oil diet (CO) until postpuberty when half of the male offspring were transferred to …


Silencing And Re-Expression Of Retinoic Acid Receptor Beta2 In Human Melanoma, Jun Fan, Linda Eastham, Melinda Varney, Adam Hall, Nicolas Adkins, Vincent Sollars, Philippe Georgel, Richard Niles Oct 2012

Silencing And Re-Expression Of Retinoic Acid Receptor Beta2 In Human Melanoma, Jun Fan, Linda Eastham, Melinda Varney, Adam Hall, Nicolas Adkins, Vincent Sollars, Philippe Georgel, Richard Niles

Linda L. Eastham

Many melanoma cells are resistant to the anti-proliferative effect of all trans retinoic acid (ATRA). Retinoic Acid Receptor-β2 (RAR-β2) mediates the ATRA growth inhibition. We found a correlation between the anti-proliferative activity of ATRA and expression of RAR-β2. There was not a strict correlation between DNA methylation of RAR-β gene and its expression. There was no difference in global and RARβ specific nucleosome repeat length (NRL) in melanoma and melanocytes or between control and ATRA treated cells. Pan-acetylation of H3 and H4 within the RAR-β gene promoter was higher in cells expressing RAR-β2. All trans retinoic acid treatment of …


Pparα/Γ Expression And Activity In Mouse And Human Melanocytes And Melanoma Cells, Linda Eastham, Caroline Mills, Richard Niles Oct 2012

Pparα/Γ Expression And Activity In Mouse And Human Melanocytes And Melanoma Cells, Linda Eastham, Caroline Mills, Richard Niles

Linda L. Eastham

Purpose. We examined the expression of PPARs and the effects of PPARα and PPARγ agonists on growth of mouse and human melanocytes and melanoma cells.

Methods. PPARα,β, and PPARγ mRNA qualitative expression in melan-a mouse melanocytes, B16 mouse melanoma, human melanocytes, and A375 and SK-mel28 human melanoma cells was determined by RT-PCR, while quantitative PPARα mRNA levels were determined by QuantiGene assay. PPARα and PPARγ protein was assessed by Western blotting. The effect of natural and synthetic PPAR ligands on cell growth was determined by either hemocytometer counting or crystal violet assay. PPAR transcriptional activity was determined by a PPRE-reporter …


Mussel Inspired Protein-Mediated Surface Modification To Electrospun Fibers And Their Potential Biomedical Applications, Jingwei Xie, Praveesuda Lorwattanapongsa Michael, Shaoping Zhong, Bing Ma, Matthew R. Macewan, Chwee Teck Lim Oct 2012

Mussel Inspired Protein-Mediated Surface Modification To Electrospun Fibers And Their Potential Biomedical Applications, Jingwei Xie, Praveesuda Lorwattanapongsa Michael, Shaoping Zhong, Bing Ma, Matthew R. Macewan, Chwee Teck Lim

Bing Ma

Mussel inspired proteins have been demonstrated to serve as a versatile biologic adhesive with numerous applications. The present study illustrates the use of such Mussel inspired proteins (polydopamine) in the fabrication of functionalized bio-inspired nanomaterials capable of both improving cell response and sustained delivery of model probes. X-ray photoelectron spectroscopy analysis confirmed the ability of dopamine to polymerize on the surface of plasma-treated, electrospun poly(ε-caprolactone) (PCL) fiber mats to form polydopamine coating. Transmission electron microscopy images demonstrated that self-polymerization of dopamine was induced by pH shift and that the thickness of polydopamine coating was readily modulated by adjusting the concentration …


Nuclear Receptor Expression And Characterization Of The Major Retinoic Acid Target Gene In Melanoma, Linda L. Eastham Oct 2012

Nuclear Receptor Expression And Characterization Of The Major Retinoic Acid Target Gene In Melanoma, Linda L. Eastham

Linda L. Eastham

Malignant melanoma is the primary cause of death from all diseases arising from the skin and it is one of the most resistant tumors to standard treatment options. The increasing incidence of melanoma and its poor prognosis makes the understanding of melanoma cell biology very important. Melanoma progression is a complex, multi-step process, and the molecular events leading to melanoma tumor cell proliferation and invasion still need further examination. This study is focused on measuring the expression and activity of two specific genes and their protein counterparts that are altered during melanoma progression. It also examines the mechanism through which …


Expression And Function Of Cd9 In Melanoma Cells, Jun Fan, Guo-Zhang Zhu, Richard Niles Oct 2012

Expression And Function Of Cd9 In Melanoma Cells, Jun Fan, Guo-Zhang Zhu, Richard Niles

Jun Fan

CD9, a member of the tetraspanin family, functions as an organizer in “tetraspanin webs,” through interacting with other cell adhesion molecules. It plays a role in differentiation, fertilization, and cell migration. We investigated the expression and function of CD9 in melanoma. CD9 protein expression in B16 mouse melanoma and six human melanoma cell lines was decreased compared to normal melanocytes. B16F1 clones stably overexpressing CD9 had reduced ability to form colonies in soft agar; however, paradoxically these overexpressing clones had increased ability to invade Matrigel. Similarly, transient overexpression of CD9 in the human metastatic melanoma cell line WM9 dramatically decreased …


Silencing And Re-Expression Of Retinoic Acid Receptor Beta2 In Human Melanoma, Jun Fan, Linda Eastham, Melinda Varney, Adam Hall, Nicolas Adkins, Vincent Sollars, Philippe Georgel, Richard Niles Oct 2012

Silencing And Re-Expression Of Retinoic Acid Receptor Beta2 In Human Melanoma, Jun Fan, Linda Eastham, Melinda Varney, Adam Hall, Nicolas Adkins, Vincent Sollars, Philippe Georgel, Richard Niles

Jun Fan

Many melanoma cells are resistant to the anti-proliferative effect of all trans retinoic acid (ATRA). Retinoic Acid Receptor-β2 (RAR-β2) mediates the ATRA growth inhibition. We found a correlation between the anti-proliferative activity of ATRA and expression of RAR-β2. There was not a strict correlation between DNA methylation of RAR-β gene and its expression. There was no difference in global and RARβ specific nucleosome repeat length (NRL) in melanoma and melanocytes or between control and ATRA treated cells. Pan-acetylation of H3 and H4 within the RAR-β gene promoter was higher in cells expressing RAR-β2. All trans retinoic acid treatment of …


Possible Steps Of Complete Disassembly Of Post-Termination Complex By Yeast Eef3 Deduced From Inhibition By Translocation Inhibitors., Shinya Kurata, Ben Shen, Jun O Liu, Nono Takeuchi, Akira Kaji, Hideko Kaji Oct 2012

Possible Steps Of Complete Disassembly Of Post-Termination Complex By Yeast Eef3 Deduced From Inhibition By Translocation Inhibitors., Shinya Kurata, Ben Shen, Jun O Liu, Nono Takeuchi, Akira Kaji, Hideko Kaji

Department of Biochemistry and Molecular Biology Faculty Papers

Ribosomes, after one round of translation, must be recycled so that the next round of translation can occur. Complete disassembly of post-termination ribosomal complex (PoTC) in yeast for the recycling consists of three reactions: release of tRNA, release of mRNA and splitting of ribosomes, catalyzed by eukaryotic elongation factor 3 (eEF3) and ATP. Here, we show that translocation inhibitors cycloheximide and lactimidomycin inhibited all three reactions. Cycloheximide is a non-competitive inhibitor of both eEF3 and ATP. The inhibition was observed regardless of the way PoTC was prepared with either release factors or puromycin. Paromomycin not only inhibited all three reactions …


Surveillance Of Penicillin-Resistant Streptococcus Pneumoniae In One American Metropolitan Area, 1989–1998, Raghda Sahloul, Ronald Stanek, Maurice Mufson Sep 2012

Surveillance Of Penicillin-Resistant Streptococcus Pneumoniae In One American Metropolitan Area, 1989–1998, Raghda Sahloul, Ronald Stanek, Maurice Mufson

Maurice A. Mufson

The emergence of invasive penicillin-resistant (PRSP) and multidrug-resistant (MDRP) Streptococcus pneumoniae was tracked from 1989 to 1998 in one medium-sized metropolitan area in the USA, encompassing western West Virginia, including Huntington, the only major city, and neighboring sections of Kentucky and Ohio. Capsular serotyping and antibiotic sensitivity tests were performed on 350 community-acquired isolates comprising 93.1% of all pneumococcal isolates identified. The incidence of PRSP increased from 3 to 10% during the 10 years of the study. Twenty-nine (22.1%) of 131 isolates of serotypes 6, 9, 14, 19, and 23 were PRSP (one-fourth were MDRP) and 1 (0.5%) of 219 …


Differential Expression Of Chemokines In A Mouse Model Of Wound Healing, Susan H. Jackman, Matthew B. Yoak, Shivaleela Keerthy, Bonnie L. Beaver Sep 2012

Differential Expression Of Chemokines In A Mouse Model Of Wound Healing, Susan H. Jackman, Matthew B. Yoak, Shivaleela Keerthy, Bonnie L. Beaver

Susan H. Jackman

Macrophages have a multifaceted role in wound healing. While their initial activity may be in the degradation and elimination of damaged tissue, macrophages also produce and secrete a variety of mediators that can participate in the repair process as well. To perform these functions, macrophages must be recruited to a wound site. Our purpose was to examine the temporal and spatial expression of macrophage chemoattracting cytokines (chemokines) at a surgical wound site. A surgical wound was prepared on the dorsal aspect of B6AFI/J mice. Biopsies were obtained from the wound and a comparable nonwounded area between 6 and 72 hr …


Serotyping Group B Streptococci In A Small Community Hospital: An Analysis Of Distribution And Site Of Isolation, Jennifer M. Smith, Jason A. Rexroth, David G. Chaffin, Susan H. Jackman Sep 2012

Serotyping Group B Streptococci In A Small Community Hospital: An Analysis Of Distribution And Site Of Isolation, Jennifer M. Smith, Jason A. Rexroth, David G. Chaffin, Susan H. Jackman

Susan H. Jackman

Objective: To determine the prevalence and site of isolation of different serotypes of group B streptococcus (GBS) colonization or infection at a small community hospital. Methods: GBS isolates were obtained from a small community hospital and were then serotyped as la, Ib, II, III, IV, V or non-typeable. Hospital records were reviewed for patient sex, age and pregnancy status as well as the site of GBS isolation. Results: GBS serotypes Ia, III and V were most common and accounted for over 60% of the total number of isolates. Serotype Ia was most prevalent in reproductive-age females, while serotypes V and …


Il-7 Is A Critical Factor In Modulating Lesion Development In Skn-Directed Autoimmunity, Pamela Staton, A. Carpenter, Susan Jackman Sep 2012

Il-7 Is A Critical Factor In Modulating Lesion Development In Skn-Directed Autoimmunity, Pamela Staton, A. Carpenter, Susan Jackman

Susan H. Jackman

In a murine model of autoimmunity targeted against the epidermal cell Ags, Skn, adoptive transfer of Skn-immune T cells to immunosuppressed recipients elicits skin lesions in areas of mild epidermal trauma. In this study, we examined peripheral regulation of Skn-induced autoreactivity disrupted by rendering the mice immunoincompetent. We found that regulation of Skn-directed autoimmunity was restored by cotransfer of normal syngeneic spleen cells at twice the concentration of Skn-immune cells and was evidenced by significantly reduced lesion severity by days 5–7 post-cotransfer compared with animals given injections of Skn-immune cells alone. Enrichment and depletion of normal CD4 or CD8 spleen …


Immunologic Effects Of Gliotoxin In Rats: Mechanisms For Prevention Of Autoimmune Diabetes Mellitus, Honggang Liu, Susan H. Jackman, Henry Driscoll, Bryan Larsen Sep 2012

Immunologic Effects Of Gliotoxin In Rats: Mechanisms For Prevention Of Autoimmune Diabetes Mellitus, Honggang Liu, Susan H. Jackman, Henry Driscoll, Bryan Larsen

Susan H. Jackman

Various fungal products, such as gliotoxin (GT), have immunomodulating activity, a fact exploited previously by our group for prevention of autoimmune diabetes mellitus in BB/Wor rats. To understand better the immunologic effects in GT-treated rats, splenocytes from 65-day-old prediabetic diabetes-prone rats were phenotypically characterized after chronic treatment with GT. A parallel study examined the direct effects of GT on splenocyte preparations incubated with the mycotoxin. In vitro treatment of splenocytes with GT revealed relative decreases in CD4+ and increases in CD8+ T-cell subsets, whereas in vivo treatment with GT did not result in detectable alterations in relative CD4+ and CD8+ …


Mg624, An A7-Nachr Antagonist, Inhibits Angiogenesis Via The Egr-1/Fgf2 Pathway, Kathleen Brown, Jamie Lau, Aaron Dom, Theodore Witte, Haitao Luo, Clayton Crabtree, Yashoni Shah, Brandon Shiflett, Aileen Marcelo, Nancy Proper, W. Hardman, Richard Egleton, Yi Chen, Elsa Mangiarua, Piyali Dasgupta Sep 2012

Mg624, An A7-Nachr Antagonist, Inhibits Angiogenesis Via The Egr-1/Fgf2 Pathway, Kathleen Brown, Jamie Lau, Aaron Dom, Theodore Witte, Haitao Luo, Clayton Crabtree, Yashoni Shah, Brandon Shiflett, Aileen Marcelo, Nancy Proper, W. Hardman, Richard Egleton, Yi Chen, Elsa Mangiarua, Piyali Dasgupta

Elsa I. Mangiarua

Small cell lung cancer (SCLC) demonstrates a strong etiological association with smoking. Although cigarette smoke is a mixture of about 4,000 compounds, nicotine is the addictive component of cigarette smoke. Several convergent studies have shown that nicotine promotes angiogenesis in lung cancers via the α7-nicotinic acetylcholine receptor (α7-nAChR) on endothelial cells. Therefore, we conjectured that α7-nAChR antagonists may attenuate nicotine-induced angiogenesis and be useful for the treatment of human SCLC. For the first time, our study explores the anti-angiogenic activity of MG624, a small-molecule α7-nAChR antagonist, in several experimental models of angiogenesis. We observed that MG624 potently suppressed the proliferation …


Immunologic Effects Of Gliotoxin In Rats: Mechanisms For Prevention Of Autoimmune Diabetes Mellitus, Honggang Liu, Susan H. Jackman, Henry Driscoll, Bryan Larsen Sep 2012

Immunologic Effects Of Gliotoxin In Rats: Mechanisms For Prevention Of Autoimmune Diabetes Mellitus, Honggang Liu, Susan H. Jackman, Henry Driscoll, Bryan Larsen

Henry Driscoll

Various fungal products, such as gliotoxin (GT), have immunomodulating activity, a fact exploited previously by our group for prevention of autoimmune diabetes mellitus in BB/Wor rats. To understand better the immunologic effects in GT-treated rats, splenocytes from 65-day-old prediabetic diabetes-prone rats were phenotypically characterized after chronic treatment with GT. A parallel study examined the direct effects of GT on splenocyte preparations incubated with the mycotoxin. In vitro treatment of splenocytes with GT revealed relative decreases in CD4+ and increases in CD8+ T-cell subsets, whereas in vivo treatment with GT did not result in detectable alterations in relative CD4+ and CD8+ …


Il-7 Is A Critical Factor In Modulating Lesion Development In Skn-Directed Autoimmunity, Pamela Staton, A. Carpenter, Susan Jackman Sep 2012

Il-7 Is A Critical Factor In Modulating Lesion Development In Skn-Directed Autoimmunity, Pamela Staton, A. Carpenter, Susan Jackman

Pamela J. Staton

In a murine model of autoimmunity targeted against the epidermal cell Ags, Skn, adoptive transfer of Skn-immune T cells to immunosuppressed recipients elicits skin lesions in areas of mild epidermal trauma. In this study, we examined peripheral regulation of Skn-induced autoreactivity disrupted by rendering the mice immunoincompetent. We found that regulation of Skn-directed autoimmunity was restored by cotransfer of normal syngeneic spleen cells at twice the concentration of Skn-immune cells and was evidenced by significantly reduced lesion severity by days 5–7 post-cotransfer compared with animals given injections of Skn-immune cells alone. Enrichment and depletion of normal CD4 or CD8 spleen …


Murine Epidermal Cell Antigen (Skn)-Directed Autoimmunity Induced By Transfer Of Cd4+ T Cells, Susan H. Jackman, Shivaleela Keerthy, Giselle Perry Sep 2012

Murine Epidermal Cell Antigen (Skn)-Directed Autoimmunity Induced By Transfer Of Cd4+ T Cells, Susan H. Jackman, Shivaleela Keerthy, Giselle Perry

Susan H. Jackman

While pathogenic T cells have been identified for several diseases with epithelial cell damage, an autoimmune T cell-mediated response targeted against a known keratinocyte antigen has not been reported. Previously we described an autoimmune response directed to the mouse epidermal cell antigens, Skn. For our murine model, primed Skn-immune lymphocytes are adoptively transferred to recipients, which develop lesions at the site of mild skin trauma. In this study we investigated the nature of the autoimmune component of the Skn response. A time-course study demonstrated a relationship between the number of primed Sknimmune cells injected and the severity of skin lesions …


Non-Helicobacter Pylori Related Duodenal Ulcer Disease In Children, Yoram Elitsur, Zandra Lawrence Sep 2012

Non-Helicobacter Pylori Related Duodenal Ulcer Disease In Children, Yoram Elitsur, Zandra Lawrence

Yoram Elitsur

Background. In spite of the worldwide distribution of Helicobacter pylori infection, recent data have reported an increased rate of non-H. pylori, non-NSAIDs-duodenal ulcer disease in adults. The estimated rate of these ulcers in children is unknown. We aimed to investigate the prevalence of non-H. pylori, non-NSAIDs-peptic ulcer disease in our pediatric patients who undergo upper endoscopic procedures. Methods. A retrospective analysis of 622 upper endoscopic reports was performed. Reports that documented mucosal ulcerations were included in our study. The demographic, clinical, endoscopic, and histological data were retrieved. The H. pylori-negative, duodenal/gastric ulcer-positive patients were compared with H. pylori-positive, duodenal/gastric ulcer-positive …


Helicobacter Pylori Serology And The Diagnosis Of H. Pylori Infection In Children, Yoram Elitsur, Rafah Aflak, Cheryl Neace, W. E. Triest Sep 2012

Helicobacter Pylori Serology And The Diagnosis Of H. Pylori Infection In Children, Yoram Elitsur, Rafah Aflak, Cheryl Neace, W. E. Triest

Yoram Elitsur

Serological screening accuracy rate may be dependent on clinical and pathological determinants. The aim of this study was to evaluate the accuracy of Hp serology test (Roche Biomedical Lab., Labcorp), In the diagnosis of Hp infection in 121 children who were seen in the Pediatric Gastoenterology Clinic at the Marshall University Joan C. Edwards School of Medicine In Huntington. Positive serology detected children with Hpassociated gastritis with a sensitivity of 51.6%. Positive serology significantly correlated with the degree of gastric inflammation and density of Hp organisms in the gastric mucosa (ANOVA p < 0.001). The Labcorp. Hp-ELISA test had a poor …