Medicine and Health Sciences Commons^™

A Central Role For Carbon-Overflow Pathways In The Modulation Of Bacterial Cell Death., Vinai Chittezham Thomas, Marat Sadykov, Sujata S. Chaudhari, Joselyn Jones, Jennifer L. Endres, Todd J. Widhelm, Jong-Sam Ahn, Randeep S. Jawa, Matthew C. Zimmerman, Kenneth W. Bayles

Journal Articles: Pathology and Microbiology

Similar to developmental programs in eukaryotes, the death of a subpopulation of cells is thought to benefit bacterial biofilm development. However mechanisms that mediate a tight control over cell death are not clearly understood at the population level. Here we reveal that CidR dependent pyruvate oxidase (CidC) and α-acetolactate synthase/decarboxylase (AlsSD) overflow metabolic pathways, which are active during staphylococcal biofilm development, modulate cell death to achieve optimal biofilm biomass. Whereas acetate derived from CidC activity potentiates cell death in cells by a mechanism dependent on intracellular acidification and respiratory inhibition, AlsSD activity effectively counters CidC action by diverting carbon flux …

Functional Proteomic Analysis Reveals The Involvement Of Kiaa1199 In Breast Cancer Growth, Motility And Invasiveness., Mohammad-Saeid Jami, Jinxuan Hou, Miao Liu, M L. Varney, Hesham Hassan, Jixin Dong, Liying Geng, J. Wang, Fang Yu, Xin Huang, Hong Peng, Kai Fu, Yan Li, Rakesh Singh, Shi-Jian Ding

Journal Articles: Pathology and Microbiology

BACKGROUND: KIAA1199 is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the functional significance of KIAA1199 expression in breast cancer growth, motility and invasiveness.

METHODS: We validated the previous microarray observation by tissue microarray immunohistochemistry using a TMA slide containing 12 breast tumor tissue cores and 12 corresponding normal tissues. We performed the shRNA-mediated knockdown of KIAA1199 in MDA-MB-231 and HS578T cells to …

Myd88-Dependent Signaling Influences Fibrosis And Alternative Macrophage Activation During Staphylococcus Aureus Biofilm Infection., Mark L. Hanke, Amanda Angle, Tammy Kielian

Journal Articles: Pathology and Microbiology

Bacterial biofilms represent a significant therapeutic challenge based on their ability to evade host immune and antibiotic-mediated clearance. Recent studies have implicated IL-1β in biofilm containment, whereas Toll-like receptors (TLRs) had no effect. This is intriguing, since both the IL-1 receptor (IL-1R) and most TLRs impinge on MyD88-dependent signaling pathways, yet the role of this key adaptor in modulating the host response to biofilm growth is unknown. Therefore, we examined the course of S. aureus catheter-associated biofilm infection in MyD88 knockout (KO) mice. MyD88 KO animals displayed significantly increased bacterial burdens on catheters and surrounding tissues during early infection, which …

Sox11 Expression Is Highly Specific For Mantle Cell Lymphoma And Identifies The Cyclin D1-Negative Subtype., Ana Mozos, Cristina Royo, Elena Hartmann, Daphne De Jong, Cristina Baró, Alexandra Valera, Kai Fu, Dennis D. Weisenburger, Jan Delabie, Shih-Sung Chuang, Elaine S. Jaffe, Carmen Ruiz-Marcellan, Sandeep Dave, Lisa Rimsza, Rita Braziel, Randy D. Gascoyne, Francisco Solé, Armando López-Guillermo, Dolors Colomer, Louis M. Staudt, Andreas Rosenwald, German Ott, Pedro Jares, Elias Campo

Journal Articles: Pathology and Microbiology

BACKGROUND: Cyclin D1-negative mantle cell lymphoma is difficult to distinguish from other small B-cell lymphomas. The clinical and pathological characteristics of patients with this form of lymphoma have not been well defined. Overexpression of the transcription factor SOX11 has been observed in conventional mantle cell lymphoma. The aim of this study was to determine whether this gene is expressed in cyclin D1-negative mantle cell lymphoma and whether its detection may be useful to identify these tumors.

DESIGN AND METHODS: The microarray database of 238 mature B-cell neoplasms was re-examined. SOX11 protein expression was investigated immunohistochemically in 12 cases of cyclin …

Modulation Of Edna Release And Degradation Affects Staphylococcus Aureus Biofilm Maturation., Ethan E. Mann, Kelly C. Rice, Blaise R. Boles, Jennifer L. Endres, Dev Ranjit, Lakshmi Chandramohan, Laura H. Tsang, Mark S. Smeltzer, Alexander R. Horswill, Kenneth W. Bayles

Journal Articles: Pathology and Microbiology

Recent studies have demonstrated a role for Staphylococcus aureus cidA-mediated cell lysis and genomic DNA release in biofilm adherence. The current study extends these findings by examining both temporal and additional genetic factors involved in the control of genomic DNA release and degradation during biofilm maturation. Cell lysis and DNA release were found to be critical for biofilm attachment during the initial stages of development and the released DNA (eDNA) remained an important matrix component during biofilm maturation. This study also revealed that an lrgAB mutant exhibits increased biofilm adherence and matrix-associated eDNA consistent with its proposed role as an …

Stromal Gene Signatures In Large-B-Cell Lymphomas., G Lenz, G Wright, S S Dave, W Xiao, J Powell, H Zhao, W Xu, B Tan, N Goldschmidt, Javeed Iqbal, Julie M. Vose, M Bast, Kai Fu, D D. Weisenburger, T C Greiner, James O. Armitage, A Kyle, L May, R D Gascoyne, J M Connors, G Troen, H Holte, S Kvaloy, D Dierickx, G Verhoef, J Delabie, E B Smeland, P Jares, A Martinez, A Lopez-Guillermo, E Montserrat, E Campo, R M Braziel, T P Miller, L M Rimsza, J R Cook, B Pohlman, J Sweetenham, R R Tubbs, R I Fisher, E Hartmann, A Rosenwald, G Ott, H-K Muller-Hermelink, D Wrench, T A Lister, E S Jaffe, W H Wilson, W C. Chan, L M Staudt

Journal Articles: Pathology and Microbiology

BACKGROUND: The addition of rituximab to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), or R-CHOP, has significantly improved the survival of patients with diffuse large-B-cell lymphoma. Whether gene-expression signatures correlate with survival after treatment of diffuse large-B-cell lymphoma is unclear.

METHODS: We profiled gene expression in pretreatment biopsy specimens from 181 patients with diffuse large-B-cell lymphoma who received CHOP and 233 patients with this disease who received R-CHOP. A multivariate gene-expression-based survival-predictor model derived from a training group was tested in a validation group.

RESULTS: A multivariate model created from three gene-expression signatures--termed "germinal-center B-cell," "stromal-1," and "stromal-2"--predicted …

Clinical Implication Of Genome-Wide Profiling In Diffuse Large B-Cell Lymphoma And Other Subtypes Of B-Cell Lymphoma., Javeed Iqbal, Shantaram Joshi, Kavita N. Patel, Sofi I. Javed, Can Kucuk, Afeera Aabida, Francesco D'Amore, Kai Fu

Journal Articles: Pathology and Microbiology

The differentiation of lymphoid cells is tightly regulated by transcription factors at various stages during their development. During the maturation processes, different genomic alterations or aberrations such as chromosomal translocation, mutation and deletions may occur that can eventually result in distinct biological and clinical tumors. The different differentiation stages create heterogeneity in lymphoid malignancies, which can complicate the diagnosis. The initial diagnostic scheme for lymphoid diseases was coined by Rappaport followed by Revised European and American Classification of Lymphoid Neoplasms (REAL) and World Health Organization (WHO) classifications. These classification methods were based on histological, immunophenotypic and cytogenetic markers and widely …