Medical Specialties Commons^™

Demographic And Clinical Features Of Dengue Fever In Pakistan From 2003-2007: A Retrospective Cross-Sectional Study., Erum Khan, Mehreen Kisat, Nabil Khan, Amna Nasir, Salma Ayub, Rumina Hasan

Department of Pathology and Laboratory Medicine

Background: Demographic features of dengue fever have changed tremendously in Pakistan over the past two decades. Small scale studies from all over the country have reported different aspects of individual outbreaks during this time. However, there is scarcity of data looking at the overall trend of dengue virus infection in the country. In this study, we examined annual trends, seasonality, and clinical features of dengue fever in the Pakistani population.
Methods: Demographic information and dengue IgM status of all patients tested for dengue IgM antibody at Aga Khan University Hospital from January 2003 to December 2007 were analyzed to look …

Pattern Of Drugs Of Abuse Identified In Chemical Samples, Farhan Javed Dar, Aysha Habib Khan, Imran Siddiqui, Farooq Ghani

Department of Pathology and Laboratory Medicine

OBJECTIVE: To determine the pattern of drugs of abuse in urine and blood samples processed at referral laboratory in Pakistan so that information on the type of drugs used can be identified and used for ready reference for future strategy. Study Design: Observational study.

PLACE AND DURATION OF STUDY: Clinical Laboratory of The Aga Khan University Hospital, Karachi, from July 2006 to March 2008. Methodology: Retrospective review of records were done for the common drugs that are used for screening at the Clinical Laboratory include alcohol, amphetamine, barbiturates, benzodiazepines, cannabinoids, cocaine and opiates. Alcohol was tested in blood and others …

Inducible Clindamycin Resistance Due To Expression Of Erm Genes In Staphylococcus Aureus: Report From A Tertiary Care Hospital Karachi, Pakistan, Naima Fasih, Seema Irfan, Afia Zafar, Erum Khan, Rumina Hasan

Department of Pathology and Laboratory Medicine

OBJECTIVE: To assess the frequency of phenotypic expression of inducible resistance of clindamycin due to expression of erm genes, in clinical isolates of Staphylococcus aureus (S. aureus), by double disk diffusion test (D-test).

METHOD: This was a cross sectional study conducted in the clinical laboratory of Aga Khan University Hospital, Karachi. A total of 2432, non duplicate clinical isolates of S. aureus, consisting of 1562 methicillin sensitive S. aureus (MSSA) and 870 methicillin resistant S. aureus (MRSA), were selected from February 2007 to January 2008. One hundred and thirty eight isolates of S. aureus were selected based on discordant resistance …

One Year Survival With Poorly Differentiated Metastatic Pancreatic Carcinoma Following Chemoembolization With Gemcitabine And Cisplatin., Daniel B Brown, Carin F Gonsalves, Charles J Yeo, Agnes K Witkiewicz, Brian I Carr

Department of Radiology Faculty Papers

While hepatic arterial chemoembolization is efficacious for a number of malignancies, there is scant data regarding treatment of pancreatic adenocarcinoma. We report a complete radiographic response at one year from diagnosis of metastatic pancreatic carcinoma. Gemcitabine/cisplatin based chemoembolization may be of potential benefit for patients with liver-dominant metastases from pancreatic carcinoma. Given the typical survival of 6 months or less in this patient group with standard therapies, further research is warranted.

Quebec Platelet Disorder, Anwar Hussain Abbasi, Quratulain Shaikh, Syed Ather Hussain

Department of Pathology and Laboratory Medicine

A case of Quebec platelet disorder is hereby reported. A 33 years old woman presented with history of epistaxis and gum bleeding since childhood and menorrhagia and bleeding per vaginum after puberty, also had history of excessive blood loss after birth of child. Her coagulation profile was normal but platelet function testing by platelet aggregation assay showed abnormal aggregation of platelet with epinephrine. This type of response is seen in "Quebec platelet disorder" which is a rare autosomal dominant disorder of platelet function characterized by increased bleeding after any injury or trauma.

Trends In Undergraduate Teaching Of Parasitology In Medical Schools Of Pakistan, Vikram Mehraj, Taimur Saleem, Saima Lalani, Nadia Sani, Imran Khan, Fatima Afridi, Hina Irfan, Mohammad Asim Beg

Department of Pathology and Laboratory Medicine

OBJECTIVE: Parasitic diseases are a major public health problem in the tropical and sub tropical countries including the subcontinent region. We aimed to assess methods of Parasitology education in medical schools of Karachi Pakistan.

METHODS: Ten medical schools in Karachi, Pakistan were sent a structured questionnaire collecting information on different aspects of Parasitology education. The collected data was analyzed using SPSS version 14.0.

RESULTS: The response rate of this study was 90%. Majority of the schools in Karachi, Pakistan (78%) taught Parasitology concurrently with Microbiology, Pathology, Pharmacology and Forensic medicine in third and fourth year of undergraduate training. More than …

Immunophenotypic Profile Of Acute Leukemias At Agakhan University Hospital, Nairobi, Beatrice M. Kabera

Master of Medicine in Clinical Pathology

Background: Reliable distinction between AML and ALL is important for the selection of appropriate therapy. The final diagnosis of acute leukemia should be based on clinico-pathological, morphological, cytochemical and molecular cytogenetics data, together with immunophenotypic information. Flow cytometry has become the preferred method for the lineage assignment and maturational analysis of malignant cells in acute leukemias. Immunophenotyping has also allowed the detection of aberrant antigen co expression and the analysis of heterogeneity and clonality of malignant cells in acute leukemias. It is insufficient to merely make a diagnosis of acute leukemia, or even AML or ALL. Further classification is essential …

Detection Of Extended Spectrum Beta Lactamases Genotypes And Their Association With Cephalosporin Susceptibility In Community Acquired Enterobacteriaceae Infections, Daniel W. Maina

Master of Medicine in Clinical Pathology

Background: Infections caused by Extended Spectrum Beta-Lactamases (ESBLs) producing enterobacteriaceae have become a global problem. Initially confined to the hospital set-up, they are increasingly being reported in the community. These infections are often resistant to a wide variety of B- lactams including extended spectrum cephalosporins, with clinical and epidemiological implications for healthcare systems and necessitate surveillance measures based on local data. Local information on the genotypes of ESBLs and their association with cephalosporin resistance in community acquired ESBL-producing Enterobacteriaceae isolates is scanty, hence the need for this study. Aim: To detect ESBLs genotypes and correlate these with susceptibility to cephalosporins …

Nipple Adenoma Of Breast: A Masquerader Of Malignancy, Kanwal Aftab, Romana Idress

Department of Pathology and Laboratory Medicine

Nipple adenoma is a benign condition simulating malignancy such as breast carcinoma and/or Paget’s disease clinically. In this study 19 cases diagnosed as nipple adenoma over a period of 14 years are described. The diagnosis was confirmed by histology alone. All patients were females with age ranging from 23 to 63 years. Most of the cases presented clinically with in duration and ulceration accompanied by pain and itching. The diagnosis was clinically suspected in only 3 cases. This highlights the importance of histological diagnosis in all suspicious breast lesions. In one case, the clinical and histological diagnosis was incorrect leading …

Patterns Of Fatal Gunshot Injuries In Nairobi: A Prospective Forensic Study, Ancent K. Nzioka

Master of Medicine in Anatomic Pathology

Introduction: Gunshot injuries are one of the leading causes of fatal and non fatal injury in many countries (1) .All over the world, injury studies show an increasing preference for the gun as the weapon of choice for homicides and suicides (2).Firearms are more lethal compared to other portable and concealable weapons (2). Gunshot injuries impact severely on the criminal justice as well as health care systems (3, 4). There is no available published statistics on fatal gunshot injuries inKenya. Some basic statistics are important in understanding the magnitude and severity of the socio-economic burden caused by gunshot injuries. Objective: …

Expression Patterns Of Β–Catenin, Cox-2 And P27 In Colorectal Carcinomas At Aga Khan University Hospital, Nairobi, Patricia Okiro

Master of Medicine in Anatomic Pathology

Introduction: Colorectal cancer is the third most common cancer worldwide, as indicated by WHO. Local published and unpublished data indicate that patients in the developing world with colorectal cancer tend to present at an early age, and possibly at a more advanced stage than described in the developed world. The reason for this difference is unclear, and as yet undefined. The Wnt/APC pathway, Microsatellite instability pathway and the Epigenetic pathway are three pathogenetically distinct pathways that have been implicated in the development of colorectal cancer. Exploration of these patterns may allow us to elucidate possible reasons for these differences. Objectives: …

High-Throughput Experimental Studies To Identify Mirna Targets Directly, With Special Focus On The Mammalian Brain, Peter T. Nelson, Marianthi Kiriakidou, Zissimos Mourelatos, Grace S. Tan, Mary H. Jennings, Kevin Xie, Wang-Xia Wang

Pathology and Laboratory Medicine Faculty Publications

We review the pertinent literature on methods used in high-throughput experimental identification of microRNA (miRNA) "targets" with emphasis on neurochemical studies. miRNAs are short regulatory noncoding RNAs that play important roles in the mammalian brain. The functions of miRNAs are related to their binding of RNAs including mRNAs. Since mammalian miRNAs tend to bind to target mRNAs via imperfect complementarity, understanding exactly which target mRNAs are recognized by which specific miRNAs is a challenge. Based on early experimental evidence, a set of "binding rules" for miRNAs has been described. These have focused on the 5' "seed" region of miRNAs binding …

Labrad : Vol 35, Issue 2 - June 2010, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• The Atypical Lymphocytes
• High Performance Liquid Chromatography (HPLC): An Effective Tool for the Diagnosis of Various Hemoglobinopathies
• Platelet Transfusions: What We Need to Know
• Measuring Homocysteine Levels
• Parathyroid Hormone: A Marker of Vitamin D Deficiency and Insufficiency
• Surrogate Measures of Insulin Sensitivity
• Foetal Autopsy
• Laboratory Diagnosis of Vaginitis due to Trichomonas Vaginalis
• AKU Clinical Laboratory Continuing Medical Education Seminars

Epistatic Relationships Between Sara And Agr In Staphylococcus Aureus Biofilm Formation., Karen E. Beenken, Lara N. Mrak, Linda M. Griffin, Agnieszka K. Zielinska, Lindsey N. Shaw, Kelly C. Rice, Alexander R. Horswill, Kenneth W. Bayles, Mark S. Smeltzer

Journal Articles: Pathology and Microbiology

BACKGROUND: The accessory gene regulator (agr) and staphylococcal accessory regulator (sarA) play opposing roles in Staphylococcus aureus biofilm formation. There is mounting evidence to suggest that these opposing roles are therapeutically relevant in that mutation of agr results in increased biofilm formation and decreased antibiotic susceptibility while mutation of sarA has the opposite effect. To the extent that induction of agr or inhibition of sarA could potentially be used to limit biofilm formation, this makes it important to understand the epistatic relationships between these two loci.

METHODOLOGY/PRINCIPAL FINDINGS: We generated isogenic sarA and agr mutants in clinical isolates of S. …

Individual Micrornas (Mirnas) Display Distinct Mrna Targeting "Rules", Wang-Xia Wang, Bernard R. Wilfred, Kevin Xie, Mary H. Jennings, Yanling Hu, Arnold J. Stromberg, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

MicroRNAs (miRNAs) guide Argonaute (AGO)-containing microribonucleoprotein (miRNP) complexes to target mRNAs.It has been assumed that miRNAs behave similarly to each other with regard to mRNA target recognition. The usual assumptions, which are based on prior studies, are that miRNAs target preferentially sequences in the 3'UTR of mRNAs,guided by the 5' "seed" portion of the miRNAs. Here we isolated AGO- and miRNA-containing miRNPs from human H4 tumor cells by co-immunoprecipitation (co-IP) with anti-AGO antibody. Cells were transfected with miR-107, miR-124,miR-128, miR-320, or a negative control miRNA. Co-IPed RNAs were subjected to downstream high-density Affymetrix Human Gene 1.0 ST microarray analyses using …

Osteopontin And Cadherin 11 Are Novel Mediators And Drug Targets For Chronic Lung Diseases, Daniel J. Schneider

Dissertations and Theses (Open Access)

Chronic lung diseases (CLDs) are a considerable source of morbidity and mortality and are thought to arise from dysregulation of normal wound healing processes. An aggressive, feature of many CLDs is pulmonary fibrosis (PF) and is characterized by excess deposition of extracellular matrix (ECM) proteins from myofibroblasts in airways. However, factors regulating myofibroblast biology are incompletely understood. Proteins in the cadherin family contribute epithelial to mesenchymal transition (EMT), a suggested source of myofibroblasts. Cadherin 11 (CDH11) contributes to developmental and pathologic processes that parallel those seen in PF and EMT. Utilizing Cdh11 knockout (Cdh11 -/-) mice, the goal of this …

Loss Of Stromal Caveolin-1 Independently Predicts Poor Disease-Free Survival And Time To Recurrence In Patients With Prostate Cancer, M. Wagner, A. Dasgupta, F. Sotgia, R. B. West, M. P. Lisanti, A. K. Witkiewicz

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Results:

Of the 167 patients originally included in the study, 43 were either lost to follow up or had insufficient clinical data for comparison. Of the remaining 124 cases, 32 showed loss of stromal Cav-1. Statistical analysis revealed no significant association between stromal Cav-1 loss and the usual markers of disease severity including Gleason grade, stage and presence of metastases. Kaplan-Meier curves showed a significant association between stromal Cav-1 loss and poor disease-free survival and time to recurrence (p<0.05), but no significant association with cancer-specific survival.

Increase In Isolation Of Extended Spectrum Beta Lactamase Producing Multidrug Resistant Non Typhoidal Salmonellae In Pakistan., Kauser Jabeen, Afia Zafar, Seema Irfan, Erum Khan, Vikram Mehraj, Rumina Hasan

Department of Pathology and Laboratory Medicine

Background:Increasing resistance to quinolones and ceftriaxone in non typhoidal Salmonellae is a global concern. Resistance to quinolone and 3rd generation cephalosporin amongst non typhoidal Salmonellae (NTS) from Pakistan has been reported in this study.

Methods:

Retrospective analysis of laboratory data was conducted (1990-2006). NTS were isolated and identified from clinical samples using standard microbiological techniques. Antimicrobial susceptibility testing was performed by Kirby Bauer. Extended spectrum beta lactamase production (ESBL) was detected using combined disc method. Ciprofloxacin sensitivity was detected by nalidixic acid screening method. Minimum inhibitory concentration (MIC) of ciprofloxacin was determined by agar dilution method. Statistical analysis was …

Trends In Salmonella Enteric Serovar Typhi In Nairobi, Kenya From 2004 To 2006, Doris M. Mengo1, Sam Kariuki, Ann W. T. Muigai, Gunturu Revathi

Pathology, East Africa

Background: Typhoid fever is a global health problem. The World Health Organization (WHO) estimates that the current annual global burden of typhoid is approximately 22 million new cases, 5% of which are fatal.

Methodology: To assess the trends in antibiotic resistance in 100 Salmonella enterica serovar Typhi strains were isolated from the blood of patients in Nairobi, Kenya, from 2004 to 2006. All isolates were tested against ampicilin, chloramphenic, nalidixic acid, ciprofloxacin, cotrimoxazole, cefuroxime, cefriaxone, amoxycillin/clavulanic acid, tetracycline and gentamycin. Susceptibility and resistance were determined using MIC and disk diffusion tests.

Results: From 2004 to 2006 a total of 100 …

Increased Isolation Of Esbl Producing Klebsiella Pneumoniae With Emergence Of Carbapenem Resistant Isolates In Pakistan: Report From A Tertiary Care Hospital, Erum Khan, Muslima Ejaz, Afia Zafar, Kauser Jabeen, Sadia Shakoor, Raunaq Inayat, Rumina Hasan

Department of Pathology and Laboratory Medicine

OBJECTIVE: To report trends of extended spectrum beta lactamase (ESBL), multidrug resistant (MDR) ESBL and emergence of carbapenem resistant ESBL producing isolates of K. pneumoniae from Pakistan.

METHODS: Retrospective analysis of laboratory data was conducted (2002-2007). K. pneumoniae were isolated and identified from clinical samples using standard microbiological techniques. Antimicrobial susceptibility testing was performed by Kirby Bauer. ESBL was detected using combined disc method. Statistical analysis was performed using SPSS version 13.

RESULTS: 15914 K. pneumoniae isolates (2002-2007) were analyzed. Significant increase in ESBL and MDR ESBL producing K. pneumoniae (p = or < 0.0001) was observed. We found significant association of ESBL positive K. pneumoniae with age less than 10 years, males and blood isolates (p = 0.001). 0.4% (n=23) of ESBL positive isolates were carbapenem resistant.

CONCLUSIONS: Increase in ESBL and carbapenem resistant …

Microrna In Situ Hybridization In The Human Entorhinal And Transentorhinal Cortex, Peter T. Nelson, James Dimayuga, Bernard R. Wilfred

Pathology and Laboratory Medicine Faculty Publications

MicroRNAs (miRNAs) play key roles in gene expression regulation in both healthy and disease brains. To better understand those roles, it is necessary to characterize the miRNAs that are expressed in particular cell types under a range of conditions. In situ hybridization (ISH) can demonstrate cell- and lamina-specific patterns of miRNA expression that would be lost in tissue-level expression profiling. In the present study, ISH was performed with special focus on the human entorhinal cortex (EC) and transentorhinal cortex (TEC). The TEC is the area of the cerebral cortex that first develops neurofibrillary tangles in Alzheimer's disease (AD). However, the …

Anti-Argonaute Rip-Chip Shows That Mirna Transfections Alter Global Patterns Of Mrna Recruitment To Microribonucleoprotein Complexes, Wang-Xia Wang, Bernard R. Wilfred, Yanling Hu, Arnold J. Stromberg, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

MicroRNAs (miRNAs) play key roles in gene expression regulation by guiding Argonaute (AGO)-containing microribonucleoprotein (miRNP) effector complexes to target polynucleotides. There are still uncertainties about how miRNAs interact with mRNAs. Here we employed a biochemical approach to isolate AGO-containing miRNPs from human H4 tumor cells by co-immunoprecipitation (co-IP) with a previously described anti-AGO antibody. Co-immunoprecipitated (co-IPed) RNAs were subjected to downstream Affymetrix Human Gene 1.0 ST microarray analysis. During rigorous validation, the "RIP-Chip" assay identified target mRNAs specifically associated with AGO complexes. RIP-Chip was performed after transfecting brain-enriched miRNAs (miR-107, miR-124, miR-128, and miR-320) and nonphysiologic control miRNA to identify …

Pulmonary Carcinosarcoma Initially Presenting As Invasive Aspergillosis: A Case Report Of Previously Unreported Combination, Ariyo O. Olobatoke, Doina David, Wasif Hafeez, Thien Van, Husain A. Saleh

Wayne State University Associated BioMed Central Scholarship

Abstract

Carcinosarcoma of the lung is a malignant tumor composed of a mixture of carcinoma and sarcoma elements. The carcinomatous component is most commonly squamous followed by adenocarcinoma. The sarcomatous component commonly comprises the bulk of the tumor and shows poorly differentiated spindle cell features. Foci of differentiated sarcomatous elements such as chondrosarcoma and osteosarcoma may be seen. Aspergillus pneumonia is the most common form of invasive aspergillosis and occurs mainly in patients with malignancy, immunocompromizing or debilitating diseases. Patients with Aspergillus pneumonia present with fever, cough, chest pain and occasionally hemoptysis. Tissue examination is the most reliable method for …

Nuclear Factor-Kappa B Localization And Function Within Intrauterine Tissues From Term And Preterm Labor And Cultured Fetal Membranes, Sonali Vora, Asad Abbas, Chong J. Kim, Taryn Ls Summerfield, Juan P. Kusanovic, Jay D. Iams, Roberto Romero, Douglas A. Kniss, William E. Ackerman Iv

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The objective of this study was to quantify the nuclear localization and DNA binding activity of p65, the major transactivating nuclear factor-kappa B (NF-kappaB) subunit, in full-thickness fetal membranes (FM) and myometrium in the absence or presence of term or preterm labor.

Methods

Paired full-thickness FM and myometrial samples were collected from women in the following cohorts: preterm no labor (PNL, N = 22), spontaneous preterm labor (PTL, N = 21), term no labor (TNL, N = 23), and spontaneous term labor (STL, N = 21). NF-kappaB p65 localization was assessed by immunohistochemistry, and DNA binding activity was …

Nuclear Expression Of Klf6 Tumor Suppressor Factor Is Highly Associated With Overexpression Of Erbb2 Oncoprotein In Ductal Breast Carcinomas, Ricardo C. Gehrau, Diego S. D'Astolfo, Catherine I. Dumur, Jose L. Bocco, Nicolas P. Koritschoner

Pathology Publications

Background

Krüppel-like factor 6 (KLF6) is an evolutionarily conserved and ubiquitously expressed protein that belongs to the mammalian Sp1/KLF family of transcriptional regulators. Though KLF6 is a transcription factor and harbors a nuclear localization signal it is not systematically located in the nucleus but it was detected in the cytoplasm of several tissues and cell lines. Hence, it is still not fully settled whether the tumor suppressor function of KLF6 is directly associated with its ability to regulate target genes.

Methodology/Principal Findings

In this study we analyzed KLF6 expression and sub-cellular distribution by immunohistochemistry in several normal and tumor tissues …

Mir-107 Is Reduced In Alzheimer's Disease Brain Neocortex: Validation Study, Peter T. Nelson, Wang-Xia Wang

Pathology and Laboratory Medicine Faculty Publications

MiR-107 is a microRNA (miRNA) that we reported previously to have decreased expression in the temporal cortical gray matter early in the progression of Alzheimer's disease (AD). Here we study a new group of well-characterized human temporal cortex samples (N=19). MiR-107 expression was assessed, normalized to miR-124 and let-7a. Correlation was observed between decreased miR-107 expression and increased neuritic plaque counts (P< 0.05) and neurofibrillary tangle counts (P< 0.02) in adjacent brain tissue. Adjusted miR-107 and BACE1 mRNA levels tended to correlate negatively (trend with regression P< 0.07). In sum, miR-107 expression tends to be lower relative to other miRNAs as AD progresses.

Leiomyosarcoma Arising In The Pancreatic Duct: A Case Report And Review Of The Current Literature, Nicole D. Riddle, Brian C. Quigley, Irwin Browarsky, Marilyn M. Bui

Pathology and Cell Biology Faculty Publications

Context. Leiomyosarcomas are rare malignant smooth muscle tumors that may arise in any organ or tissue that contains smooth muscle, commonly within the gastrointestinal tract. They are most often found in the stomach, large and small intestines, and retroperitoneum. Primary pancreatic leiomyosarcoma is extremely rare, and to the best of our knowledge only 30 cases have been reported in the world literature since 1951. Our case represents the first to have a clear origin from the main pancreatic duct. Case Report. This case was diagnosed in a large, tertiary care center in Tampa, Florida. Pertinent information was obtained …

Labrad : Vol 35, Issue 1 - January - February 2010, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• Assessment of Osteoporosis Risk by NTx- A Biochemical Marker
• Antibodies Against Cyclic Citrullinated Peptides (Anti-CCP) Assay in Rheumatoid Arthritis
• A Disintegrin and Metallopeptidase with Thrombospondin Type 1 Motif, 13 (ADAMTS-13)
• Soluble Transferrin Receptor (sTfR)
• Diagnosis of Cryptococcal Meningitis
• Infections in Thalassaemia
• CDX-2, A Reliable Diagnostic Marker for Carcinomas of Colorectal Origin
• Radiopaque Metallic Marker Insertion in Breast Cancers Prior to Neoadjuvant/Preoperative Chemotherapy
• Meeting Reports: 10TH International Radiological Conference 2009
• Continuing Medical Education Seminar Organised by Clinical Laboratory at AKUH

Application Of Magnetic Resonance Imaging To Understanding The Pathogenesis Of The X-Linked Leukodystrophy Pelizaeus-Merzbacher Disease, Jeremy Jerome Laukka

Wayne State University Dissertations

Myelin is a multilamellar membrane structure surrounding axons in both the CNS and PNS that facilitates nerve conduction. In the CNS, myelin is synthesized by oligodendrocytes, while in the PNS, myelin is synthesized by Schwann cells. In the CNS, Proteolipid protein 1 (PLP1), an integral membrane protein, is the major protein component of myelin, constituting ~50% of myelin protein. Mutations of the PLP1 gene in man cause a spectrum of neurological disease, ranging from the severe Pelizaeus-Merzbacher disease (PMD), that typically begins during infancy with nystagmus, seizures and hypotonia and evolves into spastic quadriparesis, cognitive impairment and ataxia, to ¡¥pure¡¦ …

I-Kappa-Kinase-2 (Ikk-2) Inhibition Potentiates Vincristine Cytotoxicity In Non-Hodgkin's Lymphoma, Ayad Al-Katib, Alan A. Arnold, Amro Aboukameel, Angela Sosin, Peter Smith, Anwar N. Mohamed, Frances W. Beck, Ramzi M. Mohammad

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

IKK-2 is an important regulator of the nuclear factor-κB (NF-κB) which has been implicated in survival, proliferation and apoptosis resistance of lymphoma cells. In this study, we investigated whether inhibition of IKK-2 impacts cell growth or cytotoxicity of selected conventional chemotherapeutic agents in non-Hodgkin's lymphoma.

Two established model systems were used; Follicular (WSU-FSCCL) and Diffuse Large Cell (WSU-DLCL2) Lymphoma, both of which constitutively express p-IκB. A novel, selective small molecule inhibitor of IKK-2, ML120B (N-[6-chloro-7-methoxy-9H-β-carbolin-8-yl]-2-methylnicotinamide) was used to perturb NF-κB in lymphoma cells. The growth inhibitory effect of ML120B (M) alone and in combination with cyclophosphamide monohydrate (C), …