Pathology Commons^™

Ethnic Disparity In 21-Hydroxylase Gene Mutations Identified In Pakistani Congenital Adrenal Hyperplasia Patients, Aysha Habib Khan, Muniba Aban, Jamal Raza, Naeem Ul Haq, Abdul Jabbar, Tariq Moatter

Department of Pathology and Laboratory Medicine

Background: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders caused by defects in the steroid 21 hydroxylase gene (CYP21A2). We studied the spectrum of mutations in CYP21A2 gene in a multi-ethnic population in Pakistan to explore the genetics of CAH.

Methods: A cross sectional study was conducted for the identification of mutations CYP21A2 and their phenotypic associations in CAH using ARMS-PCR assay.

Results: Overall, 29 Patients were analyzed for nine different mutations. The group consisted of two major forms of CAH including 17 salt wasters and 12 simple virilizers. There were 14 phenotypic males and 15 females …

Patterns Of Microrna Expression In Normal And Early Alzheimer's Disease Human Temporal Cortex: White Matter Versus Gray Matter, Wang-Xia Wang, Qingwei Huang, Yanling Hu, Arnold J. Stromberg, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

MicroRNA (miRNA) expression was assessed in human cerebral cortical gray matter (GM) and white matter (WM) in order to provide the first insights into the difference between GM and WM miRNA repertoires across a range of Alzheimer's disease (AD) pathology. RNA was isolated separately from GM and WM portions of superior and middle temporal cerebral cortex (N = 10 elderly females, postmortem interval < 4 h). miRNA profiling experiments were performed using state-of-the-art Exiqon^© LNA-microarrays. A subset of miRNAs that appeared to be strongly expressed according to the microarrays did not appear to be conventional miRNAs according to Northern blot analyses. Some well-characterized miRNAs were substantially enriched in WM …

Detection Of Ndm-1-Producing Klebsiella Pneumoniae In Kenya., Laurent Poirel, Gunturu Revathi, Sandrine Bernabeu, Patrice Nordmann

Pathology, East Africa

Seven carbapenem-resistant NDM-1-positive Klebsiella pneumoniae isolates were recovered from patients hospitalized between 2007 and 2009 in different wards at a referral and tertiary care center in Nairobi. Most of the isolates were obtained from urine. All isolates carried the bla_NDM-1 carbapenemase gene previously reported from India, Pakistan, and the United Kingdom. These isolates were clonally related and expressed many other resistance determinants, including β-lactamases CTX-M-15, OXA-1, OXA-9, CMY-6, and aminoglycoside resistance methylase RmtC. This work corresponds to the first report of NDM-1 producers in Africa.

Prevalence Of Resistance Associated Polymorphisms In Plasmodium Falciparum Field Isolates From Southern Pakistan, Najia Karim Ghanchi, Johan Ursing, Mohammad A. Beg, Maria I. Veiga, Sana Jafri, Andreas Martensson

Department of Pathology and Laboratory Medicine

Background:Scarce data are available on Plasmodium falciparum anti-malarial drug resistance in Pakistan. The aim of this study was, therefore, to determine the prevalence of P. falciparum resistance associated polymorphisms in field isolates from southern Pakistan.
Methods:
Blood samples from 244 Patients with blood-slide confirmed P. falciparum mono-infections were collected between 2005-2007. Single nucleotide polymorphisms in the P. falciparum chloroquine resistance transporter (pfcrt K76T), multi drug resistance (pfmdr1 N86Y), dihydrofolate reductase (pfdhfr A16V, N51I, C59R, S108N, I164L) and dihydropteroate synthetase (pfdhps A436S, G437A and E540K) genes and pfmdr1 gene copy numbers were determined using PCR based methods.
Results:The prevalence …

Neuroinflammation Leads To Region-Dependent Alterations In Astrocyte Gap Junction Communication And Hemichannel Activity., Nikolay Karpuk, Maria Burkovetskaya, Teresa Fritz, Amanda Angle, Tammy Kielian

Journal Articles: Pathology and Microbiology

Inflammation attenuates gap junction (GJ) communication in cultured astrocytes. Here we used a well-characterized model of experimental brain abscess as a tool to query effects of the CNS inflammatory milieu on astrocyte GJ communication and electrophysiological properties. Whole-cell patch-clamp recordings were performed on green fluorescent protein (GFP)-positive astrocytes in acute brain slices from glial fibrillary acidic protein-GFP mice at 3 or 7 d after Staphylococcus aureus infection in the striatum. Astrocyte GJ communication was significantly attenuated in regions immediately surrounding the abscess margins and progressively increased to levels typical of uninfected brain with increasing distance from the abscess proper. Conversely, …

Estrogen Sulfotransferase (Sult1e1) Expression And Function In Mcf10a-Series Breast Epithelial Cells: Role As A Modifier Of Breast Carcinogenesis And Regulation By Proliferation State, Jiaqi Fu

Wayne State University Dissertations

Estrogen sulfotransferase (SULT1E1) catalyzes the sulfonation of estrogens, which limits estrogen mitogenicity. TaqMan Gene Expression assays were used to profile the mRNA expression of estrogen receptor (ERα and ERβ) and estrogen metabolism enzymes including cytosolic sulfotransferases (SULT1E1, SULT1A1, SULT2A1, and SULT2B1), steroid sulfatase (STS), aromatase (CYP19), 17β-hydroxysteroid dehydrogenases (17βHSD1 and 2), CYP1B1, and catechol-O-methyltransferase (COMT) in an MCF10A-derived lineage cell culture model for basal-like human breast cancer progression and in ERα-positive luminal MCF7 breast cancer cells. Low levels of ERα and ERβ mRNA were present in MCF10A-derived cell lines. SULT1E1 mRNA was more abundant in confluent relative to subconfluent MCF10A …

Effect Of Clinical Laboratory Practitioner Licensing On Wages, Mary Hotaling

Walden Dissertations and Doctoral Studies

Professional licensing directly affects about 29% of U.S. workers and is considered a primary means to establish and maintain health care practitioner competence. Clinical laboratory practitioner licensing was largely ignored in the literature with only 2 studies 30 years apart that provided conflicting conclusions regarding wage effects. This research provided the first study of clinical laboratory practitioner licensing effects on wages after controlling for human capital and individual characteristics wage determinants. This nonexperimental correlational study extended the literature on licensing effects on wages, including women's wages and professions not uniformly licensed across 50 states. The theoretical foundation relied on the …

Molecular Bases Of Cutaneous And Uveal Melanomas, Sudeep Gaudi, Jane L. Messina

Pathology and Cell Biology Faculty Publications

Intensive research in recent years has begun to unlock the mysteries surrounding the molecular pathogenesis of melanoma, the deadliest of skin cancers. The high-penetrance, low-frequency susceptibility gene CDKN2A produces tumor suppressor proteins that function in concert with p53 and retinoblastoma protein to thwart melanomagenesis. Aberrant CDKN2A gene products have been implicated in a great many cases of familial cutaneous melanoma. Sporadic cases, on the other hand, often involve constitutive signal transduction along the mitogen-activated protein kinase (MAPK) pathway, with particular focus falling upon mutated RAS and RAF protooncogenes. The proliferative effects of the MAPK pathway may be complemented by the …

Primary Colorectal Adenocarcinoma Metastatic To The Breast: Case Report And Review Of Nineteen Cases, Rodney E. Shackelford, Pushpa Allam-Nandyala, Marilyn M. Bui, John V. Kiluk, Nicole Nicosia Esposito

Pathology and Cell Biology Faculty Publications

Metastases to the breast from extramammary primaries are uncommon and account for 0.5–6% of all breast malignancies (Georgiannos et al., 2001, and Vizcaíno et al., 2001). Malignant melanoma, lymphoma, and lung and gastric carcinomas are the most frequently encountered nonmammary metastases to the breast in adults (Georgiannos et al., 2001, and Chaignaud et al., 1994). Primary colorectal adenocarcinoma (CRC) metastatic to the breast is extremely rare, with the medical literature having only 19 recorded cases. Typically CRC metastatic to the breast is indicative of widely disseminated disease and a poor prognosis. Here we present a case of poorly differentiated colon …

Pathology Of Breast Carcinoma: Diagnostic, Prognostic, And Therapeutic Issues And Challenges, Rohit Bhargava, Sunati Sahoo, Nicole Nicosia Esposito, Beiyun Chen

Pathology and Cell Biology Faculty Publications

No abstract provided.

Novel Molecular Markers Of Malignancy In Histologically Normal And Benign Breast, Aejaz Nasir, Dung-Tsa Chen, Mike Gruidl, Evita B. Henderson-Jackson, Chinnambally Venkataramu, Susan M. Mccarthy, Heyoung L. Mcbrid, Eleanor Harris, Nazanin Khakpour, Timothy J. Yeatman

Pathology and Cell Biology Faculty Publications

To detect the molecular changes of malignancy in histologically normal breast (HNB) tissues, we recently developed a novel 117-gene-malignancy-signature. Here we report validation of our leading malignancy-risk-genes, topoisomerase-2-alpha (TOP2A), minichromosome-maintenance-protein-2 (MCM2) and “budding-uninhibited-by-benzimidazoles-1-homolog-beta” (BUB1B) at the protein level. Using our 117-gene malignancy-signature, we classified 18 fresh-frozen HNB tissues from 18 adult female breast cancer patients into HNB-tissues with low-grade (HNB-LGMA; ) and high-grade molecular abnormality (HNB-HGMA; ). Archival sections of additional HNB tissues from these patients, and invasive ductal carcinoma (IDC) tissues from six other patients were immunostained for these biomarkers. TOP2A/MCM2 expression was assessed as staining index (%) and …

Ovarian Epithelial-Stromal Interactions: Role Of Interleukins 1 And 6, Kamisha T. Woolery, Patricia A. Kruk

Pathology and Cell Biology Faculty Publications

Ovarian epithelial cancer is the most lethal gynecologic malignancy. The high mortality is attributed to the fact that most cases typically present in late stage when ovarian cancer (OC) has already spread beyond the ovary. Ovarian epithelial cancer cells are shed into intraperitoneal ascites and easily disseminate throughout the peritoneal cavity with preferential metastasis to the omentum, peritoneum, and local organs. Understanding how ovarian epithelial cells interact with and modulate their microenvironment can provide insight into the molecular mechanism(s) involved with malignant transformation and progression which may eventually identify novel diagnostic, prognostic, and therapeutic targets. The objective of this paper …

A Ten-Year Review Of Neonatal Bloodstream Infections In A Tertiary Private Hospital In Kenya, Ruchika Kohli-Kochhar, Geoffrey Omuse, Gunturu Revathi

Pathology, East Africa

Introduction: Neonatal mortality in developing countries is usually due to an infectious cause. The gold standard of investigation in developing countries is a positive blood culture. It is important to know the aetiology of neonatal bloodstream infections so that empiric treatment can be effective.

Methodology: We conducted a retrospective clinical audit over ten years between January 2000 until December 2009, looking at the aetiology of both early and late onset neonatal sepsis. We analysed data from 152 (23%) patient isolates out of 662 suspected cases of neonatal sepsis.

Results: Our study revealed that Gram-positive organisms were the predominant cause of …

Malaria Rapid Testing By Community Health Workers Is Effective And Safe For Targeting Malaria Treatment: Randomised Cross-Over Trial In Tanzania, M. Mubi, A. Janson, M. Warsame, A. Martensson, K. Kallander, M.G. Petzold, B. Ngasala, G. Maganga, L.L. Gustafsson, A. Massele, G. Tomson, Zul Premji, A. Bjorkman

Pathology, East Africa

Background: Early diagnosis and prompt, effective treatment of uncomplicated malaria is critical to prevent severe disease, death and malaria transmission. We assessed the impact of rapid malaria diagnostic tests (RDTs) by community health workers (CHWs) on provision of artemisinin-based combination therapy (ACT) and health outcome in fever patients.

Methodology/Principal Findings: Twenty-two CHWs from five villages in Kibaha District, a high-malaria transmission area in Coast Region, Tanzania, were trained to manage uncomplicated malaria using RDT aided diagnosis or clinical diagnosis (CD) only. Each CHW was randomly assigned to use either RDT or CD the first week and thereafter alternating weekly. …

Pre-Referral Rectal Artesunate In Severe Malaria: Flawed Trial, K.F. Hirji, Zul Premji

Pathology, East Africa

Background:Immediate injectable treatment is essential for severe malaria. Otherwise, the afflicted risk lifelong impairment or death. In rural areas of Africa and Asia, appropriate care is often miles away. In 2009, Melba Gomes and her colleagues published the findings of a randomized, placebo-controlled trial of rectal artesunate for suspected severe malaria in such remote areas. Enrolling nearly 18,000 cases, the aim was to evaluate whether, as patients were in transit to a health facility, a pre-referral artesunate suppository blocked disease progression sufficiently to reduce these risks. The affirmative findings of this, the only trial on the issue thus far, …

Should Histologic Grade Be Incorporated Into The Tnm Classification System For Small (T1, T2) Node-Negative Breast Adenocarcinomas?, Matthew Purdom, Michael L. Cibull, Terry D. Stratton, Luis M. Samayoa, Edward Romond, Patrick C. Mcgrath, Rouzan G. Karabakhtsian

Pathology and Laboratory Medicine Faculty Publications

Prognosis of invasive ductal carcinoma (IDC) strongly correlates with tumor grade as determined by Nottingham combined histologic grade. While reporting grade as low grade/favorable (G1), intermediate grade/moderately favorable (G2), and high grade/unfavorable (G3) is recommended by American Joint Committee on Cancer (AJCC) staging system, existing TNM (Primary Tumor/Regional Lymph Nodes/Distant Metastasis) classification does not directly incorporate these data. For large tumors (T3, T4), significance of histologic grade may be clinically moot as those are nearly always candidates for adjuvant therapy. However, for small (T1, T2) node-negative (N0) tumors, grade may be clinically relevant in influencing treatment decisions, but data on …

Aplastic Anemia: Clinicohaematological Features, Treatment And Outcome Analysis, Rabia Wali, Zehra Fidoo, Salman Adil, Muhammad Ahmed Naqvi

Department of Pathology and Laboratory Medicine

Objective: To determine the clinicohaematological features, treatment and outcome of children diagnosed with aplastic anemia at a single institution.

Study Design: Observational study.

Place and Duration of Study: The Aga Khan University Hospital, Karachi, from January 1999 till December 2008.

Methodology: Medical records of children aged less than 15 years of age diagnosed with aplastic anemia were reviewed. Clinicohaematological features, treatment and its response to therapy and outcome were recorded. Results were described in percentages.

Results: Ninety patients were diagnosed to have aplastic anemia (AA); 65 were male during the study period. Age ranged from 1 to 15 years. Fever …

Immunoproliferative Small Intestinal Disease (Ipsid), Shahid Pervez, Khalid Mumtaz, Syed Siddiq Ullah, Nake Akhtar, Naureen Ali, Hina Aaqil

Department of Pathology and Laboratory Medicine

This study describes the frequency, demographics, clinical presentation, endoscopic findings, histopathological features, treatment and outcome of 'Immunoproliferative small intestinal disease' (IPSID). Archives contained a total of 27 cases of IPSID diagnosed and treated over an 18-year period. A M: F ratio of 2.4:1 was seen with a mean and median ages of 28.7 and 25 years. Most patients (68.8%) presented with abdominal pain and diarrhoea. In the majority (62.5%), duodenum was the primary site of involvement. Endoscopy showed polypoidal, raised or flat lesions. Biopsy findings included blunting or flattening of villi with dense plasma cell infiltrate and lymphoepithelial lesions. Twenty-four …

Gastric Malt Lymphoma: A Rarity, Shahid Pervez, Naureen Ali, Hina Aaqil, Khalid Mumtaz, Syed Siddiq Ullah

Department of Pathology and Laboratory Medicine

Association of Helicobacter pylori (H. Pylori) infection with gastric ‘Mucosa Associated Lymphoid Tissue’ (MALT) lymphomas (MALTomas) is well established. In this study the frequency and characteristics of gastric MALToma over a period of 18 years was evaluated. During this period 24 patients with gastric MALToma were diagnosed; out of them, 13 (54.2%) had active H. Pylori infection. The mean and median age was 49.7 and 53.5 years. The male: female ratio was 17:7. The common presenting complaints were epigastric pain (n=10) and dyspepsia (n=9). Endoscopic findings revealed mild gastric hyperemia (n=16), superficial erosions (n=4) and superficial ulcers (n=4). It was …

Efficacy And Safety Of Artemether-Lumefantrine In The Treatment Of Acute, Uncomplicated Plasmodium Falciparum Malaria: A Pooled Analysis, M. Makanga, Q. Bassat, C.O. Falade, Zul Premji, S. Krudsood, P. Hunt, V. Walter, H.-P. Beck, A.-C. Marrast, M. Cousin, P.J. Rosenthal

Pathology, East Africa

Randomized trials have confirmed the efficacy and safety of artemether-lumefantrine (AL) for treatment of uncomplicated Plasmodium falciparum malaria. Data from seven studies supported by Novartis (1996-2007), including 647 adults (> 16 years of age, 83.3% completed the study) and 1,332 children (≤ 16 years of age, 89.3% completed the study) with microscopically confirmed uncomplicated P. falciparum malaria and treated with the recommended regimen of AL, were pooled. The 28-day polymerase chain reaction-corrected parasitologic cure rate (primary efficacy endpoint) was 97.1% (495 of 510) in adults and 97.3% (792 of 814) in children (evaluable population). Gametocytemia prevalence after day was 4.2% …