Pathology Case Study: Nephrotic Syndrome and Gross Hematuria

The University of Pittsburgh School of Medicine's Department of Pathology has compiled a series of case studies to help both students and instructors in the health sciences field. The patient treated in this case is a 20 year-old man with flank pain. Information on the initial examination and lab results are provided in the âPatient Historyâ section. The âGross Description,â âMicroscopic Description,â âImmunofluorescence Examinationâ and âElectron Microscope Examinationâ sections provide key information and images that contributed to the patientâs diagnosis. Clicking on the âFinal Diagnosisâ will lead you to a thorough explanation of the diagnosis and illness from the patientâs doctors

Pathology Case Study: Dilated Cardiomyopathy

This is a case study presented by the University of Pittsburgh Department of Pathology in which a man presented with a large range of symptoms from chills and fever to underdeveloped calf muscles. Visitors are given both the microscopic and gross descriptions, including images, and are given the opportunity to diagnose the patient. This is an excellent resource for students in the health sciences to familiarize themselves with using patient history and laboratory results to diagnose disease. It is also a helpful site for educators to use to introduce or test student learning in cardiovascular pathology

Pathology Case Study: New Onset Diplopia and Mental Status Changes

This is a case study presented by the University of Pittsburgh Department of Pathology in which 48-year-old Caucasian woman, with previous bill of good health, presents with a headache, neck stiffness and diplopia. Aside from the physical symptoms, the patient was also confused and appeared to have symptoms of short-term memory loss. Lab results, images from a CT scan of the patientâs brain, and microscopic images of a stereotactic biopsy are included in the case study. The âFinal Diagnosisâ section includes a detailed description of the condition from the contributing doctors. This is an excellent resource for students in the health sciences to familiarize themselves with using patient history and laboratory results to diagnose patientâs conditions

Novel Death Defying Domain In Met Entraps The Active Site Of Caspase-3 And Blocks Apoptosis In Hepatocytes

Met, the transmembrane tyrosine kinase receptor for hepatocyte growth factor (HGF), is known to function as a potent antiapoptotic mediator in normal and neoplastic cells. Herein we report that the intracellular cytoplasmic tail of Met has evolved to harbor a tandem pair of caspase-3 cleavage sites, which bait, trap, and disable the active site of caspase-3, thereby blocking the execution of apoptosis. We call this caspase-3 cleavage motif the Death Defying Domain (DDD). This site consists of the following sequence: DNAD-DEVD-T (where the hyphens denote caspase cleavage sites). Through functional and mechanistic studies, we show that upon DDD cleavage by caspase-3 the resulting DEVD-T peptide acts as a competitive inhibitor and entraps the active site of caspase-3 akin to DEVD-CHO, which is a potent, synthetic inhibitor of caspase-3 activity. By gain- and loss-of-function studies using restoration of DDD expression in DDD-deficient hepatocytic cells, we found that both caspase-3 sites in DDD are necessary for inhibition of caspase-3 and promotion of cell survival. Employing mutagenesis studies, we show that DDD could operate independently of Met\u27s enzymatic activity as determined by using kinase-dead human Met mutant constructs. Studies of both human liver cancer tissues and cell lines uncovered that DDD cleavage and entrapment of caspase-3 by DDD occur in vivo, further proving that this site has physiological and pathophysiological relevance. Conclusion: Met can directly inhibit caspase-3 by way of a novel mechanism and promote hepatocyte survival. The results presented here will further our understanding of the mechanisms that control not only normal tissue homeostasis but also abnormal tissue growth such as cancer and degenerative diseases in which apoptotic caspases are at play. © 2014 by the American Association for the Study of Liver Diseases

Somatic mutation and functional polymorphism of a novel regulatory element in the HGF gene promoter causes its aberrant expression in human breast cancer

The HGF gene is transcriptionally silenced in normal differentiated breast epithelial cells, but its repression fails to occur in mammary carcinoma tissues and cell lines. The molecular mechanisms underpinning aberrant HGF expression in breast cancer cells are unknown. Here we report the discovery of a DNA element located 750 bp upstream from the transcription start site in the human HGF promoter that acts as a transcriptional repressor and is a target of deletion mutagenesis in human breast cancer cells and tissues. This HGF promoter element consists of a mononucleotide repeat of 30 deoxyadenosines (30As), which we have termed “deoxyadenosine tract element” (DATE). Functional studies revealed that truncation mutations within DATE have profound local and global effects on the HGF promoter region by modulating chromatin structure and DNA-protein interactions, leading to constitutive activation of the HGF promoter in human breast carcinoma cell lines. We found that 51% of African Americans and 15% of individuals of mixed European descent with breast cancer harbor a truncated DATE variant (25As or fewer) in their breast tumors and that the truncated allele is associated with cancer incidence and aberrant HGF expression. Notably, breast cancer patients with the truncated DATE variant are substantially younger than those with a wild-type genotype. We also suggest that DATE may be used as a potential genetic marker to identify individuals with a higher risk of developing breast cancer