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Expert Review of Clinical Immunology 2015Current laboratory investigation of patients with suspected immunodeficiency or immune-mediated disease includes extensive analysis of lymphocyte subsets, T-cell...
Current laboratory investigation of patients with suspected immunodeficiency or immune-mediated disease includes extensive analysis of lymphocyte subsets, T-cell receptor use, antibody profiles, cytokine profiles and genetic polymorphisms of relevant genes, all in all: big data. Clinical immunology clearly has entered the omics era, generating more and more data.
Topics: Animals; Antibodies; Data Mining; Humans; Immune System Diseases; Medical Informatics; Pathology, Molecular; Vaccination
PubMed: 26092383
DOI: 10.1586/1744666X.2015.1059277 -
Advanced Healthcare Materials Apr 2018Engineered polymer vesicles, termed as polymersomes, confer a flexibility to control their structure, properties, and functionality. Self-assembly of amphiphilic... (Review)
Review
Engineered polymer vesicles, termed as polymersomes, confer a flexibility to control their structure, properties, and functionality. Self-assembly of amphiphilic copolymers leads to vesicles consisting of a hydrophobic bilayer membrane and hydrophilic core, each of which is loaded with a wide array of small and large molecules of interests. As such, polymersomes are increasingly being studied as carriers of imaging probes and therapeutic drugs. Effective delivery of polymersomes necessitates careful design of polymersomes. Therefore, this review article discusses the design strategies of polymersomes developed for enhanced transport and efficacy of imaging probes and therapeutic drugs. In particular, the article focuses on overviewing technologies to regulate the size, structure, shape, surface activity, and stimuli- responsiveness of polymersomes and discussing the extent to which these properties and structure of polymersomes influence the efficacy of cargo molecules. Taken together with future considerations, this article will serve to improve the controllability of polymersome functions and accelerate the use of polymersomes in biomedical applications.
Topics: Animals; Drug Carriers; Humans; Nanoparticles; Particle Size; Pathology, Molecular; Polymers
PubMed: 29334183
DOI: 10.1002/adhm.201701276 -
Toxicologic Pathology Jan 2017The 35th Annual Society of Toxicologic Pathology Symposium, held in June 2016 in San Diego, California, focused on "The Basis and Relevance of Variation in Toxicologic...
The 35th Annual Society of Toxicologic Pathology Symposium, held in June 2016 in San Diego, California, focused on "The Basis and Relevance of Variation in Toxicologic Responses." In order to review the basic tenants of toxicology, a "broad brush" interactive talk that gave an overview of the Cornerstones of Toxicology was presented. The presentation focused on the historical milestones and perspectives of toxicology and through many scientific graphs, data, and real-life examples covered the three basic principles of toxicology that can be summarized, as dose matters (as does timing), people differ, and things change (related to metabolism and biotransformation).
Topics: Animals; Dose-Response Relationship, Drug; History, 19th Century; History, 20th Century; History, 21st Century; History, Ancient; Humans; Pathology; Poisoning; Toxicology
PubMed: 28068892
DOI: 10.1177/0192623316675768 -
The Veterinary Clinics of North... Sep 2022Freshwater turtles are physiologically unique in their adaptations to life on both land and freshwater habitats. Appropriate interpretation of laboratory values specific... (Review)
Review
Freshwater turtles are physiologically unique in their adaptations to life on both land and freshwater habitats. Appropriate interpretation of laboratory values specific to these species is important for both conservation efforts in free-ranging populations and in captive populations, especially because these animals become increasingly popular as pets. Although normal physiology has been well characterized, understanding of clinicopathologic changes in response to disease processes in freshwater chelonian species is relatively limited. This article reviews the current knowledge of hematology, plasma biochemistry, and urinalysis specific to freshwater turtles, with correlates to other chelonian species when specific data are unavailable.
Topics: Animals; Ecosystem; Fresh Water; Pathology, Clinical; Turtles
PubMed: 36122951
DOI: 10.1016/j.cvex.2022.05.005 -
Frontiers in Medicine 2017Eosinophilic gastrointestinal disorders (EGID) are characterized pathologically by excess eosinophils in mucosal biopsies of one or multiple sites in the... (Review)
Review
Eosinophilic gastrointestinal disorders (EGID) are characterized pathologically by excess eosinophils in mucosal biopsies of one or multiple sites in the gastrointestinal (GI) tract, simultaneously or sequentially. Eosinophilic esophagitis (EoE) is the best characterized EGID, and in most patients it is an abnormal immune-mediated response to food antigens. Current recommendations for diagnosis include signs and symptoms of esophageal dysfunction that do not respond to proton-pump inhibitor therapy, and esophageal biopsies that exhibit at least 15 intraepithelial eosinophils in at least one high power field (HPF). Therapy consists of swallowed glucocorticoids or dietary elimination. Eosinophilic gastritis (EG) is the second most common form of EGID, but like all forms of EGID except EoE consensus recommendations for either clinical or pathological diagnosis do not exist. EG may be associated clinically with peripheral blood eosinophilia, hypoalbuminemia, and anemia, and pathologically with marked expansion of lamina propria by dense eosinophilic infiltrates. Eosinophilic enteritis (EE) may be subdivided into eosinophilic duodenitis, eosinophilic jejunitis, and eosinophilic ileitis. Most investigators believe that EE rarely, if ever, exists as a solitary form of EGID and is encountered only in patients who have at least one other affected portion of the GI tract. Eosinophilic colitis (EC) is perhaps the most enigmatic EGID. Distinction of EC from inflammatory bowel disease may be problematic especially in children. Multiple possible etiologies for EGID include hypereosinophilic syndrome, drug reactions, etc. Currently, the only etiology that can be identified histologically is parasitic infestation, if a portion of an invasive parasite is found in mucosal biopsies. This review will provide guidelines for the pathologic diagnosis of the various forms of EGID.
PubMed: 29379785
DOI: 10.3389/fmed.2017.00261 -
Advances in Experimental Medicine and... 2021Oxygen is directly involved in many key pathophysiological processes. Oxygen deficiency, also known as hypoxia, could have adverse effects on mammalian cells, with... (Review)
Review
Oxygen is directly involved in many key pathophysiological processes. Oxygen deficiency, also known as hypoxia, could have adverse effects on mammalian cells, with ischemia in vital tissues being the most significant (Michiels C. Physiological and pathological responses to hypoxia. Am J Pathol 164(6): 1875-1882, 2004); therefore, timely adaptive responses to variations in oxygen availability are essential for cellular homeostasis and survival. The most critical molecular event in hypoxic response is the activation and stabilization of a transcriptional factor termed hypoxia-induced factor-1 (HIF-1) that is responsible for the upregulation of many downstream effector genes, collectively known as hypoxia-responsive genes. Multiple key biological pathways such as proliferation, energy metabolism, invasion, and metastasis are governed by these genes; thus, HIF-1-mediated pathways are equally pivotal in both physiology and pathology.As we gain knowledge on the molecular mechanisms underlying the regulation of HIF-1, a great focus has been placed on elucidating the cellular function of HIF-1, particularly the role of HIF-1 in cancer pathogenesis pathways such as proliferation, invasion, angiogenesis, and metastasis. In cancer, HIF-1 is directly involved in the shift of cancer tissues from oxidative phosphorylation to aerobic glycolysis, a phenomenon known as the Warburg effect. Although targeting HIF-1 as a cancer therapy seems like an extremely rational approach, owing to the complex network of its downstream effector genes, the development of specific HIF-1 inhibitors with fewer side effects and more specificity has not been achieved. Therefore, in this review, we provide a brief background about the function of HIF proteins in hypoxia response with a special emphasis on the unique role played by HIF-1α in cancer growth and invasiveness, in the hypoxia response context.
Topics: Animals; Cell Hypoxia; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Metabolic Networks and Pathways; Neoplasms; Neovascularization, Pathologic
PubMed: 33791987
DOI: 10.1007/978-3-030-51652-9_17 -
Circulation Aug 2023The number of heart transplants performed annually in the United States and worldwide continues to increase, but there has been little change in graft longevity and... (Review)
Review
The number of heart transplants performed annually in the United States and worldwide continues to increase, but there has been little change in graft longevity and patient survival over the past 2 decades. The reference standard for diagnosis of acute cellular and antibody-mediated rejection includes histologic and immunofluorescence evaluation of endomyocardial biopsy samples, despite invasiveness and high interrater variability for grading histologic rejection. Circulating biomarkers and molecular diagnostics have shown substantial predictive value in rejection monitoring, and emerging data support their use in diagnosing other posttransplant complications. The use of genomic (cell-free DNA), transcriptomic (mRNA and microRNA profiling), and proteomic (protein expression quantitation) methodologies in diagnosis of these posttransplant outcomes has been evaluated with varying levels of evidence. In parallel, growing knowledge about the genetically mediated immune response leading to rejection (immunogenetics) has enhanced understanding of antibody-mediated rejection, associated graft dysfunction, and death. Antibodies to donor human leukocyte antigens and the technology available to evaluate these antibodies continues to evolve. This review aims to provide an overview of biomarker and immunologic tests used to diagnose posttransplant complications. This includes a discussion of pediatric heart transplantation and the disparate rates of rejection and death experienced by Black patients receiving a heart transplant. This review describes diagnostic modalities that are available and used after transplant and the landscape of future investigations needed to enhance patient outcomes after heart transplantation.
Topics: Heart Transplantation; Pathology, Molecular; Graft Rejection; Biomarkers; Humans; Cell-Free Nucleic Acids; Gene Expression Profiling; MicroRNAs; Child; Race Factors; Antibodies; HLA Antigens; Genomics
PubMed: 37603604
DOI: 10.1161/CIRCULATIONAHA.123.062847 -
Journal of Molecular Biology Jun 2015A tumor is a heterogeneous population of cells that provides an environment in which every cell resides in a microenvironmental niche. Microscopic evaluation of tissue... (Review)
Review
A tumor is a heterogeneous population of cells that provides an environment in which every cell resides in a microenvironmental niche. Microscopic evaluation of tissue sections, based on histology and immunohistochemistry, has been a cornerstone in pathology for decades. However, the dawn of novel technologies to investigate genetic aberrations is currently adopted in routine molecular pathology. We herein describe our view on how recent developments in molecular technologies, focusing on proximity ligation assay and padlock probes, can be applied to merge the two branches of pathology, allowing molecular profiling under histologic observation. We also discuss how the use of image analysis will be pivotal to obtain information at a cellular level and to interpret holistic images of tissue sections. By understanding the cellular communications in the microecology of tumors, we will be at a better position to predict disease progression and response to therapy.
Topics: Humans; Image Processing, Computer-Assisted; In Situ Hybridization; Neoplasms; Pathology, Molecular; Proteomics; Signal Transduction; Tumor Microenvironment
PubMed: 25725260
DOI: 10.1016/j.jmb.2015.02.017 -
Annals of Surgical Oncology Oct 2016The use of neoadjuvant systemic therapy for the treatment of breast cancer patients is increasing. Pathologic response in the form of pathologic complete response (pCR)... (Review)
Review
The use of neoadjuvant systemic therapy for the treatment of breast cancer patients is increasing. Pathologic response in the form of pathologic complete response (pCR) and grading systems of partial response, such as the residual cancer burden (RCB) system, gives valuable prognostic information for patients and is used as a primary endpoint in clinical trials. The breast cancer and pathology communities are responding with efforts to standardize pathology in patients receiving neoadjuvant chemotherapy. In this review, we summarize the challenges that postneoadjuvant systemic therapy surgical specimens pose and how pathologists and the multidisciplinary team can work together to optimize handling of these specimens. Multidisciplinary communication is essential. A single, standardized approach to macroscopic and microscopic pathologic examination makes it possible to provide reliable response information. This approach employs a map of tissue sections to correlate clinical, gross, microscopic, and imaging findings in order to report the presence of pCR (ypT0 ypN0 and ypT0/is ypN0) versus residual disease, the ypT and ypN stage using the current AJCC/UICC staging system, and the RCB.
Topics: Antineoplastic Agents, Alkylating; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Humans; Interdisciplinary Communication; Neoadjuvant Therapy; Neoplasm, Residual; Pathology; Specimen Handling; Treatment Outcome
PubMed: 27380637
DOI: 10.1245/s10434-016-5317-x -
Chinese Clinical Oncology Dec 2018There is only a few of studies devoted to evaluation of pathologic response of ovarian cancer (OC) to neoadjuvant chemotherapy (NACT). Pathologic complete responses... (Review)
Review
There is only a few of studies devoted to evaluation of pathologic response of ovarian cancer (OC) to neoadjuvant chemotherapy (NACT). Pathologic complete responses (pCR), which are characterized by the lack of viable tumor cells in surgical specimens, are rarely observed in ovarian carcinomas. Multiple reports demonstrate that pCR is associated with evidently improved disease outcomes. Recommendations of the International Collaboration on Cancer Reporting suggest to use recently developed Chemotherapy Response Scoring (CRS) system, which is based on the pathological analysis of surgically removed omental masses. CRS3 (complete or near-complete response) is characterized by the lack of residual tumor cells in the omentum or presence of tumor foci up to 2 mm maximum size. It is observed after NACT in approximately 30-40% patients with high-grade serous ovarian cancer (HGSOC) and is reproducibly associated with the improvement of the disease prognosis.
Topics: Female; Humans; Neoadjuvant Therapy; Ovarian Neoplasms; Prognosis
PubMed: 30509080
DOI: 10.21037/cco.2018.09.07