bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Postgenomic Era
Authors: Kiechle Frederick L. , Zhang Xinbo 
Published: January 2021

AbstractObjectives.—To review the advances in clinically useful molecular biological techniques and to identify their applications in clinical practice, as presented at the Tenth Annual William Beaumont Hospital DNA Symposium.Data Sources.—The 11 manuscripts submitted were reviewed and their major findings were compared with literature on the same topic.Study Selection.—Manuscripts address creative thinking techniques applied to DNA discovery, extraction of DNA from clotted blood, the relationship of mitochondrial dysfunction in neurodegenerative disorders, and molecular methods to identify human lymphocyte antigen class I and class II loci. Two other manuscripts review current issues in molecular microbiology, including detection of hepatitis C virus and biological warfare. The last 5 manuscripts describe current issues in molecular cardiovascular disease, including assessing thrombotic risk, genomic analysis, gene therapy, and a device for aiding in cardiac angiogenesis.Data Synthesis.—Novel problem-solving techniques have been used in the past and will be required in the future in DNA discovery. The extraction of DNA from clotted blood demonstrates a potential cost-effective strategy. Cybrids created from mitochondrial DNA-depleted cells and mitochondrial DNA from a platelet donor have been useful in defining the role mitochondria play in neurodegeneration. Mitochondrial depletion has been reported as a genetically inherited disorder or after human immunodeficiency virus therapy. Hepatitis C viral detection by qualitative, quantitative, or genotyping techniques is useful clinically. Preparedness for potential biological warfare is a responsibility of all clinical laboratorians. Thrombotic risk in cardiovascular disorders may be assessed by coagulation screening assays and further defined by mutation analysis for specific genes for prothrombin and factor V Leiden. Gene therapy for reducing arteriosclerotic risk has been hindered primarily by complications introduced by the vectors used to introduce the therapeutic genes. Neovascularization in cardiac muscle with occluded vessels represents a promising method for recovery of viable tissue following ischemia.Conclusions.—The sequence of the human genome was reported by 2 groups in February 2001. The postgenomic era will emphasize the use of microarrays and database software for genomic and proteomic screening in the search for useful clinical assays. The number of molecular pathologic techniques and assays will expand as additional disease-associated mutations are defined. Gene therapy and tissue engineering will represent successful therapeutic adjuncts.
Influence of Platelet Collagen Receptor Polymorphisms on Risk for Arterial Thrombosis
Authors: Furihata Kenichi , Nugent Diane J. , Kunicki Thomas J. 
Published: January 2021

Abstract
Context.—Collagens are major components of the vascular subendothelium, and the interaction of platelets with collagens initiates normal hemostasis or pathologic arteriothrombosis. Genetic factors that affect the interaction of platelets with collagens could represent risk factors for either arteriothrombosis or excessive hemorrhage. In this regard, we first found that platelet levels of one of the major platelet collagen receptors, integrin α2β1, vary up to 10-fold in normal healthy individuals and that the higher-level phenotype is associated with allele 1 (807T) of the integrin α2 gene. More recently, we found that there is roughly a fivefold range in platelet glycoprotein VI content among normal individuals, which may also influence risk for thromboembolism.
Objective.—To determine if genetic polymorphisms of platelet glycoproteins involved in collagen-related function are associated with higher risk for thrombotic disorders, such as coronary heart disease, myocardial infarction, or stroke.
Methods.—We examined the genetic mechanisms responsible for variation in expression levels of the collagen receptor integrin α2β1 and the potential influence of this variation on risk for thrombotic diseases.
Results.—We found that patients with arteriothrombotic diseases have a higher frequency of α2 allele 1 (associated with higher levels of platelet integrin α2β1). We further found that platelet glycoprotein VI content directly correlates with platelet prothrombinase activity, suggesting that a higher phenotype of platelet glycoprotein VI also may contribute to increased risk of arteriothrombotic diseases.
Conclusion.—Genetic polymorphisms that influence the level or function of platelet collagen receptors need to be seriously considered as genetic risk factors for arteriothrombotic diseases.
Prospects for Microtechnology and Nanotechnology in Bioengineering of Replacement Microvessels
Authors: Moldovan Nicanor I. , Ferrari Mauro 
Published: January 2021

Abstract
Context.—Due to its anticipated curative potential, therapeutic angiogenesis recently became a major preoccupation for the biomedical research community. Most of the related work reported to date employs either biochemical or genetic tools.
Objective.—To identify opportunities for application of the current developments in microtechnology and nanotechnology to the field of therapeutic angiogenesis.
Data Sources.—Survey of recent English-language literature on microvascular tissue engineering in the context of therapeutic angiogenesis. We include our results regarding the role played by microtopographical cues in the progression of angiogenesis, such as those produced during processing of the extracellular matrix by chronic inflammatory cells.
Conclusion.—While notable accomplishments have been identified in the field of tissue engineering of larger vessels, reports on purposeful assembly of microvascular structures with the ability to be transferred in vivo by implantation are still scarce. Under these circumstances, we suggest the development of a new class of implantable biomedical microdevices, that is, “angiogenesis assist devices” (or “angiochips”), and we indicate some of their conceivable applications.
Changes in Automated Complete Blood Cell Count and Differential Leukocyte Count Results Induced by Storage of Blood at Room Temperature
Authors: Gulati Gene L. , Hyland Lawrence J. , Kocher William , Schwarting Rolland 
Published: January 2021

Abstract
Objective.—To delineate changes that occur in various parameters of automated complete blood cell count (CBC) and differential leukocyte count (differential) on prolonged storage of blood at room temperature.
Design.—A CBC and an automated differential were performed on the Coulter Gen.S on 40 K3 (tripotassium ethylenediamine-tetraacetate) EDTA-anticoagulated blood specimens once daily, specimen volume permitting, for 3 to 7 days. Specimens were kept at room temperature throughout the study. The results were tabulated using a personal computer with Excel software. Percent change or absolute difference from the initial value for each parameter for each subsequent day of the study period was calculated.
Results.—Among the CBC parameters, hemoglobin, red blood cell count, and mean corpuscular hemoglobin were stable for the duration of the study (7 days), white blood cell count was stable for at least 3 days (up to 7 days, if the count was within or above the normal range), and platelet count was stable for at least 4 days (up to 7 days, if the count was within or above the normal range). The mean corpuscular volume, mean platelet volume, hematocrit, and red blood cell distribution width each increased, and the mean corpuscular hemoglobin concentration decreased from day 2 onward. Among the differential parameters, the relative percentages and absolute numbers of neutrophils, lymphocytes, and eosinophils tended to increase, whereas those of monocytes trended downward over time. Limited data on basophils did not reveal an appreciable change.
Conclusion.—Blood specimens stored at room temperature for more than 1 day (up to 3 days or possibly longer) were found to be acceptable with some limitations for CBC but not for the differential.
Cavernous Hemangioma of Spermatic Cord
Authors: Liokumovich Pavel , Herbert Mehrdad , Sandbank Judith , Schvimer Michael , Dolberg Leah 
Published: January 2021

Abstract
We present a case of spermatic cord cavernous hemangioma. A 32-year-old man presented with a circumscribed, painless mass in the left side of the spermatic cord. An orchiectomy of the left testicle was performed. A 3 × 3 × 2.5-cm mass was present in the spermatic cord area. Histologic examination and immunohistochemical study showed a benign vascular tumor composed of vascular spaces of varying size. Although cavernous hemangioma can occur in any location, the spermatic cord is an extremely rare site, and, to our knowledge, only a few cases have been previously reported.
Mesenteric Paraganglioma
Authors: Jaffer Shabnam , Harpaz Noam 
Published: January 2021

Abstract
Approximately 5% to 10% of paragangliomas occur in extra-adrenal sites, which can extend from the upper cervical region to the pelvis, parallel to the autonomic nervous system. This distribution corresponds to the embryologic development of the paraganglia from neural crest cells. Rarely, extra-adrenal paragangliomas can also occur aberrantly outside this distribution. We report such a case of extra-adrenal paraganglioma occurring in the anterior mesentery in a 76-year-old man. Two case reports exist in the literature describing extra-adrenal paragangliomas in the posterior mesentery. Normal paraganglionic tissue has been described at the roots of the superior and inferior mesenteric arteries, theoretically explaining the origin of the posterior mesenteric paragangliomas. Our case can best be attributed to the ventral migration of paraganglionic tissue through these vessels to reach the anterior mesentery, where they could potentially give rise to paragangliomas in this site.
Epithelial-Type and Neural-Type Cadherin Expression in Malignant Noncarcinomatous Neoplasms With Epithelioid Features That Involve the Soft Tissues
Authors: Laskin William B. , Miettinen Markku 
Published: January 2021

AbstractContext.—Transmembrane adhesion molecules, epithelial-type cadherin (ECAD) and neural-type cadherin (NCAD), help in regulating transformations between epithelial and mesenchymal cells in the developing embryo and in maintaining the epithelioid phenotype. Consequently, the presence of epithelioid cells in certain malignant noncarcinomatous neoplasms raises speculation that the expression of ECAD and NCAD in these neoplasms may have diagnostic significance.Objective.—To investigate the utility of ECAD and NCAD immunoexpression in distinguishing malignant (noncarcinomatous) neoplasms with epithelioid features that involve the soft tissues.Design.—Membranous immunoreactivity of anti-ECAD and anti-NCAD was evaluated on archived cases selected from the files of the Armed Forces Institute of Pathology.Results.—Epithelial-type cadherin was found in biphasic synovial sarcoma (35 of 35 cases), malignant melanoma (13/21), monophasic fibrous synovial sarcoma (13/26), clear cell sarcoma (4/9), poorly differentiated synovial sarcoma (3/13), diffuse mesothelioma (4/20), malignant epithelioid peripheral nerve sheath tumor (1/6), and epithelioid sarcoma (5/62). Neural-type cadherin was observed in chordoma (11/11), biphasic synovial sarcoma (30/35), diffuse mesothelioma (14/20), malignant melanoma (14/25), epithelioid sarcoma (24/63), epithelioid angiosarcoma (1/4), poorly differentiated synovial sarcoma (2/13), clear cell sarcoma (1/10), and monophasic fibrous synovial sarcoma (1/26). Eighteen cases of primary cutaneous squamous cell carcinomas all tested positive for ECAD, whereas NCAD was focally observed in 5 cases. No expression of either molecule was observed in cases of epithelioid hemangioendothelioma (n = 9), alveolar soft part sarcoma (n = 8), and extraskeletal myxoid chondrosarcoma (n = 7).Conclusions.—Epithelial-type and neural-type cadherins are found in a variety of noncarcinomatous neoplasms with epithelioid features that involve the soft tissues and can be utilized, in association with other immunomarkers, in distinguishing chordoma (100% NCAD) from extraskeletal myxoid chondrosarcoma and conventional chondrosarcoma of bone (0% NCAD), squamous cell carcinoma (100% ECAD) from epithelioid sarcoma (8% ECAD), and biphasic synovial sarcoma (100% ECAD) from diffuse mesothelioma (20% ECAD).
Pathologists in a Teaching Institution Assess the Value of the Autopsy
Authors: Bayer-Garner Ilene B. , Fink Louis M. , Lamps Laura W. 
Published: January 2021

Abstract
Context.—With the advent of modern diagnostic technology, use of the autopsy as a means of assessing diagnostic accuracy has declined precipitously. Interestingly, during the same period, the rate of misdiagnosis found at autopsy has not changed.
Objectives.—To ascertain why an autopsy was requested, whether or not questions asked by clinicians were specifically addressed, and what types of misdiagnoses were found.
Design.—One hundred forty-two consecutive autopsy records from the University of Arkansas for Medical Sciences Hospital were reviewed. In the same period, 715 deaths occurred, giving an overall autopsy rate of 20.14%.
Results.—Of the 125 autopsies in which the problem-oriented autopsy request was available for review, a reason for the autopsy was given in only 69 cases (55%). One hundred three clinical questions were asked, and of these, 81 were specifically addressed in the final anatomic diagnosis, 10 were addressed in some part of the autopsy report but not in the final anatomic diagnosis, 10 were not addressed at all, and 2 could not be answered by the autopsy. Sixty-one autopsies revealed 81 misdiagnoses: 47 class I (missed major diagnosis that, if detected before death, could have led to a change in management that might have resulted in cure or prolonged survival) and 34 class II misdiagnoses (missed major diagnosis in which antemortem detection would have not led to a change in management).
Conclusions.—The autopsy continues to be a vital part of medical education and quality assurance. It is important for the clinician to provide a clinical summary and specific clinical questions to be addressed or to speak directly with the pathologist and for the pathologist to provide answers that are easily accessible within the autopsy report. In this way, a problem-oriented autopsy can be performed based on questions raised by the clinician and the pathologist as a result of the gross dissection and microscopic evaluation.
MYCC and MYCN Oncogene Amplification in Medulloblastoma
Authors: Aldosari Naji , Bigner Sandra H. , Burger Peter C. , Becker Laurence , Kepner James L. , Friedman Henry S. , McLendon Roger E. 
Published: January 2021

Abstract
Context.—Brain tumors are the most common solid tumor in childhood, and medulloblastoma is the most common malignant brain tumor in this age group. Cytogenetic abnormalities that have been described in childhood medulloblastoma include loss of 17p, amplification of MYCC (c-myc), amplification of MYCN (N-myc), and isochromosome 17q. Data on these tumors indicate that the frequency of MYCC amplification is 5% to 10%. Fluorescence in situ hybridization is a powerful tool for investigating these features on archival material.
Objectives.—To determine if intratumoral heterogeneity exists for MYCC and MYCN in medulloblastomas and if tumors with amplified MYCC or MYCN exhibit consistent histologic patterns.
Design.—In this fluorescence in situ hybridization study, we investigated the frequency and prognostic significance of MYCC and MYCN amplification in 77 medulloblastomas derived from the Children's Oncology Group.
Results.—MYCC amplification occurred in only 4 (5.2%) of 77 tumors. The 4 patients died of clinically aggressive neoplasms within 7 months of diagnosis. Similarly, 4 of 77 patients' tumors were found to exhibit MYCN amplification, but survival data are incomplete at present, therefore prognostic significance cannot be characterized.
Conclusions.—These data establish the frequency of MYCC amplification in a large cohort of children with medulloblastoma and further suggest that MYCC amplification may be a marker of poor prognosis. Intratumoral heterogeneity was identified for these oncogenes in that 1 patient's tumor exhibited evidence of both MYCN and MYCC amplification, and this patient experienced a shortened survival time.
Placental Transmogrification of the Lung Is a Histologic Pattern Frequently Associated With Pulmonary Fibrochondromatous Hamartoma
Authors: Xu Ruliang , Murray Melissa , Jagirdar Jaishree , Delgado Yara , Melamed Jonathan 
Published: January 2021

Abstract
Context.—Placental transmogrification of the lung is a term introduced to describe a peculiar histologic pattern characterized by formation of placental villuslike structures in the lung parenchyma. It has been reported to occur in association with bullous emphysema and lipomatosis.
Objectives.—To study the relationship between placental transmogrification and pulmonary hamartomas.
Design and Methods.—Reports of 38 cases of pulmonary hamartomas during 18 years (1982–1999) were reviewed. All histologic slides of these cases were examined for the presence of villuslike papillary projections and placenta-like structures. Hamartomas with prominent papillary projections or placenta-like structures were further investigated to assess the histogenesis and proliferation of epithelial and stromal cells. Immunohistochemical analysis was performed on paraffin-embedded tissue using monoclonal antibodies against Ki-67 and thyroid transcription factor 1 (TTF-1) and polyclonal antibodies against c-Kit antigen (a stem cell factor receptor/mast cell growth factor receptor) in conjunction with Leder stain for naphthol-ASD-chloroacetate esterase.
Results.—Placental transmogrification was identified in 6 of 38 cases of pulmonary fibrochondromatous hamartomas. The histologic change consisted of an abundant myxoid or edematous fibroadipose stroma with a respiratory epithelial lining, resulting in papillary projections that resembled immature placental villi. Epithelium lining the papillary projections was positive for TTF-1 (70%–90%) and Ki-67 (3%–5%). In contrast, stromal cells were negative for TTF-1 with only rare cells immunoreactive for Ki-67. A number of stromal spindle cells and occasional cells in epithelium were c-Kit immunoreactive; however, concurrent Leder stain demonstrated that these c-Kit–positive cells were mast cells and not stem cells.
Conclusions.—Placental transmogrification is frequently associated with pulmonary fibrochondromatous hamartomas and may be induced by or associated with a proliferation of lining epithelial components in the hamartomas. The significance of numerous mast cells within stroma of placental transmogrification is unclear and their possible role in inducing stromal proliferation needs to be further evaluated.
False-Positive AxSYM Cardiac Troponin I Results in a 53-Year-Old Woman
Authors: Knoblock Ronald J. , Lehman Christopher M. , Smith Ruth A. , Apple Fred S. , Roberts William L. 
Published: January 2021

AbstractA number of classes of endogenous antibodies, including heterophile, rheumatoid factor, and autoantibodies, can interfere with immunoassay measurements of many different analytes. Heterophile and rheumatoid factor antibody interferences have been described previously for the AxSYM cardiac troponin I assay. Several commercial products have been developed to neutralize heterophile antibody interferences. We describe a patient with multiple apparently falsely elevated cardiac troponin I results that were unique to the AxSYM analyzer. These cardiac troponin I results diluted linearly. When treated with 2 different heterophile-blocking reagents, the magnitudes of the falsely elevated results increased 17- and 26-fold, and these results also demonstrated dilution linearity. This interfering substance could be removed by passage through an immobilized protein A column and by polyethylene glycol precipitation. It does not appear to be a classic heterophile antibody, nor is it a paraprotein. Laboratorians must remain constantly vigilant for immunoassay interferences that lead to clinically significant inaccurate results and must recognize that accepted methods for detecting and neutralizing the interference may be ineffective.
Megakaryocytes Mimicking Metastatic Breast Carcinoma
Authors: Hoda Syed A. , Resetkova Erika , Yusuf Yasmin , Cahan Anthony , Rosen Paul P. 
Published: January 2021

Abstract
False-positive diagnosis of lymph nodes occurs when a benign element in a lymph node, or in its capsule, is interpreted as metastatic carcinoma. This report describes a patient with breast carcinoma who had megakaryocytes in axillary sentinel lymph nodes mimicking metastatic carcinoma. The patient had no history of a hematologic disease, and we found no evidence of a concurrent hematopoietic disorder. The megakaryocytes were reactive for CD31, CD61, and von Willebrand factor, but not for cytokeratin (AE1/AE3). Megakaryocytes should be added to the list of benign histologic abnormalities that may simulate metastatic carcinoma in a sentinel lymph node.
Increased Apoptosis in Infiltrating Mononuclear Cells of Colorectal Cancer
Authors: Chen George G. , Lee Janet F. Y. , Chan Ursula P. F. , Xu Hu , Ip Ping C. , Lau Wan Y. 
Published: January 2021

AbstractContext.—Disturbance in apoptosis has been proposed as one of the mechanisms involved in the immune response targeting tumor outgrowth. How colorectal cancer cells escape from attack by the immune system is not yet fully understood.Objective.—To investigate apoptotic molecules associated with colorectal cancer counterattack.Design and Setting.—Tissue samples of colon from 12 patients with colorectal cancer were collected and analyzed by immunostaining. In addition to tumorous tissues, corresponding nontumorous specimens of colon were obtained as controls.Main Outcome Measures.—We examined the expression of Bcl-2, Bcl-xl, Bax, caspase-3, and inducible nitric oxide synthase in infiltrating mononuclear cells of colorectal cancer tissues and also in colorectal cancer tissues. The TUNEL assay was used to detect in situ apoptosis.Results.—Apoptosis was barely detectable in specimens of colorectal cancer, which was consistent with an increase in Bcl-2 level and a decrease in caspase-3 level. In contrast, infiltrating mononuclear cells of tumorous tissues showed a marked increase in apoptosis compared with those of nontumorous tissues. The increased apoptosis might have resulted from an imbalance of antiapoptotic and proapoptotic molecules, as reflected by reduction of Bcl-2 level and elevation of Bax level. The elevated caspase-3 levels found in this study could be a downstream effector of the Bcl-2 and Bax apoptotic pathways. A significant increase in inducible nitric oxide synthase observed in the infiltrating mononuclear cells might contribute to immunosuppression seen in colorectal cancer.Conclusion.—It is tempting to speculate that aberrant expression of apoptotic molecules and inducible nitric oxide synthase in infiltrating mononuclear cells provides the underlying mechanism through which colorectal cancer cells escape attack by the immune system and subsequently grow without control.
Carcinomatous Arteriopathy as an Unusual Feature of Pulmonary Spread of Cholangiocarcinoma Arising in Caroli Disease
Authors: Wang Hanlin L. 
Published: January 2021

Abstract
Carcinomatous arteriopathy is a rare and distinct form of pulmonary spread of solid malignant tumors characterized by fibrointimal proliferation of small pulmonary arteries and arterioles initiated by tumor emboli. Although it has been reported in many types of adenocarcinomas, no case of carcinomatous arteriopathy induced by cholangiocarcinoma has been described in the literature. We report a unique case of cholangiocarcinoma that arose in Caroli disease. Postmortem examination revealed extensive pulmonary vascular spread in the form of carcinomatous arteriopathy.