bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperhomocysteinemia Measured by Immunoassay: A Valid Measure of Coronary Artery Atherosclerosis
Authors: Stauffenberg Michele T. , Lange Richard A. , David Hillis L. , Cigarroa Joaquin , Hsu Rebecca M. , Devaraj Sridevi , Jialal Ishwarlal 
Published: February 2021

Abstract
Context.—Homocysteine is emerging as a novel marker of atherothrombosis. Its role as an independent risk factor for cardiovascular disease is generally accepted. There is scanty data correlating homocysteine levels measured by immunoassay with cardiovascular disease. We previously validated a fluorescence polarization immunoassay for measuring homocysteine, which compared favorably with high performance liquid chromatography.
Objective.—To determine if homocysteine levels measured by immunoassay correlate with extent of atherosclerotic burden, as represented by degree of coronary artery stenosis determined by coronary angiography.
Design.—Fasting plasma samples were obtained from patients undergoing coronary angiography (N = 165). Homocysteine levels were measured by immunoassay and coronary artery stenosis was determined by coronary angiography.
Results.—Median coronary artery stenosis for the 3 homocysteine subgroups, less than 1.35, 1.35 to 6.75, and greater than 6.75 mg/L (&lt;10, 10–15, and &gt;15 μmol/L), was 75%, 90%, and 99%, respectively (P = .01 for trend). Also, folate and vitamin B12 levels decreased with increasing homocysteine levels (P = .01 and .04, respectively, for trend). Spearman's correlation showed a significant association between homocysteine level and coronary artery stenosis (r = 0.20; P = .009). When men and women were examined separately, the correlation was significant only for women (r = 0.30; P = .01).
Conclusion.—Homocysteine levels, as measured by immunoassay, show a positive correlation with cardiovascular disease in women. Thus, this is a valid measure of atherosclerotic burden and, therefore, a reliable addition to the established laboratory repertoire for the assessment of cardiovascular disease.
Molecular Diagnostics on Lymphoid Malignancies
Authors: Chan Wing C. , Fu Kai 
Published: February 2021

Abstract
Context.—Molecular diagnostics for lymphoid malignancies traditionally has focused on helping to provide a diagnosis on a tissue sample. The field has undergone substantial technical and conceptual evolution during the past 2 decades, and its role has expanded to new arenas, such as monitoring disease activities and detecting alterations in genes that are known to have a significant impact on disease outcome.
Objective.—To review the advances in molecular diagnostics on lymphoid malignancies, including recent developments that may facilitate the development of mechanism-based diagnosis for individualized therapy.
Design.—The development of molecular diagnostics in lymphoid malignancies is briefly reviewed with emphasis on the recent use of gene expression profiling for identifying important diagnostic and prognostic signatures.
Results.—Genome-scale investigations are becoming technically feasible and have provided promising results in the identification of new disease entities and new, molecularly defined prognosticators. This development can potentially revolutionize diagnostic medicine in the near future. As new genes or genetic pathways that affect the clinical and biologic behavior of tumors are defined and can be readily assayed, molecular diagnostics will be expected to provide this relevant information. Ideally, therapy will be based on this information, delivering the most appropriate treatment with the least toxicity.
Conclusions.—Molecular diagnostics in the future will be moving toward a mechanism-based diagnosis for individualized therapy.
The Value of Fluorescence In Situ Hybridization and Polymerase Chain Reaction in the Diagnosis of B-Cell Non-Hodgkin Lymphoma by Fine-Needle Aspiration
Authors: Safley Anne M. , Buckley Patrick J. , Creager Andrew J. , Dash Rajesh C. , Dodd Leslie G. , Goodman Barbara K. , Jones Claudia K. , Lagoo Anand S. , Stenzel Timothy T. , Wang Weihua , Xie Bill , Gong Jerald Z. 
Published: February 2021

Abstract
Context.—Molecular genetic analyses have been predicted to improve the diagnostic accuracy of fine-needle aspiration of B-cell non-Hodgkin lymphoma.
Objective.—To determine the value of routine molecular genetic assays, polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH), in the diagnosis of B-cell non-Hodgkin lymphoma by fine-needle aspiration (FNA).
Design.—A multiparametric method, including cytology, flow cytometry, PCR, and FISH, was prospectively evaluated in the diagnosis of B-cell non-Hodgkin lymphoma by FNA. Aspirates from 30 consecutive patients with suspected hematolymphoid malignancies were collected. All aspirates were triaged through a uniform program including cell-size analysis, B- and T-cell clonality studies, flow cytometric immunophenotyping, and bcl-1 and bcl-2 gene rearrangements by PCR and FISH. After completion of FNA evaluations, FNA results were compared with diagnoses from prior or subsequent surgical biopsies.
Results.—Monoclonal B-cell populations were detected in 18 of 20 B-cell non-Hodgkin lymphomas by flow cytometry and PCR. bcl-1 gene rearrangement was detected in 2 of 2 cases of mantle cell lymphoma. bcl-2 rearrangement was detected in 5 cases including 4 of 4 low-grade follicular lymphomas and 1 transformed follicular lymphoma. By incorporating the results of molecular genetic and ancillary diagnostics, a definitive classification was reached in 12 cases of B-cell non-Hodgkin lymphoma by FNA, including all cases of low-grade follicular lymphoma (4/4) and mantle cell lymphoma (2/2) and approximately 50% of small lymphocytic lymphoma (2/4) and large B-cell lymphoma (4/8). Ten of the 12 cases with a final classification reached by FNA had either prior or follow-up surgical biopsies, and all 10 cases showed agreement between the diagnoses rendered on FNA and surgical biopsies.
Conclusions.—With proper handling and management of specimens, FNA can routinely provide samples adequate for molecular genetic studies, in addition to cytomorphology and flow cytometry, making it possible to consistently render accurate and definitive diagnoses in a subset of B-cell non-Hodgkin lymphomas. By incorporating FISH and PCR methods, FNA may assume an expanded role for the primary diagnosis of B-cell non-Hodgkin lymphoma.
Radiographically Occult, Diffuse Intrasinusoidal Hepatic Metastases From Primary Breast Carcinomas: A Clinicopathologic Study of 3 Autopsy Cases
Authors: Allison Kimberly H. , Fligner Corinne L. , Tony Parks W. 
Published: February 2021

AbstractContext.—Liver metastases usually present as radiographically detectable mass lesions that do not significantly compromise liver function. Rarely, metastatic carcinoma can diffusely infiltrate hepatic sinusoids, a pattern of metastasis that may be missed on imaging studies, and can result in liver failure.Objective.—To describe the clinicopathologic features of 3 cases of diffuse intrasinusoidal hepatic metastases from primary breast carcinomas identified at autopsy.Design.—Clinical histories and radiographic, macroscopic, and microscopic appearances of the livers were compared. Sampled liver tissue was stained with antibodies to E-cadherin, smooth muscle actin, and CD44.Results.—Two of 3 cases had a history of infiltrating ductal carcinoma of the breast and presented with new-onset liver failure, but no hepatic metastases were identified on radiologic imaging. An additional case had no history of carcinoma, presented with a severe thrombocytopenic thrombotic purpura–like syndrome, and metastatic carcinoma of the breast was diagnosed only at autopsy. The livers in all 3 cases at autopsy were homogeneous, firm, and tan-yellow, and contained no large metastatic lesions. Microscopically, poorly differentiated carcinoma diffusely infiltrated hepatic sinusoids. Antibodies to smooth muscle actin stained activated hepatic stellate cells lining involved sinusoids. Cell surface adhesion molecules, E-cadherin or CD44, were not detected in any hepatic metastases.Conclusion.—Diffuse intrasinusoidal hepatic metastases of breast carcinoma can occupy a large percentage of the hepatic volume, yet remain occult both radiographically and macroscopically. This type of metastatic spread can present as cryptogenic liver failure. The 3 cases we studied were associated with an absence of E-cadherin and CD44 expression.
Detection of Adenocarcinoma In Situ of the Cervix in Papanicolaou Tests: Comparison of Diagnostic Accuracy With Other High-Grade Lesions
Authors: Renshaw Andrew A. , Mody Dina R. , Lozano Richard L. , Volk Emily E. , Walsh Molly K. , Davey Diane D. , Birdsong George G. 
Published: February 2021

Abstract
Context.—Adenocarcinoma in situ of the cervix is a recently recognized interpretation in the Bethesda 2001 system. Although specific morphologic criteria have been published, recognizing this entity is still difficult.
Objective.—To compare pathologists' ability to correctly identify and categorize adenocarcinoma in situ with their ability to identify and categorize adenocarcinoma, high-grade squamous intraepithelial lesion, and squamous cell carcinoma.
Design.—Pathologists' reviews in the 2001 and 2002 College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology Program, an interlaboratory comparison program for gynecologic cytology, were examined. Cases were usually reviewed by multiple pathologists. False-negative rates, the percentage of reviews with exact agreement with reference interpretations, and the percentage of cases in which all reviews were in exact agreement with the reference interpretation for adenocarcinoma in situ, adenocarcinoma, high-grade squamous intraepithelial lesion, and squamous cell carcinoma were compared.
Results.—A total of 213 reviews of cases categorized as adenocarcinoma in situ were compared with 2821 reviews of adenocarcinoma, 7535 reviews of high-grade squamous intraepithelial lesion, and 1886 reviews of squamous cell carcinoma. The false-negative rate for adenocarcinoma in situ (11.7%) was significantly higher than that for high-grade squamous intraepithelial lesion (4.6%, P &lt; .001) and squamous cell carcinoma (3.3%, P &lt; .001) but not for adenocarcinoma (8.9%, P = .16). Of all the reviews of adenocarcinoma in situ cases, 46.5% were interpreted specifically as adenocarcinoma in situ, compared to 72.2% of reviews of adenocarcinoma, 73.2% of high-grade squamous intraepithelial lesion, and 75.1% of squamous cell carcinoma. No individual case of adenocarcinoma in situ was always specifically recognized as adenocarcinoma in situ; 26.5% of cases of adenocarcinoma were specifically recognized as such in all reviews. Findings were similar with and without the inclusion of high-grade squamous intraepithelial lesion/carcinoma, not otherwise specified, as an acceptable review interpretation for cases of adenocarcinoma, squamous cell carcinoma, and high-grade squamous intraepithelial lesion.
Conclusion.—These data from expert-referenced and biopsy-proven cases suggest that adenocarcinoma in situ is not as easily recognized or categorized as other serious diagnoses.
Current Applications of Flow Cytometry in the Diagnosis of Primary Immunodeficiency Diseases
Authors: Illoh Orieji C. 
Published: February 2021

Abstract
Context.—To review the applications of flow cytometry in the diagnosis and management of primary immunodeficiency disease.
Data Sources.—Articles describing the use of flow cytometry in the diagnosis of several primary immunodeficiency diseases were obtained through the National Library of Medicine database.
Study Selection.—Publications that described novel and known applications of flow cytometry in primary immunodeficiency disease were selected. Review articles were included. Articles describing the different immunodeficiency diseases and methods of diagnosis were also selected.
Data Extraction.—Approximately 100 data sources were analyzed, and those with the most relevant information were selected.
Data Synthesis.—The diagnosis of many primary immunodeficiency diseases requires the use of several laboratory tests. Flow cytometry has become an important part of the workup of individuals suspected to have such a disorder. Knowledge of the pathogenesis of many of these diseases continues to increase, hence we acquire a better understanding of the laboratory tests that may be helpful in diagnosis.
Conclusions.—Flow cytometry is applicable in the initial workup and subsequent management of several primary immunodeficiency diseases. As our understanding of the pathogenesis and management of these diseases increases, the use of many of these assays may become routine in hospitals.
Stability of JC Virus Coding Sequences in a Case of Progressive Multifocal Leukoencephalopathy in Which the Viral Control Region Was Rearranged Markedly
Authors: Zheng Huai-Ying , Yasuda Yukiharu , Kato Shunichi , Kitamura Tadaichi , Yogo Yoshiaki 
Published: February 2021

Abstract
Context.—It is generally accepted that JC virus variants in the brains of patients with progressive multifocal leukoencephalopathy are generated from archetypal strains through sequence rearrangement (deletion and duplication, or deletion alone) in the control region. This change is thought to occur during persistence of JC virus in patients.
Objective.—The present study was performed to ascertain whether amino acid substitution in the viral proteins is involved in the generation and propagation of JCV variants with rearranged control regions.
Design.—Many complete JC DNA clones were established from brain tissues (cerebellum, occipital lobe, and brainstem) autopsied in a case of progressive multifocal leukoencephalopathy in which multiple distinct control sequences were detected. Control and coding sequences were determined and compared among the JC DNA clones.
Results.—Twenty-eight control-region and 20 coding sequences of JC virus were compared. Five rearranged control sequences were detected, but they could be classified into 3 groups that shared common structural features. Viral coding sequences were identical among clones with different control regions and among clones derived from different brain regions.
Conclusion.—In the present case, nucleotide substitution in the viral coding regions (and resultant amino acid change in the viral proteins) was involved neither in the genesis of rearranged JC virus variants nor in the proliferation of demyelinated lesions in the brain.
Bacterial Contamination of Platelet Units: A Case Report and Literature Survey With Review of Upcoming American Association of Blood Banks Requirements
Authors: Burns Kathleen H. , Werch Jochewed B. 
Published: February 2021

Abstract
The most common transfusion-associated infectious risk in the United States today is bacterial contamination of platelet components. Bacterial contamination is estimated to occur at an incidence of 1:1000 to 1:3000 in platelet units, with severe episodes estimated to occur in about one sixth of contaminated products. Increased awareness and prompt reaction of the medical team can greatly affect the outcome and save a patient's life. The following case history illustrates this issue. A young woman developed chills and rigors while receiving 1 unit of leuko-reduced apheresis platelets for severe thrombocytopenia. The transfusion was stopped, blood cultures were drawn, and the patient developed clinical signs of sepsis. Cultures of both the platelet unit and the patient's blood revealed coagulase-negative Staphylococcus. Microbial susceptibilities in both samples were identical. Pretransfusion blood cultures taken from the patient earlier that day were negative. The platelet unit had been stored for 5 days. We review this case and the literature describing the persistent problem of platelet unit contamination and at the same time highlight the efforts now directed by the American Association of Blood Banks and College of American Pathologists to address this issue. Although there is no uniform approach to dealing with bacterial contamination of platelets, the American Association of Blood Banks and the College of American Pathologists have promulgated new accreditation requirements in an effort to prevent bacterial sepsis associated with platelet transfusion. A new American Association of Blood Banks standard, which will be effective March 1, 2004, requires a combination of strategies both to limit the initial inoculation of bacteria into the blood component and to detect subsequent growth at room temperature (American Association of Blood Banks Association Bulletin #03-12). The new College of American Pathologists Checklist question, which became effective in December 2003, is a Phase 1 requirement that calls for inspected facilities to have a platelet bacteria detection method in place.
Evidence for Involvement of Transforming Growth Factor β1 Signaling Pathway in Activation of JC Virus in Human Immunodeficiency Virus 1–Associated Progressive Multifocal Leukoencephalopathy
Authors: Enam Sahnila , Sweet Thersa M. , Amini Shohreh , Khalili Kamel , Del Valle Luis 
Published: February 2021

AbstractContext.—Progressive multifocal leukoencephalopathy is a fatal demyelinating disease of the central nervous system frequently seen in patients with impaired immune systems, particularly acquired immunodeficiency syndrome. JC virus (JCV), a human neurotropic polyomavirus, is the etiologic infectious agent of this disease.Objective.—The significantly higher incidence of progressive multifocal leukoencephalopathy in patients with acquired immunodeficiency syndrome than in patients with other immunosuppressive conditions suggests that molecular interactions between human immunodeficiency virus 1 and JCV, via the Tat protein, are responsible for the activation of the JCV enhancer/promoter and the development of progressive multifocal leukoencephalopathy. An indirect mechanism through activation of cytokines, such as transforming growth factor β1 and Smads 3 and 4, may also be responsible for the enhancement of JCV gene expression.Design.—Immunohistochemical analysis in progressive multifocal leukoencephalopathy samples and chloramphenicol acetyl transferase assays on cell cultures were performed to corroborate this hypothesis.Results.—The JCV capsid protein VP-1 was found in the nuclei of oligodendrocytes and in the nuclei and cytoplasm of bizarre astrocytes. Human immunodeficiency virus proteins, including p24 and Tat, were detected in the cytoplasm of astrocytes. Tat, but not p24, was detected in oligodendrocytes, suggesting that extracellular Tat accumulates in the nuclei of oligodendrocytes, where JCV gene transcription takes place. High levels of transforming growth factor β1 and Smads 3 and 4 were detected in JCV-infected oligodendrocytes. Results from in vitro studies confirm activation of the JCV early and late promoters by Smads 3 and 4.Conclusions.—These observations support our model, suggesting that the induction of transforming growth factor β1 by human immunodeficiency virus 1 Tat can stimulate its downstream factors, including Smads 3 and 4, which in turn augment transcription of the JCV promoter in glial cells.
Quality Indices in a Cervicovaginal Cytology Service: Before and After Laboratory Accreditation
Authors: Tan Kong-Bing , Chang Satina A. E. , Soh Vanessa C. H. , Thamboo Thomas Paulraj , Nilsson Barbro , Chan Norman H. L. 
Published: February 2021

Abstract
Context.—Quality assurance practices contribute to the effectiveness of cervical screening and are formalized by participation in a laboratory accreditation program.
Objective.—To identify changes in the quality indices of our cervicovaginal cytology service preceding and following laboratory accreditation by the College of American Pathologists in 2000.
Design.—Cervicovaginal cytology quality indices for 2001 (postaccreditation) were compared with those of 1997 (preaccreditation). Performances in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology (PAP) for the years 1999–2002 were analyzed.
Results.—A comparison between data for 1997 and 2001 shows the following: (a) a higher inadequacy rate (1.3% vs 0.7%; P &lt; .001) in 2001; (b) maintenance of a low atypical squamous cells of undetermined significance–squamous intraepithelial lesion ratio (0.79 and 0.76, respectively); (c) overall positive predictive values of positive cytology of 82% and 87%, respectively; (d) relatively few changes to the original cytologic diagnoses following review of significant cytohistologic discrepancies (4 cases and 2 cases, respectively); and (e) a higher subsequent positive yield of squamous intraepithelial lesions following atypical squamous cells of undetermined significance diagnoses in 2001 (41% vs 19%; P = .02). The performance of the laboratory and cytotechnologists in the PAP program showed maintenance of a high standard with almost no major discrepancies recorded.
Conclusions.—An increased awareness of quality-related issues and participation in intradepartmental consultation/diagnostic seminars, all part of the accreditation process, have very likely contributed to the modest improvements identified in the cytology service. Future challenges include increases in workload with the anticipated launch of Singapore's national cervical screening program and adaptation to the emerging cervical screening technologies.
Survivin and Bcl-2 Expression in Prostatic Adenocarcinomas
Authors: Kaur Prabhjot , Kallakury Bhaskar S. V. , Sheehan Christine E. , Fisher Hugh A. G. , Kaufman Ronald P. , Ross Jeffrey S. 
Published: February 2021

Abstract
Context.—Dysregulated cell proliferation caused by inhibitors of programmed cell death (apoptosis) contributes to tumor progression and spread. Aberrant expression of Bcl-2, the most notable inhibitor of apoptosis, has been well characterized in several human malignancies. Recent studies have described a novel apoptosis inhibitor, survivin, in human carcinomas, although its exact role remains to be characterized.
Objective.—The purpose of this study was to evaluate the immunohistochemical expression of Bcl-2 and survivin proteins in prostate cancer and to correlate the results with clinicopathologic variables.
Design.—Formalin-fixed, paraffin-embedded tissue sections from 138 cases of prostatic adenocarcinomas (PACs) were immunostained by an automated method using specific antibodies against survivin and Bcl-2. Staining was semiquantitatively scored based on both intensity and distribution, and results were correlated with morphologic and prognostic variables.
Results.—Of the 138 PACs tested, 113 (82%) expressed survivin. We found no correlation between survivin expression and prognostic variables, including grade, stage, DNA content (ploidy), and recurrence. Bcl-2 expression was positive in 95 (69%) of these 138 cases and correlated with nondiploid DNA content. Fourteen (50%) of 28 nondiploid PACs expressed Bcl-2, compared to 17 (25%) of 68 diploid tumors (P = .02). A trend for association of Bcl-2 expression with tumor stage was noted as follows: 21 (39%) of 54 advanced-stage PACs expressed Bcl-2, in comparison with 20 (24%) of 84 low-stage tumors (P = .07). On univariate analysis, 25 (48%) of the 52 PACs that recurred expressed Bcl-2, as compared with 16 (19%) of the 86 nonrecurrent PACs (P &lt; .001). No correlation was noted between survivin and Bcl-2 expression.
Conclusion.—Survivin is expressed in a majority of PACs and is not a prognosis-related marker, but may be a potential target for apoptosis-based therapy. Overexpression of Bcl-2 correlates with other prognostic variables and predicts disease recurrence of PACs. These data also suggest that survivin and Bcl-2 may regulate cell proliferation and cell death through different mechanisms.