tbuckley/cabot-search huggingface dataset:
Abstract A2: Novel serum biomarkers for histotype specific ovarian cancer diagnosis
Authors: Laura Lehtinen, Kristiina Iljin, Johanna Hynninen, Annika Auranen, Caj Haglund, Seija Grenman, Olli Carpén
Journal: Clinical Cancer Research (2013)

Abstract Current diagnostic methods for ovarian cancer include gynecological inspection, ultrasound-imaging and detection of the serum tumor marker CA-125. Even combined, these methods are insufficient in specificity and sensitivity for detection of early disease. Since the majority of ovarian carcinomas are of epithelial origin, the carcinogenesis has thought to be induced in the epithelial layer of the ovaries or fallopian tubes. However, recent findings indicate that many ovarian cancers originate from non-ovarian tissues and therefore different ovarian cancer histotypes should be regarded as distinct diseases. Currently the histotype of ovarian carcinomas can be determined only during surgery. There is an increasing need for more sensitive and specific biomarkers for ovarian cancer diagnosis as well as for prediction of biological tumor behavior. In this study, genes with ovarian cancer specific expression profile were identified from publicly available gene-expression databases. In order to find potential serum biomarker candidates, further in silico data mining was performed utilizing the GeneSapiens database. The identified ovarian cancer specific and potentially secreted or surface-expressed genes were validated in vitro in patient samples and primary ovarian cancer cells lines with qRT-PCR, western blotting and immunohistochemical staining of tumor tissue microarrays. The presence of the candidate biomarkers in patient serum samples was studied with dot blotting and immunoprecipitation. Finally, the expression levels of the candidate genes were compared to the pre-operative CA-125 and HE-4 levels in a cohort of prospective collected advanced ovarian cancer patients. The in silico data analyses resulted in identification of altogether six novel serum biomarker candidates for serous, mucinous and clear cell ovarian tumors. Analysis of tumor samples and primary cell lines derived from ovarian cancer patient samples confirmed the expression of the candidate genes in ovarian carcinomas. Furthermore, the mRNA analysis showed evidence of histotype specificity, especially in the case of potential biomarkers for mucinous ovarian carcinoma. Immunohistochemical staining of several tumor tissue samples showed distinctive cytoplasmic expression pattern characteristic for secreted proteins. Further analysis of the presence of the biomarkers in the sera of the patients and matched controls is in progress. Citation Format: Laura Lehtinen, Kristiina Iljin, Johanna Hynninen, Annika Auranen, Caj Haglund, Seija Grenman, Olli Carpén. Novel serum biomarkers for histotype specific ovarian cancer diagnosis. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A2.
Narrative Review: Initial Management of Newly Diagnosed, Early-Stage Chronic Lymphocytic Leukemia
Authors: Tait D. Shanafelt, John C. Byrd, Timothy G. Call, Clive S. Zent, Neil E. Kay
Journal: Annals of Internal Medicine (2006)

Chronic lymphocytic leukemia is one of the most common malignant lymphoid diseases in the western world and is frequently diagnosed by internists. There have been clinically significant changes in method of diagnosis, prognostic tools, supportive care, and treatment over the past 2 decades. Most patients with chronic lymphocytic leukemia now have Rai stage 0 or I disease at diagnosis. Patients with early-stage disease are a heterogeneous group: Approximately 30% to 50% will have accelerated disease progression, and the remainder may live for decades and possibly never require therapy. Recent insights into the biological characteristics of leukemic B cells have led to the discovery of new prognostic tools (immunoglobulin variable-region heavy chain gene mutation status, cytogenetic abnormalities assessed by fluorescent in situ hybridization, and Z-chain–associated protein kinase-70 protein expression) that can identify patients with early-stage disease who are at high risk for early disease progression. These tools allow physicians to individualize counseling, follow-up, and management on the basis of disease risk. In addition, new treatments developed over the past 2 decades (purine nucleoside analogues, monoclonal antibodies, and combination chemoimmunotherapy regimens) have dramatically improved response rates and appear to prolong survival. In this review, the authors discuss the current work-up of lymphocytosis and highlight how to use recently identified prognostic tools to stratify risk in patients with newly diagnosed, early-stage chronic lymphocytic leukemia. Recommendations for patient counseling, follow-up, supportive care, and initial treatment are presented for each risk category.
Determination of Brain Death by Isotope Angiography
Authors: Julius M. Goodman
Journal: JAMA (1969)

In more than 500 studies of cerebral perfusion by isotope angiography with the scintillation camera, visualization of cerebral arteries and venous sinuses invariably occurred, except in the three patients studied with suspected brain death. Each of these patients was deeply comatose, with dilated, fixed pupils, and required artificial ventilation. At autopsy their brains had severe autolytic changes (respirator brain). This preliminary experience suggests that an isotope angiogram showing no evidence of cerebral vasculature would be valuable in corroborating the clinical impression of brain death.
Hemolytic anemia with impaired hexokinase activity
Authors: Alan S. Keitt
Journal: Journal of Clinical Investigation (1969)

Analyses of key glycolytic intermediates in freshly drawn red cells from six related individuals suggest that decreased hexokinase activity underlies the hemolytic process in the two members with overt hemolysis. Low red cell glucose 6-phosphate (G6P) was observed not only in the anemic patients but in the presumptive heterozygotes as well and served as a useful marker for the presence of the trait. Hexokinase activity was labile in distilled water hemolysates but was only slightly low when protected by glucose, mercaptoethanol, and ethylenediaminetetraacetate (EDTA). Normal red cell hexokinase was demonstrated to be dependent on glucose for maintenance of activity after heating to 45°C. The cells of the proposita are unable to utilize glucose efficiently at glucose concentrations lower than 0.2 mmole/liter whereas normal cells maintain linear glucose consumption to at least 0.05 mM glucose. These qualitative abnormalities could result from the presence of a mutant hexokinase with an abnormally reactive sulfhydryl group and altered substrate affinity in the red cells of this kindred.
PATHOLOGICAL SUGGESTIONS: (1) THE PREPARATION OF MICROSCOPIC SLIDES FOR BLOOD-FILMS; (2) THE POSSIBLE APPLICATION OF FORMALIN GELATIN AS AN ANTISEPTIC AND DISINFECTANT PROTECTIVE SKIN ; AND (3) A TRYPANOSOME-LIKE ORGANISM FOUND IN ASSOCIATION WITH SOME CHRONIC PATHOLOGICAL AFFECTION OF THE MOUTH
Authors: A WRIGHT
Journal: The Lancet (1904)
Regional variability in preproEndothelin-1 gene expression in sheep pulmonary artery and lung during the onset of air-induced chronic pulmonary hypertension. Participation Of arterial smooth muscle cells.
Authors: E Tchekneva, T Quertermous, B W Christman, M L Lawrence, B Meyrick
Journal: Journal of Clinical Investigation (1998)

We investigated preproendothelin-1 (ppET-1) gene expression in the main and midregion pulmonary artery, and peripheral lung from control sheep and from animals during the development of the structural and functional changes of air-induced chronic pulmonary hypertension (CPH). Measurement of ET-1 in lung lymph (n = 7) at 1, 4, 8, and 12 d of continuous air embolization (CAE) showed a significant increase from day 4 compared with controls (n = 4). A semiquantitative reverse transcription PCR for ppET-1 gene expression was developed using ovine-specific primers. Control sheep showed strikingly fewer ppET-1 transcripts in the midregion (22.9+/-2.3 ng cDNA equivalents) than in the main pulmonary artery and lung (736.0+/-263.7 and 705.5+/-125.7, respectively). Smooth muscle cells (SMC) isolated from the main and midregion artery of control sheep confirmed these findings and showed higher levels of intracellular ET-1 synthesis in the main versus the midregion artery. Differences in gene expression persisted during CAE. In main pulmonary artery and lung, ppET-1 transcripts fell to < 1% of controls. However, transcripts in the midregion artery showed a gradual increase. Coincubation of SMC from the midregion with ET-1 plus TGF-beta resulted in an increase in intracellular big ET-1 and a decrease in SMC from the main artery. We conclude that SMC from the main and midregion pulmonary artery are phenotypically different and suggest that local synthesis of ET-1 and TGF-beta, and increased levels of ET-1 in lung lymph, regulate ppET-1 gene expression and synthesis in arterial SMC during the development of air-induced CPH.
CD8+ T-Cell Responses against Hemoglobin-β Prevent Solid Tumor Growth
Authors: Hideo Komita, Xi Zhao, Jennifer L. Taylor, Louis J. Sparvero, Andrew A. Amoscato, Sean Alber, Simon C. Watkins, Angela D. Pardee, Amy K. Wesa, Walter J. Storkus
Journal: Cancer Research (2008)

Bone marrow-derived dendritic cells engineered using recombinant adenovirus to secrete high levels of IL-12p70 dramatically inhibited the growth of established CMS4 sarcomas in BALB/c mice after intratumoral administration. An analysis of splenic CD8(+) T cells in regressor mice revealed a strong, complex reactivity pattern against high-performance liquid chromatography (HPLC)-resolved peptides isolated by acid elution from single-cell suspensions of surgically resected CMS4 lesions. Mass spectrometry analyses defined two major overlapping peptide species that derive from the murine hemoglobin-beta (HBB) protein within the most stimulatory HPLC fractions. Although cultured CMS4 tumor cells failed to express HBB mRNA based on reverse transcription-PCR analyses, prophylactic vaccination of BALB/c mice with vaccines containing HBB peptides promoted specific CD8(+) T-cell responses that protected mice against a subsequent challenge with CMS4 or unrelated syngeneic (HBB(neg)) tumors of divergent histology (sarcoma, carcinomas of the breast or colon). In situ imaging suggested that vaccines limit or destabilize tumor-associated vascular structures, potentially by promoting immunity against HBB+ vascular pericytes. Importantly, there were no untoward effects of vaccination with the HBB peptide on peripheral RBC numbers, RBC hemoglobin content, or vascular structures in the brain or eye.
Prognostically relevant gene signatures of high-grade serous ovarian carcinoma
Authors: Roel G.W. Verhaak, Pablo Tamayo, Ji-Yeon Yang, Diana Hubbard, Hailei Zhang, Chad J. Creighton, Sian Fereday, Michael Lawrence, Scott L. Carter, Craig H. Mermel, Aleksandar D. Kostic, Dariush Etemadmoghadam, Gordon Saksena, Kristian Cibulskis, Sekhar Duraisamy, Keren Levanon, Carrie Sougnez, Aviad Tsherniak, Sebastian Gomez, Robert Onofrio, Stacey Gabriel, Lynda Chin, Nianxiang Zhang, Paul T. Spellman, Yiqun Zhang, Rehan Akbani, Katherine A. Hoadley, Ari Kahn, Martin Köbel, David Huntsman, Robert A. Soslow, Anna Defazio, Michael J. Birrer, Joe W. Gray, John N. Weinstein, David D. Bowtell, Ronny Drapkin, Jill P. Mesirov, Gad Getz, Douglas A. Levine, Matthew Meyerson
Journal: Journal of Clinical Investigation (2012)

Because of the high risk of recurrence in high-grade serous ovarian carcinoma (HGS-OvCa), the development of outcome predictors could be valuable for patient stratification. Using the catalog of The Cancer Genome Atlas (TCGA), we developed subtype and survival gene expression signatures, which, when combined, provide a prognostic model of HGS-OvCa classification, named "Classification of Ovarian Cancer" (CLOVAR). We validated CLOVAR on an independent dataset consisting of 879 HGS-OvCa expression profiles. The worst outcome group, accounting for 23% of all cases, was associated with a median survival of 23 months and a platinum resistance rate of 63%, versus a median survival of 46 months and platinum resistance rate of 23% in other cases. Associating the outcome prediction model with BRCA1/BRCA2 mutation status, residual disease after surgery, and disease stage further optimized outcome classification. Ovarian cancer is a disease in urgent need of more effective therapies. The spectrum of outcomes observed here and their association with CLOVAR signatures suggests variations in underlying tumor biology. Prospective validation of the CLOVAR model in the context of additional prognostic variables may provide a rationale for optimal combination of patient and treatment regimens.
Molecular pathogenesis of emphysema
Authors: Laimute Taraseviciene-Stewart, Norbert F. Voelkel
Journal: Journal of Clinical Investigation (2008)

Emphysema is one manifestation of a group of chronic, obstructive, and frequently progressive destructive lung diseases. Cigarette smoking and air pollution are the main causes of emphysema in humans, and cigarette smoking causes emphysema in rodents. This review examines the concept of a homeostatically active lung structure maintenance program that, when attacked by proteases and oxidants, leads to the loss of alveolar septal cells and airspace enlargement. Inflammatory and noninflammatory mechanisms of disease pathogenesis, as well as the role of the innate and adaptive immune systems, are being explored in genetically altered animals and in exposure models of this disease. These recent scientific advances support a model whereby alveolar destruction resulting from a coalescence of mechanical forces, such as hyperinflation, and more recently recognized cellular and molecular events, including apoptosis, cellular senescence, and failed lung tissue repair, produces the clinically recognized syndrome of emphysema.
PD05-01: Trans-CHER-Lob: A Biomarker Analysis of the Randomized Phase II Study of Neoadjuvant Chemotherapy Plus Trastuzumab, Lapatinib or Combined Trastuzumab and Lapatinib in HER2 Positive Operable Breast Cancer.
Authors: V Guarneri, A Frassoldati, G Ficarra, A Maiorana, S Bettelli, A Bottini, K Cagossi, G Bisagni, A Ravaioli, D Amadori, A Musolino, L Cavanna, L Orlando, G Giardina, F Piacentini, M Bagnalasta, P Conte
Journal: Cancer Research (2011)

Abstract Introduction: The CHER-Lob study is a randomized phase II trial of preoperative sequential taxanes-anthracyclines in combination with trastuzumab, lapatinib, or combined trastuzumab and lapatinib in HER2 positive, stage II-IIIA breast cancer patients. A translational program to evaluate predictors of response as well as treatment effects on tissue biomarkers was pre-planned. Methods: The CHER-Lob translational program includes the central evaluation of HER2, p95HER2, PTEN, pAKT, Ki67 on pre and post-therapy samples. All these biomarkers have been evaluated by immunohistochemistry. FISH analysis was performed in case of HER2 IHC 2+, and in all the discordant cases between central and local laboratories. Biomarkers change from baseline to surgery has been evaluated with the Wilcoxon signed-ranks matched-pair test. Results: 121 patients have been randomized. The pathologic complete response rate (breast and axillary lymphnodes) was 26% in Arm A (chemotherapy + trastuzumab), 28% in arm B (chemotherapy + lapatinib) and 44% in arm C (chemotherapy + trastuzumab and lapatinib). The concordance between central and local HER2 assessment on pre-treatment biopsy was 97%. The mean (min;max) PTEN expression pre- and post-therapy were 66% (0;100) and 68.4% (0;100) respectively. The mean (min;max) pAKT expression pre- and post-therapy were 23.3% (0;100) and 8.8% (0;90) respectively. A significant decrease was observed in the overall samples (p=0.01). When analyzing the lapatinib alone arm, the difference was no longer significant (p=0.06), while it maintained significance when evaluating the two trastuzumab containing arms (p=0.0013). The mean (min;max) ki67 expression pre- and post-therapy were 29.5% (4;90) and 16.6% (1;50) respectively. A significant decrease was observed when looking at the whole population (p&amp;lt;0.0001). A significantly higher ki67 inhibition was observed in the dual vs single anti-Her2 therapy (p= 0.003). Conclusions: The central HER2 retesting showed a high concordance with local laboratories. Treatment induced a suppression in pAKT expression, that was higher in patients receiving trastuzumab. The dual anti-HER2 blockade induced a higher KI67 inhibition as compared to single anti-Her2 blockade. The evaluation of the predictive and prognostic role of these biomarkers is ongoing. Supported by GlaxoSmithKline Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD05-01.
Systematic Review: Diagnostic Procedures to Differentiate Unilateral From Bilateral Adrenal Abnormality in Primary Aldosteronism
Authors: Marlies J.E. Kempers
Journal: Annals of Internal Medicine (2009)

Background: Computed tomography (CT), magnetic resonance imaging (MRI), and adrenal vein sampling (AVS) are used to distinguish unilateral from bilateral increased aldosterone secretion as a cause of primary aldosteronism. This distinction is crucial because unilateral primary aldosteronism can be treated surgically, whereas bilateral primary aldosteronism should be treated medically. Purpose: To determine the proportion of patients with primary aldosteronism whose CT or MRI results with regard to unilateral or bilateral adrenal abnormality agreed or did not agree with those of AVS. Data Sources: PubMed, MEDLINE, EMBASE, and Cochrane Library, 1977 to April 2009. Study Selection: Studies describing adults with primary aldosteronism who underwent CT/MRI and AVS were included. Of 472 initially identified studies, 38 met the selection criteria; extractable data were available for 950 patients. Data Extraction: The CT/MRI result was considered accurate when AVS showed unilaterally increased aldosterone secretion on the same side as the abnormality seen on CT/MRI or when AVS showed symmetric aldosterone secretion and CT/MRI revealed bilateral or no unilateral abnormality. Data Synthesis: In 37.8% of patients (359 of 950), CT/MRI results did not agree with AVS results. If only CT/MRI results had been used to determine lateralization of an adrenal abnormality, inappropriate adrenalectomy would have occurred in 14.6% of patients (where AVS showed a bilateral problem), inappropriate exclusion from adrenalectomy would have occurred in 19.1% (where AVS showed unilateral secretion), and adrenalectomy on the wrong side would have occurred in 3.9% (where AVS showed aldosterone secretion on the opposite side). Limitation: The lack of follow-up data in the included articles made it impossible to confirm that adrenalectomies were performed appropriately. Conclusion: When AVS is used as the criterion standard test for diagnosing laterality of aldosterone secretion in patients with primary aldosteronism, CT/MRI misdiagnosed the cause of primary aldosteronism in 37.8% of patients. Relying only on CT/MRI may lead to inappropriate treatment of patients with primary aldosteronism.
Variation in<i>PTX3</i>Is Associated with Primary Graft Dysfunction after Lung Transplantation
Authors: Joshua M. Diamond, Nuala J. Meyer, Rui Feng, Melanie Rushefski, David J. Lederer, Steven M. Kawut, James C. Lee, Edward Cantu, Rupal J. Shah, Vibha N. Lama, Sangeeta Bhorade, Maria Crespo, Ejigayehu Demissie, Joshua Sonett, Keith Wille, Jonathan Orens, Ann Weinacker, David Weill, Selim Arcasoy, Pali D. Shah, John A. Belperio, David Wilkes, Lorraine B. Ware, Scott M. Palmer, Jason D. Christie
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: Elevated long pentraxin-3 (PTX3) levels are associated with the development of primary graft dysfunction (PGD) after lung transplantation. Abnormalities in innate immunity, mediated by PTX3 release, may play a role in PGD pathogenesis.Objectives: Our goal was to test whether variants in the gene encoding PTX3 are risk factors for PGD.Methods: We performed a candidate gene association study in recipients from the multicenter, prospective Lung Transplant Outcomes Group cohort enrolled between July 2002 and July 2009. The primary outcome was International Society for Heart and Lung Transplantation grade 3 PGD within 72 hours of transplantation. Targeted genotyping of 10 haplotype-tagging PTX3 single-nucleotide polymorphisms (SNPs) was performed in lung transplant recipients. The association between PGD and each SNP was evaluated by logistic regression, adjusting for pretransplantation lung disease, cardiopulmonary bypass use, and population stratification. The association between SNPs and plasma PTX3 levels was tested across genotypes in a subset of recipients with idiopathic pulmonary fibrosis.Measurements and Main Results: Six hundred fifty-four lung transplant recipients were included. The incidence of PGD was 29%. Two linked 5′ region variants, rs2120243 and rs2305619, were associated with PGD (odds ratio, 1.5; 95% confidence interval, 1.1 to 1.9; P = 0.006 and odds ratio, 1.4; 95% confidence interval, 1.1 to 1.9; P = 0.007, respectively). The minor allele of rs2305619 was significantly associated with higher plasma PTX3 levels measured pretransplantation (P = 0.014) and at 24 hours (P = 0.047) after transplantation in patients with idiopathic pulmonary fibrosis.Conclusions: Genetic variants of PTX3 are associated with PGD after lung transplantation, and are associated with increased PTX3 plasma levels.
A Visit to Ehrlich
Authors: B. C. Corbus
Journal: JAMA (1910)

erly enforced.The requirements to practice medicine in most of our states should be made more thorough, not for the pur- pose of preventing foreign physicians from obtaining licenses, but to protect the public from illiterate and untrained doctors no matter where they come from.\p=m-\Ed.]erly enforced.The requirements to practice medicine in most of our states should be made more thorough, not for the pur- pose of preventing foreign physicians from obtaining licenses, but to protect the public from illiterate and untrained doctors no matter where they come from.\p=m-\Ed.
Bone Scintigraphy in Evaluation of Didronel?? Therapy for Paget??s Disease
Authors: JAI Y. LEE
Journal: Clinical Nuclear Medicine (1981)

A case of advanced Paget's disease was successfully treated with Didronel®. All indicators of disease activity have been in remission for two years post-therapy. Although sequential radiographs obtained before and after treatment showed slight changes that might have reflected a reparative process, bone scintigraphs revealed more prominent changes, so that radionuclide bone imaging could well be considered as the follow-up imaging study of choice after treatment of Paget's disease.
An 89-Year-Old Woman With Urinary Incontinence
Authors: Neil M. Resnick
Journal: JAMA (1996)

<h3>DR DALEY:</h3> Mrs S is an 89-year-old widow and retired accountant who has had urinary incontinence for 14 years. She lives in a suburb of Boston. Mrs S's incontinence occurs once or twice each night, when after being in bed for several hours, she awakens needing to void. As soon as she arises from bed, she wets herself, the 2 pads that she wears constantly, and her clothing. By the time she has reached the toilet, she has also wet the bedclothes, the bedroom floor, and the bathroom floor. She cleans herself, her clothing, and her bedroom and bathroom and returns to bed. She often remains in bed until 10AMbecause of fatigue and lack of sleep. During the day, she notes only occasional "leaking," but never when she coughs or sneezes. When her urinary incontinence began, she was treated for a urinary tract infection. She saw a urologist