tbuckley/cabot-search huggingface dataset:
Leg Vein Uptake of Tl-201 in a Patient With Venous Thrombosis in the Lower Extremity
Authors: KAZUYOSHI SUGA, YUKO ISHIKAWA, KAZUKO MOTOYAMA, NORIHIKO KUME, NAOFUMI MATSUNAGA
Journal: Clinical Nuclear Medicine (2000)

Tl-201 scintigraphy was performed in an 82-year-old man with malignant fibrous histiocytoma to identify possible systemic metastasis. Whole-body imaging unexpectedly showed abnormal tracer uptake in left lower leg varices and the ipsilateral, proximal femoropopliteal veins. Ultrasonography later revealed the presence of thrombi in the femoral vein and the varices of the left lower leg.
Endoscopy and Endosonography in Prevention of Esophageal and Gastric Bleedings and Rebleedings
Authors: AV Philin, LM Myaukina, AA Filin, EV Kim, VA Douvansky
Journal: Endoscopy (2011)

Background: Esophageal and gastric variceal bleeding is one of the basic reasons of death in patients with the portal hypertension. In spite of improvement of diagnostic and treatment (conservative and operative) this complication causes death in 20–80% cases. Endoscopic varices sclerotherapy (EVS) has many essential lacks. The quantity of complications (ulcers, perforations, bleedings, corrosive strictures) is about 10–70%. The role of endosonography (EUS) in diagnostics of esophageal and gastric varices is unclear.
SP0056 Potential therapeutic use of micrornas in rheumatology
Authors: H.-M. Jäck, M. Porstner, J. Wittmann, M. Bösl
Journal: Annals of the Rheumatic Diseases (2013)

Our long-term goal is to understand how small non-coding micro-RNAs (miRNAs) regulate and fine-tune the differentiation of mature B cells into memory B cells and antibody-secreting plasma cells. miRNAs control the expression of specific target genes at the post-transcriptional level by binding to target sequences e.g., in the 3’-untranslated region of mRNAs, which results either in a block of translation or an accelerated degradation of the respective target mRNA. Lineage-specific deletion of the miRNA-processing DICER protein as well as of individual miRNAs revealed the importance of miRNA pathway in early steps of central B cell maturation. However, the mechanisms by which miRNA-dependent circuits control the antigen-induced phase of B cell activation of mature naive B cells and their subsequent differentiation into effector cells remain largely elusive. To change this situation we established a transgenic knock-in mouse line with a floxed allele of DGCR8, an essential subunit of the nuclear miRNA processing complex. B cell-specific deletion of DGCR8 resulted in a complete maturation block at the pro-B stage, indicating that miRNA processing is essential for central B cell maturation. We have also obtained genome-wide miRNA expression profiles of all major mouse B cell subsets, including long-lived plasma cells, and found a profound upregulation of miR-ER3 in plasma cells. Ectopic expression of this plasma cell signature miRNA in primary mouse B cells accelerated the differentiation into antibody-secreting plasmablast, as indicated by upregulation of CD138 and enhanced secretion IgM secretion. We also verified several miR-ER3 targets, e.g., Bach2 and MiTF, that are part of the transcriptional circuit that controls germinal center reactions and plasma cell differentiation. These studies will provide new molecular insights into regulatory circuits that control the production of antibodies and could potentially lead to new avenues for diagnosing or treating diseases associated with aberrant plasma cell development, e.g., primary antibody deficiencies, plasma cell malignancies, and autoimmune disorders. <h3>Disclosure of Interest</h3> None Declared
Focal Increased 18F FP-CIT Uptake in a Recent Ischemic Lesion in the Frontal Lobe
Authors: Miju Cheon, Kyung-Han Lee
Journal: Clinical Nuclear Medicine (2014)

A 65-year-old male patient was referred for rapid functional decline over 1 month with dysphagia and dysarthria. Past history disclosed left side weakness for 5 years. F FP-CIT PET/CT was performed to evaluate the possibility of pseudobulbar palsy. Images showed a defect in the right posterior putamen that was consistent with an old cerebral infarction lesion. Unexpectedly, an oval area of intense F FP-CIT uptake was found in the left frontal lobe. MRI and F-FDG PET/CT indicated the lesion to be caused by recent cerebral ischemia.
The Progesterone Antagonist RU 486
Authors: Lynnette K. Nieman, Teresa M. Choate, George P. Chrousos, David L. Healy, Martin Morin, David Renquist, George R. Merriam, Irving M. Spitz, C. Wayne Bardin, Etienne-Emile Baulieu, D. Lynn Loriaux
Journal: New England Journal of Medicine (1987)

Since progesterone supports endometrial nidation of the fertilized ovum, a progesterone antagonist would theoretically block this process and thus have contraceptive potential. We have explored the ability of RU 486, a newly developed competitive progesterone antagonist, to function as a contraceptive agent. A single oral dose of 10 mg per kilogram of body weight given in the midluteal phase consistently induced menses within 72 hours in women with normal cycles and no risk of pregnancy. Bleeding was not prevented by administration of human chorionic gonadotropin in the midluteal phase. This suggested that giving a single dose of RU 486 late in the menstrual cycle might be an effective contraceptive strategy. This concept was tested in monkeys. When given to rhesus females on day 25 of the cycle, a single intramuscular dose of RU 486 (5 mg per kilogram) prevented pregnancy. The vehicle-treated control animals had a 28 percent pregnancy rate (P less than 0.05 by chi-square analysis). No side effects were noted in women or monkeys. These data suggest that a progesterone antagonist such as RU 486 has the potential to be an effective, safe, and convenient contraceptive agent. Further work will be necessary to assess the safety of long-term monthly administration and to define the optimal dose and time of administration in women.
Sustained and Diffuse 131I Avid Bone Metastases With Low Thyroglobulin Levels in a Patient With Papillary Thyroid Carcinoma
Authors: Chun-Lei Zhao, Zhong-Ling Qiu, Li-Bo Chen, Zhi-Bin Yuan, Quan-Yong Luo
Journal: Clinical Nuclear Medicine (2013)

A 63-year-old man with papillary thyroid carcinoma (PTC) and bone metastases was treated with 131I residual thyroid ablation (RTA) and 2 repeated post-ablation 131I therapies after total thyroidectomy. 131I whole-body scans (WBS) demonstrated sustained and diffuse 131I avid bone metastases, accompanied by persistent very low thyroglobulin (Tg) levels and negative antithyroglobulin antibody (TgAb) in post-ablation 131I therapies in hypothyroid state after levothyroxine withdrawal. The spread of bone metastases were found on the last therapeutical 131I WBS. The benefit of 131I therapy after levothyroxine withdrawal should be weighed even if the metastases are 131I avid in poorly differentiated thyroid carcinoma.
Cytotoxic Immune Response Blunts Long-Term Transgene Expression after Efficient Retroviral-Mediated Hepatic Gene Transfer in Rat
Authors: Dominique Aubert, Séverine Ménoret, Estelle Chiari, Virginie Pichard, Sophie Durand, Laurent Tesson, Philippe Moullier, Ignacio Anegon, Nicolas Ferry
Journal: Molecular Therapy (2002)

Vectors derived from oncoretroviruses can transduce a small proportion of hepatocytes when injected in the regenerating liver. Transgene expression may be sustained for months without immune response. In striking contrast, we observed a rapid extinction when the intravenous injection of a high input of nuclear β-galactosidase (β-gal) expression vector, one day after partial hepatectomy, led to a significant proportion of transduced cells in the liver. Extinction was associated with liver inflammation on tissue sections and appearance of antibodies against the transgene product, while vector genomes became undetectable in liver tissue by PCR. These observations suggested the elimination of transduced cells by an immune response. Transgenic rats tolerant for cytoplasmic β-gal, or normal rats depleted in CD8 T lymphocytes, steadily expressed the β-gal vector. In the spleen of normal rats, we detected cytotoxic cells directed against cells expressing β-gal after the injection of the β-gal vector. In jaundiced Gunn rats deficient in bilirubin glucuronosyl transferase (BGT1) and treated with a human BGT1 cDNA expression vector, we observed the same kinetics of extinction as well as the appearance of anti-BGT1 antibodies. This study demonstrates that retrovirus-mediated gene transfer may induce cytotoxic T lymphocytes specifically directed against transgene-expressing cells. Vectors derived from oncoretroviruses can transduce a small proportion of hepatocytes when injected in the regenerating liver. Transgene expression may be sustained for months without immune response. In striking contrast, we observed a rapid extinction when the intravenous injection of a high input of nuclear β-galactosidase (β-gal) expression vector, one day after partial hepatectomy, led to a significant proportion of transduced cells in the liver. Extinction was associated with liver inflammation on tissue sections and appearance of antibodies against the transgene product, while vector genomes became undetectable in liver tissue by PCR. These observations suggested the elimination of transduced cells by an immune response. Transgenic rats tolerant for cytoplasmic β-gal, or normal rats depleted in CD8 T lymphocytes, steadily expressed the β-gal vector. In the spleen of normal rats, we detected cytotoxic cells directed against cells expressing β-gal after the injection of the β-gal vector. In jaundiced Gunn rats deficient in bilirubin glucuronosyl transferase (BGT1) and treated with a human BGT1 cDNA expression vector, we observed the same kinetics of extinction as well as the appearance of anti-BGT1 antibodies. This study demonstrates that retrovirus-mediated gene transfer may induce cytotoxic T lymphocytes specifically directed against transgene-expressing cells.
Mitotane for 21-Hydroxylase Deficiency in an Infertile Man
Authors: Hélène Bry-Gauillard, Alejandra Cartes, Jacques Young
Journal: New England Journal of Medicine (2014)

To the Editor: In our original report, 1 we used a method based on polymerase-chain-reaction (PCR) amplification developed in our laboratory to perform KIR genotyping. 2 We have retyped 1220 of the original 1277 donor samples using three separate published or commercial genetyping methods (PCR-sequence-specific primers [SSP] and PCR-sequence-specific oligonucleotide probe [SSOP]), and we have repeated the analysis on the retyped cohort.For KIR2DS1, typing was confirmed in 1146 (94%) of the 1220 retested samples and corrected in 74 (6%) of the retested samples.For KIR3DS1, typing was confirmed in 1133 (93%) and corrected in 83 (7%).Differences in typing results came from two sources: from errors made in the performance of the original PCR-SSP-based typing and from a recombinant allele that typed as the activating KIR3DS1 in the original PCR-SSP typing but types as an inhibitory KIR3DL1 allele when contemporary typing methods (PCR-SSP and PCR-SSOP) are used.Gene frequencies in the original and retyped cohorts were nearly identical (KIR2DS1, 33% positive in the original cohort and 34% positive in the retyped cohort; KIR3DS1, 34% positive in the original cohort and 33% positive in the retyped cohort).Analysis of the clinical effect of KIR2DS1 and HLA-C in the retyped cohort revealed results that were similar to those from the original analysis.We have provided figures and associations from the original analysis of 1277 patients in juxtaposition with figures and associations from the retyped cohort of 1220 in the Supplementary Appendix, available with the full text of this letter at NEJM.org.Our conclusions regarding the protective effect of donor KIR2DS1 on relapse and the influence of donor and recipient HLA-C on this effect are unchanged.These and other conclusions are summarized in the Supplementary Appendix.
Bronchobiliary fistula as a complication after long-term stenting of hepatic ducts, applied by ERCP after hepatobiliary surgery due to hydatid cyst
Authors: H. Razak Hady, A. Baniukiewicz, M. Luba, P. Rogalski, A. Dabrowski, J. Dadan
Journal: Endoscopy (2011)

A 48-year-old white woman, who worked in agriculture, was admitted with a 4-month history of cough productive of bile-like yellow phlegm. She had been hospitalized several times previously for recurrent right-sided pneumonias. The patient had undergone surgical resection of echinococcal cysts within liver segments V, VI, and VIII, cholecystectomy, and reconstruction of the right hepatic duct damaged by parasitic cyst infiltration 6 years previously ([Fig. 1]).
Abstract 3478: CD44+CD24low+ progenitors in ER negative breast cancer have higher Notch1 activation, self-renewal, and chemo resistance and generate CD44+CD24neg cells and tumors that metastasize
Authors: Diana J. Azzam, Katherine Drews Elger, Dekuang Zhao, Prathibha Ranganathan, Tony Capobianco, Andy J. Minn, Chad Creighton, Manuel Picon, Jun Sun, Chendong Pan, Seth A. Wander, Dorraya El Ashry, Joyce M. Slingerland
Journal: Cancer Research (2012)

Abstract CD44 surface expression is associated with self renewal in several cancers. While CD44+/CD24neg/low/ESA+ breast cancer subpopulations are enriched for cancer stem cells (CSC), the relative contributions of CD24 negative versus low subpopulations to stemness and metastasis is poorly defined. Here we show that CD44+/CD24low+ CSC give rise to CD44+/CD24neg progeny with reduced tumorigenicity and altered drug sensitivities. CD44+/CD24low+ subpopulations in MDA-MB-231 and in primary dissociated ER negative breast cancers show greater sphere and soft agar colony formation, Notch1 activation, Sox2 and Nanog expression and chemo resistance compared to CD44+/CD24neg. CD44+/CD24low+ can self-renew and give rise to CD44+/CD24neg cells, while CD44+/CD24neg progeny are exclusively CD44+/CD24neg. Tumorigenicity was increased and metastasis arose exclusively from orthotopic CD44+CD24low+ xenografts. CD44+/CD24low+ had greater expression of metastasis- and embryonic stem cell- associated and Notch pathway activated genes than CD44+/CD24neg cells. Moreover, MDA-MB-231 cells overexpressing Notch1 intracellular domain (N1-ICD) had higher Sox2 expression, and higher indices of CSC self-renewal (higher % CD44+/CD24low+, ALDH1 activity, sphere and soft agar colony formation), all of which were abrogated by Sox2 knockdown. Gamma secretase inhibition reduced ES-TFs and self-renewal in CD44+CD24low+ progenitors, but had no effect on proliferation or survival of CD44+CD24neg cells supporting further clinical development of Notch targeting drugs for cancer treatment in humans. Thus, CD44+CD24low+ and CD44+CD24neg CSC in ER negative breast cancer have distinct properties. CD44+CD24low+ can self-renew and generate CD44+CD24neg progeny. Orthotopic xenograft CD44+CD24low+ tumors arose with reduced latency with higher frequent, were larger, and the sole source of metastasis. Notch1 activation of Sox2 drives CD44+CD24low+ self-renewal and is blocked by GSI providing a strong rationale for use of GSI as CSC targeting agents in ER negative breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3478. doi:1538-7445.AM2012-3478
Analysis of Topoisomerase IIa and HER2 Status in 126 Patients from the US Oncology 9735 Trial of Adjuvant Chemotherapy with Docetaxel/Cyclophosphamide (TC) vs Doxorubicin/Cyclophosphamide (AC) in Early Breast Cancer.
Authors: C. Aitelli, C. Aitelli, R. Saad, D. Mackey, L. Asmar, S. Jones, S. Jones, S. Jones, J. Pippen, J. Pippen, J. Pippen
Journal: Cancer Research (2009)

Abstract Background: HER2/neu (HER2) positive breast cancers are associated with worse survival, resistance to cyclophosphamide/methotrexate/fluorouracil, and hypothesized to be sensitive to anthracyclines. It has been postulated that only a subset of HER2 positive breast cancers are sensitive to anthracyclines. Investigators have been working on how to identify this subset of patients, thus sparing patients from anthracyclines that have potential cardiac and bone marrow toxicities. Overexpression of the topoisomerase IIa gene (TOP2A) is the putative biomarker for sensitivity to anthracyclines. Testing tumors for overexpression of this gene may help identify patients who will not benefit from anthracylines. TOP2A is located in the same amplicon as the HER2 gene and can be assessed for overexpression by a FISH assay.Materials and Methods: Paraffin tissue blocks were obtained in 126 patients entered on US Oncology trial 9735 which recruited patients between 1997 and 2000. Data on HER2 status and outcome was previously reported (JCO 27:1177-1183, 2009). TOP2A status was then assessed by fluorescent in situ hybridization (FISH) using the LSI TOP2A Spectrum Orange Probe (Vysis). A total of 20 cells were counted and a gene ratio of greater than 2.0 was considered positive. Clinical data and outcome were available for statistical analysis.Results: We found that none of the 97 HER2 negative cases demonstrated overexpression of TOP2A by FISH analysis. TOP2A was overexpressed in 43% of the 29 HER2 positive cases. An analysis of outcome will be presented at the meeting, although the number of cases limits this observation.Discussion: Our study supports the observation that TOP2A is not overexpressed in HER2 negative disease and is only observed in a subset of cancers overexpressing HER2. Clinical correlation of outcome will be necessary to confirm whether or not TOP2A is a reliable biomarker of sensitivity to anthracyclines. The ongoing US Oncology trial of TC vs. TAC in HER2 negative breast cancer (USOR Trial 06-090) should provide that evidence.Supported in part by a grant from sanofi-aventis. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2134.
Mammosphere Culture of Established Cell Lines Does Not Enrich for a More Tumorigenic Breast Cancer Stem Cell Population.
Authors: E. Iorns, J. Clarke, S. Dean, M. Lippman
Journal: Cancer Research (2009)

Abstract Background:The cancer stem cell model suggests that tumors arise from and are maintained by a relatively small proportion of cells, termed cancer stem cells. According to this model, only these cells have the capacity for self-renewal and the ability to repopulate the tumor bulk by giving rise to the phenotypically heterogeneous populations of cells that comprise the primary tumor. Evidence to support the cancer stem cell model has been provided by isolation of subpopulations of cells on the basis of differential expression of cell surface markers, followed by functional transplantation into animal models. These studies reveal that only a small subset of CD44+/CD24-/low cancer cells retain the ability to form new tumors after transplantation in immunodeficient mice, consistent with the cancer stem cell model. These results indicate that it may be necessary to target and eliminate cancer stem cells in order to eradicate tumors.Material and Methods:Previous studies have suggested that only breast stem cells have the capacity to proliferate in suspension as spherical colonies termed mammospheres, and that mammosphere derived breast cancer cells are CD44+/CD24-/low and able to form tumors that reproduce the heterogeneity of the original primary tumor when injected into the mammary fat pad of immunodeficient mice. This indicates that mammospheres are comprised of breast cancer stem cells. To identify and characterize breast cancer stem cells more completely, the mammosphere culture system was used to isolate and propagate breast cancer stem cells from three basal breast cancer cell lines (BT549, MDA231, MDA436) and three luminal breast cancer cell lines (MCF7, SKBR3, T47D). The tumorigenicity of the cultured mammospheres and parental cell lines was examined using dilution studies in immunodeficient mice and gene expression profiles were studied by microarray analysis.Results and Discussion:No significant differences in tumorigenicity were observed between breast cancer cells cultured as mammospheres versus standard culture conditions. Furthermore, no consistent differences in gene expression profiles were observed between mammosphere and parental cells across the panel of cancer cell lines. These results suggest that mammosphere culture is not capable of significantly enriching for a more tumorigenic breast cancer stem cell population from established breast cancer cell lines. This may indicate that cancer subpopulations that exist in primary tumors are lost during the long term culture of breast cancer cell lines and that these systems may not be a suitable model for breast cancer stem cell studies. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 502.
Desert Dust Outbreaks in Southern Europe: Contribution to Daily PM <sub>10</sub> Concentrations and Short-Term Associations with Mortality and Hospital Admissions
Authors: Massimo Stafoggia, Stefano Zauli-Sajani, Jorge Pey, Evangelia Samoli, Ester Alessandrini, Xavier Basagaña, Achille Cernigliaro, Monica Chiusolo, Moreno Demaria, Julio Díaz, Annunziata Faustini, Klea Katsouyanni, Apostolos G. Kelessis, Cristina Linares, Stefano Marchesi, Sylvia Medina, Paolo Pandolfi, Noemí Pérez, Xavier Querol, Giorgia Randi, Andrea Ranzi, Aurelio Tobias, Francesco Forastiere
Journal: Environmental Health Perspectives (2015)

Background:Evidence on the association between short-term exposure to desert dust and health outcomes is controversial.Objectives:We aimed to estimate the short-term effects of particulate matter ≤ 10 μm (PM10) on mortality and hospital admissions in 13 Southern European cities, distinguishing between PM10 originating from the desert and from other sources.Methods:We identified desert dust advection days in multiple Mediterranean areas for 2001–2010 by combining modeling tools, back-trajectories, and satellite data. For each advection day, we estimated PM10 concentrations originating from desert, and computed PM10 from other sources by difference. We fitted city-specific Poisson regression models to estimate the association between PM from different sources (desert and non-desert) and daily mortality and emergency hospitalizations. Finally, we pooled city-specific results in a random-effects meta-analysis.Results:On average, 15% of days were affected by desert dust at ground level (desert PM10 > 0 μg/m3). Most episodes occurred in spring–summer, with increasing gradient of both frequency and intensity north–south and west–east of the Mediterranean basin. We found significant associations of both PM10 concentrations with mortality. Increases of 10 μg/m3 in non-desert and desert PM10 (lag 0–1 days) were associated with increases in natural mortality of 0.55% (95% CI: 0.24, 0.87%) and 0.65% (95% CI: 0.24, 1.06%), respectively. Similar associations were estimated for cardio-respiratory mortality and hospital admissions.Conclusions:PM10 originating from the desert was positively associated with mortality and hospitalizations in Southern Europe. Policy measures should aim at reducing population exposure to anthropogenic airborne particles even in areas with large contribution from desert dust advections.Citation:Stafoggia M, Zauli-Sajani S, Pey J, Samoli E, Alessandrini E, Basagaña X, Cernigliaro A, Chiusolo M, Demaria M, Díaz J, Faustini A, Katsouyanni K, Kelessis AG, Linares C, Marchesi S, Medina S, Pandolfi P, Pérez N, Querol X, Randi G, Ranzi A, Tobias A, Forastiere F, MED-PARTICLES Study Group. 2016. Desert dust outbreaks in Southern Europe: contribution to daily PM10 concentrations and short-term associations with mortality and hospital admissions. Environ Health Perspect 124:413–419; http://dx.doi.org/10.1289/ehp.1409164