tbuckley/cabot-search huggingface dataset:
Fibrositis of Rectus Abdominis Muscles causing Dyspepsia
Authors: R. S. Harvey
Journal: BMJ (1944)

failed.In two patients 2 c.cm. of sterile Indian ink was injected into the abdomen, and chest taps were performed later.In each case the fluid in the chest showed the same concentration of Indian ink as that in the abdomen.That the Indian ink did not arrive in the pleural fluid by way of the blood stream was considered established by study of the blood, since no evidence of Indian ink could be found in the leucocytes on microscopical examination.This experiment suggested that the abdominal fluid may arrive in the chest by the same paths as the Indian ink, or vice versa.The probability is that the pathways are lymphatics which pass through the interstices of the serosal cells under the diaphragm, thence to the supra- diaphragmatic lymphatics and so into the chest. SummaryTwo cases of Meigs's syndrome (fibroma of the ovary with pleural effusion and ascites) areodescribed.This condition is probably rare, but without doubt some cases go unrecognized, since they are often ill and simulate advanced carci- noma of the ovary or severe cardiac, renal, pulmonary, or hepatic disease.This is most unfortunate, since such patients' would be denied an operation which gives excellent results.The syndrome must always be considered in a differential diagnosis of abdominal and chest effusions, and as only one other case has been described in the British literature in the last 20 years we feel that the occurrence of two cases within a year among a relatively small population suggests that some cases are being overlooked.
Comparison of Cladribine Plus Cyclophosphamide With Fludarabine Plus Cyclophosphamide As First-Line Therapy for Chronic Lymphocytic Leukemia: A Phase III Randomized Study by the Polish Adult Leukemia Group (PALG-CLL3 Study)
Authors: Tadeusz Robak, Krzysztof Jamroziak, Joanna Gora-Tybor, Beata Stella-Holowiecka, Lech Konopka, Bernadetta Ceglarek, Krzysztof Warzocha, Ilona Seferynska, Jarosław Piszcz, Malgorzata Calbecka, Aleksandra Kostyra, Jadwiga Dwilewicz-Trojaczek, Anna Dmoszyñska, Krystyna Zawilska, Andrzej Hellmann, Andrzej Zdunczyk, Stanislaw Potoczek, Magdalena Piotrowska, Krzysztof Lewandowski, Jerzy Z. Blonski
Journal: Journal of Clinical Oncology (2010)

PURPOSE Little is known about comparison of the activity of different purine nucleoside analogs in chronic lymphocytic leukemia (CLL). We conducted a randomized phase III trial to compare efficacy and safety of cladribine and fludarabine, each combined with cyclophosphamide, in previously untreated progressive CLL. PATIENTS AND METHODS Patients received cladribine at 0.12 mg/kg combined with cyclophosphamide at 250 mg/m(2) for 3 days intravenously (CC regimen) or fludarabine at 25 mg/m(2) combined with cyclophosphamide at 250 mg/m(2) for 3 days intravenously (FC regimen), every 28 days for up to six cycles. The primary end point was complete response (CR) rate. Secondary end points included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and treatment-related toxicity. RESULTS Of 423 randomly assigned patients (211 to CC and 212 to FC), 395 were evaluated in the final analysis. The CR and ORR reached 47% and 88% in the CC arm and 46% and 82% in the FC arm (P = .25 and P = .11, respectively). The median PFS was 2.34 years with CC and 2.27 years with FC (P = .51). OS and grade 3/4 treatment-related toxicity were also comparable. Moreover, we did not observe any significant differences in CC and FC efficacy across different patient prognostic subgroups that included patients with 17p13 (TP53 gene) deletion who had poor survival in both study arms. CONCLUSION Cladribine and fludarabine in combination with cyclophosphamide are equally effective and safe first-line regimens for progressive CLL. Both combinations have unsatisfactory activity in patients with 17p13 (TP53 gene) deletion.
IFN-γ– and IL-10–expressing virus epitope-specific Foxp3+ T reg cells in the central nervous system during encephalomyelitis
Authors: Jingxian Zhao, Jincun Zhao, Craig Fett, Kathryn Trandem, Erica Fleming, Stanley Perlman
Journal: The Journal of Experimental Medicine (2011)

Foxp3+ CD4 regulatory T cells (T reg cells) are important in limiting immunopathology in infections. However, identifying pathogen-specific epitopes targeted by these cells has been elusive. Using MHC class II/peptide tetramers and intracellular cytokine staining, we identify T reg cells recognizing two virus-specific CD4 T cell epitopes in the coronavirus-infected central nervous system as well as naive T cell precursor pools. These T reg cells are detected at the same time as effector T cells (T eff cells) exhibiting the same specificity and can suppress T eff cell proliferation after stimulation with cognate peptide. These virus-specific T reg cells may be especially effective in inhibiting the immune response during the peak of infection, when virus antigen is maximal. Furthermore, these T reg cells express both IL-10 and IFN-γ after peptide stimulation. IFN-γ expression is maintained during both acute and chronic phases of infection. Identification of T reg cell target epitopes by cytokine production is also applicable in autoimmune disease because myelin oligodendrocyte glycoprotein–specific Foxp3+ T reg cells express IL-10 and IL-17 at the peak of disease in mice with experimental autoimmune encephalomyelitis. These results show that pathogen epitope-specific Foxp3+ T reg cells can be identified on the basis of cytokine production.
Downregulation of the transforming growth factor-β/connective tissue growth factor 2 signalling pathway in venous malformations: its target potential for sclerotherapy
Authors: J.-G. Ren, G. Chen, J.-Y. Zhu, W. Zhang, Y.-F. Sun, J. Jia, J. Zhang, Y.-F. Zhao
Journal: British Journal of Dermatology (2014)

Background Previous studies have implicated vascular destabilization and changes in extracellular matrix (ECM) composition in venous malformations (VMs). Objectives To evaluate the expression levels of the connective tissue growth factor (CCN) family of matricellular proteins in VMs and explore their association with vascular destabilization. Methods The expression levels of CCNs 1–6, transforming growth factor (TGF)-β, phosphorylated Tie2 and phosphorylated platelet-derived growth factor receptor β in normal human skin tissues and VMs were detected by immunohistochemistry. Correlation between tested proteins was explored using the Spearman rank correlation test, followed by clustering analysis. In vitro studies using human umbilical vein endothelial cells (HUVECs) were performed for mechanism investigation. Results Expression of CCN2 was found to be strongly positive in fibroblast-like cells, endothelial cells and around blood vessels in normal human skin tissues, but it was significantly downregulated in VMs. Correlation analyses showed that expression levels of CCN2 and TGF-β in VMs were positively correlated. The immunoreactivity of CCN2 was also closely correlated with perivascular α-smooth muscle cell actin+ cell coverage in VMs. Moreover, in vitro studies in HUVECs indicated that CCN2 might act as a downstream target of TGF-β, as demonstrated by the findings that treatment with exogenous TGF-β or exogenous CCN2 could significantly upregulate the expression level of CCN2, and increase the expression levels of ECM components. Upregulation of the TGF-β/CCN2 pathway was also detected in bleomycin-treated VM specimens. Conclusions This study unmasks the downregulation of the TGF-β/CCN2 pathway in VMs, and indicates its target potential for sclerotherapy.
1-Antitrypsin: more than just deficiency
Authors: R A Stockley
Journal: Thorax (2004)

Abnormal levels of α1-antitrypsin represent a syndrome of clinical disease entities, some relating to a deficiency while others reflect an overload

Carl-Bertil Laurell (1919–2001) was head of the Clinical Chemistry Department at Malmo General Hospital, University of Lund, Sweden (1954–84) and continued working in the department until his death in 2001. He had an interest in the initial studies of protein biochemistry, and his early paper on electrophoresis studies of serum proteins led to the discovery of subjects with deficient bands in the α1-globulin region.1 This region showed the greatest inhibition of trypsin, and the major protein within the band became known as α1-antitrypsin. Having identified several subjects with a weak α1 band seen on paper electrophoresis, Laurell and his research fellow Eriksson investigated the patients further. Three of the original five patients had severe early onset pulmonary emphysema suggesting a cause and effect.1 For many years research focused on understanding the role of this protein in the pathogenesis of emphysema. …
Fine Needle Aspiration Cytology of Palpable and Nonpalpable Lymph Nodes to Detect Metastatic Melanoma
Authors: Christiane A. Voit, Alexander C. J. van Akkooi, Alexander M. M. Eggermont, Gregor Schäfer-Hesterberg, Martina Kron, Jens Ulrich, Wolfram Sterry, Alfred Schoengen, Jürgen Rademaker
Journal: JNCI Journal of the National Cancer Institute (2011)

Fine needle aspiration cytology (FNAC) is usually used to evaluate palpable nodes in patients with melanoma. The goal of our study is to review the sensitivity and specificity of this technique when applied to palpable but also to nonpalpable nodes.FNAC was performed during 1984-2007 in 1279 patients with suspicious lesions and/or lymph nodes. Indications for biopsy included increased size and/or palpability of nodes or abnormal ultrasound findings such as increased perfusion or focal lesions within the lymph nodes. The sensitivity, specificity, and positive and negative predictive values of FNACs guided by palpation or ultrasound were calculated for all patients and for subgroups of patients with palpable nodes or nonpalpable but sonomorphologically suspicious nodes.A total of 2446 FNACs were performed in 1279 melanoma patients, of which 2011 (82.2%) FNACs had clinically or histologically confirmed results. Increased size and/or palpability of nodes was observed in 376 (29.4%) of 1279 patients, and abnormal ultrasound findings occurred for 903 (70.6%), indicating that a biopsy was needed. FNACs guided by palpation had sensitivity, specificity, and positive and negative predictive values similar to that of FNACs guided by ultrasound (sensitivity = 98.4% vs 97.2%, specificity = 100% vs 99.8%, positive predictive value = 100% vs 99.9%, and negative predictive value = 95.2% vs 96.4%, for palpation-guided FNACs vs ultrasound-guided FNACs, respectively). Results did not differ between patients with the palpable nodes and patients with nonpalpable but sonomorphologically suspicious nodes.Ultrasound-guided FNAC of suspicious lymph nodes and lesions in melanoma patients has a high sensitivity and specificity, and FNAC should not be limited to palpable nodes. FNAC of normal-sized nodes and/or lymph nodes with abnormal ultrasound findings can be used to identify early metastatic disease.
Lactate Dehydrogenase B: A Metabolic Marker of Response to Neoadjuvant Chemotherapy in Breast Cancer
Authors: Jennifer B. Dennison, Jennifer R. Molina, Shreya Mitra, Ana M. González-Angulo, Justin M. Balko, María G. Kuba, Melinda E. Sanders, Joseph A. Pinto, Henry L. Gómez, Carlos L. Arteaga, Robert E. Brown, Gordon B. Mills
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Although breast cancers are known to be molecularly heterogeneous, their metabolic phenotype is less well-understood and may predict response to chemotherapy. This study aimed to evaluate metabolic genes as individual predictive biomarkers in breast cancer. Experimental Design: mRNA microarray data from breast cancer cell lines were used to identify bimodal genes—those with highest potential for robust high/low classification in clinical assays. Metabolic function was evaluated in vitro for the highest scoring metabolic gene, lactate dehydrogenase B (LDHB). Its expression was associated with neoadjuvant chemotherapy response and relapse within clinical and PAM50-derived subtypes. Results: LDHB was highly expressed in cell lines with glycolytic, basal-like phenotypes. Stable knockdown of LDHB in cell lines reduced glycolytic dependence, linking LDHB expression directly to metabolic function. Using patient datasets, LDHB was highly expressed in basal-like cancers and could predict basal-like subtype within clinical groups [OR = 21 for hormone receptor (HR)-positive/HER2-negative; OR = 10 for triple-negative]. Furthermore, high LDHB predicted pathologic complete response (pCR) to neoadjuvant chemotherapy for both HR-positive/HER2-negative (OR = 4.1, P &amp;lt; 0.001) and triple-negative (OR = 3.0, P = 0.003) cancers. For triple-negative tumors without pCR, high LDHB posttreatment also identified proliferative tumors with increased risk of recurrence (HR = 2.2, P = 0.006). Conclusions: Expression of LDHB predicted response to neoadjuvant chemotherapy within clinical subtypes independently of standard prognostic markers and PAM50 subtyping. These observations support prospective clinical evaluation of LDHB as a predictive marker of response for patients with breast cancer receiving neoadjuvant chemotherapy. Clin Cancer Res; 19(13); 3703–13. ©2013 AACR.
Assessment of risk area during coronary occlusion and infarct size after reperfusion with myocardial contrast echocardiography using left and right atrial injections of contrast.
Authors: F S Villanueva, W P Glasheen, J Sklenar, S Kaul
Journal: Circulation (1993)

BACKGROUND Myocardial opacification during echocardiography has been demonstrated after left (LA) and right (RA) atrial injections of contrast, and microvascular damage with reduced blood flow and impaired flow reserve has been documented in necrotic myocardial tissue. Therefore, we hypothesized that because of its ability to depict capillary perfusion, myocardial contrast echocardiography (MCE) can be used to define risk area during coronary occlusion and infarct size after reperfusion with LA and RA injections of contrast in the presence of pharmacologically induced coronary hyperemia. METHODS AND RESULTS Eighteen open-chest anesthetized dogs with 3 to 6 hours of left anterior descending artery occlusion and 15 minutes of reflow were studied in the presence of either dipyridamole (0.56 mg/kg over a period of 4 minutes) or dobutamine (15 micrograms.kg-1.min-1). Technetium autoradiography was performed for risk area assessment; infarct size was measured with triphenyl tetrazolium chloride; and in 11 dogs, myocardial blood flow was measured with radiolabeled microspheres. A close linear relation was noted between the MCE defect size and autoradiographic risk area during coronary occlusion both during LA (y = 0.95x-0.25, r = .97, P &lt; .001) and RA (y = 0.90x+0.98, r = .86, P &lt; .001) injections of contrast. During reperfusion, the contrast defect size on MCE was always less transmural than during occlusion and correlated closely with infarct size during both LA (y = 1.07x-2.37, r = .98, P &lt; .001) and RA (y = 1.02x-0.61, r = .95, P &lt; .001) injections of contrast. In the 11 dogs in whom radiolabeled microsphere-derived blood flow was measured during reperfusion, an inverse relation was noted between infarct size and transmural blood flow (y = -1.12x+121, r = -.95, P = .001), implying that MCE defects after reperfusion indicate necrotic regions with reduced blood flow or impaired microvascular flow reserve. A close linear relation (y = 0.79x-0.001, r = .98, P &lt; .001) was also noted between endocardial/epicardial ratio of background-subtracted peak video intensity on MCE and endocardial/epicardial blood flow ratio in the eight dogs with infarction who underwent this measurement after reperfusion. CONCLUSIONS MCE performed with LA and RA injections of contrast in the presence of pharmacologically induced coronary hyperemia can be used to determine, in vivo, the risk area during coronary occlusion and infarct size after reperfusion. These results could have important implications in this era of myocardial reperfusion.
Interleukin-6 Modulates Graft-versus-Host Responses after Experimental Allogeneic Bone Marrow Transplantation
Authors: Isao Tawara, Motoko Koyama, Chen Liu, Tomomi Toubai, Dafydd Thomas, Rebecca Evers, Peter Chockley, Evelyn Nieves, Yaping Sun, Kathleen P. Lowler, Chelsea Malter, Norihiro Nishimoto, Geoffrey R. Hill, Pavan Reddy
Journal: Clinical Cancer Research (2010)

Abstract Purpose: The graft-versus-tumor (GVT) effect is a potent form of immunotherapy against many hematologic malignancies and some solid tumors. The beneficial GVT effect after allogeneic bone marrow transplantation (BMT) is tightly linked to its most significant complication, graft-versus-host disease (GVHD). The role of interleukin-6 (IL-6) after allogeneic BMT is not well understood. This study used a series of complementary knockout and antibody blockade strategies to analyze the impact of IL-6 in multiple clinically relevant murine models of GVHD and GVT. Experimental Design: We examined the effect of the source of IL-6 by analyzing the role IL-6 deficiency in donor T cells, donor bone marrow or in host tissues. We confirmed and extended the relevance of IL-6 deficiency on GVHD and GVT by treating BMT recipients with anti-mouse IL-6 receptor (IL-6R), MR16-1. Results: Deficiency of IL-6 in donor T cells led to prolongation of survival. Total inhibition of IL-6 with MR16-1 caused an even greater reduction in GVHD-induced mortality. The reduction in GVHD was independent of the direct effects on T effector cell expansion or donor regulatory T cells. GVT responses were preserved after treatment with MR16-1. Conclusion: MR16-1 treatment reduced GVHD and preserved sufficient GVT. Tocilizumab, a humanized anti–IL-6R monoclonal antibody (mAb), is approved in several countries including the United States and European Union for the treatment of rheumatoid arthritis and other inflammatory diseases. Blockade of IL-6 with anti–IL-6R mAb therapy may be testable in clinical trials as an adjunct to prevent GVHD in BMT patients without a significant loss of GVT. Clin Cancer Res; 17(1); 77–88. ©2010 AACR.
Dynamic injection of the digital flexor tendon sheaths.
Authors: N Liu, J J Canoso
Journal: Annals of the Rheumatic Diseases (1990)

Stenosing tenosynovitis and flexor tenosynovitis are commonly encountered in a rheumatological practice.' 2 Before surgical intervention (tenosynovectomy or tenolysis), which is seldom required, conservative treatments, including splinting or local corticosteroid injections, are usually recommended.The safety and efficacy
Structural Design of Engineered Costimulation Determines Tumor Rejection Kinetics and Persistence of CAR T Cells
Authors: Zeguo Zhao, Maud Condomines, Sjoukje J.C. van der Stegen, Fabiana Perna, Christopher C. Kloss, Gertrude Gunset, Jason Plotkin, Michel Sadelain
Journal: Cancer Cell (2015)
Amoebic Abscess Diagnosed on Fluorodeoxyglucose Positron Emission Tomography Scan in Patient With Recurrent Oropharyngeal Squamous Cell Carcinoma
Authors: Wulfran Cacheux, Vincent Servois, Benoit Paulmier, Jacques Girodet, Fereshteh Farkhondeh, Slavomir Petras
Journal: Journal of Clinical Oncology (2011)
Androgen Receptor Rediscovered: The New Biology and Targeting the Androgen Receptor Therapeutically
Authors: Charles J. Ryan, Donald J. Tindall
Journal: Journal of Clinical Oncology (2011)

Discoveries over the past decade suggest that castration-resistant prostate cancer (CRPC) is sensitive, but not resistant to, further manipulation of the androgen–androgen receptor (AR) axis. Several new therapies that target this axis have demonstrated clinical activity. In this article, preclinical and clinical findings occurring in the field of AR-targeted therapies are reviewed. Reviews of scientific and clinical development are divided into those occurring prereceptor (androgen production and conversion) and at the level of the receptor (AR aberrations and therapies targeting AR directly). Intracrine androgen production and AR amplification, among others, are among the principal aberrancies driving CRPC growth. Phase III data with abiraterone acetate and phase II data with MDV-3100, along with other similar therapies, confirm for the clinician that the scientific findings related to persistent AR signaling in a castrate milieu can be harnessed to produce significant clinical benefit for patients with the disease. Studies aimed at optimizing the timing of their use and exploring the mechanisms of resistance to these therapies are under way. The clinical success of therapies that directly target androgen synthesis as well as the most common aberrancies of the AR confirm that prostate cancer retains dependence on AR signaling, even in the castrate state.
A hypermorphic IκBα mutation is associated with autosomal dominant anhidrotic ectodermal dysplasia and T cell immunodeficiency
Authors: Gilles Courtois, Asma Smahi, Janine Reichenbach, Rainer Döffinger, Caterina Cancrini, Marion Bonnet, Anne Puel, Christine Chable-Bessia, Shoji Yamaoka, Jacqueline Feinberg, Sophie Dupuis-Girod, Christine Bodemer, Susanna Livadiotti, Francesco Novelli, Paolo Rossi, Alain Fischer, Alain Israël, Arnold Munnich, Françoise Le Deist, Jean-Laurent Casanova
Journal: Journal of Clinical Investigation (2003)

X-linked anhidrotic ectodermal dysplasia with immunodeficiency (XL-EDA-ID) is caused by hypomorphic mutations in the gene encoding NEMO/IKKγ, the regulatory subunit of the IκB kinase (IKK) complex. IKK normally phosphorylates the IκB-inhibitors of NF-κB at specific serine residues, thereby promoting their ubiquitination and degradation by the proteasome. This allows NF-κB complexes to translocate into the nucleus where they activate their target genes. Here, we describe an autosomal-dominant (AD) form of EDA-ID associated with a heterozygous missense mutation at serine 32 of IκBα. This mutation is gain-of-function, as it enhances the inhibitory capacity of IκBα by preventing its phosphorylation and degradation, and results in impaired NF-κB activation. The developmental, immunologic, and infectious phenotypes associated with hypomorphic NEMO and hypermorphic IKBA mutations largely overlap and include EDA, impaired cellular responses to ligands of TIR (TLR-ligands, IL-1β, and IL-18), and TNFR (TNF-α, LTα1/β2, and CD154) superfamily members and severe bacterial diseases. However, AD-EDA-ID but not XL-EDA-ID is associated with a severe and unique T cell immunodeficiency. Despite a marked blood lymphocytosis, there are no detectable memory T cells in vivo, and naive T cells do not respond to CD3-TCR activation in vitro. Our report highlights both the diversity of genotypes associated with EDA-ID and the diversity of immunologic phenotypes associated with mutations in different components of the NF-κB signaling pathway.
Estimates of the Effect of Natural Selection on Protein-Coding Content
Authors: V. B. Yap, H. Lindsay, S. Easteal, G. Huttley
Journal: Molecular Biology and Evolution (2009)

Analysis of natural selection is key to understanding many core biological processes, including the emergence of competition, cooperation, and complexity, and has important applications in the targeted development of vaccines. Selection is hard to observe directly but can be inferred from molecular sequence variation. For protein-coding nucleotide sequences, the ratio of nonsynonymous to synonymous substitutions (omega) distinguishes neutrally evolving sequences (omega = 1) from those subjected to purifying (omega < 1) or positive Darwinian (omega > 1) selection. We show that current models used to estimate omega are substantially biased by naturally occurring sequence compositions. We present a novel model that weights substitutions by conditional nucleotide frequencies and which escapes these artifacts. Applying it to the genomes of pathogens causing malaria, leprosy, tuberculosis, and Lyme disease gave significant discrepancies in estimates with approximately 10-30% of genes affected. Our work has substantial implications for how vaccine targets are chosen and for studying the molecular basis of adaptive evolution.