tbuckley/cabot-search huggingface dataset:
Overexpression of squamous cell carcinoma antigen in idiopathic pulmonary fibrosis: clinicopathological correlations
Authors: F Calabrese, F Lunardi, C Giacometti, G Marulli, M Gnoato, P Pontisso, M Saetta, M Valente, F Rea, E Perissinotto, C Agostini
Journal: Thorax (2008)

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disorder with a poor prognosis. Epithelial instability is a crucial step in the development and progression of the disease, including neoplastic transformation. Few tissue markers for epithelial instability have been reported in IPF. Squamous cell carcinoma antigen (SCCA) is a serine protease inhibitor typically expressed by dysplastic and neoplastic cells of epithelial origin, more often in squamous cell tumours. At present, no information is available on its expression in IPF.SCCA and transforming growth factor beta (TGFbeta) expression in surgical lung biopsies from 22 patients with IPF and 20 control cases was examined. An in vitro study using A549 pneumocytes was also conducted to investigate the relationship between SCCA and TGFbeta expression. SCCA and TGFbeta epithelial expression was evaluated by immunohistochemistry and reverse transcription-PCR (RT-PCR). SCCA values were correlated with different pathological and clinical parameters. Time course analysis of TGFbeta expression in A549 pneumocytes incubated with different SCCA concentrations was assessed by real time RT-PCR.SCCA was expressed in many metaplastic alveolar epithelial cells in all IPF cases with a mean value of 24.9% while it was seen in only two control patients in up to 5% of metaplastic cells. In patients with IPF, SCCA correlated positively with extension of fibroblastic foci (r = 0.49, p = 0.02), expression of TGFbeta (r = 0.78, p<0.0001) and with carbon monoxide transfer factor decline after 9 months of follow-up (r = 0.59, p = 0.01). In vitro experiments showed that incubation of cultured cells with SCCA induced TGFbeta expression, with a peak at 24 h.Our findings provide for the first time a potential mechanism by which SCCA secreted from metaplastic epithelial cells may exert a profibrotic effect in IPF. SCCA could be an important biomarker in this incurable disease.
Registration of Three-Dimensional Left Atrial Computed Tomographic Images With Projection Images Obtained Using Fluoroscopy
Authors: Jasbir Sra, David Krum, Angela Malloy, Melissa Vass, Barry Belanger, Elisabeth Soubelet, Regis Vaillant, Masood Akhtar
Journal: Circulation (2005)

Anatomic structures such as the left atrium and the pulmonary veins (PVs) are not delineated by fluoroscopy because there is no contrast differentiation between them and the surrounding anatomy. Representation of an anatomic structure via a 3D model obtained from computed tomography (CT) imaging and subsequent projection of these images over the fluoroscopy system may help in navigation of the mapping and ablation catheter to the appropriate sites during electrophysiology procedures.In this feasibility study, in vitro experiments were performed with a plastic heart model (phantom) with 2 catheters or radiopaque platinum beads placed in the phantom at the time of CT imaging and fluoroscopy. Subsequently, 20 consecutive patients underwent contrast-enhanced, ECG-gated CT scanning. Left atrial volumes were generated from the reconstructed data at &75% of the R-R interval during the cardiac cycle. Similarly, the superior vena cava and the coronary sinus were also reconstructed from these images. During the electrophysiology procedure, digital records (cine sequences) were obtained. Using predetermined algorithms, both the phantom model and the patients' 3D left atrial models derived from the CT were registered with projection images of fluoroscopy. Registration was performed with a transformation that linked the superior vena cava and the coronary sinus from the CT model with a catheter placed inside the coronary sinus via the superior vena cava. Registration was successfully accomplished with the plastic phantom and in all 20 patients. Registration accuracy was assessed in the phantom by assessing the overlapping beads seen both in the CT and the fluoroscopy images. The mean registration error was 1.4 mm (range 0.9 to 2.3 mm). Accuracy of the registered images was assessed in patients with recordings from a basket catheter placed sequentially in the superior PVs and by injecting contrast into the PVs to assess overlapping of contrast-filled PVs with the corresponding vessels on the registered images. The images could be calibrated quite accurately. Any rotational error, which was usually minor, could be corrected by rotating the images as needed.Registration of 3D models of the left atrium and PVs with fluoroscopic images of the same is feasible and could enable appropriate navigation and localization of the mapping and ablation catheter during procedures such as atrial fibrillation ablation.
Synonymous codon bias is related to gene length in Escherichia coli: selection for translational accuracy?
Authors: A. Eyre-Walker
Journal: Molecular Biology and Evolution (1996)

The levels of synonymous codon bias is shown to be positively correlated to gene length in Escherichia coli genes which are thought to be expressed at similar levels; these are genes whose products are present in multimeric proteins in equimolar amounts. It is argued that the positive correlation could be caused by selection to avoid missense errors during translation. Since the cost of producing a protein is proportional to its length, selection in favor of codons which increase accuracy should be greater in longer genes, and long genes should therefore have higher synonymous codon bias. It is also shown that there is variation in synonymous codon use which is independent of either expression level, gene length, amino acid composition, or chromosomal location. This variation is consistent with selection for translational accuracy but may have other origins.
Common variable immunodeficiency presenting in a girl as lung infiltrates and mediastinal adenopathies leading to severe "superior vena caval" syndrome
Authors: O Sacco, B Fregonese, P Picco, M Faraci, P Facchetti, V Pistoia, GA Rossi
Journal: European Respiratory Journal (1996)

Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder characterized by decreased levels of circulating immunoglobulins (Ig) and increased susceptibility to infections. We describe the case of a girl, progressively developing CVID, whose first clinical manifestations were noninfectious diffuse pulmonary infiltrates and rapidly developing hilar and mediastinal lymphadenopathies causing a severe "superior vena caval syndrome". Histological evaluation of surgical samples showed follicular and paracortical hyperplasia of the lymph nodes and poorly organized, non-necrotizing, noninfectious, "reactive" granulomata in lymph nodes and pulmonary tissue. Daily treatment with azathioprine and prednisone induced resolution of the intrathoracic abnormalities but was associated with a progressive decrease of circulating IgG and IgA levels and natural killer (NK) lymphocytes that was not related to treatment. This case demonstrates that granulomatous inflammatory changes may be the first manifestations of common variable immunodeficiency, and that this disorder must be included in the differential diagnosis of lymphoid interstitial pneumonitis and of bilateral mediastinal lymph node enlargement leading to superior vena caval syndrome.
4E-Binding Protein 1, A Cell Signaling Hallmark in Breast Cancer that Correlates with Pathologic Grade and Prognosis
Authors: Federico Rojo, Laura Najera, José Lirola, José Jiménez, Marta Guzmán, M. Dolors Sabadell, Jose Baselga, Santiago Ramon y Cajal
Journal: Clinical Cancer Research (2007)

Cell signaling pathways include a complex myriad of interconnected factors from the membrane to the nucleus, such as erbB family receptors and the phosphoinositide-3-kinase/Akt/mTOR and Ras-Raf-ERK cascades, which drive proliferative signals, promote survival, and regulate protein synthesis.
B cells drive lymphocyte activation and expansion in mice with the CD45 wedge mutation and Fas deficiency
Authors: Vikas A. Gupta, Michelle L. Hermiston, Gail Cassafer, David I. Daikh, Arthur Weiss
Journal: The Journal of Experimental Medicine (2008)

CD45 and Fas regulate tyrosine phosphorylation and apoptotic signaling pathways, respectively. Mutation of an inhibitory wedge motif in CD45 (E613R) results in hyperresponsive thymocytes and B cells on the C57BL/6 background, but no overt autoimmunity, whereas Fas deletion results in a mild autoimmune disease on the same genetic background. In this study, we show that these two mutations cooperate in mice, causing early lethality, autoantibody production, and substantial lymphoproliferation. In double-mutant mice, this phenotype was dependent on both T and B cells. T cell activation required signaling in response to endogenous or commensal antigens, demonstrated by the introduction of a transgenic T cell receptor. Genetic deletion of B cells also prevented T cell activation. Similarly, T cells were necessary for B cell autoantibody production. However, B cells appeared to be intrinsically activated even in the absence of T cells, suggesting that they may drive the phenotype of these mice. These results reveal a requirement for careful control of B cell signaling and cell death in preventing inappropriate lymphocyte activation and autoimmunity.
Diabetes Self-management Education and Support in Type 2 Diabetes: A Joint Position Statement of the American Diabetes Association, the American Association of Diabetes Educators, and the Academy of Nutrition and Dietetics
Authors: Margaret A. Powers, Joan Bardsley, Marjorie Cypress, Paulina Duker, Martha M. Funnell, Amy Hess Fischl, Melinda D. Maryniuk, Linda Siminerio, Eva Vivian
Journal: Diabetes Care (2015)

Diabetes is a chronic disease that requires a person with diabetes to make a multitude of daily self-management decisions and to perform complex care activities. Diabetes self-management education and support (DSME/S) provides the foundation to help people with diabetes to navigate these decisions and activities and has been shown to improve health outcomes (1–7). Diabetes self-management education (DSME) is the process of facilitating the knowledge, skill, and ability necessary for diabetes self-care. Diabetes self-management support (DSMS) refers to the support that is required for implementing and sustaining coping skills and behaviors needed to self-manage on an ongoing basis. (See further definitions in Table 1.) Although different members of the health care team and community can contribute to this process, it is important for health care providers and their practice settings to have the resources and a systematic referral process to ensure that patients with type 2 diabetes receive both DSME and DSMS in a consistent manner. The initial DSME is typically provided by a health professional, whereas ongoing support can be provided by personnel within a practice and a variety of community-based resources. DSME/S programs are designed to address the patient’s health beliefs, cultural needs, current knowledge, physical limitations, emotional concerns, family support, financial status, medical history, health literacy, numeracy, and other factors that influence each person’s ability to meet the challenges of self-management.

View this table:

Table 1 
Key definitions



It is the position of the American Diabetes Association (ADA) that all individuals with diabetes receive DSME/S at diagnosis and as needed thereafter (8). This position statement focuses on the particular needs of individuals with type 2 diabetes. The needs will be similar to those of people with other types of diabetes (type 1 diabetes, prediabetes, and gestational diabetes mellitus); however, the research and examples referred to in this article focus …
Autoimmune T lymphocytes in myasthenia gravis. Determination of target epitopes using T lines and recombinant products of the mouse nicotinic acetylcholine receptor gene.
Authors: A Melms, S Chrestel, B C Schalke, H Wekerle, A Mauron, M Ballivet, T Barkas
Journal: Journal of Clinical Investigation (1989)

Oligoclonal and cloned T lines from peripheral blood or thymuses of patients with myasthenia gravis (MG) were selected for reactivity against nicotinic acetylcholine receptors (AChR) from Torpedo california, or against a recombinant fusion peptide, X4, representing the extracellular portion of the mouse AChR alpha-chain. All cell lines expressed the CD4 membrane phenotype, and their antigen reactivity was blocked by antibodies against monomorphic HLA DR/DP determinants. Using a panel of fusion proteins of different, overlapping mouse AChR alpha-chain sequences, a major T cell epitope was localized between amino acid positions 85 and 142. This determinant was distinct from the humoral main immunogenic region, which has been identified on the sequence 61-76. The response pattern of uncloned T lines from three patients with different HLA haplotypes suggests, however, that in any one MG patient T lymphocytes may recognize more than one autoantigenic epitope on the AChR alpha-chain, and that the T lymphocyte response profiles vary among individual patients.
BRAF Inhibition Is Associated with Enhanced Melanoma Antigen Expression and a More Favorable Tumor Microenvironment in Patients with Metastatic Melanoma
Authors: Dennie T. Frederick, Adriano Piris, Alexandria P. Cogdill, Zachary A. Cooper, Cecilia Lezcano, Cristina R. Ferrone, Devarati Mitra, Andrea Boni, Lindsay P. Newton, Chengwen Liu, Weiyi Peng, Ryan J. Sullivan, Donald P. Lawrence, F. Stephen Hodi, Willem W. Overwijk, Gregory Lizée, George F. Murphy, Patrick Hwu, Keith T. Flaherty, David E. Fisher, Jennifer A. Wargo
Journal: Clinical Cancer Research (2013)

To evaluate the effects of BRAF inhibition on the tumor microenvironment in patients with metastatic melanoma.Thirty-five biopsies were collected from 16 patients with metastatic melanoma pretreatment (day 0) and at 10 to 14 days after initiation of treatment with either BRAF inhibitor alone (vemurafenib) or BRAF + MEK inhibition (dabrafenib + trametinib) and were also taken at time of progression. Biopsies were analyzed for melanoma antigens, T-cell markers, and immunomodulatory cytokines.Treatment with either BRAF inhibitor alone or BRAF + MEK inhibitor was associated with an increased expression of melanoma antigens and an increase in CD8+ T-cell infiltrate. This was also associated with a decrease in immunosuppressive cytokines [interleukin (IL)-6 and IL-8] and an increase in markers of T-cell cytotoxicity. Interestingly, expression of exhaustion markers TIM-3 and PD1 and the immunosuppressive ligand PDL1 was increased on treatment. A decrease in melanoma antigen expression and CD8 T-cell infiltrate was noted at time of progression on BRAF inhibitor alone and was reversed with combined BRAF and MEK inhibition.Together, these data suggest that treatment with BRAF inhibition enhances melanoma antigen expression and facilitates T-cell cytotoxicity and a more favorable tumor microenvironment, providing support for potential synergy of BRAF-targeted therapy and immunotherapy. Interestingly, markers of T-cell exhaustion and the immunosuppressive ligand PDL1 are also increased with BRAF inhibition, further implying that immune checkpoint blockade may be critical in augmenting responses to BRAF-targeted therapy in patients with melanoma.
Livedo reticularis*.
Authors: P.W.M. COPEMAN
Journal: British Journal of Dermatology (1975)

The clinical sign of livedo reticularis derives from stasis of blood in the superficial venous drainage systems of the skin. Many factors can delay the flow of de-oxygenated blood away from the skin, notably hyperviscosity of the blood itself and obstruction due to disease affecting dermal arteries, capillaries, or venules.
European guidelines on the clinical management of HIV-1 tropism testing
Authors: LPR Vandekerckhove, AMJ Wensing, R Kaiser, F Brun-Vézinet, B Clotet, A De Luca, S Dressler, F Garcia, AM Geretti, T Klimkait, K Korn, B Masquelier, CF Perno, JM Schapiro, V Soriano, A Sönnerborg, A-M Vandamme, C Verhofstede, H Walter, M Zazzi, CAB Boucher
Journal: The Lancet Infectious Diseases (2011)
Location and function of intrahepatic shunts in anaesthetised rats
Authors: X Li
Journal: Gut (2003)

<b>Background:</b> In the present study we determined the proportion of shunt flow due to patent intrahepatic portal systemic shunts in the normal rat liver and its relationship with microsphere induced portal hypertension. <b>Methods:</b> Systemic and hepatic haemodynamics were measured continuously before, during, and after intraportal injection of 15 μm diameter microspheres in anaesthetised male Wistar rats. Functional hepatic blood flow and intrahepatic shunt flow were determined by the use of constant intraportal infusion of sorbitol and simultaneous measurements in the portal vein, hepatic vein, and carotid artery. The percentage of large shunts of diameter &gt;15 μm were estimated by intraportal injection of <sup>51</sup>Cr labelled 15 μm diameter microspheres. <b>Results:</b> Hepatic sorbitol uptake was 97.9 (0.5)% in normal control rats, with functional hepatic blood flow equalling total hepatic blood flow (2.52 (0.23) ml/min/100 g body weight). Microsphere injection decreased sorbitol uptake to 12.8 (4.3)% and further to 4.1 (0.7)% when followed by hepatic arterial ligation. In the latter two groups, intrahepatic shunt flow (1.46 (0.15) and 1.16 (0.19) ml/min/100 g body weight, respectively) was not significantly different from portal venous flow (1.36 (0.20) and 1.20 (0.20) ml/min/100 g body weight, respectively). Portal venous flow remained at 70% of basal values and portal venous pressure only increased by 50% from baseline. <sup>51</sup>Cr labelled microsphere shunt fraction through large shunts (&gt;15 μm) was less than 1.0%. <b>Conclusion:</b> The site of confluence between the hepatic artery and portal vein is in zone II. Intrahepatic shunts originate in presinusoidal regions in zone I in the normal liver and, when activated by intraportal injection of microspheres, divert 70% of the total portal blood flow away from zone III and thereby reduce acute increases in portal venous pressure.
Controlling multipotent stromal cell migration by integrating “course-graining” materials and “fine-tuning” small molecules via decision tree signal-response modeling
Authors: Shan Wu, Alan Wells, Linda G. Griffith, Douglas A. Lauffenburger
Journal: Biomaterials (2011)

Biomimetic scaffolds have been proposed as a means to facilitate tissue regeneration by multi-potent stromal cells (MSCs). Effective scaffold colonization requires a control of multiple MSC responses including survival, proliferation, differentiation, and migration. As MSC migration is relatively unstudied in this context, we present here a multi-level approach to its understanding and control, integratively tuning cell speed and directional persistence to achieve maximal mean free path (MFP) of migration. This approach employs data-driven computational modeling to ascertain small molecule drug treatments that can enhance MFP on a given materials substratum. Using poly(methyl methacrylate)-graft-poly(ethylene oxide) polymer surfaces tethered with epidermal growth factor (tEGF) and systematically adsorbed with fibronectin, vitronectin, or collagen-I to present hTERT-immortalized human MSCs with growth factor and extracellular matrix cues, we measured cell motility properties along with signaling activities of EGFR, ERK, Akt, and FAK on 19 different substrate conditions. Speed was consistent on collagen/tEGF substrates, but low associated directional persistence limited MFP. Decision tree modeling successfully predicted that ERK inhibition should enhance MFP on collagen/tEGF substrates by increasing persistence. Thus, we demonstrated a two-tiered approach to control MSC migration: materials-based "coarse-graining" complemented by small molecule "fine-tuning".
Cytoplasmic Mislocalization of p27Kip1 Protein Is Associated with Constitutive Phosphorylation of Akt or Protein Kinase B and Poor Prognosis in Acute Myelogenous Leukemia
Authors: Yoo Hong Min, June-Won Cheong, Ji Yeon Kim, Ju In Eom, Seung Tae Lee, Jee Sook Hahn, Yun Woong Ko, Mark Hong Lee
Journal: Cancer Research (2004)

Abstract Cyclin-dependent kinase inhibitor p27Kip1 functions at the nuclear level by binding to cyclin E/cyclin-dependent kinase-2. It was shown that Akt or protein kinase B (Akt/PKB)-dependent phosphorylation of p27Kip1 led to the cytoplasmic mislocalization of p27Kip1, suggesting the potential abrogation of its activity. Here, we evaluated the localization of p27Kip1 protein in leukemic blasts in relation to Akt/PKB phosphorylation and clinical outcomes in acute myelogenous leukemia (AML). Western blot analysis of the nuclear and cytoplasmic fractions revealed a heterogenous localization pattern of p27Kip1 in AML. Cytoplasmic mislocalization of p27Kip1 was significantly associated with the constitutive serine473 Akt/PKB phosphorylation in AML cells (P &amp;lt; 0.05). Transfection of U937 cells with an expression construct encoding the constitutively active form of Akt/PKB resulted in a remarkable increase in the levels of cytoplasmic p27Kip1. Whereas the transfection of U937 cells with a construct encoding dominant-negative Akt/PKB resulted in a recovery of nuclear localization of p27Kip1. Both the disease-free survival and overall survival are significantly shorter in AML cases with high cytoplasmic to nuclear ratio of p27Kip1 localization compared with the cases with low cytoplasmic to nuclear ratio (P = 0.0353, P = 0.0023, respectively). Multivariate analysis indicated that the cytoplasmic to nuclear ratio of p27Kip1 localization was an independent prognostic variable for both disease-free survival and overall survival (P = 0.043, P = 0.008, respectively). These findings additionally extend our understanding of the role of p27Kip1 in AML, and buttress the case of p27Kip1 mislocalization as a prognostic indicator and Akt/PKB/p27Kip1 pathway as a ready target for antileukemia therapy.
Phase I Study of the Intratumoral Administration of Recombinant Canarypox Viruses Expressing B7.1 and Interleukin 12 in Patients with Metastatic Melanoma
Authors: Pierre L. Triozzi, Karen O. Allen, Ronda R. Carlisle, Mark Craig, Albert F. LoBuglio, Robert M. Conry
Journal: Clinical Cancer Research (2005)

The objective of this study was to evaluate the safety and activity of the intratumoral administration of the immune costimulatory molecule, B7.1, encoded by a vector derived from the canarypox virus, ALVAC (ALVAC-B7.1), alone and with the intratumoral injection of ALVAC encoding the immune-stimulatory cytokine, interleukin 12 (ALVAC-IL-12). Fourteen patients with metastatic melanoma who had s.c. nodules received intratumoral injections on days 1, 4, 8, and 11. Nine patients were given escalating doses of up to 25 x 10(8) plaque-forming units of ALVAC-B7.1. Five patients were given 25 x 10(8) plaque-forming units of ALVAC-B7.1 combined with ALVAC-IL-12 50% tissue culture infective dose of 2 x 10(6). Toxicity was mild to moderate and consisted of inflammatory reactions at the injection site and fever, chills, myalgia, and fatigue. Higher levels of B7.1 mRNA were observed in ALVAC-B7.1-injected tumors compared with saline-injected control tumors. Higher levels of intratumoral vascular endothelial growth factor and IL-10, cytokines with immune suppressive activities, were also observed in ALVAC-B7.1- and ALVAC-IL-12-injected tumors compared with saline-injected controls. Serum levels of vascular endothelial growth factor increased at day 18 and returned to baseline at day 43. All patients developed antibody to ALVAC. Intratumoral IL-12 and IFN-gamma mRNA decreased. Changes in serum IL-12 and IFN-gamma levels were not observed. Tumor regressions were not observed. The intratumoral injections of ALVAC-B7.1 and ALVAC-IL-12 were well tolerated at these dose levels and at this schedule and resulted in measurable biological response. This response included the production of factors that may suppress the antitumor immunologic activity of these vectors.