tbuckley/cabot-search huggingface dataset:
Molecular modeling of human APOBEC3G to predict the binding modes of the inhibitor compounds IMB26 and IMB35
Authors: Zhixin Zhang, Congjie Zhai, Zeyun Mi, Jiwei Ding, Yongxin Zhang, Xing Shi, Xiaoyu Li, Liyan Yu, Zhuorong Li, Jiandong Jiang, Jinming Zhou, Shan Cen
Journal: Acta Pharmaceutica Sinica B (2013)

APOBEC3G(A3G) is a host cytidine deaminase that incorporates into HIV-1 virions and efficiently inhibits viral replication. The virally encoded protein Vif binds to A3G and induces its degradation, thereby counteracting the antiviral activity of A3G. Vif-mediated A3G degradation clearly represents a potential target for anti-HIV drug development. Currently, there is an urgent need for understanding the three dimensional structure of full-length A3G. In this work, we use a homology modeling approach to propose a structure for A3G based on the crystal structure of APOBEC2 (APO2) and the catalytic domain structure of A3G. Two compounds, IMB26 and IMB35, which have been shown to bind to A3G and block degradation by Vif, were docked into the A3G model and the binding modes were generated for further analysis. The results may be used to design or optimize molecules targeting Vif–A3G interaction, and lead to the development of novel anti-HIV drugs.
Increased levels of serum IgA as IgA1 monomers in ankylosing spondylitis.
Authors: H Hocini, S Iscaki, C Benlahrache, L Vitalis, X Chevalier, B Larget-Piet, J P Bouvet
Journal: Annals of the Rheumatic Diseases (1992)

The various subsets of serum IgA were determined in 43 patients with ankylosing spondylitis to investigate the putative mucosal origin of increased IgA concentrations in this disease. Total IgA was shown to be increased and weakly correlated with the erythrocyte sedimentation rate (ESR). In contrast, although the mean concentration (but not the median) of secretory IgA (SIgA) was slightly increased, no correlation was found with total IgA nor the ESR. Moreover, molecular sieving of nine serum samples selected for their high concentrations of total IgA, and absorption with insoluble jacalin showed these immunoglobulins to be essentially monomers of the IgA1 subclass. These results are consistent with a non-secretory origin of the increase of serum IgA, which must be ascribed to the central immune system.
Abstract 5432: Spirooxindole derivative (SOID-8) inhibits proliferation and induces apoptosis by blocking JAK2/STAT3 signaling in melanoma cells
Authors: Yan Tian, Sangkil Nam, Lucy Liu, Fumiko Yakushijin, Ralf Buettner, Wei Liang, Fan Yang, David Horne, Richard Jove
Journal: Cancer Research (2011)

Abstract Melanoma is the most malignant skin cancer, and is generally refractory to current chemotherapy, so new treatment strategies are needed. In this study, we show that a spirooxindole derivative, SOID-8, which is a synthetic analogue inspired by the natural product, spirotryprostatin B, significantly inhibits cell proliferation in four established human melanoma cell lines. This decrease in viability of A2058 and A375 melanoma cells is associated with apoptosis, as confirmed by an increase in poly(ADP-ribose)polymerase cleavage. In addition, the antiapoptotic protein Mcl-1, a member of the Bcl-2 family, is downregulated and correlated with SOID-8 induced apoptosis. Morevoer, SOID-8 inhibits tyrosine phosphorylation of Signal Transducer and Activator of Transcription 3 (STAT3) in both melanoma cell lines in a dose- and time-dependent manner. In contrast, phosphorylation of AKT (protein kinase B) is reduced by SOID-8 only at high concentrations, and phosphorylation of MAPK (extracellular signal-regulated kinase 1/2) is not inhibited at all by SOID-8 in these cells. Furthermore, this compound decreases the phosphorylated Janus kinase-2 (JAK2) levels in a dose- and time-dependent fashion. Importantly, SOID-8 inhibits phosphorylation of STAT3 and JAK2 induced by IL-6 stimulation in A2058 and A375 cells. In summary, our results show that SOID-8 selectively blocks JAK2/STAT3 signaling as well as expression of apoptosis regulatory proteins, associated with inhibition of cell proliferation and induction of apoptosis in melanoma cells. These data suggest that antitumor activity of the spirooxindole derivative SOID-8 is at least partially due to inhibition of JAK2/STAT3 signaling in melanoma cells and is a promising small molecule candidate for melanoma therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5432. doi:10.1158/1538-7445.AM2011-5432
Phosphorylation of GSK-3β by cGMP-dependent protein kinase II promotes hypertrophic differentiation of murine chondrocytes
Authors: Yosuke Kawasaki, Fumitaka Kugimiya, Hirotaka Chikuda, Satoru Kamekura, Toshiyuki Ikeda, Naohiro Kawamura, Taku Saito, Yusuke Shinoda, Akiro Higashikawa, Fumiko Yano, Toru Ogasawara, Naoshi Ogata, Kazuto Hoshi, Franz Hofmann, James R. Woodgett, Kozo Nakamura, Ung-il Chung, Hiroshi Kawaguchi
Journal: Journal of Clinical Investigation (2008)

cGMP-dependent protein kinase II (cGKII; encoded by PRKG2) is a serine/threonine kinase that is critical for skeletal growth in mammals; in mice, cGKII deficiency results in dwarfism. Using radiographic analysis, we determined that this growth defect was a consequence of an elongated growth plate and impaired chondrocyte hypertrophy. To investigate the mechanism of cGKII-mediated chondrocyte hypertrophy, we performed a kinase substrate array and identified glycogen synthase kinase–3β (GSK-3β; encoded by Gsk3b) as a principal phosphorylation target of cGKII. In cultured mouse chondrocytes, phosphorylation-mediated inhibition of GSK-3β was associated with enhanced hypertrophic differentiation. Furthermore, cGKII induction of chondrocyte hypertrophy was suppressed by cotransfection with a phosphorylation-deficient mutant of GSK-3β. Analyses of mice with compound deficiencies in both protein kinases (Prkg2–/–Gsk3b+/–) demonstrated that the growth retardation and elongated growth plate associated with cGKII deficiency were partially rescued by haploinsufficiency of Gsk3b. We found that β-catenin levels decreased in Prkg2–/– mice, while overexpression of cGKII increased the accumulation and transactivation function of β-catenin in mouse chondroprogenitor ATDC5 cells. This effect was blocked by coexpression of phosphorylation-deficient GSK-3β. These data indicate that hypertrophic differentiation of growth plate chondrocytes during skeletal growth is promoted by phosphorylation and inactivation of GSK-3β by cGKII.
Functional gamma chain-associated T cell receptors on cerebrospinal fluid-derived natural killer-like T cell clones.
Authors: S L Ang, J G Seidman, G M Peterman, A D Duby, D Benjamin, S J Lee, D A Hafler
Journal: The Journal of Experimental Medicine (1987)

We have derived 33 independent T cell clones from the cerebrospinal fluid (CSF) of a patient with subacute sclerosing panencephalitis using a single T cell cloning method. 6% (2 of 33) of these clones express the T cell receptor gamma (TCR-gamma) protein and are called CSF TCR-gamma clones. Phenotypic analyses of the CSF TCR-gamma clones indicate that they are WT-31-, CD3+, CD4-, and CD8-. The TCR-gamma protein exists on the cell surface as part of an 85-kD disulphide-linked dimer noncovalently associated with the CD3 polypeptides. The CSF TCR-gamma clones have NK-like activity that can be inhibited by anti-CD3 mAbs. Both CSF TCR-gamma clones proliferated in response to anti-CD3 mAbs coupled to Sepharose beads and/or IL-2. Furthermore, stimulation of one of these clones with anti-CD3 mAbs results in a rapid rise in intracellular calcium. These data suggest that T cells bearing the CD3-TCR-gamma protein complex are functional and play a role in the human immune response.
Sudden death among postoperative patients with tetralogy of Fallot: a follow-up study of 243 patients for an average of twelve years.
Authors: T G Quattlebaum, J Varghese, C A Neill, J S Donahoo
Journal: Circulation (1976)

Two hundred and forty-three patients were evaluated following total correction of tetralogy of Fallot with special emphasis on postoperative conduction disturbances and on the occurrence of sudden death. The average follow-up period was 12 years with a range of 6 1/2 to 16 1/2 years. Sudden death occurred in seven patients. Four deaths were among those with right bundle branch block pattern (RBBB) and three of the four had premature ventricular contractions (PVC) for more than one month postoperatively. PVCs were documented in ten of the 158 patients with RBBB; sudden death occurred in three (30%). Three of the ten (30%) patients with trifascicular block pattern (TB) died suddenly, while no deaths occurred in 24 patients with bifascicular block pattern (BB). Progression of RBBB to BB and TB occurred in 18 patients from one month to seven years postoperatively (58% of BB and 40% of TB). The risk of sudden death in patients with RBBB and PVCs following tetralogy repair is high and warrants consideration of suppressive therapy. TB also carries a high risk. The finding that RBBB may progress to BB or TB mandates long-term careful follow-up of all tetralogy patients with postoperative conduction disturbances.
LONG-TERM FOLLOW-UP OF ARTERIAL AND ATRIAL SWITCH OPERATION FOR TRANSPOSITION OF THE GREAT ARTERIES
Authors: Claudia Junge, Stephan Schoof, Mechtild Westhoff-Bleck, Reiner Buchhorn, Gerhard Ziemer, Siegfried Geyer, Kambiz Norozi
Journal: Journal of the American College of Cardiology (2013)
Percentage of CD4 Lymphocytes and Risk of AIDS-Reply
Authors: James Goedert
Journal: JAMA (1995)

<h3>In Reply.</h3> —Log or square root transformation of CD4 values is quite reasonable to assess their relationship to AIDS because the relative hazard increases in a nonlinear way. The effect of such transformation on other predictive markers, however, depends on their mutual relationships. In the three-variable Cox proportional model of our baseline values, the relative hazards of AIDS were 2.59 (95% confidence interval [CI], 1.02 to 6.56) with a decrement of one log in CD4 percentage, 2.46 (95% CI, 1.04 to 5.88) with p24 antigenemia, and 1.77 (95% CI, 1.01 to 3.10) per log<sub>10</sub>HIV-1 RNA. Thus, even if there is a marginally better fit of the CD4 values, p24 log<sub>10</sub>antigenemia and HIV-1 RNA levels remain independent predictive markers of AIDS risk.
Abstract 1006: Soluble epoxide hydrolase gene deficiency attenuates colitis-induced carcinogenesis in IL-10 knockout mice
Authors: Wanying Zhang, Jie Liao, Haonan Li, Hua Dong, Han Bai, Allison Liao Yang, Bruce D. Hammack, Guang-Yu Yang
Journal: Cancer Research (2012)

Abstract Soluble epoxide hydrolase (sEH) can quickly inactivate epoxyeicosatrienoic acids (EETs) anti-inflammatory function via converting it to dihydroxyeicosatrienoic acid (DHETs). Inhibition of sEH has shown effects against inflammation. But little is studied about the effect of sEH on colitis-induced carcinogenesis. In this study, we determined the role of sEH gene deficiency in suppressing the development of colitis-induced tumor using chronic colitis mouse model in IL-10 knockout mice combined with sEH gene deficiency. Tumor formation in the bowel was examined at age of 25 weeks for male mice and 35 weeks for female mice. Our results showed that sEH (-/-)/IL-10 (-/-) mice exhibited a significant decrease of tumor multiplicity (2 tumor/mouse vs. 1 tumor/mouse) and tumor size (344.55±71.73 vs. 126.94±23.18 mm3, p=0.028) as compared to IL-10(-/-) mice. But no difference was observed for tumor incidence. Colitis-induced dysplasia was further identified by Ki67-labeled luminal surface epithelial cell proliferation combined with morphologic features and revealed that the number of dysplasia was significantly decreased in sEH (-/-)/IL-10 (-/-) mice. Histopathological analysis of inflammatory activity in the bowel showed the significantly lower inflammation scores, including inflammation-involved area (1.4±0.18 vs. 0.70±0.16, P=0.007), ulcer (2.15±0.18 vs. 1.55±0.35, P=0.032), and myeloperoxidase-labeled inflammatory cell infiltrates in sEH (-/-)/ IL-10(-/-) mice compared to IL-10(-/-) mice. qPCR and western blotting assays showed a downregulation of inflammatory cytokines and NF-kB signals. Analysis of eicsanoid acid metabolic profile confirmed sEH functional deficiency and showed a significant increase in the ratios of EETs/DHET and EpOME/DiOME in sEH (-/-)/IL-10 (-/-) mice compared to IL-10(-/-) mice. The results indicate that sEH gene plays an important role in the development of chronic colitis-induced carcinoma and could serve as a crucial target of cancer chemoprevention. (Supported by NIH R01 grant CA137467) 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 1006. doi:1538-7445.AM2012-1006
THE TREATMENT OF CORNEAL ULCERS.Read before the Milwaukee Medical Society, February 9, 1892.
Authors: J. A. BACH
Journal: JAMA (1892)

One of the most formidable pathological processes of the eye the physician has to deal with is what is known as suppurative keratitis, or ulceration of the cornea. It is safe to state that more eyes are partially or totally destroyed through corneal ulcerations than through any other ocular disease, including injuries and operations. It is with great anxiety that, when any of the purulent ophthalmies present themselves to the physician for treatment, he carefully opens the eyelids to inspect whether or not the cornea shows any evidence of ulceration. A sense of relief is felt to find the negative true. But not only in the suppurative ophthalmies is this so, ulcerations under many other circumstances may become equally unpleasant and formidable. The many staphylomatous and white eyes, and often no eyes at all, one sees in the various institutions for the blind, as well as on the streets, are
SYNTHESIS AND ASSEMBLY OF IMMUNOGLOBULINS BY MALIGNANT HUMAN PLASMACYTES
Authors: Susan Zolla, Joel Buxbaum, E. C. Franklin, M. D. Scharff
Journal: The Journal of Experimental Medicine (1970)

Three basic patterns of gamma-globulin synthesis are described in malignant human plasmacytes: extreme unbalanced synthesis where only L chains are synthesized; unbalanced synthesis in which intact gammaG globulin and an excess of free L chains are synthesized and secreted; and balanced synthesis where H and L chains appear to be synthesized in equimolar amounts. Studies of the cellular products appear to reflect the biosynthetic processes of the cells in a more reliable fashion than does analysis of serum or urinary proteins. The absence of Bence Jones proteins from the urine does not necessarily indicate that free L chains are not being synthesized and secreted at the cellular level. Similarly, the completed globulin molecule secreted by malignant plasma cells may not be demonstrable by examination of serum. Patterns of globulin synthesis in human myelomatous tissues vary as do patterns of globulin synthesis in mouse plasmacytomas. Pulse-chase studies of the cells from one patient showed that a gammaG myeloma protein was assembled via an HL (half molecule) intermediate.
Renal Sympathetic-Nerve Ablation for Uncontrolled Hypertension
Authors: Markus P. Schlaich, Paul A. Sobotka, Henry Krum, Elisabeth Lambert, Murray D. Esler
Journal: New England Journal of Medicine (2009)

evidence of the efficacy of bevacizumab in patients with HHT.Both cases also show that symptoms and transfusion requirements improve with this therapy, without an appreciable change in arteriovenous malformations.Like Oosting et al., we found no difference in the size of our patient's pulmonary arteriovenous malformations on CT before and after bevacizumab.Their experience demonstrates the long-term safety and tolerability of bevacizumab in such patients.Our patient continues to report symptomatic benefit more than a year after completing therapy, and he has required only one intravenous infusion of iron during this time.His hemoglobin levels have remained stable at 14 to 15 g per deciliter.The cost of our patient's regimen (a total of 30 mg per kilogram over four cycles) would be approximately $12,000 today.The costs of continuing the drug in the long term, especially without a Food and Drug Administration-approved indication, would be prohibitive.Our case shows that intermittent dosing allows for long-term, symptomatic improvement and stability of pulmonary arteriovenous malformations.
Amplification of FRS2 and Activation of FGFR/FRS2 Signaling Pathway in High-Grade Liposarcoma
Authors: Keqiang Zhang, Kevin Chu, Xiwei Wu, Hanlin Gao, Jinhui Wang, Yate-Ching Yuan, Sofia Loera, Kimberley Ho, Yafan Wang, Warren Chow, Frank Un, Peiguo Chu, Yun Yen
Journal: Cancer Research (2013)

Abstract Fibroblast growth factor (FGF) receptor (FGFR) substrate 2 (FRS2) is an adaptor protein that plays a critical role in FGFR signaling. FRS2 is located on chromosome 12q13-15 that is frequently amplified in liposarcomas. The significance of FRS2 and FGFR signaling in high-grade liposarcomas is unknown. Herein, we first comparatively examined the amplification and expression of FRS2 with CDK4 and MDM2 in dedifferentiated liposarcoma (DDLS) and undifferentiated high-grade pleomorphic sarcoma (UHGPS). Amplification and expression of the three genes were identified in 90% to 100% (9–11 of 11) of DDLS, whereas that of FRS2, CDK4, and MDM2 were observed in 55% (41 of 75), 48% (36 of 75), and 44% (33/75) of clinically diagnosed UHGPS, suggesting that these “UHGPS” may represent DDLS despite lacking histologic evidence of lipoblasts. Immunohistochemical analysis of phosphorylated FRS2 protein indicated that the FGFR/FRS2 signaling axis was generally activated in about 75% of FRS2-positive high-grade liposarcomas. Moreover, we found that FRS2 and FGFRs proteins are highly expressed and functional in three high-grade liposarcoma cell lines: FU-DDLS-1, LiSa-2, and SW872. Importantly, the FGFR selective inhibitor NVP-BGJ-398 significantly inhibited the growth of FU-DDLS-1 and LiSa-2 cells with a concomitant suppression of FGFR signal transduction. Attenuation of FRS2 protein in FU-DDLS-1 and LiSa-2 cell lines decreased the phosphorylated extracellular signal–regulated kinase 1/2 and AKT and repressed cell proliferation. These findings indicate that analysis of FRS2 in combination with CDK4 and MDM2 will more accurately characterize pathologic features of high-grade liposarcomas. Activated FGFR/FRS2 signaling may play a functional role in the development of high-grade liposarcomas, therefore, serve as a potential therapeutic target. Cancer Res; 73(4); 1298–307. ©2012 AACR.
Volume spirometers need automated internal temperature sensors.
Authors: L R Johnson, P L Enright, H T Voelker, D P Tashkin
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Spirometer temperature was measured automatically during all years of the Lung Health Study. Short- and long-term changes in temperature were analyzed for the 23 dry-rolling-seal volume spirometers used at the 10 clinical centers involved in the study. Within-test-session spirometer temperature increased a mean of 0.3 degrees C, and as much as 3.0 degrees C during methacholine challenge testing. The maximal change in spirometer temperature during a test day exceeded 4 degrees C more than 5% of the time. Month-to-month changes of more than 15 degrees C were not uncommon. If ambient temperature had been assumed to apply to all maneuvers and used for BTPS corrections, FEV1, and FVC measurement errors of up to 6% would have occurred. When using volume spirometers, the temperature of air inside the spirometer should be measured accurately during each breathing maneuver.
Measures are needed to allow elderly inpatients to vote in general elections
Authors: V Aylett, G Cook, O J Corrado
Journal: BMJ (1998)

Outcome of pregnancy in women with insulin dependent diabetes Centralisation of care leads to better outcomeEditor-The finding of a persistently poor outcome of pregnancy in women with insulin dependent diabetes in two (northern) English regions is an important statement of the problem. 1 2 Both studies provide figures and show outcomes that are no different from those widely reported in the past.Unfortunately, neither give evidence of any degree of centralisation of obstetric or diabetic care, with on-site neonatal intensive care, although this is a proved means of improving the outcome of pregnancy for diabetic mothers. 3 The St Vincent declaration guidelines on the outcome of pregnancy, referred to in the accompanying editorial (p 263), are based on the Scandinavian reports held up as examples of good practice and state that "an interdisciplinary team should provide centralized diabetic pregnancy care in a hospital treating at least 20-30 cases a year.Pregnant diabetic
Anaesthesia for patients with coronary disease
Authors: A Padfield
Journal: BMJ (1980)

oxidase, for example, accepts many sterols as substrates.1 2 It is, of course, unusual for other sterols to occur in major proportions in plasma: one recalls the early studies of triparanol as a drug which led to reduced levels of cholesterol but caused concomitant accumulation of desmosterol.Such gross changes are rare, but it cannot be assumed that sterols present in quite low concentrations are devoid of effects.Moreover, some dietary sterols besides cholesterol can be absorbed from the digestive tract, and attention has recently been drawn4 to the possibility of deleterious effects resulting from the ingestion of oxygenated sterols present in foods.
Abstract 3562: Building workflows for gene fusion detection by RNA-seq
Authors: Stephen Gross, Lisa Watson, Smita Pathak, Irina Khrebtukova, Gary Schroth
Journal: Cancer Research (2014)

Abstract Many cancers are associated with chromosomal rearrangements, which in some cases yield fusions between disparate genes and impact cancer phenotypes. Rapid discovery of gene fusions in cancer can facilitate a deeper understanding of specific cancers and may become an important diagnostic tool in clinical settings informing decisions on cancer treatment. An attractive and cost-effective method to identify and study gene fusions is by massively-parallel RNA sequencing (RNA-seq), which provides rich transcriptome profiling data and, with appropriate computational analysis, can discover fusions between transcribed genes. Herein we present data exploring the robustness of gene fusion detection by RNA-seq on Illumina sequencing platforms with TopHat-Fusion, a RNA-seq read aligner specifically designed to detect expressed gene fusions. Using a set of synthetic fusion transcripts to spike in to human RNA samples, we demonstrate quantitative detection of gene fusions by RNA-seq. Additionally, we report the sensitivity of gene fusion discovery across different RNA-seq library preparation methods, including mRNA enrichment by poly-A selection, rRNA-depletion, and exome enrichment by targeted capture. This data helps build workflow recommendations for the detection and study of gene fusions by RNA-seq. Citation Format: Stephen Gross, Lisa Watson, Smita Pathak, Irina Khrebtukova, Gary Schroth. Building workflows for gene fusion detection by RNA-seq. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3562. doi:10.1158/1538-7445.AM2014-3562
182 RETROSPECTIVE STUDY OF ACUTE LIVER FAILURE IN RESIDENTS OF A METROPOLITAN AREA IN GERMANY: INFLUENCE OF CHOLESTATIC ENZYMES AND BODY MASS INDEX ON CLINICAL OUTCOME
Authors: A. Canbay, C. Jochum, L.P. Bechmann, S. Festag, Z. Yüksel, F. Saner, G. Gerken
Journal: Journal of Hepatology (2008)