tbuckley/cabot-search huggingface dataset:
Lack of full CD8 functional restoration after antiviral treatment for acute and chronic hepatitis C virus infection
Authors: Gabriele Missale, Massimo Pilli, Alessandro Zerbini, Amalia Penna, Lara Ravanetti, Valeria Barili, Alessandra Orlandini, Atim Molinari, Massimo Fasano, Teresa Santantonio, Carlo Ferrari
Journal: Gut (2012)

St. John9s wort (SJW) has been described to show anti-inflammatory properties due to its inhibitory effects on the expression of pro-inflammatory genes like cyclooxygenase-2, interleukin-6, and inducible nitric-oxide synthase (iNOS). Since iNOS plays a critical role in chronic inflammatory diseases, we have focused our attention on the regulation of iNOS expression by SJW in two different human epithelial cell lines, alveolar A549/8 and colon DLD-1 cells. SJW extract concentration dependently inhibited human iNOS expression evaluated by measuring the amounts of iNOS mRNA, iNOS protein, and NO production in both cell lines. This inhibitory effect resulted from transcriptional inhibition as shown in reporter gene experiments. With electrophoretic mobility shift experiments, we found a SJW-mediated down-regulation of the DNA binding activity of the transcription factor signal transducer and activator of transcription-1α (STAT-1α), but not of nuclear factor-κB. This down-regulation of the STAT-1α DNA binding was shown to result from reduced tyrosine phosphorylation of the STAT-1α protein. The diminished STAT-1α tyrosine phosphorylation resulted from SJW-mediated reduction of Janus kinase 2 activity. These data suggest that extracts from SJW may be a promising anti-inflammatory principle in chronic inflammatory diseases.
TREATMENT OF TUBERCULOSIS AND TUBERCULIN INOCULATION
Authors: T. W. Brown
Journal: BMJ (1905)

r in o attack of indigestion set in.Next day he had much pain and tenderness in the gastro-hepatic region, accompanied by slight jaundice and retching, Collapse set in, and he died on July 20th.There was evidently chronic disease of the liver, possibly malignant.CASE CXXVIII.Hospital patient, sent by Dr. Lloyd Williams, Stone, Staffordshire.Vesioal calculus removed by litholapaxy two years previously Catheter employed for three years.Residual urine 21 OZ., foul, alkaline, con- taining much pus; specific gravity 1012.On September 28th, 1904, I removed the prostate, which weighed 3i OZ.The operation was easily accomplished and well borne, but the patient died uraemic on October sth.The kidneys were found extensively diseased.CASE CXXXVIII.
PTPμ suppresses glioma cell migration and dispersal
Authors: Adam M. Burgoyne, Juan M. Palomo, Polly J. Phillips-Mason, Susan M. Burden-Gulley, Denice L. Major, Anita Zaremba, Shenandoah Robinson, Andrew E. Sloan, Michael A. Vogelbaum, Robert H. Miller, Susann M. Brady-Kalnay
Journal: Neuro-Oncology (2009)

The cell-surface receptor protein tyrosine phosphatase mu (PTPmu) is a homophilic cell adhesion molecule expressed in CNS neurons and glia. Glioblastomas (GBMs) are the highest grade of primary brain tumors with astrocytic similarity and are characterized by marked dispersal of tumor cells. PTPmu expression was examined in human GBM, low-grade astrocytoma, and normal brain tissue. These studies revealed a striking loss of PTPmu protein expression in highly dispersive GBMs compared to less dispersive low-grade astrocytomas and normal brain. We hypothesized that PTPmu contributes to contact inhibition of glial cell migration by transducing signals in response to cell adhesion. Therefore, loss of PTPmu may contribute to the extensive dispersal of GBMs. The migration of brain tumor cells was assessed in vitro using a scratch wound assay. Parental U-87 MG cells express PTPmu and exhibited limited migration. However, short-hairpin RNA (shRNA)-mediated knockdown of PTPmu induced a morphological change and increased migration. Next, a brain slice assay replicating the three-dimensional environment of the brain was used. To assess migration, labeled U-87 MG glioma cells were injected into adult rat brain slices, and their movement was followed over time. Parental U-87 MG cells demonstrated limited dispersal in this assay. However, PTPmu shRNA induced migration and dispersal of U-87 MG cells in the brain slice. Finally, in a mouse xenograft model of intracranially injected U-87 MG cells, PTPmu shRNA induced morphological heterogeneity in these xenografts. Together, these data suggest that loss of PTPmu in human GBMs contributes to tumor cell migration and dispersal, implicating loss of PTPmu in glioma progression.
Case of 'Le Petit Mal': With Some Observations on the Responsibility of Epileptics
Authors: J. T. Dickson
Journal: BMJ (1867)

Background: The most commonly reported primary lung cancer subtype is adenocarcinoma, which is associated with a poor prognosis and short survival. Proteomic studies on human body fluids such as bronchoalveolar lavage fluid (BALF) have become essential methods for biomarker discovery, examination of tumor pathways and investigation of potential treatments. Aim: This study used quantitative proteomics to investigate the up-regulation of novel proteins in BALF from patients with primary lung adenocarcinoma in order to identify potential biomarkers. Materials and Methods: BALF samples from individuals with and without primary lung adenocarcinoma were analyzed using liquid chromatography-mass spectrometry. Results: One thousand and one hundred proteins were identified, 33 of which were found to be consistently overexpressed in all lung adenocarcinoma samples compared to non-cancer controls. A number of overexpressed proteins have been previously shown to be related to lung cancer progression including S100-A8, annexin A1, annexin A2, thymidine phosphorylase and transglutaminase 2. Conclusion: The overexpression of a number of specific proteins in BALF from patients with primary lung adenocarcinoma may be used as a potential biomarker for lung adenocarcinoma.
Differential Expression of Ion Channel Transcripts in Atrial Muscle and Sinoatrial Node in Rabbit
Authors: James O. Tellez, Halina Dobrzynski, Ian D. Greener, Gillian M. Graham, Emma Laing, Haruo Honjo, Simon J. Hubbard, Mark R. Boyett, Rudi Billeter
Journal: Circulation Research (2006)

The aim of the study was to identify ion channel transcripts expressed in the sinoatrial node (SAN), the pacemaker of the heart. Functionally, the SAN can be divided into central and peripheral regions (center is adapted for pacemaking only, whereas periphery is adapted to protect center and drive atrial muscle as well as pacemaking) and the aim was to study expression in both regions. In rabbit tissue, the abundance of 30 transcripts (including transcripts for connexin, Na + , Ca 2+ , hyperpolarization-activated cation and K + channels, and related Ca 2+ handling proteins) was measured using quantitative PCR and the distribution of selected transcripts was visualized using in situ hybridization. Quantification of individual transcripts (quantitative PCR) showed that there are significant differences in the abundance of 63% of the transcripts studied between the SAN and atrial muscle, and cluster analysis showed that the transcript profile of the SAN is significantly different from that of atrial muscle. There are apparent isoform switches on moving from atrial muscle to the SAN center: RYR2 to RYR3, Na v 1.5 to Na v 1.1, Ca v 1.2 to Ca v 1.3 and K v 1.4 to K v 4.2. The transcript profile of the SAN periphery is intermediate between that of the SAN center and atrial muscle. For example, Na v 1.5 messenger RNA is expressed in the SAN periphery (as it is in atrial muscle), but not in the SAN center, and this is probably related to the need of the SAN periphery to drive the surrounding atrial muscle.
Plasma Membrane Calcium ATPase Overexpression in Arterial Smooth Muscle Increases Vasomotor Responsiveness and Blood Pressure
Authors: Robert Gros, Talat Afroze, Xiao-Mang You, Golam Kabir, Ryan Van Wert, Waseem Kalair, Abunasr E. Hoque, Imran N. Mungrue, Mansoor Husain
Journal: Circulation Research (2003)

In vascular smooth muscle cells (SMCs), several mechanisms act in concert to regulate the intracellular calcium concentration [Ca 2+ ] i , which may in turn affect vascular tone. One such mechanism is the extrusion of Ca 2+ by the plasma membrane calcium ATPase (PMCA). To address, in particular, the role of the neuronal nitric oxide synthase (nNOS)-associating isoform PMCA4b in regulating vascular tone, a doxycycline-responsive transgene for human PMCA4b was overexpressed in arterial SMCs of mice. Overexpression of hPMCA4b resulted in a 2-fold increase in total aortic PMCA4 protein expression and significant real-time RT-PCR-documented differences in the levels of endogenous mouse PMCA1, PMCA4, SERCA2, and IP3R1 gene expression in arterial SMCs. Whereas no significant difference in basal [Ca 2+ ] i or Ca 2+ sensitivity was observed in vascular SMCs or mesenteric arteries, respectively, from hPMCA4b-overexpressing versus control mice, hPMCA4b-overexpressing mice revealed a reduced set-point and increased extent of myogenic response and heightened sensitivity to vasoconstrictors. Treatment of arteries with an nNOS inhibitor resulted in a reduced set-point and increased extent of the myogenic response in control but not hPMCA4b-overexpressing mice. Moreover, aortic SMCs from hPMCA4b-overexpressing mice exhibited reduced levels of cGMP under both basal and phenylephrine-stimulated conditions. These changes were associated with significant doxycycline-reversible elevations in blood pressure. Taken together, these data show that overexpression of hPMCA4b in arterial SMCs increases vascular reactivity and blood pressure, an effect that may be mediated in part by negative regulation of nNOS.
The Clinical and Environmental Determinants of Airway Transcriptional Profiles in Allergic Asthma
Authors: Ivana V. Yang, John Tomfohr, Jaspal Singh, Catherine M. Foss, Harvey E. Marshall, Loretta G. Que, Erin McElvania-Tekippe, Sarita Florence, John S. Sundy, David A. Schwartz
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Gene expression profiling of airway epithelial and inflammatory cells can be used to identify genes involved in environmental asthma.Airway epithelia and inflammatory cells were obtained via bronchial brush and bronchoalveolar lavage (BAL) from 39 subjects comprising three phenotypic groups (nonatopic nonasthmatic, atopic nonasthmatic, and atopic asthmatic) 4 hours after instillation of LPS, house dust mite antigen, and saline in three distinct subsegmental bronchi. RNA transcript levels were assessed using whole genome microarrays.Baseline (saline exposure) differences in gene expression were related to airflow obstruction in epithelial cells (C3, ALOX5AP, CCL18, and others), and to serum IgE (innate immune genes and focal adhesion pathway) and allergic-asthmatic phenotype (complement genes, histone deacetylases, and GATA1 transcription factor) in inflammatory cells. LPS stimulation resulted in pronounced transcriptional response across all subjects in both airway epithelia and BAL cells, with strong association to nuclear factor-κB and IFN-inducible genes as well as signatures of other transcription factors (NRF2, C/EBP, and E2F1) and histone proteins. No distinct transcriptional profile to LPS was observed in the asthma and atopy phenotype. Finally, although no consistent expression changes were observed across all subjects in response to house dust mite antigen stimulation, we observed subtle differences in gene expression (e.g., GATA1 and GATA2) in BAL cells related to the asthma and atopy phenotype.Our results indicate that among individuals with allergic asthma, transcriptional changes in airway epithelia and inflammatory cells are influenced by phenotype as well as environmental exposures.
Context-Dependent Hormone-Refractory Progression Revealed through Characterization of a Novel Murine Prostate Cancer Cell Line
Authors: Philip A. Watson, Katharine Ellwood-Yen, Jennifer C. King, John Wongvipat, Michelle M. LeBeau, Charles L. Sawyers
Journal: Cancer Research (2005)

Abstract Insights into the molecular basis of hormone-refractory prostate cancer have principally relied on human prostate cancer cell lines, all of which were derived from patients who had already failed hormonal therapy. Recent progress in developing genetically engineered mouse prostate cancer models provides an opportunity to isolate novel cell lines from animals never exposed to hormone ablation, avoiding any potential bias conferred by the selective pressure of the castrate environment. Here we report the isolation of such a cell line (Myc-CaP) from a c-myc transgenic mouse with prostate cancer. Myc-CaP cells have an amplified androgen receptor gene despite no prior exposure to androgen withdrawal and they retain androgen-dependent transgene expression as well as androgen-dependent growth in soft agar and in mice. Reexpression of c-Myc from a hormone-independent promoter rescues growth in androgen-depleted agar but not in castrated mice, showing a clear distinction between the molecular requirements for hormone-refractory growth in vitro versus in vivo. Myc-CaP cells represent a unique reagent for dissecting discreet steps in hormone-refractory prostate cancer progression and show the general utility of using genetically engineered mouse models for establishing new prostate cancer cell lines. (Cancer Res 2005; 65(24): 11565-71)
Analgesic Use and Renal Function in Men
Authors: Kathryn M. Rexrode
Journal: JAMA (2001)

Context Several case-control studies suggest an association between analgesic use and increased risk of chronic renal disease, but few cohort studies have examined this association. Objective To determine whether analgesic use is associated with risk of renal dysfunction. Design and Setting Cohort study of analgesic use data from the Physicians' Health Study, which lasted 14 years from September 1982 to December 1995 with annual follow-up. Participants A total of 11 032 initially healthy men who provided blood samples and self-report of analgesic use. Main Outcome Measures Elevated creatinine level defined as 1.5 mg/dL (133 µmol/L) or higher and a reduced creatinine clearance defined as 55 mL/min (0.9 mL/s) or less, and self-reported use of acetaminophen, aspirin, and other nonsteroidal anti-inflammatory drugs (never [<12 pills]; 12-1499 pills; 1500-2499 pills; and ≥2500 pills). Results A total of 460 men had elevated creatinine levels (4.2%) and 1258 had reduced creatinine clearance (11.4%). Mean creatinine levels and creatinine clearances were similar among men who did not use analgesics and those who did, even at total intakes of 2500 or more pills. In multivariable analyses adjusted for age; body mass index; history of hypertension, elevated cholesterol, and diabetes; occurrence of cardiovascular disease; physical activity; and use of other analgesics, the relative risks of elevated creatinine level associated with intake of 2500 or more pills were 0.83 (95% confidence interval [CI], 0.50-1.39; P for trend = .05) for acetaminophen, 0.98 (95% CI, 0.53-1.81; P for trend = .96) for aspirin, and 1.07 (95% CI, 0.71-1.64; P for trend = .86) for other nonsteroidal anti-inflammatory drugs. No association was observed between analgesic use and reduced creatinine clearance. Conclusions Moderate analgesic use in this cohort study of initially healthy men was not associated with increased risk of renal dysfunction.
Prognosis, Imatinib Dose, and Benefit of Sunitinib in GIST: Knowing the Genotype
Authors: Ian R. Judson
Journal: Journal of Clinical Oncology (2008)

The introduction of the tyrosine kinase inhibitor imatinib has transformed the therapy of advanced or metastatic gastrointestinal stromal tumor (GIST). 1,2However, despite truly remarkable early results, it soon became apparent that this treatment did not result in cure but, rather, in a high objective response and disease stabilization rate.In the European Organisation for Research and Treatment of Cancer (EORTC) phase I study, 19 of 36 patients with GIST achieved a partial response, and 13 had minor responses or stable disease, which led to a clinical benefit rate of 89%. 3 In the subsequent phase II study conducted at the maximum-tolerated dose (MTD) of imatinib 800 mg daily, 24 (89%) of 27 patients with GIST responded or had stable disease. 4Similarly, in the US B2222 study, which compared 400-mg and 600-mg imatinib doses, 81.6% of patients achieved partial response or prolonged stable disease. 5However, primary imatinib resistance was observed in all trials-11% in both EORTC studies, and 13.6% in study B2222.Of these patients, one in the EORTC phase I study and three in B2222 had disease stabilization or better after an increase in the imatinib dosage. 3,5The long-term follow-up on study B2222 was recently published in Journal of Clinical Oncology, and it indicated that the overall objective remission rate had improved with time to 68.1%, that the median duration of response was 29 months, and that neither response rate nor duration were different between the two doses. 6o explore additionally the impact of imatinib dosage, two phase III trials were performed that compared the standard 400-mg dose (which represented the dose established as efficacious in chronic myeloid leukemia trials) with the 800-mg MTD from the EORTC study.Both study 62005, performed in Europe and Australia, and the North American study S0033 allowed patients initially treated with imatinib 400 mg daily who failed to respond, or who progressed after an initial response, to cross over to 800 mg.This resulted in disease stabilization in 28% to 29% of patients, some of whom (18% in the EORTC trial) were still receiving treatment a year later. 2,7he relationship between GIST and activating mutations in KIT was first reported by Hirota et al. 8 In addition to the commonest mutation in exon 11, which codes for the juxtamembrane domain, mutations in exons 9 and 12 were also described. 9Heinrich et al 10 also reported activating mutations in the platelet-derived growth factor receptor ␣ gene (PDGFRA) and found that PDGFRA and KIT mutations appeared to be mutually exclusive.In a study of the genotype of 127 patients in study B2222, Heinrich et al 11 reported the frequency of different KIT and PDGFRA mutations and demonstrated that these had a marked impact on the outcome of patients treated with ima-
In-vitro mobility of the lumbar spine.
Authors: R C Hilton, J Ball, R T Benn
Journal: Annals of the Rheumatic Diseases (1979)

As part of a systematic study of the spine between D11 and S1 the response to stress has been assessed by measuring radiologically the total and segmental mobility of 103 specimens. The method was shown to be reproducible to within 10% of total mobility. No significant sex difference was seen. Total mobility varied widely, but mean total mobility fell with age. All lumbar segments became less mobile up to the fifth decade. Between the fifth and the eighth decade the mobility of the fifth lumbar segment continued to fall, whereas other lumbar segments became more mobile. The mobility of each segment also varied widely, but the mean segmental mobility fell progressively from L5 to D11. However, this smooth pattern of movement was seen in only 16 cases, mostly adolescents and young adults. Among the remainder, in which movement was irregularly distributed, there were 7 cases (4 aged less than 30 years) in which the mobility of at least 1 segment was more than 2 standard deviations above the mean. The cause of this hypermobility was not evident radiologically. It is suggested that segments with abnormally high mobility may be at risk.
Single-breath method for assessing the viscoelastic properties of the respiratory system
Authors: V Antonaglia, A Grop, P Demanins, F Beltrame, U Lucangelo, A Peratoner, L De Simoni, A Gullo, J Milic-Emili
Journal: European Respiratory Journal (1998)

In order to explain the time dependency of resistance and elastance of the respiratory system, a linear viscoelastic model (Maxwell body) has been proposed. In this model the maximal viscoelastic pressure (Pvisc.max) developed within the tissues of the lung and chest wall at the end of a constant-flow (V') inflation of a given time (tI) is given by: Pvisc,max = R2V'(1-e(-tI/tau2), where R2 and tau2 are, respectively, the resistance and time constant of the Maxwell body. After rapid airway occlusion at t1, tracheal pressure (Ptr) decays according to the following function: Ptr(t) = Pvisc(t) + Prs,st = Pvisc,max(etocc/tau2)+ Prs,st, where tocc/is time after occlusion and Prs,st is static re-coil pressure of the respiratory system. By fitting Ptr after occlusion to this equation, tau2 and Pvisc,max are obtained. Using these values, together with the V' and tI pertaining to the constant-flow inflation preceding the occlusion, R2 can be calculated from the former equation. Thus, from a single breath, the constants tau2, R2 and E2 (R2/tau2) can be obtained. This method was used in 10 normal anaesthetized, paralysed, mechanically ventilated subjects and six patients with acute lung injury. The results were reproducible in repeated tests and similar to those obtained from the same subjects and patients with the time-consuming isoflow, multiple-breath method described previously.
Abnormal glucose homeostasis in skeletal muscle–specific PGC-1α knockout mice reveals skeletal muscle–pancreatic β cell crosstalk
Authors: Christoph Handschin, Cheol Soo Choi, Sherry Chin, Sheene Kim, Dan Kawamori, Amarnath J. Kurpad, Nicole Neubauer, Jiang Hu, Vamsi K. Mootha, Young-Bum Kim, Rohit N. Kulkarni, Gerald I. Shulman, Bruce M. Spiegelman
Journal: Journal of Clinical Investigation (2007)

The transcriptional coactivator PPARgamma coactivator 1alpha (PGC-1alpha) is a strong activator of mitochondrial biogenesis and oxidative metabolism. While expression of PGC-1alpha and many of its mitochondrial target genes are decreased in the skeletal muscle of patients with type 2 diabetes, no causal relationship between decreased PGC-1alpha expression and abnormal glucose metabolism has been established. To address this question, we generated skeletal muscle-specific PGC-1alpha knockout mice (MKOs), which developed significantly impaired glucose tolerance but showed normal peripheral insulin sensitivity. Surprisingly, MKOs had expanded pancreatic beta cell mass, but markedly reduced plasma insulin levels, in both fed and fasted conditions. Muscle tissue from MKOs showed increased expression of several proinflammatory genes, and these mice also had elevated levels of the circulating IL-6. We further demonstrated that IL-6 treatment of isolated mouse islets suppressed glucose-stimulated insulin secretion. These data clearly illustrate a causal role for muscle PGC-1alpha in maintenance of glucose homeostasis and highlight an unexpected cytokine-mediated crosstalk between skeletal muscle and pancreatic islets.