tbuckley/cabot-search huggingface dataset:
Impaired binding properties of thyroxine-binding globulin in hepatocellular carcinoma and chronic liver disease
Authors: Winston L. Hutchinson, Yvette S. White, Elizabeth A. Fagan, Philip J. Johnson, Roger Williams
Journal: Hepatology (1991)

To determine the factors underlying the apparent reduction in binding ability of thyroxine-binding globulin in hepatocellular carcinoma, hormone-binding characteristics were further examined in patients with this disease and in control subjects. No differences in affinity constants with respect to triodothyronine or serum thyroxine-binding globulin from hepatocellular carcinoma, cirrhotic and normal subjects were found. The affinity for thyroxine was significantly reduced in hepatocellular carcinoma (0.41 +/- 0.13 x 10(10) mol-1) and cirrhotic (0.65 +/- 0.1 x 10(10) mol-1) patients compared with normal subjects (0.94 +/- 0.7 x 10(10) mol-1). Investigations carried out on liver tissue obtained from patients with hepatocellular carcinoma and chronic liver disease showed that thyroxine-binding globulin within tumor tissue was elevated and bound less exogenous tracer hormone compared with that obtained from nontumor tissue. Tumor-derived thyroxine-binding globulin with altered binding properties is, at least partly, responsible for the abnormal behavior of the serum protein in patients with hepatocellular carcinoma.
Study on human tracheal bronchial epithelial cells secreting cytokines in vitro by nontypeable haemophilus influenzae
Authors: Jianmei Qian, Chunxue Bai, Guifang Wang
Journal: European Respiratory Journal (2012)

Obstrucive  To study the interaction of nontypeable haemophilus influenzae strain ATCC49247 with primary human bronchial epithelial cells (HBEC) and the NTHi-induced release and expression of proinflammoraty cytokine in the HBEC.  Methods  HBEC were isolated by using low temperature protease digestion and cultured in serum-free medium. Confluent epithelial cell cultures were incubated with NTHi, NTHi +erythromycin(0.1mg/L), NTHi + erythromycin(10mg/L), NTHi + gentamicin(100mg/L), NTHi+dexamethasone(100uM)and normal untreated control cells after 24h. Release of IL-8 and TNF-a into the supernatant was assayed by enzyme-linked immunosorbent assay; The expression of ICAM-1 was examined by immunohistochemistry staining.  Results  (1) Some HBECs were transformed and died after 24h. (2) HBEC: NTHi-induced cells released significantly greater amounts of IL-8 and TNF-a (2172.18±131.83, 7.22±2.17 pg/ml, respectively) than normal untreated cells (1115.76±57.63,2.84±1.04pg/ml)(p Conclusions  HBEC can release IL-8 and TNF-a. NTHi may increase significantly release and expression of proinflammatory cytokine. Gentamicin have no anti-inflammatory effects. Erythromycin may have anti-inflammatory effects. Dexamethasone has distinct anti-inflammatory effects.
Identification of Receptor Ligands by Screening Phage-Display Peptide Libraries Ex Vivo on Microdissected Kidney Tubules
Authors: ALEX ODERMATT, ANNETTE AUDIGÉ, CHRISTOPH FRICK, BRUNO VOGT, BRIGITTE M. FREY, FELIX J. FREY, LUCA MAZZUCCHELLI
Journal: Journal of the American Society of Nephrology (2001)

Abstract. A novel method to identify receptor ligands for defined renal tubular segments has been developed. Ex vivo screening of phage-display peptide libraries on isolated intact rat proximal convoluted tubules (PCT) and cortical collecting ducts (CCD) allowed the direct access of phage to the basolateral surface of tubular epithelial cells. Two distinct peptide motifs were selected for CCD and PCT, indicating differential expression of some membrane receptors on the basolateral surface of defined kidney tubule segments. Using the linear peptide motif ELRGD(R/M)AX(W/L), recovered from freshly isolated rat CCD, mediated 16-fold selectivity of phage binding to CCD compared with PCT. Binding to CCD was 39-fold higher than that of a random control phage. Binding and subsequent internalization of phage, most likely by an integrin-mediated endocytosis pathway, was abolished by the addition of the corresponding synthetic peptide. Furthermore, the results demonstrate that presentation and flanking amino acids determine the specific binding properties of RGD ligands to their putative integrin receptors. The results emphasize the need of a native cell system for the identification of renal epithelial cell surface ligands. Such ligands are of potential relevance for the analysis of interactions between extracellular matrix and kidney tubules or for the development of improved vectors for kidney-specific drug delivery or gene transfer.
Tumorigenicity of Human Malignant Lymphoblasts: Comparative Study With Unmanipulated Nude Mice, Antilymphocyte Serum-Treated Nude Mice, and X-Irradiated Nude Mice23
Authors: Yoshiyuki Ohsugi, M. Eric Gershwin, Robert B. Owens, Walter A. Nelson-Rees
Journal: JNCI Journal of the National Cancer Institute (1980)

The ability of unmanipulated, antilymphocyte serum (ALS)-treated, and X-irradiated nude BALB/c female mice (in their 13th backcross generation) to serve as hosts for 10 human lymphoblastoid cell lines as well as for peripheral blood lymphocytes from healthy humans was compared. The 10 lymphoma lines included 7 previously characterized and reported in the literature. Significant differences with respect to both latency period for tumor appearance and success rate for tumor transplantation were detected among the 3 experimental groups. The unmanipulated mice were poor recipients for lymphoma heterotransplants, and tumors were produced in only two instances. In contrast, 6 tumor lines were successfully transplanted in mice inoculated with ALS, and all 10 lines were successfully transplanted in X-irradiated recipients. Although tumors were readily produced in ALS-treated and X-irradiated mice, no gross or histologic evidence of local or distant metastases was apparent. Human lymphoblastoid cells were recultured, essentially unchanged, from the heterotransplants from 6 of 7 tumors tested. Although the tumor line HT 1460, originally from a human lymphoma, was successfully transplanted in all 3 groups, only mouse cells were recultured. The use of X-radiation, rather than ALS, to immunosuppress nude mice offers a more standardized method for heterotransplanting human tumor cell lines and permits ready comparisons between laboratories. Furthermore, X-radiation permits transplantation and subsequent study of lymphoblastoid tumors that are otherwise difficult to successfully transplant in nude mice.
Electrophysiological Effects of Diphenylhydantoin on Canine Purkinje Fibers
Authors: J. THOMAS BIGGER, ARTHUR L. BASSETT, BRIAN F. HOFFMAN
Journal: Circulation Research (1968)

The effects of diphenylhydantoin (DPH) were studied on isolated, perfused Purkinje fibers over a range of concentrations from 10 -8 to 10 -4 M . The time course of repolarization of the transmembrane action potential shortened due to abbreviation of all phases of repolarization. The effective refractory period also shortened during exposure to DPH, but to a lesser extent than the action potential. As a result the earliest effective test stimulus elicited action potentials with greater amplitude and dv/dt of phase 0 than under control conditions. In driven fibers with normal action potentials, DPH had little effect on the amplitude or rate of rise (dv/dt) of phase 0 of the action potential. In driven fibers which were partially depolarized, or those with low dv/dt of phase 0 despite normal resting potentials, DPH caused an increase in the rate of rise of phase 0 of the action potential. DPH caused a decrease in the firing rate of normal automatic fibers by decreasing the slope of phase 4 depolarization. In automatic fibers which showed generalized diastolic depolarization and decreased maximum diastolic potential, DPH caused an increase in the latter as well as a decrease in the slope of phase 4 depolarization.
Diabetes and risk of physical disability in adults: a systematic review and meta-analysis
Authors: Evelyn Wong, Kathryn Backholer, Emma Gearon, Jessica Harding, Rosanne Freak-Poli, Christopher Stevenson, Anna Peeters
Journal: The Lancet Diabetes & Endocrinology (2013)

According to previous reports, the risk of disability as a result of diabetes varies from none to double. Disability is an important measure of health and an estimate of the risk of disability as a result of diabetes is crucial in view of the global diabetes epidemic. We did a systematic review and meta-analysis to estimate this risk.We searched Ovid, Medline, Embase, Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature up to Aug 8, 2012. We included studies of adults that compared the risk of disability-as measured by activities of daily living (ADL), instrumental activities of daily living (IADL), or mobility-in people with and without any type of diabetes. We excluded studies of subpopulations with specific illnesses or of people in nursing homes. From the studies, we recorded population characteristics, how diabetes was diagnosed (by doctor or self-reported), domain and definition of disability, and risk estimates for disability. We calculated pooled estimates by disability type and type of risk estimate (odds ratio [OR] or risk ratio [RR]).Our systematic review returned 3224 results, from which 26 studies were included in our meta-analyses. Diabetes increased the risk of mobility disability (15 studies; OR 1.71, 95% CI 1.53-1.91; RR 1.51, 95% CI 1.38-1.64), of IADL disability (ten studies; OR 1.65, 95% CI 1.55-1.74), and of ADL disability (16 studies; OR 1.82, 95% CI 1.63-2.04; RR 1.82, 95% CI 1.40-2.36).Diabetes is associated with a strong increase in the risk of physical disability. Efforts to promote healthy ageing should account for this risk through prevention and management of diabetes.Monash University, Baker IDI Bright Sparks Foundation, Australian Postgraduate Award, VicHealth, National Health and Medical Research Council, Australian Research Council, Victorian Government.
Consecutive use of hormonally defined serum-free media to establish highly differentiated human renal proximal tubule cells in primary culture.
Authors: F Courjault-Gautier, J Chevalier, C C Abbou, D K Chopin, H J Toutain
Journal: Journal of the American Society of Nephrology (1995)

Highly differentiated human proximal tubule (HPT) cells in primary culture were established from heterogeneous suspension of tubules prepared from the human renal cortex by an original two-step procedure. First, gluconeogenic-competent HPT cells were selected by using a hormonally defined serum-free medium without glucose or insulin; then, the selected HPT cells were grown in a medium containing a low concentration of glucose (1 mM) and insulin (0.5 micrograms/mL) but no antibiotics. HPT cells grown on plastic support formed confluent, cobblestone-like monolayers with numerous mitochondria and pinocytosis vacuoles, solitary cilia, junctional complexes, and a well-developed brush border consisting of densely packed microvilli. Compared with cell monolayers on plastic support, HPT cells grown on porous filter membranes showed better morphologic differentiation. HPT cell monolayers expressed the following differentiated functions of the proximal tubule in situ: a low-affinity, high-capacity Na(+)-dependent glucose transport system inhibited by phlorizin, a high-affinity Na(+)-dependent phosphate transport system, a basolateral organic cation uptake inhibited by mepiperphenidol, parathyroid hormone-sensitive cAMP synthesis, brush-border hydrolase activities, gluconeogenesis-associated enzymes, glutathione-S-transferases and N-acetyl-beta-D-glucosaminidase. The medium containing low glucose and insulin concentrations markedly limited the increase in glycolysis but did not prevent the falls in gluconeogenesis and brush-border hydrolase activity at any time of the culture period. Similar decreases of brush border enzyme activities were obtained for HPT cells grown either on plastic or on porous filter membrane. A thorough characterization study demonstrated that this simple and preparative experimental approach makes it possible to establish highly differentiated HPT cells in primary culture suitable for investigating human renal proximal tubular cell function.
Regulation of activation-induced deaminase stability and antibody gene diversification by Hsp90
Authors: Alexandre Orthwein, Anne-Marie Patenaude, El Bachir Affar, Alain Lamarre, Jason C. Young, Javier M. Di Noia
Journal: The Journal of Experimental Medicine (2010)

Activation-induced deaminase (AID) is the mutator enzyme that initiates somatic hypermutation and isotype switching of the antibody genes in B lymphocytes. Undesired byproducts of AID function are oncogenic mutations. AID expression levels seem to correlate with the extent of its physiological and pathological functions. In this study, we identify AID as a novel Hsp90 (heat shock protein 90 kD) client. We find that cytoplasmic AID is in a dynamic equilibrium regulated by Hsp90. Hsp90 stabilizes cytoplasmic AID, as specific Hsp90 inhibition leads to cytoplasmic polyubiquitination and proteasomal degradation of AID. Consequently, Hsp90 inhibition results in a proportional reduction in antibody gene diversification and off-target mutation. This evolutionarily conserved regulatory mechanism determines the functional steady-state levels of AID in normal B cells and B cell lymphoma lines. Thus, Hsp90 assists AID-mediated antibody diversification by stabilizing AID. Hsp90 inhibition provides the first pharmacological means to down-regulate AID expression and activity, which could be relevant for therapy of some lymphomas and leukemias.
Frequent Overexpression of <i>HMGA2</i> in Human Atypical Teratoid/Rhabdoid Tumor and Its Correlation with <i>let-7a3/let-7b</i> miRNA
Authors: Keqiang Zhang, Hanlin Gao, Xiwei Wu, Jinhui Wang, Wendi Zhou, Guihua Sun, Jinghan Wang, Yafan Wang, Bing Mu, Charles Kim, Peiguo Chu, Donald M. Ho, David K. Ann, Tai-Tong Wong, Yun Yen
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive pediatric malignancies characterized by biallelic inactivation of the SMARCB1 tumor suppressor gene. We searched for novel genomic aberrations by investigating the copy number and expression alterations of let-7a3/let-7b microRNA (miRNA) and correlated these with expression of high-mobility group AT-hook 2 (HMGA2) oncoprotein, a target of let-7 miRNA family, in 18 AT/RT samples to elucidate potential roles of HMGA2 in the pathogenesis of AT/RT. Experimental Design: Genomic aberrations, let-7a3/let-7b miRNA and HMGA2 expression in AT/RT tissues were identified using quantitative PCR, reverse transcription PCR (RT-PCR), and immunohistochemistry. The impact of let-7b miRNA on HMGA2 expression and the malignant potential of human rhabdoid tumor cell G401 (SMARCB1−/−) were investigated by antisense inhibition and ectopic overexpression studies. Results: The copy number of let-7a3/let-7b miRNA was substantially decreased in 4 of 11 AT/RT samples. A significantly inverse correlation between let-7a3/let-7b miRNA expression and HMGA2 mRNA expression was observed in AT/RT tissues (R = −0.34; P &amp;lt; 0.05). Immunohistochemistry analysis demonstrated that HMGA2 was highly overexpressed in 83.3% (15 of 18) of AT/RT tissues. Restoration of let-7 miRNA or knockdown of HMGA2 expression significantly suppressed proliferation and colony formation, and almost abolished the invasive potential of G401 cells. Conclusion: Reduction of let-7a3/let-7b miRNA may be one of mechanisms leading to overexpression of HMGA2 in AT/RT tissues. HMGA2 oncoprotein plays critical roles in the pathogenesis of AT/RT development; and reconstitution of let-7 miRNA or knockdown of HMGA2 oncoprotein may provide a novel therapeutic strategy for the treatment of patients with AT/RT. Clin Cancer Res; 20(5); 1179–89. ©2014 AACR.
Deletion of TLR5 results in spontaneous colitis in mice
Authors: Matam Vijay-Kumar, Catherine J. Sanders, Rebekah T. Taylor, Amrita Kumar, Jesse D. Aitken, Shanthi V. Sitaraman, Andrew S. Neish, Satoshi Uematsu, Shizuo Akira, Ifor R. Williams, Andrew T. Gewirtz
Journal: Journal of Clinical Investigation (2007)

Activation of TLRs by bacterial products results in rapid activation of genes encoding products designed to protect the host from perturbing microbes. In the intestine, which is colonized by a large and diverse population of commensal bacteria, TLR signaling may not function in a simple on/off mode. Here, we show that the flagellin receptor TLR5 has an essential and nonredundant role in protecting the gut from enteric microbes. Mice lacking TLR5 (TLR5KO mice) developed spontaneous colitis, as assessed by well-defined clinical, serologic, and histopathologic indicators of this disorder. Compared with WT littermates, TLR5KO mice that had not yet developed robust colitis exhibited decreased intestinal expression of TLR5-regulated host defense genes despite having an increased bacterial burden in the colon. In contrast, such TLR5KO mice displayed markedly increased colonic expression of hematopoietic-derived proinflammatory cytokines, suggesting that elevated levels of bacterial products may result in activation of other TLRs that drive colitis in TLR5KO mice. In accordance, deletion of TLR4 rescued the colitis of TLR5KO mice in that mice lacking both TLR4 and TLR5 also had elevated bacterial loads in the colon but lacked immunological, histopathological, and clinical evidence of colitis. That an engineered innate immune deficiency ultimately results in spontaneous intestinal inflammation supports the notion that an innate immune deficiency might underlie some instances of inflammatory bowel disease.
A systematic review of the psychological factors associated with returning to sport following injury
Authors: Clare L Ardern, Nicholas F Taylor, Julian A Feller, Kate E Webster
Journal: British Journal of Sports Medicine (2012)

Psychological factors have been shown to be associated with the recovery and rehabilitation period following sports injury, but less is known about the psychological response associated with returning to sport after injury. The aim of this review was to identify psychological factors associated with returning to sport following sports injury evaluated with the self-determination theory framework.Systematic review.Electronic databases were searched from the earliest possible entry to March 2012. Quantitative studies were reviewed that included athletes who had sustained an athletic injury, reported the return to sport rate and measured at least one psychological variable. The risk of bias in each study was appraised with a quality checklist.Eleven studies that evaluated 983 athletes and 15 psychological factors were included for review. The three central elements of self-determination theory-autonomy, competence and relatedness were found to be related to returning to sport following injury. Positive psychological responses including motivation, confidence and low fear were associated with a greater likelihood of returning to the preinjury level of participation and returning to sport more quickly. Fear was a prominent emotional response at the time of returning to sport despite the fact that overall emotions became more positive as recovery and rehabilitation progressed.There is preliminary evidence that positive psychological responses are associated with a higher rate of returning to sport following athletic injury, and should be taken into account by clinicians during rehabilitation.
Genetic variants associated with colorectal cancer risk: comprehensive research synopsis, meta-analysis, and epidemiological evidence
Authors: Xiangyu Ma, Ben Zhang, Wei Zheng
Journal: Gut (2013)

<h3>Objective</h3> In the past two decades, approximately 1000 reports have been published regarding associations between genetic variants in candidate genes and risk of colorectal cancer (CRC). Study results are inconsistent. We aim to provide a synopsis of the current understanding of genetic factors for CRC risk through systematically evaluating results from previous studies. <h3>Design</h3> We searched PubMed and Google Scholar to identify papers that investigated associations between genetic variants and CRC risk and published through 25 December 2012. With data from 950 papers, we conducted 910 meta-analyses for 267 genetic variants in 150 candidate genes with at least three data sources. We used Venice criteria and false-positive report probability tests to grade levels of cumulative epidemiological evidence of significant associations with CRC risk. <h3>Results</h3> Sixty-two variants in 50 candidate genes showed a nominally significant association with CRC risk (p&lt;0.05). Cumulative epidemiological evidence for a significant association with CRC risk was graded strong for eight variants in five genes (adenomatous polyposis coli (<i>APC</i>), <i>CHEK2</i>, <i>DNMT3B, MLH1</i> and <i>MUTYH</i>), moderate for two variants in two genes (<i>GSTM1</i> and <i>TERT</i>), and weak for 52 variants in 45 genes. Additionally, 40 variants in 33 genes showed convincing evidence of no association with CRC risk in meta-analyses including at least 5000 cases and 5000 controls. <h3>Conclusions</h3> Approximately 4% of genetic variants evaluated to date in candidate-gene association studies showed moderate to strong cumulative epidemiological evidence of an association with CRC risk. These genetic variants, if confirmed, may explain approximately 5% of familial CRC risk.
<i>PIK3CA</i> Mutations in Ovarian Cancer
Authors: Ian G. Campbell, Sarah E. Russell, Wayne A. Phillips
Journal: Clinical Cancer Research (2005)

To the Editor: In the April 15 issue of Clinical Cancer Research, Levine et al. ([1][1]) reported the frequent occurrence of somatic mutations in the phosphatidylinositol 3-kinase p110α catalytic subunit gene PIK3CA in breast and ovarian cancer. While their study broadly supports the conclusions of
Personality in frozen shoulder
Authors: A. Fleming, S. Dodman, T. C. Beer, S. Crown
Journal: Annals of the Rheumatic Diseases (1976)

Fifty-six patients with frozen shoulder have had their personality profiles investigated by means of the Middlesex Hospital Questionnaire. Females showed significantly increased somatic anxiety compared with controls. It is suggested that this may be important both to aetiology and treatment. Males and females should be assessed separately in future studies of frozen shoulder.