tbuckley/cabot-search huggingface dataset:
Enhanced Expression of Interleukin-6 in Primary Human Renal Cell Carcinomas
Authors: J. Takenawa, Y. Kaneko, M. Fukumoto, A. Fukatsu, T. Hirano, H. Fukuyama, H. Nakayama, J. Fujita, O. Yoshida
Journal: JNCI Journal of the National Cancer Institute (1991)

We have demonstrated interleukin-6 (IL-6) production by human renal carcinoma cells. The IL-6 gene expression was detected by Northern blot analysis in 22 of 43 primary renal cell carcinoma tissues and in five of seven renal cell carcinoma cell lines. Immunohistochemical analysis confirmed the expression of IL-6 by the tumor cells. Patients with a high-level expression of IL-6 had significantly greater incidences of lymph node metastasis and a larger increase in serum C-reactive protein than those without it. We have also probed for the presence of IL-6 receptor by Northern blot analysis; we detected this receptor in 11 of the 43 primary renal cell carcinoma tissues but in none of the seven renal cell carcinoma cell lines. However, by use of the complementary DNA-polymerase chain reaction, the IL-6 receptor transcript was detected in all specimens, including the seven cell lines. No expression of the interleukin-3 (IL-3) gene was identified in any of the 43 primary renal cell tumors. These data provide evidence that IL-6 and its receptor may play a role in promoting the transformation and/or proliferation of renal cell carcinomas as well as in teh development of symptoms.
In Vivo Microbial Stimulation Induces Rapid CD40 Ligand–independent Production of Interleukin 12 by Dendritic Cells and their Redistribution to T Cell Areas
Authors: Caetano Reis e Sousa, Sara Hieny, Tanya Scharton-Kersten, Dragana Jankovic, Hugues Charest, Ronald N. Germain, Alan Sher
Journal: The Journal of Experimental Medicine (1997)

The early induction of interleukin (IL)-12 is a critical event in determining the development of both innate resistance and adaptive immunity to many intracellular pathogens. Previous in vitro studies have suggested that the macrophage (MPhi) is a major source of the initial IL-12 produced upon microbial stimulation and that this response promotes the differentiation of protective T helper cell 1 (Th1) CD4+ lymphocytes from precursors that are primed on antigen-bearing dendritic cells (DC). Here, we demonstrate by immunolocalization experiments and flow cytometric analysis that, contrary to expectation, DC and not MPhi are the initial cells to synthesize IL-12 in the spleens of mice exposed in vivo to an extract of Toxoplasma gondii or to lipopolysaccharide, two well characterized microbial stimulants of the cytokine. Importantly, this production of IL-12 occurs very rapidly and is independent of interferon gamma priming or of signals from T cells, such as CD40 ligand. IL-12 production by splenic DC is accompanied by an increase in number of DCs, as well as a redistribution to the T cell areas and the acquisition of markers characteristic of interdigitating dendritic cells. The capacity of splenic DC but not MPhi to synthesize de novo high levels of IL-12 within hours of exposure to microbial products in vivo, as well as the ability of the same stimuli to induce migration of DC to the T cell areas, argues that DC function simultaneously as both antigen-presenting cells and IL-12 producing accessory cells in the initiation of cell-mediated immunity to intracellular pathogens. This model avoids the need to invoke a three-cell interaction for Th1 differentiation and points to the DC as both a sentinel for innate recognition and the dictator of class selection in the subsequent adaptive response.
Setting our minds to implementation
Authors: Evert Verhagen, Caroline F Finch
Journal: British Journal of Sports Medicine (2011)

It is now well accepted that to prevent sports injuries we need more intervention studies.1 Therefore, it is somewhat alarming that most sports injury studies still only focus on the first two steps of the four-step prevention sequence of van Mechelen et al 2: only counting injuries and describing causal factors. This has clearly been shown by Klugl et al ,3 who reviewed approximately 5274 original sports injury publications, of which only 492 studies intended to establish the preventive value of a measure or programme. This review showed that although the number of efficacy/effectiveness studies has slowly increased over the years, this is still lagging behind the approximately 4000 descriptive and aetiological studies.

A similar issue is apparent in relation to implementation research.4 Consider the hierarchy in research questions: efficacy questions being on the fundamental scientific knowledge side, effectiveness questions in the middle and implementation questions on the practical end of the spectrum. Klugl et al 3 unmistakably show that, just as with the sequence of prevention, we are stuck somewhere halfway. The field is starting to set a solid foundation of efficacy evidence but has not progressed to addressing the effectiveness questions, let alone beyond.

This is where we are facing an important knowledge gap because positive prevention …
Homozygous Deletion Mapping in Myeloma Samples Identifies Genes and an Expression Signature Relevant to Pathogenesis and Outcome
Authors: Nicholas J. Dickens, Brian A. Walker, Paola E. Leone, David C. Johnson, José L. Brito, Athanasia Zeisig, Matthew W. Jenner, Kevin D. Boyd, David Gonzalez, Walter M. Gregory, Fiona M. Ross, Faith E. Davies, Gareth J. Morgan
Journal: Clinical Cancer Research (2010)

Myeloma is a clonal malignancy of plasma cells. Poor-prognosis risk is currently identified by clinical and cytogenetic features. However, these indicators do not capture all prognostic information. Gene expression analysis can be used to identify poor-prognosis patients and this can be improved by combination with information about DNA-level changes.Using single nucleotide polymorphism-based gene mapping in combination with global gene expression analysis, we have identified homozygous deletions in genes and networks that are relevant to myeloma pathogenesis and outcome.We identified 170 genes with homozygous deletions and corresponding loss of expression. Deletion within the "cell death" network was overrepresented and cases with these deletions had impaired overall survival. From further analysis of these events, we have generated an expression-based signature associated with shorter survival in 258 patients and confirmed this signature in data from two independent groups totaling 800 patients. We defined a gene expression signature of 97 cell death genes that reflects prognosis and confirmed this in two independent data sets.We developed a simple 6-gene expression signature from the 97-gene signature that can be used to identify poor-prognosis myeloma in the clinical environment. This signature could form the basis of future trials aimed at improving the outcome of poor-prognosis myeloma.
High Prevalence of Abnormal Nocturnal Oximetry in Patients With Hypertrophic Cardiomyopathy
Authors: Mackram F. Eleid, Tomas Konecny, Marek Orban, Partho P. Sengupta, Virend K. Somers, James M. Parish, Farouk Mookadam, Peter A. Brady, Barbara L. Sullivan, Bijoy K. Khandheria, Steve R. Ommen, A. Jamil Tajik
Journal: Journal of the American College of Cardiology (2009)
Commented glossary for rheumatic spinal diseases, based on pathology.
Authors: R J Francois, F Eulderink, E G Bywaters
Journal: Annals of the Rheumatic Diseases (1995)

OBJECTIVES--To redefine and comment on terms on a pathological basis, in order to avoid the confusion due to the use of terms with different meanings, to standardise usage among clinicians, radiologists and pathologists, and to facilitate literature searches. METHODS--Within the Committee of Pathology of the European League against Rheumatism, a study group was set up to analyse the medical literature and common practice concerning the nomenclature of rheumatic spinal diseases. The group tried to amalgamate the main trends in the field, to reconcile etymology, historical background, morphology, and common practice. RESULTS--The group warns against use of the terms 9acquired hyperostosis syndrome9, 9(von) Bechterew9s disease9, 9Kümmel9s disease9, 9pseudospondylolisthesis9, 9rheumatoid spondylitis9, 9spondylarthropathy9 in the sense of spondarthritis, and 9spondylosis9. It recommends intercorporal or interapophyseal rather than intervertebral (osteo) chondrosis, zygapophyseal diverticulum rather than cyst, disc hernia rather than prolapse, spondyloarthritis rather than spondyloarthropathy, marginal rather than anterior spondylitis, and discarthrosis. It proposes 9zygarthrosis9 to designate zygapophyseal osteoarthrosis. CONCLUSIONS--Knowledge of the pathological basis of diseases and an understanding of the original definitions given by those who coined new terms make it possible to avoid most of the confusion arising from improper use of spinal terms.
Genetic Determinants for Promoter Hypermethylation in the Lungs of Smokers: A Candidate Gene-Based Study
Authors: Shuguang Leng, Christine A. Stidley, Yushi Liu, Christopher K. Edlund, Randall P. Willink, Younghun Han, Maria Teresa Landi, Michael Thun, Maria A. Picchi, Shannon E. Bruse, Richard E. Crowell, David Van Den Berg, Neil E. Caporaso, Christopher I. Amos, Jill M. Siegfried, Yohannes Tesfaigzi, Frank D. Gilliland, Steven A. Belinsky
Journal: Cancer Research (2011)

The detection of tumor suppressor gene promoter methylation in sputum-derived exfoliated cells predicts early lung cancer. Here, we identified genetic determinants for this epigenetic process and examined their biologic effects on gene regulation. A two-stage approach involving discovery and replication was used to assess the association between promoter hypermethylation of a 12-gene panel and common variation in 40 genes involved in carcinogen metabolism, regulation of methylation, and DNA damage response in members of the Lovelace Smokers Cohort (N = 1,434). Molecular validation of three identified variants was conducted using primary bronchial epithelial cells. Association of study-wide significance (P < 8.2 × 10(-5)) was identified for rs1641511, rs3730859, and rs1883264 in TP53, LIG1, and BIK, respectively. These single-nucleotide polymorphisms (SNP) were significantly associated with altered expression of the corresponding genes in primary bronchial epithelial cells. In addition, rs3730859 in LIG1 was also moderately associated with increased risk for lung cancer among Caucasian smokers. Together, our findings suggest that genetic variation in DNA replication and apoptosis pathways impacts the propensity for gene promoter hypermethylation in the aerodigestive tract of smokers. The incorporation of genetic biomarkers for gene promoter hypermethylation with clinical and somatic markers may improve risk assessment models for lung cancer.
Hypoglycemia Prevalence in Prepubertal Children With Type 1 Diabetes on Standard Insulin Regimen: Use of Continuous Glucose Monitoring System
Authors: Rakesh Amin, Karen Ross, Carlo L. Acerini, Julie A. Edge, Justin Warner, David B. Dunger
Journal: Diabetes Care (2003)

OBJECTIVE—To determine hypoglycemia prevalence in prepubertal children on thrice (TID) and twice (BID) daily insulin regimens, using the Medtronic Minimed Continuous Glucose Monitoring System. RESEARCH DESIGN AND METHODS—Twenty-eight children aged &amp;lt;12 years (median 9.8, range 6.9–11.8) wore the sensor for three consecutive days and nights. Hypoglycemia was defined as glucose &amp;lt;60 mg/dl for &amp;gt;15 min. Data are expressed as the percentage of time period spent hypoglycemic. RESULTS—Hypoglycemia prevalence was 10.1% (mean 2.6 h · subject−1 · day−1). Hypoglycemia was more common at night compared with daytime (18.81 vs. 4.4%, P &amp;lt; 0.001); 78 and 43% of subjects showed hypoglycemia on at least one night and two or more nights, respectively. Nocturnal episodes were prolonged (median 3.3 h) and asymptomatic (91% of episodes). Prevalence was greater between 0400 and 0730 h than between 2200 and 0400 h (25.5 vs. 15.4%, P &amp;lt; 0.001). On a TID compared with a BID regimen, nocturnal hypoglycemia prevalence was reduced, particularly between 0400–0730 h (22.9 vs. 27.4%, P = 0.005), whereas hypoglycemia the following morning (0730–1200 h) was greater (7.8 vs. 2.8%, P &amp;lt; 0.001). Nocturnal hypoglycemia risk was associated with decreasing age (by a factor of 0.6 for a year less in age), increased insulin dose (by 1.6 for an increase of 0.1 units · kg−1 · day−1), insulin regimen (by 0.2 on a BID compared with a TID regimen), and increased weight standard deviation score (SDS) (by 2.7 for a one SDS rise). CONCLUSIONS—Use of standard insulin regimens results in high prevalence and large intraindividual variation in hypoglycemia, particularly at night. Independent risk factors for nocturnal hypoglycemia were younger age, greater daily insulin dose, insulin regimen, and increasing weight.
Obesity and Oxidative Stress Predict AKI after Cardiac Surgery
Authors: Frederic T. Billings, Mias Pretorius, Jonathan S. Schildcrout, Nathaniel D. Mercaldo, John G. Byrne, T. Alp Ikizler, Nancy J. Brown
Journal: Journal of the American Society of Nephrology (2012)

Obesity increases oxidative stress, endothelial dysfunction, and inflammation, but the effect of obesity on postoperative AKI is not known. We examined the relationship between body mass index (BMI) and AKI in 445 patients undergoing cardiac surgery and whether oxidative stress (F2-isoprostanes), inflammation (IL-6), or antifibrinolysis (plasminogen activator inhibitor-1 [PAI-1]) contribute to any identified relationship. Overall, 112 (25%) of the 445 patients developed AKI. Higher BMI was independently associated with increased odds of AKI (26.5% increase per 5 kg/m2 [95% confidence interval, 4.3%–53.4%]; P=0.02). Baseline F2-isoprostane (P=0.04), intraoperative F2-isoprostane (P=0.003), and intraoperative PAI-1 (P=0.04) concentrations also independently predicted AKI. BMI no longer predicted AKI after adjustment for the effect of F2-isoprostanes, suggesting that obesity may affect AKI via effects on oxidative stress. In contrast, adjustment for IL-6 or PAI-1 did not substantially alter the association between BMI and AKI. Further, deconstruction of the obesity-AKI relationship into direct (i.e., independent of candidate pathways) and indirect (i.e., effect of BMI on AKI via each candidate pathway) effects indicated that F2-isoprostanes, but not IL-6 or PAI-1, partially mediate the relationship between obesity and AKI (P=0.001). In conclusion, obesity independently predicts AKI after cardiac surgery, and oxidative stress may partially mediate this association.
Reduced transplant lung volumes after single lung transplantation for chronic obstructive pulmonary disease.
Authors: A F Cheriyan, E R Garrity, R Pifarre, P J Fahey, J M Walsh
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Single lung transplantation is now an extremely successful option for the treatment of end-stage chronic obstructive pulmonary disease (COPD). This procedure involves placing a normal sized lung in a hyperinflated hemithorax. Preliminary observations of these patients suggest that the transplanted lung volume is smaller than expected and often the native (COPD) lung increases in volume. The purpose of this investigation was to quantify the volume contributions of the transplant and native lung to the total lung capacity. In seven patients who underwent single lung transplant for end-stage COPD the transplant and native lung volumes were measured by computer-analyzed planimetry immediately after transplant and the following 6 mo post-transplant. The transplant lung volume was smaller than predicted immediately after transplant at only 33 +/- 5% (mean +/- SD) of predicted TLC. This did not change significantly over the next 6 mo. Native lung volume increased following transplant to 74 +/- 19% predicted TLC at 1 mo and 80 +/- 16% at 6 mo. Five of the seven patients subsequently underwent measurement of pleural pressures at TLC. The mean static pleural pressure at TLC was low at -16 +/- 5.1 cm H2O. In summary, following single lung transplantation for COPD the transplanted lung is significantly restricted. We conclude that the likely mechanism of this restriction is due to low transpulmonary pressure generation.
The incomplete Bucindolol Evaluation in Acute myocardial infarction Trial (BEAT)
Authors: Christian Torp‐Pedersen, Lars Køber, Stephen Ball, Alistair Hall, Bente Brendorp, Michael Mundt Ottesen, Jens Berning, Gorm Jensen, John Hampton, Peter Zilles, Siegfried Eberle, Jan Carlsen
Journal: European Journal of Heart Failure (2002)
Risk factors for self-reported hospitalizations among stable outpatients with COPD
Authors: David Coultas, Bradford Jackson, Minyong Uhm, Karan Singh, Sejong Bae
Journal: European Respiratory Journal (2013)

Background: Investigations of risk factors for hospitalizations among patients with COPD have focused on selected patients with COPD hospitalizations and readmissions (COPD-H).  Objectives: To minimize potential selection bias, risk factors associated with COPD-H and non-COPD-H (NCOPD-H) were examined in a sample of 325 stable outpatients.  Methods: Analysis of baseline data from patients enrolled in a clinical trial. Characteristics examined included demographics, smoking, symptoms, physiologic impairment, co-morbidities, and health-related quality of life. Multiple logistic regression was used to examine independent associations with COPD-H and NCOPD-H.  Results: Of patients enrolled mean age (SD) was 69 (10) years, 51% female, 92% white. COPD-H and NCOPD-H were reported by 14.2% and 9.5%, respectively. Significant (p  Conclusions: Depressive symptoms are consistently associated with all hospitalizations. Whereas, fatigue, emotional coping, severity of COPD impairment are also associated with COPD-H. These factors offer potential targets to prevent hospitalizations among patients with COPD.  Funding: NIH R18 HL092955.
Association of increased telomere lengths in limited scleroderma, with a lack of age-related telomere erosion
Authors: A MacIntyre, S W Brouilette, K Lamb, K Radhakrishnan, L McGlynn, M M Chee, E K Parkinson, D Freeman, R Madhok, P G Shiels
Journal: Annals of the Rheumatic Diseases (2008)

Telomere erosion, a feature of biological ageing, is implicated in a wide range of diseases. Its impact on autoimmune diseases remains unclear although autoantibodies against many telomere nucleoprotein components are prevalent in these diseases. We aimed to assess if telomere biology was abnormal in a cohort of patients with limited cutaneous systemic sclerosis (lcSSc).Telomere lengths in peripheral blood leucocytes (PBL) were determined using Southern blotting methods in a cohort of lcSSc subjects (n=43; age range 37-80 years) and a control population (n=107; age range 21-65 years).Telomere lengths in lcSSc subjects were longer than controls (p<0.001), did not show age-related telomere erosion and differed significantly from age-matched controls only after 50 years of age (p<0.001).This is the first report of maintenance of telomere lengths in an autoimmune disease state. These data indicate aberrant telomere biology and irregular biological ageing from the fifth decade of life. These findings provide insight into compromised DNA damage repair in lcSSc. Whether these observations indicate a causal or consequential relationship requires further investigation. This in turn, may provide potential novel targets for therapeutic intervention.
Thiazolidinedione- and tumor necrosis factor alpha–induced downregulation of peroxisome proliferator–activated receptor gamma mRNA in differentiated 3T3-L1 adipocytes
Authors: Stéphane Perrey, Shun Ishibashi, Naoya Yahagi, Jun-ichi Osuga, Ryuichi Tozawa, Hiroaki Yagyu, Ken Ohashi, Takanari Gotoda, Kenji Harada, Zhong Chen, Yoko Iizuka, Futoshi Shionoiri, Nobuhiro Yamada
Journal: Metabolism (2001)
The effect of topically applied progesterone on sebum excretion rate
Authors: N.B. SIMPSON, P.E. BOWDEN, R.A. FORSTER, W.J. CUNLIFFE
Journal: British Journal of Dermatology (1979)

There is evidence that anti-androgens may help in the treatment of acne vulgaris. We therefore performed a double-blind trial to assess the effect of topically applied progesterone on sebum excretion rate. Thirty-eight patients took part in the trial which was for 3 months. The preparation had no etfect in males. However, a signiticant reduction in sebum excretion rate was found in females, the etfect being maximal at the end of the second month. There was a significant loss of effect at the end of the third month and this was not related to deterioration of the progesterone preparation.
How should Helicobacter pylori positive dyspeptic patients be managed?
Authors: N J Talley
Journal: Gut (1999)

Dyspepsia, according to the internationally accepted Rome criteria, refers to pain or discomfort centred in the upper abdomen; patients with predominant heartburn are excluded from this group, although minor or infrequent heartburn is commonly associated with dyspepsia. It is an important condition not only because it is common and costly, but because it may indicate the presence of serious disease such as peptic ulcer or gastric cancer. However, the most frequent causes of dyspepsia are functional dyspepsia and gastro-oesophageal reflux disease. The discovery of Helicobacter pylori has resulted in important advances in the management of dyspepsia. The clinician faced with a patient who has persistent or recurrent dyspepsia needs to differentiate clearly those patients who have not been previously investigated from patients documented to have functional dyspepsia after investigation (fig 1). Here, the management of H pylori positive dyspeptic patients who have and have not been fully investigated will be reviewed.
Evolution of the Insect Desaturase Gene Family with an Emphasis on Social Hymenoptera
Authors: Martin Helmkampf, Elizabeth Cash, Jürgen Gadau
Journal: Molecular Biology and Evolution (2014)

Desaturase genes are essential for biological processes, including lipid metabolism, cell signaling, and membrane fluidity regulation. Insect desaturases are particularly interesting for their role in chemical communication, and potential contribution to speciation, symbioses, and sociality. Here, we describe the acyl-CoA desaturase gene families of 15 insects, with a focus on social Hymenoptera. Phylogenetic reconstruction revealed that the insect desaturases represent an ancient gene family characterized by eight subfamilies that differ strongly in their degree of conservation and frequency of gene gain and loss. Analyses of genomic organization showed that five of these subfamilies are represented in a highly microsyntenic region conserved across holometabolous insect taxa, indicating an ancestral expansion during early insect evolution. In three subfamilies, ants exhibit particularly large expansions of genes. Despite these expansions, however, selection analyses showed that desaturase genes in all insect lineages are predominantly undergoing strong purifying selection. Finally, for three expanded subfamilies, we show that ants exhibit variation in gene expression between species, and more importantly, between sexes and castes within species. This suggests functional differentiation of these genes and a role in the regulation of reproductive division of labor in ants. The dynamic pattern of gene gain and loss of acyl-CoA desaturases in ants may reflect changes in response to ecological diversification and an increased demand for chemical signal variability. This may provide an example of how gene family expansions can contribute to lineage-specific adaptations through structural and regulatory changes acting in concert to produce new adaptive phenotypes.