tbuckley/cabot-search huggingface dataset:
An evaluation of 75Se Selenomethionine scanning as a test of pancreatic function compared with the secretin-pancreozymin test
Authors: J. Braganza, M. Critchley, H. T. Howat, H. J. Testa, H. B. Torrance
Journal: Gut (1973)

The uptake of 75Se Selenomethionine by the pancreas has been evaluated in 102 patients and compared with the secretin-pancreozymin test of pancreatic function.In groups of patients with chronic pancreatitis and cancer of the pancreas abnormal scans closely parallel the diminished exocrine secretion, especially bicarbonate output, following a submaximal dose of secretin.Thirty per cent of the group with no pancreatic abnormality have abnormal scans, though the secretin- pancreozymin test is normal.Though a normal scan excludes the presence of chronic pancreatitis and cancer of the pancreas with a probability greater than 90%, an abnormal scan is found so frequently in normal subjects that it does not provide a reliable index of impaired pancreatic function.383 Reasonfor Omission No. of Cases Incomplete follow up 5 Gastro-jejunostomy 2 Incomplete record of data from secretin-pancreozymin test 1 1 Patient intolerant of gastroduodenal tube 3 Specimen lost or broken
Respiratory education: a dangerous drift away from academia?
Authors: M. Polkey, T. Howes, G. Burns, S. G. Spiro
Journal: European Respiratory Journal (2008)

The education of specialist doctors in respiratory medicine has evolved over a long time. The importance of the clinical apprenticeship was stressed by Hippocrates and evolved through European medicine into the 20th century. Part of this clinical apprenticeship has developed into an early exposure to medical research. A minority of medical students are able to be involved in this process before final examinations, but in past decades junior doctors gained their initial experience during the first few years of their career. Many senior doctors remember these experiences with great fondness. These small pieces of clinical research, and the resultant abstracts at local meetings produced by these junior doctors, sowed the seeds for a life-long interest in medical research.

Over recent years, the taught element of junior doctors’ training, at least in the UK, has increased. In many ways, this has benefited the training process. However, the pressures to achieve parity of training across Europe, and to shorten training to meet a perceived need for an expansion in the number of senior doctors to cope with all that respiratory medicine has to cover, has led to a perception that research in training is much less sought after and important to those trainees planning …
CXCL9, but not CXCL10, Promotes CXCR3-Dependent Immune-Mediated Kidney Disease
Authors: Julia Menke, Geraldine C. Zeller, Eriya Kikawada, Terry K. Means, Xiao R. Huang, Han Y. Lan, Bao Lu, Joshua Farber, Andrew D. Luster, Vicki R. Kelley
Journal: Journal of the American Society of Nephrology (2008)

Chemokines are instrumental in macrophage- and T cell-dependent diseases. The chemokine CCL2 promotes kidney disease in two models of immune-mediated nephritis (MRL-Fas(lpr) mice and the nephrotoxic serum nephritis model), but evidence suggests that multiple chemokines are involved. For identification of additional therapeutic targets for immune-mediated nephritis, chemokine ligands and receptors in CCL2-/- and wild-type (WT) MRL-Fas(lpr) kidneys were profiled. The focus was on intrarenal chemokine ligand/receptor pairs that were highly upregulated downstream of CCL2; the chemokine CXCL10 and its cognate receptor, CXCR3, stood out as potential therapeutic targets. However, renal disease was not suppressed in CXCL10-/- MRL-Fas(lpr) mice, and CXCL10-/- C57BL/6 mice were not protected from nephrotoxic serum nephritis compared with WT mice. Because CXCR3 engages with the ligand CXCL9, CXCR3-/- , CXCL9-/- , and CXCL10-/- B6 mice were compared with WT mice with nephrotoxic serum nephritis. Kidney disease, measured by loss of renal function and histopathology, was suppressed in both CXCR3-/- and CXCL9-/- mice but not in CXCL10-/- mice. With nephrotoxic serum nephritis, CXCR3-/- and CXCL9-/- mice had fewer intrarenal activated T cells and activated macrophages. Both IgG glomerular deposits and antigen-specific IgG in serum were reduced in these mice, suggesting that although CXCR3 and CXCL9 initiate nephritis through cell-mediated events, renal inflammation may be sustained by their regulation of IgG. It is concluded that specific blockade of CXCL9
Extracorporeal pumpless interventional lung assist in clinical practice: determinants of efficacy
Authors: T. Müller, M. Lubnow, A. Philipp, T. Bein, A. Jeron, A. Luchner, L. Rupprecht, M. Reng, J. Langgartner, C. E. Wrede, M. Zimmermann, D. Birnbaum, C. Schmid, G. A. J. Riegger, M. Pfeifer
Journal: European Respiratory Journal (2008)

Respiratory acidosis can become a serious problem during protective ventilation of severe lung failure. A pumpless arteriovenous interventional lung assist (iLA) for extracorporeal carbon dioxide removal has been used increasingly to control critical respiratory situations. The present study sought to evaluate the factors determining the efficacy of iLA and calculate its contribution to gas exchange. In a cohort of 96 patients with severe acute respiratory distress syndrome, haemodynamic parameters, oxygen consumption and carbon dioxide production as well as gas transfer through the iLA were analysed. The measurements demonstrated a significant dependency of blood flow via the iLA device on cannula size (mean± sd 1.59±0.52 L·min −1 for 15 French (Fr), 1.94±0.35 L·min −1 for 17 Fr, and 2.22 ±0.45 L·min −1 for 19 Fr) and on mean arterial pressure. Oxygen transfer capacity averaged 41.7±20.8 mL·min −1 , carbon dioxide removal was 148.0±63.4 mL·min −1 . Within two hours of iLA treatment, arterial oxygen partial pressure/inspired oxygen fraction ratio increased significantly and a fast improvement in arterial carbon dioxide partial pressure and pH was observed. Interventional lung assist eliminates ∼50% of calculated total carbon dioxide production with rapid normalisation of respiratory acidosis. Despite limited contribution to oxygen transfer it may allow a more protective ventilation in severe respiratory failure.
In Vitro Evidence Of The Synergistic Effect Of Non Steroidal Anti Inflammatory Drugs (NSAIDs) Into Ig-E Mediated Food Allergy Response In Basophils
Authors: J. Bartra, M. Pascal, R. Vilella, J. Mila, R. Muñoz-Cano, J. Sanchez-Lopez, A. Valero, C. Picado
Journal: Journal of Allergy and Clinical Immunology (2011)
Controlled attenuation parameter (CAP) for the diagnosis of steatosis: A prospective study of 5323 examinations
Authors: Victor de Lédinghen, Julien Vergniol, Maylis Capdepont, Faiza Chermak, Jean-Baptiste Hiriart, Christophe Cassinotto, Wassil Merrouche, Juliette Foucher, Le Bail Brigitte
Journal: Journal of Hepatology (2014)
<i>RHPN2</i> Drives Mesenchymal Transformation in Malignant Glioma by Triggering RhoA Activation
Authors: Carla Danussi, Uri David Akavia, Francesco Niola, Andreja Jovic, Anna Lasorella, Dana Pe'er, Antonio Iavarone
Journal: Cancer Research (2013)

Mesenchymal transformation is a hallmark of aggressive glioblastoma (GBM). Here, we report the development of an unbiased method for computational integration of copy number variation, expression, and mutation data from large datasets. Using this method, we identified rhophilin 2 (RHPN2) as a central genetic determinant of the mesenchymal phenotype of human GBM. Notably, amplification of the human RHPN2 gene on chromosome 19 correlates with a dramatic decrease in the survival of patients with glioma. Ectopic expression of RHPN2 in neural stem cells and astrocytes triggered the expression of mesenchymal genes and promoted an invasive phenotype without impacting cell proliferation. Mechanistically, these effects were implemented through RHPN2-mediated activation of RhoA, a master regulator of cell migration and invasion. Our results define RHPN2 amplification as a central genetic determinant of a highly aggressive phenotype that directs the worst clinical outcomes in patients with GBM.
Survival and Late Effects in Children With Hodgkin's Lymphoma Treated With MOPP/ABV and Low-Dose, Extended-Field Irradiation
Authors: Lionel M.L. Chow, Paul C. Nathan, David C. Hodgson, Derek Jenkin, Sheila Weitzman, Ronald M. Grant, David Manson, Adee Bross, John J. Doyle, Cyril Danjoux, Mark L. Greenberg
Journal: Journal of Clinical Oncology (2006)

Reduced-intensity protocols for pediatric Hodgkin's lymphoma are aimed at preserving excellent relapse-free survival while decreasing the incidence of late effects.We retrospectively reviewed the outcome of 123 children treated consecutively for Hodgkin's lymphoma at a single institution. Patients with stages I-IIIB disease received three cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/ doxorubicin, bleomycin, and vinblastine (ABV) followed by 15 Gy of extended-field irradiation, while those with stage IV disease were treated with six to eight cycles of MOPP/ABV chemotherapy with or without radiotherapy.At a median follow-up of 8.5 years (range, 1.4 to 15.5 years), the estimated 10-year overall survival and event-free survival are 94% (SE, 2.2%) and 88% (SE, 3.1%) respectively. There have been 12 treatment failures and six disease-related deaths. A very large mediastinal mass ( 50% of the maximal thoracic diameter) was associated with a 10-year event-free survival of 50% (SE, 14%) compared with 91% (SE, 4.0%) for smaller masses (P < .001). Late cardiopulmonary toxicity is largely absent, and the incidence of hypothyroidism is 14%. There have been no cases of secondary leukemia and four secondary solid malignancies observed to date.MOPP/ABV and low-dose, extended-field radiotherapy is an effective treatment for pediatric Hodgkin's lymphoma. With median follow-up of 8.5 years, late cardiopulmonary effects and secondary malignancies from this treatment regimen are infrequent. Continued longitudinal observations, particularly for breast cancer in female patients and gonadotoxicity, will determine whether the goal of decreasing treatment-related complications while maintaining excellent survival has been achieved.
MyD88 Primes Macrophages for Full-Scale Activation by Interferon-γ yet Mediates Few Responses to <i>Mycobacterium tuberculosis </i>
Authors: Shuangping Shi, Carl Nathan, Dirk Schnappinger, Jörg Drenkow, Michele Fuortes, Ellen Block, Aihao Ding, Thomas R. Gingeras, Gary Schoolnik, Shizuo Akira, Kiyoshi Takeda, Sabine Ehrt
Journal: The Journal of Experimental Medicine (2003)

Macrophages are activated from a resting state by a combination of cytokines and microbial products. Microbes are often sensed through Toll-like receptors signaling through MyD88. We used large-scale microarrays in multiple replicate experiments followed by stringent statistical analysis to compare gene expression in wild-type (WT) and MyD88-/- macrophages. We confirmed key results by quantitative reverse transcription polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay. Surprisingly, many genes, such as inducible nitric oxide synthase, IRG-1, IP-10, MIG, RANTES, and interleukin 6 were induced by interferon (IFN)-gamma from 5- to 100-fold less extensively in MyD88-/- macrophages than in WT macrophages. Thus, widespread, full-scale activation of macrophages by IFN-gamma requires MyD88. Analysis of the mechanism revealed that MyD88 mediates a process of self-priming by which resting macrophages produce a low level of tumor necrosis factor. This and other factors lead to basal activation of nuclear factor kappaB, which synergizes with IFN-gamma for gene induction. In contrast, infection by live, virulent Mycobacterium tuberculosis (Mtb) activated macrophages largely through MyD88-independent pathways, and macrophages did not need MyD88 to kill Mtb in vitro. Thus, MyD88 plays a dynamic role in resting macrophages that supports IFN-gamma-dependent activation, whereas macrophages can respond to a complex microbial stimulus, the tubercle bacillus, chiefly by other routes.
Increased Expression of Mitotic Checkpoint Genes in Breast Cancer Cells with Chromosomal Instability
Authors: Bibo Yuan, Yi Xu, Ju-Hyung Woo, Yunyue Wang, Young Kyung Bae, Dae-Sung Yoon, Robert P. Wersto, Ellen Tully, Kathleen Wilsbach, Edward Gabrielson
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Most breast cancers have chromosomal instability that seems related to defective mitotic spindle checkpoints. Because the molecular basis of this defect is unknown, we evaluated breast cancer cell lines and tissues for possible defects involving the major mitotic checkpoint genes responsible for maintaining chromosomal stability. Experimental Design: We analyzed sequences and expression levels (RNA and protein) of eight major spindle checkpoint genes (MAD1L1, MAD2L1, MAD2L2, BUB1, BUB1B, BUB3, CDC20, and TTK) in a panel of 12 breast cancer cell lines, most with established genetic instability and defective spindle damage checkpoint response. mRNA levels of these genes were also measured in primary tumor samples, and immunohistochemical staining was used to evaluate BUB1B protein levels in a panel of 270 additional cases of breast cancer. Results: No functionally significant sequence variations were found for any of the eight genes in the breast cancer cell lines with chromosomal instability. More surprisingly, the mRNA and protein levels for these checkpoint genes are significantly higher in the genetically unstable breast cancer cell lines and in high-grade primary breast cancer tissues than in the stable (and checkpoint proficient) MCF-10A and normal mammary epithelial cells, or in normal breast tissues. In fact, overexpression of the BUB1B protein is a marker that recognizes nearly 80% of breast cancers in paraffin-embedded tissues. Conclusions: Defective mitotic spindle checkpoints in breast cancer are most likely not caused by low expression or mutations of these eight checkpoint genes. High levels of these particular transcripts could represent a cellular compensation for defects in other molecular components of the mitotic spindle damage checkpoint, and increased expression of these genes might be markers of breast cancers with chromosomal instability.
Randomized Placebo-Controlled Trial of Ursodeoxycholic Acid With Vitamin E in Nonalcoholic Steatohepatitis
Authors: Jean–François Dufour, Carl M. Oneta, Jean–Jacques Gonvers, Florian Bihl, Andreas Cerny, Jean–Michel Cereda, Jean–Franco Zala, Beat Helbling, Michael Steuerwald, Arthur Zimmermann
Journal: Clinical Gastroenterology and Hepatology (2006)
Childhood Abuse and Psychiatric Disorders Among Single and Married Mothers
Authors: Ellen L. Lipman, Harriet L. MacMillan, Michael H. Boyle
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: This study examined the prevalence of, and association between, childhood abuse and psychiatric disorders in single and married mothers. METHOD: Single and married mothers who participated in the Ontario Health Survey, a province-wide study derived from a probability sample of the general population of Ontario aged 15 years and older (N=1,471), were included. Sociodemographic and mental health characteristics were collected by means of interviewer-administered questionnaires. A self-administered questionnaire was used to collect information on childhood physical and sexual abuse. RESULTS: Compared with married mothers, single mothers reported substantially lower incomes as well as higher rates of childhood abuse and all psychiatric morbidities examined (current and lifetime affective or anxiety disorders and substance use disorders). Childhood abuse had a consistent and significant association with adult mental health, even when other risk variables were controlled. No interaction among childhood abuse and marital status and outcome was found. CONCLUSIONS: Single mothers reported more childhood abuse and experienced higher levels of poverty and psychiatric disorders than married mothers. Childhood abuse was associated with more psychiatric problems in both single and married mothers. Research, clinical, and policy implications of these findings are discussed.
Ovarian Cancer Risk After Salpingectomy: A Nationwide Population-Based Study
Authors: H. Falconer, L. Yin, H. Gronberg, D. Altman
Journal: JNCI Journal of the National Cancer Institute (2015)

Background:Recent genetic and morphologic studies have challenged the traditional view on the pathogenesis of ovarian cancer; suggesting that ovarian cancer predominantly arises within the fallopian tubes or the uterus. We hypothesize that surgical removal of the fallopian tubes is associated with a reduced risk for ovarian cancer.
White Matter Structural Differences in Young Children With Type 1 Diabetes: A Diffusion Tensor Imaging Study
Authors: Tandy Aye, Naama Barnea-Goraly, Christian Ambler, Sherry Hoang, Kristin Schleifer, Yaena Park, Jessica Drobny, Darrell M. Wilson, Allan L. Reiss, Bruce A. Buckingham
Journal: Diabetes Care (2012)

To detect clinical correlates of cognitive abilities and white matter (WM) microstructural changes using diffusion tensor imaging (DTI) in young children with type 1 diabetes.Children, ages 3 to <10 years, with type 1 diabetes (n = 22) and age- and sex-matched healthy control subjects (n = 14) completed neurocognitive testing and DTI scans.Compared with healthy controls, children with type 1 diabetes had lower axial diffusivity (AD) values (P = 0.046) in the temporal and parietal lobe regions. There were no significant differences between groups in fractional anisotropy and radial diffusivity (RD). Within the diabetes group, there was a significant, positive correlation between time-weighted HbA(1c) and RD (P = 0.028). A higher, time-weighted HbA(1c) value was significantly correlated with lower overall intellectual functioning measured by the full-scale intelligence quotient (P = 0.03).Children with type 1 diabetes had significantly different WM structure (as measured by AD) when compared with controls. In addition, WM structural differences (as measured by RD) were significantly correlated with their HbA(1c) values. Additional studies are needed to determine if WM microstructural differences in young children with type 1 diabetes predict future neurocognitive outcome.
Molecular interactions of ErbB1 (EGFR) and integrin- 1 in astrocytoma frozen sections predict clinical outcome and correlate with Akt-mediated in vitro radioresistance
Authors: M. Petras, T. Lajtos, E. Friedlander, A. Klekner, E. Pintye, B. G. Feuerstein, J. Szollosi, G. Vereb
Journal: Neuro-Oncology (2013)

Treatment of astrocytoma is frequently hampered by radioresistance of the tumor. In addition to overexpression of ErbB1/EGFR, functional crosstalk between receptor tyrosine kinases and cell adhesion molecules may also contribute to therapy resistance. Acceptor photobleaching FRET was implemented on frozen sections of clinical astrocytoma to check the role of ErbB1–integrin-β1 interaction. U251 glioma subclones were obtained by introducing extra CHR7 material or the ErbB1 gene to test the relevance and mechanism of this interaction in vitro. Grade IV tumors showed higher ErbB1 and integrin-β1 expression and greater ErbB1–integrin-β1 heteroassociation than did grade II tumors. Of these, the extent of molecular association was a single determinant of tumor grade and prognosis in stepwise logistic regression. In vitro, integrin-β1 was upregulated, and radiosensitivity was diminished by ectopic ErbB1 expression. Great excess of ErbB1 provided colony forming advantage over medium excess but did not yield better radiation resistance or faster proliferation and decreased to medium level over time, whereas integrin-β1 levels remained elevated and defined the extent of radioresistance. Increased expression of ErbB1 and integrin-β1 was paralleled by decreasing ErbB1 homoassociation and increasing ErbB1–integrin-β1 heteroassociation. Microscopic two-sided FRET revealed that pixels with higher ErbB1–integrin-β1 heteroassociation exhibited lowed ErbB1 homoassociation, indicating competition for association partners among these molecules. Boosted Akt phosphorylation response to EGF accompanied this shift toward heteroassociation, and the consequentially increased radioresistance could be reverted by inhibiting PI3K. The clinically relevant ErbB1–integrin-β1 heteroassociation may be used as a target of both predictive diagnostics and molecular therapy.
Injuries in World Cup telemark skiing: a 5-year cohort study
Authors: Melissa Woll Johansen, Sophie E Steenstrup, Tone Bere, Roald Bahr, Lars Nordsletten
Journal: British Journal of Sports Medicine (2015)

There are limited data on injuries in World Cup (WC) telemark skiing.To describe the injury incidence and injury pattern seen among WC telemark skiers during the competitive season.We interviewed all WC athletes (or their coach, if the athlete was not present) at the end of five winter seasons from 2008 until 2013. All acute injuries occurring in the competitive season that required the attention of medical personnel were registered. Exposure was calculated based on the official International Ski Federation (FIS) results database.149 acute injuries were registered during 565 WC skier seasons. The absolute injury incidence was 26.4 injuries per 100 athletes per season (95% CI 22.1 to 30.6), higher for females than males (risk ratio (RR) 1.49, 95% CI 1.07 to 2.08). During the FIS WC competitions, 69 injuries were registered, corresponding to a relative incidence of 8.2 injuries per 1000 runs (95% CI 6.3 to 10.1). The most frequently injured body part was the knee (21%) followed by the hand-finger-thumb (20%), ankle (13%) and shoulder/clavicle (13%). The absolute risk of knee and shoulder/clavicle injuries was higher for females versus males (RR for knee injuries 2.72, 95% CI 1.35 to 5.51; RR for shoulder/clavicle injuries 2.55, 95% CI 1.06 to 6.14). No differences were detected in the injury incidence between disciplines.Female telemark skiers are at 1.5 times greater risk of injury than male skiers. The most commonly injured body part was the knee. The risk of knee and shoulder/clavicle injuries was higher for female athletes than for male athletes.
Segment-specific differences in the inward rectifier K+ current along the renal interlobular artery
Authors: Lisa Chilton, Sergey V. Smirnov, Kathy Loutzenhiser, Xuemei Wang, Rodger Loutzenhiser
Journal: Cardiovascular Research (2011)

Aims:We investigated the role of the inward rectifier K + channel (K IR ) in the renal interlobular artery (ILA).The ILA supplies the afferent arteriole and ranges in diameter from >100 µm near its origin at the arcuate artery to <30 µm at its most distal segment. Methods and Results:Vasodilatory responses to elevated extracellular K + (15 mmol/L) and vasoconstrictor responses due to K IR blockade by Ba 2+ (10-100 µmol/L) were assessed in in vitro perfused hydronephrotic rat kidneys.The distal ILA (26±1 µm) exhibited K + -induced dilation and Ba 2+ -induced vasoconstriction; whereas, neither response was observed in the proximal ILA (108±3 µm).The intermediate ILA (55±1 µm) exhibited a modest K + -induced vasodilatation, but no Ba 2+ -induced vasoconstriction.The K + -induced dilations were blocked by Ba 2+ , but not by ouabain.Ba 2+ -induced depolarization, measured in ILA segments from normal kidneys, decreased with the increasing diameter.Patch clamp studies demonstrated that the K IR current (I KIR ) density also was inversely correlated with ILA segment diameter.Myocytes from afferent arterioles and distal ILAs exhibited similarly large I KIR , whereas, this current was absent in proximal ILA myocytes.Finally, we found that Ba 2+ attenuated myogenic vasoconstriction, suggesting an involvement of I KIR .The previously shown pattern of myogenic reactivity of the ILA (distal > intermediate>proximal) mirrors the distribution of I KIR reported in the present study, further supporting a role for I KIR . Conclusions:Our findings indicate differences in the magnitude of I KIR along the ILA and suggest that the influence of K IR on reactivity increases as vessel diameter decreases from proximal to distal regions.