tbuckley/cabot-search huggingface dataset:
Further emergent evidence for the vitamin D endocrine system involvement in autoimmune rheumatic disease risk and prognosis
Authors: Maurizio Cutolo
Journal: Annals of the Rheumatic Diseases (2013)

Recently, vitamin D has received increased worldwide attention for its involvement in reducing risk for several chronic diseases including many cancers, infectious diseases, type 1 diabetes and notably autoimmune rheumatic diseases.1

The final active metabolite of vitamin D (1,25(OH)D3) is considered a steroid hormone for its origin from cholesterol (D-hormone), and like glucocorticoids exerts immunomodulatory activities (figure 1).2 ,3



Figure 1 
Newly identified target genes for calcitriol (D hormone) reveal multiple molecular pathways of anti-inflammatory actions for 1,25(OH)D3 in several cell types. These include: inhibition of prostaglandin (PG) synthesis and biological actions; inhibition of p38 stress kinase activation and production of proinflammatory cytokines such as IL-6 (via induction of MAP kinase phosphatase 5 (MKP5 expression); inhibition of nuclear factor κB (NF-κB) signalling which results in the attenuation of the synthesis of proinflammatory cytokines such as interleukin-8 (IL-8) (via up-regulation of the expression of insulin-like growth factor binding protein-3 (IGFBP-3); inhibition of angiogenesis due to suppressive effects on the expression of proangiogenic factors such as hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor; increase in the expression of E-cadherin, leading to the inhibition of invasion and metastasis. Solid lines indicate direct actions of calcitriol, and dotted lines indicate downstream effects of calcitriol.



Pathophysiological investigations confirm that severe hypovitaminosis D, in genetically predisposed subjects, can impair self tolerance and immune responses by compromising the regulation of dendritic cells, regulatory T-lymphocytes (Tregs), Th1 cells and B cell function.3

Cross-sectional studies have shown that deficient serum levels of vitamin D (25(OH)D) (<20 ng/ml) are present in a significant percentage, not only in patients with autoimmune diseases such as multiple sclerosis (MS), type 1 diabetes, systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA), but also in healthy subjects.4 ,5 In addition, the presence of severe 25(OH)D deficiency (<10 ng/ml) …
Reproducibility of ambulatory oesophageal pH monitoring.
Authors: F Johnsson, B Joelsson
Journal: Gut (1988)

To evaluate the reproducibility of ambulatory 24 hour intraoesophageal pH monitoring, 20 patients were randomly selected to undergo two consecutive investigations. Fifteen patients were classified as either abnormal, or normal on both test days. The amount of acid reflux, expressed as percentage of time with oesophageal pH below 4.0 during the two 24 hour periods, showed 77% concordance. The upright and recumbent periods of measurement showed different degrees of concordance: 83% and 62%, respectively. The reproducibility during time periods of different length was found to increase with increasing length of day time pH recording. A 16 hour period during evening and night had a reproducibility of only 58%, however. It is concluded that there is fairly good reproducibility when measuring gastro-oesophageal reflux over 24 hours, but that the reproducibility is poorer at night, during the postprandial period and when daytime monitoring is shorter than 10 hours.
Professionalism in medicine: can patients trust in managed care?
Authors: J. La Puma
Journal: JAMA (1996)

<h3>In Reply.</h3> —Dr La Puma is correct in noting the gap between our vision of how medicine should be practiced and uncomfortable realities. Leaders in medicine have a responsibility to forcefully articulate appropriate norms and use their leverage to influence practice arrangements and the education of future physicians. We believe our recommendations have more potential (and are more controversial) than La Puma's characterization suggests. We called for disclosure of physician incentive payments and suggested that the Health Care Financing Administration's proposed regulations were too limited, but even these regulations face vigorous opposition. We oppose physician-sponsored health care plans because they further confuse conflicting interests between plan financing and organization and physicians' responsibilities to their patients. Even more important, we believe that the profession of medicine must use its educational and regulatory opportunities to reaffirm repeatedly its commitment to full and open communication with patients and speak vigorously in support of this ethic.
Incomplete stimulus representations and the loss of cognitive access in cerebral achromatopsia
Authors: Robert William Kentridge
Journal: Behavioral and Brain Sciences (2007)

Abstract When processing of stimuli occurs without attention, phenomenal experience, as well as cognitive access, may be lost. Sensory representations are, however, constructed by neural machinery extending far beyond sensory receptors. In conditions such as cerebral achromatopsia incomplete sensory representations may still elicit phenomenal experience but these representations might be too aberrant to be integrated into the wider cognitive workspace.
EFFECT OF B-CELL MITOGENS ON LYMPHOCYTE SUBPOPULATIONS POSSESSING C'3 AND Fc RECEPTORS
Authors: Göran Möller
Journal: The Journal of Experimental Medicine (1974)

By the use of a rosette method allowing the detection at the cellular level of lymphocytes simultaneously binding Fc- and C'3-sensitized red cells it was found that about 70% of the rosette-forming cells from spleens of nude and normal mice possessed receptors for both Fc and C'3, whereas 30% only had Fc receptors. Very few, if any, lymphocytes possessed only C'3 receptors. The B-cell mitogens, purified-protein derivative of tuberculin (PPD), lipopolysaccharide from Escherichia coli (LPS), and pneumococcal polysaccharide type SIII (SIII), induced marked changes of these receptor-bearing lymphocytes. PPD caused a rapid loss of cells capable of binding C'3 and a concomitant increase of only Fc-binding cells, which was detected after only 24 h. LPS and SIII induced analogous changes, but they were not detected until 48 h and were not complete until after 72 h. It is suggested that immature lymphocytes possess both Fc and C'3 receptors and lose the latter receptor upon differentiation induced by B-cell mitogens PPD. and LPS would affect different populations of B cells, PPD-activating cells that have already reached a higher differentiation stage, whereas LPS and SIII would activate more immature B cells.
Insulin-Lowering Agents in the Management of Polycystic Ovary Syndrome
Authors: Vincenzo De Leo, Antonio la Marca, Felice Petraglia
Journal: Endocrine Reviews (2003)

Polycystic ovary syndrome (PCOS) is a medical condition that has brought multiple specialists together. Gynecologists, endocrinologists, cardiologists, pediatricians, and dermatologists are all concerned with PCOS patients and share research data and design clinical trials to learn more about the syndrome. Insulin resistance is a common feature of PCOS and is more marked in obese women, suggesting that PCOS and obesity have a synergistic effect on the magnitude of the insulin disorder. Hyperinsulinemia associated with insulin resistance has been causally linked to all features of the syndrome, such as hyperandrogenism, reproductive disorders, acne, hirsutism, and metabolic disturbances. Women with PCOS should be evaluated for cardiovascular risk factors, such as lipid profile and blood pressure. Modification of diet and lifestyle should be suggested to those who are obese. Several insulin-lowering agents have been tested in the management of PCOS. In particular, metformin is the only drug currently in widespread clinical use for treatment of PCOS. In a high percentage of patients, treatment with metformin is followed by regularization of menstrual cycle, reduction in hyperandrogenism and in cardiovascular risk factors, and improvement in response to therapies for induction of ovulation.
Clinical significance of vascular endothelial growth factor and basic fibroblast growth factor gene expression in liver tumor
Authors: M Mise, S Arii, H Higashituji, M Furutani, M Niwano, T Harada, S Ishigami, Y Toda, H Nakayama, M Fukumoto, J Fujita, M Imamura
Journal: Hepatology (1996)

Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. However, the relationship between the vascularity of HCC and the expression of angiogenic factors has not been investigated. In addition, no detailed studies have examined the possible involvement of angiogenic factors in the grade of malignancy of HCC. The aim of this study was to determine which angiogenic factors regulate tumor angiogenesis and contribute to the invasive ability of liver tumors, especially of HCC. Northern blot analysis was used to examine the transcriptional expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF), and acidic FGF in resected surgical specimens (20 HCC and 9 metastatic liver tumors). Correlations between messenger RNA (mRNA) expression and arteriographic findings, as well as histopathological findings, were evaluated. Immunohistochemistry was performed to identify the localization of cells expressing VEGF in HCC. Higher levels of VEGF mRNA were observed in 12 of 20 HCC and 2 of 9 metastatic liver tumors than in corresponding nontumorous tissues. The degree of VEGF mRNA expression was significantly correlated with the intensity of tumor staining in angiograms ( P &lt;.01). On immunohistochemical observation, VEGF protein was intensely detected in HCC cells. Furthermore, basic FGF mRNA was detected in 9 of 20 HCC and was related to the capsular infiltration of cancer cells ( P &lt;.05). In contrast, no significant difference was observed in the very low levels of acidic FGF mRNA found in the tumorous and nontumorous portions of the liver. In conclusion, these results suggest that VEGF contributes to angiogenesis of liver tumors, whereas basic FGF may be involved in the invasion of HCC into the surrounding tissues.
ERYSIPELOID: AN OCCUPATIONAL DISEASE
Authors: T.H. B. BEDFORD
Journal: British Journal of Dermatology (1932)

Journal Article ERYSIPELOID: AN OCCUPATIONAL DISEASE Get access T.H. B. BEDFORD, M.Sc, M.B., Ch.B.Leeds, M.R.C.P.Lond. T.H. B. BEDFORD, M.Sc, M.B., Ch.B.Leeds, M.R.C.P.Lond. Late Medical Receiving Officer to the Leeds General Infirmary Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 44, Issue 7, 1 July 1932, Pages 368–380, https://doi.org/10.1111/j.1365-2133.1932.tb09617.x Published: 01 July 1932
In vivo confocal microscopy for detection and grading of dysplastic nevi: A pilot study
Authors: Giovanni Pellacani, Francesca Farnetani, Salvador Gonzalez, Caterina Longo, Anna Maria Cesinaro, Alice Casari, Francesca Beretti, Stefania Seidenari, Melissa Gill
Journal: Journal of the American Academy of Dermatology (2011)
Increased Vascular Endothelial Growth Factor-C Expression Is Insufficient to Induce Lymphatic Metastasis in Human Soft-Tissue Sarcomas
Authors: Guy Lahat, Alexander Lazar, Xuemei Wang, Wei-Lien Wang, Quan-Sheng Zhu, Kelly K. Hunt, Raphael E. Pollock, Dina Lev
Journal: Clinical Cancer Research (2009)

Unlike carcinomas, soft-tissue sarcoma (STS) rarely exhibit lymphatic spread. Consequently, we examined expression and function of vascular endothelial growth factor (VEGF)-C and STS-associated lymphatic vessel density (LVD) components of this process.VEGF-C and VEGF-A mRNA and VEGF-C protein expression were evaluated in STS, STS cell lines, and breast cancers (reverse transcription-PCR, quantitative reverse transcription-PCR, and ELISA). STS cell conditioned medium after VEGF-C knockdown was examined for endothelial cell proliferation and migration effects (MTS and migration assays). Paraffin-embedded human lymph node-negative and lymph node-positive STS and lymph node-negative and lymph node-positive breast cancers were examined for VEGF-C, D2-40, and CD31 expression (immunohistochemistry). LVD differences were analyzed by Wilcoxon rank-sum tests.STS and breast cancer VEGF-C expression was comparable and higher than normal tissue levels. STS cells secreted functional VEGF-C: STS conditioned medium induced lymphatic endothelial cell proliferation and migration, which was abrogated by STS cell VEGF-C knockdown. STS and breast cancer intratumoral LVD was similar. STS peritumoral LVD (PT-LVD) was reduced versus breast cancer PT-LVD (P < 0.001). Significantly higher PT-LVD was observed in lymph node-positive versus lymph node-negative STS; lymphatic spreading STS subtypes also had higher LVD. STS VEGF-C expression and PT-LVD lacked correlation, and many lymph node-negative STS had high PT-LVD, suggesting complexity in this metastatic process.Compared with breast cancers, STS exhibited lower PT-LVD independent of VEGF-C expression, which may underlie STS lymph node metastasis rarity. Moreover, lymphatic vessels appear necessary but not sufficient to sustain STS lymphatic spread. Examining STS "nonlymphatic" dissemination may help elucidate mechanisms of lymphatic spread, insights critically important to cancer metastasis control.
PTP1B: a new therapeutic target for Rett syndrome
Authors: Lutz Tautz
Journal: Journal of Clinical Investigation (2015)

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder that is characterized by successive loss of acquired cognitive, social, and motor skills and development of autistic behavior. RTT affects approximately 1 in 10,000 live female births and is the second most common cause of severe mental retardation in females, after Down syndrome. Currently, there is no cure or effective therapy for RTT. Approved treatment regimens are presently limited to supportive management of specific physical and mental disabilities. In this issue, Krishnan and colleagues reveal that the protein tyrosine phosphatase PTP1B is upregulated in patients with RTT and in murine models and provide strong evidence that targeting PTP1B has potential as a viable therapeutic strategy for the treatment of RTT.
Increasing incidence of paediatric inflammatory bowel disease in Ontario, Canada: evidence from health administrative data
Authors: E I Benchimol, A Guttmann, A M Griffiths, L Rabeneck, D R Mack, H Brill, J Howard, J Guan, T To
Journal: Gut (2009)

<h3>Objective:</h3> Health administrative databases can be used to track chronic diseases. The aim of this study was to validate a case ascertainment definition of paediatric-onset inflammatory bowel disease (IBD) using administrative data and describe its epidemiology in Ontario, Canada. <h3>Methods:</h3> A population-based clinical database of patients with IBD aged &lt;15 years was used to define cases, and patient information was linked to health administrative data to compare the accuracy of various patterns of healthcare use. The most accurate algorithm was validated with chart data of children aged &lt;18 years from 12 medical practices. Administrative data from the period 1991–2008 were used to describe the incidence and prevalence of IBD in Ontario children. Changes in incidence were tested using Poisson regression. <h3>Results:</h3> Accurate identification of children with IBD required four physician contacts or two hospitalisations (with International Classification of Disease (ICD) codes for IBD) within 3 years if they underwent colonoscopy and seven contacts or three hospitalisations within 3 years in those without colonoscopy (children &lt;12 years old, sensitivity 90.5%, specificity &gt;99.9%; children &lt;15 years old, sensitivity 89.6%, specificity &gt;99.9%; children &lt;18 years old, sensitivity 91.1%, specificity 99.5%). Age- and sex-standardised prevalence per 100 000 population of paediatric IBD has increased from 42.1 (in 1994) to 56.3 (in 2005). Incidence per 100 000 has increased from 9.5 (in 1994) to 11.4 (in 2005). Statistically significant increases in incidence were noted in 0–4 year olds (5.0%/year, p = 0.03) and 5–9 year olds (7.6%/year, p&lt;0.0001), but not in 10–14 or 15–17 year olds. <h3>Conclusion:</h3> Ontario has one of the highest rates of childhood-onset IBD in the world, and there is an accelerated increase in incidence in younger children.
Serine protease HtrA1 modulates chemotherapy-induced cytotoxicity
Authors: J. Chien
Journal: Journal of Clinical Investigation (2006)

Resistance to chemotherapy presents a serious challenge in the successful treatment of various cancers and is mainly responsible for mortality associated with disseminated cancers. Here we show that expression of HtrA1, which is frequently downregulated in ovarian cancer, influences tumor response to chemotherapy by modulating chemotherapy-induced cytotoxicity. Downregulation of HtrA1 attenuated cisplatin- and paclitaxel-induced cytotoxicity, while forced expression of HtrA1 enhanced cisplatin- and paclitaxel-induced cytotoxicity. HtrA1 expression was upregulated by both cisplatin and paclitaxel treatment. This upregulation resulted in limited autoproteolysis and activation of HtrA1. Active HtrA1 induces cell death in a serine protease-dependent manner. The potential role of HtrA1 as a predictive factor of clinical response to chemotherapy was assessed in both ovarian and gastric cancer patients receiving cisplatin-based regimens. Patients with ovarian or gastric tumors expressing higher levels of HtrA1 showed a higher response rate compared with those with lower levels of HtrA1 expression. These findings uncover what we believe to be a novel pathway by which serine protease HtrA1 mediates paclitaxel- and cisplatin-induced cytotoxicity and suggest that loss of HtrA1 in ovarian and gastric cancers may contribute to in vivo chemoresistance.
Viral factors and predicting disease outcomes in chronic hepatitis B
Authors: Peter Revill, Stephen Locarnini
Journal: Gut (2014)

One of the conundrums of chronic infection with the hepatitis B virus (HBV) is identifying those individual patients who are at risk for the development of the serious sequelae of cirrhosis and hepatocellular carcinoma (HCC). It has been estimated that 25–40% of patients with chronic hepatitis B (CHB) who acquire the virus early in life (perinatal or early horizontal transmission from an HBeAg-positive source) will eventually develop these serious and disastrous consequences.1 Viral factors associated with the outcome of CHB include hepatitis B e antigen (HBeAg) status, HBV DNA and HBsAg levels (>2000 IU/mL) in serum, HBV genotype and HBV variants, all of which have been shown to positively enhance the risk for disease progression.2–4 The viral variants considered significant risk factors include the basal core promoter (BCP) mutants A1762T/G1764A which have been strongly associated with the development of HCC.5 However, these viral factor associations are not absolute and the need for a viral biomarker that achieves such a goal in patients with CHB is very strong.

Dr Tai-Chung Tseng and colleagues6 from Taiwan provide compelling evidence that the presence of BCP mutants A1762T/G1764A in patients 1 year after HBeAg seroconversion significantly increases risk of cirrhosis in Asian subjects. Moreover, using a quantitative molecular analysis based on pyrosequencing, they also found that patients harbouring a higher percentage (≥45%) of A1762T BCP mutant, had a higher risk for liver cirrhosis than those with a lower A1762T BCP mutant percentage (<10%). By contrast, the A1762T …
Q fever in the Netherlands: an update on the epidemiology and control measures
Authors: W van der Hoek, F Dijkstra, B Schimmer, P M Schneeberger, P Vellema, C Wijkmans, R ter Schegget, V Hackert, Y van Duynhoven
Journal: Eurosurveillance (2010)

Since the steady rise in human cases which started in 2007, Q fever has become a major public health problem in the Netherlands with 2,357 human cases notified in the year 2009. Ongoing research confirms that abortion waves on dairy goat farms are the primary source of infection for humans, primarily affecting people living close (under 5 km) to such a dairy goat farm. To reverse the trend of the last three years, drastic measures have been implemented, including the large-scale culling of pregnant goats on infected farms.
The Endocannabinoid System as an Emerging Target of Pharmacotherapy
Authors: Pál Pacher, Sándor Bátkai, George Kunos
Journal: Pharmacological Reviews (2006)

The recent identification of cannabinoid receptors and their endogenous lipid ligands has triggered an exponential growth of studies exploring the endocannabinoid system and its regulatory functions in health and disease. Such studies have been greatly facilitated by the introduction of selective cannabinoid receptor antagonists and inhibitors of endocannabinoid metabolism and transport, as well as mice deficient in cannabinoid receptors or the endocannabinoid-degrading enzyme fatty acid amidohydrolase. In the past decade, the endocannabinoid system has been implicated in a growing number of physiological functions, both in the central and peripheral nervous systems and in peripheral organs. More importantly, modulating the activity of the endocannabinoid system turned out to hold therapeutic promise in a wide range of disparate diseases and pathological conditions, ranging from mood and anxiety disorders, movement disorders such as Parkinson9s and Huntington9s disease, neuropathic pain, multiple sclerosis and spinal cord injury, to cancer, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, and osteoporosis, to name just a few. An impediment to the development of cannabinoid medications has been the socially unacceptable psychoactive properties of plant-derived or synthetic agonists, mediated by CB<sub>1</sub> receptors. However, this problem does not arise when the therapeutic aim is achieved by treatment with a CB<sub>1</sub> receptor antagonist, such as in obesity, and may also be absent when the action of endocannabinoids is enhanced indirectly through blocking their metabolism or transport. The use of selective CB<sub>2</sub> receptor agonists, which lack psychoactive properties, could represent another promising avenue for certain conditions. The abuse potential of plant-derived cannabinoids may also be limited through the use of preparations with controlled composition and the careful selection of dose and route of administration. The growing number of preclinical studies and clinical trials with compounds that modulate the endocannabinoid system will probably result in novel therapeutic approaches in a number of diseases for which current treatments do not fully address the patients9 need. Here, we provide a comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy.