tbuckley/cabot-search huggingface dataset:
Increased degradation of type I collagen in patients with inflammatory bowel disease.
Authors: J Silvennoinen, L Risteli, T Karttunen, J Risteli
Journal: Gut (1996)

To assess the mechanisms of osteopenia in inflammatory bowel disease (IBD), the serum markers of bone formation (osteocalcin and carboxyterminal propeptide of type I procollagen (PICP)) and bone degradation (carboxyterminal telopeptide of type I collagen (ICTP)), the bone mineral density (BMD) of the lumbar spine and the proximal femur and calcium intake of 150 unselected IBD patients and 73 healthy controls were investigated. The patients had higher ICTP values (3.69 (SD 1.40) microgram/l) than the healthy controls (3.25 (1.00) microgram/l, p = 0.035), but no differences in serum PICP and osteocalcin between these groups were detected. In the patients, the ICTP, PICP, and osteocalcin values did not have any significant correlation with BMD, but the patients with ICTP values above 3.6 microgram/l had significantly lower Z scores than those with lower ICTP. In the controls, however, a positive correlation between serum ICTP and BMD was found. The ulcerative colitis patients with total colitis had higher values of ICTP (3.96 (1.58) microgram/l) than those with a left sided disease (3.04 (0.86) micrograms/l, p = 0.009). The patients with a history of clinically active disease (n = 20) had higher ICTP (4.58 (1.55) microgram/l) and osteocalcin (12.56 (5.64) microgram/l) values than the patients (n = 130) with quiescent disease (ICTP 3.56 (1.33), p = 0.002, and osteocalcin 9.76 (3.62), p = 0.017). Increased serum osteocalcin, PICP, and ICTP concentrations and reduced BMD Z scores were found in a subgroup of Crohn9s disease patients with a history of an active disease (n = 11). Raised serum ICTP and normal values of osteocalcin and PICP in IBD patients show increased breakdown of type I collagen without a compensatory increase in its synthesis suggesting an increased rate of bone degradation as a probable mechanism for osteopenia in IBD. Raised ICTP values are related to reduced bone mineral densities.
Celsius: a community resource for Affymetrix microarray data
Authors: Allen Day, Marc RJ Carlson, Jun Dong, Brian D O'Connor, Stanley F Nelson
Journal: Genome biology (2007)

Abstract Celsius is a data warehousing system to aggregate Affymetrix CEL files and associated metadata. It provides mechanisms for importing, storing, querying, and exporting large volumes of primary and pre-processed microarray data. Celsius contains ten billion assay measurements and affiliated metadata. It is the largest publicly available source of Affymetrix microarray data, and through sheer volume it allows a sophisticated, broad view of transcription that has not previously been possible.
C/EBP-Homologous Protein (CHOP) in Vascular Smooth Muscle Cells Regulates Their Proliferation in Aortic Explants and Atherosclerotic Lesions
Authors: Alex-Xianghua Zhou, Xiaobo Wang, Chyuan Sheng Lin, Jaeseok Han, Jing Yong, Marissa J. Nadolski, Jan Borén, Randal J. Kaufman, Ira Tabas
Journal: Circulation Research (2015)

Myeloid-derived C/EBP-homologous protein (CHOP), an effector of the endoplasmic reticulum stress-induced unfolded protein response, promotes macrophage apoptosis in advanced atherosclerosis, but the role of CHOP in vascular smooth muscle cells (VSMCs) in atherosclerosis is not known.To investigate the role of CHOP in SM22α(+) VSMCs in atherosclerosis.Chop(fl/fl) mice were generated and crossed into the Apoe(-/-) and SM22α-CreKI(+) backgrounds. SM22α-CreKI causes deletion of floxed genes in adult SMCs. After 12 weeks of Western-type diet feeding, the content of α-actin-positive cells in aortic root lesions was decreased in Chop(fl/fl)SM22α-CreKI(+)Apoe(-/-) versus control Chop(fl/fl)Apoe(-/-) mice, and aortic explant-derived VSMCs from the VSMC-CHOP-deficient mice displayed reduced proliferation. Krüppel-like factor 4 (KLF4), a key suppressor of VSMC proliferation, was increased in lesions and aortic VSMCs from Chop(fl/fl)SM22α-CreKI(+)Apoe(-/-) mice, and silencing Klf4 in CHOP-deficient VSMCs restored proliferation. CHOP deficiency in aortic VSMCs increased KLF4 through 2 mechanisms mediated by the endoplasmic reticulum stress effector activating transcription factor 4: transcriptional induction of Klf4 mRNA and decreased proteasomal degradation of KLF4 protein.These findings in SM22α-CHOP-deficient mice imply that CHOP expression in SM22α(+) VSMCs promotes cell proliferation by downregulating KLF4. The mechanisms involve newly discovered roles of CHOP in the transcriptional and post-translational regulation of KLF4.
Power Doppler ultrasonography and synovitis: correlating ultrasound imaging with histopathological findings and evaluating the performance of ultrasound equipments
Authors: J M Koski, S Saarakkala, M Helle, U Hakulinen, J O Heikkinen, H Hermunen
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objectives:</b> To examine the validity of power Doppler ultrasound imaging to identify synovitis, using histopathology as gold standard, and to assess the performance of ultrasound equipments. <b>Methods:</b> 44 synovial sites in small and large joints, bursae and tendon sheaths were depicted with ultrasound. A synovial biopsy was performed on the site depicted and a synovial sample was taken for histopathological evaluation. The performance of three ultrasound devices was tested using flow phantoms. <b>Results:</b> A positive Doppler signal was detected in 29 of 35 (83%) of the patients with active histological inflammation. In eight additional samples, histological examination showed other pathological synovial findings and a Doppler signal was detected in five of them. No significant correlation was found between the amount of Doppler signal and histological synovitis score (r = 0.239, p = NS). The amount of subsynovial infiltration of polymorphonuclear leucocytes and surface fibrin correlated significantly with the amount of power Doppler signal: r = 0.397 (p&lt;0.01) and 0.328 (p&lt;0.05), respectively. The ultrasound devices differed in showing the smallest detectable flow. <b>Conclusions:</b> A negative Doppler signal does not exclude the possibility of synovitis. A positive Doppler signal in the synovium is an indicator of an active synovial inflammation in patients. A Doppler signal does not correlate with the extent of the inflammation and it can also be seen in other synovial reactions. It is important that the quality measurements of ultrasound devices are reported, because the results should be evaluated against the quality of the device used.
Psychosocial Stress at Work Doubles the Risk of Type 2 Diabetes in Middle-Aged Women
Authors: Alexandros Heraclides, Tarani Chandola, Daniel R. Witte, Eric J. Brunner
Journal: Diabetes Care (2009)

OBJECTIVE To investigate the effect of psychosocial stress at work on risk of type 2 diabetes, adjusting for conventional risk factors, among a sample of British, white-collar, middle-aged men and women. RESEARCH DESIGN AND METHODS This was a prospective analysis (1991–2004) from the Whitehall II cohort study. The current sample consists of 5,895 Caucasian middle-aged civil servants free from diabetes at baseline. Type 2 diabetes was ascertained by an oral glucose tolerance test supplemented by self-reports at baseline and four consecutive waves of data collection including two screening phases. The job strain and iso-strain models were used to assess psychosocial work stress. RESULTS Iso-strain in the workplace was associated with a twofold higher risk of type 2 diabetes in age-adjusted analysis in women but not in men (hazard ratio 1.94 [95% CI 1.17–3.21). This effect remained robust to adjustment for socioeconomic position and outside work stressors and was only attenuated by 20% after adjustment for health behaviors, obesity, and other type 2 diabetes risk factors. CONCLUSIONS Psychosocial work stress was an independent predictor of type 2 diabetes among women after a 15-year follow-up. This association was not explained by potential confounding and mediating factors. More evidence from prospective studies using the same work stress models is needed to support the current findings and provide further information on sex differences.
Regulation of Cell Cycle Progression by Calcium/Calmodulin-Dependent Pathways
Authors: Christina R. Kahl, Anthony R. Means
Journal: Endocrine Reviews (2003)

Many hormones, growth factors, and cytokines regulate proliferation of their target cells. Perhaps the most universal signaling cascades required for proliferative responses are those initiated by transient rises in intracellular calcium (Ca(2+)). The major intracellular receptor for Ca(2+) is calmodulin (CaM). CaM is a small protein that contains four EF-hand Ca(2+) binding sites and is highly conserved among eukaryotes. In all organisms in which the CaM gene has been deleted, it is essential. Although Ca(2+)/CaM is required for proliferation in both unicellular and multicellular eukaryotes, the essential targets of Ca(2+)/CaM-dependent pathways required for cell proliferation remain elusive. Potential Ca(2+)/CaM-dependent targets include the serine/threonine phosphatase calcineurin and the family of multifunctional Ca(2+)/CaM-dependent protein kinases. Whereas these enzymes are essential in Aspergillus nidulans, they are not required under normal growth conditions in yeast. However, in mammalian cells, studies demonstrate that both types of enzymes contribute to the regulation of cell cycle progression. Unfortunately, the mechanism by which Ca(2+)/CaM and its downstream targets, particularly calcineurin and the Ca(2+)/CaM-dependent protein kinases, regulate key cell cycle-regulatory proteins, remains enigmatic. By understanding how Ca(2+)/CaM regulates cell cycle progression in normal mammalian cells, we may gain insight into how hormones control cell division and how cancer cells subvert the need for Ca(2+) and its downstream targets to proliferate.
Concussion in youth rugby union and rugby league: a systematic review
Authors: Graham Kirkwood, Nikesh Parekh, Richard Ofori-Asenso, Allyson M Pollock
Journal: British Journal of Sports Medicine (2015)

Background Children and adolescents who play rugby are at increased risk of concussion and its effects. Competitive rugby union and rugby league feature as major sports in the school sport curriculum in the UK. There is a need for a thorough understanding of the epidemiology of concussion in youth rugby, the mechanisms involved in injuries and predisposing risk factors. Data Sources The publication databases Pubmed, Embase and SportDISCUS were searched in April 2014 for primary research studies of child and adolescent rugby union and rugby league (under 20 years) in English language with data on concussion injuries. The review was conducted within a larger all injury systematic review on rugby union and rugby league where key words used in the search included rugby, injury and concussion with child, adolescent, paediatric and youth. Results There were 25 studies retrieved with data on child or adolescent rugby and concussion, 20 were on rugby union, three on rugby league and in two the code of rugby was unspecified. There was significant heterogeneity in the definitions of injuries and of concussion. The incidence of child and adolescent match concussion ranged from 0.2 to 6.9 concussions per 1000 player-hours for rugby union and was 4.6 and 14.7 concussions per 1000 player-hours for rugby league, equivalent to a probability of between 0.3% and 11.4% for rugby union and of 7.7% and 22.7% for rugby league. Conclusions There is a significant risk of concussion in children and adolescents playing rugby union and rugby league evident from the studies included in this systematic review. There is a need for reliable data through routine monitoring and reporting in schools and clubs and in hospital emergency departments in order to inform prevention. Concussion protocols should be implemented and tested.
T cell self-reactivity forms a cytokine milieu for spontaneous development of IL-17+ Th cells that cause autoimmune arthritis
Authors: Keiji Hirota, Motomu Hashimoto, Hiroyuki Yoshitomi, Satoshi Tanaka, Takashi Nomura, Tomoyuki Yamaguchi, Yoichiro Iwakura, Noriko Sakaguchi, Shimon Sakaguchi
Journal: The Journal of Experimental Medicine (2007)

This report shows that highly self-reactive T cells produced in mice as a result of genetically altered thymic T cell selection spontaneously differentiate into interleukin (IL)-17–secreting CD4+ helper T (Th) cells (Th17 cells), which mediate an autoimmune arthritis that clinically and immunologically resembles rheumatoid arthritis (RA). The thymus-produced self-reactive T cells, which become activated in the periphery via recognition of major histocompatibility complex/self-peptide complexes, stimulate antigen-presenting cells (APCs) to secrete IL-6. APC-derived IL-6, together with T cell–derived IL-6, drives naive self-reactive T cells to differentiate into arthritogenic Th17 cells. Deficiency of either IL-17 or IL-6 completely inhibits arthritis development, whereas interferon (IFN)-γ deficiency exacerbates it. The generation, differentiation, and persistence of arthritogenic Th17 cells per se are, however, insufficient for producing overt autoimmune arthritis. Yet overt disease is precipitated by further expansion and activation of autoimmune Th17 cells, for example, via IFN-γ deficiency, homeostatic proliferation, or stimulation of innate immunity by microbial products. Thus, a genetically determined T cell self-reactivity forms a cytokine milieu that facilitates preferential differentiation of self-reactive T cells into Th17 cells. Extrinsic or intrinsic stimuli further expand these cells, thereby triggering autoimmune disease. Intervention in these events at cellular and molecular levels is useful to treat and prevent autoimmune disease, in particular RA.
Haplotype-assisted accurate non-invasive fetal whole genome recovery through maternal plasma sequencing
Authors: Shengpei Chen, Huijuan Ge, Xuebin Wang, Xiaoyu Pan, Xiaotian Yao, Xuchao Li, Chunlei Zhang, Fang Chen, Fuman Jiang, Peipei Li, Hui Jiang, Hancheng Zheng, Lei Zhang, Lijian Zhao, Wei Wang, Songgang Li, Jun Wang, Jian Wang, Huanming Yang, Yingrui Li, Xiuqing Zhang
Journal: Genome Medicine (2013)

The applications of massively parallel sequencing technology to fetal cell-free DNA (cff-DNA) have brought new insight to non-invasive prenatal diagnosis. However, most previous research based on maternal plasma sequencing has been restricted to fetal aneuploidies. To detect specific parentally inherited mutations, invasive approaches to obtain fetal DNA are the current standard in the clinic because of the experimental complexity and resource consumption of previously reported non-invasive approaches.Here, we present a simple and effective non-invasive method for accurate fetal genome recovery-assisted with parental haplotypes. The parental haplotype were firstly inferred using a combination strategy of trio and unrelated individuals. Assisted with the parental haplotype, we then employed a hidden Markov model to non-invasively recover the fetal genome through maternal plasma sequencing.Using a sequence depth of approximately 44X against a an approximate 5.69% cff-DNA concentration, we non-invasively inferred fetal genotype and haplotype under different situations of parental heterozygosity. Our data show that 98.57%, 95.37%, and 98.45% of paternal autosome alleles, maternal autosome alleles, and maternal chromosome X in the fetal haplotypes, respectively, were recovered accurately. Additionally, we obtained efficient coverage or strong linkage of 96.65% of reported Mendelian-disorder genes and 98.90% of complex disease-associated markers.Our method provides a useful strategy for non-invasive whole fetal genome recovery.
A CASE OF GLIOMA OF THE FRONTAL LOBE WITH INVASION OF THE OPPOSITE HEMISPHERE
Authors: E. R Southard
Journal: American Journal of Psychiatry (1906)

I. Man of forty one, dying ten weeks after onset of symptoms pointing to cerebral disease, showed three apparently discrete nodular lesions of the right frontal lobe, one of which had pierced the pia mater of the longitudinal fissure and invaded the left rostral convolution. 2. Examination of the hemorrhagic and edematous tissue of the medullary center beneath the nodules showed bands of tissue like that in the nodules. If the tumor started from one focus in the medullary center, the extent and character of the lesion may be due to rapid growth, unequal along different radii. Thrombosis accounts for the necrotic and cystic center of the mass. 3. The tumor is a glioma, rapidly growing and malignant in a sense unusual for cerebral gliomata, in that it invades non-nervous tissue.
Effect of rHuKGF in vegf dependent cell survival progression in emphysematous condition via akt signalling pathway
Authors: Jai Prakash Muyal, Dhananjay Kumar Tripathi, Vandana Muyal, Amit Tyagi, Sudhir Kotnala
Journal: European Respiratory Journal (2013)

Background: It has been reported that the rHuKGF supplementation has the possibility to induce alveolar epithelium proliferation in emphysematous lungs. Also, it’s evident that keratinocyte growth factor stimulate VEGF synthesis which in turn confers the maintenance of the normal lung structure via Akt pathway. Objective: To study the effect of rHuKGF in the emphysematous mice lungs on AKT mediated signalling pathway. Methods: Three experimental groups [i.e., emphysema (ES), therapy for emphysema (EK) and control (SS)] were prepared. Subsequently, lungs from each mouse were collected for histopathology & QPCR based analyses and protease levels were studied by gelatin zymography. Results: Histopathological based analysis clearly represented that the loss of alveolar septa was reversed in (EK), which were significantly lost in (ES). The mRNA levels of VEGF, VEGFR 2, PI3K & AKT were significantly downregulated in (ES) than (SS) & were highly upregulated in (EK) when compared with (ES). Moreover, the mRNA levels of these genes were well comparable with (SS). The mRNA levels of Pten, Caspase-9 & Bad were significantly upregulated in (ES) than (SS) & were highly downregulated in (EK) when compared with (ES). Independently, using BAL fluid, enzymatic activity was detectable for MMP-2 by zymography. Densitometry based quantitative analysis of gels revealed that MMP-2 activity was induced to 2 fold in (ES) than (SS) and (EK) shows 3.5 fold reduction than (ES). Conclusion: The therapeutic application of exogenous rHuKGF into emphysematous lungs is able to induce alveolar cell survival pathway in the emphysematous lung.
Understanding the delayed onset of action of azathioprine in IBD: are we there yet?
Authors: I. Atreya, M. F Neurath
Journal: Gut (2009)

In this issue of Gut , Ben-Horin et al propose an innovative explanation for the well known phenomenon of the delayed onset of action of thiopurines ( see page 396 ). They thereby contribute to an improved insight into the exact mode of action of the classic immunosuppressive drug azathioprine.1

Developing azathioprine as an innovative immunosuppressive drug in 1957, Gertrude Elion and George Hitchings laid the basis for the currently utilised concept of steroid-sparing treatment strategies in inflammatory bowel diseases (IBD).2 With regard to the evidence-based immunosuppressive capacity and clinical efficacy of azathioprine in the context of IBD as well as considering the proven long-term safety of this drug, which has been confirmed in numerous trials, the primary obstacle to the successful use of azathioprine in the treatment of acute flares of IBD is its delayed onset of action.3 4 As it often takes several months after initiating treatment with azathioprine until the first clinical effects can be monitored, it is sometimes impossible to avoid completely the parallel use of fast-acting steroids in order to control acute flares of intestinal inflammation.3 5 However, do we really have to accept this shortcoming of our old ally azathioprine in the induction of remission in IBD, or might there today, five decades after the birth of azathioprine, exist modern tools of biochemical and medical science which possibly can enable us to overcome these limitations by a rational design of innovative azathioprine-based immunosuppressive formulas? Thinking about this point, subsequently the question arises of what exactly should such a possible biochemical modification of azathioprine look like, in order to speed up its immunosuppressive capacity, and this would then automatically lead to the fundamental issue in this context—that is, do we really understand the detailed molecular mechanism of azathioprine and its metabolites which are …
A Neuroleptic Malignantlike Syndrome due to Levodopa Therapy Withdrawal
Authors: Joseph H. Friedman
Journal: JAMA (1985)

Three cases of a syndrome resembling neuroleptic malignant syndrome are described in patients never exposed to neuroleptics. Each patient had a long history of Parkinson's disease treated with a carbidopa-levodopa combination. Two patients developed the syndrome when administration of the drug was discontinued temporarily. One developed the syndrome before the "drug holiday," and then died during the holiday because of this complication.
Alteration of xanthine oxidase activity in sinusoidal endothelial cells and morphological changes of kupffer cells in hypoxic and reoxygenated rat liver
Authors: Sabine Angermüller, Marcus Schunk, Klaus Kusterer
Journal: Hepatology (1995)

In the model of the perfused rat liver, we investigated the alterations of sinusoidal cells in the pathogenesis of liver injury caused by hypoxia and reperfusion. In sinusoidal endothelial cells, the activity of xanthine oxidase (XOX), a cytoplasmic marker enzyme, was located cytochemically and determined biochemically. Kupffer cells, identified by their endogenous peroxidase staining, were studied with regard to changes in their ultrastructure. In our experiments, parenchymal cells were shown to be severely damaged in contrast to sinusoidal lining cells, which showed minor signs of injury. In comparison with the control group, XOX activity increased significantly in the sinusoidal endothelial cells after low-flow hypoxia; however, after reoxygenation of only 5 minutes, that activity was lower after hypoxia but higher after control perfusion. In Kupffer cells, hypoxia resulted in a strong suppression of phagocytic and endocytotic activity and in a disappearance of the lamellopodia. Kupffer cells were flattened, resembling sinusoidal endothelial cells. After reoxygenation phagocytic vesicles, lamellopodia, and cell volume of Kupffer cells increased markedly in comparison with the control group. In the hypoxia/reperfusion injury model, our observations revealed significant alterations of sinusoidal lining cells. It appears that sinusoidal endothelial cells respond to the hypoxic phase by producing oxygen-derived free radicals and that Kupffer cells respond to the subsequent reperfusion phase by activation followed by the release of toxic mediators.
Uncomplicated Urinary Tract Infection
Authors: Thomas M. Hooton
Journal: New England Journal of Medicine (2012)

Nitrofurantoin, trimethoprim–sulfamethoxazole, fosfomycin, and pivmecillinam are considered first-line agents for cystitis. Fluoroquinolones should not be routine first-line choices for cystitis, although they are first-line empirical therapy for pyelonephritis.