tbuckley/cabot-search huggingface dataset:
Cytokine-robbing cells
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

TIM-2 soaks up ferritinThe TIM (T cell immunoglobulin mucin) proteins have emerged as key regulators of allergic and autoimmune diseases due to their influence on T helper (Th)-1 and Th-2 responses.On page 955, Chen and colleagues show that one member of this family, TIM-2, multitasks as a receptor for H-ferritin, a component of the iron storage protein ferritin.Ferritin was not what the group expected to find when they launched a search for TIM-2 ligands."Ferritin is not something immunologists think about much," says senior author William Seaman.Although circulating H-ferritin had been shown to increase during inflammation and to bind to T and B cells, the consequences of these observations were largely unknown.Chen et al. now show that although TIM-2 is most highly expressed in the liver, the primary iron storage organ, this protein is also found on splenic B cells.TIM-2 expression was particularly high on germinal center B cells that were actively responding to antigenic stimulation.Using a TIM-2 reporter cell line, they showed that a soluble product of activated macrophages bound to TIM-2.That product was H-ferritin.Binding triggered endocytosis of the receptor-ligand pair, suggesting that the interaction was functional.The authors are now investigating the consequences of the ferritin-TIM-2 interaction.A recent study showed that intracellular H-ferritin is required for the antiapoptotic effect of NF-B activation in fibroblasts, prompting Seaman to speculate that H-ferritin uptake in activated germinal center B cells might have a similar antiapoptotic effect.
Positive Selection and Expression Divergence Following Gene Duplication in the Sunflower CYCLOIDEA Gene Family
Authors: M. A. Chapman, J. H. Leebens-Mack, J. M. Burke
Journal: Molecular Biology and Evolution (2008)

Members of the CYCLOIDEA (CYC)/TEOSINTE-BRANCHED1 (TB1) group of transcription factors have been implicated in the evolution of zygomorphic (i.e., bilaterally symmetric) flowers in Antirrhinum and Lotus and the loss of branching phenotype during the domestication of maize. The composite inflorescences of sunflower (Helianthus annuus L. Asteraceae) contain both zygomorphic and actinomorphic (i.e., radially symmetric) florets (rays and disks, respectively), and the cultivated sunflower has evolved an unbranched phenotype in response to domestication from its highly branched wild progenitor; hence, genes related to CYC/TB1 are of great interest in this study system. We identified 10 members of the CYC/TB1 gene family in sunflower, which is more than found in any other species investigated to date. Phylogenetic analysis indicates that these genes occur in 3 distinct clades, consistent with previous research in other eudicot species. A combination of dating the duplication events and linkage mapping indicates that only some of the duplications were associated with polyploidization. Cosegregation between CYC-like genes and branching-related quantitative trait loci suggest a minor, if any, role for these genes in conferring differences in branching. However, the expression patterns of one gene suggest a possible role in the development of ray versus disk florets. Molecular evolutionary analyses reveal that residues in the conserved domains were the targets of positive selection following gene duplication. Taken together, these results indicate that gene duplication and functional divergence have played a major role in diversification of the sunflower CYC gene family.
Alpha2-macroglobulin and eosinophil cationic protein in the allergic airway mucosa in seasonal allergic rhinitis
Authors: P Meyer, CG Persson, M Andersson, P Wollmer, M Linden, C Svensson, L Greiff
Journal: European Respiratory Journal (1999)

As previously demonstrated in seasonal allergic rhinitis, increased microvascular permeability and eosinophil activation are key features of allergic airway inflammation. In the present study, the hypothesis that exudation of alpha2-macroglobulin may cause the appearance of eosinophil cationic protein (ECP) in the airway lumen was explored. Nasal lavages were carried out using the nasal pool device before and during the pollen season both at baseline and after histamine challenge in 10 children with allergic rhinitis. Nasal lavage fluid levels of alpha2-macroglobulin and ECP were determined. All patients experienced nasal symptoms of allergic rhinitis during the pollen season (p&lt;0.01-0.05). Baseline nasal lavage fluid levels of alpha2-macroglobulin and ECP were increased during the season (p&lt;0.01-0.05) and were found to be well correlated (p&lt;0.0001). Histamine produced concentration-dependent plasma exudation before and during the pollen season, but it was only during the pollen season that this caused an increase in the lavage fluid levels of ECP (p&lt;0.05). These data suggest that exudation of plasma and increased tissue levels and output of eosinophil cationic protein characterize nasal mucosal inflammation in children with seasonal allergic rhinitis. The plasma exudation process in part may account for lumenal entry of eosinophil cationic protein molecules that have been released in mucosal tissue compartments. A combination of induced exudation and nasal lavage may improve the yield of important markers of inflammation in studies of nasal diseases.
Gammaherpesviruses and Lymphoproliferative Disorders
Authors: Ethel Cesarman
Journal: Annual Review of Pathology Mechanisms of Disease (2013)

Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV), formally designated human herpesvirus 4 (HHV-4) and 8 (HHV-8), respectively, are viruses that can cause a variety of cancers in humans. EBV is found in non-Hodgkin and Hodgkin lymphomas, as well as in lymphoproliferative disorders, which occur more commonly but not exclusively in individuals with immunodeficiency. EBV also causes nonlymphoid malignancies such as nasopharyngeal carcinoma. KSHV causes primary effusion lymphomas, multicentric Castleman's disease, and Kaposi's sarcoma. The frequency of lymphoid malignancies related to infection by one of these two herpesviruses is greatly increased in individuals with immunodeficiency, whether primary or acquired, for example, as a consequence of HIV infection and AIDS or in the case of therapeutic immunosuppression for organ transplantation. Our current understanding indicates that EBV and KSHV contribute to lymphomagenesis by affecting genomic stability and by subverting the cellular molecular signaling machinery and metabolism to avoid immune surveillance and enhance tumor cell growth and survival. Understanding the viral associations in specific lymphoproliferative disorders and the molecular mechanisms of viral oncogenesis will lead to better prevention, diagnosis, and treatment strategies for these diseases.
Creutzfeldt-Jakob disease: implications for gastroenterology
Authors: M G Bramble
Journal: Gut (2002)

The current clinical views regarding variant Creutzfeldt-Jakob disease, and in particular transmission via endoscopy, of those representing both gastroenterology and the Spongiform Encephalopathy Advisory Committee are presented in an attempt to guide clinicians as to “best practice” given the current state of our knowledge.
Sequence of Radiotherapy With Tamoxifen in Conservatively Managed Breast Cancer Does Not Affect Local Relapse Rates
Authors: Peter H. Ahn, Ha Thanh Vu, Donald Lannin, Edward Obedian, Michael P. DiGiovanna, Barbara Burtness, Bruce G. Haffty
Journal: Journal of Clinical Oncology (2004)

Purpose To evaluate whether the sequencing of tamoxifen (TAM) relative to radiation (RT) affects outcome in breast cancer patients treated with conservative surgery (CS) plus RT (lumpectomy with RT). Methods Between 1976 and 1999, 1,649 patients with stage I or II breast cancer were treated with CS plus RT at Yale-New Haven Hospital (New Haven, CT). TAM was administered to 500 patients. The timing of TAM relative to RT was documented for each patient. Of the 500 patients, the timing of TAM was unclear in five patients, was administered concurrently with RT in 254 patients (CON-TAM), and was administered sequentially after completion of RT in 241 patients (SEQ-TAM). Results There were no differences between the CON-TAM and SEQ-TAM group in T stage, estrogen and progesterone status, nodal status, histology, or margin status. The CON-TAM group was slightly older than the SEQ-TAM group (62 v 58 years) and received chemotherapy in addition to TAM less frequently (14% v 38%). As of September 2002, with a median follow-up of 10.0 years, there were no significant differences between the CON-TAM and SEQ-TAM groups in overall survival (84% v 82%; hazard ratio [HR], 1.234; 95% CI, 0.42 to 2.05; P = .45), distant–metastasis-free rate (82% v 78%; HR, 1.55; 95% CI, 0.89 to 2.68; P = .12), ipsilateral breast-relapse–free rate (90% v 86%; HR, 0.932; 95% CI, 0.42 to 2.05; P = .86), or contralateral breast-relapse–free rate (95% v 93%; HR, 0.892; 95% CI, 0.53 to 1.48; P = .66). Conclusion Although the concurrent use of TAM with RT may theoretically render cancer cells less responsive to RT, this retrospective study suggests that in practical application, concurrent administration of TAM with RT does not compromise local control.
Prostaglandin synthesis by glomeruli isolated from rats with glycerol-induced acute renal failure.
Authors: J D Sraer, L Moulonguet-Doleris, F Delarue, J Sraer, R Ardaillou
Journal: Circulation Research (1981)

In vitro PG synthesis by glomeruli isolated from rats with glycerol-induced acute renal failure (ARF) was measured by radiometric high performance liquid chromatography after incubation with [14C]arachidonic acid and radioimmunoassay (RIA). The four PGs, 6-keto-PGF1 alpha, TXB2, PGF2 alpha, and PGE2 were each synthesized by glomeruli from both control and treated rats but the synthesis rates were greater after glycerol. This increase was not apparent 1 hour after injection but, at 24 hours, all PGs were produced in greater amounts by glomeruli of treated rats. Thus, we studied PGE2, PGE2 alpha, and TXB2 synthesis by glomeruli at various time intervals after induction of ARF using direct RIA, PGF 2 alpha and TXB2 synthesis were greater only at 24 hours and only in the presence of arachidonic acid, whereas PGE2 synthesis was greater at 24 hours, irrespective of arachidonic acid, but at 48 hours only with arachidonic acid. The stimulatory effect of arachidonic acid was always greater in glycerol-treated than in control rats for these three PGs in the later period, whereas a significant decrease for PGE2 was observed at 1 hour. The late increase in PG synthesis may be due to stimulation of the renin-angiotensin system since it was abolished in rats pretreated for 48 hours with captopril. A late increase in PG synthesis by the papilla of the treated rats also was observed. We concluded that any increase in the glomerular production of vasoconstrictor PGs could contribute to the maintenance of acute renal failure, whereas the early fall in the stimulatory effect of arachidonic acid on PGE2 synthesis could play a role in its initiation.
Managing change in the culture of general practice: qualitative case studies in primary care trusts
Authors: M. N Marshall
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objectives</b> To explore the potential tension between the need for managers to produce measurable change and the skills required to produce cultural change, and to investigate how managers of primary care trusts are attempting to deal with this tension. <b>Design</b> Qualitative case studies using data derived from semistructured interviews and a review of published documents. An established cultural framework was to used to help interpret the findings. <b>Setting</b> Six primary care trusts in England purposefully sampled to represent a range of cultural, structural, geographical, and demographic characteristics. <b>Participants</b> 42 interviews with 39 different senior and middle primary care trust managers conducted over an 18 month period. <b>Results</b> We found two distinct and polarised styles of management. One group of managers adopts a directive style and challenges the prevailing norms and values of clinicians, an approach characteristically seen in organisations with hierarchical cultures. This group is made up mostly of senior managers who are driven principally by the imperative to deliver a political agenda. Managers in the second group are more inclined to work with the prevailing cultures found in general practice, attempting to facilitate change from within rather than forcing change from outside. This management style is characteristically seen in organisations with a clan-type culture. The approach was manifest mostly by middle managers, who seem to act as buffers between the demands of senior managers and their own perception of the ability and willingness of health professionals to cope with change. The different management approaches can lead to tension and dysfunction between tiers of management. <b>Conclusions</b> The development of primary care depends on high quality managers who are able to draw on a range of different management skills and styles. Managers are most likely to be effective if they appreciate the merits and drawbacks of their different styles and are willing to work in partnership.
Mood, mileage and the menstrual cycle.
Authors: I M Cockerill, A M Nevill, N C Byrne
Journal: British Journal of Sports Medicine (1992)

Forty women took part in a study to determine the effects of high-intensity training and the menstrual cycle on mood states. Half of the sample were competitive distance runners following a training load of between 50 km and 130 km running per week. Seven athletes were amenorrhoeic and 13 either eumenorrhoeic or oligomenorrhoeic. The remaining 20 subjects were inactive women who menstruated regularly. The mean age of all 40 subjects was 29 years. Each subject completed two identical Profile of Mood States (POMS) questionnaires. The 33 menstruating subjects completed both a premenstrual and a midcycle form and the amenorrhoeic athletes completed the questionnaires at a 3-week interval, which acted as a control for the potential effects of premenstrual syndrome (PMS) among the menstruating females. Results showed highly significant differences in mood profiles among amenorrhoeic athletes, non-amenorrhoeic athletes and inactive women. The greatest difference was between premenstrual and midcycle measures for the inactive group. PMS appears to cause marked negative mood swings among menstruating women which the POMS inventory is sensitive in detecting. While the lower-intensity-training runners appeared to benefit psychologically from a training distance of approximately 50 km week-1, high-intensity training had an adverse effect on mood.
Innate left handedness and risk of breast cancer: case-cohort study: table 1
Authors: Made K Ramadhani, Sjoerd G Elias, Paulus A H van Noord, Diederick E Grobbee, Petra H M Peeters, Cuno S P M Uiterwaal
Journal: BMJ (2005)

Among the proposed origins of breast cancer are intrauterine influences, such as exposure to sex hormones. 1Such exposure may also influence cerebral lateralisation, with hand preference being one of its manifestations.We know only of case-control studies on a putative common origin of left handedness and breast cancer, some of which show an association. 2 We assessed the association between handedness and incidence of breast cancer in a population based prospective cohort of healthy, middle aged women followed up for 16 years.
Oligoclonal T lymphocytes in the cerebrospinal fluid of patients with multiple sclerosis.
Authors: D A Hafler, A D Duby, S J Lee, D Benjamin, J G Seidman, H L Weiner
Journal: The Journal of Experimental Medicine (1988)

We have investigated the T cell populations in the cerebrospinal fluid (CSF) of chronic progressive multiple sclerosis (MS) patients. Individual T cells from the CSF and blood were cloned before expansion and their clonotypes were defined by analysis of rearranged T cell receptor beta chain and gamma chain genes. 87 T cell clones from blood and CSF of two patients with chronic progressive MS were examined for common TCR gene rearrangement patterns. In one patient, 18 of 28 CSF-derived T cell clones demonstrated common TCR gene rearrangements indicating oligoclonal T cell populations; in the blood, two patterns were found twice among 26 T cell clones. In another patient, 5 of 27 CSF-derived clones had common TCR gene rearrangement patterns. In contrast, no common beta chain rearrangement pattern was found among 67 T cell clones derived from the blood or CSF of a patient with subacute sclerosing panencephalitis, among 20 clones from the CSF of a patient with herpes zoster meningoencephalitis, or among 66 clones from a normal subject. A subject with atypical, fatal MS of 8-mo duration was also studied and did not have oligoclonal T cells in the CSF or blood. These results demonstrate that distinct oligoclonal T cell populations can be found in the CSF immune compartment of subjects with nonmalignant inflammatory disease and they can create a new avenue for the investigation of the specificity of the T cell response within the central nervous system.
Impaired high-density lipoprotein anti-oxidant capacity in human abdominal aortic aneurysm
Authors: Sandrine Delbosc, Devy Diallo, Tiphaine Dejouvencel, Zohra Lamiral, Liliane Louedec, Jose-Luis Martin-Ventura, Patrick Rossignol, Guy Leseche, Jean-Baptiste Michel, Olivier Meilhac
Journal: Cardiovascular Research (2013)

AimsAbdominal aortic aneurysm (AAA) is a particular form of atherothrombotic disease characterized by the dilation of the aortic wall and the presence of an intraluminal thrombus (ILT). The objective of the present study was to evaluate the pro-oxidant properties of the ILT and to characterize the anti-oxidant capacity of high-density lipoproteins (HDLs).
ET-49 * ANTICANCER POTENTIAL AND MECHANISM OF ACTION OF MANGO GINGER (CURCUMA AMADA ROXB.) SUPERCRTICAL EXTRACTS IN HUMAN GLIOBLASTOMA CELL LINES
Authors: C. Ramachandran, I. Lollett, K.-W. Quirin, E. Escalon, Z. Khatib, S. Melnick
Journal: Neuro-Oncology (2014)

Brain tumors are the most common form of solid tumors in children accounting for about 20-25% of all pediatric cancers. Chemotherapy options for brain tumor treatment are very much limited because of the blood brain barrier and emergence of drug resistance in brain tumor cells. The genus Curcuma contains several herbs like mango ginger (Curcuma amada Roxb.), turmeric (C. longa L.) and Javanese turmeric (C. xanthorrhiza Roxb.) that are suggested to have anticancer properties. Previous studies have indicated that curcumin, the major active ingredient in turmeric is cytotoxic to brain tumor cells. In this investigation, we show that the supercritical extract of mango ginger (CA) is superior in terms of cytotoxic effects than turmeric extract (CL), Javanese turmeric extract (CX), curcumin and turmeric forceTM (a nutraceutical containing supercritical and hydroethanolic extract of turmeric) against human glioblastoma cell lines (U-87MG and U-188MG). The cytotoxicity profile of CA is significantly better than temozolomide and etoposide as it has induced >90% death of tumor cells. The combination index values calculated according to Chou and Talalay's equations indicated that CA is synergistic (<1) for cytotoxic effects with temozolomide, etoposide and irinotecan in glioma cell lines. Gene expression analysis to explore the mechanism of action indicated that CA downregulates the expression of genes associated with inflammation (NF-kB, COX-2 and STAT3), apoptosis (p21, p53, Bcl-2/Bax ratio), telomerase (hTERT), drug resistance (MRP, DRP, LRP) and oncogenes (N-myc, V-Jun) in the RT-PCR assay. These positive results suggest the need for further evaluation of CA in nude mice xenograft studies and human clinical trials.
Exploratory analyses of the association of MRI with clinical, laboratory and radiographic findings in patients with rheumatoid arthritis
Authors: P. Emery, D. van der Heijde, M. Ostergaard, P. G. Conaghan, M. C. Genovese, E. C. Keystone, R. Fleischmann, E. C. Hsia, W. Xu, S. Xu, M. U. Rahman
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> Evaluate relationships between MRI and clinical/laboratory/radiographic findings in rheumatoid arthritis (RA). <h3>Methods</h3> 637 methotrexate-naive patients (GO-BEFORE) and 444 patients with active RA despite methotrexate (GO-FORWARD) were randomly assigned to subcutaneous placebo + methotrexate, golimumab 100mg + placebo, golimumab 50mg + methotrexate, or golimumab 100mg + methotrexate every-4-weeks. In GO-BEFORE(n=318) and GO-FORWARD(n=240) substudies, MRI of dominant wrist/metacarpophalangeal joints were scored for synovitis, bone oedema and bone erosion (RA MRI scoring (RAMRIS) system). Relationships between RAMRIS scores and serum C-reactive protein (CRP), 28-joint count disease activity score (DAS28–CRP) and van der Heijde modified Sharp (vdH-S) scores were assessed. <h3>Results</h3> Baseline and weeks 24/28 DAS28–CRP, CRP, and vdH-S generally correlated well with baseline and week 24 RAMRIS synovitis, oedema and erosion scores. Early (week 4) CRP changes correlated with later (week 12) RAMRIS synovitis/oedema change scores; earlier (week 12) changes in some RAMRIS scores correlated with later (weeks 24/28) changes in vdH-S. Significant correlations between RAMRIS change scores and clinical/radiographic change scores were weak. <h3>Conclusions</h3> MRI and clinical/laboratory/radiographic measures generally correlated well. Associations between earlier changes in CRP and later changes in RAMRIS synovitis/osteitis were observed. Changes in MRI and clinical/radiographic measures did not correlate well, probably because MRI is more sensitive than radiographs and more objective than DAS28–CRP.
Association between genetic variants in the tumour necrosis factor/lymphotoxin α/lymphotoxin β locus and primary Sjögren's syndrome in Scandinavian samples
Authors: Anne Isine Bolstad, Stephanie Le Hellard, Gudlaug Kristjansdottir, Lilian Vasaitis, Marika Kvarnström, Christopher Sjöwall, Svein Joar Auglænd Johnsen, Per Eriksson, Roald Omdal, Johan G Brun, Marie Wahren-Herlenius, Elke Theander, Ann-Christine Syvänen, Lars Rönnblom, Gunnel Nordmark, Roland Jonsson
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> Lymphotoxin β (<i>LTB</i>) has been found to be upregulated in salivary glands of patients with primary Sjögren9s syndrome (pSS). An animal model of pSS also showed ablation of the lymphoid organisation and a marked improvement in salivary gland function on blocking the LTB receptor pathway. This study aimed to investigate whether single-nucleotide polymorphisms (SNP) in the lymphotoxin α (<i>LTA)/LTB/</i>tumour necrosis factor (<i>TNF</i>) gene clusters are associated with pSS. <h3>Methods</h3> 527 pSS patients and 532 controls participated in the study, all of Caucasian origin from Sweden and Norway. 14 SNP markers were genotyped and after quality control filtering, 12 SNP were analysed for their association with pSS using single marker and haplotype tests, and corrected by permutation testing. <h3>Results</h3> Nine markers showed significant association with pSS at the p=0.05 level. Markers rs1800629 and rs909253 showed the strongest genotype association (p=1.64E-11 and p=4.42E-08, respectively, after correcting for sex and country of origin). When the analysis was conditioned for the effect of rs1800629, only the association with rs909253 remained nominally significant (p=0.027). In haplotype analyses the strongest effect was observed for the haplotype rs909253G_rs1800629A (p=9.14E-17). The associations were mainly due to anti-Ro/SSA and anti-La/SSB antibody-positive pSS. <h3>Conclusions</h3> A strong association was found between several SNP in the <i>LTA/LTB/TNF</i>α locus and pSS, some of which led to amino acid changes. These data suggest a role for this locus in the development of pSS. Further studies are needed to examine if the genetic effect described here is independent of the known genetic association between HLA and pSS.