tbuckley/cabot-search huggingface dataset:
Human CMV infection induces 5-lipoxygenase expression and leukotriene B4 production in vascular smooth muscle cells
Authors: Hong Qiu, Klas Strååt, Afsar Rahbar, Min Wan, Cecilia Söderberg-Nauclér, Jesper Z. Haeggström
Journal: The Journal of Experimental Medicine (2008)

Leukotrienes (LTs) are powerful proinflammatory lipid mediators that may play a central role in cardiovascular diseases, including arteriosclerosis, myocardial infarction, and stroke. Owing to restricted expression of 5-lipoxygenase (5-LO), the enzyme required for their synthesis, LTs are almost exclusively produced by myeloid cells. Here, we report that human cytomegalovirus (HCMV) infection of human vascular smooth muscle cells (SMCs) increases 5-LO mRNA levels by up to 170-fold in a dose- and time-dependent manner. Infected cells expressed 5-LO protein, as shown by immunohistochemistry, enabling them to synthesize bioactive LTB4. HCMV-infected vascular SMCs expressing 5-LO protein were readily detected in tissue samples from CMV-infected patients with inflammatory bowel disease or AIDS. Thus, pathogen-induced LT production in HCMV-infected tissues may contribute to local inflammation, consistent with the ability of HCMV to control cellular and immunological functions. HCMV-induced LT biosynthesis in SMCs offers a molecular mechanism to explain HCMV-induced pathogenesis in inflammatory diseases.
A prediction rule for the development of arthritis in seropositive arthralgia patients
Authors: Lotte Arwen van de Stadt, Birgit I Witte, Wouter H Bos, Dirkjan van Schaardenburg
Journal: Annals of the Rheumatic Diseases (2012)

To predict the development of arthritis in anticyclic citrullinated peptide antibodies and/or IgM rheumatoid factor positive (seropositive) arthralgia patients.A prediction rule was developed using a prospective cohort of 374 seropositive arthralgia patients, followed for the development of arthritis. The model was created with backward stepwise Cox regression with 18 variables.131 patients (35%) developed arthritis after a median of 12 months. The prediction model consisted of nine variables: Rheumatoid Arthritis in a first degree family member, alcohol non-use, duration of symptoms <12 months, presence of intermittent symptoms, arthralgia in upper and lower extremities, visual analogue scale pain ≥50, presence of morning stiffness ≥1 h, history of swollen joints as reported by the patient and antibody status. A simplified prediction rule was made ranging from 0 to 13 points. The area under the curve value (95% CI) of this prediction rule was 0.82 (0.75-0.89) after 5 years. Harrell's C (95% CI) was 0.78 (0.73-0.84). Patients could be categorised in three risk groups: low (0-4 points), intermediate (5-6 points) and high risk (7-13 points). With the low risk group as a reference, the intermediate risk group had a hazard ratio (HR; 95% CI) of 4.52 (2.42-8.77) and the high risk group had a HR of 14.86 (8.40-28.32).In patients presenting with seropositive arthralgia, the risk of developing arthritis can be predicted. The prediction rule that was made in this patient group can help (1) to inform patients and (2) to select high-risk patients for intervention studies before clinical arthritis occurs.
Association of IgG4-related disease and sarcoidosis
Authors: L. Michel, R. Clairand, A. Neel, A. Masseau, E. Frampas, M. Hamidou
Journal: Thorax (2011)

MS-based analytical technique.The principal findings of this study are (i) PTR-MS evidence for the flow dependency of exhaled acetone; (ii) changing minute ventilation can both increase and decrease the concentrations of selected exhaled trace gases; and (iii) concentrations of certain volatiles were not significantly altered by respiratory manoeuvres in healthy volunteers.These preliminary observations may have important implications regarding the standardisation requirement for measuring and reporting the concentrations of exhaled trace gases in the future.Further larger studies both in healthy and diseased subjects are necessary to expand on these observations and to provide mechanistic insights into exchange kinetics of affected volatiles.Such studies may help to further define the exact role of on-line MS technologies in non-invasive diagnosis and monitoring pulmonary and systemic diseases.
Recombinant Human Relaxin in the Treatment of Scleroderma
Authors: James R. Seibold, Joseph H. Korn, Robert Simms, Phillip J. Clements, Larry W. Moreland, Maureen D. Mayes, Daniel E. Furst, Naomi Rothfield, Virginia Steen, Michael Weisman, David Collier, Fredrick M. Wigley, Peter A. Merkel, Mary Ellen Csuka, Vivien Hsu, Susan Rocco, Mark Erikson, John Hannigan, W. Scott Harkonen, Martin E. Sanders
Journal: Annals of Internal Medicine (2000)

Background: Relaxin is a pregnancy-related hormone that has tissue remodeling and antifibrotic effects. Systemic sclerosis (scleroderma) is characterized by fibrosis of the skin, vasculature, and internal organs. Objective: To assess the efficacy, safety, and dose–response effect of recombinant human relaxin in patients with scleroderma. Design: Multicenter, parallel-group, randomized, double-blind, placebo-controlled trial. Setting: Academic referral centers. Patients: 68 patients who had had stable, diffuse scleroderma (moderate to severe) for less than 5 years. Intervention: Recombinant human relaxin, 25 or 100 µg/kg of body weight per day, or placebo administered by continuous subcutaneous infusion over 24 weeks. Measurements: Modified Rodnan skin score was the primary efficacy measure. Secondary measurements were pulmonary function, the Health Assessment Questionnaire, and other measures of scleroderma that reflected fibrosis. Results: Patients who received 25 µg/kg of recombinant human relaxin per day had significantly lower skin scores than those who received placebo (mean change, −3.6 at 4 weeks [P = 0.021], −7.5 at 12 weeks [P < 0.001], and −8.7 at 24 weeks [P = 0.040]). Similar trends were noted in other outcome measures, including forced vital capacity, measures of oral aperture and hand extension, functional status, and global assessment. Patients who received 100 µg/kg of relaxin per day did not differ from those who received placebo. Drug-related adverse events included menometrorrhagia, reversible anemia, and complications of the subcutaneous drug administration system (site irritation and local infection). Conclusions: Twenty-four weeks of recombinant human relaxin, 25 µg/kg per day, is associated with reduced skin thickening, improved mobility, and improved function in patients with moderate to severe diffuse scleroderma.
Radiotherapeutic Prophylaxis of Gynecomastia
Authors: Daniel Thönnessen, Frederik Wenz
Journal: Journal of Clinical Oncology (2005)

particular importance if we consider the close putative connection between the biologic mechanisms underlying the function of EGFR and the possibility of using it as a therapeutic target.The biologic phenomenon that has been described in both studies (ie, lack of correlation of EGFR status between primary and metastatic sites) is possibly related to somatic genetic changes that still need to be fully investigated and that could also account for resistance to EGFR-targeted treatments in EGFR-positive tumors.Now that anti-EGFR drugs are becoming more widely available for the treatment of colorectal cancer patients, clinical data along with molecular findings can help us to better define the biologic profile of "responding" tumors.In other words, it is time, once again, to get back from bedside to bench.
598 IN VITRO EFFECT OF n-6/n-3 POLYUNSATURATED FATTY ACIDS ON PLATELET NOX2-MEDIATED OXIDATIVE STRESS IN LIVER CIRRHOSIS
Authors: V. Raparelli, L. Napoleone, O. Riggio, M. Merli, F. Angelico, M. Del Ben, M. Proietti, R. Carnevale, P. Pignatelli, S. Basili, F. Violi
Journal: Journal of Hepatology (2013)
Colorectal cancer screening in the UK: Joint Position Statement by the British Society of Gastroenterology, the Royal College of Physicians, and the Association of Coloproctology of Great Britain and Ireland
Authors: J. RHODES
Journal: Gut (2000)

Colorectal (large bowel) cancer is the second commonest cause of cancer related death in the western world and there are more than 30 000 new cases per annum in the UK with an average five year survival of 40%.1-3 Symptoms of colorectal cancer include change in bowel habit, rectal bleeding, anaemia, and abdominal pain but patients with colorectal cancer often have no symptoms until the cancer is advanced. Ninety per cent of cases are currently not diagnosed until the cancer has penetrated through the bowel wall or spread to lymph nodes or elsewhere (Dukes' stages B–D).4 Such cases have a much worse chance of surviving five years (64%, 38%, and 3%, respectively for Dukes' B, C, and D) than patients who present with cancer confined to the bowel wall (Dukes' A) who have approximately 83% chance of surviving five years. Because so many patients with colorectal cancer do not develop symptoms until their cancer is advanced, detection of a greater proportion of cases at an earlier stage can only be achieved by screening of asymptomatic individuals.

It is thought that 70–90% of cases of colorectal cancer arise from premalignant (adenomatous) polyps.5 They often have a stalk which consists of healthy tissue and allows them to be removed simply and completely by endoscopic snaring. This polyp to cancer sequence adds a strong intellectual argument in support of screening for colon cancer as it provides an opportunity not only to achieve early diagnosis (for example of Dukes' stage A carcinomas) but actually to prevent cancer development by removal of premalignant polyps.

There is evidence that approximately 10% of colorectal cancers are due to genetic causes but that about 90% of the cause is accounted for by environmental factors, particularly diet.6 The dietary factors involved are not fully understood …
Synovial infection with Mycobacterium kansasii.
Authors: M Leader, P Revell, G Clarke
Journal: Annals of the Rheumatic Diseases (1984)

Atypical mycobacteria have been recognised as saprophytic organisms for many years, but it was only with the development of better microbiological culture techniques that they became recognised as potentially pathogenic to man. Infections of tendon sheaths and joints by these organisms may present diagnostic problems, and we report here 3 cases in which Mycobacterium kansasii was responsible for disease at the hand and wrist.
Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125b and miR-132
Authors: Dieter Edbauer, Joel R. Neilson, Kelly A. Foster, Chi-Fong Wang, Daniel P. Seeburg, Matthew N. Batterton, Tomoko Tada, Bridget M. Dolan, Phillip A. Sharp, Morgan Sheng
Journal: Neuron (2010)
Atherogenic lipoproteins stimulate mesangial cell p42 mitogen-activated protein kinase.
Authors: B V Bassa, D D Roh, M A Kirschenbaum, V S Kamanna
Journal: Journal of the American Society of Nephrology (1998)

Previously, it has been shown that atherogenic lipoproteins, through the activation of glomerular cells, stimulate pathobiological processes involved in monocyte infiltration into the mesangium. This study examined the role of LDL and its oxidatively modified variants (mildly oxidatively modified LDL [mm-LDL] and oxidatively modified LDL [ox-LDL]) on the activation of mesangial cell p42 mitogen-activated protein kinase (MAP kinase), a key intracellular signaling mechanism associated with cell proliferation. The incubation of mesangial cells with either LDL, mm-LDL, or ox-LDL induced the activation of MAP kinase dose dependently. The activation of MAP kinase by these lipoproteins in mesangial cells occurred biphasically: initially at 15 min of incubation period and at later time points of 8 to 24 h. No activation of MAP kinase was noted between 30 min (except in LDL) and 6 h. The induction of MAP kinase by both mm-LDL and ox-LDL was greater by 1.5- to 2-fold when compared with LDL. Similarly, these atherogenic lipoproteins stimulated mesangial cell proliferation. Lysophosphatidylcholine, a component of both oxidatively modified variants of LDL, markedly stimulated mesangial cell MAP kinase activity at early incubation times (5 to 30 min) but not at later time points (3 to 24 h), suggesting that lysophosphatidylcholine may, at least in part but not solely, act as an active component of ox-LDL-mediated effects. These data define putative key signal transduction events associated with lipoprotein-mediated induction of mesangial cell proliferation.
ETIOPATHOGENESIS AND TREATMENT OF PSYCHOSIS
Authors: T. J. Crow, C. A. Harrington
Journal: Annual Review of Medicine (1994)

▪ Abstract Psychotic illnesses (schizophrenia and schizoaffective and affective psychosis) have a lifetime prevalence of 2–3% and probably occur at a similar rate in all human societies. No etiologically significant environmental precipitants have been identified, and this suggests that these diseases are primarily genetic. Brain studies reveal that in schizophrenic patients, development of cerebral asymmetry is arrested, which may be associated with a small reduction in cortical mass. Episodes of illness can be ameliorated by dopamine (in particular D 2 ) antagonists, drugs that are antipsychotic rather than merely antischizophrenic. The discovery of at least five dopamine receptor subtypes and their genes paves the way for new approaches to treatment. However, whether psychotic patients undergo a primary disturbance of dopaminergic transmission remains unclear.
Mammalian Zinc Transporters: Nutritional and Physiologic Regulation
Authors: Louis A. Lichten, Robert J. Cousins
Journal: Annual Review of Nutrition (2009)

Research advances defining how zinc is transported into and out of cells and organelles have increased exponentially within the past five years. Research has progressed through application of molecular techniques including genomic analysis, cell transfection, RNA interference, kinetic analysis of ion transport, and application of cell and animal models including knockout mice. The knowledge base has increased for most of 10 members of the ZnT family and 14 members of the Zrt-, Irt-like protein (ZIP) family. Relative to the handling of dietary zinc is the involvement of ZnT1, ZIP4, and ZIP5 in intestinal zinc transport, involvement of ZIP10 and ZnT1 in renal zinc reabsorption, and the roles of ZIP5, ZnT2, and ZnT1 in pancreatic release of endogenous zinc. These events are major factors in regulation of zinc homeostasis. Other salient findings are the involvement of ZnT2 in lactation, ZIP14 in the hypozincemia of inflammation, ZIP6, ZIP7, and ZIP10 in metastatic breast cancer, and ZnT8 in insulin processing and as an autoantigen in diabetes.
A Small-molecule Inhibitor Directed against the Chemokine Receptor CXCR4 Prevents its Use as an HIV-1 Coreceptor
Authors: Benjamin J. Doranz, Kathie Grovit-Ferbas, Matthew P. Sharron, Si-Hua Mao, Matthew Bidwell Goetz, Eric S. Daar, Robert W. Doms, William A. O'Brien
Journal: The Journal of Experimental Medicine (1997)

The chemokine receptor CXCR4 is the major coreceptor used for cellular entry by T cell– tropic human immunodeficiency virus (HIV)-1 strains, whereas CCR5 is used by macrophage (M)-tropic strains. Here we show that a small-molecule inhibitor, ALX40-4C, inhibits HIV-1 envelope (Env)-mediated membrane fusion and viral entry directly at the level of coreceptor use. ALX40-4C inhibited HIV-1 use of the coreceptor CXCR4 by T- and dual-tropic HIV-1 strains, whereas use of CCR5 by M- and dual-tropic strains was not inhibited. Dual-tropic viruses capable of using both CXCR4 and CCR5 were inhibited by ALX40-4C only when cells expressed CXCR4 alone. ALX40-4C blocked stromal-derived factor (SDF)-1α–mediated activation of CXCR4 and binding of the monoclonal antibody 12G5 to cells expressing CXCR4. Overlap of the ALX40-4C binding site with that of 12G5 and SDF implicates direct blocking of Env interactions, rather than downregulation of receptor, as the mechanism of inhibition. Thus, ALX40-4C represents a small-molecule inhibitor of HIV-1 infection that acts directly against a chemokine receptor at the level of Env-mediated membrane fusion.
Hormones and Growth Factors in Milk
Authors: CLARK E. GROSVENOR, MARY FRANCES PICCIANO, CRAIG R. BAUMRUCKER
Journal: Endocrine Reviews (1993)

MILK and colostrum contain a variety of proteins, peptides, and steroids that possess biological activity. In studies in which the concentration of hormone/growth factor has been measured in both colostrum and milk, the highest concentrations occur in colostrum (1). This review will discuss pituitary, hypothalamic, pancreatic, thyroid, parathyroid, adrenal, gonadal, and gut hormones as well as growth factors, prostaglandins, and neuropeptides found in milk (see Table 1). Other biologically important proteins and peptides in milk such as the immunoglobulins, allergins, opiates, enzymes, casomorphins, and cyclic nucleotides will not be addressed. The reader is referred to excellent recently published reviews regarding hormones and other bioactive substances present in milk (2–4). Of the hormones and growth factors present in milk many exist in concentrations that exceed those found in maternal plasma (see Table 2). Some are rapidly transported into milk from the maternal circulation unchanged in structure and activity; others appear to be modified by glycosylation, phosphorylation, and proteolysis within the mammary gland and/ or milk. Several hormones [thyroid hormones, relaxin, PTHreleasing peptide (PTHrP), estrogen, GnRH. PRL], growth factors [insulin-like growth factor (IGF), epidermal growth factor (EGF)], and nonhormonal bioactive substances (lactoferrin, transferrin, casomorphins) appear to be synthesized within the mammary gland as well as transported from the maternal circulation (see Table 2).
Progesterone Receptor (PR) Promoter Methylation – Role as a Predictive and Prognostic Marker in Breast Cancer.
Authors: T. Pathiraja, J. Jelinek, R. He, P. Shetty, R. Hartmaier, A. Margossian, S. Hilsenbeck, J. Issa, S. Oesterreich
Journal: Cancer Research (2009)

Abstract Estrogen receptor α expression is a well known and clinically utilized predictor of endocrine treatment response. In addition, loss of expression of the progesterone receptor (PR), an estrogen induced gene, has been shown to be associated with resistance to endocrine therapy. PR is known to be epigenetically regulated by DNA methylation, but only a few studies have correlated PR DNA methylation with its expression in breast cancer. Previous studies are contradictory and have been limited by small sample size. There is also evidence that differential expression of the two PR isoforms, PRA and PRB, might contribute to breast tumorigenesis, and altered hormone response. Whether PRA and/or PRB DNA methylation could predict response to endocrine therapy remains an open question. Further, there are no published studies so far testing whether PRA and/or PRB methylation have prognostic significance.Our objective was 1) to determine whether there was an association between PRA and/or PRB methylation levels with total PR expression in breast tumors, and 2) to determine if PRA and/or PRB methylation would have predictive and/or prognostic value. For this study, we utilized tumor DNA from patients with ER-positive breast tumors which were treated with adjuvant tamoxifen after surgery (n=500), and from patients treated with surgery only (n=500). PR expression was determined by ligand binding assay, and PRA and PRB promoter methylation was measured by bisulfite pyrosequencing.Both PRA and PRB methylation were significantly (p&amp;lt;0.0001) associated with PR expression, in an inverse relationship. Low PR expression was significantly (p=0.02) associated with worse overall survival (OS), and there was a trend towards shorter disease free survival (DFS) in the tamoxifen treated group. There was no association between PR expression and survival in the untreated group. PRA methylation was significantly (p&amp;lt;0.0001) associated with PRB methylation. Intriguingly, increased PRA methylation was significantly associated with shorter DFS (p=0.047) and OS (p=0.0067) in tamoxifen treated patients, and with shorter OS (p=0.008) in the untreated patients. In contrast, there was no significant association between PRB methylation and survival in either tamoxifen treated or untreated patients.Our results show that PR expression is significantly associated with PR methylation. The data suggest that PRA methylation is a predictive marker for tamoxifen response and also a prognostic marker for breast cancer progression. This is the largest study so far to elucidate the association of PRA and PRB methylation with PR status, response to tamoxifen, and tumor prognosis, and we believe that it provides useful insights into the role of PR methylation in breast tumorigenesis. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2002.
The CD8+ Dendritic Cell Subset Selectively Endocytoses Dying Cells in Culture and In Vivo
Authors: Tomonori Iyoda, Susumu Shimoyama, Kang Liu, Yoshiki Omatsu, Yuji Akiyama, Yasuhiro Maeda, Kazuhiko Takahara, Ralph M. Steinman, Kayo Inaba
Journal: The Journal of Experimental Medicine (2002)

Dendritic cells (DCs) are able in tissue culture to phagocytose and present antigens derived from infected, malignant, and allogeneic cells. Here we show directly that DCs in situ take up these types of cells after fluorescent labeling with carboxyfluorescein succinimidyl ester (CFSE) and injection into mice. The injected cells include syngeneic splenocytes and tumor cell lines, induced to undergo apoptosis ex vivo by exposure to osmotic shock, and allogeneic B cells killed by NK cells in situ. The CFSE-labeled cells in each case are actively endocytosed by DCs in vivo, but only the CD8+ subset. After uptake, all of the phagocytic CD8+ DCs can form major histocompatibility complex class II–peptide complexes, as detected with a monoclonal antibody specific for these complexes. The CD8+ DCs also selectively present cell-associated antigens to both CD4+ and CD8+ T cells. Similar events take place with cultured DCs; CD8+ DCs again selectively take up and present dying cells. In contrast, both CD8+ and CD8− DCs phagocytose latex particles in culture, and both DC subsets present soluble ovalbumin captured in vivo. Therefore CD8+ DCs are specialized to capture dying cells, and this helps to explain their selective ability to cross present cellular antigens to both CD4+ and CD8+ T cells.
Atrial selectivity in Na+channel blockade by acute amiodarone
Authors: Tomoyuki Suzuki, Mikio Morishima, Sara Kato, Norihiro Ueda, Haruo Honjo, Kaichiro Kamiya
Journal: Cardiovascular Research (2013)

Na(+) channel blockers are often used to treat atrial fibrillation (AF), but may sometimes cause ventricular contractile dysfunction. However, amiodarone, a multi-channel blocker with Na(+) channel block, causes less contractile dysfunction. In this study, we tested the hypothesis that Na(+) channel block by amiodarone is selective in atrial myocytes (AM) compared with ventricular myocytes (VM).Na(+) currents (INa) were measured using whole-cell patch-clamp technique in isolated rabbit AM and VM. Amiodarone inhibited INa in AM (IC50: 1.8 ± 1.1 μM; n = 8) much more than in VM (40.4 ± 11.9 μM; n = 7, P < 0.01). Amiodarone at 10 μM shifted the steady-state inactivation relationship in AM (-16.2 ± 1.7 mV shift, n = 12) compared with VM (-5.9 ± 0.7 mV shift; n = 13; P < 0.01). For mexiletine, the inhibition of INa and inactivation curve shifts were comparable for AM and VM. The effects of amiodarone and mexiletine on conduction velocity (CV) in Langendorff-perfused rabbit hearts were evaluated using an optical mapping system. The decrease of CV by 3 μM amiodarone was significantly larger in the atrium (-18.9 ± 3.8% change; n = 5) compared with the ventricle (-3.7 ± 3.7%; n = 5; P < 0.01). In contrast, mexiletine reduced CV equally in the atrium and the ventricle.Amiodarone preferentially inhibits INa of AM compared with VM. Atrial selective Na(+) channel block by amiodarone may contribute to treating AF with less effect on ventricular contractility than other Na(+) channel blockers.