tbuckley/cabot-search huggingface dataset:
Genome-wide RIP-Chip analysis of translational repressor-bound mRNAs in the Plasmodium gametocyte
Authors: Ana Guerreiro, Elena Deligianni, Jorge M Santos, Patricia AGC Silva, Christos Louis, Arnab Pain, Chris J Janse, Blandine Franke-Fayard, Celine K Carret, Inga Siden-Kiamos, Gunnar R Mair
Journal: Genome biology (2014)

Following fertilization, the early proteomes of metazoans are defined by the translation of stored but repressed transcripts; further embryonic development relies on de novo transcription of the zygotic genome. During sexual development of Plasmodium berghei, a rodent model for human malaria species including P. falciparum, the stability of repressed mRNAs requires the translational repressors DOZI and CITH. When these repressors are absent, Plasmodium zygote development and transmission to the mosquito vector is halted, as hundreds of transcripts become destabilized. However, which mRNAs are direct targets of these RNA binding proteins, and thus subject to translational repression, is unknown.
Immunoregulatory Molecule B7-H1 (CD274) Contributes to Skin Carcinogenesis
Authors: Yujia Cao, Lu Zhang, Pacharee Ritprajak, Fumihiko Tsushima, Pornpan Youngnak-Piboonratanakit, Yosuke Kamimura, Masaaki Hashiguchi, Miyuki Azuma
Journal: Cancer Research (2011)

Abstract B7-H1 (CD274), a member of the B7 family of coinhibitory molecules, is often induced in human tumors and its expression is closely correlated with a poor prognosis or higher malignancy grade. Tumor-associated B7-H1 is implicated in mechanisms of immune escape. Under inflammatory conditions, B7-H1 is also inducible in normal epithelial cells, but little is known about its involvement in the conversion of normal cells to tumor cells. We recently found that skin-specific expression of B7-H1 accelerates chemically induced carcinogenesis of squamous cell carcinoma (SCC), despite impaired skin inflammatory responses, in B7-H1 transgenic (B7-H1tg) mice. B7-H1tg–derived keratinocytes (KC) and SCCs exhibited a marked reduction of E-cadherin, and B7-H1tg–originated SCCs showed elevated expression of the transcription factors Slug and Twist, suggesting that B7-H1 overexpression in KCs promotes the epithelial–mesenchymal transition and accelerates carcinogenesis. This review discusses the diverse functions of B7-H1 in carcinogenesis and cancer progression, and considers future directions for developing cancer therapy targeting B7-H1. Cancer Res; 71(14); 4737–41. ©2011 AACR.
<i>All-trans</i>-Retinoic Acid Improves Differentiation of Myeloid Cells and Immune Response in Cancer Patients
Authors: Noweeda Mirza, Mayer Fishman, Ingo Fricke, Mary Dunn, Anthony M. Neuger, Timothy J. Frost, Richard M. Lush, Scott Antonia, Dmitry I. Gabrilovich
Journal: Cancer Research (2006)

Abstract Abnormal dendritic cell differentiation and accumulation of immature myeloid suppressor cells (ImC) is one of the major mechanisms of tumor escape. We tested the possibility of pharmacologic regulation of myeloid cell differentiation using all-trans-retinoic acid (ATRA). Eighteen patients with metastatic renal cell carcinoma were treated with ATRA followed by s.c. interleukin 2 (IL-2). Eight healthy individuals comprised a control group. As expected, the cancer patients had substantially elevated levels of ImC. We observed that ATRA dramatically reduced the number of ImC. This effect was observed only in patients with high plasma concentration of ATRA (&amp;gt;150 ng/mL), but not in patients with lower ATRA concentrations (&amp;lt;135 ng/mL). Effects of ATRA on the proportions of different dendritic cell populations were minor. However, ATRA significantly improved myeloid/lymphoid dendritic cell ratio and the ability of patients' mononuclear cells to stimulate allogeneic T cells. This effect was associated with significant improvement of tetanus-toxoid–specific T-cell response. During the IL-2 treatment, the ATRA effect was completely eliminated. To assess the role of IL-2, specimens from 15 patients with metastatic renal cell carcinoma who had been treated with i.v. IL-2 alone were analyzed. In this group also, IL-2 significantly reduced the number and function of dendritic cells as well as T-cell function. These data indicate that ATRA at effective concentrations eliminated ImC, improved myeloid/lymphoid dendritic cell ratio, dendritic cell function, and antigen-specific T-cell response. ATRA treatment did not result in significant toxicity and it could be tested in therapeutic combination with cancer vaccines. (Cancer Res 2006; 66(18): 9299-307)
Protection against Lethal Enterovirus 71 Challenge in Mice by a Recombinant Vaccine Candidate Containing a Broadly Cross-Neutralizing Epitope within the VP2 EF Loop
Authors: Longfa Xu, Delei He, Zhiqun Li, Jun Zheng, Lisheng Yang, Miao Yu, Hai Yu, Yixin Chen, Yuqiong Que, James Wai Kuo Shih, Gang Liu, Jun Zhang, Qinjian Zhao, Tong Cheng, Ningshao Xia
Journal: Theranostics (2014)

Human enterovirus 71 (EV71) is the main causative agent of hand, foot, and mouth disease (HFMD) and is associated with several severe neurological complications in the Asia-Pacific region.Here, we evaluated that while passive transfer of neutralizing monoclonal antibody (nMAb) against the VP2 protein protect against lethal EV71 infection in BALB/c mice.Protective nMAb were mapped to residues 141-155 of VP2 by peptide ELISA.High-resolution structural analysis showed that the epitope is part of the VP2 EF loop, which is the "puff" region that forms the "southern rim" of the canyon.Moreover, a three-dimensional structural characterization for the puff region with prior neutralizing epitopes and receptor-binding sites that can serve to inform vaccine strategies.Interestingly, using hepatitis B virus core protein (HBc) as a carrier, we demonstrated that the cross-neutralizing EV71 antibodies were induced, and the VP2 epitope immunized mice serum also conferred 100% in vivo passive protection.The mechanism of in vivo protection conferred by VP2 nMAb is in part attributed to the in vitro neutralizing titer and ability to bind authentic viral particles.Importantly, the anti-VP2(aa141-155) antibodies could inhibit the binding of human serum to EV71 virions showed that the VP2 epitope is immunodominant.Collectively, our results suggest that a broad-spectrum vaccine strategy targeting the high-affinity epitope of VP2 EF loop may elicits effective immune responses against EV71 infection.
Effects of xiao‐qing‐long‐tang (XQLT) on bronchoconstriction and airway eosinophil infiltration in ovalbumin‐sensitized guinea pigs: <i>in vivo</i> and <i>in vitro</i> studies
Authors: S‐T. Kao, C‐S. Lin, C‐C. Hsieh, W‐T. Hsieh, J‐G. Lin
Journal: Allergy (2001)

Background: Xiao‐qing‐long‐tang (XQLT sho‐seiru‐to), a traditional Chinese medicine, has been used to treat patients with bronchial asthma in Oriental countries for several centuries. However, the therapeutic mechanisms of this Chinese medicine remain a matter of considerable debate. Therefore, a series of experiments using ovalbumin‐sensitized guinea pigs was performed to elucidate the possible antiasthmatic effect of XQLT. Methods: The effect of XQLT on ovalbumin‐induced airway inflammation in a guinea pig model of allergic asthma was examined, and early and late asthmatic responses were measured in terms of airway resistance and extent of eosinophil infiltration. Furthermore, the bronchorelaxing effect of XQLT was measured in isolated guinea pig trachea. Results: XQLT significantly inhibited the antigen‐induced immediate asthmatic response (IAR) and late asthmatic response (LAR) in actively sensitized guinea pigs. Cumulative administration of XQLT caused concentration‐dependent relaxation of the carbachol‐precontracted guinea pig trachea. The bronchorelaxing effect of XQLT was reversed by ICI‐118551, a selective β2‐adrenoceptor antagonist. Furthermore, examination of bronchoalveolar lavage fluid (BALF) revealed that XQLT significantly suppressed the increase in eosinophils (24 h after antigen challenge) in the airway. In addition, XQLT significantly attenuated the increase in eosinophils at 1, 6, 24, 48, and 72 h after antigen challenge when it was administered once daily from the day of sensitization to the day of challenge. Histopathologic examination results showed that XQLT suppressed eosinophil infiltration into lung tissue. Conclusions: These results demonstrate that the antiasthmatic effects of XQLT appear to be partly mediated by stimulation of β2‐adrenoceptors, leading to bronchorelaxation, and that XQLT inhibits the infiltration of eosinophils into the airway. Thus, XQLT may be useful for the prevention or treatment of asthma.
Dietary intake in sensitized children with recurrent wheeze and healthy controls: a nested case–control study
Authors: C. S. Murray, B. Simpson, G. Kerry, A. Woodcock, A. Custovic
Journal: Allergy (2005)

Background: The rising prevalence of asthma and allergic disease remains unexplained. Several risk factors have been implicated including diet, in particular poly‐unsaturated fats and antioxidant intake. Methods: A nested case–control study comparing the dietary intake of sensitized children with recurrent wheeze (age 3–5 years) and nonsensitized children who had never wheezed was carried out within an unselected population‐based cohort. Cases and controls were matched for age, sex, parental atopy, indoor allergen exposure and pet ownership. Dietary intake was assessed using a validated semi‐quantitative food frequency questionnaire and nutrient analysis program. Results: Thirty‐seven case–control pairs (23 male, mean age 4.4 years) participated. Daily total polyunsaturated fat intake was significantly higher in sensitized wheezers (g/day, geometric mean, 95% confidence intervals: 7.1, 6.4–7.9) compared with nonsensitized nonwheezy children (5.6, 5.0–6.3, P = 0.003). Daily omega‐3 and omega‐6 fat intakes were not significantly different between the two groups. No significant differences were found in intake of any antioxidant or antioxidant cofactors between the groups. Conclusions: Young sensitized wheezy children had a significantly higher total polyunsaturated fat intake compared with nonsensitized nonwheezy children. However, we were unable to distinguish a significant difference in specific poly‐unsaturated fat intakes. Otherwise the children in both groups had a very similar nutritional intake.
Location of superoxide anion generation in human colonic mucosa obtained by biopsy.
Authors: N Oshitani, A Kitano, H Okabe, S Nakamura, T Matsumoto, K Kobayashi
Journal: Gut (1993)

To identify which cells generate superoxide, inflamed human mucosa was tested with nitro-blue tetrazolium as a probe, because it is reduced by strong reducing agents to form insoluble blue formazan, which then precipitates in tissues. Biopsy specimens from control subjects and patients with ulcerative colitis were studied. The specimens were organ cultured with bubbling air or nitrogen, and inhibition of the reduction by catalase (a hydrogen peroxide scavenger), para-benzoquinone (a tissue permeable superoxide scavenger), or superoxide dismutase (a superoxide scavenger) was assayed. The dye was reduced by epithelial cells, vascular endothelium, and infiltrating mononuclear cells of the mucosa. Its reduction by vascular endothelium and infiltrating mononuclear cells was greater in inflamed mucosa. The reduction by vascular endothelium and infiltrating mononuclear cells was inhibited in cultures with nitrogen saturation or with 1 mM para-benzoquinone. The vascular endothelium seems to produce superoxide in the inflamed mucosa, which would exacerbate tissue injury in ulcerative colitis.
A single tumour necrosis factor haplotype influences the response to adalimumab in rheumatoid arthritis
Authors: C Miceli-Richard, E Comets, C Verstuyft, R Tamouza, P Loiseau, P Ravaud, H Kupper, L Becquemont, D Charron, X Mariette
Journal: Annals of the Rheumatic Diseases (2007)

To determine whether tumour necrosis factor (TNF) gene polymorphisms and/or the shared epitope are genetic predictors of the response to adalimumab (ADA) in rheumatoid arthritis (RA).This ancillary study to the Research in Active Rheumatoid Arthritis (ReAct) Phase IIIb study included a large cohort of Caucasian patients with RA from France (n = 388) treated with ADA plus methotrexate (MTX) (n = 182), ADA plus any other DMARD (n = 98) or ADA alone (n = 108). The primary outcome was ACR50 at 12 weeks. Patients underwent genotyping for HLA-DRB1 and three TNF gene polymorphisms (-238A/G,-308A/G and-857C/T). Extended haplotypes involving HLA-DRB1 and TNF loci were reconstructed using the PHASE program.A total of 151 patients (40%) had an ACR50 response at week 12. Neither the number of HLA-DRB1 shared epitope copies nor presence of the three TNF polymorphisms tested separately was significantly associated with ACR50 response at week 12. However, haplotype reconstruction of the TNF locus revealed that the GGC haplotype (-238G/-308G/-857C) in a homozygous form (i.e. present in more than half of the patients) was significantly associated with a lower ACR50 response to ADA at 12 weeks (34% vs. 50% in patients without the haplotype) (p = 0.003; pa = 0.015). This effect was more important in the subgroup of patients concomitantly treated with MTX.This large pharmacogenetic study provides preliminary data indicating that a single TNF locus haplotype (-238G/-308G/-857C), present on both chromosomes is associated with a lower response to ADA, mainly in patients treated with ADA and MTX.
Immunoglobulin idiotopes expressed by T cells. I. Expression of distinct idiotopes detected by monoclonal antibodies on antigen-specific suppressor T cells.
Authors: J Cerny, C Heusser, R Wallich, G J Hammerling, D D Eardley
Journal: The Journal of Experimental Medicine (1982)

The idiotopic repertoire expressed by antigen-specific suppressor T cells (Ts) generated by Streptococcus pneumoniae strain R36a (Pn) in BALB/c strain mice was investigated using a panel of five monoclonal anti-idiotopic antibodies against TEPC-15/HOPC-8 myeloma proteins. Previous studies suggested that the anti-idiotopic antibodies recognize distinct idiotopic determinants within the T15 idiotype, and that Pn-reactive B cells express all of those idiotopes as shown by a specific inhibitory effect of the anti-idiotopic antibodies on induction of anti-Pn response in vitro as well as on the mature antibody plaque-forming cells. In this study we asked the question of whether anti-idiotopic (Id) can block the inductive and/or effector phases of generation of Ts which act on the Pn-reactive B cells. The presence of anti-Id during the activation of T cells with Pn did not prevent the generation of Ts. However, suppression mediated by Ts on responder lymphocytes (cultures of spleen cells or B cels) was inhibited (reversed) by four out of five anti-Id. Some of the antibodies recognize hapten (phosphorylcholine)-inhibitable Id in the paratope of Ig whereas others are directed against nonparatopic Id. These data indicate that the antigen receptor on Ts includes VH sequences both within and without the immunoglobulin in paratope, and that the Id repertoir of Ts overlaps with that of B cells.
T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines.
Authors: F Fossiez, O Djossou, P Chomarat, L Flores-Romo, S Ait-Yahia, C Maat, J J Pin, P Garrone, E Garcia, S Saeland, D Blanchard, C Gaillard, B Das Mahapatra, E Rouvier, P Golstein, J Banchereau, S Lebecque
Journal: The Journal of Experimental Medicine (1996)

Analysis of the cDNA encoding murine interleukin (IL) 17 (cytotoxic T lymphocyte associated antigen 8) predicted a secreted protein sharing 57% amino acid identity with the protein predicted from ORF13, an open reading frame of Herpesvirus saimiri. Here we report on the cloning of human IL-17 (hIL-17), the human counterpart of murine IL-17. hIL-17 is a glycoprotein of 155 amino acids secreted as an homodimer by activated memory CD4+ T cells. Although devoid of direct effects on cells of hematopoietic origin, hIL-17 and the product of its viral counterpart, ORF13, stimulate epithelial, endothelial, and fibroblastic cells to secrete cytokines such as IL-6, IL-8, and granulocyte-colony-stimulating factor, as well as prostaglandin E2. Furthermore, when cultured in the presence of hIL-17, fibroblasts could sustain the proliferation of CD34+ hematopoietic progenitors and their preferential maturation into neutrophils. These observations suggest that hIL-17 may constitute (a) an early initiator of the T cell-dependent inflammmatory reaction; and (b) an element of the cytokine network that bridges the immune system to hematopoiesis.
Comparison of continuous ambulatory peritoneal dialysis and hemodialysis patient survival with evaluation of trends during the 1980s.
Authors: C B Nelson, F K Port, R A Wolfe, K E Guire
Journal: Journal of the American Society of Nephrology (1992)

To evaluate the mortality of continuous ambulatory peritoneal dialysis (CAPD) patients relative to hemodialysis (HD) patients, all Michigan residents 20 to 59 yr of age who initiated therapy for ESRD during the 1980s (N = 4,288) were studied. The study population was stratified by primary renal diagnosis (glomerulonephritis, hypertension, diabetes, other), and analyses were conducted within each group by Cox proportional hazards methods controlling for age, race, sex, and year in which chronic dialysis was initiated. Intent-to-treat (ITT) and treatment history (RxHx) censoring criteria were used. For patients with hypertension or other reported causes of ESRD, there was no significant difference in CAPD and HD patient mortality (relative risk (RR) = 0.99 and 1.05, respectively). In the ITT analysis, both glomerulonephritic (RR = 0.73; P = 0.10) and diabetic patients using CAPD experienced mortality rates lower than their HD counterparts. Among diabetics, this difference ranged from a RR of 0.40 to 0.70, being lowest for younger diabetics and statistically significant (P < or = 0.05) for ages 20 to 52 yr. Evaluation of mortality trends showed a significant (P < 0.01) decrease in diabetic CAPD mortality rates during the decade, whereas diabetic HD mortality rates increased (P = 0.06). Among diabetics, men had higher mortality rates than women (ITT--RxHx; RR = 1.22 to 1.27; P < 0.001) and white patients had higher mortality rates than black patients (ITT--RxHx, RR = 1.34 to 1.44; P < 0.001). Differences in mortality by sex and race were not found among nondiabetics, but mortality did increase significantly with age in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Local delivery of a recombinant adenoassociated vector containing a tumour necrosis factor antagonist gene in inflammatory arthritis: a phase 1 dose-escalation safety and tolerability study
Authors: P J Mease, K Hobbs, A Chalmers, H El-Gabalawy, A Bookman, E Keystone, D E Furst, P Anklesaria, A E Heald
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> To examine the safety and tolerability of a single intra-articular injection of rAAV2-TNFR:Fc, an adenoassociated virus serotype 2 vector containing the cDNA for the human tumour necrosis factor–immunoglobulin Fc fusion gene (tgAAC94), in subjects with inflammatory arthritis. <h3>Methods:</h3> In a double-blind, placebo-controlled, phase 1, dose-escalation study, 15 subjects with inflammatory arthritis (14 with rheumatoid arthritis and 1 with ankylosing spondylitis) not receiving tumour necrosis factor α (TNFα) inhibitors with persistent moderate (grade 2) or severe (grade 3) swelling in a target joint due to inflammatory arthritis received a single intra-articular injection of rAAV2-TNFR:Fc at 1×10<sup>10</sup> (n = 5) or 1×10<sup>11</sup> (n = 6) DNase resistant particles per ml joint volume or placebo (n = 4) into a knee (n = 14) or ankle (n = 1). Safety was assessed through adverse event monitoring. As a secondary objective, changes in injected joint tenderness and swelling scores, each measured on a four-point scale, were evaluated. <h3>Results:</h3> Intra-articular injections of rAAV2-TNFR:Fc were well tolerated with no major safety issues. One event, mild knee pruritis, was considered probably related. Synovial fluid TNFR:Fc protein was not detected (nor expected) at the doses used. At 12 weeks after injection, a two-point decrease in swelling was noted in 2/11 and 2/4 subjects injected with rAAV2-TNFR:Fc and placebo, respectively. <h3>Conclusion:</h3> A single dose of intra-articular rAAV2-TNFR:Fc appears to be safe and well tolerated in subjects without concurrent systemic TNFα antagonist use. It is thus feasible to proceed with larger trials to further test the safety and efficacy of local TNFR:Fc gene transfer as a therapeutic modality for patients with inflammatory arthritis.
The validity of capillary blood sampling in the determination of human growth hormone concentration during exercise in men
Authors: R J Godfrey, G Whyte, J McCarthy, A Nevill, A Head
Journal: British Journal of Sports Medicine (2004)

Background: Studies measuring human growth hormone (hGH) in blood during exercise have mainly used venous sampling. The invasive nature of this procedure makes evaluation of hGH impossible in various exercise environments. Objective: To determine whether capillary sampling could offer an alternative sampling method. Methods: Capillary and venous blood samples were collected for determination of hGH at the end of each exercise stage during an incremental exercise test in 16 male club level competitive cyclists (mean (SD) age 30.8 (8.0) years, body mass 72.2 (7.1) kg, body fat 12.9 (3.5)%, peak oxygen consumption 4.18 (0.46) l⋅min −1 ). Linear regression, from a plot of venous v capillary blood hGH concentration, showed a correlation coefficient of r = 0.986 (p&lt;0.001). When geometric means and log transformations were used, a coefficient of variation of 14.2% was demonstrated between venous and capillary flow for hGH concentration. The mean ratio limits of agreement were 0.62 (1.72)—that is, 95% of the ratios were contained between 0.36 and 1.07, with a mean of 0.62. Conclusions: Capillary blood sampling is an acceptable alternative to venous sampling for determining hGH concentration during rest and exercise. Sample sites should not be used interchangeably: one site should be chosen and its use standardised.
Estrogen receptor α mediates the nongenomic activation of endothelial nitric oxide synthase by estrogen
Authors: Zhong Chen, Ivan S. Yuhanna, Zoya Galcheva-Gargova, Richard H. Karas, Michael E. Mendelsohn, Philip W. Shaul
Journal: Journal of Clinical Investigation (1999)

Estrogen is an important vasoprotective molecule that causes the rapid dilation of blood vessels by activating endothelial nitric oxide synthase (eNOS) through an unknown mechanism. In studies of intact ovine endothelial cells, 17β-estradiol (E2) caused acute (five-minute) activation of eNOS that was unaffected by actinomycin D but was fully inhibited by concomitant acute treatment with specific estrogen receptor (ER) antagonists. Overexpression of the known transcription factor ERα led to marked enhancement of the acute response to E2, and this was blocked by ER antagonists, was specific to E2, and required the ERα hormone-binding domain. In addition, the acute response of eNOS to E2 was reconstituted in COS-7 cells cotransfected with wild-type ERα and eNOS, but not by transfection with eNOS alone. Furthermore, the inhibition of tyrosine kinases or mitogen-activated protein (MAP) kinase kinase prevented the activation of eNOS by E2, and E2 caused rapid ER-dependent activation of MAP kinase. These findings demonstrate that the short-term effects of estrogen central to cardiovascular physiology are mediated by ERα functioning in a novel, nongenomic manner to activate eNOS via MAP kinase–dependent mechanisms.