tbuckley/cabot-search huggingface dataset:
Effect of IL15 on T cell clonality in vitro and in the synovial fluid of patients with rheumatoid arthritis
Authors: K. Masuko-Hongo
Journal: Annals of the Rheumatic Diseases (2000)

Recent studies have suggested that interleukin (IL) 15 induces T cell accumulation in synovial lesions of rheumatoid arthritis (RA). This study aimed at determining whether this cytokine could explain in vivo T cell clonality in RA.Peripheral blood mononuclear cells (PBMC) from patients with RA were stimulated in vitro with IL15 or IL2. After isolation of mRNA from stimulated cells and synovial T cells, genes coding the V-D(N)-J (CDR3) region of T cell receptor beta chains were amplified by a reverse transcriptase polymerase chain reaction. A single strand conformation polymorphism analysis was used to detect the clonotype(s) of accumulating T cells. Nucleotide and amino acid sequencing was also performed.Stimulation of PBMC with IL15 resulted in oligoclonal expansion of T cells. However, IL15 induced clones from PBMC were mostly different from the dominantly expanding T cell clones in synovial fluid. Furthermore, IL15 and IL2 responding clones were only partially identical.Although IL15 results in clonal accumulation of T cells, T cell clonality in rheumatoid joints could not be explained by the effect of IL15 alone. The results indicated the requirement of other factor(s), in addition to IL15, in the pathological process affecting RA joints. The results also suggested different responses by each T cell clone to IL15 or IL2.
A rare cause of an ileocaecal mass and lymphadenopathy
Authors: Emma L Culver, Eleanor Barnes, David Delaney, Antony J Ellis, Bruce George, Roger W Chapman
Journal: Gut (2011)

A 56-year-old gentleman presented with a 6-week history of fatigue, drenching night sweats and 6 kg of weight loss. Clinical examination revealed a palpable right iliac fossa mass. He had a history of hypertension. Full blood count, differential white count and blood film were unremarkable. Inflammatory markers were elevated: …
Macrophage Targeted Theranostics as Personalized Nanomedicine Strategies for Inflammatory Diseases
Authors: Sravan Kumar Patel, Jelena M. Janjic
Journal: Theranostics (2014)

Inflammatory disease management poses challenges due to the complexity of inflammation and inherent patient variability, thereby necessitating patient-specific therapeutic interventions. Theranostics, which integrate therapeutic and imaging functionalities, can be used for simultaneous imaging and treatment of inflammatory diseases. Theranostics could facilitate assessment of safety, toxicity and real-time therapeutic efficacy leading to personalized treatment strategies. Macrophages are an important cellular component of inflammatory diseases, participating in varied roles of disease exacerbation and resolution. The inherent phagocytic nature, abundance and disease homing properties of macrophages can be targeted for imaging and therapeutic purposes. This review discusses the utility of theranostics in macrophage ablation, phenotype modulation and inhibition of their inflammatory activity leading to resolution of inflammation in several diseases.
Re: Semen of Smokers and Cervical Cancer Risk
Authors: P. Whidden
Journal: JNCI Journal of the National Cancer Institute (1997)

Tokudome (1) suggested that key constituents of tobacco smoke inhaled by women are conveyed internally to the cervical mucus. He also said that another route for carcinogenic agents in tobacco smoke to be introduced into the cervical mucus is through the direct application of ‘‘tobacco-related mutagens/ carcinogens in a smoking sex partner’s semen/seminal fluid.’’ Two early reports (2,3) about cervical cancer that dealt with male partners’ smoking habits brought up the possibility that important agents in tobacco smoke adhering to the male’s fingers could be introduced into the vaginal mucus by ‘‘men using their fingers regularly within the vagina and on the clitoris during coital caressing’’ ( 3). The fingers of a male smoker might well be a very heavily coated part of his anatomy as regards the tar of tobacco smoke. Thus, these three routes of exposure for the cervix to mutagenic and carcinogenic agents derived from tobacco smoke—inhalation, including that by passive smokers (4); contaminated semen/seminal fluid; and digital stimulation of the vagina by fingers coated with tobacco tars—might well add up to a significant burden and might provide a trigger for a rise in risk for cervical cancer in women whose long-time male sexual partners are smokers.
Sacral nerve stimulation for intractable constipation
Authors: M. A. Kamm, T. C. Dudding, J. Melenhorst, M. Jarrett, Z. Wang, S. Buntzen, C. Johansson, S. Laurberg, H. Rosen, C. J. Vaizey, K. Matzel, C. Baeten
Journal: Gut (2010)

Traditional surgical procedures for intractable idiopathic constipation are associated with a variable outcome and substantial morbidity. The symptomatic response, physiological effect and effect on quality of life of sacral nerve stimulation (SNS) were evaluated in patients with constipation (slow transit and normal transit with impaired evacuation).In a prospective study at five European sites patients who failed conservative treatment underwent 21 days test stimulation. Patients with >50% improvement in symptoms underwent permanent neurostimulator implantation. Primary end points were increased defecation frequency, decreased straining and decreased sensation of incomplete evacuation.62 patients (55 female, median age 40 years) underwent test stimulation, of whom 45 (73%) proceeded to chronic stimulation. 39 (87%) of these 45 patients achieved treatment success. After a median 28 (range 1-55) months follow-up, defecation frequency increased from 2.3 to 6.6 evacuations per week (p<0.001). Days per week with evacuation increased from 2.3 to 4.8 (p<0.001). There was a decrease in time spent toileting (10.5 to 5.7 min, p=0.001), straining (75-46% of successful evacuations, p<0.001), perception of incomplete evacuation (71.5-46% of successful evacuations, p<0.001) and subjective rating of abdominal pain and bloating (p<0.001). Cleveland Clinic constipation score (0=no to 30=severe constipation) decreased from 18 to 10 (p<0.001). Visual analogue scale (VAS) score (0=severe to 100=no symptoms) increased from 8 to 66 (p<0.001). Patients with slow and normal transit benefited. Quality of life significantly improved. Colonic transit normalised in half of those with baseline slow transit (p=0.014).SNS is effective in the treatment of idiopathic slow and normal transit constipation resistant to conservative treatment. Clinical Trial Number NCT00200005.
Role of Protein Tyrosine Phosphatase 1B in Vascular Endothelial Growth Factor Signaling and Cell–Cell Adhesions in Endothelial Cells
Authors: Yoshimasa Nakamura, Nikolay Patrushev, Hyoe Inomata, Dolly Mehta, Norifumi Urao, Ha Won Kim, Masooma Razvi, Vidisha Kini, Kalyankar Mahadev, Barry J. Goldstein, Ronald McKinney, Tohru Fukai, Masuko Ushio-Fukai
Journal: Circulation Research (2008)

Vascular endothelial growth factor (VEGF) binding induces phosphorylation of VEGF receptor (VEGFR)2 in tyrosine, which is followed by disruption of VE-cadherin-mediated cell-cell contacts of endothelial cells (ECs), thereby stimulating EC proliferation and migration to promote angiogenesis. Tyrosine phosphorylation events are controlled by the balance of activation of protein tyrosine kinases and protein tyrosine phosphatases (PTPs). Little is known about the role of endogenous PTPs in VEGF signaling in ECs. In this study, we found that PTP1B expression and activity are markedly increased in mice hindlimb ischemia model of angiogenesis. In ECs, overexpression of PTP1B, but not catalytically inactive mutant PTP1B-C/S, inhibits VEGF-induced phosphorylation of VEGFR2 and extracellular signal-regulated kinase 1/2, as well as EC proliferation, whereas knockdown of PTP1B by small interfering RNA enhances these responses, suggesting that PTP1B negatively regulates VEGFR2 signaling in ECs. VEGF-induced p38 mitogen-activated protein kinase phosphorylation and EC migration are not affected by PTP1B overexpression or knockdown. In vivo dephosphorylation and cotransfection assays reveal that PTP1B binds to VEGFR2 cytoplasmic domain in vivo and directly dephosphorylates activated VEGFR2 immunoprecipitates from human umbilical vein endothelial cells. Overexpression of PTP1B stabilizes VE-cadherin-mediated cell-cell adhesions by reducing VE-cadherin tyrosine phosphorylation, whereas PTP1B small interfering RNA causes opposite effects with increasing endothelial permeability, as measured by transendothelial electric resistance. In summary, PTP1B negatively regulates VEGFR2 receptor activation via binding to the VEGFR2, as well as stabilizes cell-cell adhesions through reducing tyrosine phosphorylation of VE-cadherin. Induction of PTP1B by hindlimb ischemia may represent an important counterregulatory mechanism that blunts overactivation of VEGFR2 during angiogenesis in vivo.
ON THE DIALYSABILITY OF THE GROWTH-ACTIVATING PRINCIPLE CONTAINED IN EXTRACTS OF EMBRYONIC TISSUES
Authors: G. Payling Wright
Journal: The Journal of Experimental Medicine (1926)

These experiments appear to indicate that whatever substance in embryonic tissue extracts excites mitosis, and therefore would appear to be the growth-stimulating substance, is capable of passing through a collodion membrane which is impermeable to proteins, at all events in such concentration as would give rise to any biuret reaction. The substance is therefore diffusible.
Predominance of Intraglomerular T-bet or GATA3 May Determine Mechanism of Transplant Rejection
Authors: Qiquan Sun, Dongrui Cheng, Mingchao Zhang, Qunpeng He, Zhaohong Chen, Zhihong Liu
Journal: Journal of the American Society of Nephrology (2011)

The transcription factors T-bet and GATA3 determine the differentiation of helper T cells into Th1 or Th2 cells, respectively. An altered ratio of their relative expression promotes the pathogenesis of certain immunological diseases, but whether this may also contribute to the pathogenesis of antibody-mediated rejection (ABMR) versus T cell-mediated rejection (TCMR) is unknown. Here, we characterized the intragraft expression of T-bet and GATA3 and determined the correlation of their levels with the presence of typical lesions of ABMR and TCMR. We found a predominant intraglomerular expression of T-bet in patients with ABMR, which was distinct from that in patients with TCMR. In ABMR, interstitial T-bet expression was typically located in peritubular capillaries, although the overall quantity of interstitial T-bet was less than that observed in TCMR. The expression of intraglomerular T-bet correlated with infiltration of CD4+ and CD8+ lymphocytes, which express T-bet, as well as intraglomerular CD68+ monocyte/macrophages, which do not express T-bet. The predominance of intraglomerular T-bet expression relative to GATA3 expression associated with poor response to treatment with bolus steroid. In summary, predominance of intraglomerular T-bet expression correlates with antibody-mediated rejection and resistance to steroid treatment.
Autologous transplantation gives encouraging results for young adults with favorable-risk acute myeloid leukemia, but is not improved with gemtuzumab ozogamicin
Authors: Hugo F. Fernandez, Zhuoxin Sun, Mark R. Litzow, Selina M. Luger, Elisabeth M. Paietta, Janis Racevskis, Gordon Dewald, Rhett P. Ketterling, Jacob M. Rowe, Hillard M. Lazarus, Martin S. Tallman
Journal: Blood (2011)
Weight Lifting and Physical Function Among Survivors of Breast Cancer: A Post Hoc Analysis of a Randomized Controlled Trial
Authors: Justin C. Brown, Kathryn H. Schmitz
Journal: Journal of Clinical Oncology (2015)

Survivors of breast cancer may experience deterioration of physical function. This is important because poor physical function may be associated with premature mortality, injurious falls, bone fracture, and disability. We conducted a post hoc analysis to explore the potential efficacy of slowly progressive weight lifting to reduce the incidence of physical function deterioration among survivors of breast cancer.Between October 2005 and August 2008, we conducted a single-blind, 12-month, randomized controlled trial of twice-per-week slowly progressive weight lifting or standard care among 295 survivors of nonmetastatic breast cancer. In this post hoc analysis of data from the Physical Activity and Lymphedema Trial, we examined incident deterioration of physical function after 12 months, defined as a ≥ 10-point decrease in the physical function subscale of the Medical Outcomes Short-Form 36-item questionnaire.The proportion of participants who experienced incident physical function deterioration after 12 months was 16.3% (24/147) in the control group and 8.1% (12/148) in the weight lifting group (relative risk, 0.49; 95% CI, 0.25 to 0.96; P = .04). No serious or unexpected adverse events occurred that were related to weight lifting.Slowly progressive weight lifting compared with standard care reduced the incidence of physical function deterioration among survivors of breast cancer. These data are hypothesis generating. Future studies should directly compare the efficacy of weight lifting with other modalities of exercise, such as brisk walking, to appropriately inform the development of a confirmatory study designed to preserve physical function among survivors of breast cancer.
A map of human microRNA variation uncovers unexpectedly high levels of variability
Authors: José Carbonell, Eva Alloza, Pablo Arce, Salud Borrego, Javier Santoyo, Macarena Ruiz-Ferrer, Ignacio Medina, Jorge Jiménez-Almazán, Cristina Méndez-Vidal, María González-del Pozo, Alicia Vela, Shomi S Bhattacharya, Guillermo Antiñolo, Joaquín Dopazo
Journal: Genome Medicine (2012)

MicroRNAs (miRNAs) are key components of the gene regulatory network in many species. During the past few years, these regulatory elements have been shown to be involved in an increasing number and range of diseases. Consequently, the compilation of a comprehensive map of natural variability in a healthy population seems an obvious requirement for future research on miRNA-related pathologies. Data on 14 populations from the 1000 Genomes Project were analyzed, along with new data extracted from 60 exomes of healthy individuals from a population from southern Spain, sequenced in the context of the Medical Genome Project, to derive an accurate map of miRNA variability. Despite the common belief that miRNAs are highly conserved elements, analysis of the sequences of the 1,152 individuals indicated that the observed level of variability is double what was expected. A total of 527 variants were found. Among these, 45 variants affected the recognition region of the corresponding miRNA and were found in 43 different miRNAs, 26 of which are known to be involved in 57 diseases. Different parts of the mature structure of the miRNA were affected to different degrees by variants, which suggests the existence of a selective pressure related to the relative functional impact of the change. Moreover, 41 variants showed a significant deviation from the Hardy-Weinberg equilibrium, which supports the existence of a selective process against some alleles. The average number of variants per individual in miRNAs was 28. Despite an expectation that miRNAs would be highly conserved genomic elements, our study reports a level of variability comparable to that observed for coding genes.
Joint Effect of Mutagen Sensitivity and Insulin-Like Growth Factors in Predicting the Risk of Developing Secondary Primary Tumors and Tumor Recurrence in Patients with Head and Neck Cancer
Authors: Xifeng Wu, Jian Gu, Qiong Dong, Maosheng Huang, Kim-Anh Do, Waun Ki Hong, Margaret R. Spitz
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Early-stage head and neck cancer patients are at high risks for tumor recurrence and secondary primary tumor (SPT) development. We hypothesized that latent genetic instability and proliferation potential may be associated with elevated risks of SPT and recurrence. Experimental Design: We conducted a nested case-control study within a randomized, placebo-controlled chemoprevention trial in patients with early-stage head and neck cancer. We compared prediagnostic bleomycin-induced chromatid breaks in peripheral blood lymphocyte cultures (as an indicator of latent genetic instability) between 298 cases (patients with SPT/recurrence) and 693 controls (patients without SPT/recurrence). We also determined the joint effects of latent genetic instability and elevated proliferation potential [indicated by serum insulin-like growth factor (IGF) level] in modulating the risk of SPT and recurrence. Results: In the Cox proportional hazards model, patients with higher mutagen sensitivity (using a cutoff of ≥0.50 breaks per cell) exhibited a significantly increased risk of developing SPT/recurrence [hazard ratio, 1.38; 95% confidence interval (95% CI), 1.02-1.86]. Cases also exhibited significantly higher levels of IGF-I and IGF-binding protein-3 than controls (P = 0.022 and 0.042, respectively). Moreover, there were joint effects between mutagen sensitivity and IGFs in modulating SPT/recurrence risk. Using patients with low IGF-I level and low mutagen sensitivity profile as the reference group, the odds ratios of developing SPT/recurrence for patients with high IGF-I level alone, high mutagen sensitivity alone, and both high IGF-I level and high mutagen sensitivity were 2.85 (95% CI, 0.92-8.82), 3.92 (95% CI, 1.28-11.97), and 6.16 (95% CI, 2.03-18.71), respectively. A similar joint effect was observed for mutagen sensitivity and IGF-binding protein-3 level. Conclusions: This is the largest prospective study to evaluate mutagen sensitivity as a prognosis marker in head and neck cancer because mutagen sensitivity data were derived from baseline samples drawn before the development of SPT or tumor recurrence. The results also show for the first time that latent genetic instability and elevated proliferation potential jointly elevate the risk of second tumors in early-stage head and neck cancers.
Tranquillisers and plasma prolactin.
Authors: J D Wilson, D J King, B Sheridan
Journal: BMJ (1979)

above, and to refer to dialysis and trans- plantation treatment as "extraordinary" is surely an unjustifiable judgment.At a time when the referral rate to nephrologists clearly indicates that many patients are dying from end-stage renal failure without the benefit of proper assess- ment, the general medical profession should be clearly aware of the real benefits of renal replacement therapy.
Ischemic Preconditioning Activates MAPKAPK2 in the Isolated Rabbit Heart
Authors: Atsushi Nakano, Christopher P. Baines, Sung O. Kim, Steven L. Pelech, James M. Downey, Michael V. Cohen, Stuart D. Critz
Journal: Circulation Research (2000)

Recent studies suggest that p38 mitogen-activated protein kinase (MAPK) may be involved in ischemic preconditioning (PC). To further test this possibility, the regulation of MAPK-activated protein kinase 2 (MAPKAPK2), a kinase immediately downstream from p38 MAPK, and the activity of c-Jun NH(2)-terminal kinase (JNK), a second MAPK, were examined in preconditioned hearts. Isolated, perfused rabbit hearts were subjected to 20 to 30 minutes of global ischemia. Ventricular biopsies before treatment and after 20 minutes of ischemia were homogenized, and the activities of MAPKAPK2 and JNK were evaluated. For the MAPKAPK2 experiments, 7 groups were studied, as follows: control hearts; preconditioned hearts; hearts treated with 500 nmol/L R(-) N(6)-(2-phenylisopropyl) adenosine (PIA), an A(1)-adenosine receptor agonist; preconditioned hearts pretreated with 100 micromol/L 8-(p-sulfophenyl) theophylline (SPT), an adenosine receptor antagonist; preconditioned hearts also treated with SB 203580, a potent inhibitor of p38 MAPK activation; hearts treated with 50 ng/mL anisomycin (a p38 MAPK/JNK activator); and hearts treated with both anisomycin (50 ng/mL) and the tyrosine kinase inhibitor genistein (50 micromol/L). MAPKAPK2 activity was not altered in control hearts after 20 minutes of global ischemia. By contrast, there was a 3.8-fold increase in activity during ischemia in preconditioned hearts. Activation of MAPKAPK2 in preconditioned hearts was blocked by both SPT and SB 203580. MAPKAPK2 activity during ischemia increased 3.5-fold and 3.3-fold in hearts pretreated with PIA or anisomycin, respectively. MAPKAPK2 activation during ischemia in hearts pretreated with anisomycin was blocked by genistein. In separate hearts, anisomycin mimicked the anti-infarct effect of PC, and that protection was abolished by genistein. JNK activity was measured in control and preconditioned hearts. There was a comparable, modest decline in activity during 30 minutes of global ischemia in both groups. As a positive control, a third group of hearts was treated with anisomycin before global ischemia, and in these, JNK activity increased by 290% above baseline. These results confirm that the p38 MAPK/MAPKAPK2 pathway is activated during ischemia only if the heart is in a preconditioned state. These data further support p38 MAPK as an important signaling component in ischemic PC.
Prognostic Significance of Tumor Response at the End of Therapy in Group III Rhabdomyosarcoma: A Report From the Children's Oncology Group
Authors: David A. Rodeberg, Julie A. Stoner, Andrea Hayes-Jordan, Simon C. Kao, Suzanne L. Wolden, Steve J. Qualman, William H. Meyer, Douglas S. Hawkins
Journal: Journal of Clinical Oncology (2009)

Some patients with rhabdomyosarcoma (RMS) achieve less than a complete response (CR) despite receiving all planned therapy. We assessed the impact of best response at the completion of all therapy on patient outcome.We studied 419 clinical group III participants who completed all protocol therapy without developing progressive disease for Intergroup Rhabdomyosarcoma Study (IRS) IV. Response (complete resolution [CR], partial response [PR; > or = 50% decrease], or no response [NR; < 50% decrease and < 25% increase]) was determined by radiographic measurement and categorized by the best response.At the end of therapy, 341 participants (81%) achieved a best response of CR and 78 (19%) had a best response of PR/NR. Five-year failure-free survival was similar for participants achieving CR (80%) and PR/NR (78%). After adjustment for age, nodal status, primary site, and histology, there was no significant indication of lower risk of failure (hazard ratio [HR], 0.77; 95% CI, 0.46 to 1.27; P = .3) nor death (HR, 0.63; 95% CI, 0.36 to 1.09; P = .1) for CR versus PR/NR participants. Seventeen participants with a best response of PR/NR had surgical procedures; eight (50%) of 16 with available pathology reports had residual viable tumor and only three achieved a complete resection. Resection of residual masses was not associated with improved outcome.CR status at the end of protocol therapy in clinical group III participants was not associated with a reduction of disease recurrence and death. Aggressive alternative therapy may not be warranted for RMS patients with a residual mass at the end of planned therapy.
Safety and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine: a randomised, double-blind, placebo-controlled, exploratory phase 2 trial
Authors: David W Dodick, Peter J Goadsby, Stephen D Silberstein, Richard B Lipton, Jes Olesen, Messoud Ashina, Kerri Wilks, David Kudrow, Robin Kroll, Bruce Kohrman, Robert Bargar, Joe Hirman, Jeff Smith
Journal: The Lancet Neurology (2014)