tbuckley/cabot-search huggingface dataset:
* Can we categorise patients with inflammatory bowel disease unclassified (IBDU) wirelessly?
Authors: R. Kalla, M. E. McAlindon, R. Sidhu
Journal: Gut (2011)

<h3>Introduction</h3> Capsule endoscopy (CE) has developed an established role in the investigation of patients with Crohn9s disease. However, there remains a paucity of published literature on the use of CE in the setting of patients with indeterminate colitis (IBDU). We investigated the diagnostic yield of CE in patients with (IBDU) and impact on subsequent diagnosis and management. <h3>Methods</h3> Patients referred to the CE service routinely from 2003 to 2009 with a diagnosis of IBDU, were identified retrospectively. Data was collected for patient demographics, previous investigations, medications and findings at CE. Patients with findings of three or more ulcers with the presence of erythema and oedema were classed as Crohn9s disease. Follow up data was collected on all patients to assess the impact of CE on final outcomes. <h3>Results</h3> A total of thirty seven patients with histological indeterminate colitis were identified. There were 78% females with median age of 47 years (range 18–81 years).The majority of patients (78%) had symptoms of diarrhoea. Abdominal pain represented 60% while 78% of patients (n=29) had evidence of raised inflammatory markers. All patients had prior colonoscopy with terminal ileal (TI) intubation in 65% (n=24).Forty two percent of patients (n=10/24) had macroscopic abnormalities at TI, of which 10 % were normal and 90% (n=9) showed non specific changes histologically. The mean follow up period was 19 months (±2). Small bowel changes including ulceration or erosions, oedema, petechiae and erythema were identified in 43% (n=16/37) of patients on CE. There were no complications with CE. The diagnosis of Crohn9s was made in 14 patients at follow up (41%) with 1 patient lost to follow up and one patient with a diagnosis of non-steroidal ant-inflammatory drug (NSAID) enteropathy. Seven of these patients had a normal small bowel radiology prior to CE. Management was altered in 78% of patients (n=11/14). Two patients had medication change; steroids (n=1) and anti-TNF (n=1) and histological verification with a repeat ileo-colonoscopy or double-balloon enteroscopy was performed in nine patients. While in two patients, Crohn9s disease was confirmed, in seven patients, despite changes of ulcers or stricturing, biopsies showed focal active ulceration which fell short for the histological criteria for Crohn9s disease. There was no change in management in 3 patients due to symptom resolution. On logistic regression, hypoalbuminaemia(p=0.059) and diarrhoea (p=0.058) were predictive of a positive diagnosis on CE. The diagnosis of IBDU remained in 59% of patients (n=21). <h3>Conclusion</h3> CE is useful for identifying patients classed as IBDU who may have underlying Crohn9s disease with a positive impact on their management. Further larger studies are required to validate these results.
BLOCKING AND REDISTRIBUTION ("CAPPING") OF ANTIGEN RECEPTORS ON T AND B LYMPHOCYTES BY ANTI-IMMUNOGLOBULIN ANTIBODY
Authors: Georges Roelants, Luciana Forni, Benvenuto Pernis
Journal: The Journal of Experimental Medicine (1973)

Antigen-binding T and B lymphocytes were studied by combined autoradiography and immunofluorescence; mouse spleen lymphocytes binding the antigens, [(125)I]MSH or [(125)I]TIGAL, were incubated with rhodamine-labeled anti-Ig reagents or with a rhodamine-labeled IgG fraction of anti-theta serum. B cells were identified as Ig+ or theta-, T cells as Ig- or theta+. It was found that: (a) 20% (1-2 mo after priming) to 30% (3.5-4 mo after priming) of the antigen-binding cells were T cells. (b) The range of antigen molecules bound by B and T cells was similar. (c) Binding of antigen to B and T cells was inhibited by polyvalent anti-Ig, anti-micro, or anti-L reagents. Binding to T cells was more readily inhibited than to B cells. Normal rabbit serum, antimouse lymphocyte serum, or anti-theta did not inhibit antigen binding. (d) When Ig at the surface of B cells was induced, by noninhibiting concentrations of anti-Ig reagents, to redistribute into polar caps and the cells subsequently exposed to [(125)I)antigen under noncapping conditions, the [(125)I]antigen silver grains were distributed in caps superimposed on the Ig fluorescent cap. Of crucial importance, antigen was found in cap in the same proportion of T cells as B cells. Significant capping of antigen receptors was not induced in B or T cells with normal rabbit serum or by anti-Ig reagents absorbed with mouse Ig. The main conclusions of this series of experiments using direct visualization of antigen-binding B and T lymphocytes is that T cells have antigen-specific receptors, probably of IgM nature, and that the number of these receptors appears to range in the order of thousands.
Convection-Enhanced Delivery of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand with Systemic Administration of Temozolomide Prolongs Survival in an Intracranial Glioblastoma Xenograft Model
Authors: Ryuta Saito, John R. Bringas, Amith Panner, Matyas Tamas, Russell O. Pieper, Mitchel S. Berger, Krystof S. Bankiewicz
Journal: Cancer Research (2004)

Abstract Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent activator of cell death, preferentially killing neoplastic cells over normal cells, the efficacy of TRAIL for the treatment of glioma might be limited due to cellular resistance and, importantly, poor distribution after systemic administration. TRAIL and temozolomide (TMZ) were recently shown to have a synergistic antitumor effect against U87MG glioma cells in vitro. Convection-enhanced delivery (CED) can effectively distribute TRAIL protein throughout a brain tumor mass. In this study, we evaluated CED of TRAIL, alone and in conjunction with systemic TMZ administration, for antitumor efficacy. CED of TRAIL demonstrated safe and effective distribution in both normal brain and a U87MG intracranial xenograft model. Individually, both CED of TRAIL and systemic TMZ administration prolonged survival in tumor-bearing rats. However, the combination of these two treatments was significantly more effective than either treatment alone. CED of TRAIL in conjunction with systemic TMZ treatment is a promising strategy for the treatment of malignant gliomas.
Constraints on HIV-1 evolution and immunodominance revealed in monozygotic adult twins infected with the same virus
Authors: Rika Draenert, Todd M. Allen, Yang Liu, Terri Wrin, Colombe Chappey, Cori L. Verrill, Guillem Sirera, Robert L. Eldridge, Matthew P. Lahaie, Lidia Ruiz, Bonaventura Clotet, Christos J. Petropoulos, Bruce D. Walker, Javier Martinez-Picado
Journal: The Journal of Experimental Medicine (2006)

The predictability of virus-host interactions and disease progression in rapidly evolving human viral infections has been difficult to assess because of host and genetic viral diversity. Here we examined adaptive HIV-specific cellular and humoral immune responses and viral evolution in adult monozygotic twins simultaneously infected with the same virus. CD4 T cell counts and viral loads followed similar trajectories over three years of follow up. The initial CD8 T cell response targeted 17 epitopes, 15 of which were identical in each twin, including two immunodominant responses. By 36 months after infection, 14 of 15 initial responses were still detectable in both, whereas all new responses were subdominant and remained so. Of four responses that declined in both twins, three demonstrated mutations at the same residue. In addition, the evolving antibody responses cross-neutralized the other twin's virus, with similar changes in the pattern of evolution in the envelope gene. These results reveal considerable concordance of adaptive cellular and humoral immune responses and HIV evolution in the same genetic environment, suggesting constraints on mutational pathways to HIV immune escape.
Replication of EPHA1 and CD33 associations with late-onset Alzheimer's disease: a multi-centre case-control study
Authors: Minerva M Carrasquillo, Olivia Belbin, Talisha A Hunter, Li Ma, Gina D Bisceglio, Fanggeng Zou, Julia E Crook, V Shane Pankratz, Sigrid B Sando, Jan O Aasly, Maria Barcikowska, Zbigniew K Wszolek, Dennis W Dickson, Neill R Graff-Radford, Ronald C Petersen, Peter Passmore, Kevin Morgan, Steven G Younkin
Journal: Molecular Neurodegeneration (2011)

A recently published genome-wide association study (GWAS) of late-onset Alzheimer's disease (LOAD) revealed genome-wide significant association of variants in or near MS4A4A, CD2AP, EPHA1 and CD33. Meta-analyses of this and a previously published GWAS revealed significant association at ABCA7 and MS4A, independent evidence for association of CD2AP, CD33 and EPHA1 and an opposing yet significant association of a variant near ARID5B. In this study, we genotyped five variants (in or near CD2AP, EPHA1, ARID5B, and CD33) in a large (2,634 LOAD, 4,201 controls), independent dataset comprising six case-control series from the USA and Europe. We performed meta-analyses of the association of these variants with LOAD and tested for association using logistic regression adjusted by age-at-diagnosis, gender, and APOE ε4 dosage.We found no significant evidence of series heterogeneity. Associations with LOAD were successfully replicated for EPHA1 (rs11767557; OR = 0.87, p = 5 × 10-4) and CD33 (rs3865444; OR = 0.92, p = 0.049), with odds ratios comparable to those previously reported. Although the two ARID5B variants (rs2588969 and rs494288) showed significant association with LOAD in meta-analysis of our dataset (p = 0.046 and 0.008, respectively), the associations did not survive adjustment for covariates (p = 0.30 and 0.11, respectively). We had insufficient evidence in our data to support the association of the CD2AP variant (rs9349407, p = 0.56).Our data overwhelmingly support the association of EPHA1 and CD33 variants with LOAD risk: addition of our data to the results previously reported (total n > 42,000) increased the strength of evidence for these variants, providing impressive p-values of 2.1 × 10-15 (EPHA1) and 1.8 × 10-13 (CD33).
Herbal medicines for asthma: a systematic review
Authors: A Huntley
Journal: Thorax (2000)

Asthma is one of the most common chronic diseases in modern society and there is increasing evidence to suggest that its incidence and severity are increasing. There is a high prevalence of usage of complementary medicine for asthma. Herbal preparations have been cited as the third most popular complementary treatment modality by British asthma sufferers. This study was undertaken to determine if there is any evidence for the clinical efficacy of herbal preparations for the treatment of asthma symptoms.Four independent literature searches were performed on Medline, Pubmed, Cochrane Library, and Embase. Only randomised clinical trials were included. There were no restrictions on the language of publication. The data were extracted in a standardised, predefined manner and assessed critically.Seventeen randomised clinical trials were found, six of which concerned the use of traditional Chinese herbal medicine and eight described traditional Indian medicine, of which five investigated Tylophora indica. Three other randomised trials tested a Japanese Kampo medicine, marihuana, and dried ivy leaf extract. Nine of the 17 trials reported a clinically relevant improvement in lung function and/or symptom scores.No definitive evidence for any of the herbal preparations emerged. Considering the popularity of herbal medicine with asthma patients, there is urgent need for stringently designed clinically relevant randomised clinical trials for herbal preparations in the treatment of asthma.
Isolated Growth Hormone Deficiency (GHD) in Childhood and Adolescence: Recent Advances
Authors: Kyriaki S. Alatzoglou, Emma Alice Webb, Paul Le Tissier, Mehul T Dattani
Journal: Endocrine Reviews (2014)

The diagnosis of GH deficiency (GHD) in childhood is a multistep process involving clinical history, examination with detailed auxology, biochemical testing, and pituitary imaging, with an increasing contribution from genetics in patients with congenital GHD. Our increasing understanding of the factors involved in the development of somatotropes and the dynamic function of the somatotrope network may explain, at least in part, the development and progression of childhood GHD in different age groups. With respect to the genetic etiology of isolated GHD (IGHD), mutations in known genes such as those encoding GH (GH1), GHRH receptor (GHRHR), or transcription factors involved in pituitary development, are identified in a relatively small percentage of patients suggesting the involvement of other, yet unidentified, factors. Genome-wide association studies point toward an increasing number of genes involved in the control of growth, but their role in the etiology of IGHD remains unknown. Despite the many years of research in the area of GHD, there are still controversies on the etiology, diagnosis, and management of IGHD in children. Recent data suggest that childhood IGHD may have a wider impact on the health and neurodevelopment of children, but it is yet unknown to what extent treatment with recombinant human GH can reverse this effect. Finally, the safety of recombinant human GH is currently the subject of much debate and research, and it is clear that long-term controlled studies are needed to clarify the consequences of childhood IGHD and the long-term safety of its treatment.
Polymorphisms in microRNA target sites modulate risk of lymphoblastic and myeloid leukemias and affect microRNA binding
Authors: Agnieszka Dzikiewicz-Krawczyk, Anna Macieja, Ewa Mały, Danuta Januszkiewicz-Lewandowska, Maria Mosor, Marta Fichna, Ewa Strauss, Jerzy Nowak
Journal: Journal of Hematology & Oncology (2014)

MicroRNA dysregulation is a common event in leukemia. Polymorphisms in microRNA-binding sites (miRSNPs) in target genes may alter the strength of microRNA interaction with target transcripts thereby affecting protein levels. In this study we aimed at identifying miRSNPs associated with leukemia risk and assessing impact of these miRSNPs on miRNA binding to target transcripts. We analyzed with specialized algorithms the 3′ untranslated regions of 137 leukemia-associated genes and identified 111 putative miRSNPs, of which 10 were chosen for further investigation. We genotyped patients with acute myeloid leukemia (AML, n = 87), chronic myeloid leukemia (CML, n = 140), childhood acute lymphoblastic leukemia (ALL, n = 101) and healthy controls (n = 471). Association between SNPs and leukemia risk was calculated by estimating odds ratios in the multivariate logistic regression analysis. For miRSNPs that were associated with leukemia risk we performed luciferase reporter assays to examine whether they influence miRNA binding. Here we show that variant alleles of TLX1 _rs2742038 and ETV6 _rs1573613 were associated with increased risk of childhood ALL (OR (95% CI) = 3.97 (1.43-11.02) and 1.9 (1.16-3.11), respectively), while PML _rs9479 was associated with decreased ALL risk (OR = 0.55 (0.36-0.86). In adult myeloid leukemias we found significant associations between the variant allele of PML _rs9479 and decreased AML risk (OR = 0.61 (0.38-0.97), and between variant alleles of IRF8 _ rs10514611 and ARHGAP26 _rs187729 and increased CML risk (OR = 2.4 (1.12-5.15) and 1.63 (1.07-2.47), respectively). Moreover, we observed a significant trend for an increasing ALL and CML risk with the growing number of risk genotypes with OR = 13.91 (4.38-44.11) for carriers of ≥3 risk genotypes in ALL and OR = 4.9 (1.27-18.85) for carriers of 2 risk genotypes in CML. Luciferase reporter assays revealed that the C allele of ARHGAP26 _rs187729 creates an illegitimate binding site for miR-18a-3p, while the A allele of PML _rs9479 enhances binding of miR-510-5p and the C allele of ETV6 _rs1573613 weakens binding of miR-34c-5p and miR-449b-5p. Our study implicates that microRNA-binding site polymorphisms modulate leukemia risk by interfering with the miRNA-mediated regulation. Our findings underscore the significance of variability in 3′ untranslated regions in leukemia.
Acute exercise in cystic fibrosis patients increases neutrophilic pulmonary inflammation
Authors: Mikhael Laskine, Stanislaw Ptaszynski, Claude Poirier, Alphonse Jeanneret-Grosjean, Annie Landry, Guylaine Lebeuf, Celine Bergeron
Journal: European Respiratory Journal (2012)

Background:  Neutrophilic inflammation mainly from recurrent bacterial infection characterizes cystic fibrosis (CF) airways. Repeated inflammatory insults may lead to progressive lung function decline. Acute exercise is reported to trigger a systemic inflammatory response, but inflammation pattern has been poorly studied. As exercise is part of a healthy lifestyle, we aim to depict the modulation of inflammation after an acute exercise in CF.  Methods:  12 subjects with mild to moderate stable CF (FEV1>50% of p.v.) underwent a constant load exercise test at 80% of their maximal load. Sputum and blood were sampled before and 1 hour after exercise and analysed for differential leucocyte counts.  Results:  6 females and 6 males completed the study with a mean FEV1 of 72.2% and a mean exercice time of 4.6 minutes. No desaturation was reported. Table 1 summarizes the differential leucocytes counts in blood and sputum. Exercise induces a 2.2 fold increase in airway neutrophils (p=0.019) and 1.4 fold increase in blood neutrophils (p=0.01).  Conclusion:  We demonstrate that acute exercise increases the peripheral and airway inflammation in stable CF subjects. This burst of neutrophils might have a dual role in which it might improve local defense against infections and participate in airway destruction through release of elastase and other mediators. The modulation of this inflammatory response by exercise training has to be explored.
Risk of Urinary Tract Cancers Following Kidney or Ureter Stones
Authors: W.-H. Chow, G. Gridley, M. S. Linet, G. A. Pennello, J. F. Fraumeni, P. Lindblad, O. Nyren, J. K. McLaughlin, H.-O. Adami
Journal: JNCI Journal of the National Cancer Institute (1997)

A relationship has been suggested between kidney or ureter stones and the development of urinary tract cancers. In this study, a population-based cohort of patients hospitalized for kidney or ureter stones in Sweden was followed for up to 25 years to examine subsequent risks for developing renal cell, renal pelvis/ureter, or bladder cancer.Data from the national Swedish In-patient Register and the national Swedish Cancer Registry were linked to follow 61,144 patients who were hospitalized for kidney or ureter stones from 1965 through 1983. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were computed on the basis of nationwide cancer incidence rates, after adjustment for age, sex, and calendar year.Risk of renal cell cancer was not elevated in this cohort. Significant excesses of renal pelvis/ureter cancer (SIR = 2.5; 95% CI = 1.8-3.3) and bladder cancer (SIR = 1.4; 95% CI = 1.3-1.6) were observed, but the SIRs for women were more than twice those for men. Risks varied little by age or duration of follow-up. Risks of renal pelvis/ureter cancer and bladder cancer among patients with an associated diagnosis of urinary tract infection were more than double those among patients without such infection, although the risks were significantly elevated in both groups.Individuals hospitalized for kidney or ureter stones are at increased risk of developing renal pelvis/ureter or bladder cancer, even beyond 10 years of follow-up. Chronic irritation and infection may play a role, since kidney or ureter stones were located on the same side of the body as the tumors in most patients with renal pelvis/ureter cancer evaluated in our study.
Expression of thioredoxin in granulomas of sarcoidosis: possible role in the development of T lymphocyte activation
Authors: T. Koura
Journal: Thorax (2000)

<h3>BACKGROUND</h3> Activated T lymphocytes are one of the characteristic features of sarcoidosis. The mechanism of T cell activation, expressing various activation markers including interleukin 2 receptor (IL-2R), has been extensively investigated but the precise mechanism remains unknown. Although thioredoxin (TRX) displays a number of biological activities including IL-2R inducing activity, its role in the induction of IL-2R expression on T cells in sarcoidosis has not been determined. The expression of TRX and IL-2R in granulomas of patients with sarcoidosis has been studied to clarify a possible role for TRX in the induction of IL-2R expression. <h3>METHODS</h3> Granulomas in specimens of lung tissue and lymph nodes from five patients with sarcoidosis were immunohistochemically stained with anti-TRX antibody and anti-IL-2Rα chain antibody and the concentration of TRX in the bronchoalveolar lavage (BAL) fluid from 20 patients with pulmonary sarcoidosis was measured. <h3>RESULTS</h3> Granulomas in lung and lymph node tissue from patients with sarcoidosis showed strong reactivity with anti-TRX antibody. Positive staining was present in the macrophages, epithelioid cells, and Langhans9 type giant cells but not in lymphocytes. IL-2R was expressed on lymphocytes in the same granulomas. By contrast, positive immunoreactivity was not found in lung tissue specimens from 12 control subjects. Concentrations of TRX in BAL fluid were higher in patients with pulmonary sarcoidosis (median (range) 122.6 (20.9–303.3) ng/ml) than in control subjects (32.9 (16.8–52.8) ng/ml, p&lt;0.05). <h3>CONCLUSIONS</h3> TRX is highly expressed and is locally produced by granulomas in patients with sarcoidosis. The coexistence of immunoreactive TRX and IL-2R in the same granulomas suggests that TRX might act as a local inducing factor for IL-2R expression on T cells.