tbuckley/cabot-search huggingface dataset:
Association between obstructive lung disease and markers of HIV infection in a high-risk cohort
Authors: M Bradley Drummond, Gregory D Kirk, Jacquie Astemborski, Mariah M Marshall, Shruti H Mehta, John F McDyer, Robert H Brown, Robert A Wise, Christian A Merlo
Journal: Thorax (2011)

<h3>Background</h3> Evidence suggests an association between HIV infection and the presence of obstructive lung disease (OLD). However, the associations between specific markers of HIV infection and OLD remain unclear. A study was undertaken to determine the independent associations of HIV infection, CD4 cell count and plasma HIV viral load with the presence of OLD in an urban cohort. <h3>Methods</h3> Clinical, laboratory and spirometric data from the AIDS Linked to the Intravenous Experience (ALIVE) study, an observational study of current and former injection drug users in Baltimore, Maryland, were analysed. Multivariable logistic regression models were generated to identify HIV infection indices independently associated with OLD. <h3>Results</h3> Of 1077 participants (mean±SD age 48±8 years), 89% were African-American, 65% were men and 86% were current smokers. A total of 303 (28%) were HIV infected and 176 (16%) had spirometry-defined OLD. Higher viral load was independently associated with OLD. HIV-infected individuals with viral load &gt;200 000 copies/ml had a 3.4-fold increase in the odds of OLD compared with HIV-negative participants (95% CI 1.24 to 9.39; p=0.02). The association between higher HIV viral load and OLD persisted after accounting for antiretroviral therapy use (OR 4.06, 95% CI 1.41 to 11.7; p=0.01). No association was observed between HIV serostatus or CD4 cell count and the presence of OLD. <h3>Conclusion</h3> In a cohort at risk for OLD and HIV infection, high viral load but not CD4 cell count was associated with an increased prevalence of spirometry-defined OLD. These findings suggest that higher viral load may contribute mechanistically to the increased risk of OLD in patients with HIV infection.
Retardation of the development of hypertension in DOCA salt rats by taurine supplement
Authors: A. INOUE, H. TAKAHASHI, L.-C. LEE, S. SASAKI, Y. KOHNO, K. TAKEDA, M. YOSHIMURA, M. NAKAGAWA
Journal: Cardiovascular Research (1988)

To study the antihypertensive effects of orally administered taurine in DOCA salt hypertension, urinary excretion of catecholamines, electrolytes, and arg-vasopressin was measured over four weeks in 20 taurine treated DOCA rats (group 1), 20 taurine untreated DOCA rats (group 2), and seven taurine untreated sham operated rats (group 3). Additional experiments were performed to determine whether or not the pressor and sympathetic responses to hypothalamic stimulation were altered after taurine treatment in DOCA rats. Systolic blood pressure decreased significantly in group 1 after the first week compared with that in group 2, and the differences became progressively more evident thereafter. At the fifth week the mean blood pressure was significantly lower in group 1 than in group 2, as was the heart rate. Although urinary excretion of adrenaline decreased significantly in group 1 at the first and fourth weeks, the difference in urinary excretion of noradrenaline between groups 1 and 2 was not significant. Urinary excretion of adrenaline and noradrenaline in group 3 was significantly lower than that in both hypertensive groups (groups 1 and 2). Urinary sodium excretion increased significantly in group 1 at the first and second week compared with group 2. With graded electrical stimulation of the ventromedial hypothalamus, resulting pressor and sympathetic responses were significantly smaller in group 1 than in group 2. These results suggest that the hypotensive effects of orally administered taurine in DOCA hypertensive rats are caused by suppression of the peripheral sympathetic nervous activity and by the resulting natriuresis.
Microarray analysis of pediatric ependymoma identifies a cluster of 112 candidate genes including four transcripts at 22q12.1-q13.3
Authors: Blanca Suarez-Merino, Mike Hubank, Tamas Revesz, William Harkness, Richard Hayward, Dominic Thompson, John L. Darling, David G.T. Thomas, Tracy J. Warr
Journal: Neuro-Oncology (2005)

Ependymomas are glial cell-derived tumors characterized by varying degrees of chromosomal abnormalities and variability in clinical behavior. Cytogenetic analy-sis of pediatric ependymoma has failed to identify consistent patterns of abnormalities, with the exception of monosomy of 22 or structural abnormalities of 22q. In this study, a total of 19 pediatric ependymoma samples were used in a series of expression profiling, quantitative real-time PCR (Q-PCR), and loss of heterozygosity experiments to identify candidate genes involved in the development of this type of pediatric malignancy. Of the 12,627 genes analyzed, a subset of 112 genes emerged as being abnormally expressed when compared to three normal brain controls. Genes with increased expression included the oncogene WNT5A; the p53 homologue p63; and several cell cycle, cell adhesion, and proliferation genes. Underexpressed genes comprised the NF2 interact-ing gene SCHIP-1 and the adenomatous polyposis coli (APC)-associated gene EB1 among others. We validated the abnormal expression of six of these genes by Q-PCR. The subset of differentially expressed genes also included four underexpressed transcripts mapping to 22q12.3-13.3. By Q-PCR we show that one of these genes, CBX7 (22q13.1), was deleted in 55% of cases. Other genes mapping to cytogenetic hot spots included two overexpressed and three underexpressed genes mapping to 1q31-41 and 6q21-q24.3, respectively. These genes represent candidate genes involved in ependymoma tumorigenesis. To the authors' knowledge, this is the first time microarray analysis and Q-PCR have been linked to identify heterozygous/homozygous deletions.
Sunscreen photopatch testing: a series of 157 children
Authors: A.K. Haylett, Y.Z. Chiang, Z. Nie, T.C. Ling, L.E. Rhodes
Journal: British Journal of Dermatology (2014)

Photoprotection including sunscreen use in children is encouraged by health campaigns. While sunscreen chemicals are common causes of photoallergic (PA) contact reactions in adults, limited data are available in children.To assess the frequency of PA and contact allergy (CA) to sunscreens in children aged < 18 years undergoing investigation for suspected photosensitivity.Retrospective analysis of data on children who underwent photopatch testing to a standard series of nine ultraviolet (UV) filters and to sunscreen products in a single photoinvestigation centre (2000-11). Duplicate series of UV filters and the children's own sunscreen products were applied to the back, with readings taken at sample removal, and at 24 and 48 h after 5 J cm(-2) UVA exposure of one series.The analysis comprised 157 children (aged 3-17 years, 69 male and 88 female). In total 10 children (6·4%) showed positive photopatch responses to UV filters and/or their sunscreen products (4·5% to UV filters, 5·7% to their sunscreen products). The responsible UV filters most often identified were benzophenone-3 and octyl methoxycinnamate. Additionally, CA reactions were observed in nine children (5·7%), with 16 children (10·2%) showing PA and/or CA to UV filters and/or sunscreen products.This is the largest series of photopatch testing reported in children, and shows that both sunscreen PA and CA are quite frequent in those undergoing photoinvestigation. Photopatch testing should be considered in children presenting with features of photosensitivity.
POTE Paralogs Are Induced and Differentially Expressed in Many Cancers
Authors: Tapan K. Bera, Ashley Saint Fleur, Yoomi Lee, Andre Kydd, Yoonsoo Hahn, Nicholas C. Popescu, Drazen B. Zimonjic, Byungkook Lee, Ira Pastan
Journal: Cancer Research (2006)

To identify new antigens that are targets for the immunotherapy of prostate and breast cancer, we used expressed sequence tag and genomic databases and discovered POTE, a new primate-specific gene family. Each POTE gene encodes a protein that contains three domains, although the proteins vary greatly in size. The NH2-terminal domain is novel and has properties of an extracellular domain but does not contain a signal sequence. The second and third domains are rich in ankyrin repeats and spectrin-like helices, respectively. The protein encoded by POTE-21, the first family member discovered, is localized on the plasma membrane of the cell. In humans, 13 highly homologous paralogs are dispersed among eight chromosomes. The expression of POTE genes in normal tissues is restricted to prostate, ovary, testis, and placenta. A survey of several cancer samples showed that POTE was expressed in 6 of 6 prostate, 12 of 13 breast, 5 of 5 colon, 5 of 6 lung, and 4 of 5 ovarian cancers. To determine the relative expression of each POTE paralog in cancer and normal samples, we employed a PCR-based cloning and analysis method. We found that POTE-2alpha, POTE-2beta, POTE-2gamma, and POTE-22 are predominantly expressed in cancers whereas POTE expression in normal tissues is somewhat more diverse. Because POTE is primate specific and is expressed in testis and many cancers but only in a few normal tissues, we conclude POTE is a new primate-specific member of the cancer-testis antigen family. It is likely that POTE has a unique role in primate biology.
A critical role for Egr-1 during vascular remodelling in pulmonary arterial hypertension
Authors: Michael G Dickinson, Piotr S Kowalski, Beatrijs Bartelds, Marinus A J Borgdorff, Diederik van der Feen, Hannie Sietsma, Grietje Molema, Jan A A M Kamps, Rolf M F Berger
Journal: Cardiovascular Research (2014)

Pulmonary arterial hypertension (PAH) is characterized by the development of unique neointimal lesions in the small pulmonary arteries, leading to increased right ventricular (RV) afterload and failure. Novel therapeutic strategies are needed that target these neointimal lesions. Recently, the transcription factor Egr-1 (early growth response protein 1) was demonstrated to be up-regulated early in experimental neointimal PAH. Its effect on disease development, however, is unknown. We aimed to uncover a novel role for Egr-1 as a molecular inductor for disease development in PAH. In experimental flow-associated PAH in rats, we investigated the effects of Egr-1 down-regulation on pulmonary vascular remodelling, including neointimal development, and disease progression. Intravenous administration of catalytic oligodeoxynucleotides (DNA enzymes, DNAzymes) resulted in down-regulation of pulmonary vascular Egr-1 expression. Compared with vehicle or scrambled DNAzymes, DNAzymes attenuated pulmonary vascular remodelling, including the development of occlusive neointimal lesions. Selective down-regulation of Egr-1 in vivo led to reduced expression of vascular PDGF-B, TGF-β, IL-6, and p53, resulting in a reduction of vascular proliferation and increased apoptosis. DNAzyme treatment further attenuated pulmonary vascular resistance, RV systolic pressure, and RV hypertrophy. In contrast, in non-neointimal PH rodents, DNAzyme treatment had no effect on pulmonary vascular and RV remodelling. Finally, pharmacological inhibition of Egr-1 with pioglitazone, a peroxisome proliferator activated receptor-γ ligand, attenuated vascular remodelling including the development of neointimal lesions. These results indicate that Egr-1 governs pulmonary vascular remodelling and the development of characteristic vascular neointimal lesions in flow-associated PAH. Egr-1 is therefore a potential target for future PAH treatment.
Health potential of a low glycaemic index diet
Authors: S. Colagiuri
Journal: BMJ (2015)

Clear for people with diabetes but evidence is weaker for those without

What we eat affects our health, but there is considerable debate about the optimal diet. Consequently, the general public is bewildered by an avalanche of conflicting dietary information—a web search for “diet and health” generates around 460 million results. Many of these links feature the health potential of diets with a low glycaemic index (GI). 

Carbohydrates are a large source of daily energy intake and the main dietary component affecting postprandial glycaemia and insulin secretion. We know that glycaemic and insulin responses are influenced by both the amount and the type of carbohydrate. In 1981, the GI was developed to rank foods according to their glycaemic effect, expressed as a percentage of the response to an equivalent carbohydrate portion of a reference food.1 The term glycaemic load was introduced in 1997 to quantify the overall glycaemic effect of a food and is calculated as the mathematical product of the food’s GI and carbohydrate content.2 Although the validity of the GI applied to individual foods is accepted, debate continues about the comparative clinical effects of high and low GI diets.

In people with …
Kappa B-type enhancers are involved in lipopolysaccharide-mediated transcriptional activation of the tumor necrosis factor alpha gene in primary macrophages.
Authors: A N Shakhov, M A Collart, P Vassalli, S A Nedospasov, C V Jongeneel
Journal: The Journal of Experimental Medicine (1990)

We have explored the cis-acting elements necessary for the LPS-mediated activation of the mouse TNF-alpha promoter by transfecting a set of 5' deletion mutants linked to the CAT reporter gene into primary bone marrow-derived macrophages. A major drop in inducibility by LPS was seen upon deletion of a region mapping between nt -655 and nt -451. Gel retardation assays revealed that LPS induced the appearance in this region of several specific DNA-protein complexes mapping to sequence motifs with strong homology to the kappa B enhancer. Constructs containing two or more copies of one of the kappa B enhancer motifs linked to a heterologous promoter were inducible by LPS. Additional deletion of a region between nt -301 and nt -241, which contains a MHC class II-like "Y box" and formed a Y box-specific complex with a protein whose concentration was increased by LPS, caused a nearly complete loss of inducibility by LPS. We speculate that NF-kappa B and/or related proteins are involved in the LPS-induced transcriptional activation of the TNF-alpha gene, and that factors interacting with the Y box can additionally modulate the activity of the gene in macrophages.
Discordant practice and limited histopathological assessment in gastrointestinal neuromuscular disease
Authors: J. E. Martin, T. W. Hester, H. Aslam, S. Sinha, C. H. Knowles
Journal: Gut (2009)

Gastrointestinal neuromuscular diseases (GINMD) are relatively rare but severe disorders manifest commonly as impaired motor activity and slowed or obstructed transit with or without visceral dilatation.1 Primary diagnoses include enteric dysmotility, intestinal pseudo-obstruction and slow-transit constipation. These conditions result in considerable individual morbidity and mortality including intestinal failure and suicide.2

Although surgery is best avoided for most patients with GINMD2 resection or biopsy is sometimes an “end-of-line” procedure for symptom relief or diagnosis. Tissues derived include colectomy specimens from patients with slow transit constipation, and full thickness or seromuscular bowel biopsies are now increasingly performed laparoscopically3 4 Other biopsies may be taken at laparotomy or stoma formation. Information regarding underlying GI neuromuscular pathology is of value to allow better certainty of diagnosis to facilitate discussion regarding the disorder and prognosis, to give patients a more objective correlate for their condition and occasionally guide therapy. Implicit is the assumption that findings are accurate. Anecdotal evidence suggests a great deal of variation in techniques …
Lymphatic Mapping and Sentinel Node Biopsy in the Patient With Breast Cancer
Authors: John J. Albertini
Journal: JAMA (1996)

To identify the sentinel lymph node(s) (SLN[s]) (the first node[s] draining the primary tumor in the regional lymphatic basin) in patients with invasive breast cancer and to test the hypothesis that the histologic characteristics of the SLN predict the histologic characteristics of the remaining lymph nodes in the axilla.A prospective trial.Sixty-two patients with newly diagnosed invasive breast cancers.Patients underwent intraoperative lymphatic mapping using a combination of a vital blue dye and filtered technetium-labeled sulfur colloid. The SLN was identified and removed, followed by a definitive cancer operation, including a complete axillary node dissection.The metastatic distribution in the axilla was determined in patients with occult nodal disease.The SLN was successfully identified in 57 (92%) of 62 patients using the 2 lymphatic mapping procedures. After localization, 18 patients (32%) were found to have metastatic disease, and the SLN tested positive in all 18 patients. There were no "skip" metastases, defined as an SLN that tested negative with higher nodes that tested positive. In 12 (67%) of 18 patients with metastatic disease, the SLN was the only site of disease. The metastatic distribution significantly favored SLN involvement. Among subjects with discordant nodal involvement, the probability of observing the distribution of SLN involvement by chance is very small (P<.001).This study confirms that lymphatic mapping is technically possible in the patient with breast cancer and that the histologic characteristics of the SLN probably reflect the histologic characteristics of the rest of the axillary lymph nodes. The procedure also allows the pathologist to focus the histologic examination on 1 or 2 nodes, potentially increasing the yield of positive dissections and the accuracy of staging.
Neurogenic Mechanisms Contribute to Hypertension in Mice With Disruption of the K-Cl Cotransporter KCC3
Authors: Marco B. Rust, Jörg Faulhaber, Mareike K. Budack, Carsten Pfeffer, Tanja Maritzen, Michael Didié, Franz-Xaver Beck, Thomas Boettger, Rudolf Schubert, Heimo Ehmke, Thomas J. Jentsch, Christian A. Hübner
Journal: Circulation Research (2006)

The neurodegenerative disorder Andermann syndrome is caused by mutations of the K-Cl cotransporter KCC3. Mice with a targeted disruption of the corresponding gene, Slc12a6 , reproduce neurodegeneration of the peripheral and central nervous system (CNS) and display arterial hypertension. Kcc3 is expressed in numerous tissues, including the CNS and vascular smooth muscle cells. As the intracellular chloride concentration may influence myogenic tone and hence blood pressure, we measured the chloride concentration in vascular smooth muscle cells. It was indeed increased in superficial brain arteries and saphenous arteries of Kcc3 −/− mice. Isolated saphenous arteries and their third-order branches, however, reacted indistinguishably to changes in intravascular pressure, stimulation of α 1 -adrenoreceptors, exogenous nitric oxide, or blockade of calcium-activated chloride channels. Likewise, the responses to α 1 -adrenergic stimulation or exogenous nitric oxide in vivo were identical in both genotypes. These results argue against a major vascular-intrinsic component of arterial hypertension in Kcc3 −/− mice. In contrast, either α 1 -adrenergic blockade or inhibition of ganglionic transmission abolished the difference in arterial blood pressure between both genotypes. This demonstrates a neurogenic component in the maintenance of this phenotype, which is further supported by an increase of urinary norepinephrine and epinephrine excretion in Kcc3 −/− mice. Our data indicate that local control of myogenic tone does not require KCC3 and that hypertension in Kcc3 −/− mice depends on an elevated sympathetic tone.
Learners favour high resolution oesophageal manometry with better diagnostic accuracy over conventional line tracings
Authors: A Samad Soudagar, Gregory S Sayuk, C Prakash Gyawali
Journal: Gut (2011)

<h3>Background</h3> High resolution manometry (HRM) provides a colourful representation of oesophageal motility. Novice and intermediate learners were tested to compare HRM Clouse plots and conventional manometry for accuracy, ease of interpretation and knowledge retention. <h3>Methods</h3> 36 learners evaluated 60 randomised motility sequences (30 HRM Clouse plots with corresponding line tracings) 4 months apart, following a tutorial. Learners rated prior knowledge of oesophageal pathophysiology and manometry and scored ease and speed of interpretation on 10 cm visual analogue scales (VAS). <h3>Results</h3> Understanding of oesophageal pathophysiology was low in all cohorts (2.9±0.4 on VAS) and knowledge of HRM and conventional motility studies was even lower (1.9±0.4 and 1.8±0.3, respectively, p=NS). After the tutorial, diagnostic accuracy was significantly higher with HRM Clouse plots than with line tracings (p&lt;0.001). HRM gains in diagnostic accuracy were evident over line tracings (43.1%), particularly with aperistalsis (36.1%), oesophageal body hypomotility (25.8%) and relaxation of the lower oesophageal sphincter (21.0%) (p&lt;0.001 for each comparison); these were maintained at the second evaluation. Gains were independent of academic level (F=0.56, p=0.5) and did not correlate with prior experience of learners (r=−0.18, p=0.29). Learners favoured HRM Clouse plots (80.6%) over line tracings and reported faster interpretation (94.4%). <h3>Conclusions</h3> HRM Clouse plots provide ease of interpretation that translates into higher diagnostic accuracy and better knowledge retention in novice and intermediate learners of oesophageal manometry. These results implicate the value of pattern recognition in HRM interpretation, irrespective of academic level and prior understanding of oesophageal motor function.
Bovine gamma/delta T cells bind E-selectin via a novel glycoprotein receptor: first characterization of a lymphocyte/E-selectin interaction in an animal model.
Authors: B Walcheck, G Watts, M A Jutila
Journal: The Journal of Experimental Medicine (1993)

E-Selectin is an inducible adhesion protein expressed by endothelial cells and recognized by leukocytes during their extravasation from the blood into inflamed tissues. Originally, E-selectin was defined as a myeloid cell-specific adhesion protein, but recent studies have shown it to be recognized by human lymphocytes as well. These lymphocytes represent a memory T cell subset and have been shown to express the HECA-452 carbohydrate epitope (CLA+ lymphocytes). We extend these findings and show that ruminant gamma/delta T cells bind E-selectin as well; and we provide preliminary evidence that this interaction is mediated by a novel glycoprotein receptor on the lymphocyte. Unlike conventional T cells (alpha/beta T cells), gamma/delta T cells from neonatal and mature animals bind E-selectin, suggesting that prior antigen stimulation and differentiation to a memory lymphocyte are not required for this interaction. Neuraminidase treatment of the gamma/delta T cells or addition of ethylenediaminetetraacetic acid (EDTA) to the assay abrogates binding, demonstrating the importance of sialic acid and divalent cations, which is consistent with other E-selectin-mediated adhesion events. However, previously defined E-selectin carbohydrate ligands, such as sialyl Lewis x on neutrophils and the HECA-452 epitope on human memory lymphocytes, are antigenically different than the carbohydrates on ruminant gamma/delta T cells since the mAbs CSLEX and HECA-452 do not recognize these cells. Protease treatment of gamma/delta T cells significantly inhibits their binding to E-selectin; however, previously characterized adhesion glycoproteins, such as L-selectin, CD44, and CD18, are not involved in the adhesive event. An E-selectin affinity column purifies a single glycoprotein of 250 kD (280 kD under reducing conditions) from gamma/delta T cell detergent lysates. Neuraminidase digestion of the 250-kD product as well as EDTA abolishes binding to E-selectin. Finally, E-selectin expression in vivo appears to mediate gamma/delta T cell accumulation. Stimulation of bovine skin with tumor necrosis factor alpha induced an increase in E-selectin expression that was associated with an influx of gamma/delta T cells at the same site.