tbuckley/cabot-search huggingface dataset:
Nutritional Determinants of the Timing of Puberty
Authors: Eduardo Villamor, Erica C. Jansen
Journal: Annual Review of Public Health (2015)

The timing of puberty has important public health, clinical, and social implications. The plasticity of sexual development onset could be a mechanism that adapts to prevailing environmental conditions. Early-life nutrition may provide cues for the environment's suitability for reproduction. This review focuses on recent developments in our understanding of the role of diet in the timing of sexual maturation. Population-based observational studies consistently indicate that childhood obesity is related to the earlier onset of puberty in girls. Similarly, intake of animal foods has been associated with earlier sexual development, whereas vegetable protein intake is related to delayed maturation. Evidence for prenatal nutrition, infant feeding practices, and childhood intake of fat, carbohydrate, and micronutrients is inconsistent. Secondary analyses of prenatal and early-life randomized nutritional interventions with extended follow-up through peripubertal years would help clarify the role of nutrition in the timing of sexual maturation.
Insulin-Like Growth Factor Type 1 Receptor Expression Correlates to Good Prognosis in Highly Malignant Soft Tissue Sarcoma
Authors: Jan Åhlén, Johan Wejde, Otte Brosjö, Anette von Rosen, Wen-Hui Weng, Leonard Girnita, Olle Larsson, Catharina Larsson
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To evaluate known and suggested prognostic markers, especially insulin-like growth factor type 1 receptor (IGF-1R), in highly malignant soft tissue sarcomas (STS). Experimental Design: A cohort of 101 patients with primary STS of high malignancy grade was studied with respect to development of metastasis, local recurrence, and survival during a minimum of 5 years follow-up. All tumors were analyzed by immunohistochemistry for expression of Ki-67, p53, p27, Bcl-2, IGF-1R, and microvessel density. The traditional clinical variables size, malignancy grade (3 or 4), necrosis, mitotic frequency, infiltrative tumor growth, vascular invasion, depth, and surgical margins were also evaluated. Results: A significant association was shown between high expression of IGF-1R and favorable outcome. Among STS with positive IGF-1R immunoreactivity, cases with high expression (76-100% positive cells) had the best outcome, whereas cases with the lowest expression (1-25% positive cells) had the worst. As expected, large tumor size (&amp;gt;11 cm), presence of necrosis, high mitotic count, intralesional surgery, and deep location were all significantly associated with poor outcome, both in univariate and multivariate analyses. No difference in outcome was observed between cases of malignancy grade 3 versus 4, whereas the included and more objective variables necrosis and mitotic count were found to be reliable prognostic markers. Conclusion: IGF-1R expression is a common feature of highly malignant STS. Further elucidation of the role of IGF-1R and the IGF system in STS may both provide a basis for development of new prognostic tools in STS, as well as shed light on the basic mechanisms of the STS development.
Reperfusion and readmission of oxygen. Pathophysiological relevance of oxygen-derived free radicals to arrhythmogenesis.
Authors: M Yamada, D J Hearse, M J Curtis
Journal: Circulation Research (1990)

We have examined the pathophysiological role of readmission of oxygen (and hence production of oxygen-derived free radicals) in the initiation of reperfusion-induced arrhythmias by separating, on a temporal basis, readmission flow from readmission of oxygen. Isolated rat hearts (n = 12/group) were subjected to 10 minutes of regional ischemia and 10 minutes of reperfusion. In controls reperfused with oxygenated solution (Po2 greater than 600 mm Hg), 92% of hearts developed ventricular fibrillation (VF) during the first 20 seconds of reperfusion, whereas in hearts reperfused with hypoxic solution (Po2 9.3-12.2 mm Hg), the incidence of VF was only 17% (p less than 0.05). Subsequent readmission of control solution (Po2 greater than 600 mm Hg) to the latter group led, within 20 seconds, to the appearance of VF in seven of the 10 hearts (70%) that had not previously fibrillated. To examine whether hypoxic reperfusion had prevented VF or merely delayed its onset, the studies were repeated in separate groups of hearts with the duration of hypoxic reperfusion extended to 5 minutes. In addition, to examine the partial pressure dependence of the relation, the Po2 in the reperfusion solution was set at one of five different levels: greater than 600, 150-192.7, 69-85.6, 9.2-14.8, or 0.0 mm Hg. It was found that hypoxia merely delayed VF onset by 20-40 seconds and did not significantly reduce the incidence of VF, which was 83%, 92%, 67%, 58%, and 58%, respectively. This indicated that readmission of oxygen is unnecessary for the initiation of VF during reperfusion. The hearts that reverted to sinus rhythm during the ensuing 5 minutes (n = 8, 4, 5, 9, and 8, respectively) were used to assess the arrhythmogenic consequences of readmission of oxygen. When control solution (Po2 greater than 600 mm Hg) was readmitted, new episodes of VF were elicited within 20 seconds in a manner that was inversely proportional to the preceding Po2 (p less than 0.05), the incidence of new episodes of VF being 0%, 0%, 40%, 67%, and 86%, respectively. The arrhythmogenic effect of readmission of oxygen was not the result of a sudden increase in heart rate, because a similar arrhythmogenic effect of readmission of oxygen was seen in separate groups of hearts that were paced (350 beats/min) throughout hypoxia and readmission of oxygen. In conclusion, readmission of flow and readmission of oxygen are independent determinants of reperfusion-induced arrhythmias.(ABSTRACT TRUNCATED AT 400 WORDS)
Is minocycline therapy in acne associated with antineutrophil cytoplasmic antibody positivity? A cross-sectional study
Authors: H. Marzo-Ortega, K. Baxter, R.M. Strauss, S. Drysdale, B. Griffiths, S.A. Misbah, A. Gough, W.J. Cunliffe, P. Emery
Journal: British Journal of Dermatology (2007)

Minocycline (MN), one of the commonly prescribed therapies for acne, is known to be associated with autoimmune disorders including drug-induced lupus. However, data are sparse regarding the prevalence of autoimmune disease in acne or in patients with acne treated with MN.To establish the prevalence of antinuclear antibodies (ANA), antineutrophil cytoplasmic antibodies (ANCA) and new autoimmune syndromes in an MN-exposed and unexposed population with acne.In a cross-sectional study, 252 patients with acne vulgaris were assessed. Sixty-nine per cent had been exposed to MN at some point or were taking the drug at the time of the interview. Data recorded included duration of disease (acne) and drug history as well as possible side-effects of drugs, in particular joint symptoms (pain and swelling). In addition, blood was taken for ANA, ANCA, liver function tests and HLA analysis.There was no statistical difference in the prevalence of ANA positivity between patients exposed (13%) or not exposed (11%) to MN. However, higher titres of ANA (1/160 or higher) were found in the MN-exposed group (45% compared with 12% in the unexposed group). ANCA positivity was found in 7% of the MN-exposed group but no positivity was found in the unexposed cohort (P = 0.022). In 58% of cases, the ANCA detected were of the perinuclear pattern (p-ANCA) with myeloperoxidase specificity, and this finding was associated with clinical symptoms in the majority of cases. Two p-ANCA-positive patients were thought in retrospect to have developed a drug-induced lupus syndrome.ANA positivity is seen in patients with acne irrespective of exposure to MN; however, p-ANCA appear to be a serological marker for developing autoimmune disease in patients receiving MN.
Host Cell Invasion by <i>TRYPANOSOMA cRUZI</i> Is Potentiated by Activation of Bradykinin B2 Receptors
Authors: Julio Scharfstein, Veronica Schmitz, Veronica Morandi, Marcia M. A. Capella, Ana Paula C. A. Lima, Alexandre Morrot, Luiz Juliano, Werner Müller-Esterl
Journal: The Journal of Experimental Medicine (2000)

The parasitic protozoan Trypanosoma cruzi employs multiple molecular strategies to invade a broad range of nonphagocytic cells. Here we demonstrate that the invasion of human primary umbilical vein endothelial cells (HUVECs) or Chinese hamster ovary (CHO) cells overexpressing the B(2) type of bradykinin receptor (CHO-B(2)R) by tissue culture trypomastigotes is subtly modulated by the combined activities of kininogens, kininogenases, and kinin-degrading peptidases. The presence of captopril, an inhibitor of bradykinin degradation by kininase II, drastically potentiated parasitic invasion of HUVECs and CHO-B(2)R, but not of mock-transfected CHO cells, whereas the B(2)R antagonist HOE 140 or monoclonal antibody MBK3 to bradykinin blocked these effects. Invasion competence correlated with the parasites' ability to liberate the short-lived kinins from cell-bound kininogen and to elicit vigorous intracellular free calcium ([Ca(2+)](i)) transients through B(2)R. Invasion was impaired by membrane-permeable cysteine proteinase inhibitors such as Z-(SBz)Cys-Phe-CHN(2) but not by the hydrophilic inhibitor 1-trans-epoxysuccinyl-l-leucyl-amido-(4-guanidino) butane or cystatin C, suggesting that kinin release is confined to secluded spaces formed by juxtaposition of host cell and parasite plasma membranes. Analysis of trypomastigote transfectants expressing various cysteine proteinase isoforms showed that invasion competence is linked to the kinin releasing activity of cruzipain, herein proposed as a factor of virulence in Chagas' disease.
Rapid-eye-movement-specific sleep-disordered breathing: a possible cause of excessive daytime sleepiness.
Authors: J E Kass, S M Akers, T C Bartter, M R Pratter
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Some patients referred for polysomnography with complaints of excessive daytime sleepiness (EDS) and clinically suspected obstructive sleep apnea (OSA) have a respiratory disturbance index (RDI) < 10. Many would consider these patients not to have OSA. We reviewed 34 such patients to determine whether respiratory disturbances confined primarily to rapid eye movement (REM) sleep correlated with an objective criterion for EDS: a mean sleep latency (MSL) < 10 min. REM-specific events were quantified with indices calculated for REM sleep alone. Univariate linear regression showed that a REM-specific respiratory disturbance index (REM-RDI) and the transient arousal index (TAI) computed for REM sleep (REM-TAI) were associated with a low MSL (R2 = -0.35, p = 0.001; and R2 = -0.27, p = 0.01, respectively). In our subjectively sleepy patients with an overall RDI < 10, a REM-RDI > or = 15 had the highest predictive accuracy (82%) for an MSL < 10 min. Seventeen of the 34 study patients had a REM-RDI > or = 15. Their mean MSL was 8.3 +/- 0.8 min. We conclude that within a group of patients with daytime sleepiness, suspected OSA, and a normal RDI, there may be a subset who have clinically significant REM-specific sleep-disordered breathing.
Fumarates vs. methotrexate in moderate to severe chronic plaque psoriasis: a multicentre prospective randomized controlled clinical trial
Authors: S. Fallah Arani, H. Neumann, W.C.J. Hop, H.B. Thio
Journal: British Journal of Dermatology (2010)

Methotrexate and fumarates are effective systemic therapies for moderate to severe psoriasis according to the European S3 guidelines.We conducted a randomized controlled trial comparing the effectiveness and the adverse events of methotrexate and fumarates.Sixty patients with moderate to severe psoriasis vulgaris were randomly assigned to treatment for 16 weeks with either methotrexate (30 patients; 15 mg per week) or fumarates (30 patients; 30 mg, followed by 120 mg according to a standard progressive dosage regimen) and were followed up for 4 weeks. The primary endpoint with respect to the efficacy was the difference in mean change from baseline in Psoriasis Area and Severity Index (PASI) after 12 weeks of treatment. The study was powered to detect a difference of five points. Analyses were by intention to treat.Six patients were excluded because five were not eligible and one withdrew consent. Two patients in the methotrexate group and one in the fumarate group dropped out during the 12 weeks of treatment because of nonappearance at the outpatient clinic. In total, 25 patients in the methotrexate group and 26 in the fumarate group were evaluated in the primary analysis. After 12 weeks of treatment, the mean ± SD PASI decreased from 14·5 ± 3·0 at baseline to 6·7 ± 4·5 in the 25 patients treated with methotrexate, whereas it decreased from 18·1 ± 7·0 to 10·5 ± 6·7 in the 26 patients treated with fumarates. After adjustment for baseline values, the absolute difference (fumarates minus methotrexate) in the mean values at 12 weeks was 1·4 (95% confidence interval -2·0 to 4·7; P = 0·417).In this randomized trial methotrexate and fumarates were found to be equally effective in the treatment of patients with moderate to severe psoriasis. No serious or irreversible adverse events were observed in any of the patients.
Synovial sarcomas usually metastasize after &gt;5 years: a multicenter retrospective analysis with minimum follow-up of 10 years for survivors
Authors: A.H. Krieg, F. Hefti, B.M. Speth, G. Jundt, L. Guillou, U.G. Exner, A.R. von Hochstetter, M.D. Cserhati, B. Fuchs, E. Mouhsine, A. Kaelin, F.M. Klenke, K.A. Siebenrock
Journal: Annals of Oncology (2010)
The Pancreas Cancer Microenvironment
Authors: Christine Feig, Aarthi Gopinathan, Albrecht Neesse, Derek S. Chan, Natalie Cook, David A. Tuveson
Journal: Clinical Cancer Research (2012)

Pancreatic ductal adenocarcinoma (PDA) is a common and lethal malignancy resulting in more than 250,000 deaths per year worldwide. Despite extensive efforts, cytotoxic and targeted therapies have provided only limited efficacy for patients with PDA to date. One contributing factor to the failure of systemic therapies may be the abundant tumor stromal content that is the characteristic of PDA. The PDA stroma, aptly termed the tumor microenvironment, occupies the majority of the tumor mass, and consists of a dynamic assortment of extracellular matrix components and nonneoplastic cells including fibroblastic, vascular, and immune cells. Recent work has revealed that the PDA stroma supports tumor growth and promotes metastasis and simultaneously serves as a physical barrier to drug delivery. Accordingly, methods that alter stromal composition or function, for instance interference with the vasculature via Notch/Hedgehog pathway inhibition or relief of vascular compression by hyaluronidase, are under active investigation. Here, we will review our current understanding of the PDA tumor microenvironment, and highlight opportunities for further exploration that may benefit patients.
Adaptive Evolution of the IgA Hinge Region in Primates
Authors: Kenta Sumiyama, Naruya Saitou, Shintaroh Ueda
Journal: Molecular Biology and Evolution (2002)

IgA is a major component that prevents the penetration of pathogenic bacteria into mucosal surfaces. The IgA antibody is cleaved at the IgA hinge region with high specificity by IgA-specific proteases produced by several pathogenic bacteria. We conducted a genomic sequence analysis of the IgA genes of a wide spectrum of primates, including the first intron and second exon, which consist of the hinge region and the CH2 domain, to find evidence of positive selection. Because the hinge region is quite small, we combined the largest collection of sequences that could be clearly aligned and evaluated the total numbers of synonymous and nonsynonymous substitutions on the phylogenetic tree. The nonsynonymous to synonymous substitution ratio (dN/dS test) showed that hominoids, Old World monkeys, and New World monkeys have dN/dS ratios of 5.4, 6.3, and 4.2, respectively. Fisher's exact probability tests showed statistical significance for the Old World monkey. Because the substitution rates of the flanking sequences are more or less similar to the synonymous rates of the hinge region, these high values of dN/dS should be the result of positive selection at the hinge region. Combining the high sequence variability in each population and the highly accelerated nonsynonymous substitution rates in the hinge region, we conclude that this unusual IgA evolution is a molecular evidence of adaptive evolution possibly caused by the host-parasite relationship.
The impact of depressive symptoms on recovery and outcome of hospitalised COPD exacerbations
Authors: Andriana I. Papaioannou, Konstantinos Bartziokas, Stamatoula Tsikrika, Foteini Karakontaki, Emmanouil Kastanakis, Winston Banya, Aikaterini Haniotou, Spyros Papiris, Stelios Loukides, Vlassis Polychronopoulos, Konstantinos Kostikas
Journal: European Respiratory Journal (2012)

The impact of depressive symptoms on outcomes of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) has not been thoroughly evaluated in prospective studies. We prospectively enrolled 230 consecutive patients hospitalised for AECOPD, without previous diagnosis of depression. Depressive symptoms were evaluated with Beck's depression inventory. Pulmonary function tests, arterial blood gases, COPD assessment test (CAT) and Borg dyspnoea scale were recorded on admission and on days 3, 10 and 40. Patients were evaluated monthly for 1 year. Patients with depressive symptoms required longer hospitalisation (mean ± sd 11.6 ± 3.7 versus 5.6 ± 4.1 days, p<0.001). Clinical variables improved during the course of AECOPD, but depressive symptoms on admission had a significant impact on dyspnoea (p<0.001) and CAT score (p = 0.012) improvement. Patients with depressive symptoms presented more AECOPD (p<0.001) and more hospitalisations for AECOPD (p<0.001) in 1 year. In multivariate analysis, depressive symptoms were an independent predictor of mortality (hazard ratio 3.568, 95% CI 1.302-9.780) and risk for AECOPD (incidence rate ratio (IRR) 2.221, 95% CI 1.573-3.135) and AECOPD hospitalisations (IRR 3.589, 95% CI 2.319-5.556) in 1 year. The presence of depressive symptoms in patients admitted for AECOPD has a significant impact on recovery and is related to worse survival and increased risk for subsequent COPD exacerbations and hospitalisations in 1 year.
Luminal bacteria and proteases together decrease adherence of Entamoeba histolytica trophozoites to Chinese hamster ovary epithelial cells: a novel host defence against an enteric pathogen.
Authors: E P Variyam
Journal: Gut (1996)

BACKGROUND: Factors that prevent colonic mucosal invasion by pathogenic Entamoeba histolytica are not understood. A key initial step in pathogenesis of injury induced by amoeba is adherence to target cells mediated by a surface glycoprotein lectin on E histolytica. Mucin degrading bacteria normally present in the colon lumen produce glycosidases that degrade soluble or cell surface glycoconjugates. AIM: To determine whether glycosidases produced by mucin degrading bacteria, alone or in combination with proteases present in colon lumen, can decrease E histolytica adherence to target epithelial cells by degrading E histolytica adherence lectin. METHODS: The effects of exposure of E histolytica trophozoites strains HM1:IMSS and 200:NIH to faecal culture supernatant fluids, culture supernatant preparations of mucin degrading bacteria, and luminal proteases on their adherence to Chinese hamster ovary (CHO) cells were determined. The amount of surface adherence lectin on E histolytica trophozoites before and after treatment with glycosidases and proteases was determined by immunofluorescence. The effect of glycosidases and proteases on purified E histolytica lectin was determined by gel electrophoresis. RESULTS: Incubation of E histolytica with culture supernatant preparations or proteases alone did not modify their CHO cell adherence. However, 24 hour incubation of trophozoites with culture supernatant preparations together with pancreatic proteases decreased CHO cell adherence of HM1:IMSS strain by 71.1% (p &lt; 0.001) and of 200: NIH strain by 95% (p &lt; 0.05). Incubation of trophozoites for 24 hours with faecal extracts which contain bacterial and host hydrolases decreased the adherence of the HM1:IMSS strain by 69.2% (p &lt; 0.01) and of the 200: NIH strain by 83.0%. Reduction of trophozoite adherence to CHO cells by hydrolases was promoted by 7.5 mM cycloheximide, and was reversible on incubation in an enzyme free medium. Decrease in CHO cell adherence of trophozoites was associated with decreased lectin on trophozoites as determined by immunofluorescence using a monoclonal antibody to the lectin. Purified lectin was degraded by the mixture of faecal culture supernant preparations and proteases, but not by either alone. CONCLUSIONS: Mucin degrading bacterial glycosidases and colonic luminal proteases together, but not alone, degrade the key adherence lectin on E histolytica trophozoites resulting in decreased epithelial cell adherence. These in vitro findings suggest a potential novel host defence mechanism in the human colon wherein the invasiveness of a pathogen could be curtailed by the combined actions of bacterial and host hydrolases. This mechanism may be responsible for preventing mucosal invasion by pathogenic E histolytica.
Evolutionary Dynamics of the T-Cell Receptor VB Gene Family as Inferred from the Human and Mouse Genomic Sequences
Authors: Chen Su, Masatoshi Nei
Journal: Molecular Biology and Evolution (2001)

The diversity of T-cell receptors is generated primarily by the variable-region gene families, each of which is composed of a large number of member genes. The entire genomic sequence of the variable region (VB) of the T- cell receptor β chain from humans and mice has become available. To understand the evolutionary dynamics of the VB gene family, we conducted a phylogenetic analysis of all VB genes from humans and mice, as well as a detailed analysis of internal DNA duplications in the human genomic VB region. The phylogenetic tree obtained shows that human and mouse VB genes intermingle extensively rather than forming two separate clusters and that many gene duplications occurred both before and after the divergence between primates and rodents. Analyzing the genomic maps of transposable elements (e.g., LINEs and SINEs) and relic VB genes in the VB gene region, we present evidence that a 20-kb VB region duplicated tandemly four times in the human lineage during the last 32 Myr, and 6 out of the 15 VB genes in this region have become nonfunctional during this period. Our results show that the VB gene family is subject to evolution by a birth-and-death process rather than to concerted evolution.
ACTIVITE CHOLINESTERASIQUE: POUVOIR IIISTAMINOLYTIQUE ET DOSAGE DE L'HISTAMINE DANS LA PEAU DE SUJETS SAINS ET ATTEINT DE CERTAINES DERMATOSES ALLERGIQUES RAPPORT HISTAMINE ‐ MASTOCYTES
Authors: L. LEVI, C. L. MENEGHINI, F. RANTUCCIO
Journal: Allergy (1959)
Running, walking, and hyperventilation causing asthma in children.
Authors: H Kilham, M Tooley, M Silverman
Journal: Thorax (1979)

To examine further the relation between type of exercise, workload, ventilation, and exercise-induced asthma, we compared treadmill walking with treadmill running and treadmill running with isocapnic hyperventilation in separate studies in children and adolescents. Inspired air conditions were identical during each pair of tests. Walking and running with similar minute ventilation and oxygen consumption were followed by similar falls in peak expiratory flow rate as were running and hyperventilation with similar minute ventilation and end-tidal carbon dioxide tension. This study supports the concept that hyperventilation is a central mechanism in exercise-induced asthma.