tbuckley/cabot-search huggingface dataset:
Multidrug-resistant Neisseria gonorrhoeae with reduced cefotaxime susceptibility is increasingly common in men who have sex with men, Amsterdam, the Netherlands
Authors: H JC de Vries, J J van der Helm, M F Schim van der Loeff, A P van Dam
Journal: Eurosurveillance (2009)

Antimicrobial resistance is an increasing problem in Neisseria gonorrhoeae (NG) treatment. Presently, third-generation parenteral cephalosporins, like ceftriaxone and cefotaxime, are the first option. Resistance to oral, but not to parenteral, third-generation cephalosporins has been reported previously. We analysed the microbial susceptibility (as minimum inhibitory concentration - MIC) of NG cultures obtained from high-risk visitors of the largest Dutch outpatient clinic for sexually transmitted infections (STI) in Amsterdam, the Netherlands. Among 1,596 visitors, we identified 102 patients with at least one NG isolate with reduced susceptibility to cefotaxime (0.125 microg/ml < MIC < or = 0.5 microg/ml). The percentage of NG isolates with reduced susceptibility to cefotaxime rose from 4.8% in 2006 to 12.1% in 2008 (chi2 17.5, p<0.001). With multivariate logistic regression, being a man who has sex with men (MSM) was significantly associated with reduced susceptibility to cefotaxime (p<0.001). Compared to susceptible NG isolates, those with decreased susceptiblity to cefotaxime were more often resistant also to penicillin (16.5% vs. 43.3%), tetracycline (21.5% vs. 68.9%) and ciprofloxacin (44.4% vs. 90.0%, all p<0.001). The increased prevalence of NG strains with reduced susceptibility to cefotaxime among MSM may herald resistance to third-generation parenteral cephalosporins. A considerable proportion of these strains show resistance to multiple antibiotics which could limit future NG treatment options.
Altered P2 receptor expression profile in sputum cells of patients with COPD
Authors: Zsofia Lazar, Korcan Ayata, Wolfram Meschede, Ildiko Horvath, Marco Idzko
Journal: European Respiratory Journal (2014)

Introduction:  Purinergic signalling is implicated in the pathomechanism of COPD, however the contribution of individual P2 receptors to airway inflammation is not fully elucidated.   Aim : To study messenger RNA expression of P2 receptors in sputum cells from patients with COPD and control subjects.   Methods:  Induced or spontaneous sputum from control smoking/ex-smoking subjects (n=17, g10 pack-years) and patients with stable COPD (mild-moderate: n=16, severe-very severe: n=19) was collected and processed with 0.1% dithiotreitol. Quantitative polymerase chain reaction was carried out for P2X1, P2X4, P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, P2Y14 receptor messenger RNA of sputum cells (Taqman, 480 Lightcycler). Gene transcription relative to β 2 -microglobulin transcription was analysed with non-parametric tests.   Results:  The relative expression of P2Y14 was elevated in sputum cells from patients with mild-moderate and severe-very severe COPD in comparison with control subjects (pl0.01 and pl0.001; respectively) while showing a positive correlation to sputum neutrophil count (pl0.01, r=0.46). P2Y1 transcription was decreased in patients with severe-very severe COPD (vs. control pl0.01). The expressions of P2Y11 and P2Y12 receptors were lower in severe-very severe patients compared to control subjects and patients with mild-moderate disease (all comparisons: pl0.01), and inversely correlated to sputum neutrophil percentage (all relations: pl0.01; r=0.-74 and r=0.-51, respectively).   Conclusion:  Patients with COPD show an altered messenger RNA expression profile of P2 receptors in sputum cells. Further studies should clarify the functional roles of P2 receptors in airway inflammation in COPD.
UNAIDS celebrates success in halting spread of HIV and sets goals for 2030
Authors: Bob Roehr
Journal: BMJ (2015)

The millennium development goal of halting and reversing the spread of HIV has been achieved, says a new report by UNAIDS unveiled at the Third International Conference on Financing for Development, held in Addis Ababa, Ethiopia.1

The goal was set in 2000, when new HIV infections were occurring at a rate of 3.1 million a year. Modelling suggested that, under the rates of prevention and treatment at the time, they would grow to six million a year by 2015.

But new infections fell to two million last year, …
A Prospective, Multinational Observational Study of Men with Later-Stage Prostate Cancer, a New Global Study to Examine Patterns of Care and Outcomes
Authors: M. De Santis, M.R. Cooperberg, Y. Chang, N.W. Clarke, A.J. Costello, T. Pickles, R. Curiel, A.C. Pompeo
Journal: Annals of Oncology (2014)
Regulation of Parathyroid Vitamin D Receptor Expression by Extracellular Calcium
Authors: Bartolome[Combining Acute Accent] Garfia, Sagrario Can[Combining Tilde]adillas, Antonio Canalejo, Fernando Luque, Emilio Siendones, Manuel Quesada, Yolanda Almade[Combining Acute Accent]n, Escola[Combining Acute Accent]stico Aguilera-Tejero, Mariano Rodri[Combining Acute Accent]guez
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Low extracellular calcium (Ca) stimulates parathyroid hormone (PTH) secretion and also increases the renal synthesis of calcitriol (CTR), which is known to decrease PTH production. This study began with the hypothesis that the parathyroid cell response to CTR may be modulated by extracellular Ca concentration through an effect on parathyroid cell vitamin D receptor (VDR). In the present study, rat parathyroid glands were incubated in low (0.6 mM) and high (1.5 mM) Ca concentration. The parathyroid VDRmRNA was higher in 1.5 than 0.6 mM Ca. Furthermore, this effect was not observed in incubated slices of kidney cortex and medulla, tissues which also possess both Ca and vitamin D receptors. Experiments were also performed to evaluate the effect of Ca on VDR expression in vivo. Male Wistar rats received intraperitoneal injections of CaCl2 or a single intramuscular injection of EDTA to obtain 6 h of hypercalcemic (ionized Ca, 1.4 to 1.6 mM) or hypocalcemic (ionized Ca, 0.85 to 0.95 mM) clamp; a third group of rats was used as control. A small dose of CTR was administered to hypercalcemic rats to match the serum CTR levels of hypocalcemic rats. Parathyroid gland VDRmRNA and VDR protein were increased in hypercalcemic rats as compared with hypocalcemic rats. Increasing doses of CTR upregulated VDRmRNA and VDR only in hypercalcemic rats. Additional experiments showed that the decrease in VDR in hypocalcemic rats prevented the inhibitory effect of CTR on PTHmRNA. In conclusion, our study shows that extracellular Ca regulates VDR expression by parathyroid cells independently of CTR and that by this mechanism hypocalcemia may prevent the feedback of CTR on the parathyroids.
Ecotropic Leukemia Viruses in Congenic C57BL Mice: Natural Dissemination by Milk-Borne Infection2
Authors: C. J. M. Melief, Stephen Louie, Robert S. Schwartz
Journal: JNCI Journal of the National Cancer Institute (1975)

The incidence of infectious murine leukemia virus (MuLV) in congenic-resistant C57BL mice was studied. No constant relationship between the incidence of MuLV and the H-2 complex was apparent. Two lines, B10 and B10.A, were examined in detail because the incidence of MuLV in B10 was low and the virus appeared relatively late in life, whereas B10.A animals had a relatively high incidence of infection by MuLV early in life. Further studies of B10.A mice revealed an almost universal concordance between the virologic status of the mother and her offspring. This was particularly evident when (B10 times B10.A)F1 animals were compared with (B10.A times B10)F1 mice: Although genetically identical, the incidence of MuLV in the latter was high, whereas in the former it was low. Transmission of MuLV by milk was proved by foster-nursing experiments; when the infants of MuLV-positive B10.A mothers were suckled on MuLV-negative B10.A mothers, they were free of MuLV. Milk-borne infection may account for the natural dissemination of MuLV among some inbred lines of mice.
Association of a Guardian's Report of a Child Acting Abnormally With Traumatic Brain Injury After Minor Blunt Head Trauma
Authors: Daniel K. Nishijima, James F. Holmes, Peter S. Dayan, Nathan Kuppermann
Journal: JAMA Pediatrics (2015)

Increased use of computed tomography (CT) in children is concerning owing to the cancer risk from ionizing radiation, particularly in children younger than 2 years. A guardian report that a child is acting abnormally is a risk factor for clinically important traumatic brain injury (ciTBI) and may be a driving factor for CT use in the emergency department.To determine the prevalence of ciTBIs and TBIs in children younger than 2 years with minor blunt head trauma and a guardian report of acting abnormally with (1) no other findings or (2) other concerning findings for TBI.Secondary analysis of a large, prospective, multicenter cohort study that included 43 399 children younger than 18 years with minor blunt head trauma evaluated in 25 emergency departments. The study was conducted on data obtained between June 2004 and September 2006. Data analysis was performed between August 21, 2014, and March 9, 2015.A guardian report that the child was acting abnormally after minor blunt head trauma.The prevalence of ciTBI (defined as death, neurosurgery, intubation for >24 hours, or hospitalization for ≥2 nights in association with TBI on CT imaging) and TBI on CT imaging in children with a guardian report of acting abnormally with (1) no other findings and (2) other concerning findings for TBI.Of 43 399 children in the cohort study, a total of 1297 children had reports of acting abnormally, of whom 411 (31.7%) had this report as their only finding. Reported as percentage (95% CI), 1 of 411 (0.2% [0-1.3%]) had a ciTBI, and 4 TBIs were noted on the CT scans in 185 children who underwent imaging (2.2% [0.6%-5.4%]). In children with reports of acting abnormally and other concerning findings for TBI, 29 of 886 (3.3% [2.2%-4.7%]) had ciTBIs and 66 of 674 (9.8% [7.7%-12.3%]) had TBIs on CT.Clinically important TBIs are very uncommon, and TBIs noted on CT are uncommon in children younger than 2 years with minor blunt head trauma and guardian reports of the child acting abnormally with no other clinical findings suspicious for TBI. Computed tomographic scans are generally not indicated in these children although observation in the emergency department may be warranted.
Ras Signaling Is a Key Determinant for Metastatic Dissemination and Poor Survival of Luminal Breast Cancer Patients
Authors: Katherine L. Wright, Jessica R. Adams, Jeff C. Liu, Amanda J. Loch, Ruth G. Wong, Christine E.B. Jo, Lauren A. Beck, Divya R. Santhanam, Laura Weiss, Xue Mei, Timothy F. Lane, Sergei B. Koralov, Susan J. Done, James R. Woodgett, Eldad Zacksenhaus, Pingzhao Hu, Sean E. Egan
Journal: Cancer Research (2015)

Abstract Breast cancer is associated with alterations in a number of growth factor and hormone-regulated signaling pathways. Mouse models of metastatic breast cancer typically feature mutated oncoproteins that activate PI3K, Stat3, and Ras signaling, but the individual and combined roles of these pathways in breast cancer progression are poorly understood. In this study, we examined the relationship between oncogenic pathway activation and breast cancer subtype by analyzing mouse mammary tumor formation in which each pathway was activated singly or pairwise. All three oncogenes showed cooperation during primary tumor formation, but efficient dissemination was only dependent on Ras. In addition, transcriptional profiling demonstrated that Ras induced adenocarcinomas with molecular characteristics related to human basal-like and HER2+ tumors. In contrast, Ras combined with PIK3CAH1047R, an oncogenic mutant linked to ERα+/luminal breast cancer in humans, induced metastatic luminal B-like tumors. Consistent with these data, elevated Ras signaling was associated with basal-like and HER2+ subtype tumors in humans and showed a statistically significant negative association with estrogen receptor (ER) signaling across all breast cancer. Despite this, there are luminal tumors with elevated Ras signaling. Importantly, when considered as a continuous variable, Ras pathway activation was strongly linked to reduced survival of patients with ERα+ disease independent of PI3K or Stat3 activation. Therefore, our studies suggest that Ras activation is a key determinant for dissemination and poor prognosis of ERα+/luminal breast cancer in humans, and hormone therapy supplemented with Ras-targeting agents may be beneficial for treating this aggressive subtype. Cancer Res; 75(22); 4960–72. ©2015 AACR.
Pseudomonas: is chronic infection behind acute exacerbations in COPD?
Authors: K Lindsay
Journal: Thorax (2009)

Approximately half of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with bacterial infection, and Pseudomonas aeruginosa is increasingly recognised as an important pathogen. Up to 13% of AECOPD are associated with P aeruginosa in patients with severe airflow obstruction. Whether chronic infection with P aeruginosa predisposes to AECOPD is not entirely clear. …
The pathogen-host interactions in pulmonary tuberculosis (PT)
Authors: Olga Titarenko, Marina Dyakova, Viacheslav Zhuravlev, Olga Manicheva, Diljara Esmedlyaeva, Nina Alexeyeva
Journal: European Respiratory Journal (2014)

Design: Biochemical characteristics of the 42 newly diagnosed patients with PT. Blood levels of acute phases reactants-ARP: ceruloplasmin-CP, haptoglobin-Hg, C-reactive protein-CRP, orosomucoid-AGP, albumin-A, neopterin-Np, elastase-El, alpha1-protease inhibitor- alpha1-IP, adenosine deaminase activities-ADA; were tested before the start of treatment. Test results were analyzed considering clinical, radiologic and bacteriologic examination data after three months of adequate anti-TB therapy. Sputum negativation and closing of cavities were classified as an outcome significant improvement (SI) while sputum negativation - as improvement (I).  Mycobacterium tuberculosis (MBT) isolate (the Pathogen) from sputum collected before the to treatment start had been studied as: MBT genotype (by spoligotyping), drug resistance patterns (DR), cytotoxicity (CT; MBT ability to stimulate THP-1 cells death). The data were analyzed according to MBT genotype Beijing (Bj) or another families and the therapy effect.  Results. Both SI and I outcomes were observed regardless MBT genotypes. Nevertheless Bj-genotype (MBT-B) was associated with I (41% and 70%; p=0,05) and high levels of ARPs, CT and DR. Low levels of ARPs were associated with SI while their high levels with I. Discriminative analysis revealed the constellation of four ARPs (CP, Hg, El, ADA) as the complex with the highest predictive value of the 3 month chemotherapy outcome with a prognostic accuracy in 95,2% for MBT-B patients and in 100% for those with MBT of other genotypes families.  Conclusion: In H-PS tuberculosis development is mainly determined by the host properties expressed as ARP levels. Complex of CP, Hg, El, ADA blood levels proved to be of the most prognostic value.
EGFR, KRAS, HER2, BRAF and PI3KCA mutation status in metastatic cancer patients: Thoracic cytological specimens obtained in routine clinical practice
Authors: Thomas Vandemoortele, Isabelle Nanni-Metellus, Elise Kaspi, VÃ©ronique Secq, Sophie Laroumagne, Patrice Roll, Elisa Roca, HervÃ© Dutau, AndrÃ©e Robaglia, Philippe Astoul
Journal: European Respiratory Journal (2013)

Background: Epidermal Growth Factor Receptor (EGFR) activating mutations and KRAS mutations guide treatment selection in advanced Non-Small Cell Lung Cancer (NSCLC), whereas BRAF and HER2 mutations play a role in metastatic melanoma and in breast cancer, respectively. We aimed to determine the feasibility of routine multigene mutation analysis for EGFR, KRAS, BRAF, HER2 and PI3KCA in thoracic samples from patients with carcinoma.  Methods: From March 2011 until October 2012, genetic mutations were analyzed from thoracic samples obtained by thoracentesis or during diagnostic bronchoscopy using broncho-alveolar lavage (BAL) or bronchial cytobrush in 42 patients with NSCLC and other metastatic carcinoma. 32 patients had pleural fluid samples, 4 had BAL and 6 had bronchial cytobrush samples. PCR and direct sequencing of EGFR exons 18 to 21, KRAS exon 2, BRAF exon 15, HER2 exon 20 and PI3KCA exons 9 and 20 were performed.  Results : Mutation analysis was completed for all samples (100%). Mutations were detected in 20 patients (47,6%) : 9 (21,4%) EGFR, 8 (19,0%) KRAS, 2 (4,8%) BRAF and 1 (2,4%) HER2 mutations. Molecular biology analyses were performed both on cytological samples and biopsy samples in 17 patients (40,5%), of which 16 had concordant results. One patient had a discrepancy between the different tissue samples, with a mutation detected in the pleural fluid sample,but none in the pleural biopsy sample obtained during a different procedure.  Conclusions: Mutations of the EGFR, KRAS, BRAF, HER2 and PI3KCA genes can be detected in cytological samples routinely obtained by thoracentesis, BAL and bronchial cytobrushing.
Use of genomic DNA-chip hybridizations (matrix-CGH/array-CGH) for detection of novel genetic alterations in pancreatic carcinomas
Authors: Heike Weber, Umesh Bhanot, Hans Kestler, Holger Kohlhammer, Swen Wessendorf, Carsten Schwaenen, Hartmut Döhner, Thomas M. Gress, Karlheinz Holzmann
Journal: Clinical Cancer Research (2006)

A72   Genetic aberrations of the DNA copy number level, such as deletions, amplifications and unbalanced translocations, are among the main pathogenetic mechanisms underlying human genetic disorders. Analysis of chromosomal aberrations is particularly important in cancer, where amplification of oncogenes, cell cycle regulators and / or deletion of tumor suppressor genes are involved in the multi-step process of cancer development.Therefore, rapid and accurate identification of such genetic imbalances could be important for the understanding of physiological and pathophysiological processes and may serve as a starting point for new diagnostic methods or strategies for therapy.By classic comparative genome hybridization (CGH) studies, a few recurrent aberrations have been identified in pancreatic carcinoma, but due to the limited spatial resolution of this method those findings have not yet resulted in the identification of biologically relevant genes.To overcome the limitations of CGH to chromosomal targets, a new array-based approach has been developed, termed matrix-CGH. For matrix-CGH, metaphase preparations are substituted by a set of well-defined genomic DNA fragments from BAC or PAC clones, spotted on conventional glass slides to serve as hybridization target for genomic test (e.g. tumor DNA) and reference DNA. By use of matrix-CGH it is now possible to screen for genomic imbalances with a 20- to 100-fold higher resolution compared to conventional CGH.After a preliminary study in which we investigated 13 cell lines as well as 6 primary tumors using an array with about 800 clones demonstrating the usefulness of this approach, we initiated a more comprehensive study with a new array-generation. This new array consists of 2800 clones resulting in a spatial resolution of 2 Mbp across the whole genome.With this array we screened 28 primary tumors and detected 46 commonly amplified regions of which about 20 regions have not yet been described in pancreatic carcinoma.As the resolution of this chip is still too small for target gene identification, we constructed a pancreatic carcinoma specific contig-chip, with a complete coverage of all recurrently amplified regions. The detection of minimal amplified regions in combination with expression analysis of the relevant target genes has now resulted in the identification of new candidate genes and serve as a starting point for a much more focused investigation of the pathobiology of this tumor type.
Tumor Formation in Preneoplastic Mammary Nodule Lines in Mice Treated With Nafoxidine, Testosterone, and 2-Bromo- α -ergocryptine 2
Authors: Daniel Medina
Journal: JNCI Journal of the National Cancer Institute (1977)

The tumor potentials of five preneoplastic mammary nodule lines were examined in BALB/cCrgl mice treated with either nafoxidine, an estrogen antagonist; 2-bromo-alpha-ergocryptine, a prolactin suppressant; or testosterone. The inhibitory effect of any of the three agents was dependent on the individual nodule line and was not correlated with the effects of ovariectomy. Nafoxidine inhibited tumor formation only in nodule line D2; testosterone inhibited tumor formation in lines C3 and C4; and 2-bromo-alpha-ergocryptine failed to inhibit tumor formation in any of the nodule lines. These results provided information on the range of responses of mouse preneoplastic mammary tissues to a variety of antihormone treatments and suggested that responses to ovariectomy need not be correlated with responses to specific antihormone treatments.
The Emergence and Future of Global Surgery in the United States
Authors: Haile T. Debas
Journal: JAMA Surgery (2015)

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