tbuckley/cabot-search huggingface dataset:
Evolutionary instability of operon structures disclosed by sequence comparisons of complete microbial genomes
Authors: T. Itoh, K. Takemoto, H. Mori, T. Gojobori
Journal: Molecular Biology and Evolution (1999)

Gene orders have been shown to be generally unstable by comprehensive analyses in several complete genomes. In this study, we examined instability of genome structures within operons, where functionally related genes are clustered. We compared gene orders of known operons obtained from Escherichia coli and Bacillus subtilis with corresponding those of operons in 11 complete genome sequences. We found that in many cases, gene orders within operons could be shuffled frequently during evolution, although several operon structures, such as ribosomal protein operons, were well conserved. This suggests that shuffling of a genome structure is virtually neutral in long-term evolution. Moreover, degrees of instability of the operon structures depended on the genomes examined. Variation in degrees of instability of the genome structures was likely to be related to differences in amounts of insertion sequences. Effects on transcription regulation are also discussed in association with operon destruction.
Low-Dose Physiological Growth Hormone in Patients With HIV and Abdominal Fat Accumulation
Authors: Janet Lo
Journal: JAMA (2008)

Antiretroviral therapy can be associated with visceral adiposity and metabolic complications, increasing cardiovascular risk, and reduced growth hormone (GH) secretion may be a contributing factor.To investigate the effects of low-dose physiological GH administration on body composition, glucose, and cardiovascular parameters in patients with human immunodeficiency virus (HIV) having abdominal fat accumulation and relative GH deficiency.A randomized, double-blind, placebo-controlled trial of 56 patients with HIV, abdominal fat accumulation, and reduced GH secretion (peak GH <7.5 ng/mL) conducted at a US academic medical center between November 2003 and October 2007.Patients were randomly assigned to receive either subcutaneous GH or matching placebo titrated to the upper quartile of normal insulinlike growth factor 1 (IGF-1) range for 18 months. Starting dose was 2 microg/kg/d and increased to maximum dose of 6 microg/kg/d (average dose, 0.33 mg/d).Change in body composition assessed by computed tomographic scan and dual-energy x-ray absorptiometry. Secondary outcomes included glucose, IGF-1, blood pressure (BP), and lipids. Treatment effect was the difference in the change between GH and placebo groups, using all available data.Fifty-five patients (26 with GH and 29 with placebo) were included in the safety analyses and 52 patients (25 with GH and 27 with placebo) were included in the efficacy analyses. Visceral adipose tissue area (treatment effect [last-value-carried-forward analysis {n = 56}, -19 cm(2); 95% confidence interval {CI}, -37 to -0.3 cm(2)], -19 cm(2); 95% CI, -38 to -0.5 cm(2); P = .049); trunk fat (-0.8 kg; 95% CI, -1.5 to -0.04 kg; P = .04); diastolic BP (-7 mm Hg; 95% CI, -11 to -2 mm Hg; P = .006); and triglycerides (-7 mg/dL, P = .002) improved but 2-hour glucose levels on glucose tolerance testing increased in the GH group vs the placebo group (treatment effect, 22 mg/dL; 95% CI, 6-37 mg/dL; P = .009). The IGF-1 levels increased (treatment effect, 129 ng/mL; 95% CI, 95-164 ng/mL; P < .001). Adverse events were not increased for GH vs placebo (23%; 95% CI, 9%-44% vs 28%; 95% CI, 13%-47%; P = .70).In HIV-associated abdominal fat accumulation and relative GH deficiency, low-dose GH received for 18 months resulted in significantly reduced visceral fat and truncal obesity, triglycerides, and diastolic BP, but 2-hour glucose levels on glucose tolerance testing were increased.clinicaltrials.gov Identifier: NCT00100698.
Localization of a Skeletal Imaging Agent in Nonmalignant Ascites
Authors: WEI-JEN SHIH, PEGGY A. DOMSTAD
Journal: Clinical Nuclear Medicine (1988)

Accumulation of a skeletal imaging agent in ascitic fluid has been described exclusively in malignancies. Therefore, when increased peritoneal activity is detected in Tc-99m phosphonate bone images, ascites due to a malignant tumor has been strongly suggested. A patient with nonmalignant ascites in whom bone imaging showed diffuse uptake in the abdomen is presented.
Abstract 113: Effect of targeting Aurora kinase A in human oral squamous cell carcinoma cells
Authors: Hiroshi Tanaka, Koh-ichi Nakashiro, Ryota Oka, Hiroyuki Hamakawa
Journal: Cancer Research (2012)

Abstract Oncogene addiction has provided therapeutic opportunities in many human malignancies, but molecular targeted therapy for oral squamous cell carcinoma (OSCC) is not available. In this study, we identified an appropriate molecule for treatment of patients with OSCC. We determined the gene expression profiles in 10 human OSCC cell lines and a non-neoplastic keratinocyte cell line by microarray analysis, and then identified Aurora kinase A (AURKA) as a cancer-related gene which was commonly overexpressed in OSCC cells. We also confirmed the overexpression of AURKA mRNA in OSCC tissues and compared to normal oral mucosa tissues by quantitative RT-PCR. AURKA plays an essential role in centrosome duplication, mitoic entry, and spindle assembly. Overexpression of AURKA in human malignancies is associated with gene amplification, genetic instability, poor histological differentiation, and poor prognosis. To determine if the AURKA is a plausible therapeutic target, we investigated the effect of small interfering RNAs specific for AURKA(siAURKA) and an AURKA selective inhibitor MLN8237 on the growth of human OSCC cells in vitro and in vivo. Knockdown of AURKA by RNA interference (RNAi) markedly inhibited the growth of OSCC cells and observed the change of colony formation and cell size looked like cell cycle arrest. We examined the RNAi effect of siAURKA in OSCC cells by Western blotting. Compared with non-target siRNA, the protein expression level of AURKA was almost completely suppressed. MLN8237 also reduced the cell growth, but showed relatively resistant to cells expressing AURKA at high levels. Transfection of siAURKA inhibited the growth of OSCC cells more potent than treatment with MLN8237 in vitro. Furthermore, we confirmed the effect of siAURKA and MLN8237 on the growth of human OSCC tumors which had been subcutaneously xenografted in athymic nude mice. Atelocollagen-siAURKA (8 nmol) complexes were injected into the tail vein every 3 days and MLN8237 (30 mg/kg) were received orally for 14 consecutive days. We found that siAURKA and MLN8237 significantly reduced the size of subcutaneously xenografted OSSC tumors. Interestingly, the combination of siAURKA and MLN8237 induced remarkable anti-tumor activity compared with single agent groups. These results suggest that AURKA functions as a critical gene for supporting the growth of human OSCC cells and targeting AURKA may be a useful therapeutic strategy for OSCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 113. doi:1538-7445.AM2012-113
Serum Sodium
Authors: Leonard B. Berman
Journal: JAMA (1974)

SODIUM concentrations have become a part of every patient's hospital record. Interpreting them correctly depends on two fundamental facts. First, a concentration is a<i>ratio</i>—the amount of sodium compared with the amount of plasma (plasma water) in which it is dissolved. Thus, an abnormal value may result from a change in the amount of sodium, a change in the amount of water, or a change in the amount of both. This leads to situations that all have a low serum sodium concentration but arise from different mechanisms and call for different treatments. The second key fact is that the serum concentration of sodium gives no information about the concentration inside the cells and other special compartments such as bone. It is therefore possible for serum sodium concentration and total body sodium to vary in opposite directions. The two most common types of hyponatremia are illustrated as follows: <i>Depletional</i>hyponatremia
Plan to end age discrimination in NHS is launched
Authors: Z. Kmietowicz
Journal: BMJ (2001)

The first national plan to end age discrimination in the NHS and improve the quality of care provided for older people was launched this week by the Department of Health.

The National Service Framework for Older People gives a frank acknowledgement that the NHS has been riddled with discrimination against older people in the past and confirms the government's commitment to tackle it head-on to raise standards in the clinical and social care provided for older people.

At the heart …
On Societies as Organisms
Authors: Lewis Thomas
Journal: New England Journal of Medicine (1971)

VIEWED from a suitable height, the aggregating clusters of medical scientists in the bright sun-light of the boardwalk at Atlantic City, swarmed there from everywhere for the annual meetings, have the look of assemblages of social insects. There is the same vibrating, ionic movement, interrupted by the darting back and forth of jerky individuals to touch antennae and exchange small bits of information; periodically, the mass casts out, like a trout-line, a long single file unerringly toward Childs's. If the boards were not fastened down, it would not be a surprise to see them put together a nest of sorts. . . .
The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer
Authors: Irving C. Allen, Erin McElvania TeKippe, Rita-Marie T. Woodford, Joshua M. Uronis, Eda K. Holl, Arlin B. Rogers, Hans H. Herfarth, Christian Jobin, Jenny P.-Y. Ting
Journal: The Journal of Experimental Medicine (2010)

Colitis-associated cancer (CAC) is a major complication of inflammatory bowel diseases. We show that components of the inflammasome are protective during acute and recurring colitis and CAC in the dextran sulfate sodium (DSS) and azoxymethane + DSS models. Mice lacking the inflammasome adaptor protein PYCARD (ASC) and caspase-1 demonstrate increased disease outcome, morbidity, histopathology, and polyp formation. The increased tumor burden is correlated with attenuated levels of IL-1β and IL-18 at the tumor site. To decipher the nucleotide-binding domain, leucine-rich-repeat-containing (NLR) component that is involved in colitis and CAC, we assessed Nlrp3 and Nlrc4 deficient mice. Nlrp3−/− mice showed an increase in acute and recurring colitis and CAC, although the disease outcome was less severe in Nlrp3−/− mice than in Pycard−/− or Casp1−/− animals. No significant differences were observed in disease progression or outcome in Nlrc4−/− mice compared with similarly treated wild-type animals. Bone marrow reconstitution experiments show that Nlrp3 gene expression and function in hematopoietic cells, rather than intestinal epithelial cells or stromal cells, is responsible for protection against increased tumorigenesis. These data suggest that the inflammasome functions as an attenuator of colitis and CAC.
Persistent survival of luminescent mycobacterium avium subspecies paratuberculosis in peripheral blood monocytes from both crohn's disease and healthy controls is associated with differential cytokine response
Authors: T. Elliott, R. Linedale, B. Hudspith, N. Rayment, J. Hermon-Taylor, T. Bull, J. Sanderson
Journal: Gut (2011)

<h3>Introduction</h3> Abnormal intestinal macrophage function which could allow persistence of candidate bacterial triggering agents such as <i>E coli</i> and <i>Mycobacterium avium</i> subspecies <i>paratuberculosis</i> (MAP), has been implicated in the pathogenesis of Crohn9s disease (CD).1 Prolonged survival of <i>E coli</i> in CD-derived peripheral blood monocytes (PBM) has been demonstrated,2 however current methods of determining MAP infection are difficult and time-consuming. The application of a luminescent MAP strain in a novel rapid technique may improve survival assays.3 <h3>Aims</h3> Determine the sensitivity and accuracy of a method to quantify luminescent MAP and develop an intracellular survival assay. Monitor cytokine profiles induced during MAP infection in CD and healthy controls (HC). <h3>Methods</h3> Quantitative real-time PCR (qRT PCR) was used to calibrate a standard curve of luminescence from MAP ‘Lux’ 19 698 strain. Monocytes from CD and HC were isolated and infected with MAP lux 19 698 (multiplicity of infection 4:1) for up to 4 weeks. Luminescence was recorded at intervals to determine killing activity compared to medium only controls. Intracellular uptake was visualised using an anti-MAP antibody and confocal microscopy. Cytokine release (TNFα, IL10, IL6 and IL23) from PBM was measured using ELISA pre and 24 h post infection. <h3>Results</h3> A close linear relationship (R<sup>2</sup>= 0.9999) was seen between luminescence and number of MAP organisms by qRT PCR. Sensitivities were also similar. Monocytes from 8 CD patients and 7 HC infected with MAP lux 19 698 assayed over a mean of 15 days (range 8 to 27) showed some killing during the experiment time course. However a majority of MAP survived intracellularly (visualised by confocal microscopy) in all samples and the degree of killing was not significantly different between CD and HC. Cytokine profiling showed only a proportion of all subject9s (CD or HC) PBM responded to MAP infection. Of these responders, there was a difference in cytokine profiles between CD and HC and in particular there was a strong trend to greater IL6 response in CD. <h3>Conclusion</h3> This study provides initial validation for a luminescent MAP intracellular survival assay. Consistent, persistent survival of MAP was demonstrated in both CD and controls. Alterations in cytokine responses to MAP infection between CD and normals suggest that this agent is perceived and processed differently by CD monocytes.
Magnetic resonance jet velocity mapping in mitral and aortic valve stenosis.
Authors: P J Kilner, C C Manzara, R H Mohiaddin, D J Pennell, M G Sutton, D N Firmin, S R Underwood, D B Longmore
Journal: Circulation (1993)

BACKGROUND Magnetic resonance (MR) phase-shift velocity mapping is an established method for measurement of nonturbulent intravascular flow. Shortening the echo time of the MR sequence to 3.6 msec allowed application of the technique to turbulent jet flow. The objective of this study was validation of MR jet velocity mapping in patients with cardiac valve stenosis. METHODS AND RESULTS We used a 0.5-T Picker MR machine to measure peak poststenotic jet velocity in 15 consecutive patients recruited with known valve disease (six mitral stenosis, three of these restudied after valvoplasty, and 11 aortic stenosis). On the same day as the MR study, these patients underwent independent Doppler echocardiographic measurement of peak jet velocity. The results of 10 further MR investigations of aortic stenosis are also reported and compared with Doppler studies performed within 6 months. Of the 29 MR studies, 28 (97%) produced interpretable velocity maps, the one failure being attributed to misplacement of the imaging slice in a case of severe aortic stenosis. Agreement between MR and Doppler measurements of peak jet velocity in the recruited group was as follows: n = 18; range, 1.4-6.1 m/sec; mean, 3 m/sec; mean of differences (MR-Doppler), 0.23 m/sec; standard deviation of differences, 0.49 m/sec. CONCLUSIONS In vivo MR peak jet velocity measurements agree well with those made by Doppler ultrasound. The technique, which is not subject to restricted windows of access and has potential for further refinements, could contribute to improved evaluation of stenoses, especially at locations where ultrasonic access is limited.
Postmenopausal Estrogen Therapy
Authors: Joseph W. Goldzieher
Journal: JAMA (1974)

<h3>To the Editor.—</h3> I wish to add a comment to the useful letter of Marshall (227:76, 1974). Dr. Marshall repeats oft-quoted statistics to the effect that 30% of patients receiving postmenopausal estrogen therapy develop uterine bleeding, and that approximately 5% to 8% of these women will be found to have endometrial carcinoma. Simple calculations indicate that these figures are rank nonsense. Conjugated estrogens occupy a place in the first half dozen drugs in order of sales volume. Since most of this medication is used by postmenopausal women, there is little question that millions of women at any one time are using postmenopausal estrogen therapy. If 30% of these patients develop bleeding, and 5% to 8% have carcinoma, this represents an incidence of 1.5% to 2.4% endometrial carcinoma in women receiving these estrogens. This would mean 15,000 to nearly 24,000 cases of endometrial carcinoma per million women taking these drugs—an epidemic
TCT-775 Transapical Transcatheter Aortic Valve Implantation in Patients with Reduced Left Ventricular Ejection Fraction: Comparison of Balloon-expandable and Self-expanding Prostheses
Authors: Johannes Schirmer, Moritz Seiffert, Hermann Reichenspurner, Patrick Diemert, Hendrik Treede
Journal: Journal of the American College of Cardiology (2014)
Goldberger’s war:The life and work of a public health crusader
Authors: Jesse Roth
Journal: Journal of Clinical Investigation (2004)

In the early twentieth century, over 100,000 poor Southerners, young and old, black and white, sharecroppers and mill hands, were afflicted annually with pellagra, a mysterious and frequently fatal disease characterized by skin lesions, delirium, and gastrointestinal disturbances (1).Each flood of the Mississippi River or collapse in the price of cotton pushed up the incidence.As fatalities rose, Joseph Goldberger, an up-and-coming bacteriologist in the US Public Health Service, assigned in 1914 to investigate the growing epidemic, concluded that the widely accepted infectious etiology was incorrect.Through careful field work in prisons and orphanages, Goldberger provided strong evidence for an underlying dietary deficiency (1-7).To convince the scientific public that pellagra was not transmissible, Goldberger, his coworkers, and his wife received injections of blood and excrement from affected prisoners.That none of them came down with pellagra is part of the saga, but that they escaped hepatitis or syphilis or some other common disease was indeed fortuitous.Because pellagra's victims were poor and socially unconnected, Goldberger's original cure, a diet rich in lean meat, eggs, and milk, was considered unacceptable because it was too expensive.Returning to the federal government's Hygienic Laboratory in Washington, Goldberger validated a model of the disease in dogs and showed that brewer's yeast, at pennies a day, could do as well as the expensive diet.Political barriers, however, impeded the adoption of this inexpensive remedy.The result was that the total conquest of pellagra was delayed until 25 years after Goldberger's discovery of a cure and ten years after his death.Alan Kraut's book is a skilled recounting of Goldberger's life and complements nicely Elizabeth W. Etheridge's 1972 masterpiece, The butterfly caste: the social history of pellagra (3).Kraut
Magnesium Intake in Relation to Risk of Colorectal Cancer in Women
Authors: Susanna C. Larsson
Journal: JAMA (2005)

Context Animal studies have suggested that dietary magnesium may play a role in the prevention of colorectal cancer, but data in humans are lacking.Objective To evaluate the hypothesis that a high magnesium intake reduces the risk of colorectal cancer in women. Design, Setting, and ParticipantsThe Swedish Mammography Cohort, a population-based prospective cohort of 61 433 women aged 40 to 75 years without previous diagnosis of cancer at baseline from 1987 to 1990. Main Outcome Measure Incident invasive colorectal cancer.Results During a mean of 14.8 years (911042 person-years) of follow-up, 805 incident colorectal cancer cases were diagnosed.After adjustment for potential confounders, we observed an inverse association of magnesium intake with the risk of colorectal cancer (P for trend=.006).Compared with women in the lowest quintile of magnesium intake, the multivariate rate ratio (RR) was 0.59 (95% confidence interval [CI], 0.40-0.87)for those in the highest quintile.The inverse association was observed for both colon (RR, 0.66; 95% CI, 0.41-1.07)and rectal cancer (RR, 0.45; 95% CI, 0.22-0.89). ConclusionThis population-based prospective study suggests that a high magnesium intake may reduce the occurrence of colorectal cancer in women.
P3-148: Evaluation of efficacy and safety of erlotinib as monotherapy for Japanese patients with advanced non–small cell lung cancer (NSCLC); integrated analysis of two Japanese phase II studies
Authors: Tomohide Tamura, Yutaka Nishiwaki, Koshiro Watanabe, Kazuhiko Nakagawa, Kaoru Matsui, Toshiaki Takahashi, Yoshihiko Segawa, Yukito Ichinose, Masahiro Fukuoka, Nagahiro Saijo
Journal: Journal of Thoracic Oncology (2007)
In vivo suppression of NF-kappa B and preservation of I kappa B alpha by interleukin-10 and interleukin-13.
Authors: A B Lentsch, T P Shanley, V Sarma, P A Ward
Journal: Journal of Clinical Investigation (1997)

IL-10 and IL-13 have powerful antiinflammatory activities in vitro and in vivo. In the IgG immune complex model of lung injury in rats, exogenously administered IL-10 or IL-13 have recently been shown to suppress neutrophil recruitment and ensuing lung injury by greatly depressing pulmonary production of TNF alpha. Transcriptional control of the TNF alpha gene is regulated by the nuclear factor kappa B (NF-kappa B). Activation of NF-kappa B involves the degradation of its cytoplasmic inhibitor I kappa B alpha, allowing the nuclear translocation of NF-kappa B, with ensuing transcriptional activation. In this study, we sought to determine whether the protective effects of IL-10 and IL-13 in IgG immune complex-induced lung injury were mediated by inhibition of NF-kappa B activation. Electrophoretic mobility shift analysis of nuclear extracts from alveolar macrophages and whole lung tissues demonstrated that both IL-10 and IL-13 suppressed nuclear localization of NF-kappa B after in vivo deposition of IgG immune complexes. Western blot analysis indicated that these effects were due to preserved protein expression of I kappa B alpha in both alveolar macrophages and whole lungs. Northern blot analysis of lung mRNA showed that, in the presence of IgG immune complexes, IL-10 and IL-13 augmented I kappa B alpha mRNA expression. These findings suggest that in vivo, IL-10 and IL-13 may operate by suppressing NF-kappa B activation through preservation of I kappa B alpha.
Interpretation of subjective symptoms in double‐blind placebo‐controlled food challenges – interobserver reliability
Authors: M. Gellerstedt, J. Magnusson, U. Gråjö, S. Ahlstedt, U. Bengtsson
Journal: Allergy (2004)

Background: Subjective symptoms after food challenges are difficult to interpret and no standard is available. We discuss a strategy for how to interpret a diary. Furthermore, the interobserver reliability is evaluated. Methods: Diaries for 32 patients with subjective symptoms were used. The diaries were re‐evaluated with a predefined strategy by three independent observers. Results: The proportion of positives was 21.9% among the old diagnoses, according to the new approach 34.4% (observers I and II) and 37.5% (observer III) were positive. The new approach had high interobserver reliability (97 and 100%). Conclusions: The proportion of positives depends on how subjective symptoms are interpreted. Interpretations of subjective symptoms in diaries could be made with high interobserver reliability.