tbuckley/cabot-search huggingface dataset:
Intracerebroventricular injection of interleukin 1 induces high circulating levels of interleukin 6.
Authors: M G De Simoni, M Sironi, A De Luigi, A Manfridi, A Mantovani, P Ghezzi
Journal: The Journal of Experimental Medicine (1990)

IL-1 is known to have a central role in the induction of acute-phase response, and some of its activities (including induction of some acute-phase proteins) were reported to be mediated by an induction of IL-6. Administration to rats of 200 ng of human rIL-1 by intracerebroventricular injection resulted in a more marked induction of circulating IL-6 than the same dose of IL-1 administered systemically (intravenously or intraperitoneally). Induction of serum IL-6 by centrally administered IL-1 was also observed in hypophysectomized or adrenalectomized rats, suggesting that activation of the hypothalamus-pituitary-adrenal axis is not essential for this effect of IL-1. IL-6 induction was also observed after pretreatment with indomethacin, indicating that the effect was dissociated from the pyrogenic activity of IL-1. Induction of IL-6 by a central action could represent a novel pathway in IL-1-induced acute-phase response.
<i>MYB</i> Is Essential for Mammary Tumorigenesis
Authors: Rebecca Yu Miao, Yvette Drabsch, Ryan Stanley Cross, Dane Cheasley, Sandra Carpinteri, Lloyd Pereira, Jordane Malaterre, Thomas J. Gonda, Robin L. Anderson, Robert G. Ramsay
Journal: Cancer Research (2011)

MYB oncogene upregulation is associated with estrogen receptor (ER)-positive breast cancer, but disease requirements for MYB function in vivo have not been explored. In this study, we provide evidence of a critical requirement for MYB functions in models of human and murine breast cancer. In human breast cancer, we found that MYB expression was critical for tumor cell growth both in vitro and in vivo in xenograft settings. In transgenic knockout mice, tissue-specific deletion of the murine MYB gene caused a transient defect in mammary gland development that was reflected in delayed ductal branching and defective apical bud formation. In mouse mammary tumor virus (MMTV)-NEU mice where tumors are initiated by activation of HER2, MYB deletion was sufficient to abolish tumor formation. In the more aggressive MMTV-PyMT model system, MYB deletion delayed tumorigenesis significantly. Together, the findings in these transgenic knockout models implied that MYB was critical during an early window in mammary development when it was essential for tumor initiation, even though MYB loss did not exert a lasting impact upon normal mammary function. Two important MYB-target genes that promote cell survival, BCL2 and GRP78/BIP, were each elevated compared with nontransformed mammary epithelial cells, thereby promoting survival as confirmed in colony formation assays in vitro. Taken together, our findings establish a role for MYB at the hub of ER- and HER2-dependent pathways in mammary carcinogenesis.
Rethinking Professional Ethics in the Cost-Sharing Era
Authors: G. Caleb Alexander, Mark A. Hall, John D. Lantos
Journal: The American Journal of Bioethics (2006)

Changes in healthcare financing increasingly rely upon patient cost-sharing to control escalating healthcare expenditures. These changes raise new challenges for physicians that are different from those that arose either under managed care or traditional indemnity insurance. Historically, there have been two distinct bases for arguing that physicians should not consider costs in their clinical decisions--an "aspirational ethic" that exhorts physicians to treat all patients the same regardless of their ability to pay, and an "agency ethic" that calls on physicians to be trustworthy advisors to their patients. In the setting of greater patient cost-sharing, physicians' aspiration and agency roles increasingly conflict. Satisfactorily navigating the new terrain of consumer-driven healthcare requires physicians to consider these two roles and how they can best be reconciled so as to maximize quality of care while respecting the heterogeneity of patients' financial resources and willingness to pay.
Defensins and innate host defence of the gastrointestinal tract
Authors: C L BEVINS, E MARTIN-PORTER, T GANZ
Journal: Gut (1999)

When viewed from the perspective of host defence, the mammalian digestive tract presents many challenges. At the outset food contains various micro-organisms that could thrive in the rich growth medium of digested nutrients. Because a large surface area is required for the absorption of nutrients, there are abundant potential sites for microbial attachment and invasion in the long digestive tube with its many folds, villi and microvilli. The requirements of efficient nutrient absorption also place limits on the barrier components of host defence. Indeed, unlike the skin, vaginal epithelium or oral mucosa, intestinal mucosa is comprised of only a single layer of epithelial cells. This delicate barrier is further threatened by the effects of acid, bile salts, and hydrolytic enzymes required for digestion. Although some of these molecules are toxic to microbes, and hence may help to control microbial proliferation and survival, these agents may also subtly damage the mucosa and compromise its barrier functions. The potential for cumulative damage may explain why this epithelium is rapidly and continually replaced throughout the lifetime of mammals. As a result of the need for epithelial renewal, stem cell proliferation and differentiation are critical for normal function of the gastrointestinal tract. Damage to, or parasitisation of stem cells would have severe consequences for the maintenance of the normal digestive epithelium.

A continuous microbial threat is also posed by a wide array of colonising microbes throughout the gut, with especially large numbers in the mouth and colon. Infectious complications that often follow treatment with antibiotics suggest that colonising symbionts contribute to host defence against pathogens. Yet, in the absence of effective defence mechanisms, even symbiotic microbes can multiply rapidly and overwhelm the mammalian host. Despite the presence of microbes, normal digestive tract surfaces generally show little evidence of inflammation, the coordinated pattern of vasodilatation, …
A novel 3017-bp deletion mutation in the<i>FERMT1</i>(<i>KIND1</i>) gene in a Chinese family with Kindler syndrome
Authors: C. Zhou, S. Song, J. Zhang
Journal: British Journal of Dermatology (2009)

Conflicts of interest: none declared. Sir, Kindler syndrome (KS; OMIM 173650) is a rare autosomal recessive genodermatosis characterized by congenital acral blister formation and a variable degree of photosensitivity, which resolve slowly with age, followed by generalized progressive poikiloderma with extensive cutaneous atrophy. Gingival fragility, progressive periodontitis and gastrointestinal involvement occur in some patients.1, 2 The KS causative gene, FERMT1 (formerly KIND1), encodes a 677‐amino acid protein, kindlin‐1, which is implicated in the organization and anchorage of the actin cytoskeleton to integrin‐associated platforms.3, 4 It was reported that loss of kindlin‐1 in keratinocytes leads to loss of cell polarity, decreased adhesion, reduced cell proliferation and increased apoptosis.5 Thus far, 33 different FERMT1 (KIND1) mutations have been identified in more than 100 cases of KS. Most of the reported mutations are point mutations, small insertions or deletions, which could be identified by routinely used strategies based on polymerase chain reaction (PCR) amplification of each coding exon and flanking intronic regions, followed by direct sequencing.6, 7
Randomized, phase 2 trial of low-dose cytarabine with or without volasertib in AML patients not suitable for induction therapy
Authors: Hartmut Döhner, Michael Lübbert, Walter Fiedler, Loic Fouillard, Alf Haaland, Joseph M. Brandwein, Stephane Lepretre, Oumedaly Reman, Pascal Turlure, Oliver G. Ottmann, Carsten Müller-Tidow, Alwin Krämer, Emmanuel Raffoux, Konstanze Döhner, Richard F. Schlenk, Florian Voss, Tillmann Taube, Holger Fritsch, Johan Maertens
Journal: Blood (2014)
HOMA-Estimated Insulin Resistance Is an Independent Predictor of Cardiovascular Disease in Type 2 Diabetic Subjects
Authors: Enzo Bonora, Gianni Formentini, Francesco Calcaterra, Simonetta Lombardi, Franco Marini, Luciano Zenari, Francesca Saggiani, Maurizio Poli, Sandro Perbellini, Andrea Raffaelli, Vittorio Cacciatori, Lorenza Santi, Giovanni Targher, Riccardo Bonadonna, Michele Muggeo
Journal: Diabetes Care (2002)

OBJECTIVE—To evaluate whether homeostasis model assessment-estimated insulin resistance (HOMA-IR) is an independent predictor of cardiovascular disease (CVD) in type 2 diabetes. RESEARCH DESIGN AND METHODS—Conventional CVD risk factors (sex, age, smoking, plasma lipids, blood pressure, and metabolic control) and insulin resistance (estimated by HOMA) were evaluated at baseline in 1,326 patients with type 2 diabetes examined within the Verona Diabetes Complications Study. At baseline and after a mean follow-up of 4.5 years, CVD was assessed by medical history, physical examination, electrocardiography, and echo-Doppler of carotid and lower limb arteries. Death certificates and medical records of subjects who died during the follow-up were carefully scrutinized to identify cardiovascular deaths. In statistical analyses, CVD was an aggregate end point including both fatal and nonfatal coronary, cerebrovascular, and peripheral vascular disease as well as ischemic electrocardiographic abnormalities and vascular lesions identified by echo-Doppler. RESULTS—At baseline, 441 subjects were coded positive for CVD (prevalent cases). Incident cases numbered 126. Multiple logistic regression analyses showed that, along with sex, age, smoking, HDL/total cholesterol ratio, and hypertension, HOMA-IR was an independent predictor of both prevalent and incident CVD. A 1-unit increase in (log)HOMA-IR value was associated with an odds ratio for prevalent CVD at baseline of 1.31 (95% CI 1.10–1.56, P = 0.002) and for incident CVD during follow-up of 1.56 (95% CI 1.14–2.12, P &amp;lt; 0.001). CONCLUSIONS—HOMA-IR is an independent predictor of CVD in type 2 diabetes. The improvement of insulin resistance might have beneficial effects not only on glucose control but also on CVD in patients with type 2 diabetes.
Hospital outbreak of vancomycin-resistant enterococci caused by a single clone of Enterococcus raffinosus and several clones of Enterococcus faecium
Authors: M. Kawalec, J. Kedzierska, A. Gajda, E. Sadowy, J. Wegrzyn, S. Naser, A.B. Skotnicki, M. Gniadkowski, W. Hryniewicz
Journal: Clinical Microbiology and Infection (2007)
Electrohydraulic lithotripsy of gall stones--in vitro and animal studies.
Authors: J Harrison, D L Morris, J Haynes, A Hitchcock, C Womack, D C Wherry
Journal: Gut (1987)

Electrohydraulic lithotripsy of human gall stones was investigated in vitro in a bath of saline and in a saline perfused bile duct. The technique was effective--only two stones could not be shattered. Electrohydraulic lithotripsy power requirement correlated with mechanical strength of stones, but not with biochemical composition. A trend toward higher power requirement was recorded with larger stones and stones over 2 cm in diameter could not be fragmented. Safety studies indicated that electrohydraulic lithotripsy was safe, provided the probe tip was not in contact with the bile duct wall. In vivo studies did not show any late effects after 10 days. Electrohydraulic lithotripsy is likely to be useful in the management of biliary calculi.
Evaluation of text-mining systems for biology: overview of the Second BioCreative community challenge
Authors: Martin Krallinger, Alexander Morgan, Larry Smith, Florian Leitner, Lorraine Tanabe, John Wilbur, Lynette Hirschman, Alfonso Valencia
Journal: Genome biology (2008)

Genome sciences have experienced an increasing demand for efficient text-processing tools that can extract biologically relevant information from the growing amount of published literature. In response, a range of text-mining and information-extraction tools have recently been developed specifically for the biological domain. Such tools are only useful if they are designed to meet real-life tasks and if their performance can be estimated and compared. The BioCreative challenge (Critical Assessment of Information Extraction in Biology) consists of a collaborative initiative to provide a common evaluation framework for monitoring and assessing the state-of-the-art of text-mining systems applied to biologically relevant problems.The Second BioCreative assessment (2006 to 2007) attracted 44 teams from 13 countries worldwide, with the aim of evaluating current information-extraction/text-mining technologies developed for one or more of the three tasks defined for this challenge evaluation. These tasks included the recognition of gene mentions in abstracts (gene mention task); the extraction of a list of unique identifiers for human genes mentioned in abstracts (gene normalization task); and finally the extraction of physical protein-protein interaction annotation-relevant information (protein-protein interaction task). The 'gold standard' data used for evaluating submissions for the third task was provided by the interaction databases MINT (Molecular Interaction Database) and IntAct.The Second BioCreative assessment almost doubled the number of participants for each individual task when compared with the first BioCreative assessment. An overall improvement in terms of balanced precision and recall was observed for the best submissions for the gene mention (F score 0.87); for the gene normalization task, the best results were comparable (F score 0.81) compared with results obtained for similar tasks posed at the first BioCreative challenge. In case of the protein-protein interaction task, the importance and difficulties of experimentally confirmed annotation extraction from full-text articles were explored, yielding different results depending on the step of the annotation extraction workflow. A common characteristic observed in all three tasks was that the combination of system outputs could yield better results than any single system. Finally, the development of the first text-mining meta-server was promoted within the context of this community challenge.
Somatic diversification in the absence of antigen-driven responses is the hallmark of the IgM+IgD+CD27+ B cell repertoire in infants
Authors: Sandra Weller, Maria Mamani-Matsuda, Capucine Picard, Corinne Cordier, Damiana Lecoeuche, Frédéric Gauthier, Jean-Claude Weill, Claude-Agnès Reynaud
Journal: The Journal of Experimental Medicine (2008)

T cell–dependent immune responses develop soon after birth, whereas it takes 2 yr for humans to develop T cell–independent responses. We used this dissociation to analyze the repertoire diversification of IgM+IgD+CD27+ B cells (also known as “IgM memory” B cells), comparing these cells with switched B cells in children &amp;lt;2 yr of age, with the aim of determining whether these two subsets are developmentally related. We show that the repertoire of IgM+IgD+CD27+ B cells in the spleen and blood displays no sign of antigen-driven activation and expansion on H-CDR3 spectratyping, despite the many antigenic challenges provided by childhood vaccinations. This repertoire differed markedly from those of switched B cells and splenic germinal center B cells, even at the early stage of differentiation associated with μ heavy chain expression. These data provide evidence for the developmental diversification of IgM+IgD+CD27+ B cells, at least in very young children, outside of T cell–dependent and –independent immune responses.
Sacral nerve stimulation for faecal incontinence due to systemic sclerosis
Authors: N J Kenefick
Journal: Gut (2002)

Faecal incontinence occurs in over one third of patients with systemic sclerosis. The aetiology is multifactorial. Conventional treatment is often unsuccessful. Sacral nerve stimulation is a new effective treatment for resistant faecal incontinence.To evaluate sacral nerve stimulation in patients with systemic sclerosis.Five women, median age 61 years (30-71), with scleroderma associated faecal incontinence were evaluated. All had failed maximal conventional treatment. Median number of preoperative weekly episodes of incontinence was 15 (7-25), median duration of incontinence was five years (5-9), and scleroderma 13 years (4-29).All patients were screened with temporary stimulation. Those who benefited underwent permanent implantation. At baseline and after stimulation a bowel diary, the SF-36 quality of life assessment, endoanal ultrasound, and anorectal physiology were performed.Four patients were continent at a median follow up of 24 months (6-60). One patient failed temporary stimulation and was not permanently implanted. The weekly episodes of incontinence decreased from 15, 11, 23, and 7 to 0. Urgency resolved (median time to defer <1 minute (0-1) v 12.5 minutes (5-15)). Quality of life, especially social function, improved. Endoanal ultrasound showed an atrophic internal anal sphincter (median width 1.0 mm (0-1.6)). Anorectal physiology showed an increase in median resting pressure (37 pre v 65 cm H(2)O post) and squeeze pressure (89 v 105 cm H(2)O). Stimulation produced enhanced rectal sensitivity to distension. There were no major complications.Sacral nerve stimulation is a safe and effective treatment for resistant faecal incontinence secondary to scleroderma. The benefit is maintained in the medium term.
THE OCCURRENCE OF ACID MUCOPOLYSACCHARIDES IN HUMAN LEUKOCYTES AND URINE 1
Authors: Grace P. Kerby
Journal: Journal of Clinical Investigation (1955)

Acid mucopolysaccharides have been found in urine (1) but have not been consistently demon- strated in the blood of normal subjects.Bassiouni (2) recently isolated a substance from leukocytes which he noted to be similar to chondroitin sul- fate.In our laboratory leukocytes have been found to contain appreciable quantities of a sub- stance resembling chondroitin sulfate.A direct relationship between this substance and the simi- lar substance found in the urine has not been established. METHODSSubjects.Human subjects were used.These were hospital and laboratory personnel and patients who were unselected except for the omission of individuals with primary hematologic, metabolic, or rheumatic diseases.Preparation of leukocytes.Siliconed needles, syringes, and glassware were used throughout the preparation un- til the step in which the cells were deliberately disinte- grated.Venous blood (40 to 70 ml.)was drawn and distributed immediately in 10-ml.amounts to tubes con- taining 1.0 ml. of 5 per cent sodium citrate in a balanced salt solution.2The red blood cells were sedimented rapidly by mixing 2.5 ml. of 5 per cent dextran with the blood in each tube.3The supernatant leukocyte-platelet suspension in plasma was centrifuged at 85 g for 7 min- utes, and the sedimented leukocytes were washed gently one time in 11.0 ml. of physiologic saline.Following recentrifuging, they were then pooled in 20 ml. of saline, counted, made up to 25 ml.with saline in process of trans- ferring to a Raytheon Sonic Oscillator, and oscillated at 9 Kc. per second for 8 minutes.
Pathological Narcissism and Narcissistic Personality Disorder
Authors: Aaron L. Pincus, Mark R. Lukowitsky
Journal: Annual Review of Clinical Psychology (2009)

We review the literature on pathological narcissism and narcissistic personality disorder (NPD) and describe a significant criterion problem related to four inconsistencies in phenotypic descriptions and taxonomic models across clinical theory, research, and practice; psychiatric diagnosis; and social/personality psychology. This impedes scientific synthesis, weakens narcissism's nomological net, and contributes to a discrepancy between low prevalence rates of NPD and higher rates of practitioner-diagnosed pathological narcissism, along with an enormous clinical literature on narcissistic disturbances. Criterion issues must be resolved, including clarification of the nature of normal and pathological narcissism, incorporation of the two broad phenotypic themes of narcissistic grandiosity and narcissistic vulnerability into revised diagnostic criteria and assessment instruments, elimination of references to overt and covert narcissism that reify these modes of expression as distinct narcissistic types, and determination of the appropriate structure for pathological narcissism. Implications for the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders and the science of personality disorders are presented.
Identification of the motility-related protein (MRP-1), recognized by monoclonal antibody M31-15, which inhibits cell motility.
Authors: M Miyake, M Koyama, M Seno, S Ikeyama
Journal: The Journal of Experimental Medicine (1991)

A murine monoclonal antibody (M31-15) was identified using the penetration-inhibiting assay of a human lung adenocarcinoma cell line (MAC10) and remarkably inhibited the phagokinetic tract motility of various cancer cell lines. The antigen, motility-related protein (MRP-1), recognized by M31-15, was 25- and 28-kD proteins, and M31-15 was used to isolate a cDNA clone from a human breast carcinoma cDNA library. Sequence analysis revealed that MRP-1 had strong similarity with a B cell surface antigen (CD37), a melanoma-associated antigen (ME491), the target of an antiproliferative antibody (TAPA-1), a human tumor-associated antigen (CO-029), and the Sm23 antigen of the trematode parasite Schistosoma mansoni.
Bacteriological evidence of antibiotic failure in pneumococcal lower respiratory tract infections
Authors: K.P. Klugman
Journal: European Respiratory Journal (2002)

The global pandemic of antimicrobial resistance, particularly in the pneumococcus, has had a major impact on the management of community-acquired pneumonia. A number of prospective and retrospective studies have analysed the impact of penicillin resistance on clinical outcome in pneumonia. Pharmacodynamic principles predicting success when the antibiotic dose exceeds the minimum inhibitory concentration (MIC) for 40–50% of the dosing interval have proved remarkably accurate. There is no evidence of bacteriological failure of penicillins active against resistant strains. There is a single report of the failure of the less active agent, ticarcillin. High dose oral and intravenous amoxicillin should treat strains with MICs ≤4 µg·mL −1 , as should high doses of intravenous penicillin, ceftriaxone and cefotaxime. Strains of pneumococci resistant to these agents at an MIC ≥8 µg·mL −1 are rare at the present time. Most other cephalosporins are less active and should not be used empirically for drug-resistant Streptococcus pneumoniae . Bacteriological failures of cefazolin, cefuroxime and ceftazidime have been reported. There is increasing evidence of bacteriologically confirmed macrolide failure of pneumonia therapy at MICs ≥4 µg·mL −1 . The molecular basis of the resistance is irrelevant if the MIC is in that range or higher. Double mutants in the parC and gyrA genes lead to fluoroquinolone resistance that has been found to cause bacteriological failure of the fluoroquinolones, particularly levofloxacin and ciprofloxacin, in the management of pneumonia and exacerbations of chronic bronchitis. Two mutations in these genes can greatly increase the MICs of all the marketed fluoroquinolones, and raise the prospect of failure of therapy even with the more active ones. However, demonstration of bacteriological failure of gatifloxacin or moxifloxicin has not yet been reported. High dose, active β‐lactams or fluoroquinolones with enhanced activity against Gram positive pathogens remain the drugs of choice for the management of community-acquired pneumonia caused by the drug-resistant pneumococcus.