tbuckley/cabot-search huggingface dataset:
Osteonecrosis of the Jaw and the Role of Macrophages
Authors: M. Pazianas
Journal: JNCI Journal of the National Cancer Institute (2010)

Nitrogen-containing bisphosphonates have been associated with the development of osteonecrosis of the jaws (ONJ), but the lack of reliable epidemiological data and appropriate animal models has restricted our understanding of ONJ pathophysiology and limited its management. The best available information is from histopathologic findings, which implicate bone necrosis and infection, although it is not clear which is primary. However, there are data suggesting that macrophages could well be the central factor in allowing the infection to develop first, followed by local necrosis, which could also account for the development of ONJ in patients treated with denosumab, a human monoclonal antibody to the receptor activator of nuclear factor-κB ligand. This review examines the evidence that macrophages could play a prominent role in development of ONJ and the proposal that it may be more appropriate to view ONJ as a drug and not only a bisphosphonate-related complication.
Suicide Attempts in Substance Abusers: Effects of Major Depression in Relation to Substance Use Disorders
Authors: Efrat Aharonovich, Xinhua Liu, Edward Nunes, Deborah S. Hasin
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: The authors' goal was to investigate whether subtypes of DSM-IV depression predict suicidal behavior among patients with substance dependence. METHOD: Major depression among 602 patients with substance dependence was classified as occurring before dependence, during abstinence, or exclusively during periods of substance use. Analyses of patients with the three types of depression included logistic and linear regression. RESULTS: All three types of depression increased the risk for making a suicide attempt. Major depression that occurred before the patient became substance dependent predicted severity of suicidal intent. Major depression that occurred during abstinence predicted number of attempts. CONCLUSIONS: These results suggest the importance of establishing DSM-IV subtypes of depression based on the timing of the occurrence of depression in relation to substance dependence in evaluating suicidal risk among substance-dependent patients.
Effect of continuous positive airway pressure on ventricular ectopy in heart failure patients with obstructive sleep apnoea
Authors: C M Ryan
Journal: Thorax (2005)

Obstructive sleep apnoea (OSA) elicits a number of cardiovascular perturbations that could lead acutely or chronically to increased ventricular ectopy in patients with heart failure (HF). We tested the hypothesis that treatment of OSA with continuous positive airway pressure (CPAP) in patients with HF would reduce the frequency of ventricular premature beats (VPBs) during sleep in association with reduced sympathetic nervous system activity.Following optimisation of medical treatment, 18 HF patients with OSA and >10 VPBs per hour of sleep were randomised to a control group (n = 8) or a treatment group who received CPAP (n = 10). The frequency of VPBs and urinary norepinephrine (noradrenaline) concentrations during total sleep time were determined at baseline and after 1 month.Control patients did not experience any significant changes in apnoea-hypopnoea index (AHI), mean nocturnal O(2) saturation, or the frequency of VPBs. In contrast, there was a significant reduction in AHI (p<0.001), an increase in minimum O(2) saturation (p = 0.05), a reduction in urinary norepinephrine concentrations (p = 0.009), and a 58% reduction in the frequency of VPBs during total sleep (from mean (SE) 170 (65) to 70 (28) per hour, p = 0.011) after 1 month of CPAP treatment.In patients with HF, treatment of co-existing OSA by CPAP reduces the frequency of VPBs during sleep. These data suggest that reductions in VPBs and other ventricular arrhythmias through treatment of OSA might improve the prognosis in patients with HF.
EXPERIENCES OF TREATING ALLERGIC RHINITIS WITH INTRA‐NASAL BECLOMETHASONE DIPROPIONATE
Authors: E. HOLOPAINEN, H. MALMBERG, E. TARKIAINEN
Journal: Allergy (1977)

The effect of locally acting intra-nasal beclomethasone dipropionate was observed in 42 patients suffering from seasonal allergic rhinitis and 50 patients suffering from perennial rhinitis. The study consists of three parts: 1) a simple double-blind trial in seasonal rhinitis, 2) a double-blind crossover trial in perennial rhinitis, 3) a 1-year follow-up of the perennial group. The active drug was significantly superior to placebo when comparing subjective symptoms, nasal resistance and secretion eosinophilia in the patients. In long-term use it was possible to reduce the initial dose considerably. On objective examination no significant changes were seen in the epithelium following long-term use. No suppression of the hypothalamic-pituitary-adrenal axis was observed after 1 year's regular use of beclomethasone dipropionate. The side effects were mild, the most common complaint being irritation of the nasal mucous membrane, apparently caused by the propellant gas.
Survival benefit with erlotinib maintenance therapy in patients with advanced non-small-cell lung cancer (NSCLC) according to response to first-line chemotherapy
Authors: B. Coudert, T. Ciuleanu, K. Park, Y.-L. Wu, G. Giaccone, W. Brugger, P. Gopalakrishna, F. Cappuzzo
Journal: Annals of Oncology (2011)
The usefulness of magnetic resonance imaging (MRI) for disseminated trichosporosis of the gastrocnemius muscles
Authors: Akiko Meguro-Hashimoto, Masaaki Takatoku, Ken Ohmine, Masaki Toshima, Masaki Mori, Tadashi Nagai, Kazuo Muroi, Keiya Ozawa
Journal: Journal of Infection (2006)
Exercise induced bronchospasm in Ghana: differences in prevalence between urban and rural schoolchildren
Authors: E. O. Addo Yobo, A. Custovic, S. C. Taggart, A. P. Asafo-Agyei, A. Woodcock
Journal: Thorax (1997)

BACKGROUND: As more developing countries adopt a westernised style of living, an increase in the prevalence of asthma can be expected to occur in these areas. A study was undertaken to establish the normal response to exercise in Ghanaian children and to use these normal values to determine the prevalence of exercise induced bronchospasm (EIB) in urban rich (UR), urban poor (UP), and rural (R) school children. Skin test reactivity to common inhalant allergens in UR, UP, and R children with and without EIB was also investigated. METHODS: Two hundred children aged 9-16 years without a previous history of respiratory symptoms were randomly selected and underwent free running exercise testing. A normal response to exercise was defined as the group mean change in peak expiratory flow rate (PEFR) +/- 2 standard deviations. This value was used to identify the prevalence of EIB in UR, UP, and R schoolchildren. A total of 1095 children from three different schools underwent exercise testing (220 UP, 599 UR, 276 R), after which 916 children underwent skin prick testing to six common inhalant allergens (D farinae, D pteronyssinus, cat, dog, Aspergillus flavus and Candida albicans). RESULTS: From the results of exercise testing in asymptomatic children the normal range was defined as a fall in PEFR of &lt; 12.5% after exercise. Thirty four children were classified as having EIB on the basis of the above definition, giving an overall prevalence of 3.1%. The prevalence of EIB was significantly higher in UR children (4.7%) than in both UP (2.2%; p &lt; 0.05) and R children (1.4%; p &lt; 0.01). However, the prevalence rates in the UP and R children were similar. The prevalence of atopy in the whole population was 4.4%. Of the children with EIB, 10% were skin test positive to at least one of the allergens tested. The prevalence of atopy was significantly higher in UR children (6.55%, 95% confidence interval (CI) 4.5% to 9.2%) than in UP (2.9%, 95% CI 0.9% to 6.7%) and R children (1.5%, 95% CI 0.4% to 3.7%), respectively (p &lt; 0.005). CONCLUSIONS: The prevalence of EIB and atopy is higher in urban rich than in urban poor or rural children suggesting that, in addition to genetic predisposition, social and environmental factors such as wealth, life style, and housing are important determinants of these phenotypes.
The Membrane-Associated Guanylate Kinase Protein MAGI-1 Binds Megalin and Is Present in Glomerular Podocytes
Authors: KEVIN M. PATRIE, ANDREW J. DRESCHER, MEERA GOYAL, ROGER C. WIGGINS, BEN MARGOLIS
Journal: Journal of the American Society of Nephrology (2001)

Abstract. The transmembrane endocytic receptor glycoprotein 330/megalin (hereafter referred to as megalin) is localized to the apical membrane domain of epithelial cells, where it is involved in the uptake of proteins from extracellular sources. The cytoplasmic domain of megalin contains amino acid motifs that have the potential to bind to other proteins, which may influence its localization or function. The yeast two-hybrid system was used to search for proteins that bind to the cytoplasmic tail of megalin, and a protein fragment from a mouse embryonic cDNA library that contained a single PDZ domain was identified. This protein, which was named g lycoprotein 330- as sociated p rotein (GASP), appears to be a truncated mouse counterpart of the human and rat proteins atrophin-1-interacting protein-1 and synaptic scaffolding molecule, respectively. The interaction of GASP with megalin is mediated by the PDZ domain of GASP binding to the DSDV motif found at the carboxyl-terminus of megalin. A mutant version of megalin that lacks the terminal valine is unable to bind to GASP, illustrating the PDZ domain-dependent interaction between these two proteins. A close homolog of GASP, i.e. , membrane-associated guanylate kinase with inverted orientation-1 (MAGI-1), is more ubiquitous in its tissue distribution (including kidney) and is also able to specifically bind to megalin via its fifth PDZ domain. Immunofluorescence studies of adult kidney revealed that MAGI-1 is expressed in the glomerulus of the kidney, in a manner that parallels the expression of the podocyte-specific protein glomerular epithelial protein 1. Western analysis of endogenous MAGI-1 from glomerular preparations suggests that it is associated with the cytoskeleton and seems to be expressed in a different form, compared with cell line-derived endogenous MAGI-1. The association of megalin with MAGI-1 may allow the assembly of a multiprotein complex, in which megalin may serve a nonendocytic function in glomerular podocytes.
Somatic structural rearrangements in genetically engineered mouse mammary tumors
Authors: Ignacio Varela, Christiaan Klijn, Phillip J Stephens, Laura J Mudie, Lucy Stebbings, Danushka Galappaththige, Hanneke van der Gulden, Eva Schut, Sjoerd Klarenbeek, Peter J Campbell, Lodewyk FA Wessels, Michael R Stratton, Jos Jonkers, P Andrew Futreal, David J Adams
Journal: Genome biology (2010)

Here we present the first paired-end sequencing of tumors from genetically engineered mouse models of cancer to determine how faithfully these models recapitulate the landscape of somatic rearrangements found in human tumors. These were models of Trp53-mutated breast cancer, Brca1- and Brca2-associated hereditary breast cancer, and E-cadherin (Cdh1) mutated lobular breast cancer. We show that although Brca1- and Brca2-deficient mouse mammary tumors have a defect in the homologous recombination pathway, there is no apparent difference in the type or frequency of somatic rearrangements found in these cancers when compared to other mouse mammary cancers, and tumors from all genetic backgrounds showed evidence of microhomology-mediated repair and non-homologous end-joining processes. Importantly, mouse mammary tumors were found to carry fewer structural rearrangements than human mammary cancers and expressed in-frame fusion genes. Like the fusion genes found in human mammary tumors, these were not recurrent. One mouse tumor was found to contain an internal deletion of exons of the Lrp1b gene, which led to a smaller in-frame transcript. We found internal in-frame deletions in the human ortholog of this gene in a significant number (4.2%) of human cancer cell lines. Paired-end sequencing of mouse mammary tumors revealed that they display significant heterogeneity in their profiles of somatic rearrangement but, importantly, fewer rearrangements than cognate human mammary tumors, probably because these cancers have been induced by strong driver mutations engineered into the mouse genome. Both human and mouse mammary cancers carry expressed fusion genes and conserved homozygous deletions.
Contrasting Inotropic Effects of Endogenous Endothelin in the Normal and Failing Human Heart
Authors: Philip A. MacCarthy, Richard Grocott-Mason, Bernard D. Prendergast, Ajay M. Shah
Journal: Circulation (2000)

Background —Endothelin-1 (ET-1) is a potent positive inotrope in vitro, but its physiological effects on intrinsic myocardial contractile function in humans in vivo are unknown. Plasma ET-1 levels are elevated in heart failure, and ET-1 may be involved in the pathophysiology of this condition. However, its effects on contractile function of the failing human heart are also unknown. Methods and Results —A specific ET A receptor antagonist, BQ123, was infused (40 nmol/min, 16 minutes) into the left coronary artery in 8 patients with atypical chest pain (normal left ventricular [LV] function and coronary arteries) and 8 patients with nonischemic dilated cardiomyopathy (DCM) who were undergoing diagnostic catheterization. In normal subjects, BQ123 rapidly induced a significant reduction in LV dP/dt max (−270±71 mm Hg/s after 16 minutes; P &lt;0.05) and in LV dP/dt at a developed pressure of 40 mm Hg (LV dP/dt 40 ) (−179±54 mm Hg/s; P &lt;0.05). In DCM patients, however, BQ123 caused no reductions in LV dP/dt max (62±49 mm Hg/s after 16 minutes) or LV dP/dt 40 (83±51 mm Hg/s; P &lt;0.05 compared with normal subjects). BQ123 had no effect on heart rate, LV relaxation, LV end-diastolic pressure, right atrial pressure, or pulmonary pressure in either patient group. Conclusions —Endogenous ET-1 has a tonic positive inotropic effect in normal subjects, independent of effects on the peripheral vasculature and unmasked by inhibition of ET A receptors. However, the effect of short-term ET A blockade in DCM patients was opposite to that in normal subjects, which suggests that ET-1 may cause negative inotropic effects in the failing heart.
Treating infant colic with the probiotic Lactobacillus reuteri: double blind, placebo controlled randomised trial
Authors: V. Sung, H. Hiscock, M. L. K. Tang, F. K. Mensah, M. L. Nation, C. Satzke, R. G. Heine, A. Stock, R. G. Barr, M. Wake
Journal: BMJ (2014)

<b>Objective:</b> To estimate the overall incidence of acute and overuse volleyball injuries, and to describe factors associated with ankle sprains. <b>Methods:</b> 486 players from the second and third Dutch national volleyball divisions participated in the study and were followed prospectively during a whole season. Three measurements were made during the season (baseline, follow up 1, and follow up 2), where all players completed a questionnaire on demographic variables (only at baseline), sports participation, use of preventive measures, and previous injuries. Volleyball exposure during training and matches was recorded for each individual player by the coach on a weekly exposure form. In case of injury the coach provided the injured player with an injury registration form, which had to be completed within one week after the onset of injury. <b>Results:</b> 100 injuries were reported, resulting in an overall injury incidence of 2.6 injuries/1000 hours. The incidence of acute injuries was 2.0/1000 hours. Ankle sprains (n = 41) accounted for most of the acute injuries, and 31 (75%) of all players with an ankle sprain reported a previous ankle sprain. Twenty five overuse injuries were reported. The overall incidence of overuse injuries was 0.6/1000 hours; the back and the shoulder were the most common sites. <b>Conclusions:</b> Ankle sprain is the most common injury in volleyball, accounting for 41% of all volleyball related injuries. Previous injury seems to be an important risk factor for an ankle sprain. Injury prevention programmes should focus on ankle sprains and concentrate on players with previous ankle sprains.
Tenofovir for Hepatitis Delta
Authors: Vincent Soriano, Pablo Barreiro, Carmen de Mendoza
Journal: Hepatology (2015)

Potential conflict of interest: Nothing to report. To the Editor: We read with interest the clinical observation from James et al.1 of a 34‐year‐old male with advanced cirrhosis attributable to hepatitis delta virus (HDV) infection who experienced clinical improvement, normalization of liver enzymes, suppression of serum HDV RNA and hepatitis B surface antigen (HBsAg) clearance after 2 years of oral tenofovir monotherapy. The authors concluded that tenofovir should be tried in patients with hepatitis delta with contraindications for interferon use. As acknowledged by the authors, we firstly reported a potential benefit of tenofovir on delta hepatitis.2 More recently we have had the opportunity to assess 19 individuals with hepatitis delta who were treated with tenofovir for an average of 58 months, as part of their antiretroviral combination for human immunodeficiency viral infection.3 All experienced significant declines in serum HDV RNA, and 10 (53%) achieved undetectable viral load. Moreover, hepatic fibrosis, as measured using elastometry, significantly improved in the subset of individuals who reached complete HDV suppression. Serum HBsAg became negative in three patients, but none of them seroconverted to antibody to HBsAg, as happened in the case reported by James et al.1 We then decided to give four double doses of the hepatitis B virus vaccine to these three patients, but none elicited an antibody response to HBsAg. Given that removal of tenofovir could be risky, we have decided to keep all of our patients on tenofovir. Hepatitis delta is often a neglected condition, despite being the most severe form of chronic viral hepatitis. Misdiagnosis of HDV superinfection in HBsAg carriers often leads to wrong clinical decisions as these patients may exhibit elevated liver enzymes and rapid liver fibrosis progression despite undetectable hepatitis B virus DNA. More than 15 million people are infected with HDV worldwide, with large differences in prevalence across distinct geographical regions and/or risk groups.4 Pegylated interferon is currently the only recommended treatment for chronic hepatitis delta, with disappointing results. Hopes for new drugs, such as myrcludex‐B or lonafarnib, are still too preliminary. As James et al.1 stopped tenofovir in their patient, it would be important to report if HDV rebound occurred thereafter. The achievement of HDV eradication would be supported if the benefit persists. Moreover, what happened with HBsAg? Did it reappear, and did chronic liver disease resume as hepatitis B alone?
Blood-pressure in Undernourished Javanese
Authors: K. V. Bailey
Journal: BMJ (1963)

Many observations have been made indicating that arterial blood-pressure, especially systolic, tends to be lower in undernourished subjects (Keys et al., 1950).During studies of nutrition made for the Indonesian Nutrition Institute in Java in 1957-9 blood-pressures were measured with a view to comparing the relative effects of low-calorie and low-protein diets on pressures.The geographical and dietary circumstances are described elsewhere (Bailey, 1960, 1961).Materials and Methods Blood-pressure was studied in three villages.One, Pakem, was in the densely populated irrigated ricefield area near Jogjakarta.The other two, Tjuwelo and Kedungpoh, were in the unfertile limestone hill region of Gunung Kidul, further east of Jogjakarta, where cassava (tapioca) was the staple foodstuff.In these villages all available people were mustered at the headman's home or office where I measured the blood- pressures.About half the adult population in each village were measured.Factors determining the composition of the sample in each village were similar, absentees being chiefly men and women under 30 who were out in the fields working, and some decrepit old people who stayed at home.Casual blood-pressures were measured in the same way as those in Pacific Islanders reported by Lovell et al. (1960) except that diastolic pressure was taken at the point of disappearance of sounds.Weights, heights, and arm circumferences midway between acromion and olecranon were also measured.The ages recorded were guesses based on the knowledge of the village headman of certain dates, such as the two world wars, and on my own impression based on four years' residence in Java.
Comparative reduction of theories — or over-simplification?
Authors: Edgar Koerner
Journal: Behavioral and Brain Sciences (1996)

Abstract To model the organization of levels' of cortical dynamics, at least some general scheme for hierarchy, functional diversity, and proper intrinsic control must be provided. Rhythmic control forces the system to iterate its state by short trajectories, which makes it much more stable and predictable without discarding the desirable ability of chaotic systems to make rapid phase transitions. Rhythmic control provides a fundamentally different systems dynamics, one not provided by models that allow the emergence of continuous trajectories in the systems state space.
Discovery of permuted and recently split transfer RNAs in Archaea
Authors: Patricia P Chan, Aaron E Cozen, Todd M Lowe
Journal: Genome biology (2011)

As in eukaryotes, precursor transfer RNAs in Archaea often contain introns that are removed in tRNA maturation. Two unrelated archaeal species display unique pre-tRNA processing complexity in the form of split tRNA genes, in which two to three segments of tRNAs are transcribed from different loci, then trans-spliced to form a mature tRNA. Another rare type of pre-tRNA, found only in eukaryotic algae, is permuted, where the 3' half is encoded upstream of the 5' half, and must be processed to be functional. Using an improved version of the gene-finding program tRNAscan-SE, comparative analyses and experimental verifications, we have now identified four novel trans-spliced tRNA genes, each in a different species of the Desulfurococcales branch of the Archaea: tRNAAsp(GUC) in Aeropyrum pernix and Thermosphaera aggregans, and tRNALys(CUU) in Staphylothermus hellenicus and Staphylothermus marinus. Each of these includes features surprisingly similar to previously studied split tRNAs, yet comparative genomic context analysis and phylogenetic distribution suggest several independent, relatively recent splitting events. Additionally, we identified the first examples of permuted tRNA genes in Archaea: tRNAiMet(CAU) and tRNATyr(GUA) in Thermofilum pendens, which appear to be permuted in the same arrangement seen previously in red alga. Our findings illustrate that split tRNAs are sporadically spread across a major branch of the Archaea, and that permuted tRNAs are a new shared characteristic between archaeal and eukaryotic species. The split tRNA discoveries also provide new clues to their evolutionary history, supporting hypotheses for recent acquisition via viral or other mobile elements.