tbuckley/cabot-search huggingface dataset:
Using Genome-Wide Association Studies to Identify Genes Important in Serious Adverse Drug Reactions
Authors: Ann K. Daly
Journal: The Annual Review of Pharmacology and Toxicology (2011)

Genome-wide association (GWA) studies have detected novel associations for serious, idiosyncratic, adverse drug reactions including liver toxicity, hypersensitivity, skin rash, and myotoxicity. Human leukocyte antigen (HLA) genotype has been established as an important predictor of susceptibility to drug-induced liver injury, including injury with some drugs where immune-related toxicity was not suspected previously. Similarly, GWA studies have shown a key role for HLA genotype in susceptibility to carbamazepine-related skin rash and hypersensitivity. HLA genotype is not a risk factor for all forms of drug-induced liver injury or for myotoxicity or cardiotoxicity. For simvastatin-related myotoxicity, a strong association with SLCO1B1, which encodes the hepatic statin uptake transporter, has been detected. Genome-wide studies have not yet found clear associations for drug-induced cardiotoxicity, but for bisphosphonate-induced necrosis of the jaw, polymorphisms in the cytochrome P450 CYP2C8 may predict susceptibility. Larger GWA studies and whole-genome sequencing may provide additional insights into all these toxicities.
Histopathology of early and late human allograft rejection
Authors: Boris H. Ruebner, Mary Patricia Pauly, Neville Pimstone, Richard E. Ward, John M. Vierling, Robert H. Fennell, Antonio Monarca, Roberto Natangelo, Valeria Azzolini, B. A. Runyon, Y. Peled, J. Rattan, T. Gilat, Z. Fireman
Journal: Hepatology (1987)
Abstract 4300: Selective GFP labeling of cancer with a telomerase-specific adenovirus (OBP-401) to report future recurrence after resection
Authors: Hiroyuki Kishimoto, Ryoichi Aki, Yasuo Urata, Michael Bouvet, Masashi Momiyama, Noriaki Tanaka, Toshiyoshi Fujiwara, Robert M. Hoffman
Journal: Cancer Research (2011)

Abstract We have previously developed a telomerase-specific replicating adenovirus expressing GFP (OBP-401). Intraperitoneal (i.p.) injection of OBP-401 specifically labeled peritoneal tumors with GFP enabling real-time surgical navigation. However, technical difficulty of removing microscopic tumors still remains, which makes it difficult to eradicate disease completely, even after so-called complete resection. In this study we report an additional advantage of OBP-401. Weeks after surgical navigation with OBP-401, recurrent tumor nodules were observed with GFP imaging, indicating that OBP-401 treatment for peritoneal disseminated disease enabled detection of its subsequent recurrence after surgical navigation. Thus tumor labeling with a genetic reporter has important advantages over antibody and other non-genetic labeling since reminant disease remains labeled and can be further resected. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4300. doi:10.1158/1538-7445.AM2011-4300
Characterisation of relaxation of the lower oesophageal sphincter in healthy premature infants.
Authors: T I Omari, K Miki, G Davidson, R Fraser, R Haslam, W Goldsworthy, M Bakewell, J Dent
Journal: Gut (1997)

BACKGROUND: Gastro-oesophageal reflux disease causes significant morbidity in premature infants, but the role of dysfunction of the lower oesophageal sphincter (LOS) in this condition is unclear. METHODS: Oesophageal manometry was performed after gavage feeding in 13 healthy preterm neonates (postmenstrual age &gt; or = 33 weeks) with a perfused sleeve with side hole assembly. Swallow related (both single and multiple) and transient LOS relaxations (TLOSRs) were identified and the characteristics of these events defined. Reflux was identified with manometric criteria (common cavity episodes). RESULTS: Five hundred and eleven relaxation of the LOS were observed, 55% related to single swallows, 23% related to multiple swallows, and 22% TLOSRs. The time to maximal LOS relaxation was longer for TLOSRs than for single or multiple swallows (mean (SEM) 5.0 (0.3) s v 3.0 (0.1) s and 3.3 (0.1) s, p &lt; 0.0001 and p &lt; 0.005). The durations of multiple swallows and TLOSRs were longer than single swallows (12.2 (0.5) s and 11.2 (0.4) s v 5.3 (0.2) s, p &lt; 0.0001). Most of the oesophageal body common cavity episodes (94%) occurred during TLOSRs. CONCLUSIONS: In healthy preterm infants (postmenstrual age &gt; or = 33 weeks) the motor events associated with LOS relaxation were similar to those seen in healthy adults. TLOSRs may be an important mechanism of reflux in premature infants.
Relation between phase of the menstrual cycle and asthma presentations in the emergency department
Authors: B E Brenner
Journal: Thorax (2005)

The phase of the menstrual cycle is thought to influence the course of asthma in women. One recent study reported a large increase in exacerbations during the perimenstrual phase, while another found a preovulatory increase. A study was undertaken to determine the relation between phase of the menstrual cycle and acute asthma in patients presenting to the emergency department (ED).All women aged 18-54 years presenting with a diagnosis of acute asthma exacerbation were considered for enrollment in the study. Women who were pregnant, postmenopausal, following hysterectomy, with a >28 day menstrual cycle or incomplete reproductive history were excluded. The 792 eligible women were classified by menstrual phase based on both date of symptom onset and date of ED visit.When classified by date of symptom onset, 28% were preovulatory (days 5 to 11), 25% were periovulatory (days 12 to 18), 21% were postovulatory (days 19 to 25), and 27% were perimenstrual (days 26 to 4; p = 0.03). When classified by date of ED visit, 28% were preovulatory, 22% were periovulatory, 22% were postovulatory, and 27% were perimenstrual (p = 0.004). Using either approach, there were no significant differences in demographic factors or in asthma severity of women in the various menstrual phase groups.Acute asthma exacerbations do not markedly increase during the perimenstrual phase. The results support the suggestion that both preovulatory and perimenstrual phases are actual triggers of asthma exacerbation in some women, or that these two phases serve as "co-factors" that worsen other recognised triggers of acute asthma.
Placing Lymph for Vaccination
Authors: P. J. O'Brien
Journal: BMJ (1952)

firmed at necropsy.The second writer (M.C.) had seen a similar case in London in 1947, in which the duodenal lesion was confirmed at operation.The combination of these two relatively rare conditions seems to us especially significant in so far as it may point to a limited interval of time, when the developmental abnormality leading to mongolism occurs.Duodenal atresia probably results from a failure of the duodenum to recanalize during the fourth to seventh weeks of gestation.The septal defects unusually common in mongols result from a developmental aberration between the fourth and ninth weeks of foetal life.Any attempt to explain the condition must also! take into account the known rise in incidence of mongolism in the later years of the reproductive period.We feel that a detailed study of the early weeks of pregnancy in mothers over 40 years of age may possibly throw some light on the aetiology of mongolism.-Weare, etc., V. SMALLPEICE.
Don't blame individuals for organisational failures
Authors: D. Mitchell, R. Naylor, M. Wyatt
Journal: BMJ (2012)

Insufficient autophagic degradation has been implicated in accelerated cellular senescence during chronic obstructive pulmonary disease (COPD) pathogenesis. Aging-linked and cigarette smoke (CS)–induced functional deterioration of lysosomes may be associated with impaired autophagy. Lysosomal membrane permeabilization (LMP) is indicative of damaged lysosomes. Galectin-3 and tripartite motif protein (TRIM) 16 play a cooperative role in recognizing LMP and inducing lysophagy, a lysosome-selective autophagy, to maintain lysosome function. In this study, we sought to examine the role of TRIM16-mediated lysophagy in regulating CS-induced LMP and cellular senescence during COPD pathogenesis by using human bronchial epithelial cells and lung tissues. CS extract (CSE) induced lysosomal damage via LMP, as detected by galectin-3 accumulation. Autophagy was responsible for modulating LMP and lysosome function during CSE exposure. TRIM16 was involved in CSE-induced lysophagy, with impaired lysophagy associated with lysosomal dysfunction and accelerated cellular senescence. Airway epithelial cells in COPD lungs showed an increase in lipofuscin, aggresome and galectin-3 puncta, reflecting accumulation of lysosomal damage with concomitantly reduced TRIM16 expression levels. Human bronchial epithelial cells isolated from COPD patients showed reduced TRIM16 but increased galectin-3, and a negative correlation between TRIM16 and galectin-3 protein levels was demonstrated. Damaged lysosomes with LMP are accumulated in epithelial cells in COPD lungs, which can be at least partly attributed to impaired TRIM16-mediated lysophagy. Increased LMP in lung epithelial cells may be responsible for COPD pathogenesis through the enhancement of cellular senescence.
REDUCED IMMEDIATE ISCHEMIC EVENTS WITH CANGRELOR IN PCI USING THE UNIVERSAL DEFINITION OF MI: POOLED ANALYSIS OF THE CANGRELOR VERSUS STANDARD THERAPY TO ACHIEVE OPTIMAL MANAGEMENT OF PLATELET INHIBITION TRIALS
Authors: Harvey D. White, Derek P. Chew, Harold L. Dauerman, Kenneth W. Mahaffey, C. Michael Gibson, Robert A. Harrington, Deepak L. Bhatt
Journal: Journal of the American College of Cardiology (2011)
Prevention of Hypoglycemia During Exercise in Type I Diabetes
Authors: Friedrich W Kemmer
Journal: Diabetes Care (1992)

Insulin-dependent (type I) diabetic subjects who exercise for whatever reason do this at the risk of hypoglycemia. To enjoy physical activities without major metabolic complications, diabetic patients can take measures to prevent exercise-induced hypoglycemia. These measures basically include preventing accelerated insulin absorption, mimicking physiological insulin secretion during exercise, supplying additional carbohydrates during exercise, and providing effective diabetes education. When adapting the insulin dose, duration and intensity of the work load, time of day, prevailing insulin levels, and the state of nutrition must be considered. Additional carbohydrates can prevent hypoglycemia when exercise is spontaneous and insulin dose reduction is impossible. Prevention of exercise-induced hypoglycemia may be best achieved if patients participate in intensive and comprehensive teaching programs for self-management of diabetes.
Abstract 46: Loss of CADM1 expression is associated with poor prognosis and brain metastasis in breast cancer patients
Authors: Harriet Wikman, Laura Westphal, Felicitas Schmid, Markus Glatzel, Jakob Matschke, Manfred Westphal, Sirkku Pollari, Kristiina Iljin, Luigi Terracciani, Heini Huhtala, Anne Kallioniemi, Guido Sauter, Volkmar Müller, Isabell Witzel, Katrin Lamszus, Dirk Kemming, Klaus Pantel
Journal: Cancer Research (2014)

Abstract Purpose: Breast cancer brain metastases (BCBM) are detected with increasing incidence. Therefore, identification of genes involved in BCBM formation is of great interest. Eperimental Design: In order to detect potential genes involved in BCBM, we first screened for genes down-regulated by methylation in cell lines with site-specific metastatic ability. The expression of five genes, CADM1, SPARC, RECK, TNFAIP3 and CXCL14, which were also found down-regulated in gene expression profiling analyses of BCBM tissue samples, were verified by qRT-PCR in a larger patient cohort. CADM1 was chosen for further down-stream analyses. Results: A higher incidence of CADM1 methylation, correlating with the expression levels, was found in BCBM as compared to non-matched primary BC. Similarly, loss of CADM1 protein expression was detected more commonly among BCBM samples as well as among primary breast tumors with subsequent brain relapse. The prognostic role of CADM1 expression was finally verified in two publicly available data sets (n=418) and in two large independent primary breast cancer TMA tumor cohorts (n=1718). The immunohistochemical analyses revealed an association between loss of CADM1 protein expression and risk factors such as disease stage, lymph node status, and tumor size in primary BC. Furthermore, all analyses revealed a significant association between CADM1 and shorter survival. In multivariate analyses, survival was significantly longer for patients with CADM1-positive primary tumors for both TMA data sets (p= 0.04 and p=0.01). Conclusions: Loss of CADM1 expression is an independent prognostic factor especially associated with the development of brain metastases in breast cancer patients. Citation Format: Harriet Wikman, Laura Westphal, Felicitas Schmid, Markus Glatzel, Jakob Matschke, Manfred Westphal, Sirkku Pollari, Kristiina Iljin, Luigi Terracciani, Heini Huhtala, Anne Kallioniemi, Guido Sauter, Volkmar Müller, Isabell Witzel, Katrin Lamszus, Dirk Kemming, Klaus Pantel. Loss of CADM1 expression is associated with poor prognosis and brain metastasis in breast cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 46. doi:10.1158/1538-7445.AM2014-46
Notes on O—a, and the B— C—, with a Few Words on Quackery in General.
Authors: Martin Matter
Journal: JAMA (1896)

Chicago, June 15, 1896. <h3>To the Editor:</h3> —In my letter of May 2, on Omnicura and the Bracelin cure, I refrained from taking much space in theJournal, because the smallness of the subjects did not warrant it. But in the number of June 6 I find J. J. Russell spreading himself over four, columns, ostensibly to answer my criticisms. And there I find that the omnicura has now become a waif and an orphan, disowned and rejected by the very one into whose lap she has poured her golden treasures. But strange as this may seem, it was his only means for smuggling his letter into print, and use mine as a pretext for sponging a free advertisement out of theJournal. In this he has succeeded as usual and it was necessary that he should. Experience shows that it is difficult to land a shark without giving him
Free-Thyroxine Index
Authors: Martin L. Nusynowitz
Journal: JAMA (1975)

THE CIRCULATING concentration of free thyroxine indicates, with rare exception, the physiologic status in regard to euthyroidism, hyperthyroidism, or hypothyroidism. Yet only a very small portion (about 0.05%) of the serum total thyroxine exists in this form. The remainder is bound to the thyroxine-binding proteins, notably thyroxine-binding globulin.  Measurement of total serum thyroxine (TT 4 ) levels do not necessarily reflect the physiologic status of the patient since an increase or diminution in the binding protein concentration will cause a corresponding change in the serum TT 4 level without affecting either the free thyroxine concentration or the euthyroid state.  These same binding-protein changes produce an opposite effect on another test of thyroid function, the triiodothyronine (resin, red blood cell [RBC], or surface adsorbent) uptake test (T 3 uptake). In this test, the free protein-binding sites of the serum compete in the test tube with resin (or RBCs or adsorbent) for added
A Promising Animal Model of Alzheimer's Disease
Authors: R E Tanzi
Journal: New England Journal of Medicine (1995)

A critical component of the development of drugs targeted at treating complex disorders is a reliable animal model that can predict efficacy in clinical trials. Until now, attempts to devise treatments for Alzheimer's disease have been hindered by the lack of such a model. A team of scientists has recently described a transgenic mouse1 that may remedy this problem. The Athena mouse strain, termed PDAPP (platelet-derived growth factor promoter expressing amyloid precursor protein), has neuropathologic features characteristic of those observed in Alzheimer's disease. Specifically, these include amyloid plaques, dystrophic neurites, activated glia, and loss of synapses in the hippocampus and . . .
Molecular Evolution and Phylogenetic Utility of Wolbachia ftsZ and wsp Gene Sequences with Special Reference to the Origin of Male-Killing
Authors: J. Hinrich G. v. d. Schulenburg, Gregory D. D. Hurst, Ties M. E. Huigens, Marnix M. M. van Meer‡, Francis M. Jiggins, Michael E. N. Majerus
Journal: Molecular Biology and Evolution (2000)

A detailed assessment of the evolution and phylogenetic utility of two genes, ftsZ and wsp, was used to investigate the origin of male-killing Wolbachia, previously isolated from the ladybird Adalia bipunctata and the butterfly Acraea encedon. The analysis included almost all available sequences of B-group Wolbachia and two outgroup taxa and showed that (1) the two gene regions differ in phylogenetic utility, (2) sequence variation is here correlated with phylogenetic information content, (3) both genes show significant rate heterogeneity between lineages, (4) increased substitution rates are associated with homoplasy in the data, (5) wsp sequences of some taxa appear to be subject to positive selection, and (6) only a limited number of clades can be inferred with confidence due to either lack of phylogenetic information or the presence of homoplasy. With respect to the evolution of male-killing, the two genes nevertheless seemed to provide unbiased information. However, they consistently produce contradictory results. Current data therefore do not permit clarification of the origin of this behavior. In addition, A. bipunctata was found to be a host to two recently diverged strains of male-killing Wolbachia that showed increased substitution rates for both genes. Moreover, the wsp gene, which codes for an outer membrane protein, was found to be subject to positive selection in these taxa. These findings were postulated to be the product of high selection pressures due to antagonistic host-symbiont interactions in this ladybird species. In conclusion, our study demonstrates that the results of a detailed phylogenetic analysis, including characterization of the limitations of such an approach, can serve as a valuable basis for an understanding of the evolution of Wolbachia bacteria. Moreover, particular features of gene evolution, such as elevated substitution rates or the presence of positive selection, may provide information about the dynamics of Wolbachia-host associations.
Inhaled Corticosteroids, Combined with Long-acting β<sub>2</sub>-Agonists, Improve the Perception of Bronchoconstriction in Asthma
Authors: I. D. BIJL-HOFLAND, S. G. M. CLOOSTERMAN, H. Th. M. FOLGERING, F. J. J. van den ELSHOUT, C. van WEEL, C. P. van SCHAYCK
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The relationship between asthma medication and the perception of asthma symptoms is of interest for daily practice. Poor perception of asthma symptoms might influence patients' health care behavior and subsequently might lead to undertreatment and deterioration of their disease. This study investigated the influence of the chronic use of short-acting and long-acting β2-agonists, compared with the additional use of inhaled corticosteroids on the perception of histamine-induced bronchoconstriction. Patients with asthma (33 male and 31 female, mean age 35 ± 11 yr, FEV1 87 ± 14% of the reference value, PC20 geometric mean 1.08 mg/ml (95% CI: 0.76–1.52) were selected and randomly allocated to the use of either a short-acting β2-agonists (salbutamol, n = 22) or a long-acting β2-agonists (formoterol, n = 22) or placebo (n = 20), which has been used for 12 wk. This medication treatment was repeated exactly 1 yr later, with patients receiving the same medication plus an inhaled corticosteroid. Perception of histamine-induced bronchoconstriction was measured at the start of each treatment period and every 4 wk thereafter. Subjects quantified their sensation of respiratory discomfort during the challenge tests on a modified Borg scale. The perceptive "sensitivity" for changes in FEV1 was analyzed by the linear regression slope ( α ) "Borg versus percentage fall in FEV1." The "absolute perceptual magnitude" was determined by the perception score at the 20% fall in FEV1 (PS20). The additional use of inhaled corticosteroids during the second year resulted in an improved perception of histamine-induced bronchoconstriction (slope α ) compared with the first year for only the long-acting β2-agonists group (p value 0.036). This improvement was not observed for the "absolute perceptual magnitude" (PS20). The additional use of inhaled corticosteroids during chronic use of long-acting β2-agonists improves the perceptive "sensitivity" for changes in FEV1 during histamine-induced bronchoconstriction, which was not observed for short-acting bronchodilators. This result might indicate that the positive effects on perception of airway obstruction might be another reason (besides the beneficial effects on the clinical condition) for prescribing a combination of long-acting β2-agonists and inhaled steroids.Keywords: inhaled corticosteroids; long-acting beta 2 agonists; perception of bronchoconstriction; asthma
PERIDENTAL MEMBRANE AND VITALITY OF TEETH
Authors: Anna H. Cluthe
Journal: JAMA (1925)

<h3>To the Editor:</h3> —On page 1943,The Journal, Dec. 13, 1924, you say, among other things, "if the peridental membrane dies, then and<i>only</i>then does a tooth become dead or necrosed." About 45,000 dentists in this country have been repeatedly told and educated by histologists of the medical and dental profession to believe that no nourishment is given any tooth from the peridental membrane. Every long practicing dentist knows that fully 50 per cent, of tooth pains he is called on to treat are the result of a diseased or inflamed peridental membrane. You say<i>only</i>when the membrane dies. You also advise that only when the entire membrane, not a portion, is dead, is it expedient to extract a tooth. Thousands of dentists and physicians will not agree with your statement. Many other pathologic conditions exist of only slight portions of the peridental membrane when the oralogist, dentist,
Systemic and cardiovascular effects of airway injury and inflammation: ultrafine particle exposure in humans.
Authors: M W Frampton
Journal: Environmental Health Perspectives (2001)

The concentration of particles in the ambient air is associated with deaths from cardiovascular disease, and determining the biologic mechanisms involved has been identified as a high-priority research need. Hypotheses have focused on the possibility of direct cardiac effects, or indirect effects related to inflammatory responses, including increased blood viscosity or increased blood coagulability. Ultrafine particles (UFPs; those smaller than 100 nm) may be important in cardiovascular effects because of their very high deposition efficiency in the pulmonary region, and their high propensity to penetrate the epithelium and reach interstitial sites. We have initiated human clinical studies of the health effects of UFPs using a mouthpiece exposure system. Healthy, nonsmoking subjects 18-55 years of age are exposed at rest for 2 hr to 10 microg/m3 carbon UFPs and to filtered air as a control. Preliminary findings indicate a relatively high overall deposition fraction (0.66 +/- 0.12 by particle number) consistent with model predictions and an absence of particle-associated symptoms or changes in lung function. Planned studies examine responses in susceptible subject groups, and the effects of particles of varying composition. Human clinical studies using model particles will complement other approaches such as epidemiologic, animal exposure, and in vitro studies in determining the mechanisms for heath effects related to ambient particle exposure.