tbuckley/cabot-search huggingface dataset:
Small-airways deposition of dornase alfa in children with asthma and persistent airway obstruction
Authors: E. Marije Bakker, Els C. van der Wiel-Kooij, Bernhard Müllinger, Philipp Kroneberg, Wim C.J. Hop, Harm A.W.M. Tiddens
Journal: Journal of Allergy and Clinical Immunology (2013)
Bioluminescence-Activated Deep-Tissue Photodynamic Therapy of Cancer
Authors: Yi Rang Kim, Seonghoon Kim, Jin Woo Choi, Sung Yong Choi, Sang-Hee Lee, Homin Kim, Sei Kwang Hahn, Gou Young Koh, Seok Hyun Yun
Journal: Theranostics (2015)

Optical energy can trigger a variety of photochemical processes useful for therapies.Owing to the shallow penetration of light in tissues, however, the clinical applications of light-activated therapies have been limited.Bioluminescence resonant energy transfer (BRET) may provide a new way of inducing photochemical activation.Here, we show that efficient bioluminescence energy-induced photodynamic therapy (PDT) of macroscopic tumors and metastases in deep tissue.For monolayer cell culture in vitro incubated with Chlorin e6, BRET energy of about 1 nJ per cell generated as strong cytotoxicity as red laser light irradiation at 2.2 mW/cm 2 for 180 s.Regional delivery of bioluminescence agents via draining lymphatic vessels killed tumor cells spread to the sentinel and secondary lymph nodes, reduced distant metastases in the lung and improved animal survival.Our results show the promising potential of novel bioluminescence-activated PDT.
Is There Evidence for Convergent Evolution around Human Microsatellites?
Authors: M. T. Webster, J. Hagberg
Journal: Molecular Biology and Evolution (2007)

A study by Vowles and Amos (2004) identified atypical patterns of base composition around human microsatellites and argued that microsatellites generate mutational biases in their flanking regions. Here, we perform simulations of molecular evolution using a simple model that suggest similar patterns can be produced without any such biases in genome evolution.
Additive Effects of HIV and Chronic Methamphetamine Use on Brain Metabolite Abnormalities
Authors: Linda Chang, Thomas Ernst, Oliver Speck, Charles S. Grob
Journal: American Journal of Psychiatry (2005)

Proton magnetic resonance spectroscopy (1H-MRS) showed decreased neuronal marker N-acetylaspartate and increased glial marker myo-inositol in subjects with chronic methamphetamine use and in subjects infected with HIV. The authors sought to determine whether HIV and a history of chronic methamphetamine use might have additive or interactive effects on brain metabolite abnormalities.1H-MRS was performed in 68 HIV-positive subjects (24 with a history of chronic methamphetamine use with a lifetime exposure of a mean of 2,167 g [SD=2,788] and last use a mean of 4.9 months earlier [SD=6.0]; 44 with no history of drug abuse) and 75 HIV-negative subjects (36 with a history of chronic methamphetamine use with a lifetime exposure of a mean of 8,241 g [SD=16,850] and last use a mean of 6.3 months earlier [SD=7.8]; 39 with no history of drug abuse). Concentrations of N-acetylaspartate, creatine, choline, and myo-inositol were measured in the frontal cortex, frontal white matter, and basal ganglia.HIV-negative subjects with a history of chronic methamphetamine use showed lower concentrations of the neuronal marker N-acetylaspartate in the frontal white matter and basal ganglia and higher concentrations of choline compounds and the glial marker myo-inositol in the frontal cortex, relative to subjects with no history of drug abuse. HIV-positive status was associated with lower concentrations of N-acetylaspartate and creatine in the frontal cortex and higher concentrations of myo-inositol in the white matter, compared with HIV-negative status. Compared to the mean concentrations of metabolites in HIV-negative subjects with no history of drug abuse, the mean concentrations in subjects with HIV and chronic methamphetamine use showed additive effects on N-acetylaspartate in all three regions (-9% in the basal ganglia, -7% in the frontal white matter, and -6% in the frontal gray matter), on creatine in the basal ganglia (-7%), and on myo-inositol in the frontal white matter (+11%).The combined effects of HIV and chronic methamphetamine use were consistent with an additive model, suggesting additional neuronal injury and glial activation due to the comorbid conditions.
1317 PRETREATMENT OF HEPATOMA CELL LINES WITH IL28B DELAYS INTERFERON-INDUCED ISG EXPRESSION, WHEREAS PRETREATMENT WITH NEUTRALIZING ANTIBODIES AGAINST IL28B REDUCES EXPRESSION LEVELS OF IFN RECEPTORS
Authors: H. Abe, H. Ochi, C.N. Hayes, D. Mild, M. Tsuge, N. Hiraga, M. Imamura, S. Takahashi, K. Chayama
Journal: Journal of Hepatology (2011)
Deranged smooth muscle -actin expression as a biomarker of intestinal pseudo-obstruction
Authors: E Jaynes
Journal: Gut (2005)

We read with interest the article by Knowles and colleagues ( Gut 2004; 53 :1583–9) in which the authors concluded that immunostaining of the adult jejunum with smooth muscle α-actin (ASMA) may be a valuable biomarker of chronic idiopathic intestinal pseudo-obstruction (CIIP). We recently published a similar study in which 17 archival formalin fixed, paraffin wax embedded samples of small intestine and 12 samples of large intestine were immunostained with ASMA, desmin, and smooth muscle myosin heavy …
Topotecan-Triggered Degradation of Topoisomerase I Is p53-Dependent and Impacts Cell Survival
Authors: Maja T. Tomicic, Markus Christmann, Bernd Kaina
Journal: Cancer Research (2005)

Abstract The anticancer drug topotecan belongs to the group of topoisomerase I (topo I) inhibitors. In the presence of topotecan, topo I cleaves the DNA but is unable to religate the single-strand break. This leads to stabilization of topo I-DNA–bound complexes and the accumulation of DNA strand breaks that may interfere with DNA replication. The molecular mechanism of controlling the repair of topo I-DNA covalent complexes and its impact on sensitivity of cells to topotecan is largely unknown. Here, we used mouse embryonic fibroblasts expressing wild-type p53 and deficient in p53, in order to elucidate the role of p53 in topotecan-induced cell death. We show that p53-deficient mouse embryonic fibroblasts are significantly more sensitive to topotecan than wild-type cells, displaying a higher frequency of topotecan-induced apoptosis and DNA strand breaks. Treatment of p53 wild-type cells with pifithrin-α, an inhibitor of the trans-activating activity of p53, caused reversal of the phenotype, making wild-type cells more sensitive to topotecan. Upon topotecan treatment, topo I was degraded in wild-type but not in p53-deficient cells. Topo I degradation was attenuated by the proteosomal inhibitor MG132. Similar data were obtained with human glioblastoma cells. U138 cells (p53 mutated) were significantly more sensitive to topotecan than U87 cells (p53 wild-type). Furthermore, U87 cells showed significant degradation of topo I upon topotecan treatment, whereas in U138 cells, this response was abrogated. Topo I degradation was again attenuated by pifithrin-α. The data suggests that p53 causes resistance of cells to topo I inhibitors due to stimulation of topotecan-triggered topo I degradation which may impact topotecan-based cancer therapy.
Later Psychosocial Sequelae of Early Childhood Illness (Severe Croup)
Authors: J. J. SIGAL, L. CHAGOYA, C. VILLENEUVE, J. MAYEROVITCH
Journal: American Journal of Psychiatry (1973)

Twelve families in which only one child had had severe croup before the age of five were examined several years later. Parents rated the behavior of the proband and one of his siblings separately, and each child rated his parents' attitudes toward him. The data confirm that severe early childhood illness results in later disturbances in the parent-child relationship, and they permit a clear description of the "vulnerable child syndrome."
Effect of statin treatment on short term mortality after pneumonia episode: cohort study
Authors: I. Douglas, S. Evans, L. Smeeth
Journal: BMJ (2011)

<b>Objective </b>To determine whether statins protect against all cause mortality after a diagnosis of pneumonia. <b>Design </b>Cohort study using propensity score based method to control for differences between people prescribed and not prescribed statins. <b>Setting </b>United Kingdom Health Improvement Network database, which contains electronic primary care medical records of more than six million patients. <b>Participants </b>Every patient starting a statin between 1995 and 2006 (129 288) matched with up to five non-statin users (n=600 241); 9073 patients had a recorded diagnosis of pneumonia, of whom 1398 were using a statin. <b>Main outcome measure </b>All cause mortality within six months of diagnosis of pneumonia. <b>Results </b>Among users and non-users of statins with comparable propensity scores, 95/942 users and 686/3615 non-users died on the day that pneumonia was diagnosed. In the following six month period, 109/847 statin users died compared with 578/2927 non-users, giving an adjusted hazard ratio of 0.67 (0.49 to 0.91). If these observed benefits translated into clinical practice, 15 patients would need to be treated with a statin for six months after pneumonia to prevent one death. <b>Conclusions </b>Compared with people who were not taking statins, the risk of dying in the six month period after pneumonia was substantially lower among people who were already established on long term statin treatment when the pneumonia occurred. Whether some or all of this protective effect would be obtained if statin treatment begins when a patient first develops pneumonia is not known. However, given that statins are cheap, safe, and well tolerated, a clinical trial in which people with pneumonia are randomised to a short period of statin treatment is warranted.
Hearing loss in motorcyclists: occupational and medicolegal aspects
Authors: A. W McCombe
Journal: Journal of the Royal Society of Medicine (2003)

Motorcycles have been around as a mode of transport since the latter part of the 19th century, and have long been regarded as irritating and noisy. However, regulations to prevent excess vehicular noise in both urban and sports settings1,2 seem to be reasonably successful. Kamperman3 has shown that, in an urban setting, accelerating motorcycles with standard exhausts are no louder than motorcars, and measurements by the Transport Research Laboratory have shown overall motorcycle noise to be within UK legislative limits4.

One might assume that, as well as sparing the public noise nuisance, these regulations would also protect the rider. However, over the past 10-15 years, as motorcycle development has led to quieter machines with radically improved performance, there has been increasing concern that riders are exposed to excessive noise through turbulent airflow around the helmet—so-called wind-noise5,6,7,8,9,10,11,12. The seminal report on this topic (although not the first) was that of Van Moorhem et al. in 19816. Apart from the work of our group, there have since been only six published reports on the subject7,8,9,10,11,12.
Liver involvement in multiple myeloma
Authors: R. Perez‐Soler, R. Esteban, E. Allende, C. Tornos Saloma, A. Julia, J. Guardia
Journal: American Journal of Hematology (1985)

One hundred twenty-eight records of patients with multiple myeloma were reviewed to assess the incidence and manifestations of liver involvement. Histologic study of the liver was available in 21 patients. Diffuse infiltration of the liver by plasma cells was observed in 10 patients, myeloid metaplasia in four, amyloidosis in two, toxic hepatitis in two, and extrahepatic cholestasis secondary to infiltration of the peripancreatic tissue by plasma cells in one. The clinical signs of plasma cell infiltration of the liver consisted of hepatomegaly in seven patients, mild elevation of liver enzymes in five, and portal hypertension in two. Jaundice was only observed in patients with hepatitis or extrahepatic cholestasis. Liver infiltration by plasma cells did not appear to have a major prognostic significance.
Ancient Origin of Elicitin Gene Clusters in Phytophthora Genomes
Authors: Rays H. Y. Jiang, Brett M. Tyler, Stephen C. Whisson, Adrienne R. Hardham, Francine Govers
Journal: Molecular Biology and Evolution (2005)

The genus Phytophthora belongs to the oomycetes in the eukaryotic stramenopile lineage and is comprised of over 65 species that are all destructive plant pathogens on a wide range of dicotyledons. Phytophthora produces elicitins (ELIs), a group of extracellular elicitor proteins that cause a hypersensitive response in tobacco. Database mining revealed several new classes of elicitin-like (ELL) sequences with diverse elicitin domains in Phytophthora infestans, Phytophthora sojae, Phytophthora brassicae, and Phytophthora ramorum. ELIs and ELLs were shown to be unique to Phytophthora and Pythium species. They are ubiquitous among Phytophthora species and belong to one of the most highly conserved and complex protein families in the Phytophthora genus. Phylogeny construction with elicitin domains derived from 156 ELIs and ELLs showed that most of the diversified family members existed prior to divergence of Phytophthora species from a common ancestor. Analysis to discriminate diversifying and purifying selection showed that all 17 ELI and ELL clades are under purifying selection. Within highly similar ELI groups there was no evidence for positively selected amino acids suggesting that purifying selection contributes to the continued existence of this diverse protein family. Characteristic cysteine spacing patterns were found for each phylogenetic clade. Except for the canonical clade ELI-1, ELIs and ELLs possess C-terminal domains of variable length, many of which have a high threonine, serine, or proline content suggesting an association with the cell wall. In addition, some ELIs and ELLs have a predicted glycosylphosphatidylinositol site suggesting anchoring of the C-terminal domain to the cell membrane. The eli and ell genes belonging to different clades are clustered in the genomes. Overall, eli and ell genes are expressed at different levels and in different life cycle stages but those sharing the same phylogenetic clade appear to have similar expression patterns.
Seat-belt legislation.
Authors: G Avery
Journal: BMJ (1979)

bearing-down reflex had been abolished, because these mothers.exhibited the least accumulation of metabolic acidosis (those epidural mothers who retained the bearingdown reflex were rather more acidotic because, presumably, of the greater exertion involved).3The important point, however, is that at each designated duration of the second stage the "epidural" infants were less acidotic at delivery than were the "non-epidural" infants.It appears from the reports of their studies4 5 that Professor Derom and his colleagues found no significant difference in the acid-base state of neonates referable to epidural analgesia, but they did not introduce into their analysis the duration of the second stage as a variable factor.I would contend that in the circum- stances under review it is the contrast between the absolute values of neonatal acidosis which is of importance, and not the difference between the values of feto-maternal gradients.
A Multicenter Phase II Study of Single-Agent Enzastaurin in Previously Treated Waldenström Macroglobulinemia
Authors: Irene M. Ghobrial, Philippe Moreau, Brianna Harris, Tiffany Poon, Eric Jourdan, Hervé Maisonneuve, Karim A. Benhadji, Anwar M. Hossain, Tuan S. Nguyen, James E. Wooldridge, Veronique Leblond
Journal: Clinical Cancer Research (2012)

Enzastaurin is a serine/threonine kinase inhibitor that showed antiangiogenic, antiproliferative, and proapoptotic properties in vitro and antitumor activity in vivo in a xenograft Waldenström macroglobulinemia (WM) model. These findings provided the rationale for a multicenter phase II trial of oral enzastaurin in previously treated patients with WM.Patients who were treated with 1 to 5 prior regimens and who had a baseline immunoglobulin M level 2 times or more the upper limit of normal received oral enzastaurin 250 mg twice daily (500 mg total) after a single loading dose (day 1, cycle 1) of 375 mg 3 times daily (1,125 mg total) for 8 cycles of 28 days each or until progressive disease. Six patients who progressed during treatment with enzastaurin had dexamethasone added per protocol.From July 2008 to December 2010, 42 patients were enrolled. The objective response rate (RR) was 38.1% (2 partial and 14 minor responses). One patient had grade 3 leukopenia and one patient died during the study from septic shock; both events were considered drug related. A statistically significant association between RR and interleukin 15 (IL-15) was observed, suggesting that higher concentration levels of IL-15 may be associated with better response.Enzastaurin was active and well tolerated in previously treated patients with WM. Because of the small sample size of this uncontrolled study, further assessment of the relationship between IL-15 and response to enzastaurin in patients with WM is required. These results warrant further investigation of enzastaurin for the treatment of WM.
Effects of Intensive Blood Pressure Lowering on Cardiovascular and Renal Outcomes: A Systematic Review and Meta-Analysis
Authors: Xinfang Xie, Emily Atkins, Jicheng Lv, Alexander Bennett, Bruce Neal, Toshiharu Ninomiya, Mark Woodward, Stephen MacMahon, Fiona Turnbull, Graham S Hillis, John Chalmers, Jonathan Mant, Abdul Salam, Kazem Rahimi, Vlado Perkovic, Anthony Rodgers
Journal: PLoS Medicine (2012)

Background Guidelines recommend intensive blood pressure (BP) lowering in patients at high risk. While placebo-controlled trials have demonstrated 22% reductions in coronary heart disease (CHD) and stroke associated with a 10-mmHg difference in systolic BP, it is unclear if more intensive BP lowering strategies are associated with greater reductions in risk of CHD and stroke. We did a systematic review to assess the effects of intensive BP lowering on vascular, eye, and renal outcomes. Methods and Findings We systematically searched Medline, Embase, and the Cochrane Library for trials published between 1950 and July 2011. We included trials that randomly assigned individuals to different target BP levels. We identified 15 trials including a total of 37,348 participants. On average there was a 7.5/4.5-mmHg BP difference. Intensive BP lowering achieved relative risk (RR) reductions of 11% for major cardiovascular events (95% CI 1%–21%), 13% for myocardial infarction (0%–25%), 24% for stroke (8%–37%), and 11% for end stage kidney disease (3%–18%). Intensive BP lowering regimens also produced a 10% reduction in the risk of albuminuria (4%–16%), and a trend towards benefit for retinopathy (19%, 0%–34%, p = 0.051) in patients with diabetes. There was no clear effect on cardiovascular or noncardiovascular death. Intensive BP lowering was well tolerated; with serious adverse events uncommon and not significantly increased, except for hypotension (RR 4.16, 95% CI 2.25 to 7.70), which occurred infrequently (0.4% per 100 person-years). Conclusions Intensive BP lowering regimens provided greater vascular protection than standard regimens that was proportional to the achieved difference in systolic BP, but did not have any clear impact on the risk of death or serious adverse events. Further trials are required to more clearly define the risks and benefits of BP targets below those currently recommended, given the benefits suggested by the currently available data. Please see later in the article for the Editors' Summary.
Systemic Complications of Acromegaly: Epidemiology, Pathogenesis, and Management
Authors: Annamaria Colao, Diego Ferone, Paolo Marzullo, Gaetano Lombardi
Journal: Endocrine Reviews (2004)

This review focuses on the systemic complications of acromegaly. Mortality in this disease is increased mostly because of cardiovascular and respiratory diseases, although currently neoplastic complications have been questioned as a relevant cause of increased risk of death. Biventricular hypertrophy, occurring independently of hypertension and metabolic complications, is the most frequent cardiac complication. Diastolic and systolic dysfunction develops along with disease duration; and other cardiac disorders, such as arrhythmias, valve disease, hypertension, atherosclerosis, and endothelial dysfunction, are also common in acromegaly. Control of acromegaly by surgery or pharmacotherapy, especially somatostatin analogs, improves cardiovascular morbidity. Respiratory disorders, sleep apnea, and ventilatory dysfunction are also important contributors in increasing mortality and are beneficially advantaged by controlling GH and IGF-I hypersecretion. An increased risk of colonic polyps, which more frequently recur in patients not controlled after treatment, has been reported by several independent investigations, although malignancies in other organs have also been described, but less convincingly than at the gastrointestinal level. Finally, the most important cause of morbidity and functional disability of the disease is arthropathy, which can be reversed at an initial stage, but not if the disease is left untreated for several years.
Response to Letter Regarding Article, “Plasmin Cleavage of von Willebrand Factor as an Emergency Bypass for ADAMTS13 Deficiency in Thrombotic Microangiopathy”
Authors: Claudia Tersteeg, Steven de Maat, Simon F. De Meyer, Michel W.J. Smeets, Arjan D. Barendrecht, Mark Roest, Gerard Pasterkamp, Rob Fijnheer, Karen Vanhoorelbeke, Philip. G. de Groot, Coen Maas
Journal: Circulation (2015)
Lymphadenopathy in rheumatic patients.
Authors: F D Hart
Journal: Annals of the Rheumatic Diseases (1987)

SL SLE q%' t ' 1 ~) -7 SLE Fig. 1 Histograms to show the age of in male andfemale patients.The shaded referrals during the two year period unc HLA, may be useful in explaining thes In this regard the observation that diabetes is associated with DR3/4 in DR3/9 in Orientals is of interest.
EZH2 polymorphism and benefit from bevacizumab in colorectal cancer: another piece to the puzzle
Authors: L. Fornaro, F. Crea, G. Masi, E. Paolicchi, F. Loupakis, F. Graziano, L. Salvatore, M. Ronzoni, V. Ricci, C. Cremolini, M. Schirripa, R. Danesi, A. Falcone
Journal: Annals of Oncology (2012)
Multi-Institutional Phase I Trials of Anticancer Agents
Authors: Afshin Dowlati, Sudhir Manda, Joseph Gibbons, Scot C. Remick, Lauren Patrick, Pingfu Fu
Journal: Journal of Clinical Oncology (2008)

Physicians involved in the conduct of phase I studies of novel anticancer agents have raised concerns about the emergence of multi-institutional phase I trials and about using the optimal biologic dose (OBD) as an alternative to the maximum-tolerated dose (MTD) as the primary end point in early drug development. We sought to determine the factors associated with multi-institutional phase I studies and OBD determination.We reviewed all published phase I trials between January 1998 and June 2006 from two major clinical cancer journals. The following components from each trial were determined: number of participating sites, sponsor, nation where study was conducted, MTD or OBD established, number of patients accrued, mechanism of action of the studied agent, accrual time, and tumor type.We identified 463 trials. Fifty-six percent were performed in single institutions. Only 30% reported accrual time. The number of patients enrolled on single institution studies was significantly lower than on multi-institutional studies (P < .05), but there was no difference in accrual time. There was no association between the number of institutions and the sponsor or the mechanism of drug action. National Institutes of Health-sponsored trials enrolled fewer patients per trial than pharmaceutical-sponsored trials (P < .05). Although 99% of trials with cytotoxic agents determined an MTD, only 64% of trials with targeted agents did.Multi-institutional phase I studies do not decrease the time to study completion and result in an increase in number of patients per trial. One third of trials with targeted agents failed to determine an MTD.