tbuckley/cabot-search huggingface dataset:
Physiological evidence that emphysema is not a feature of byssinosis.
Authors: D Honeybourne, C A Pickering
Journal: Thorax (1986)

The projections from the retina through the lateral geniculate nucleus to the visual cortex in the cat are comprised of three parallel, independent pathways. These three pathways involve, respectively, W-, X- , and Y-cells in the retina and the lateral geniculate nucleus. In this study, we investigated the morphology of those neurons in the C laminae of the lateral geniculate nucleus that receive input from retinal W- cells. Micropipettes filled with horseradish peroxidase (HRP) were used to record the responses of single geniculate neurons identified as W-, X-, or Y-cells. Five W-cells in the C laminae then were stained intracellularly by impalement of the cell with the microelectrode followed by iontophoresis of HRP. Each of these neurons has a small to medium size soma and fine dendrites oriented roughly parallel to the plane of the geniculate laminar borders. These geniculate W-cells differ among themselves mainly in the detail of their dendritic processes. Three of these cells have virtually no dendritic appendages, while the other two have complex appendages not previously reported among neurons in the C laminae. Also, the degree of horizontal orientation of the dendrites differs considerably among these cells. Overall, the morphology of these W-cells is generally consistent with the class 4 cell briefly described by Guillery (Guillery, R. W. (1966) J. Comp. Neurol. 128: 21–50), and consequently, our data indicate that class 4 neurons are the morphological correlate of neurons physiologically classified as W-cells. Since greater morphological detail is presented by these HRP-filled cells than by previous Golgi- impregnated preparations, we can describe more completely the morphology of class 4 cells.
Treatment with -blockers may reduce exacerbations and mortality in patients with COPD
Authors: L. Castle
Journal: Thorax (2010)

Cardiovascular disease is a significant burden in patients with chronic obstructive pulmonary disease (COPD). Shortness of breath and fatigue may be misinterpreted as symptoms of COPD, leaving cardiovascular disease unrecognised. Beta-blockers improve survival in ischaemic heart disease and heart failure. Many physicians avoid prescribing β-blockers in COPD because of concerns regarding bronchoconstriction and …
Cystic Fibrosis Transmembrane Conductance Regulator Function Is Suppressed in Cigarette Smokers
Authors: André M. Cantin, John W. Hanrahan, Ginette Bilodeau, Lynda Ellis, Annie Dupuis, Jie Liao, Julian Zielenski, Peter Durie
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: Cigarette smoke extract inhibits chloride secretion in human bronchial epithelial cells. Oxidants decrease gene expression, protein expression, and function of the cystic fibrosis transmembrane conductance regulator (CFTR).Objectives: Because cigarette smoke is a rich source of oxidants, we verified the hypothesis that CFTR may be suppressed by exposure to cigarette smoke in vitro and in vivo.Methods: The effects of cigarette smoke exposure on Calu-3 and T84 cell CFTR expression and function were observed. Also studied were the nasal potential differences (PDs) in 26 men (9 smokers, 17 nonsmokers) who had no detectable CFTR gene mutations as determined during investigations for infertility. CFTR expression and function were determined by Northern blotting, Western blotting, and cAMP-dependent 125I efflux assays. Extensive CFTR genotyping was performed in each subject. Nasal PD measurements were made at baseline and during amiloride, chloride-free buffer, and isoproterenol perfusions.Main Results: Cigarette smoke decreased CFTR expression and function in Calu-3 and T84 cell lines. Furthermore, the nasal PDs of cigarette smokers showed a pattern typical of CFTR deficiency with a blunted response to chloride-free buffer and isoproterenol compared with nonsmokers (−9.6 ± 4.0 vs. −22.3 ± 10.1 mV; p < 0.001).Conclusions: We conclude that cigarette smoke decreases the expression of CFTR gene, protein, and function in vitro and that acquired CFTR deficiency occurs in the nasal respiratory epithelium of cigarette smokers. We suggest that acquired CFTR deficiency may contribute to the physiopathology of cigarette-induced diseases such as chronic bronchitis.
MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study
Authors: Paolo A Ascierto, Dirk Schadendorf, Carola Berking, Sanjiv S Agarwala, Carla ML van Herpen, Paola Queirolo, Christian U Blank, Axel Hauschild, J Thaddeus Beck, Annie St-Pierre, Faiz Niazi, Simon Wandel, Malte Peters, Angela Zubel, Reinhard Dummer
Journal: The Lancet Oncology (2013)
Mechanism and Regulation of Class Switch Recombination
Authors: Janet Stavnezer, Jeroen E.J. Guikema, Carol E. Schrader
Journal: Annual Review of Immunology (2008)

Antibody class switching occurs in mature B cells in response to antigen stimulation and costimulatory signals. It occurs by a unique type of intrachromosomal deletional recombination within special G-rich tandem repeated DNA sequences [called switch, or S, regions located upstream of each of the heavy chain constant (C(H)) region genes, except Cdelta]. The recombination is initiated by the B cell-specific activation-induced cytidine deaminase (AID), which deaminates cytosines in both the donor and acceptor S regions. AID activity converts several dC bases to dU bases in each S region, and the dU bases are then excised by the uracil DNA glycosylase UNG; the resulting abasic sites are nicked by apurinic/apyrimidinic endonuclease (APE). AID attacks both strands of transcriptionally active S regions, but how transcription promotes AID targeting is not entirely clear. Mismatch repair proteins are then involved in converting the resulting single-strand DNA breaks to double-strand breaks with DNA ends appropriate for end-joining recombination. Proteins required for the subsequent S-S recombination include DNA-PK, ATM, Mre11-Rad50-Nbs1, gammaH2AX, 53BP1, Mdc1, and XRCC4-ligase IV. These proteins are important for faithful joining of S regions, and in their absence aberrant recombination and chromosomal translocations involving S regions occur.
Tamoxifen and Depression: More Evidence From the National Surgical Adjuvant Breast and Bowel Project's Breast Cancer Prevention (P-1) Randomized Study
Authors: R Day, P A Ganz, J P Costantino
Journal: JNCI Journal of the National Cancer Institute (2001)

Concerns have been raised that tamoxifen may be associated with depression. To investigate this question, we examined the psychological effects of tamoxifen treatment for breast cancer prevention on women at different levels of risk for clinical depression who were enrolled in the National Surgical Adjuvant Breast and Bowel Project's Breast Cancer Prevention (P-1) Study.A total of 11 064 women were randomly assigned to receive for 5 years daily doses of 20 mg of tamoxifen or placebo in the P-1 study, a multicenter, double-blind, placebo-controlled chemoprevention trial. Each woman was prospectively assessed for depression risk on the basis of medical history items collected at the baseline examination and placed in a high-, medium-, or low-risk group. Every 6 months, for a total of 36 months, the participants were assessed for depressive symptoms by completing the Center for Epidemiological Studies-Depression (CES-D) questionnaire. Scores of 16 or higher were indicative of an episode of affective distress. Differences between the risk groups and treatment arms were analyzed by logistic regression. All statistical tests were two-sided.Women in the higher risk depression groups were more likely to score 16 or higher on the CES-D (percent follow-up examinations with a score of > or = 16: high-risk group = 35.7%, with 95% confidence interval [CI] = 32.5% to 38.9%; medium-risk group = 19.2%, with 95% CI = 18.1% to 20.3%; and low-risk group = 8.7%, with 95% CI = 8.3 to 9.1%) and to have these scores more frequently and for longer periods than women in the lower risk groups. Within each depression risk group, there was no difference in the proportion of women scoring 16 or higher by treatment assignment (tamoxifen versus placebo) (odds ratio = 0.98; 95% CI = 0.93 to 1.02). A post-hoc analysis indicated that the lack of a tamoxifen effect was not a result of differential missing data.Physicians need not be overly concerned that treatment with tamoxifen will increase the risk for or exacerbate existing depression in women. Nevertheless, physicians should continue to screen for and treat or refer potential cases of depression encountered in routine clinical practice.
Wet combing to eradicate head lice
Authors: F. Fry, J. Ibarra, J. Smith, C. Wickenden
Journal: Journal of the Royal Society of Medicine (2002)

Dr Vander Stichele and his colleagues (July 2002 JRSM1) make a welcome contribution to the debate on the merits of wet combing for the detection and treatment of head lice. The comb they have tested is the Bug Buster comb2. This forms part of the kit now available in the UK on NHS prescription to assist parents who are encouraged to remedy head lice at home. However, the Belgian researchers do not seem to have tested the full Bug Busting method. In our experience, dry and damp lice move swiftly away from disturbance created by combing, thus evading detection. We find that it is important to shampoo and rinse the hair before applying conditioner. This takes moisture (which temporarily immobilizes lice) to the hair roots, their main habitat. The omission of shampooing in the Belgian study produces a protocol which is easier for school screening, but not the most effective.
Targeting receptor kinases by a novel indolinone derivative in multiple myeloma: abrogation of stroma-derived interleukin-6 secretion and induction of apoptosis in cytogenetically defined subgroups
Authors: Guido Bisping, Martin Kropff, Doris Wenning, Britta Dreyer, Sergey Bessonov, Frank Hilberg, Gerald J. Roth, Gerd Munzert, Martin Stefanic, Matthias Stelljes, Christian Scheffold, Carsten Müller-Tidow, Peter Liebisch, Nicola Lang, Jöelle Tchinda, Hubert L. Serve, Rolf M. Mesters, Wolfgang E. Berdel, Joachim Kienast
Journal: Blood (2005)
OC-112 Utility of cyst fluid amylase in the differentiation of suspected pancreatic neoplastic cysts
Authors: K Oppong, K Elamin, J Leeds, M Dawwas, M K Nayar
Journal: Gut (2012)

<h3>Introduction</h3> The Differentiation of mucinous (MCA, IPMN) from non-mucinous pancreatic cysts is important because of the malignant potential of the former. Cyst fluid amylase is known to be elevated in cysts with overt communication with the pancreatic duct (Pseudocysts and IPMN) recent data has also suggested it may be elevated in MCA and that malignant mucinous cysts have a significantly lower level than benign.<sup>1</sup> We aimed to assess the diagnostic performance of cyst fluid amylase in a large cohort of histologically confirmed pancreatic cysts. <h3>Methods</h3> The study population comprised all patients with suspected neoplastic pancreatic cysts who underwent EUS-FNA between June 2003 and October 2011.The study group consisted of all patients with a definitive diagnosis (resection histology, biopsy histology or malignant cytology) in whom a cyst amylase value had been recorded. Test performance was compared using Mann–Whitney U test and an ROC curve was generated to characterise the diagnostic performance of cyst fluid amylase to differentiate pseudocyst from non pseudocyst. <h3>Results</h3> During the study period 334 cyst EUS-FNA procedures were performed. A definitive diagnosis was available for 93 individuals, an amylase level was available for 59/93 (63.4%) of cases. 37 mucinous cyst (24 benign, 13 malignant), 22 non-mucinous (eight pseudocysts). Median values (IU/L) and IQR for differing categories of cyst were IPMN 9188 (IQR, 587–20 105), MCA 1291 (IQR, 469–85 100), benign mucinous 6385 (IQR, 372–23 050), malignant mucinous 115 (IQR, 36.5–5123) pseudocysts 31 762 (IQR 20 051–53 610) non-pseudocysts 200 (IQR, 53.2–9710). There was a significant difference (p&lt;0.001) between pseudocysts and non pseudocysts, but not between benign and malignant mucinous cysts (p=0.06) or between IPMN and MCA (p=1.0). An ROC curve was constructed, the calculated optimal cutoff for differentiating between pseudocysts and non-pseudocysts was 3977 IU/l this was associated with a sensitivity of 100%, specificity 70.6% and an accuracy of 74.5%. The area under the ROC curve was 0.87 (95% CI 0.76 to 0.94). An elevated fluid amylase showed modest specificity for diagnosing pseudocyst as some IPMN and MCA had very high levels. Malignant mucinous cysts had a reduced amylase compared to benign mucinous cysts but this did not achieve statistical significance. <h3>Conclusion</h3> Cyst fluid amylase while significantly elevated in pseudocycts cannot be solely relied upon to distinguish from mucinous cysts and cannot be used to differentiate between IPMN and MCA. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <b>Park WG</b>, <i>et al.</i> Diagnostic performance of cyst fluid carcinoembryonic antigen and amylase in histologically confirmed pancreatic cysts. <i>Pancreas</i> 2011;<b>40</b>:42–5.
Central Serotonergic Responsiveness in Neurocardiogenic Syncope
Authors: George N. Theodorakis, Manolis Markianos, Efthimios G. Livanis, Elias Zarvalis, Panagiota Flevari, Dimitrios T. Kremastinos
Journal: Circulation (1998)

Central serotonergic mechanisms appear to participate in the pathogenesis of recurrent neurally mediated syncope. The aim of the study was to investigate the responsiveness of the central serotonergic system by measuring the prolactin and cortisol responses to intravenous administration of the serotonin reuptake inhibitor clomipramine.Twenty subjects free of any medical treatment were tested. Twelve had a history of recurrent syncopal attacks and positive tilt test (patient group, mean age 47+/-18 years, 8 men); 8 subjects without syncope and a negative tilt test result served as control subjects (mean age 49+/-10 years, 5 men). Twenty-five milligrams of clomipramine was administered intravenously within 15 minutes, and blood samples were taken at 0, 15, 30, 45, and 60 minutes. Two days later, a tilt test was performed at 60 degrees for 30 minutes and blood samples were taken at 0, 10, 20, and 30 minutes. During the clomipramine challenge, plasma prolactin levels increased in both groups. The levels at 30 minutes were higher in the patient group compared with the control group (17.3+/-7.2 vs 9.3+/-7.6 ng/mL, P=0.05). Similar results were observed for cortisol at 30 minutes (172+/-15 vs 118+/-21 ng/mL P=0. 04) and at 45 minutes (189+/-20 vs 116+/-23 ng/mL, P=0.03). The tilt test was positive in 8 (67%) out of 12 of the patient group and negative in all control subjects. In the samples taken during the tilt test, significant increases in prolactin and cortisol were observed only in the subjects with positive tilt test results.Patients with a history of neurocardiogenic syncope show a higher responsiveness of the central serotonergic system to clomipramine challenge. The results support the view that central serotonergic mechanisms are involved in the pathophysiology of the syndrome.
Polymorphic Variants of Adrenoceptors: Pharmacology, Physiology, and Role in Disease
Authors: Andrea Ahles, Stefan Engelhardt
Journal: Pharmacological Reviews (2014)

The human genome encodes nine different adrenoceptor genes. These are grouped into three families, namely, the <i>α</i><sub>1</sub>-, <i>α</i><sub>2</sub>-, and <i>β</i>-adrenoceptors, with three family members each. Adrenoceptors are expressed by most cell types of the human body and are primary targets of the catecholamines epinephrine and norepinephrine that are released from the sympathetic nervous system during its activation. Upon catecholamine binding, adrenoceptors change conformation, couple to and activate G proteins, and thereby initiate various intracellular signaling cascades. As the primary receivers and transducers of sympathetic activation, adrenoceptors have a central role in human physiology and disease and are important targets for widely used drugs. All nine adrenoceptor subtypes display substantial genetic variation, both in their coding sequence as well as in adjacent regions. Despite the fact that some of the adrenoceptor variants range among the most frequently studied genetic variants assessed in pharmacogenetics to date, their functional relevance remains ill defined in many cases. A substantial fraction of the associations reported from early candidate gene approaches have not subsequently been confirmed in different cohorts or in genome-wide association studies, which have increasingly been conducted in recent years. This review aims to provide a comprehensive overview of all adrenoceptor variants that have reproducibly been detected in the larger genome sequencing efforts. We evaluate these variants with respect to the modulation of receptor function and expression and discuss their role in physiology and disease.
Sleep Disorders and Diaphragmatic Function in Patients with Amyotrophic Lateral Sclerosis
Authors: ISABELLE ARNULF, THOMAS SIMILOWSKI, FRANÇOIS SALACHAS, LUCILE GARMA, SELMA MEHIRI, VALERIE ATTALI, VALERIE BEHIN-BELLHESEN, VINCENT MEININGER, JEAN-PHILIPPE DERENNE
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

In amyotrophic lateral sclerosis (ALS), the progressive loss of upper and lower motor neurons leads to respiratory failure, often with predominant diaphragm dysfunction, and death. Because the diaphragm is the only active inspiratory muscle during rapid eye movement (REM) sleep, there is a high theoretical risk of respiratory disorders during REM sleep in patients with ALS. To assess this hypothesis, we studied sleep characteristics (polysomnography) in 21 patients with ALS, stratified according to the presence or absence of diaphragmatic dysfunction. Diaphragmatic dysfunction was defined as an absent or delayed diaphragm response to cervical or cortical magnetic stimulation, abdominal paradox, or respiratory pulse (Group 1, 13 patients). These patients did not differ in age, clinical course, or form (bulbar or spinal) from the eight others, who did not have diaphragmatic dysfunction (Group 2). REM sleep was reduced in Group 1 (7 ± 7% of total sleep time; mean ± SD) and normal in Group 2 (18 ± 6%, p = 0.004). Apneas or hypopneas were rare in both groups. In Group 1, REM sleep was absent or minimal (less than 3 min) in five patients. An unusual and remarkable preservation of phasic inspiratory sternomastoid activation during REM was associated with longer REM sleep duration in six of the other patients with diaphragmatic dysfunction. Median survival time was dramatically shorter (217 d) in Group 1 than in Group 2 (619 d, p = 0.015). Arnulf I, Similowski T, Salachas F, Garma L, Mehiri S, Attali V, Behin-Bellhesen V, Meininger V, Derenne J-P. Sleep disorders and diaphragmatic function in patients with amyotrophic lateral sclerosis.
Biochemical and histopathological correlation in liver transplant: The first 180 days
Authors: Keith S. Henley, Michael R. Lucey, Henry D. Appelman, Prabhakar Baliga, Kimberly A. Brown, Gordon D. Burtch, Darrell A. Campbell, John M. Ham, Robert M. Merion, Jeremiah G. Turcotte
Journal: Hepatology (1992)

It is not known whether the histopathology of the liver allograft can be predicted from biochemical measurements in serum with the same confidence as in the native liver. To answer this question we compared the histopathological diagnoses in 170 biopsy specimens from 70 adult transplant recipients obtained during the first 180 days, with the concentrations of the serum bilirubin and the activities of AST, ALT and alkaline phosphatase measured at the same time. The most frequent diagnosis was cholestasis (n = 45), which was mild, moderate or severe and which may have been complicated by rejection (n = 28) or ischemia (n = 14). Hepatitis (n = 14), ischemia with rejection (n = 6) and spotty focal necrosis (n = 6) were diagnosed less frequently. Fifteen biopsy specimens were reported as histopathologically normal. In general, biochemical measurements discriminated poorly between different histopathological diagnoses. The histopathologically normal liver often showed an abnormal pattern of enzymes and an increase in the serum bilirubin level. As a result histopathologically normal biopsy specimens were indistinguishable biochemically from those with hepatitis. When two pathological conditions were found to coexist (e.g., cholestasis with either rejection or ischemic necrosis, or ischemic necrosis with rejection), the effect on the serum biochemistry was usually not additive and in some instances returned the biochemical abnormalities toward normal. With the exception of the serum bilirubin level, which increased with the severity of uncomplicated cholestasis, we could not identify a specific pattern of biochemical changes corresponding to a given histopathological diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Nuclear Expression of BCL10 or Nuclear Factor Kappa B Predicts <i>Helicobacter pylori</i>–Independent Status of Early-Stage, High-Grade Gastric Mucosa-Associated Lymphoid Tissue Lymphomas
Authors: Sung-Hsin Kuo, Li-Tzong Chen, Kun-Huei Yeh, Ming-Shiang Wu, Hui-Chen Hsu, Pei-Yen Yeh, Tsui-Lien Mao, Chi-Long Chen, Shin-Lian Doong, Jaw-Town Lin, Ann-Lii Cheng
Journal: Journal of Clinical Oncology (2004)

A high percentage of early-stage, high-grade gastric mucosa-associated lymphoid tissue (MALT) lymphomas remain Helicobacter pylori dependent. t(11;18)(q21;q21), a genetic aberration highly predictive of H. pylori-independent status in low-grade gastric MALT lymphoma, is rarely detected in its high-grade counterpart. This study examined whether nuclear expression of BCL10 or nuclear factor kappa B (NF-kappaB) is useful in predicting H. pylori-independent status in patients with stage IE high-grade gastric MALT lymphomas.Twenty-two patients who had participated in a prospective study of H. pylori eradication for stage IE high-grade gastric MALT lymphomas were studied. The expression of BCL10 and NF-kappaB in pretreatment paraffin-embedded lymphoma tissues was evaluated by immunohistochemistry and confocal immunofluorescence microscopy. The presence of t(11;18)(q21;q21) was identified by a multiplex reverse transcriptase polymerase chain reaction of the API2-MALT1 chimeric transcript.Aberrant nuclear expression of BCL10 was detected in seven (87.5%) of eight H. pylori-independent and in none of 14 H. pylori-dependent high-grade gastric MALT lymphomas (P <.001). All seven patients with nuclear BCL10 expression had nuclear expression of NF-kappaB, compared with only two of 15 patients without nuclear BCL10 expression (P =.002). As a single variable, the frequency of nuclear expression of NF-kappaB was also significantly higher in H. pylori-independent tumors than in H. pylori-dependent tumors (seven of eight [87.5%] v two of 15 [12.3%]; P =.002). The API2-MALT1 fusion transcript was detected in only one (12.5%) of eight H. pylori-independent lymphomas.Nuclear expression of BCL10 or NF-kappaB is highly predictive of H. pylori-independent status in high-grade gastric MALT lymphoma, and coexpression of these two markers in the nuclei is frequent.
Genome-Wide Association Study of Cognitive Decline in Schizophrenia
Authors: Ryota Hashimoto, Masashi Ikeda, Kazutaka Ohi, Yuka Yasuda, Hidenaga Yamamori, Motoyuki Fukumoto, Satomi Umeda-Yano, Dwight Dickinson, Branko Aleksic, Masao Iwase, Hiroaki Kazui, Norio Ozaki, Daniel R. Weinberger, Nakao Iwata, Masatoshi Takeda
Journal: American Journal of Psychiatry (2013)