tbuckley/cabot-search huggingface dataset:
Episodic Neurologic Disorders: Syndromes, Genes, and Mechanisms
Authors: Jonathan F. Russell, Ying-Hui Fu, Louis J. Ptáček
Journal: Annual Review of Neuroscience (2013)

Many neurologic diseases cause discrete episodic impairment in contrast with progressive deterioration. The symptoms of these episodic disorders exhibit striking variety. Herein we review what is known of the phenotypes, genetics, and pathophysiology of episodic neurologic disorders. Of these, most are genetically complex, with unknown or polygenic inheritance. In contrast, a fascinating panoply of episodic disorders exhibit Mendelian inheritance. We classify episodic Mendelian disorders according to the primary neuroanatomical location affected: skeletal muscle, cardiac muscle, neuromuscular junction, peripheral nerve, or central nervous system (CNS). Most known Mendelian mutations alter genes that encode membrane-bound ion channels. These mutations cause ion channel dysfunction, which ultimately leads to altered membrane excitability as manifested by episodic disease. Other Mendelian disease genes encode proteins essential for ion channel trafficking or stability. These observations have cemented the channelopathy paradigm, in which episodic disorders are conceptualized as disorders of ion channels. However, we expand on this paradigm to propose that dysfunction at the synaptic and neuronal circuit levels may underlie some episodic neurologic entities.
Diagnosis of Thyroid Nodules
Authors: J. Martin Miller
Journal: JAMA (1979)

The accuracy of diagnosis of 455 thyroid nodules evaluated by cytological and histological specimens obtained by fine- and large-needle biopsy, respectively, was compared with that for 1,094 nodules previously evaluated by clinical methods. The use of cytohistological data halved the number of patients with suspected cancer and doubled the number of patients to be observed. Cancers identified at operation for high and intermediate cancer-risk patients increased 75%, and operation for diagnosis of benign disease decreased 70%. Forty-two of 47 excised cancers were included in the cytohistological probable cancer group. Only 29 of these cancers were so classified clinically. Two cancers not diagnosed cytologically were suspected histologically and vice versa for one cancer. All 51 excised cytohistologically benign nodules were benign. There were more false-positive findings with cytological than with histological specimens.
Comparison of utility measures and their relationship with other health status measures in 1041 patients with rheumatoid arthritis
Authors: S. Lillegraven, I. S. Kristiansen, T. K. Kvien
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objectives</h3> The aim of this study was to compare three health utility instruments (15D, EQ-5D, SF-6D) and a rating scale for health (EQ-Visual Analogue Scale (VAS)) and to investigate their relationship to clinical parameters in patients with rheumatoid arthritis (RA). <h3>Methods</h3> Data were collected from 1041 patients with RA. Agreement between the instruments was assessed with Bland–Altman plots. Linear regression models were fitted for the different instruments and Health Assessment Questionnaire (HAQ) scores, age, gender, patient global, disease duration and educational level. Differences in utility scores across levels of global health and disability, were investigated as well as correlations with disease-specific health status measures. <h3>Results</h3> The score range in the 1041 patients with RA was 0.41–1.0 for 15D, −0.48 to 1.0 for EQ-5D, 0.0–1.0 for EQ-VAS and 0.30–1.0 for SF-6D, with a bimodal distribution for EQ-5D. Bland–Altman plots indicated poor agreement between EQ-5D and SF-6D/15D and moderate agreement between SF-6D and 15D. Utility scores were correlated with disease-specific measures, pain and fatigue (r&gt;0.60). Mean utilities ranged from 0.30 (EQ-5D) to 0.69 (15D) in patients rating their own health as poor. When correcting for a non-linear relationship between HAQ and EQ-5D/SF-6D in linear regression models, the estimated utilities had non-overlying CI for HAQ values &gt;1.4. <h3>Conclusions</h3> Diverging scores were observed across utility instruments, especially in patients with high HAQ scores. The choice of utility instrument may have an impact on the results of cost-utility analyses, with large hypothetical differences in price per quality-adjusted life year.
PPI-induced hypergastrinaemia and Barrett's mucosa: the fog thickens
Authors: H. L. Waldum, O. Hauso, A. K. Sandvik
Journal: Gut (2010)

We read with interest the study by Obszynska and co-workers1 on proton pump inhibitors (PPIs) and Barrett's oesophagus, and the accompanying editorial.2 The background for the study1 was whether PPIs are beneficial or harmful to patients with Barrett's oesophagus. They assessed the risks of PPI treatment by focusing on hypergastrinaemia, the presence of the cholecystokinin 2 (CCK2) receptor in different tissues by immunohistochemistry, and gene expression analysis. Furthermore, they analysed the effect of gastrin on cell lines transfected with the CCK2 receptor.

They found gastrin mRNA expression as expected in the antral mucosa, but also in the normal oesophageal mucosa as well as in Barrett's mucosa. Moreover, CCK2 mRNA expression was found not only in the oxyntic mucosa but also …
Acute autoimmune encephalomyelitis in mice. II. Susceptibility is controlled by the combination of H-2 and histamine sensitization genes.
Authors: D S Linthicum, J A Frelinger
Journal: The Journal of Experimental Medicine (1982)

The expression of acute experimental autoimmune encephalomyelitis (EAE) in mice is controlled by several dominant genes, H-2 and histamine sensitization genes. SJL/J and SWR/J, which are H-2s and H-2q, respectively, are susceptible to EAE and sensitive to Bordetella pertussis histamine-sensitizing factor (HSF), which produces a vasoactive amine hypersensitivity. Other H-2s or H-2q strains such as A.SW, B10.Q and several others do not develop acute EAE and are not sensitive to B. pertussis HSF. One strain tested, DDD (KsIsD?) is HSF sensitive but does not develop EAE (presumably because it lacks the appropriate responder H-2 haplotype). However, F1 hybrids between B10.S and DDD are sensitive to HSF and develop EAE. The induction and effector phases of acute EAE are apparently controlled by the combination of H-2 and HSF genes. A combination of the correct H-2 hapotype and histamine sensitivity is required for the development of acute EAE.
Endoplasmic Reticulum Stress Signal Mediators Are Targets of Selenium Action
Authors: Yue Wu, Haitao Zhang, Yan Dong, Young-Mee Park, Clement Ip
Journal: Cancer Research (2005)

A monomethylated selenium metabolite, called methylseleninic acid (MSA), has recently been shown to cause global thiol redox modification of proteins. These changes represent a form of cellular stress due to protein misfolding or unfolding. An accumulation of aberrantly folded proteins in the endoplasmic reticulum (ER) triggers a defined set of transducers to correct the defects or commit the cells to apoptosis if the rescue effort is exhausted. Treatment of PC-3 human prostate cancer cells with MSA was found to induce a number of signature ER stress markers: (a) the survival/rescue molecules such as phosphorylated protein kinase-like ER-resident kinase (phospho-PERK), phosphorylated eukaryotic initiation factor-2alpha (phospho-eIF2alpha), glucose-regulated protein (GRP)-78, and GRP94; and (b) the apoptotic molecules such as caspase-12, caspase-7, and CAAT/enhancer binding protein homologous protein or growth arrest DNA damage-inducible gene 153 (CHOP/GADD153). Additional evidence suggested that CHOP/GADD153 might be an important transcription factor in apoptosis induction by MSA. In general, a higher concentration of MSA was required to elicit the apoptotic markers compared with the rescue markers. The apoptotic markers increased proportionally with the dose of MSA, whereas the rescue markers failed to keep pace with the increasing challenge from MSA. GRP78 is the rheostat of the ER stress transducers. In GRP78-overexpressing cells, the ability of MSA to up-regulate phospho-PERK, phospho-eIF2alpha, GRP94, caspase-12, caspase-7, and CHOP/GADD153 was significantly muted. A generous supply of GRP78 would allow cells to cope better with ER stress, thereby improving the odds for survival and negating the commitment to apoptotic death. The present study thus provides strong evidence to support an important role of ER stress response in mediating the anticancer effect of selenium.
Inhibition of Pulmonary and Skeletal Metastasis by a Transforming Growth Factor-β Type I Receptor Kinase Inhibitor
Authors: Abhik Bandyopadhyay, Joseph K. Agyin, Long Wang, Yuping Tang, Xiufen Lei, Beryl M. Story, John E. Cornell, Bradley H. Pollock, Gregory R. Mundy, Lu-Zhe Sun
Journal: Cancer Research (2006)

Abstract Transforming growth factor-β (TGF-β) signaling has been shown to promote invasion and metastasis in various models of human cancers. In this study, we investigated the efficacy of a TGF-β type I receptor kinase inhibitor (TβRI-I) to limit early systemic metastases in an orthotopic xenograft model of lung metastasis and in an intracardiac injection model of experimental bone and lung metastasis using human breast carcinoma MDA-MB-435-F-L cells, a highly metastatic variant of human breast cancer MDA-MB-435 cells, expressing the enhanced green fluorescent protein (EGFP). Treatment of the cells with the TβRI-I had no effect on their growth but blocked TGF-β-stimulated expression of integrin αvβ3 and cell migration in vitro. Systemic administration of the TβRI-I via i.p. injection effectively reduced the number and size of the lung metastasis in both orthotopic xenograft and experimental metastasis models with no effects on primary tumor growth rate compared with controls. TβRI-I treatment also reduced the incidence of widespread early skeletal metastases in the femur, tibia, mandible, and spine detected by whole-body EGFP fluorescence imaging. Tumor burden in femora and tibiae was also reduced after TβRI-I treatment as detected by histomorphometry analysis compared with the placebo controls. Our results indicate for the first time that abrogation of TGF-β signaling by systemic administration of the TβRI-I can inhibit both early lung and bone metastasis in animal model systems and suggest antimetastatic therapeutic potential of the TβRI-I.(Cancer Res 2006; 66(13): 6714-21)
Adenotonsillectomy in children with mild symptoms: Watchful waiting may deny children opportunity for development
Authors: Simon C Langton Hewer, Claire D Langton Hewer, Yvonne Pamula, James Martin, Declan Kennedy
Journal: BMJ (2004)

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Credit: DR P MARAZZI/SPL

EDITOR—van Staaij et al report a large study examining the effectiveness of adenotonsillectomy in children with mild symptoms of throat infection or adenotonsillar hypertrophy.1 They conclude that adenotonsillectomy confers no major clinical benefits over watchful waiting.

We are concerned that …

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Quantification of aspirated air volume reduces treatment time in pneumothorax
Authors: O Engdahl, J Boe
Journal: European Respiratory Journal (1990)

In 62 consecutive cases of pneumothorax, suction treatment was applied by a new method using a recently-developed vacuum pump (Pleupump) allowing the quantification of the volume of air through the chest drain. The previous 62 cases of pneumothorax treated with standard suction equipment were used as a control group. The new technique resulted in a statistically significant reduction in the mean suction treatment time from 8.1 to 4.8 days in patients with spontaneous pneumothorax. The mean total number of days in hospital was reduced from 10.0 to 6.5. This was accomplished without an increase in the number of complications or recurrences of the pneumothorax.
Stretch-induced changes in constricted lung parenchymal strips: role of extracellular matrix
Authors: F.G. Salerno, A. Fust, M.S. Ludwig
Journal: European Respiratory Journal (2003)

Large amplitude oscillations of contracted airway smooth muscle cause relative relaxation of the preparation. However, little is known about the effect of mechanical stretch on distal lung behaviour. Rat parenchymal strips were suspended in an organ bath and attached at one end to a force transducer and at the other end to a servo-controlled lever arm that effected length changes. Mechanical impedance of the strip was measured by applying a complex signal consisting of pseudorandom length oscillations of varying frequencies (0.5–19.75 Hz). A constant phase model was fit to changes in length and tension to calculate tissue damping (G) and elastance (H). Hysteresivity was calculated as G/H. Impedance was measured before and after sinusoidal length oscillation at different amplitudes (1, 3, 10 and 25% of resting length) at a frequency of 1 Hz under baseline conditions and after acetylcholine-induced constriction. Oscillations of 10 and 25% amplitudes significantly decreased the G and H of the lung strip. The effect of length oscillations was no different in control versus constricted strips. These data suggest that in the distal lung, large stretches affect the structural components of the extracellular matrix rather than the contractile elements.
MENTAL HEALTH AND MANAGED CARE
Authors: Mary L. Durham
Journal: Annual Review of Public Health (1998)

Managed care has become the dominant method for financing and delivering care for common mental health problems and for people with severe, chronic mental health conditions. Despite the rapid growth of managed mental health care, there is very little research available to guide policy choices. Managed care has led to decreased costs for employers and other payers, mostly through reducing hospital admissions or length of stay. Managed care organizations use staff with lesser levels of training (e.g. social workers instead of psychiatrists) and are more likely to offer group outpatient programs and manualized treatment than their fee-for-service counterparts. Despite these differences, there is no clear evidence that health outcomes are worse for patients in managed care. There is an urgent need for researchers to turn their attention to issues such as cost, quality, access, satisfaction, and functional outcomes associated with managed mental health care. The impact of parity of mental health with insurance coverage for physical conditions is another important question that needs to be addressed.
mRNA Expression Signatures of Human Skeletal Muscle Atrophy Identify a Natural Compound that Increases Muscle Mass
Authors: Steven D. Kunkel, Manish Suneja, Scott M. Ebert, Kale S. Bongers, Daniel K. Fox, Sharon E. Malmberg, Fariborz Alipour, Richard K. Shields, Christopher M. Adams
Journal: Cell Metabolism (2011)
Inferring the History of Population Size Change from Genome-Wide SNP Data
Authors: Christoph Theunert, Kun Tang, Michael Lachmann, Sile Hu, Mark Stoneking
Journal: Molecular Biology and Evolution (2012)

Dense, genome-wide single-nucleotide polymorphism (SNP) data can be used to reconstruct the demographic history of human populations. However, demographic inferences from such data are complicated by recombination and ascertainment bias. We introduce two new statistics, allele frequency-identity by descent (AF-IBD) and allele frequency-identity by state (AF-IBS), that make use of linkage disequilibrium information and show defined relationships to the time of coalescence. These statistics, when conditioned on the derived allele frequency, are able to infer complex population size changes. Moreover, the AF-IBS statistic, which is based on genome-wide SNP data, is robust to varying ascertainment conditions. We constructed an efficient approximate Bayesian computation (ABC) pipeline based on AF-IBD and AF-IBS that can accurately estimate demographic parameters, even for fairly complex models. Finally, we applied this ABC approach to genome-wide SNP data and inferred the demographic histories of two human populations, Yoruba and French. Our results suggest a rather stable ancestral population size with a mild recent expansion for Yoruba, whereas the French seemingly experienced a long-lasting severe bottleneck followed by a drastic population growth. This approach should prove useful for new insights into populations, especially those with complex demographic histories.
Chloramphenicol Induces Abnormal Differentiation and Inhibits Apoptosis in Activated T Cells
Authors: Zeng-Rong Yuan, Yufang Shi
Journal: Cancer Research (2008)

Abstract Chloramphenicol is a broad-spectrum antibiotic used for the treatment of many infectious diseases and has become one of the major seafood contaminants. Hematologic disorders such as aplastic anemia and leukemia induced by chloramphenicol are a major concern. However, the mechanism underlying chloramphenicol-induced leukemogenesis is not known. By investigating the effects of chloramphenicol on the activation of mouse T cells stimulated with anti-CD3 antibody or staphylococcal enterotoxin B, we found that chloramphenicol induces the differentiation of activated T cells into lymphoblastic leukemia-like cells, characterized by large cell size, multiploid nuclei, and expression of CD7, a maker for immature T cells and T-cell lymphocytic leukemia, thus phenotypically indicating differentiation toward leukemogenesis. High expression of cyclin B1, but not p53, c-myc, and CDC25A, was detected in chloramphenicol-treated activated T cells, which may relate to abnormal cell differentiation. Chloramphenicol inhibited the activation-induced cell death of mouse and human T-cell receptor–activated T cells by down-regulating the expression of Fas ligand. Our findings show that abnormal cell differentiation and inhibition of apoptosis may contribute to the development of leukemia associated with clinical applications of chloramphenicol. [Cancer Res 2008;68(12):4875–81]
Genetic evolution of pancreatic cancer: lessons learnt from the pancreatic cancer genome sequencing project
Authors: Christine A Iacobuzio-Donahue
Journal: Gut (2011)

Pancreatic cancer is a disease caused by the accumulation of genetic alterations in specific genes. Elucidation of the human genome sequence, in conjunction with technical advances in the ability to perform whole exome sequencing, have provided new insight into the mutational spectra characteristic of this lethal tumour type. Most recently, exomic sequencing has been used to clarify the clonal evolution of pancreatic cancer as well as provide time estimates of pancreatic carcinogenesis, indicating that a long window of opportunity may exist for early detection of this disease while in the curative stage. Moving forward, these mutational analyses indicate potential targets for personalised diagnostic and therapeutic intervention as well as the optimal timing for intervention based on the natural history of pancreatic carcinogenesis and progression.
UK will review partial smoking ban in 2010, MPs' committee told
Authors: >Adrian O'Dowd
Journal: BMJ (2005)

The government will review its policy on its partial ban on smoking in public places three years after the new legislation is introduced in summer 2007, MPs were told last week.

Speaking to the parliamentary select committee on health on the same day that she unveiled the Health Bill, the secretary of state for health, Patricia Hewitt, said the bill would mean smoking is banned in “virtually” every enclosed work place and public place in England. …
Mechanical Strain Increases Smooth Muscle and Decreases Nonmuscle Myosin Expression in Rat Vascular Smooth Muscle Cells
Authors: Peter Reusch, Hisham Wagdy, Regina Reusch, Emily Wilson, Harlan E. Ives
Journal: Circulation Research (1996)

The effect of cyclic (1-Hz) mechanical strain on expression of myosin heavy chain isoforms was examined in neonatal rat vascular smooth muscle cells cultured on silicone elastomer plates. Myosin heavy chain isoforms were identified by immunoblot using antibodies recognizing (1) smooth muscle myosin heavy chain isoforms SM-1 and SM-2, (2) SM-1 exclusively, and (3) nonmuscle myosin heavy chains A and B. In response to 36 to 72 hours of strain, SM-1 and SM-2 increased by fourfold to sixfold, whereas nonmuscle myosin A decreased to 30% of control. Nonmuscle myosin B was unaffected by strain. SM-1 mRNA increased by twofold to threefold after 12 hours of strain but decreased toward control levels thereafter. SM-2 mRNA was only barely detectable. Nonmuscle myosin A mRNA decreased to 50% of control after 3 hours of strain and then returned to the control level. Since these cells secrete platelet-derived growth factor (PDGF) in response to strain, we assessed the effects of PDGF on myosin isoform expression. Exogenous PDGF (10 ng/mL) decreased SM-1 expression by 35% and increased nonmuscle myosin expression twofold, opposite the effect of strain. In cells exposed to strain with neutralizing antibodies to PDGF-AB, the strain-induced increase in SM-1 was enhanced 10-fold, and nonmuscle myosin A was reduced to 40% of control. Finally, the effect of extracellular matrix on transduction of the strain signal was studied. Forty-eight hours of cyclic strain increased SM-1 by twofold in cells cultured on collagen type I and threefold in cells cultured on laminin. In fibronectin-cultured cells, strain elicited no increase in SM-1. Thus, mechanical strain, sensed through specific interactions with the matrix, can alter myosin isoform expression toward that found in a more differentiated state.
A reductionist cell-free major histocompatibility complex class II antigen processing system identifies immunodominant epitopes
Authors: Isamu Z Hartman, AeRyon Kim, Robert J Cotter, Kimberly Walter, Sarat K Dalai, Tatiana Boronina, Wendell Griffith, David E Lanar, Robert Schwenk, Urszula Krzych, Robert N Cole, Scheherazade Sadegh-Nasseri
Journal: Nature Medicine (2010)
Skeletal muscle pathology in endurance athletes with acquired training intolerance
Authors: L A Grobler, M Collins, M I Lambert, C Sinclair-Smith, W Derman, A St Clair Gibson, T D Noakes
Journal: British Journal of Sports Medicine (2004)

Background: It is well established that prolonged, exhaustive endurance exercise is capable of inducing skeletal muscle damage and temporary impairment of muscle function. Although skeletal muscle has a remarkable capacity for repair and adaptation, this may be limited, ultimately resulting in an accumulation of chronic skeletal muscle pathology. Case studies have alluded to an association between long term, high volume endurance training and racing, acquired training intolerance, and chronic skeletal muscle pathology. Objective: To systematically compare the skeletal muscle structural and ultrastructural status of endurance athletes with acquired training intolerance (ATI group) with asymptomatic endurance athletes matched for age and years of endurance training (CON group). Methods: Histological and electron microscopic analyses were carried out on a biopsy sample of the vastus lateralis from 18 ATI and 17 CON endurance athletes. The presence of structural and ultrastructural disruptions was compared between the two groups of athletes. Results: Significantly more athletes in the ATI group than in the CON group presented with fibre size variation (15 v 6; p = 0.006), internal nuclei (9 v 2; p = 0.03), and z disc streaming (6 v 0; p = 0.02). Conclusions: There is an association between increased skeletal muscle disruptions and acquired training intolerance in endurance athletes. Further studies are required to determine the nature of this association and the possible mechanisms involved.