tbuckley/cabot-search huggingface dataset:
Rhythmic transcription: the molecular basis of circadian melatonin synthesis
Authors: Nicholas S. Foulkes, Paolo assone-Corsi, Jimo Borjigin, Solomon H. Snyder, Solomon H. Snyder
Journal: Trends in Neurosciences (1997)

Adaptation to a changing environment is an essential feature of physiological regulation. The day–night rhythm is translated into hormonal oscillations governing the metabolism of all living organisms. In mammals the pineal gland is responsible for the synthesis of the hormone melatonin in response to signals originating from the endogenous clock located in the hypothalamic suprachiasmatic nucleus (SCN). The molecular mechanisms involved in rhythmic synthesis of melatonin involve the cAMP response element modulator (crem) gene, which encodes transcription factors responsive to activation of the cAMP signalling pathway. The CREM product, inducible cAMP early repressor (ICER), is rhythmically expressed and participates in a transcriptional autoregulatory loop that also controls the amplitude of oscillations of 5-HT N-acetyl transferase, the rate-limiting enzyme of melatonin synthesis. Thus, a transcription factor modulates the oscillatory levels of a hormone.
Technetium-99m sestamibi tomographic evaluation of residual ischemia after anterior myocardial infarction
Authors: Claudio Marcassa, Michele Galli, Pier Luigi Temporelli, Riccardo Campini, Pedro Silva Orrego, Orazio Zoccarato, Amerigo Giordano, Pantaleo Giannuzzi
Journal: Journal of the American College of Cardiology (1995)
[614] HOST AND VIRAL BASELINE CHARACTERISTICS IN HEPATITIS C NAIVE AND NON-RESPONDER PATIENTS: COMPARISON OF THREE LARGE RANDOMISED MULTINATIONAL TRIALS
Authors: S.T. Hadziyannis, S. Zeuzem, M. Diago, M. Rizzetto, C.E. Brandao-Mello, C. Smith, K.R. Reddy, A. Lin, D. Jensen
Journal: Journal of Hepatology (2007)
Doctor to The Archers.
Authors: S. Dover
Journal: BMJ (1989)

BrMedJ 1989;299:1623-5 The BBC advertised for a doctor to advise The Archers the BBC's daily radio story of country folk. I applied. I spent a happy couple of hours with the editor gossiping about mutual friends, the Ambridge characters, over lunch. Afterwards she showed me the studio and production office. I would have been pleased even without getting the job. The story is decided at a monthly script meeting. Four writers, the production team, and specialist advisers sit for a day and hammer out the plot. Usually we'd discussed ideas beforehand, but I could never predict which would be runners. Ideas came from hospital life, colleagues, and the medical press, par? ticularly Personal View in the BMJ and In England Now in the Lancet. Script meetings were fun so I went whenever invited. The writers are intelligent, stimu? lating, and articulate, but their job is lonely and they made the most of the meetings. I tried to resist joining in discussions of non-medical stories. The story is now about two months off transmission. My next job was to produce concise clear notes trying to anticipate the writers' problems. Like a real general practitioner, I sought advice from friends and colleagues, most of whom were pleased. One evening after a meeting when two pregnancies had been planned?one unplanned?I was worrying about recruiting an obstetrician when I saw one sitting in his car listening to the programme. Now he is closely involved, helping with infertility, too. My father and other general practitioner friends helped with adminis? trative and financial aspects of general practice. Peggy Archer's poly my algia rheumatica was conceived over supper.
Drug-induced linear IgA disease: target antigens are heterogeneous
Authors: C. PAUL, P. WOLKENSTEIN, C. PROST, F. CAUX, G. ROSTOKER, M. HELLER, J. WECHSLER, J. REVUZ, J.C. ROUJEAU
Journal: British Journal of Dermatology (1997)

No information is available concerning the target antigen(s) involved in drug‐induced linear IgA disease. The purpose of this study was to define better drug‐induced linear IgA desease by studying its immunopathological, immunoultrastructural and immunochemical characteristics in three patients. In the first patient. IgA deposits were seen in the lamina lucida. In the second and the third patients. IgA deposits were seen on each side of the lamina densa. Immunoblotting of the first patient's serum showed that IgA reacted with a protein of 230 kDa similar to the bullous pemphigoid‐associated antigen 1 (BPAG 1). The second patient's serum did not react with specific bands. In the third patient IgA antibodies reacted with a protein of 97 kDa on epidermal extracts. Our findings suggest that, as in idiopathic forms, the target antigen is not unique in drug‐induced linear IgA disease. In some patients, drug‐induced linear IgA disease may represent an IgA class response to the BPAG 1.
What does Stat3 do?
Authors: David E. Levy, Chien-kuo Lee
Journal: Journal of Clinical Investigation (2002)

The Stat protein family was discovered in the course of studies of signaling specificity from IFN receptors (1). The initial finding of a family of related proteins, each activated by a different cytokine receptor, suggested that these proteins would fulfill the requirements predicted for carriers of intracellular signaling information capable of retaining the specificity inherent in cytokine-receptor interactions (2). While studies in cell culture systems belied some of this early promise, the initial findings with genetically manipulated mice, especially using gene-targeting approaches, generally suggested a high degree of specificity for the various Stat proteins in individual signaling pathways. As reviewed elsewhere in this Perspective series, the analysis of mice lacking one or more Stat genes has shown relatively discrete phenotypes, assigning each Stat protein to a relatively specific pathway. Not so with Stat3.

Unlike all other members of the Stat gene family, ablation of Stat3 leads to embryonic lethality (3). This finding, along with evidence of its activation by a wide variety of cytokines, growth factors, and other stimuli (4, 5), implied that Stat3 might be more generally deployed than its relatives and has led to the suggestion that it might represent a primordial Stat protein. Recent data, especially from the analysis of conditional loss of Stat3 protein in adult tissues, confirm that Stat3 participates in a wide variety of physiological processes and even directs seemingly contradictory responses.
Correction of Irregular Astigmatism with the Excimer Laser
Authors: Richard Gibralter, Stephen L. Trokel
Journal: Ophthalmology (1994)

Correction of irregular astigmatism has not been possible using available keratorefractive technology.The authors used a topographic map as a guide and created a custom excimer ablation program, designed to create a more regular surface. The program consisted of a combination of phototherapeutic and photorefractive ablation patterns. The amount of tissue to be removed was calculated on the basis of the diameter and steepness of the irregular areas of the corneal surface.A more regular surface, as evidenced by topographic analysis, reduced astigmatism, and improved uncorrected visual acuity, was produced.Using the corneal topographical map as a guide, excimer laser ablation can be used to create a more regular optical surface with improved visual function.
Aerosols containing neomycin.
Authors: I Friedmann
Journal: BMJ (1977)

clinical, and therapeutic aspects.If the disease is shown to be an irreversible one, then ancillary workers are most helpful in assisting with the difficult and important skills of subsequent psychosocial adjustment and management.But please, Sir, when we are discussing illness (as opposed to the more vague, pure social maladjustments of contemporary society) let us not be falsely persuaded by the fashion- able soft sciences into abrogating our in- alienable role as leader of the clinical team.
Roles of Trans and Cis Variation in Yeast Intraspecies Evolution of Gene Expression
Authors: Huang-Mo Sung, Tzi-Yuan Wang, Daryi Wang, Yu-Shan Huang, Jen-Pey Wu, Huai-Kuang Tsai, Jengnan Tzeng, Chih-Jen Huang, Yi-Chen Lee, Peggy Yang, Joyce Hsu, Tiffany Chang, Chung-Yi Cho, Li-Chuan Weng, Tso-Ching Lee, Tien-Hsien Chang, Wen-Hsiung Li, Ming-Che Shih
Journal: Molecular Biology and Evolution (2009)

Both cis and trans mutations contribute to gene expression divergence within and between species. We used Saccharomyces cerevisiae as a model organism to estimate the relative contributions of cis and trans variations to the expression divergence between a laboratory (BY) and a wild (RM) strain of yeast. We examined whether genes regulated by a single transcription factor (TF; single input module, SIM genes) or genes regulated by multiple TFs (multiple input module, MIM genes) are more susceptible to trans variation. Because a SIM gene is regulated by a single immediate upstream TF, the chance for a change to occur in its trans-acting factors would, on average, be smaller than that for a MIM gene. We chose 232 genes that exhibited expression divergence between BY and RM to test this hypothesis. We examined the expression patterns of these genes in a BY–RM coculture system and in a BY–RM diploid hybrid. We found that trans variation is far more important than cis variation for expression divergence between the two strains. However, because in 75% of the genes studied, cis variation has significantly contributed to expression divergence, cis change also plays a significant role in intraspecific expression evolution. Interestingly, we found that the proportion of genes with diverged expression between BY and RM is larger for MIM genes than for SIM genes; in fact, the proportion tends to increase with the number of transcription factors that regulate the gene. Moreover, MIM genes are, on average, subject to stronger trans effects than SIM genes, though the difference between the two types of genes is not conspicuous.
Enhancing liver mitochondrial fatty acid oxidation capacity in obese mice improves insulin sensitivity independently of hepatic steatosis
Authors: Julia Monsénégo, Abdelhak Mansouri, Marie Akkaoui, Véronique Lenoir, Catherine Esnous, Véronique Fauveau, Valentin Tavernier, Jean Girard, Carina Prip-Buus
Journal: Journal of Hepatology (2011)
Hypotension During Sham Apheresis in a Patient Taking ACE Inhibitors
Authors: Alessandra Petrucco
Journal: JAMA (1995)

<h3>To the Editor.</h3> —Dr Agishi<sup>1</sup>discusses the evidence that anaphylactoid reactions could occur during low-density lipoprotein (LDL) apheresis performed with the dextran sulfate— cellulose (DSC) adsorption columns<sup>2</sup>in patients taking angiotensin converting enzyme (ACE) inhibitors.<sup>3</sup>This adverse reaction is triggered by the entrapment of the Hageman factor, high-molecular-weight kininogen, and prekallikrein into the DSC column, leading to kallikrein activation and bradykinin generation. Bradykinin is usually inactivated rapidly by kinases I and II,<sup>3</sup>which are identical to ACE and are inhibited by ACE inhibitors. Therefore, increased generation and decreased catabolism of bradykinin may explain this adverse reaction during the LDL apheresis. Recently, we observed a case of hypotension in a patient treated with an ACE inhibitor during an LDL-apheretic procedure without the DSC column (sham apheresis). After obtaining informed consent, we routinely perform sham apheresis in candidates for chronic LDL apheresis to check its feasibility (eg, adequate
The role of emergency room echocardiography in triaging patients with chest pain at intermediate risk for acute myocardial infarction: a substudy of CHEER
Authors: M. Allen, J.K. Oh, M.E. Farkouth, A.R. Zinsmeister, P.A. Smars, J.B. Seward, G.S. Reeder
Journal: Journal of the American College of Cardiology (1998)
Let us keep our ontology and epistemology separate!
Authors: William R. Uttal
Journal: Behavioral and Brain Sciences (1999)

Gold &amp; Stoljar are right in their thesis but incomplete in not pointing out that there are many other arguments from cognate sciences suggesting that a radical eliminativist neuroreductionism is unlikely to be achieved. The radical neuron doctrine they criticize is only a hoped for dogma that cannot be verified, whereas a constrained monistic materialism (with only partial reductionism) is subject to immediate test by applying such criteria as combinatorial complexity and thermodynamic irreversibility.
Artificial Baroreflex
Authors: Fumiyasu Yamasaki, Takahiro Ushida, Takeshi Yokoyama, Motonori Ando, Koichi Yamashita, Takayuki Sato
Journal: Circulation (2006)

Background— We proposed a novel therapeutic strategy against central baroreflex failure: implementation of an artificial baroreflex system to automatically regulate sympathetic vasomotor tone, ie, a bionic baroreflex system (BBS), and we tested its efficacy in a model of sudden hypotension during surgery. Methods and Results— The BBS consisted of a computer-controlled negative-feedback circuit that sensed arterial pressure (AP) and automatically computed the frequency (STM) of a pulse train required to stimulate sympathetic nerves via an epidural catheter placed at the level of the lower thoracic spinal cord. An operation rule was subsequently designed for the BBS using a feedback correction with proportional and integral gain factors. The transfer function from STM to AP was identified by a white noise system identification method in 12 sevoflurane-anesthetized patients undergoing orthopedic surgery involving the cervical vertebrae, and the feedback correction factors were determined with a numerical simulation to enable the BBS to quickly and stably attenuate an external disturbance on AP. The performance of the designed BBS was then examined in a model of orthostatic hypotension during knee joint surgery (n=21). Without the implementation of the BBS, a sudden deflation of a thigh tourniquet resulted in a 17±3 mm Hg decrease in AP within 10 seconds and a 25±2 mm Hg decrease in AP within 50 seconds. By contrast, during real-time execution of the BBS, the decrease in AP was 9±2 mm Hg at 10 seconds and 1±2 mm Hg at 50 seconds after the deflation. Conclusions— These results suggest the feasibility of a BBS approach for central baroreflex failure.
Idiopathic light‐chain proteinuria: Case report and review of the literature
Authors: Vincent Audard, Ghandi Damaj, Marie Thérèse Rubio, Pièrre Aucouturier, Olivier Hermine, Bruno Varet
Journal: American Journal of Hematology (2004)

Abstract Isolated Bence Jones proteinuria (BJP) is a distinct form of monoclonal gammopathy of undetermined significance (MGUS) rarely described. The prognosis of the disease is apparently good. We report here a case of idiopathic BJP and review the literature. Am. J. Hematol. 76:293–294, 2004. © 2004 Wiley‐Liss, Inc.
Abstract P3-04-05: Amplification driven expression of KIAA0020, a PARP1 interacting gene, facilitates repair of replication associated DNA damage in triple-negative breast cancers
Authors: A Grigoriadis, E Noel, D Weekes, V Shah, B Sidhu, P Gazinska, J Watkins, P Marra, A Tutt
Journal: Cancer Research (2013)

Abstract Approximately 25% of triple-negative breast cancers display increased copy number in the region of 9p24. Since several genes mapping to this genomic locus have been shown to be involved in the biology of triple-negative breast cancers, a copy number-dependent transcriptional influence of genes at 9p24 on the malignant phenotypes has been suggested. Given the limited options of targeted therapy for triple-negative breast cancer patients, further studies of genes located at this locus could therefore provide potential novel targets or companion biomarkers for this disease. By integrating microarray-based DNA copy number and gene expression of genes located on 9p24 in 111 triple-negative breast cancers, we identified among a wider set of genes three hypothetical genes, KIAA0020, KIAA1432 and KIAA2026 whose expression was highly correlated with their copy number status. External validation through analysis of several comprehensive breast cancer cohorts, confirmed KIAA0020 as being highly abundant in basal-like/ triple-negative breast cancers. Involvement of KIAA0020 in PARP1 activity and the DNA damage response has previously been suggested. To elucidate KIAA0020's functional involvement in cell growth, cell cycle progression, apoptosis and DNA damage response in this subtype of breast cancer, breast cancer cell lines with and without increased 9p24 copy number levels were used as in vitro models. In cell lines with increased DNA copy number at 9p24, depletion of KIAA0020 expression selectively impaired growth causing an accumulation in S-phase and a decrease in cell proliferation. Furthermore, KIAA0020-silencing in such cell lines resulted in decreased repair of hydroxyurea induced replication associated DNA damage, accumulation of DNA double strand breaks and decreased occurrence of RAD51 and PAR foci, all pointing to a decreased repair of inactivated replication forks. Taken together, our data supports the notion that genes of unknown function, residing in the 9p24 copy number aberrant region are involved in DNA repair and may thereby also contribute to the tumourigenesis of triple-negative breast cancers. A subset of such triple-negative tumours seemed to have developed a dependency on the expression of KIAA0020, a PARP1 interacting gene, for replication fork associated repair. Thus, greater understanding of KIAA0020's molecular function may provide additional information for patient selection with regards to DNA damaging chemotherapeutics or PARP inhibitors within triple-negative breast cancers. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-04-05.
Low-Birth-Weight Infants
Authors: Julius Richmond
Journal: JAMA (1990)

The remarkable advances of the past two decades in neonatology have resulted in saving the lives of many low-birth-weight infants. As birth-weight-specific mortality declines, concern about developmental disabilities among the survivors becomes appropriate. Attention properly has focused on efforts to enhance the developmental potentialities of these infants. A pioneering study reported in this issue ofThe Journalsheds considerable light on this matter.<sup>1</sup>The study is pioneering in several respects: (1) The prospective, sound design, formulated at the outset, gave reasonable assurance of providing answers to an important clinical and public policy issue. (2) It demonstrated that the well-accepted multicenter design of clinical trials is applicable to research in human development. (3) It demonstrated that it is feasible to apply a comprehensive intervention in a variety of communities. (4) It illustrates that private foundations can play an important role in identifying important policy issues and supporting the acquisition of the
Lancet withdraws its support of document on collaboration between doctors and drug industry
Authors: N. Hawkes
Journal: BMJ (2013)

The Lancet has withdrawn its support from a document outlining how healthcare professionals could collaborate with the drug industry. 

In an editorial titled “Falling out with pharma,”1 the journal’s editor, Richard Horton, said that the statements the document made did not match the latest evidence on the behaviour of drug companies today and that this evidence undermined the principles to which he originally signed up in an attempt “to forge a new and more constructive partnership between medicine and the pharmaceutical industry.”

The four page document was published in 2012 by the Ethical Standards in Health and Life Sciences Group,2 which is co-chaired by the president of the Royal College of Physicians, Richard Thompson, and the president of the Association of the British Pharmaceutical Industry, Deepak Khanna. The group’s members include several royal colleges, the BMA, the Department of Health for England, and the Lancet . The document is available on the websites of the RCP and the ABPI.3

Horton …
Atrial Dissociation and Uniatrial Fibrillation
Authors: GEORGE W. DEITZ, HENRY J.L. MARRIOTT, EVAN FLETCHER, SAMUEL BELLET
Journal: Circulation (1957)

Three cases of atrial dissociation are illustrated with electrocardiograms. The coexisting atrial rhythms observed in published cases permit us to offer a convenient classification. Two possible explanations of this rare phenomenon are discussed.
Jun kinase modulates tumor necrosis factor-dependent apoptosis in liver cells
Authors: Christian Liedtke, Jörg Plümpe, Stefan Kubicka, Cynthia A. Bradham, Michael P. Manns, David A. Brenner, Christian Trautwein
Journal: Hepatology (2002)

Tumor necrosis factor (TNF) triggers distinct pathways in liver cells through TNF receptor 1 (TNF-R1) via adapter molecules, including the intracellular cascades leading to apoptosis, nuclear factor-κB (NF-κB), and Jun kinase (JNK) activation. TNF-dependent activation of NF-κB induces the transcription of antiapoptotic genes that renders liver cells resistant against TNF-induced apoptosis. In contrast, the role of JNK during TNF-induced apoptosis is less clear, so we studied its role during this process. Hepatoma cells treated with TNF and cycloheximide undergo apoptosis, which is proceeded by a strong activation of JNK. Adenoviral vectors (adv) were tested to block TNF-dependent JNK activation selectively. An adv expressing dominant-negative (dn) TRAF2 inhibited only JNK and not ERK or NF-κB activation. However, the effect of inhibiting JNK activation with a dn TAK1 virus was also specific but was stronger than that via dn TRAF2. In further experiments, the inhibitory effect of dn TAK1 on JNK was used to define its role during TNF-dependent apoptosis. Inhibition of JNK by adv dn TAK1 resulted in an earlier and stronger induction of apoptosis. Interestingly, TAM67, a dn form of c-Jun, did not mediate the JNK-dependent effect on TNF-dependent apoptosis, indicating that other molecular targets are essential to confer this mechanism. However, the modified apoptosis pattern could be inhibited by adv expressing Bcl-2 or dn FADD. In conclusion, we define TAK1 as a kinase specifically involved in TNF-induced JNK activation in hepatoma cells and show that JNK transduces antiapoptotic signals, which modulate the strength and time course of FADD-dependent cell death involving mitochondrial permeability transfer.
Associations between Intimate Partner Violence and Termination of Pregnancy: A Systematic Review and Meta-Analysis
Authors: Megan Hall, Lucy C. Chappell, Bethany L. Parnell, Paul T. Seed, Susan Bewley
Journal: PLoS Medicine (2014)

Lucy Chappell and colleagues conduct a systematic review and meta analysis to investigate a possible association between intimate partner violence and termination of pregnancy. Please see later in the article for the Editors' Summary
Some aspects of cadmium flow in the U.S.
Authors: K J Yost
Journal: Environmental Health Perspectives (1979)

A team of Purdue University engineers and scientists has been involved in studying sources, translocation mechanisms, and fate of cadmium in the environment. One of the principal results of this work has been the development of a cadmium flow model for the U. S. which involves simulating sources, use patterns, waste treatment and recovery techniques, waste disposal options, and environmental flow mechanisms. A series of model calculations performed specify cadmium environmental flow, fate, and human exposure for a variety of use pattern, waste treatment/recovery, and disposal scenarios over a ten-year-simulation period.
Don't try this at home?
Authors: R. Coombes
Journal: BMJ (2009)

Home fetal heart monitors have become widely available in recent years and cheap enough for big UK retailers such as Mothercare to market the devices as one of the “pregnancy essentials.” The Medicines and Healthcare Products Regulatory Agency, which is responsible for those fetal monitors that are categorised as medical devices, said it had concerns these products were being increasingly used by lay people. A spokesperson for the agency said: “We are aware of a case where a mother, concerned by lack of fetal movement, was reassured by an apparent fetal heartbeat from her monitor. However, it appears that the monitor was reacting to the maternal heartbeat and the child was later stillborn.”

The agency said it can take action …