tbuckley/cabot-search huggingface dataset:
Indian president signs ordinance to dissolve medical council
Authors: Z. Kmietowicz
Journal: BMJ (2010)

<h3>Abstract</h3> Binge eating (BE) is a maladaptive repetitive feeding behavior present across nearly all eating disorder diagnoses. BE is associated with poor psychosocial outcomes (e.g., suicidal ideation) and increased risk for obesity. Despite the substantial negative impact of BE, its underlying neural mechanisms are largely unknown. Many other repetitive behavior disorders (e.g., obsessive compulsive disorder) show dysfunction within corticostriatal circuitry. Additionally, previous pre-clinical and clinical work has highlighted an imbalance between goal-directed and habitual responding in BE. The aim of the current study was to longitudinally examine <i>in vivo</i> neural activity within corticostriatal regions associated with habitual behavior– the infralimbic cortex (IL) and dorsolateral striatum (DLS)– in a robust pre-clinical model for BE. Female C57BL/6 mice (N = 32) were randomized to receive: 1) intermittent (daily, 2-hour) binge-like access to palatable food (BE mice), or 2) continuous, non-intermittent (24-hour) access to palatable food (non-BE mice). <i>In vivo</i> calcium imaging was performed via fiber photometry at the baseline timepoint and after 4 weeks (chronic timepoint) of engagement in the model for BE. Feeding behaviors (feeding bout onset, offset) during the recordings were captured using contact lickometers which generated TTL outputs for precise alignment of BE behavior to neural data. Results in the IL showed no specific changes in neural activity related to BE. However, BE animals showed decreased DLS activity from the baseline to chronic timepoint at feeding onset and offset. Additionally, BE mice had significantly lower DLS activity at feeding onset and offset during the chronic time point compared to non-BE mice. These results point to a role for DLS hypofunction in chronic BE, highlighting a potential target for future treatment intervention.
Maintaining Low HIV Seroprevalence Among Injecting Drug Users-Reply
Authors: Samuel R. Friedman
Journal: JAMA (1996)

<h3>In Reply.</h3> —Drs Wong and Lee present an interesting description of the situation of HIV infection among IDUs in Hong Kong. We were aware of the Hong Kong drug treatment program seroprevalence data, but not of their unpublished data from IDUs not in treatment. It would appear that Hong Kong meets our criteria for "stable low HIV prevalence" among IDUs.<sup>1</sup>We did consider pharmacy sales as "provision of sterile injection equipment" if pharmacists did not discriminate against IDUs and IDUs could carry injection equipment without fear of arrest or harassment by police. The data from Hong Kong thus seem fully parallel to the data from the five cities in our study. Given the effectiveness of methadone maintenance treatment in reducing heroin injection (and therefore HIV risk),<sup>2</sup>we would agree that the Hong Kong methadone treatment program probably was important in reducing HIV transmission there. We would also note
Is the Synonymous Substitution Rate in Mammals Gene-Specific?
Authors: Elizabeth J. B. Williams, Laurence D. Hurst
Journal: Molecular Biology and Evolution (2002)

There is a great deal of variation in silent rates of evolution (Ks) between genes in the same species pair comparison (Bernardi, Mouchiroud, and Gautier 1993;Wolfe and Sharp 1993;Mouchiroud, Gautier, and Bernardi 1995).This may represent random fluctuation (Kumar and Subramanian 2002) or may be deterministically caused.Evidence for the latter comes from the finding that the rate of silent site evolution of a gene is repeatable across independent lineages (Bulmer, Wolfe, and Sharp 1991;Mouchiroud, Gautier, and Bernardi 1995;Bielawski, Dunn, and Yang 2000).Most notably, Mouchiroud, Gautier, and Bernardi (1995) found that the number of synonymous substitutions per synonymous site (Ks) for a gene in the human-cow comparison was a very strong predictor of the Ks of the same gene in the mouse-rat comparison.This repeatability has been used as evidence (Mouchiroud, Gautier, and Bernardi 1995) for selection acting upon silent sites in orthologous genes.One argument holds, for example, that if purifying selection favors a particular amino acid at a given site, it should also favor the translationally most accurate codon and codon usage bias would be selected for.The repeatability of Ks and the Ka-Ks correlation are then attributed to the same selectionist cause.However, this interpretation is questionable on a number of counts.Most notably, with one possible exception (Debry and Marzluff 1994), there is no compelling evidence that codon usage bias in mammals is the result of selection (Eyre-Walker 1991;Karlin and Mrazek 1996;Urrutia and Hurst 2001).Alternative interpretations of the putative fact are also possible.These include gene-or chromosome-specific mutation rates and gene-specific rates of biased gene conversion, all of which could give repeatable Ks and a Ka-Ks correlation.Leaving the difficulties of interpretation aside, we wish to note two potential problems with the prior analysis, that of Mouchiroud, Gautier, and Bernardi.First, these authors did not constrain the orthologs to be autosomal.Mammalian X-linked genes often have a low Ks, most probably in part because of the relatively short time spent in the male germ line (for review see Hurst and Ellegren 1998).A data set with numerous X and autosomal genes could give repeatability of Ks, but this may represent repeatability at the chromosomal level (and be mutationally driven) rather than be on account of selection on silent sites.To address this we analyze a data set of orthologs known to be autosomal.
Progress in the Treatment of Colorectal Cancer
Authors: Giora M. Mavligit
Journal: JAMA (1976)

Colorectal cancer is a major public health problem. Unfortunately, treatment results have not improved much over the past two decades, in spite of surgery and rediotherapy. The most effective single, chemotherapeutic agent for carcinoma of the large bowel<sup>1</sup>has been fluorouracil, first used in clinical trials in 1958 by Curreri and associates.<sup>2</sup>Partial remissions have occurred in 20% to 30% of patients with metastatic disease in whom fluorouracil has been used. Further progress may result from prompt and more aggressive approaches that combine therapeutic modalities. One such approach is adjuvant systemic therapy (chemotherapy or immunotherapy or both) immediately following surgery with or without radiotherapy in the early stages of the disease. This is especially true in patients with Dukes stage C lesions, where the likelihood of surgical failure is approximately 70% to 75%, due to the presence of foci of micrometastases at adjacent or distant organs at the
CD44 Is the Signaling Component of the Macrophage Migration Inhibitory Factor-CD74 Receptor Complex
Authors: Xuerong Shi, Lin Leng, Tian Wang, Wenkui Wang, Xin Du, Ji Li, Courtney McDonald, Zun Chen, James W. Murphy, Elias Lolis, Paul Noble, Warren Knudson, Richard Bucala
Journal: Immunity (2006)
An Unusual Cause of an Isolated, Focal Splenic Defect Demonstrated By Liver-Spleen Scintigraphy
Authors: ROY M. WALLER, WILLIAM A. FAJMAN
Journal: Clinical Nuclear Medicine (1982)

Metastatic involvement of the spleen is uncommon. Lymphoma is the most common cause of primary and secondary malignant lesions of the spleen, whereas splenic metastases from carcinoma are rare and usually occur in a setting of concomitant carcinomatosis with melanoma, breast, ovary and lung accounting for the principal primary tumors. We report a case of an isolated, focal splenic defect demonstrated by Tc-99m-sulfur colloid scintigraphy which was the only visual evidence of metastatic adenocarcinoma of the colon. To our knowledge this unusual cause of a focal splenic defect on liver-spleen scintigraphy has not been previously described.
Patterns of Sympathetic Nerve Projections onto the Canine Heart
Authors: WALTER C. RANDALL, MATHIAS SZENTIVANYI, JOHN B. PACE, JAMES S. WECHSLER, MICHAEL P. KAYE
Journal: Circulation Research (1968)

Major branches from right and left sympathetic ganglia were electrically stimulated while force of contraction was recorded from multiple areas of the right and left ventricles. Stimulation of the stellate ganglia generally elicited alterations in force of contraction from all test segments, but excitation of selected nerve trunks induced responses in highly localized regions of the heart. Ablation of narrow strips of epicardium resulted in obliteration of contractile responses in specific, highly localized regions of the heart; thus a major fraction of the sympathetic innervation of the ventricular chambers is by way of the epicardial plexus. The anterior surface of the right ventricle is supplied by projection pathways arising within the immediately subepicardial regions of the right A-V groove and, to a lesser extent, from the tissues immediately adjacent to the left anterior descending artery. The left ventricle receives minor projections from the right A-V groove with major projections from subepicardial tissues along the left anterior descending artery. In some animals there also exists a definite left ventricular supply from the region of the left A-V groove. Whereas the thoracic vagi send dense projections to the atria, and particularly to nodal tissue, they also supply both ventricles with inhibitory and augmentor fibers. Although isolated cardiac nerves may carry predominantly sympathetic or parasympathetic fibers, many show rich intermingling of these fibers in trunks distal to the caudal cervical ganglion.
A Variant in the Promoter of<i>MUC5B</i>and Idiopathic Pulmonary Fibrosis
Authors: Yingze Zhang, Imre Noth, Joe G.N. Garcia, Naftali Kaminski
Journal: New England Journal of Medicine (2011)

In this study, a single-nucleotide polymorphism in the mucus-forming gene MUC5B was strongly associated with the presence of idiopathic pulmonary fibrosis (IPF). These results replicate the findings of other investigators, also published in this issue.
Cardiac mitochondria and arrhythmias
Authors: D. A. Brown, B. O'Rourke
Journal: Cardiovascular Research (2010)

Despite a high prevalence of sudden cardiac death throughout the world, the mechanisms that lead to ventricular arrhythmias are not fully understood.Over the last 20 years, a growing body of evidence indicates that cardiac mitochondria are involved in the genesis of arrhythmia.In this review, we have attempted to describe the role that mitochondria play in altering the heart's electrical function by introducing heterogeneity into the cardiac action potential.Specifically, we have focused on how the energetic status of the mitochondrial network can alter sarcolemmal potassium fluxes through ATP-sensitive potassium channels, creating a 'metabolic sink' for depolarizing wave-fronts and introducing conditions that favour catastrophic arrhythmia.Mechanisms by which mitochondria depolarize under conditions of oxidative stress are characterized, and the contributions of several mitochondrial ion channels to mitochondrial depolarization are presented.The inner membrane anion channel in particular opens upstream of other inner membrane channels during metabolic stress, and may be an effective target to prevent the metabolic oscillations that create action potential lability.Finally, we discuss therapeutic strategies that prevent arrhythmias by preserving mitochondrial membrane potential in the face of oxidative stress, supporting the notion that treatments aimed at cardiac mitochondria have significant potential in attenuating electrical dysfunction in the heart.
Foundations of Anesthesiology
Authors: Charles G. Roland
Journal: JAMA (1966)

ABSTRACT The history of anesthesia is one of the more manageable and fascinating specialty areas in the history of medicine. Owing to the relatively short and clearly defined time period covered, it remains within the ability of a student to encompass the history of anesthesia. The great interest of the field derives from the rapid introduction of surgical anesthesia as well as the drama associated with the various and violent priority claims.Faulconer and Keys avoid involvement in disputes of priority. They publish Long's account of his use of ether, and Wells's on nitrous oxide. But since Foundations of Anesthesiology is organized chronologically according to date of publication, and since Bigelow's and Morton's papers antedated Long's and Wells's, the former therefore appear here first. None of Jackson's publications are reprinted.The selection of material for inclusion has been, on the whole, admirable. Almost all of the 151 communications are unabridged, and
Gene-independent heritability of behavioural traits: Don't we also need to rethink the “environment”?
Authors: Christian P. Müller, Bernd Lenz, Johannes Kornhuber
Journal: Behavioral and Brain Sciences (2012)

Abstract Behavioural phenotypes have been explained by genetic and environmental factors ( E ) and their interaction. Here we suggest a rethinking of the E factor. Passively incurred environmental influences ( E pass ) and actively copied information and behaviour ( E act ) may be distinguished at shared and non-shared level. We argue that E act underlies mutation and selection and is the base of gene-independent heritability.
Newly registered elderly patients: who are they and why such delay in the transfer of their medical records?
Authors: H. J Graham, B. Livesley
Journal: BMJ (1988)

The time taken to transfer the records of elderly patients registering with a new general practice was investigated. Thirty five (5%) of a total of 671 patients aged 75 and over were entered as new patients on to the age-sex register of an urban group practice during one year. Twenty nine had moved into the area and six had changed their general practitioner for personal and other reasons. An average of 141 (range 71-296) days elapsed before dispatch of their medical records to the new practice. During this period an average of 3·5 (range 0-15) consultations with a general practitioner were recorded, indicating the need of such patients for medical care. The long delays were caused by the processing of medical records at the central register and the transfer of records between family practitioner committees and general practitioners. Delays were most apparent in the time taken for general practitioners to dispatch the necessary documents to the family practitioner committees, and these should be minimised. The use of a summary card written and updated by the general practitioner and retained by the patient would facilitate continuing care should patients change to a new practice. Meanwhile, assessment of elderly patients after registration with a new practice by a member of the primary health care team may identify problems before the records have been transferred and may help the resettlement of these high risk elderly patients.
Reimbursement Policies Constrain the Practice of Oncology
Authors: Thomas Laetz
Journal: JAMA (1991)

<h3>Objective.</h3> —To determine the prevalence of off-label anticancer drug use (ie, using drugs to treat conditions other than those listed on the Food and Drug Administration's approved drug label), the extent of reimbursement denials for these uses, and the effect of denials on the treatment of cancer patients. <h3>Design, Setting, and Participants.</h3> —A three-part questionnaire was sent to a randomized sample of oncologists taken from the 1990 membership of the American Society of Clinical Oncology in March 1990. A response rate of 56% yielded information from 681 oncologists on the drugs they prescribed to 2018 new cancer patients and on those they frequently use in treating 11 specific types of cancer. <h3>Main Outcome Measures.</h3> —The labeled uses of the drugs prescribed and frequently used in chemotherapies were checked against the indications treated to determine whether they were prescribed for off-label uses. Three drug compendia were used as cited sources of off-label drug uses. The extent of reimbursement denials over the last 12 months and their effects on treatments were based on respondent opinions. <h3>Main Results.</h3> —Off-label drug use is prevalent and dominates the chemotherapy regimens of cancers that are more difficult to treat and for which there are no cures or agreements on standardized treatment. Most oncologists reported frustration with shifting reimbursement policies in general and with an increasing rate of denials for some off-label drug uses. Indeed, a surprising number of oncologists claimed that these policies caused them to alter preferred treatments and site of care. <h3>Conclusion.</h3> —These findings suggest the need for public discussion of off-label drug use issues so that appropriate policies can be developed. (<i>JAMA</i>. 1991;266:2996-2999)
Increased risk of severe protamine reactions in NPH insulin-dependent diabetics undergoing cardiac catheterization.
Authors: W J Stewart, S M McSweeney, M A Kellett, D P Faxon, T J Ryan
Journal: Circulation (1984)

Protamine is widely used for reversing systemic heparinization after cardiac catheterization. Although rare, major reactions to protamine that simulate anaphylaxis occasionally occur and have previously been associated only with an allergic reaction to fish. Because neutral protamine Hagedorn (NPH) insulin includes protamine, it might be anticipated that NPH insulin-dependent diabetic patients would develop sensitivity to protamine. Of 866 consecutive patients undergoing cardiac catheterization over a 20 month period, 651 received protamine for reversal of heparinization. Of these, 8.5% (56/651) were diabetics and 2.3% (15/651) were NPH insulin-dependent diabetics. During this period seven patients were observed immediately after administration of protamine to have major adverse reactions that required the administration of catecholamines. One death ensued. Of the seven major reactions, four occurred in NPH insulin-dependent diabetics and one occurred in a patient with an allergy to fish. The incidence of major protamine reactions was 27% (4/15) in the NPH insulin-dependent diabetics vs 0.5% (3/636) in those with no history of NPH insulin use (p less than .001). This represents a 50-fold increased risk of a major reaction to protamine if the patient was receiving NPH insulin. Accordingly, we recommend that diabetics on NPH insulin and patients with allergies to fish undergo cardiac catheterization without the use of protamine or, when necessary, that protamine be administered cautiously in anticipation of a major adverse reaction.
Hippocampal LTD Expression Involves a Pool of AMPARs Regulated by the NSF–GluR2 Interaction
Authors: Andreas Lüthi, Ramesh Chittajallu, Fabrice Duprat, Mary J Palmer, Tim A Benke, Fleur L Kidd, Jeremy M Henley, John T.R Isaac, Graham L Collingridge
Journal: Neuron (1999)
Serum β-Glucuronidase in Diabetes Mellitus
Authors: J. W. Woollen
Journal: JAMA (1966)

<h3>To the Editor:—</h3> In contrast to the findings of Miller et al (<b>195</b>:189, 1966) we found that the plasma β-glucuronidase (and N-acetyl-β-glucosaminidase) levels in diabetic subjects correlated significantly with the blood glucose concentration.<sup>1</sup> The discrepancy between our findings and those of Miller et al, and of Dohrmann<sup>2</sup>is probably due to our use of platelet-free plasma in a sensitive fluorimetric assay procedure<sup>3</sup>in contrast to the use of serum by other workers. It has been found that there is liberation of β-glucuronidase from the formed elements of blood during clotting, and the amount is sufficiently large and variable to obscure correlations such as those described. In this connection, we also found a correlation of β-glucuronidase activity with age; this was not observed by Miller et al or by previous workers. We believe that in atherosclerotic and nonatherosclerotic diabetic subjects, plasma β-glucuronidase, N-acetyl-β-glucosaminidase and blood glucose levels
Relative Specificity: All Substrates Are Not Created Equal
Authors: Yan Zeng
Journal: Genomics Proteomics & Bioinformatics (2014)

Abstract A biological molecule, e.g., an enzyme, tends to interact with its many cognate substrates, targets, or partners differentially. Such a property is termed relative specificity and has been proposed to regulate important physiological functions, even though it has not been examined explicitly in most complex biochemical systems. This essay reviews several recent large-scale studies that investigate protein folding, signal transduction, RNA binding, translation and transcription in the context of relative specificity. These results and others support a pervasive role of relative specificity in diverse biological processes. It is becoming clear that relative specificity contributes fundamentally to the diversity and complexity of biological systems, which has significant implications in disease processes as well.
World hunger: a reasonable proposal
Authors: F. Kaufman
Journal: BMJ (2009)

Commodity markets explain why so many people are going hungry in a world of plenty

Last year saw 250 million people added to the ranks of the starving and malnourished, pushing the world total past one billion, or one in every six people on the planet.1 As I read reports of the dramatic upsurge I was reminded of a rainy afternoon in Cambridge two summers ago, when I interviewed Amartya Sen, the Harvard professor who had won the Nobel prize for economics in 1998 for his work on poverty and famine. According to Sen, hunger was not only entirely preventable but profoundly unreasonable.

I had come to Amartya Sen’s house to discuss the recent efforts of the Bill and Melinda Gates Foundation and the World Food Programme to help eradicate world hunger by means of a new programme, called Purchase for Progress. And while our discussion began with the specifics of global food aid, it eventually ranged beyond the particulars of poverty. 

“I believe in reason,” Sen told me. “There are those who want to repress reason: Christian, Muslim, and Hindu fundamentalists, and those who pick a totem market economy, the liberal economic state. These are all anti-reason.” 

Ironically, at the …
Pivotal Role of Reduced<i>let-7g</i>Expression in Breast Cancer Invasion and Metastasis
Authors: Pengxu Qian, Zehua Zuo, Zhengsheng Wu, Xianyi Meng, Gaopeng Li, Zhengzhou Wu, Weijie Zhang, Sheng Tan, Vijay Pandey, Yandan Yao, Puyue Wang, Liqing Zhao, Jun Wang, Qiang Wu, Erwei Song, Peter E. Lobie, Zhinan Yin, Tao Zhu
Journal: Cancer Research (2011)

Abstract Screening of the entire let-7 family of microRNAs (miRNA) by in situ hybridization identified let-7g as the only member, the diminished expression of which was significantly associated with lymph node metastasis and poor survival in breast cancer patients. Abrogation of let-7g expression in otherwise nonmetastatic mammary carcinoma cells elicited rapid metastasis from the orthotopic location, through preferential targets, Grb2-associated binding protein 2 (GAB2) and fibronectin 1 (FN1), and consequent activation of p44/42 mitogen-activated protein kinase (MAPK) and specific matrix metalloproteinases. Treatment with estrogen or epidermal growth factor specifically reduced the expression of mature let-7g through activation of p44/42 MAPK and subsequently stimulated expression of GAB2 and FN1, which, in turn, promoted tumor invasion. We thus identify let-7g as a unique member of the let-7 miRNA family that can serve as a prognostic biomarker in breast cancer and also propose a paradigm used by specific signaling molecules via let-7g to cooperatively promote breast cancer invasion and metastasis. Thus, let-7 family members neither possess equivalent clinicopathologic correlation nor function in breast cancer. Cancer Res; 71(20); 6463–74. ©2011 AACR.