tbuckley/cabot-search huggingface dataset:
The SPINK in chronic pancreatitis: similar finds, different minds
Authors: H Witt
Journal: Gut (2002)

SPINK mutations are strongly associated with chronic pancreatitis but may not cause the disease

Student Mephistopheles “Yet in each word some concept there must be.” “Quite true! But don't torment yourself too anxiously; For at the point where concepts fail, At the right time a word is thrust in there. With words we fitly can our foes assail, With words a system we prepare, Words we quite fitly can believe, Nor from a word a mere iota thieve.” Johann Wolfgang Goethe; Faust I 

Approximately five decades ago it was recognised for the first time that chronic pancreatitis (CP) may cluster in selected families suggesting an inherited disorder in these patients.1 However, the underlying genetic defect remained obscure for a long time. The discovery of cationic trypsinogen ( PRSS1 ) mutations in CP families provided a first clue to the underlying disease mechanisms.2 Subsequent studies revealed that PRSS1 mutations are also present in patients with idiopathic CP. Recently, mutations in the serine protease inhibitor, Kazal type 1 ( SPINK1 ) gene, a pancreatic trypsin inhibitor, were identified as associated with idiopathic or hereditary CP: in 22 of 96 paediatric patients, a SPINK1 mutation was detected. In 18 patients, a substitution of asparagine by serine at codon 34 in exon 3 was found (N34S). Six patients were homozygous for this mutation.3 These findings suggest that pancreatitis may be the result of an imbalance of proteases and their inhibitors within the pancreatic parenchyma.

In this issue of Gut , Threadgold and coworkers4 and Drenth and colleagues5 describe mutational studies of SPINK1 in two large series with different types of chronic pancreatitis [see pages 675 and 682]. Threadgold et …
IFNγ Markedly Cooperates with Intratumoral Dendritic Cell Vaccine in Dog Tumor Models
Authors: Kai Mito, Kikuya Sugiura, Kana Ueda, Takako Hori, Takashi Akazawa, Jyoji Yamate, Hiroshi Nakagawa, Shingo Hatoya, Muneo Inaba, Norimitsu Inoue, Susumu Ikehara, Toshio Inaba
Journal: Cancer Research (2010)

Abstract Dendritic cell (DC)–based immunotherapy can trigger effective immune responses against cancer in human patients. Although accompanied by little toxicity, further improvements are needed to optimize immune responses for fully satisfactory clinical outcomes. IFNγ, a potent inducer of T helper type 1 immune responses, is considered an important tool to realize improvements. In this study, we sought to clarify the effect of IFNγ on the maturation and activation of DCs and the clinical outcome of DC-based cancer therapy in dogs. In vitro experiments indicated that IFNγ significantly enhanced the expression of immune stimulatory molecules and interleukin-12 by DCs derived from canine monocytes. IFNγ also significantly strengthened DC-mediated growth suppression against tumor cell lines. DC inoculation with concomitant delivery of IFNγ into primary or recurrent tumors elicited significant clinical responses, including four complete responses and two partial responses against malignant tumors, also eliciting partial responses against benign but actively growing tumors. Together, our results indicate that combining IFNγ and DCs could induce strong immune responses against tumors, significantly improving clinical outcomes. The present study of dogs bearing common types of cancer in humans offers a unique line of support for the development of human cancer therapies. Cancer Res; 70(18); 7093–101. ©2010 AACR.
Impact of Patient Distance to Radiation Therapy on Mastectomy Use in Early-Stage Breast Cancer Patients
Authors: Anneke T. Schroen, David R. Brenin, Maria D. Kelly, William A. Knaus, Craig L. Slingluff
Journal: Journal of Clinical Oncology (2005)

Purpose Treatment access underlies quality cancer care. We hypothesize that mastectomy rates in a rural state are independently influenced by distance to radiation therapy (XRT) and by changing XRT access through opening new facilities. Patients and Methods Early-stage breast cancer patients diagnosed from 1996 to 2000 were identified in the Virginia state registry. Distance from patient zip code to nearest XRT facility was calculated with geographical software. Distance to XRT facility (≤ 10, &gt; 10 to 25, &gt; 25 to 50, and &gt; 50 miles), American Joint Committee on Cancer tumor stage, age, race, and diagnosis year were evaluated for influencing mastectomy rate. Mastectomy use within 15 miles of five new facilities was assessed before and after opening. Results Among 20,094 patients, 43% underwent mastectomy, 53% underwent lumpectomy, and therapy of 4% of patients is unknown. Twenty-nine percent of patients lived more than 10 miles from XRT facility. Mastectomy increased with distance to XRT facility (43% at ≤ 10 miles, 47% at &gt; 10 to 25 miles, 53% at &gt; 25 to 50 miles, and 58% at &gt; 50 miles; P &lt; .001). Among 11,597 patients with T1 (&lt; 2 cm) tumors, mastectomy also varied by distance (31% at ≤ 10 miles, 36% at &gt; 10 to 25 miles, 41% at &gt; 25 to 50 miles, and 49% at &gt; 50 miles; P &lt; .001). In multivariate analysis, mastectomy use was independently influenced by XRT distance after adjusting for age, race, T stage, and diagnosis year. Over the study period, mastectomy rates declined from 48% to 43% across Virginia, and there were similar declines in a 15-mile area around four new radiation facilities in urban settings. However, mastectomies decreased from 61% to 45% around a new XRT facility in a rural setting. Conclusion Distance to XRT facility significantly impacts mastectomy use. Opportunities for increasing breast-conservation rates through improved XRT access exist.
High SUV uptake on FDG–PET/CT predicts for an aggressive B-cell lymphoma in a prospective study of primary FDG–PET/CT staging in lymphoma
Authors: J Y Y Ngeow, R H H Quek, D C E Ng, S W Hee, M Tao, L C Lim, Y H Tan, S T Lim
Journal: Annals of Oncology (2009)
A 2-h diagnostic protocol to assess patients with chest pain symptoms in the Asia-Pacific region (ASPECT): a prospective observational validation study
Authors: Martin Than, Louise Cullen, Christopher M Reid, Swee Han Lim, Sally Aldous, Michael W Ardagh, W Frank Peacock, William A Parsonage, Hiu Fai Ho, Hiu Fai Ko, Ravi R Kasliwal, Manish Bansal, Sunarya Soerianata, Dayi Hu, Rongjing Ding, Qi Hua, Kang Seok-Min, Piyamitr Sritara, Ratchanee Sae-Lee, Te-Fa Chiu, Kuang-Chau Tsai, Fang-Yeh Chu, Wei-Kung Chen, Wen-Han Chang, Dylan F Flaws, Peter M George, A Mark Richards
Journal: The Lancet (2011)
Sesame Allergy In The Canadian Pediatric Population: A Descriptive Study
Authors: L.M. Segal, A. Clarke, M. Primeau, L. Joseph, C. Neville, K. Kilorn, A. Gancia-Godoy, D. Lejtenyi, Y. St. Pierre, R. Alizadehfar
Journal: Journal of Allergy and Clinical Immunology (2010)
Baseline and treatment completion chest radiographs in pulmonary and extra-pulmonary tuberculosis
Authors: Suzanne Bartington, Susan Hopkins, Charlotte Cash, Joanne Cleverley, Ian Cropley, Marc Lipman
Journal: European Respiratory Journal (2011)

Background:  Chest radiographs (CXR) are key to the diagnosis & management of tuberculosis (TB). End-treatment CXR (E-CXR) provide information on therapy response & risk of post-treatment pulmonary sequelae.   Objectives:  1.To report factors associated with baseline CXR (B-CXR) in pulmonary TB (PTB) & extra-pulmonary TB (EPTB).  2.To document the use of E-CXR in subjects with abnormal (abN) baseline CXR (B-CXR).   Study design:  Retrospective data for TB patients at our hospital (1.1.06 - 31.12.08) were obtained from the London TB Register. Patients were classified by TB notification as PTB, EPTB or EPTB with pulmonary involvement (EPTB+PTB). B-CXR (2mths pre- to 1mth post- start TB treatment) & E-CXR (2mths peri-end TB treatment) were reviewed blind by 2 respiratory radiologists.   Results:  Of 305 patients, 113 (37.0%) were diagnosed with PTB, 155 (50.8%) EPTB & 37 (12.1%) EPTB+PTB. 285 (93.4%) had B-CXR performed in the correct time period (early/late 5.6%, not performed 1.0%) with no significant difference by TB clinical status. Female patients were less likely to have a B-CXR (F: 89.6%, M: 97.4%, p   Conclusion:  B-CXR was performed in 99% cases. E-CXR use was sub-optimal in those with baseline abnormalities, especially as one-fifth of those performed remained abnormal and often suggestive of active disease.
Women's rugby league injury claims and costs in New Zealand
Authors: D A King, P A Hume, P Milburn, S Gianotti
Journal: British Journal of Sports Medicine (2009)

There is scarce information on rugby league injuries in female players. This paper provides an overview of the epidemiology of women's rugby league injuries requiring medical treatment and associated costs in New Zealand.New Zealand Accident Compensation Corporation injury data for the period 1999-2007 were searched for rugby league injury cases occurring in females. Data were analysed by demographics, body region, nature/severity of injury, and medical procedure and costs.There were 320 moderate to serious injury claims recorded for females participating in rugby league activities over the study period. There was a mean (SD) of 37.9 (9.5) injury claims per year. The mean cost per year for the study period was $196 514 ($99,133) (£76,066 (£38,374)) with half of the injury claims occurring in New Zealand Maori. Concussion/brain injuries accounted for 3.8% of total female moderate to serious injury claims but accounted for 5.4% of female injury costs ($84,399 (£32,688)) with the highest mean cost per claim ($7033 (£2724)). The lower limb accounted for 65% of the total female injury claims and 58.7% of total injury costs ($922,296 (£356,968)). The mean cost per claim was higher for the lower limb ($4434 (£1714)) than the upper ($3331 (£1288)) limb. Clerks recorded 16.3% of the total injury claims, 20.3% of total injury costs ($319,474 (£123,211)) and had the highest mean cost per claim ($6144 (£2370)). The 25-29 age group recorded 31.9% of injury claims and 33.8% of injury costs. The 35-39 age group recorded the highest mean cost per claim ($6200 (£2392)) but only 10.9% of total claims and 13.8% of total costs.When compared with other studies in rugby league injuries, it appears that females incur substantially fewer injuries (5.7%) than males (94.3%). Although no participation data by sex are available, it is likely that participation percentages are reflected in the injury percentages. The high frequency (65%) and cost proportion (58.7%) for lower limb injuries was higher in females than in male rugby league players (previously reported as 42.4% of the injury claims and 31.5% of the total injury claim costs for the lower limb).Injury prevention programmes for women's rugby league should focus on the 25-29 age group and address ways to prevent concussion and lower limb injuries.
Principles From Clinical Trials Relevant to Clinical Practice: Part I
Authors: Robert M. Califf, David L. DeMets
Journal: Circulation (2002)

parts of this review discussed lessons learned from cardiovascular clinical trials about the design and interpretation of clinical trials.In the next 2 parts, we will attempt to apply these lessons to decision-making in clinical practice.We undertake this effort with trepidation, recognizing that translating research findings into the care of an individual patient is a frontier that has not been adequately explored.Yet the potential for an empirical-based medical practice that would improve on the intuitive-based practice of the past, when combined with traditional clinical skills and patient preferences, demands that we move forward to apply what we have learned in populations to the care of individual patients.Principle 2: Qualitative Interactions Are Uncommon, but Quantitative Interactions Are UsualClinical thinking has traditionally been oriented toward finding the exception rather than the rule.Yet the aggregate of
Update on Harm-Reduction Policy and Intervention Research
Authors: G. Alan Marlatt, Katie Witkiewitz
Journal: Annual Review of Clinical Psychology (2010)

Harm reduction is a pragmatic approach to reduce the harmful consequences of alcohol and drug use or other high-risk activities by incorporating several strategies that cut across the spectrum from safer use to managed use to abstinence. The primary goal of most harm-reduction approaches is to meet individuals “where they are at” and not to ignore or condemn the harmful behaviors but rather to work with the individual or community to minimize the harmful effects of a given behavior. The current review addresses some of the newest developments with respect to harm-reduction policy, prevention, and treatment. In particular, this review highlights policies and programs that have been evaluated in peer-reviewed journals and shown to be effective at reducing the harms associated with alcohol and drug use. The overall goal of this review is to present some of the most recent developments in the field of harm reduction.
Death by a B Cell Superantigen
Authors: Carl S. Goodyear, Gregg J. Silverman
Journal: The Journal of Experimental Medicine (2003)

Amongst the many ploys used by microbial pathogens to interfere with host immune responses is the production of proteins with the properties of superantigens. These properties enable superantigens to interact with conserved variable region framework subdomains of the antigen receptors of lymphocytes rather than the complementarity determining region involved in the binding of conventional antigens. To understand how a B cell superantigen affects the host immune system, we infused protein A of Staphylococcus aureus (SpA) and followed the fate of peripheral B cells expressing B cell receptors (BCRs) with VH regions capable of binding SpA. Within hours, a sequence of events was initiated in SpA-binding splenic B cells, with rapid down-regulation of BCRs and coreceptors, CD19 and CD21, the induction of an activation phenotype, and limited rounds of proliferation. Apoptosis followed through a process heralded by the dissipation of mitochondrial membrane potential, the induction of the caspase pathway, and DNA fragmentation. After exposure, B cell apoptotic bodies were deposited in the spleen, lymph nodes, and Peyer's patches. Although in vivo apoptosis did not require the Fas death receptor, B cells were protected by interleukin (IL)-4 or CD40L, or overexpression of Bcl-2. These studies define a pathway for BCR-mediated programmed cell death that is VH region targeted by a superantigen.
Précis of<i>Evolution in Four Dimensions</i>
Authors: Eva Jablonka, Marion J. Lamb
Journal: Behavioral and Brain Sciences (2007)

Abstract In his theory of evolution, Darwin recognized that the conditions of life play a role in the generation of hereditary variations, as well as in their selection. However, as evolutionary theory was developed further, heredity became identified with genetics, and variation was seen in terms of combinations of randomly generated gene mutations. We argue that this view is now changing, because it is clear that a notion of hereditary variation that is based solely on randomly varying genes that are unaffected by developmental conditions is an inadequate basis for evolutionary theories. Such a view not only fails to provide satisfying explanations of many evolutionary phenomena, it also makes assumptions that are not consistent with the data that are emerging from disciplines ranging from molecular biology to cultural studies. These data show that the genome is far more responsive to the environment than previously thought, and that not all transmissible variation is underlain by genetic differences. In Evolution in Four Dimensions (2005) we identify four types of inheritance (genetic, epigenetic, behavioral, and symbol-based), each of which can provide variations on which natural selection will act. Some of these variations arise in response to developmental conditions, so there are Lamarckian aspects to evolution. We argue that a better insight into evolutionary processes will result from recognizing that transmitted variations that are not based on DNA differences have played a role. This is particularly true for understanding the evolution of human behavior, where all four dimensions of heredity have been important.
Identical T Cell Clones Are Located within the Mouse Gut Epithelium and Lamina Propria and Circulate in the Thoracic Duct Lymph
Authors: Tuula Arstila, T. Petteri Arstila, Sébastien Calbo, Françoise Selz, Michèle Malassis-Seris, Pierre Vassalli, Philippe Kourilsky, Delphine Guy-Grand
Journal: The Journal of Experimental Medicine (2000)

Murine gut intraepithelial (IEL) T cell receptor (TCR)-α/β1 lymphocytes bearing CD8α/β or CD8α/α coreceptors have been shown previously to express different oligoclonal TCR β chain repertoires in the same mouse, in agreement with other evidence indicating that these two populations belong to different ontogenic lineages, with only CD8α/β1 IELs being fully thymus dependent. CD8α/β1, but not CD8α/α1, T lymphocytes are also present in the lamina propria. Here, we show that CD8α/β+ lymphocytes from the lamina propria and the epithelium are both oligoclonal, and that they share the same TCR-β clonotypes in the same mouse, as is also the case for CD4+ T cells. Furthermore, identical T cell clones were detected among CD8α/β1 IELs and CD8α/β1 blasts circulating into the thoracic duct (TD) lymph of the same mouse, whereas TD small lymphocytes are polyclonal. These findings must be considered in light of previous observations showing that T blasts, but not small T lymphocytes, circulating in the TD lymph have the capacity of homing into the gut epithelium and lamina propria. These combined observations have interesting implications for our understanding of the recirculation of gut thymus-dependent lymphocytes and their precursors, and of the events leading up to the selection of their restricted TCR repertoire.
A TRANSMISSIBLE AGENT (THEILER'S VIRUS) IN THE INTESTINES OF NORMAL MICE
Authors: Peter K. Olitsky
Journal: The Journal of Experimental Medicine (1940)

Every experiment with the contents of one, or with those pooled from two to five of the normal stock of Rockefeller Institute strain of albino mice, 1 to 2 months of age, revealed the presence of a virus which, after intracerebral inoculation into normal mice, induced characteristic paralytic encephalomyelitis, indistinguishable from Theilerapos;s disease. No difference was seen in this effect of intestinal contents deriving from animals paralyzed during the course of spontaneous encephalomyelitis and from normal mice. The influence of age on carriage of virus, as well as on the persistence of the carrier state, is discussed. The present, as well as previous work has shown that the virus found in normal (or paralyzed) mice is similar to that of Theiler's disease in all of its properties thus far investigated; among the strains of the latter now at hand it can be classified with those having a low degree of invasiveness after peripheral inoculation. The virus has thus far been recovered from intestinal contents, intestinal walls, and mesenteric glands but not from the central nervous system of normal mice; from these sites, as well as from the central nervous system, in paralyzed mice. In order of concentration of virus, the contents have more, the walls less, and the glands least.
Fine scale structural variants distinguish the genomes of Drosophila melanogaster and D. pseudoobscura.
Authors: Stuart J Macdonald, Anthony D Long
Journal: Genome biology (2006)

Abstract Background A primary objective of comparative genomics is to identify genomic elements of functional significance that contribute to phenotypic diversity. Complex changes in genome structure (insertions, duplications, rearrangements, translocations) may be widespread, and have important effects on organismal diversity. Any survey of genomic variation is incomplete without an assessment of structural changes. Results We re-examine the genome sequences of the diverged species Drosophila melanogaster and D. pseudoobscura to identify fine-scale structural features that distinguish the genomes. We detect 95 large insertion/deletion events that occur within the introns of orthologous gene pairs, the majority of which represent insertion of transposable elements. We also identify 143 microinversions below 5 kb in size. These microinversions reside within introns or just upstream or downstream of genes, and invert conserved DNA sequence. The sequence conservation within microinversions suggests they may be enriched for functional genetic elements, and their position with respect to known genes implicates them in the regulation of gene expression. Although we found a distinct pattern of GC content across microinversions, this was indistinguishable from the pattern observed across blocks of conserved non-coding sequence. Conclusion Drosophila has long been known as a genus harboring a variety of large inversions that disrupt chromosome colinearity. Here we demonstrate that microinversions, many of which are below 1 kb in length, located in/near genes may also be an important source of genetic variation in Drosophila . Further examination of other Drosophila genome sequences will likely identify an array of novel microinversion events.
Measurement of Anxiety in Psychotherapy Process Research
Authors: Charlotte Feinmann, David Goldberg
Journal: Journal of the Royal Society of Medicine (1982)

A new technique designed to measure a patient's anxiety during a psychotherapeutic interview is described. Videotaped recordings were made of interviews between 2 psychotherapists and 6 patients. The anxiety levels experienced by the patients during the interview were measured in three ways. One therapist signalled his recognition of a patient's changing anxiety levels and his interventions to manipulate the patient's anxiety during the interview. Subsequently, the 2 therapists and 6 patients made independent retrospective ratings while viewing a recording of the interview. Significant agreement was found between three sets of ratings and the results suggest that the technique may be of value in psychotherapy process research.
Deubiquitinating enzyme CYLD negatively regulates the ubiquitin-dependent kinase Tak1 and prevents abnormal T cell responses
Authors: William W. Reiley, Wei Jin, Andrew Joon Lee, Ato Wright, Xuefeng Wu, Eric F. Tewalt, Timothy O. Leonard, Christopher C. Norbury, Leo Fitzpatrick, Minying Zhang, Shao-Cong Sun
Journal: The Journal of Experimental Medicine (2007)

The deubiquitinating enzyme CYLD has recently been implicated in the regulation of signal transduction, but its physiological function and mechanism of action are still elusive. In this study, we show that CYLD plays a pivotal role in regulating T cell activation and homeostasis. T cells derived from Cyld knockout mice display a hyperresponsive phenotype and mediate the spontaneous development of intestinal inflammation. Interestingly, CYLD targets a ubiquitin-dependent kinase, transforming growth factor–β-activated kinase 1 (Tak1), and inhibits its ubiquitination and autoactivation. Cyld-deficient T cells exhibit constitutively active Tak1 and its downstream kinases c-Jun N-terminal kinase and IκB kinase β. These results emphasize a critical role for CYLD in preventing spontaneous activation of the Tak1 axis of T cell signaling and, thereby, maintaining normal T cell function.