tbuckley/cabot-search huggingface dataset:
A mutation in the propeptide of Factor IX leads to warfarin sensitivity by a novel mechanism.
Authors: K Chu, S M Wu, T Stanley, D W Stafford, K A High
Journal: Journal of Clinical Investigation (1996)

The propeptide sequences of the vitamin K-dependent clotting factors serve as a recognition site for the enzyme gamma-glutamylcarboxylase, which catalyzes the carboxylation of glutamic acid residues at the NH2 terminus of the mature protein. We describe a mutation in the propeptide of Factor IX that results in warfarin sensitivity because of reduced affinity of the carboxylase for the Factor IX precursor. The proband has a Factor IX activity level of > 100% off warfarin and < 1% on warfarin, at a point where other vitamin K-dependent factors were at 30-40% activity levels. Direct sequence analysis of amplified genomic DNA from all eight exons and exon-intron junctions showed a single guanosine-->adenosine transition at nucleotide 6346 resulting in an alanine to threonine change at residue -10 in the propeptide. To define the mechanism by which the mutation resulted in warfarin sensitivity, we analyzed wild-type and mutant recombinant peptides in an in vitro carboxylation reaction. The peptides that were analyzed included the wild-type sequence, the Ala-10-->Thr sequence, and Ala-10-->Gly, a substitution based on the sequence in bone gamma-carboxyglutamic acid protein. Measurement of C02 incorporation at a range of peptide concentrations yielded a Vmax of 343 cpm/min/reaction for the wild-type peptide, and Vmax values of 638 and 726 for A-10T and A-10G respectively, a difference of only twofold. The Km values, on the other hand, showed a 33-fold difference between wild-type and the variants, with a value of 0.29 microM for wild-type, and 10.9 and 9.50 microM, respectively, for A-10T and A-10G. Similar kinetic experiments showed no substantial differences between wild-type and mutant peptides in kinetic parameters of the carboxylase-peptide complexes for reduced vitamin K. We conclude that the major defect resulting from the Factor IX Ala-l0-->Thr mutation is a reduction in affinity of the carboxylase for the mutant propeptide. These studies delineate a novel mechanism for warfarin sensitivity. In addition, the data may also explain the observation that bone Gla protein is more sensitive to warfarin than the coagulation proteins.
A PROSPECTIVE RANDOMIZED COMPARISON BETWEEN A FIXED “2C3L” APPROACH VERSUS STEPWISE APPROACH FOR CATHETER ABLATION OF PERSISTENT ATRIAL FIBRILLATION
Authors: Changsheng Ma, Hung-Fat Tse, Cai-Hua Sang, Rong-Hui Yu, De-Yong Long, Ri-Bo Tang, Chen-Xi Jiang, Xing-Peng Liu, Xin Du, Jian-Zeng Dong
Journal: Journal of the American College of Cardiology (2013)
Children with a heredity risk for asthma were less likely to develop asthma if they lived in a house with a cat: A report from the obstructive lung disease in Northern Sweden studies
Authors: Matthew S Perzanowski, Eva Rönmark, Kerstin Kemi-Björnstöm, David Riposo, Bo Lundbäck, Thomas AE Platts-Mills
Journal: Journal of Allergy and Clinical Immunology (2002)
THE SUDDEN APPEARANCE OF APNEA IN THE COURSE OF TABES DORSALIS AND ARTERIAL SCLEROSIS.
Authors: C. F. HOOVER
Journal: JAMA (1907)

The first patient, a young married woman 26 years old, had a syphilitic infection seven years ago. The past six months the patient has suffered from lancinating pains in the thighs and legs. She has also been annoyed with the feeling as though there was some substance interposed between the soles of her feet and her shoes. There have also occurred several attacks of nausea and vomiting, which, from her description, could very well have been gastric crises. Besides these attacks of nausea and vomiting there were no signs of vagus involvement. Recently the thigh and leg pains grew so intense that morphin was required to allay the pain. The patient showed no disturbance of coordination. The pupils reacted sluggishly to light. The patellar and ankle reflexes were absent. The tactile sense and perception of temperature and of tuning-fork vibrations were unimpaired. There was, however, well pronounced hypoalgesia in the
Timing of Therapeutic Intervention Determines Functional and Survival Outcomes in a Mouse Model of Late Infantile Batten Disease
Authors: Mario A Cabrera-Salazar, Eric M Roskelley, Jie Bu, Bradley L Hodges, Nelson Yew, James C Dodge, Lamya S Shihabuddin, Istvan Sohar, David E Sleat, Ronald K Scheule, Beverly L Davidson, Seng H Cheng, Peter Lobel, Marco A Passini
Journal: Molecular Therapy (2007)

Classical late infantile neuronal ceroid lipofuscinosis (cLINCL) is a monogenic disorder caused by the loss of tripeptidyl peptidase 1 (TPP1) activity as a result of mutations in CLN2. Absence of TPP1 results in lysosomal storage with an accompanying axonal degeneration throughout the central nervous system (CNS), which leads to progressive neurodegeneration and early death. In this study, we compared the efficacies of pre- and post-symptomatic injections of recombinant adeno-associated virus (AAV) for treating the cellular and functional abnormalities of CLN2 mutant mice. Intracranial injection of AAV1-hCLN2 resulted in widespread human TPP1 (hTPP1) activity in the brain that was 10-100-fold above wild-type levels. Injections before disease onset prevented storage and spared neurons from axonal degeneration, reflected by the preservation of motor function. Furthermore, the majority of CLN2 mutant mice treated pre-symptomatically lived for at least 330 days, compared with a median survival of 151 days in untreated CLN2 mutant controls. In contrast, although injection after disease onset ameliorated lysosomal storage, there was evidence of axonal degeneration, motor function showed limited recovery, and the animals had a median lifespan of 216 days. These data illustrate the importance of early intervention for enhanced therapeutic benefit, which may provide guidance in designing novel treatment strategies for cLINCL patients.
134 A SWINE LIVER TRANSPLANTATION MODEL OF ISCHEMIA/REPERFUSION INJURY: PROTECTIVE EFFECTS OF THE HEME OXYGENASE-1 PRODUCTS
Authors: V. Scuderi, A. Giuliani, B. Andria, E. Alimenti, A. Tammaro, S. Scala, C. Attanasio, M. Corona, D. Di Napoli, S. Castaldo, A. Pantaleo, F. Calise
Journal: Journal of Hepatology (2008)
Psychoendocrinology of the Menstrual Cycle
Authors: Robert M. Rose
Journal: New England Journal of Medicine (1978)

The question of what determines human sexual behavior has concerned, even preoccupied, us for a long time, during most of which we have lacked reliable scientific information. However, during this last decade, good data about human sexuality have begun to appear in scientific journals. Perhaps it is a harbinger of sorts that the Journal has published such a paper in this issue by Adams, Gold and Burt.In recent years discussion and theorizing about the nature and determinants of female sexuality have become a battleground or rallying point for many feminist writers. It is true, as they have most clearly . . .
Racism in psychiatry necessitates reappraisal of general procedures and Eurocentric theories
Authors: S P Sashidharan, E. Francis
Journal: BMJ (1999)

EDITOR—We agree with the comment in Editor's Choice (in issue of 6 March) that the effects of the Stephen Lawrence case and the inquiry into it will be far reaching and that no public institution will be exempt. We doubt, though, that the soul searching that has followed the publication of the inquiry report will result in corrective action against institutional racism in the NHS. McKenzie's editorial is an indication of this1: although he marshals the evidence to argue that institutional racism is very much part of the structure, procedures, and culture in the NHS, …
Human airway monohydroxyeicosatetraenoic acid generation and mucus release.
Authors: Z Marom, J H Shelhamer, F Sun, M Kaliner
Journal: Journal of Clinical Investigation (1983)

The effects of 5-, 8-, 9-, 11-, 12-, and 15-monohydroxyeicosatetraenoic acid (HETE) (0.1-100 nM) on mucous glycoprotein release from cultured human airways were determined. Each of the HETE was an active secretagogue of mucus at concentrations greater than 1-10 nM with 12- and 15-HETE, the most active. Both 5- and 9-hydroperoxyeicosatetraenoic acid (HPETE) were also active as secretagogues at 100 nM, although of somewhat lower potency. As cultured airways were capable of responding to HETE with mucous glycoprotein release, it was of interest to identify and quantitate airway HETE formation. Accordingly, airways were incubated with tracer quantities of [14C]arachidonate for 16-48 h, and the spontaneous formation of 5-, 12- and 11- and/or 15-HETE was measured by high-pressure liquid chromatography. Indeed, sizeable quantities of 11- and/or 15- greater than 5- greater than 12-HETE were generated. This HETE generation was increased by the addition of 25 micrograms/ml of arachidonate and was reduced somewhat after 18-21 d in continuous tissue culture. Reversed anaphylaxis of human airways using anti-human IgE markedly increased the HETE formation, resulting in the production of micromolar concentrations of 5- and 11- and/or 15-HETE. Thus, human airways not only are capable of responding to the presence of HETE with mucous glycoprotein release, but also generate (both spontaneously and in response to anaphylaxis) at least three species of HETE, and do so in quantities capable of acting as mucus secretagogues.
DEFINITION AND AETIOLOGY OF ECZEMA.*
Authors: JOHN T. INGRAM
Journal: British Journal of Dermatology (1935)

Journal Article DEFINITION AND ÆTIOLOGY OF ECZEMA. Get access JOHN T. INGRAM, M.D.Lond., M.R.C.P. Lond JOHN T. INGRAM, M.D.Lond., M.R.C.P. Lond Physician in Charge of the Skin‐Department, General Infirmary, Leeds: Lecturer on Diseases of the Skin, University of Leeds Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 47, Issue 12, 1 December 1935, Pages 502–511, https://doi.org/10.1111/j.1365-2133.1935.tb10245.x Published: 01 December 1935
Perinatal antibiotic treatment affects murine microbiota, immune responses and allergic asthma
Authors: Shannon L. Russell, Matthew J. Gold, Benjamin P. Willing, Lisa Thorson, Kelly M. McNagny, Brett B. Finlay
Journal: Gut Microbes (2013)

There is convincing evidence from recent human and animal studies that suggests the intestinal microbiota plays an important role in regulating immune responses associated with the development of allergic asthma, particularly during early infancy. Although identifying the mechanistic link between host-microbe interactions in the gut and lung mucosal tissues has proved challenging, several very recent studies are now providing significant insights. We have shown that administering vancomycin to mice early in life shifts resident gut flora and enhances future susceptibility to allergic asthma. This effect was not observed in mice given another antibiotic, streptomycin, nor when either antibiotic was administered to adult mice. In this addendum, we further analyze the link between early life administration of vancomycin and future susceptibility to asthma and describe how specific immune cell populations, which have been implicated in other asthma-related microbiota studies, are affected. We propose that shifts in gut microbiota exacerbate asthma-related immune responses when they occur shortly after birth and before weaning (perinatal period), and suggest that these effects may be mediated, at least in the case of vancomycin, by elevated serum IgE and reduced regulatory T cell populations.
A quantitative analysis of T lymphocyte populations in human liver allografts undergoing rejection: The use of monoclonal antibodies and double immunolabeling
Authors: Geoffrey W. McCaughan, Stewart J. Davies, Jenny A. Waugh, Alex G. Bishop, Bruce M. Hall, Neil D. Gallagher, John F. Thompson, Ross A. G. Sheil, Dorothy M. Painter
Journal: Hepatology (1990)

The aim of this study was to quantitate T-cell populations infiltrating portal tracts, bile ducts and hepatic lobules in 82 biopsy specimens from 25 patients after orthotopic liver transplantation. Biopsy specimens taken immediately after revascularization of the graft were used as controls. Patients studied include 18 with initial rejection episodes, 11 with unresolved rejection, five with vanishing bile duct syndrome and eight patients with other forms of liver injury. Quantitation was done in a blinded fashion for the first 20 biopsy specimens. A double immunolabeling technique was used to simultaneously immunolabel bile duct structures (with anti-major histocompatibility complex class II or antikeratins) and lymphoid populations (with anti-CD2, anti-CD4 or anti-CD8). This facilitated the accurate quantitation of intraepithelial lymphocytes within bile ducts. This technique also enabled simultaneous detection of CD4 and CD8 antigens on lymphocytes in portal tracts. The predominant lymphocyte subtype within biliary epithelium during acute and chronic rejection was of the CD2+/CD8+ phenotype. CD8+/CD4+ ratio in bile ducts was approximately 5:1 in acute, unresolved and chronic rejection. In vanishing bile duct syndrome, double immunolabeling enabled the detection of destroyed interlobular bile duct remnants that were not apparent on routine hematoxylin and eosin staining. Attached to some of these structures were CD8+ lymphocytes. Lobular CD8+ cells were not prominent in acute rejection but increased significantly in biopsy specimens from patients with unresolved and chronic rejection. In chronic rejection, a selective increase was seen in these CD8+ cells in centrizonal regions. In contrast, portal tract T-cell numbers decreased in nonresolving and chronic rejection biopsy specimens compared with acute rejection specimens. CD8+ and CD4+ T cells were present in approximately equal numbers in such infiltrates. It is concluded that in the evolution from acute to chronic rejection a selective accumulation of CD8+/CD2+ cells occurs in the biliary epithelium and hepatic lobules. The role of these cells in the actual pathogenetic process of hepatic allograft rejection remains to be established. (HEPATOLOGY 1990;12:1305-1313).
New Dutch health minister will need to compromise
Authors: T Sheldon
Journal: BMJ (1994)

A senior figure in Dutch medicine has been appointed to steer health services through the conflicting demands of a coalition government formed last week. As the Netherlands' new health minister, Professor Els Borst-Eilers has the task of picking up the pieces of reforms to the health insurance system, saving £430m in four years, and maintaining the quality and breadth of services.

Professor Borst-Eilers trained as a doctor before pursuing an academic career in immunology. She was medical director of Utrecht University Hospital for 13 years and since 1986 has been deputy chairperson of the health council, a government scientific advisory body. She has argued through the council that the use of new medical …
Association of Exposure to Violence and Potential Traumatic Events With Self-reported Physical and Mental Health Status in the Central African Republic
Authors: Patrick Vinck
Journal: JAMA (2010)

For decades, the Central African Republic (CAR) has experienced violence, economic stagnation, and institutional failure. The latest wave of violence erupted in 2001 and continues to this day in some areas. Yet there has been little attention to the conflict and even less research to document and quantify the conflict's human cost.To study levels of violence in CAR, including mortality levels, and the association between exposure to violence and traumatic events with self-reported physical and mental health status.Multistage stratified cluster random survey of 1879 adults 18 years or older in selected households conducted in 5 administrative units of CAR (3 in the south, which has been free from recent violence, and 2 in the north, in which violence continues) between October and December 2009.Mortality, morbidity, exposure to potential traumatic events, sense of insecurity, and meeting of symptom criteria for depression and anxiety using the Hopkins Symptom Checklist-25 with a cut-off score of 1.75.The crude mortality rate (CMR) was 4.9 deaths (95% confidence interval [CI], 4.6-5.1) per 1000 population per month and self-reported CMR due to violence was 0.8 deaths (95% CI, 0.6-1.0) per 1000 population per month. Thirty-five percent reported their physical health status as being good or very good while 29% described it as bad or very bad. Respondents in northern prefectures reported higher rates of mortality, exposure to trauma, and insecurity and lower levels of physical health and access to health services compared with those in the south. The estimated prevalences of symptoms of depression and anxiety were 55.3% (95% CI, 51.6%-59.0%) and 52.5% (95% CI, 48.1%-56.8%), respectively. Exposure to violence and self-reported physical health were statistically associated with mental health outcomes (P < .001). Anxiety symptom scores were higher for respondents in the northern prefectures than those in the south (t = 2.54, P = .01).A high proportion of adult respondents in CAR reported witnessing or having personally experienced traumatic events over the course of the conflicts, and more than half met symptom criteria for depression and anxiety.
Factors influencing anthralin erythema
Authors: LENNART JUHLIN
Journal: British Journal of Dermatology (1981)

Journal Article Factors influencing anthralin erythema Get access LENNART JUHLIN LENNART JUHLIN Department of Dermatology, University Hospital, 750 14 Uppsala, Sweden Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 105, Issue s20, 1 August 1981, Pages 87–91, https://doi.org/10.1111/j.1365-2133.1981.tb01018.x Published: 01 August 1981
Antenatal diagnosis of Down's syndrome.
Authors: M R Gaudoin
Journal: BMJ (1993)

aims in our new curriculum.Firstly, in relation to communication skills it addresses the develop- ment of students' skills in self awareness and reflective learning.Secondly, the workbook en- courages the students to understand their patient as a complex person whose health and wellbeing depend on more than biomedical considerations.The depth and extent of this understanding have been shown in some work of exceptional quality and insight.We believe that the integrated workbook assign- ment embodies the ideals of our curriculum and, in particular, has considerable potential for continuing the General Medical Council's recommended strands of ethics, law, behavioural science, and communication skills throughout the clinical course.
Long-term alterations of colonic nerve-mast cell interactions induced by neonatal maternal deprivation in rats
Authors: F. Barreau, C. Salvador-Cartier, E. Houdeau, L. Bueno, J. Fioramonti
Journal: Gut (2008)

Neonatal maternal deprivation induces colonic alterations in adult rats, such as hypersensitivity to distension or an increase in paracellular permeability, characteristics of irritable bowel syndrome (IBS) patients. Recent studies described neuroimmune alterations in the colonic mucosa of IBS patients.Male Wistar rats were submitted to maternal deprivation for 3 h daily during postnatal days 2-14, and were sacrificed at 4 or 12 weeks of age. Control pups were left undisturbed with their dam.Colonic mast cell hyperplasia was observed at 4 and 12 weeks in maternally deprived rats, and was associated with an increase in protease content. Mucosal nerve fibre density assessed by protein gene product (PGP) 9.5 immunoreactivity was increased at 12 weeks but not at 4 weeks, while calcitonin gene-related protein (CGRP)-immunoreactive fibres remain constant. Synaptogenesis assessed by synaptophysin immunostaining was increased at 4 weeks but not at 12 weeks. The number of mast cells in close proximity to PGP 9.5- or CGRP-immunoreactive fibres was greater at both 4 and 12 weeks. Expression of neurokinin NK(1) receptors in the spinal cord was enhanced at 12 weeks. No significant change in total mast cell number, PGP 9.5 immunoreactivity and mast cells associated with PGP 9.5-immunoreactive fibres was observed in the jejunum. Treatment of pups with anti-nerve growth factor (NGF) antibodies abolished the increases in synaptogenesis and in the number of mast cells in close proximity to nerve fibres observed 4 weeks after maternal deprivation.Neonatal maternal deprivation induces closer association of colonic mast cells with nerves, which is similar to that seen in IBS patients. NGF is a possible mediator of this effect.
Effects of Stimulus Intensity and Electrode Placement on the Efficacy and Cognitive Effects of Electroconvulsive Therapy
Authors: H A Sackeim, J Prudic, D P Devanand, J E Kiersky, L Fitzsimons, B J Moody, M C McElhiney, E A Coleman, J M Settembrino
Journal: New England Journal of Medicine (1993)

The efficacy of electroconvulsive therapy in major depression is established, but the importance of the electrical dosage and electrode placement in relation to efficacy and side effects is uncertain.
And what of human musicality?
Authors: Michael P. Lynch
Journal: Behavioral and Brain Sciences (1996)

Abstract The hypothesized brain evolution and preconditions for language may have allowed for the emergence of musicality either simultaneously with or before the emergence of language. Music and language are parallel in their hierarchical, temporally organized structure, and the evolution of hierarchical representation in hominids may have provided the basis for musical representation. Because music could have been produced manually or vocally before the production of spoken language, it remains possible that language emerged from music and that music thus served as a communicative precursor to language.
Anticalmodulin autoantibody in liver diseases: A new antibody against a cytoskeleton-related protein
Authors: Yusei Ikeda, Gotaro Toda, Naoaki Hashimoto, Shin-Ichi Aotsuka, Ryuichi Yokohari, Toshiyuki Maruyama, Hiroshi Oka
Journal: Hepatology (1987)

An ELISA has been developed for detection of auto-antibodiees against calmodulin. There was a significantly increased frequency (63.1%) of autoantibodies against calmodulin in 103 patients with chronic liver diseases as compared to that (30%) of patients with systemic lupus erythematosus and to that (6.9%) of normal subjects (p &lt; 0.01). IgG autoantibodies against calmodulin were detected in the patients with acute hepatitis (37.9%), chronic liver disease (45.6%) and also in the patients with systemic lupus erythematosus (30%). IgM autoantibodies against calmodulin were frequently found in patients with liver cirrhosis (52.2%), primary biliary cirrhosis (50%) and autoimmune chronic active hepatitis (38.7%), but rarely in patients with acute hepatitis (13.8%), chronic persistent hepatitis (9.5%) and systemic lupus erythematosus (0%). IgA autoantibodies against calmodulin were frequently found in liver cirrhosis (33.3%), primary biliary cirrhosis (452.9%) and autoimmune chronic active hepatitis (53.6%), but rarely in chronic persistent hepatitis (15.8%), chronic active hepatitis (14.3%) and systemic lupus erythematosus (0%). The occurrences of autoantibodies against calmodulin correlated neither with those of antismooth muscle antibody, antinculear antibody and antimitochondrial antibody, nor with serum IgG concentrations. Autoantibodies against calmodulin did not cross-react with troponin, myosin light chain, calf thymus DNA and actin. The titer of autoantibodies against calmodulin was decreased by absorption of serum with calmodulin and the liver plasma membrane fraction. The immunoblotting experiment revealed the bidning of autoantibodies against calmodulin to calmodulin. IgG fraction from a patient with autoimmune chronic active hepatitis inhibited the activation of phosphodiesterase by calmodulin. These results provide us with valuable information to elucidate the immunological abnormality in liver diseases.
A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans
Authors: Nikolay L Malinin, Li Zhang, Jeongsuk Choi, Alieta Ciocea, Olga Razorenova, Yan-Qing Ma, Eugene A Podrez, Michael Tosi, Donald P Lennon, Arnold I Caplan, Susan B Shurin, Edward F Plow, Tatiana V Byzova
Journal: Nature Medicine (2009)