tbuckley/cabot-search huggingface dataset:
Fibrinogen binding to the integrin αIIbβ3 modulates store-mediated calcium entry in human platelets
Authors: Juan A. Rosado, Else M. Y. Meijer, Karly Hamulyak, Irena Novakova, Johan W. M. Heemskerk, Stewart O. Sage
Journal: Blood (2001)

Abstract Effects of the occupation of integrin αIIbβ3 by fibrinogen on Ca++signaling in fura-2–loaded human platelets were investigated. Adding fibrinogen to washed platelet suspensions inhibited increases in cytosolic [Ca++] concentrations ([Ca++]i) evoked by adenosine diphosphate (ADP) and thrombin in a concentration-dependent manner in the presence of external Ca++ but not in the absence of external Ca++ or in the presence of the nonselective cation channel blocker SKF96365, indicating selective inhibition of Ca++entry. Fibrinogen also inhibited store-mediated Ca++ entry (SMCE) activated after Ca++ store depletion using thapsigargin. The inhibitory effect of fibrinogen was reversed if fibrinogen binding to αIIbβ3 was blocked using RDGS or abciximab and was absent in platelets from patients homozygous for Glanzmann thrombasthenia. Fibrinogen was without effect on SMCE once activated. Activation of SMCE in platelets occurs through conformational coupling between the intracellular stores and the plasma membrane and requires remodeling of the actin cytoskeleton. Fibrinogen inhibited actin polymerization evoked by ADP or thapsigargin in control cells and in cells loaded with the Ca++ chelator dimethyl BAPTA. It also inhibited the translocation of the tyrosine kinase p60src to the cytoskeleton. These results indicate that the binding of fibrinogen to integrin αIIbβ3 inhibits the activation of SMCE in platelets by a mechanism that may involve modulation of the reorganization of the actin cytoskeleton and the cytoskeletal association of p60src. This action may be important in intrinsic negative feedback to prevent the further activation of platelets subjected to low-level stimuli in vivo.
William G. Kaelin Jr. and Gregg L. Semenza receive the 2012 ASCI/Stanley J. Korsmeyer Award
Authors: Kathryn Claiborn
Journal: Journal of Clinical Investigation (2012)

Cells are able to sense the level of oxygen in their environment and can adapt by rapidly altering expression of various genes. This capacity has both positive and negative implications; following ischemic injury, it can help promote blood vessel growth and recovery, but in cancer, new vessel growth helps sustain developing and metastasizing tumors. In the 1990s, William Kaelin Jr. and Gregg Semenza (Figure ​(Figure1)1) revolutionized the understanding of cellular oxygen sensing by identifying many of the molecular players involved. Their continuing work in the field has led to the development of successful therapeutic strategies. In April, their contributions will be celebrated as they receive the 2012 ASCI/Stanley J. Korsmeyer Award. The JCI recently spoke to Kaelin and Semenza about their path to this prize.
Ireland announces national breast screening programme
Authors: D. Payne
Journal: BMJ (1999)

Ireland has become the fourth country in Europe to introduce a national breast screening programme, after the United Kingdom, the Netherlands, and Sweden. The first phase of the recently announced scheme-which will offer free mammograms to women in the 50-64 age group- will start in October.

The scheme is being funded by the Department of Health. Initial capital funding of IR£2m ($2.8m) has been provided for the development of two central units linked to the Mater and St Vincent's …
Effect of Intermittent Cyclical Etidronate Therapy on Bone Mass and Fracture Rate in Women with Postmenopausal Osteoporosis
Authors: Tommy Storm, Gorm Thamsborg, Torben Steiniche, Harry K. Genant, Ole Helmer Sorensen
Journal: New England Journal of Medicine (1990)

Progressive bone loss in osteoporosis results from bone resorption in excess of bone formation. We conducted a double-blind study in 66 women with postmenopausal osteoporosis of therapy with etidronate, a diphosphonate compound that reduces bone resorption by inhibiting osteoclastic activity.
Towards the safer use of traditional remedies
Authors: D J Atherton
Journal: BMJ (1994)

About 80% of the world's population does not have access to Western medicine and therefore depends on traditional medical practices. When people from less developed countries emigrate they continue to seek medical advice from traditional practitioners working in their own communities, even in countries where all citizens have free access to good quality Western medicine. Though the main reasons for this are probably cultural and linguistic, the role of mistrust and fear should not be underestimated.

Large amounts of traditional medicines are imported into Britain, legally and illegally, and use of such medicines is frequently not admitted on occasions when serious illness forces patients to consult Western medical practitioners. These medicines carry with them a risk of adverse reactions; the risk needs to be quantified and as far as possible minimised.

The safer use of traditional remedies was the subject of a one day meeting held last month at the Royal Botanic Gardens, Kew, London. The meeting was organised jointly by the National Poisons Unit (based at Guy's Hospital, London), the Royal Botanic Gardens, and the International Programme on Chemical Safety. During the past three years the National Poisons Unit has taken a special interest in toxicological problems resulting from exposure to traditional medicines, and it will be publishing its findings later this year. Despite the diverse backgrounds of participants at the meeting, who ranged from doctors and pharmacologists practising in the Western allopathic tradition to practitioners within the European, Chinese, and Indian herbal traditions, a reassuring …
Human Dendritic Cells Presenting Adenovirally Expressed Antigen Elicit<i>Mycobacterium tuberculosis</i>–Specific CD8<b><sup>+</sup></b>T Cells
Authors: Deborah A. Lewinsohn, Rebecca A. Lines, David M. Lewinsohn
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Previous studies in murine and human models have suggested an important role for CD8+ T cells in host defense to Mycobacterium tuberculosis (Mtb). Consequently, a successful tuberculosis vaccine may require the elicitation of sustained CD4+ and CD8+ T cell responses. We tested the hypothesis that the potent CD4+ T cell antigen Mtb39 is also a CD8+ T cell antigen. A recombinant adenovirus–expressing Mtb39 (adenoMtb39) was used to infect monocyte-derived dendritic cells. Using interferon-γ enzyme-linked immunospot, Mtb39-specific CD8+ T lymphocytes were detected in three healthy individuals with latent tuberculosis infection who also had strong anti–Mtb39-specific CD4+ T cell responses. An Mtb39-specific CD8+ T cell line was generated using Mtb39-expressing dendritic cells. Mtb39-specific T cell clones were obtained by limiting dilution cloning. All seven T cell clones obtained were HLA-B44 restricted. Using a panel of synthetic overlapping peptides representative of Mtb39, the peptide epitope was identified for two clones. Furthermore, all T cell clones recognized Mtb-infected dendritic cells and were cytolytic. We conclude that infection of dendritic cells with adenoviral vectors expressing Mtb proteins allows for measurement of antigen-specific CD8+ T cell responses from peripheral blood mononuclear cells. The technique will be useful in defining CD8+ T cell antigens and in measuring immunogenicity of tuberculosis vaccines.
SOME OBSERVATIONS ON THE CORRECTION OF LOW DEGREES OF ASTIGMATISM.Read in the Section of Ophthalmology, at the Forty-first Annual Meeting of the American Medical Association, Nashville, Tenn., May, 1890.
Authors: T. E. MURRELL
Journal: JAMA (1890)

Perhaps no two men entertain identical views, or have like experiences in all particulars in the matter of correcting ametropia. All fixed rules must bend to the inevitable exceptions, and certain general principles only can be said to obtain upon which experience and judgment found creditable results. It was taught by Donders that it was seldom necessary to correct an astigmatism of less than 1 D. This hypothesis was based upon the practical sharpness of vision. It was considered that when vision is so nearly normal a slight error should give rise to no appreciable annoyance. Larger experience and more extended observations have led to quite different conclusions. We now know that an astigmatism so slight as to be scarcely appreciable by ordinary tests may be the source of very considerable discomfort when the eyes are much employed. Since so few eyes are absolutely free from corneal astigmatism, the question
Current approaches are failing people at risk of heart disease, conference hears
Authors: M. Limb
Journal: BMJ (2013)

The United Kingdom risks slipping further behind other European countries in tackling cardiovascular disease unless preventive and primary care approaches are radically improved, a conference has heard.

Doctors and charity leaders warned that falling mortality rates over recent years could be reversed without better targeted and coordinated strategies in the community and general practice.

Cardiovascular disease is one of the largest causes of death and disability in the UK. Experts at a seminar held in London on 23 April by the Westminster Health Forum discussed what needed to be done to improve outcomes of the disease, commissioning of services, and patients’ experiences.

Simon Gillespie, chief executive of the British Heart Foundation, said that the NHS had seen important progress in prevention and treatment …
REPAIR OF LACERATIONS OF THE CERVIX UTERI.AN INVESTIGATION AS TO THE PROPER TIME FOR THE OPERATION.
Authors: DANIEL H. CRAIG
Journal: JAMA (1903)

The following paper embodies the conclusions derived from an investigation covering one year and five months. At the outset all preformed opinions were relinquished and a true spirit of unbiased investigation prevailed. Realizing that it is far easier to teach one wholly ignorant than to controvert preformed opinions, I placed myself in the attitude of a beginner. At the outset I was a partisan of certain operative procedures and certain methods of technic, but this investigation has shown me the narrowness of this attitude. The indications for any certain procedure or technic are inherent in the individual case, not in the predilection of the operator. It is, then, a modest following of the example of Herodotus in that it is "a setting forth of investigation." As a basis of my study I carefully tabulated the results of one hundred tracheloplastic operations performed at the Free Hospital for Women. A
Vitamin A supplements and survival in children
Authors: A. M Prentice
Journal: BMJ (2010)

New evidence points to a differential effect in girls and boysIn the linked randomised controlled trial (doi: 10.1136/bmj.c1101),Benn and colleagues assess the effect of giving high dose vitamin A supplements to low birthweight neonates in GuineaBissau.Overall, they found no effect on infant mortality, although the effect differed by sex; boys tended to benefit but a significantly harmful effect was seen on girls' survival.1In 1983 it was reported that young Indonesian children with mild xerophthalmia, Bitot's spots, and night blindness-the clinical symptoms of vitamin A deficiency-had a higher risk of death.2A subsequent randomised controlled trial of vitamin A supplementation showed an impressive benefit on all cause mortality.3This prompted further large scale trials elsewhere in Asia and Africa that confirmed the effect.A metaanalysis indicated that this cheap and simple intervention reduces child mortality by 30% in countries with evidence of at least marginal vitamin A deficiency.4The World Health Organization subsequently recommended a protocol for universal vitamin A supplementation of children aged six to 60 months, and this has been adopted as government policy in more than 60 countries worldwide.
Prospective Study of Atherosclerotic Disease Progression in the Renal Artery
Authors: Michael T. Caps, Claudio Perissinotto, R. Eugene Zierler, Nayak L. Polissar, Robert O. Bergelin, Michael J. Tullis, Kim Cantwell-Gab, Robert C. Davidson, D. Eugene Strandness
Journal: Circulation (1998)

Background —The aim of this study was to determine the incidence of and the risk factors associated with progression of renal artery disease in individuals with atherosclerotic renal artery stenosis (ARAS). Methods and Results —Subjects with ≥1 ARAS were monitored with serial renal artery duplex scans. A total of 295 kidneys in 170 patients were monitored for a mean of 33 months. Overall, the cumulative incidence of ARAS progression was 35% at 3 years and 51% at 5 years. The 3-year cumulative incidence of renal artery disease progression stratified by baseline disease classification was 18%, 28%, and 49% for renal arteries initially classified as normal, &lt;60% stenosis, and ≥60% stenosis, respectively ( P =0.03, log-rank test). There were only 9 renal artery occlusions during the study, all of which occurred in renal arteries having ≥60% stenosis at the examination before the detection of occlusion. A stepwise Cox proportional hazards model included 4 baseline factors that were significantly associated with the risk of renal artery disease progression during follow-up: systolic blood pressure ≥160 mm Hg (relative risk [RR]=2.1; 95% CI, 1.2 to 3.5), diabetes mellitus (RR=2.0; 95% CI, 1.2 to 3.3), and high-grade (&gt;60% stenosis or occlusion) disease in either the ipsilateral (RR=1.9; 95% CI, 1.2 to 3.0) or contralateral (RR=1.7; 95% CI, 1.0 to 2.8) renal artery. Conclusions —Although renal artery disease progression is a frequent occurrence, progression to total renal artery occlusion is not. The risk of renal artery disease progression is highest among individuals with preexisting high-grade stenosis in either renal artery, elevated systolic blood pressure, and diabetes mellitus.
Salmonella osteomyelitis presenting as "hand-foot syndrome" in sickle-cell disease.
Authors: W J Noonan
Journal: BMJ (1982)

Sickle-cell disease is occurring more often in Britain than before. Of 70 patients with this disease in the London Borough of Brent, more than half were born in Britain.1 Homozygous sickle-cell disease commonly presents first with recurrent swelling of the hands and feet owing to bone ischaemia?the  syndrome. The severity and duration of the swelling are variable and resolve spontaneously. The course of the disease, however, may be complicated by osteomyelitis, possibly with associated septicaemia and then death, or with chronic suppura? tion and discharging sinuses. Such complications are rare in Britain. In a recent review from the Children's Hospital, Birmingham,2 no case of osteomyelitis had been recorded for 10 years. I report on a case of salmonella osteomyelitis presenting as hand-foot syndrome in an infant who has homozygous sickle cell disease.
A new approach for detecting low-level mutations in next-generation sequence data
Authors: Mingkun Li, Mark Stoneking
Journal: Genome biology (2012)

We propose a new method that incorporates population re-sequencing data, distribution of reads, and strand bias in detecting low-level mutations. The method can accurately identify low-level mutations down to a level of 2.3%, with an average coverage of 500×, and with a false discovery rate of less than 1%. In addition, we also discuss other problems in detecting low-level mutations, including chimeric reads and sample cross-contamination, and provide possible solutions to them.
Mitogens for adult rat aortic vascular smooth muscle cells in serum-free primary culture
Authors: D. J Grainger, C. M Witchell, P. L Weissberg, J. C Metcalfe
Journal: Cardiovascular Research (1994)

Journal Article Mitogens for adult rat aortic vascular smooth muscle cells in serum-free primary culture Get access David J Grainger, David J Grainger Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, United Kingdom: D J Grainger, C M Witchell, J C Metcalfe; School of Clinical Medicine, University of Cambridge, Hills Road, Cambridge: P L Weissberg. Correspondence to Dr Grainger. Search for other works by this author on: Oxford Academic PubMed Google Scholar Christine M Witchell, Christine M Witchell Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, United Kingdom: D J Grainger, C M Witchell, J C Metcalfe; School of Clinical Medicine, University of Cambridge, Hills Road, Cambridge: P L Weissberg. Search for other works by this author on: Oxford Academic PubMed Google Scholar Peter L Weissberg, Peter L Weissberg Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, United Kingdom: D J Grainger, C M Witchell, J C Metcalfe; School of Clinical Medicine, University of Cambridge, Hills Road, Cambridge: P L Weissberg. Search for other works by this author on: Oxford Academic PubMed Google Scholar James C Metcalfe James C Metcalfe Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, United Kingdom: D J Grainger, C M Witchell, J C Metcalfe; School of Clinical Medicine, University of Cambridge, Hills Road, Cambridge: P L Weissberg. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 8, August 1994, Pages 1238–1242, https://doi.org/10.1093/cvr/28.8.1238 Published: 01 August 1994 Article history Received: 03 March 1994 Accepted: 08 April 1994 Published: 01 August 1994
G Proteins — The Disease Spectrum Expands
Authors: Allen M. Spiegel
Journal: New England Journal of Medicine (2013)

G proteins (guanine nucleotide-binding proteins) are heterotrimers composed of guanosine triphosphate–binding alpha subunits and tightly linked beta and gamma subunits. They couple a vast array of receptors (G-protein–coupled receptors, the subject of the Nobel Prize in Chemistry this past year1) to effectors that regulate diverse cellular processes. Of 15 human alpha-subunit genes, some, such as GNAS, are expressed ubiquitously; others are expressed only in specialized cells. Gs (the G protein encoded by GNAS) couples many hormone and neurotransmitter receptors to cyclic AMP stimulation, and it was the first G protein to be associated with human disease. Germline . . .
Failure in community care Inpatient care is part of the integrated approach
Authors: T Burns, A Kent, S P Sashidharan, S P Singh, S O'Connor, P Birkett, J Parker, P Dedman, D Mumford, R Brown, D A Cook, J Short, D Kingham, S Arnott, P J A Willems, A Moore
Journal: BMJ (1994)

Asymptomatic hepatitis C infectionBe cautious with liver biopsy
Apathy in Schizophrenia: Reduced Frontal Lobe Volume and Neuropsychological Deficits
Authors: Robert M. Roth, Laura A. Flashman, Andrew J. Saykin, Thomas W. McAllister, Robert Vidaver
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Apathy is a common negative symptom in schizophrenia. The authors investigated neuropsychological performance and regional brain volumes in schizophrenia patients with high versus low levels of apathy. METHOD: Schizophrenia patients with low apathy levels (N=18) and high apathy levels (N=20) and 12 healthy comparison subjects completed neuropsychological testing as well as magnetic resonance imaging scanning to obtain lobar volumes after total intracranial volume was controlled. RESULTS: The high apathy group scored lower than comparison subjects on rapid visuomotor sequencing and verbal learning/recall. The high apathy group had lower performance IQ scores than the low apathy and comparison groups. Only the high apathy group showed significantly reduced bilateral frontal lobe volumes relative to comparison subjects; both schizophrenia patient groups showed bilateral temporal lobe volume reductions. CONCLUSIONS: The present findings are consistent with studies in other disorders showing frontal lobe involvement in apathy.
Fortnightly review: Drug treatment of epilepsy
Authors: M. Feely
Journal: BMJ (1999)

It is conventional to speak of someone having epilepsy, but it might be better—particularly in relation to promoting better drug treatment—if we were to think in terms of one of the epilepsies.Appropriate management requires not only that doctors differentiate between epilepsy and other similar attacks but also that they identify correctly patients' seizure types and, in some cases, the syndrome (for example, juvenile myoclonic epilepsy). A detailed discussion of the differential diagnosis is outside the scope of this review. However, it is worth emphasising that the diagnosis is usually made from the description of the episodes obtained from the patient or eyewitnesses, or both. This information is often, but not always, supported or supplemented by findings from electroencephalography. Information on diagnosis, investigations, and general principles of treatment can be found in textbooks, 1 2 and videos illustrating different types of seizure are now fairly readily available. Ideally, the diagnosis should be made or confirmed by a specialist, who will also advise on treatment. Nonetheless, doctors who do not have a specialist interest in epilepsy will often be required to take a hand in treatment. This brief review is intended primarily for them.

#### Summary points

As a clinical pharmacologist with some training in neurology, I have been running an epilepsy clinic for many years. This review is based on a synthesis of my …
Changes in type VI adenylyl cyclase isoform expression correlate with a decreased capacity for cAMP generation in the aging ventricle.
Authors: K Tobise, Y Ishikawa, S R Holmer, M J Im, J B Newell, H Yoshie, M Fujita, E E Susannie, C J Homcy
Journal: Circulation Research (1994)

We investigated the developmental regulation of the beta-adrenergic receptor-Gs-adenylyl cyclase pathway in myocardial membranes from fetal, neonatal, adult, and mature adult rats by measuring the density of the beta-adrenergic receptor and the activities of the stimulatory guanine nucleotide-binding protein Gs and the adenylyl cyclase enzyme. Total beta-adrenergic receptor content (in femtomoles per milligram protein) was greatest in the fetal (124.4 +/- 20.5 fmol/mg) and neonatal (122.3 +/- 16.1 fmol/mg) stages and gradually decreased in the adult (90.9 +/- 8.0 fmol/mg) and mature adult (70.0 +/- 9.6 fmol/mg) stages. An equivalent pattern was seen for adenylyl cyclase activity: the basal activity of the effector enzyme or that measured in the presence of 0.1 mmol/L isoproterenol with 0.1 mmol/L Gpp(NH)p, 10 mmol/L NaF, or 0.05 mmol/L forskolin was greater in the fetus and the neonate than in the adult and the mature adult. These data suggested that decreased stimulation of the catalytic unit by Gs could be the underlying cause of diminished adenylyl cyclase activity with aging. However, quantification of Gs by reconstitution into S49 cyc- membranes (in picomoles cAMP per microgram for 10 minutes) demonstrated no significant decrease during development from fetus (1.55 +/- 0.1 pmol/microgram) to neonate (1.9 +/- 0.5 pmol/microgram) and subsequent aging to adult (2.6 +/- 0.2 pmol/micrograms) and mature adult (1.9 +/- 0.2 pmol/microgram). When Northern blot analysis was used to characterize the relative amounts of mRNA coding for Gs alpha, no significant differences were seen among the developmental stages studied.(ABSTRACT TRUNCATED AT 250 WORDS)