tbuckley/cabot-search huggingface dataset:
Wnt pathway activation functionally reprograms human antigen-specific T cells
Authors: Yen-Ling Chiu, Bo-yi Sung, Catherine Bessell, Mathias Oelke, Jonathan Schneck
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Polyfunctionality is a hallmark of protective immunity, yet the molecular mechanisms governing polyfunctional T cells are poorly understood. After TCR activation, naïve CD8+ T cells undergo proliferation and differentiation, which lead to effector functions and memory subset
Epidemic Anterior Poliomyelitis in South Derbyshire
Authors: J. H. Moir
Journal: BMJ (1911)

THBBIRMISH I6being caused on raising the head, or on attempting to straighten the legs."On admiission (October 15th), the retraction and the pains had subsided, but on attempting any passive flexion of the legs the boy at once twisted over to the opposite side, sharply arching his back, though he could bear them fully extended if lying on his back.Any attempt to obtain Kernig's sign produced this curious contraction of the spinal muscles, and was evidently very painful.
The Constitutional Right to Health Care
Authors: William J. Curran
Journal: New England Journal of Medicine (1989)

During the halcyon days of the populist political movements of the 1960s, much was said about the need for a broad-based program of publicly financed health care for all Americans. After the defeat of legislation to create such a system during the 1960s and 1970s, the idea of national health care received less and less attention. In the more conservative atmosphere of the early 1980s, no serious efforts to establish a national health care plan were advanced. In 1988, however, interest in the subject increased with the enactment of a universal health care bill in one state—Massachusetts. This column examines . . .
The developing scene: ten-year review of a psychiatric hospital population.
Authors: D F Early, M Nicholas
Journal: BMJ (1971)

An initial survey was carried out in Glenside Hospital in 1960 because it was felt that  large proportion of all patients under care in mental hospitals show no serious disturbance of behaviour, and their retention is determined largely by social factors.1 That survey was followed four years later by a similar review,2 which recommended a precise overall national plan for the future of mental hospitals with local planning in consultation with individual hospitals. The present paper reports the situation in 1970.
Points for pain: waiting list priority scoring systems
Authors: R. T. Edwards
Journal: BMJ (1999)

Doctors have long worried that the British government's emphasis on the number of people on waiting lists, and the time they spend there, obscures the need to treat patients according to clinical urgency. This concern has been voiced most recently in a report from the BMA,1 2 though others have gone further and pointed to the futility of pursuing policies to reduce, or even abolish, waiting lists.3 4 The BMA warns that additional funds earmarked for reducing NHS waiting lists and waiting times will provide an incentive for operating on large numbers of minor cases, leaving more urgent cases and potentially cost effective treatments to wait. The danger with such initiatives is that they provide only temporary relief and do not address the underlying problem of ensuring that waiting lists operate as an efficient and equitable non-price rationing mechanism. The BMA paper argues in favour of priority scoring systems, such as those developed for elective health care in New Zealand, Canada, and Sweden. 5 6 7 The success of such systems seems, however, to be mixed.

In New Zealand an evaluation of the generic surgical priority criteria at Auckland Hospital showed wide variation and poor agreement between the surgeons' clinical judgment in assessing priority and the score patients obtained on the priority score.8 In Sweden a central …
ATP-Sensitive Potassium Channels — Neonatal Diabetes Mellitus and Beyond
Authors: Mark A. Sperling
Journal: New England Journal of Medicine (2006)

The revolution in molecular biology has led to widespread appreciation of a principle first described by the British physician A.E. Garrod approximately 100 years ago — that "inborn errors of metabolism" teach us much about human biology in health and disease. Neonatal diabetes mellitus is a prime example of this principle.Neonatal diabetes mellitus is rare, with a reported incidence of 1 per 500,000 newborns and an estimated incidence of 1 per 100,000 newborns (Hattersley A: personal communication). Most newborns with neonatal diabetes mellitus are born with intrauterine growth restriction (IUGR). The degree of IUGR is proportional to the degree . . .
Identification of Genomic Predictors of Atrioventricular Conduction
Authors: Joshua C. Denny, Marylyn D. Ritchie, Dana C. Crawford, Jonathan S. Schildcrout, Andrea H. Ramirez, Jill M. Pulley, Melissa A. Basford, Daniel R. Masys, Jonathan L. Haines, Dan M. Roden
Journal: Circulation (2010)

Recent genome-wide association studies in which selected community populations are used have identified genomic signals in SCN10A influencing PR duration. The extent to which this can be demonstrated in cohorts derived from electronic medical records is unknown.
Comparison of nucleolar organiser regions and DNA flow cytometry in the evaluation of pleural effusion.
Authors: M S Huang, M S Tsai, J J Hwang, T H Wang
Journal: Thorax (1994)

BACKGROUND--In conventional cytological diagnosis of pleural effusions the assessment of morphological features plays an important part. However, false negative and false positive results may occur. In this study conventional cytology was compared with flow cytometric DNA analysis and the argyrophil staining technique for nucleolar organiser regions (AgNOR) to characterise benign and malignant effusions. METHODS--Pleural effusions from 71 patients (38 with benign lung disease, 33 with proven adenocarcinoma of lung) were studied by conventional cytology, flow cytometric DNA analysis, and the AgNOR technique. Tumour cell ploidy was determined by flow cytometry. In an attempt to detect the cell proliferative state, flow cytometric S phase fraction and the AgNOR technique were used. The correlations among conventional cytology, flow cytometric DNA ploidy, S phase fraction analysis, and nucleolar organiser regions were investigated. RESULTS--All the 38 benign pleural effusions were diploid. There were 17 (52%) aneuploid and 16 (48%) diploid malignant pleural effusions. Based on these results this type of DNA analysis had a sensitivity of 52% and a specificity of 100%. The mean (SD) numbers of flow cytometric S phase fractions of benign and malignant cases were 5.32 (1.67)% and 12.45 (3.93)% respectively. The mean numbers of S phase fractions of diploid malignant cases were higher than diploid benign cases. In each case the number of AgNORs was counted in 100 cells. The mean number of AgNOR dots per nucleus was 12.57 (3.64) for malignant pleural effusion cells and 3.96 (1.39) for benign pleural effusion cells. The mean number of AgNOR dots was 14.45 (3.36) for aneuploid malignant pleural effusion cells and 10.57 (2.82) for diploid malignant pleural effusion cells. The AgNOR numbers were higher in diploid malignant cells than in diploid benign cells. There was a significant correlation between the S phase fraction determined by flow cytometry and the mean number of AgNORs per nucleus in malignant cases. CONCLUSIONS--Both flow cytometry and the AgNOR methods provide comparable measurements in the diagnosis of pleural effusion. The study also indicates that the AgNOR method, which is rapid and easy to perform, may be a useful adjunct to flow cytometry, S phase fraction analysis and conventional cytology in the routine diagnosis of malignant pleural effusion.
Dose-Dependent Association between UGT1A1*28 Genotype and Irinotecan-Induced Neutropenia: Low Doses Also Increase Risk
Authors: Zhe-Yi Hu, Qi Yu, Qi Pei, Cheng Guo
Journal: Clinical Cancer Research (2010)

Abstract Purpose: A previous meta-analysis showed that the association between the UGT1A1*28 genotype and irinotecan-induced neutropenia was influenced by irinotecan dose and that the risk of neutropenia was similar at low doses for patients with all genotypes. However, the sample sizes for the low- and high-dose groups were small. Because additional studies have now been reported, an updated and refined meta-analysis is needed. Experimental Design: Meta-analyses were done to assess the relationship between UGT1A1*28 and neutropenia. The association between UGT1A1*28 and the relative extent of glucuronidation (REG) of SN-38 was also examined. The studies included were stratified into different dose groups. Results: A total of 1,998 patients were included for the analysis of neutropenia and 581 patients were included for REG. The risk of neutropenia at low doses was significantly higher among patients with a UGT1A1*28/*28 genotype than among those carrying the UGT1A1*1 allele(s) [relative risk (RR), 2.43; 95% confidence interval, 1.34-4.39; P = 0.003]. In addition, the RR of neutropenia at low doses was comparable with that at medium doses (2.43 versus 2.00). The RR of neutropenia at high doses was significantly higher than that at low and medium doses (7.22 versus 2.04). We found the weighted mean difference of REG (UGT1A1*1/*1 or UGT1A1*1/*28 versus UGT1A1*28/*28) increased with increasing dose of irinotecan. Conclusions: In conclusion, the UGT1A1*28/*28 genotype was associated with an increased risk of neutropenia not only at medium or high doses of irinotecan but also at low doses. The dose-dependent manner of SN-38 glucuronidation explained why the association between UGT1A1*28 and neutropenia was dose dependent. Clin Cancer Res; 16(15); 3832–42. ©2010 AACR.
Increased serum levels of soluble triggering receptor expressed on myeloid cells-1 in antineutrophil cytoplasmic antibody-associated vasculitis
Authors: T Daikeler, S Regenass, A Tyndall, M M Gencay, M Roth, M Christ-Crain, B Muller, C Hess
Journal: Annals of the Rheumatic Diseases (2007)

Antineutrophil cytoplasmic antibody-associated (ANCA) vasculitis (AAV) is characterised by necrotising inflammation of small vessel walls, largely due to the accumulation and activation of neutrophils. Disease activity can be difficult to assess.1

Triggering receptor expressed on myeloid cells-1 (TREM-1) is an activating receptor expressed on neutrophils and monocytes recruited into sites of bacterial infection.2 3 By contrast, in a number of non-infectious inflammatory diseases (immune complex vasculitis, psoriasis associated arthritis), infiltrating neutrophils were found to lack significant expression of TREM-1.2 A soluble form of TREM-1 (sTREM-1) is shed from the membrane of activated phagocytes, and has been suggested as a …
The induction of hapten-specific immunological tolerance and immunity in B lymphocytes. VI. Differential tolerance susceptibility in adult spleen as a function of B-cell maturation level.
Authors: J M Fidler
Journal: The Journal of Experimental Medicine (1979)

The maturation level of the B-lymphocyte subpopulations involved in trinitrophenyl (TNP)-specific immunological tolerance in adult mice induced by the injection of trinitrobenzenesulfonic acid (TNBS) was investigated using in vitro antigen-specific and nonspecific polyclonal stimulation. The maturity of the B-cell subsets being studied was defined by the antigen or polyclonal activator which evoked a response. Thus, the thymic independent (TI-1) antigen TNP-lipopolysaccharide (TNP-LPS) and the polyclonal stimulant LPS were used to activate immature, neonatal-type B lymphocytes, whereas mature, adult-type B cells were responsive to the TI-2 antigen, TNP-Ficoll, and the nonspecific activator, purified protein derivative (PPD). Whereas unresponsiveness in TNP-LPS-reactive (immature) B cells 4 d after TNBS treatment was previously shown to be the result of functional deletion, partially reversible receptor blockade was detected in this study early after tolerogen treatment. By the 24-h point, tolerance was irreversible, as assessed by 24-h of antigen-free incubation and cocultivation of tolerant cells with control splenocytes. Tolerance was induced more rapidly in immature, TI-1 B cells than in mature TI-2 B lymphocytes. B lymphocytes reactive to TNP-Ficoll were also less susceptible to receptor blockade. Using LPS as a nonspecific probe for immature B cells, 60% tolerance in high affinity TNP-specific cells was induced within 12 h of TNBS treatment, and complete unresponsiveness by 24 h. In contrast, no significant decrease in response to the mature B-cell activator, PPD, occurred until day 2. Furthermore, the 50% tolerance level was achieved in TNP-specific LPS-reactive B cells by 100 times less tolerogen than required for PPD-responsive cells. Thus, TNBS-induced unresponsiveness in cells reactive to TNP-LPS is initially a result of reversible receptor blockade which leads within 4 d to functional deletion. Immature, TI-1 B lymphocytes, which give polyclonal responses to LPS and antigen-specific responses to TNP-LPS, are rendered tolerant to TNBS more rapidly and at lower tolerogen does than mature, TI-2 mouse B cells which react polyclonally to PPD and specifically to TNP-Ficoll. Moreover, these data show that both the immature and the mature B lymphocyts with these characteristic tolerance susceptibilities and specific and nonspecific immune response patterns are present in the adult mouse spleen.
Dying to get home
Authors: Des Spence
Journal: BMJ (2007)

I love London—its size, the crush of all the world's humanity, the onslaught on the senses. I love watching all the people and wondering about their lives and stories. But most of all I love the anonymity, the freedom. It was a similar experience when I used to walk the hospital wards: vast institutions and thousands of people wandering the corridors with their own lives and stories. I was constantly on the move; different wards, different specialists, and different hospitals. Tired and irritable, I often …
The Moral Domain of the Medical Record: The Routine Ethics Evaluation
Authors: Alfred I. Tauber
Journal: The American Journal of Bioethics (2006)

The structure, content, and orientation of the contemporary medical record inadequately reflect the appropriate influence of patients' rights and bioethics on health care. Most tellingly, the medical chart reveals a remarkable absence of attention to medical ethics, except in the case of crisis management. But medical ethics informs both crisis decision-making and virtually all clinical interventions. Indeed, clinical care embodies a complex array of choices influenced by individual and cultural values, themselves reflecting religious beliefs, personal histories, psychologies, and social mores. But the typical medical chart, which records clinical descriptions, analyses, and rationales for treatment, rarely identifies or accounts for this value-laden dimension of care and thus both over-simplifies and distorts the depiction of a patient's illness and its treatment. To better reflect the complex moral domain of clinical care, and assist in organizing its complex structure, a systematic procedure is proposed here to evaluate the ethical status of every patient: As a routine part of the clinical evaluation, in a designated Ethical Concerns section of the medical record, an "ethics work-up' is designed to serve as a moral 'diagnostic' analogous to its scientific counterpart. Adapted to the needs of individual patients, such evaluations should identify ethical problems, coordinate related data, resources, and opinion, and define the rationale for choices made and actions pursued. In establishing improved integration of the 'epistemologies' of care and the 'ethics' of care, the goals of a more humane, patient-centered medicine may be better met.
HIF-1α is a negative regulator of plasmacytoid DC development in vitro and in vivo
Authors: Andreas Weigert, Benjamin Weichand, Divya Sekar, Weixiao Sha, Christina Hahn, Javier Mora, Stephanie Ley, Silke Essler, Nathalie Dehne, Bernhard Brüne
Journal: Blood (2012)
Prospective multicentre study of risk factors associated with delayed healing of recurrent duodenal ulcers (RUDER). RUDER Study Group.
Authors: D Armstrong, R Arnold, M Classen, M Fischer, H Goebell, A L Blum
Journal: Gut (1993)

Risk factors for delayed duodenal ulcer healing during treatment with ranitidine (300 mg daily) were examined in a multicentre German study of 1923 patients with endoscopically proved, recurrent duodenal ulceration. Healing rates, per protocol, were 39.5% at two weeks, 70.9% at four weeks, and 93.2% at eight weeks. Prospective testing of five, predefined risk factors indicated that smoking (p = 0.0039) was associated with a decreased healing rate at two weeks. Frequent prior recurrence (p = 0.464), a heavy physical workload (p = 0.145), and psychological stress (p = 0.062) were not associated with a decreased healing rate and there were too few patients at risk to allow assessment of the effect of regular NSAID intake. Exploratory analysis identified prior slow healing, a large ulcer, multiple ulcers, and prior ulcer complications, in addition to smoking, as markers of slow healing. In the absence of these risk factors, the mean healing time was 3.3 weeks (95% confidence interval 3.0, 3.5), rising to 3.7 weeks (3.5, 3.9) for one, 4.4 weeks (4.1, 4.7) for two, and 5.1 weeks (4.5, 5.6) for three to five risk factors. Delayed duodenal ulcer healing is associated with multiple factors whose effect is cumulative; for patients with two or more of five easily identified risk factors, more than four weeks9 treatment with a histamine H2 receptor antagonist is required to achieve ulcer healing.
Exome Sequencing Extends the Phenotypic Spectrum for ABHD12 Mutations
Authors: Koji M. Nishiguchi, Almudena Avila-Fernandez, Ramon A.C. van Huet, Marta Corton, Raquel Pérez-Carro, Esther Martín-Garrido, María Isabel López-Molina, Fiona Blanco-Kelly, Lies H. Hoefsloot, Wendy A. van Zelst-Stams, Pedro J. García-Ruiz, Javier del Val, Silvio Alessandro Di Gioia, B. Jeroen Klevering, Bart P.C. van de Warrenburg, Carlos Vazquez, Frans P.M. Cremers, Blanca García-Sandoval, Carel B. Hoyng, Rob W.J. Collin, Carlo Rivolta, Carmen Ayuso
Journal: Ophthalmology (2014)
Neuron loss in the 5XFAD mouse model of Alzheimer’s disease correlates with intraneuronal Aβ42 accumulation and Caspase-3 activation
Authors: William A Eimer, Robert Vassar
Journal: Molecular Neurodegeneration (2013)

Although the mechanism of neuron loss in Alzheimer’s disease (AD) is enigmatic, it is associated with cerebral accumulation of Aβ42. The 5XFAD mouse model of amyloid deposition expresses five familial AD (FAD) mutations that are additive in driving Aβ42 overproduction. 5XFAD mice exhibit intraneuronal Aβ42 accumulation at 1.5 months, amyloid deposition at 2 months, and memory deficits by 4 months of age. Here, we demonstrate by unbiased stereology that statistically significant neuron loss occurs by 9 months of age in 5XFAD mice. We validated two Aβ42-selective antibodies by immunostaining 5XFAD; BACE1−/− bigenic brain sections and then used these antibodies to show that intraneuronal Aβ42 and amyloid deposition develop in the same regions where neuron loss is observed in 5XFAD brain. In 5XFAD neuronal soma, intraneuronal Aβ42 accumulates in puncta that co-label for Transferrin receptor and LAMP-1, indicating endosomal and lysosomal localization, respectively. In addition, in young 5XFAD brains, we observed activated Caspase-3 in the soma and proximal dendrites of intraneuronal Aβ42-labeled neurons. In older 5XFAD brains, we found activated Caspase-3-positive punctate accumulations that co-localize with the neuronal marker class III β-tubulin, suggesting neuron loss by apoptosis. Together, our results indicate a temporal sequence of intraneuronal Aβ42 accumulation, Caspase-3 activation, and neuron loss that implies a potential apoptotic mechanism of neuron death in the 5XFAD mouse.
Missed Opportunities
Authors: Sumeet Subherwal, Manesh R. Patel, Lars Kober, Eric D. Peterson, William S. Jones, Gunnar H. Gislason, Jeffrey Berger, Christian Torp-Pedersen, Emil L. Fosbol
Journal: Circulation (2012)

Patients with peripheral artery disease (PAD) are at high risk of cardiovascular events and benefit from aggressive secondary prevention; however, changes in the use of cardioprotective medications after incident diagnosis of PAD have not been well described.We used Danish nationwide administrative registries (2000-2007) to identify 2 groups with incident PAD: PAD alone (n=34 160) and PAD with history of coronary artery disease (CAD) (n=9570). With the use of a comparator with incident CAD alone (n=154 183), we assessed temporal trends and comparative use of cardioprotective medications. Relative differences in medication use were examined by using multivariable logistic regression. Use of medications improved temporally among both groups: for PAD alone, any antiplatelet use increased from 29% to 59% from 2000 to 2007 (P<0.0001), whereas statin use increased 6-fold (9%-56%; P<0.0001). However, use of these therapies by 18 months after incident diagnosis for both PAD groups remained modest and lower in comparison with CAD alone (any antiplatelet, 53% versus 66%; statins, 40% versus 52%; angiotensin-converting enzyme inhibitors, 20% versus 29%). Relative to CAD alone, patients with PAD alone were less likely to use any antiplatelet (adjusted odds ratio, 0.50; 95% confidence interval, 0.49-0.52), statins (adjusted odds ratio, 0.50; 95% confidence interval, 0.48-0.52), or angiotensin-converting enzyme inhibitors (adjusted odds ratio, 0.51; 95% confidence interval, 0.49-0.53) by 18 months.Despite improvement in the use of cardioprotective medications over time, patients with PAD alone remain less likely than those with CAD alone to use these agents.
Major sources of benzene exposure.
Authors: L A Wallace
Journal: Environmental Health Perspectives (1989)

Data from EPA's TEAM Study allow us to identify the major sources of exposure to benzene for much of the U.S. population. These sources turn out to be quite different from what had previously been considered the important sources. The most important source of exposure for 50 million smokers is the mainstream smoke from their cigarettes, which accounts for about half of the total population burden of exposure to benzene. Another 20% of nationwide exposure is contributed by various personal activities, such as driving and using attached garages. (Emissions from consumer products, building materials, paints, and adhesives may also be important, although data are largely lacking.) The traditional sources of atmospheric emissions (auto exhaust and industrial emissions) account for only about 20% of total exposure. Environmental tobacco smoke is an important source, accounting for about 5% of total nationwide exposure. A number of sources sometimes considered important, such as petroleum refining operations, petrochemical manufacturing, oil storage tanks, urban-industrial areas, service stations, certain foods, groundwater contamination, and underground gasoline leaks, appear to be unimportant on a nationwide basis.