tbuckley/cabot-search huggingface dataset:
Microarray-based gene expression profiling in patients with cryopyrin-associated periodic syndromes defines a disease-related signature and IL-1-responsive transcripts
Authors: James E Balow, John G Ryan, Jae Jin Chae, Matthew G Booty, Ariel Bulua, Deborah Stone, Hong-Wei Sun, James Greene, Beverly Barham, Raphaela Goldbach-Mansky, Daniel L Kastner, Ivona Aksentijevich
Journal: Annals of the Rheumatic Diseases (2012)

Objective To analyse gene expression patterns and to define a specific gene expression signature in patients with the severe end of the spectrum of cryopyrin-associated periodic syndromes (CAPS). The molecular consequences of interleukin 1 inhibition were examined by comparing gene expression patterns in 16 CAPS patients before and after treatment with anakinra. Methods We collected peripheral blood mononuclear cells from 22 CAPS patients with active disease and from 14 healthy children. Transcripts that passed stringent filtering criteria (p values ≤ false discovery rate 1%) were considered as differentially expressed genes (DEG). A set of DEG was validated by quantitative reverse transcription PCR and functional studies with primary cells from CAPS patients and healthy controls. We used 17 CAPS and 66 non-CAPS patient samples to create a set of gene expression models that differentiates CAPS patients from controls and from patients with other autoinflammatory conditions. Results Many DEG include transcripts related to the regulation of innate and adaptive immune responses, oxidative stress, cell death, cell adhesion and motility. A set of gene expression-based models comprising the CAPS-specific gene expression signature correctly classified all 17 samples from an independent dataset. This classifier also correctly identified 15 of 16 post-anakinra CAPS samples despite the fact that these CAPS patients were in clinical remission. Conclusions We identified a gene expression signature that clearly distinguished CAPS patients from controls. A number of DEG were in common with other systemic inflammatory diseases such as systemic onset juvenile idiopathic arthritis. The CAPS-specific gene expression classifiers also suggest incomplete suppression of inflammation at low doses of anakinra.
Conception to ongoing pregnancy: the 'black box' of early pregnancy loss
Authors: N. S. Macklon
Journal: Human Reproduction Update (2002)

Even when conditions are optimal, the maximum chance of a clinically recognized pregnancy occurring in a given menstrual cycle is 30-40%. Increasing evidence points to preclinical pregnancy loss rather than failure of conception as the principal cause for the relatively low fecundity observed in humans. While sensitive assays for hCG have provided a glimpse of the events occurring between implantation and the missed menstrual period, new cytogenetic techniques have further opened this 'black box', providing novel insights into the causes of early pregnancy wastage. In this article, the evidence and causes of preclinical or 'occult' pregnancy are reviewed, and the implications for the infertile patient are addressed.
Glucose fluctuations increase the incidence of atrial fibrillation in diabetic rats
Authors: Shotaro Saito, Yasushi Teshima, Akira Fukui, Hidekazu Kondo, Satoru Nishio, Mikiko Nakagawa, Tetsunori Saikawa, Naohiko Takahashi
Journal: Cardiovascular Research (2014)

We investigated whether glucose fluctuations aggravate cardiac fibrosis and increase the occurrence of atrial fibrillation (AF) in rats with diabetes mellitus (DM). Streptozotocin-induced diabetic rats were randomly divided into three groups: uncontrolled DM (U-STZ) group, controlled DM (C-STZ) group, and DM with glucose fluctuations (STZ-GF) group. Glucose fluctuations were induced by fasting for 24 h and additional regular insulin injections (0.5 IU/kg) administered three times per week for three consecutive weeks. C-STZ rats were administered long acting insulin (20 IU/kg) twice a day to control blood glucose levels. Cardiac fibrosis evaluated by Masson trichrome staining and the expressions of collagen type 1, collagen type 3, and α-smooth muscle actin were increased in U-STZ rats compared with C-STZ rats, which were more pronounced in STZ-GF rats. The inducibility of AF was significantly larger in U-STZ rats than C-STZ rats and was greatest in STZ-GF rats. To explore the mechanism of cardiac fibrosis, we investigated the levels of reactive oxygen species (ROS) and apoptosis. The expression of malondialdehyde, an indicator of ROS levels, was significantly upregulated in STZ-GF rats compared with U-STZ rats, along with increased thioredoxin-interacting protein (Txnip) expression in STZ-GF rats. Furthermore, caspase-3 expression and the number of TUNEL-positive cells were significantly increased in STZ-GF rats compared with U-STZ and C-STZ rats. Glucose fluctuations increase the incidence of AF by promoting cardiac fibrosis. Increased ROS levels caused by upregulation of Txnip expression may be a mechanism whereby in glucose fluctuations induce fibrosis.
Do voluntary strength, proprioception, range of motion, or postural sway predict occurrence of lateral ankle sprain?
Authors: M de Noronha, K M Refshauge, R D Herbert, S L Kilbreath
Journal: British Journal of Sports Medicine (2006)

Prevention of ankle sprain, the most common sporting injury, is only possible once risk factors have been identified. Voluntary strength, proprioception, postural sway, and range of motion are possible risk factors. A systematic review was carried out to investigate these possiblities. Eligible studies were those with longitudinal design investigating ankle sprain in subjects aged ⩾15 years. The studies had to have measured range of motion, voluntary strength, proprioception, or postural sway before monitoring incidence of lateral ankle sprain. Dorsiflexion range strongly predicted risk of ankle sprain. Postural sway and possibly proprioception were also predictors. Therefore the preliminary evidence suggests that people with reduced ankle dorsiflexion range may be at increased risk of ankle sprain.
Bmi-1 Cooperates with H-Ras to Transform Human Mammary Epithelial Cells via Dysregulation of Multiple Growth-Regulatory Pathways
Authors: Sonal Datta, Mark J. Hoenerhoff, Prashant Bommi, Rachana Sainger, Wei-Jian Guo, Manjari Dimri, Hamid Band, Vimla Band, Jeffrey E. Green, Goberdhan P. Dimri
Journal: Cancer Research (2007)

Abstract Elevated expression of Bmi-1 is associated with many cancers, including breast cancer. Here, we examined the oncogenic potential of Bmi-1 in MCF10A cells, a spontaneously immortalized, nontransformed strain of human mammary epithelial cells (HMEC). Bmi-1 overexpression alone in MCF10A cells did not result in oncogenic transformation. However, Bmi-1 co-overexpression with activated H-Ras (RasG12V) resulted in efficient transformation of MCF10A cells in vitro. Although early-passage H-Ras–expressing MCF10A cells were not transformed, late-passage H-Ras–expressing cells exhibited features of transformation in vitro. Early- and late-passage H-Ras–expressing cells also differed in levels of expression of H-Ras and Ki-67, a marker of proliferation. Subsets of early-passage H-Ras–expressing cells exhibited high Ras expression and were negative for Ki-67, whereas most late-passage H-Ras–expressing cells expressed low levels of Ras and were Ki-67 positive. Injection of late-passage H-Ras–expressing cells in severe combined immunodeficient mice formed carcinomas with leiomatous, hemangiomatous, and mast cell components; these tumors were quite distinct from those induced by late-passage cells co-overexpressing Bmi-1 and H-Ras, which formed poorly differentiated carcinomas with spindle cell features. Bmi-1 and H-Ras co-overexpression in MCF10A cells also induced features of epithelial-to-mesenchymal transition. Importantly, Bmi-1 inhibited senescence and permitted proliferation of cells expressing high levels of Ras. Examination of various growth-regulatory pathways suggested that Bmi-1 overexpression together with H-Ras promotes HMEC transformation and breast oncogenesis by deregulation of multiple growth-regulatory pathways by p16INK4a-independent mechanisms. [Cancer Res 2007;67(21):10286–95]
Concomitant presentation of two chronic leukemias: Evidence for independent clonal evolution
Authors: J. A. Vilpo, P. Klemi, O. Lassila, A. De La Chapelle
Journal: American Journal of Hematology (1980)

Abstract A case of chronic lymphocytic leukemia (CLL) occurring simultaneously with Philadelphia chromosome‐positive chronic granulocytic leukemia (CGL) in a 58‐year‐old man is described. The patient presented with typical CGL (all bone marrow mitoses having a Philadelphia chromosome), but during the course of busulfan therapy, CLL became more prominent, less than half of the bone marrow mitoses having a Philadelphia chromosome. The patient is in good clinical condition after a follow‐up of 3.5 years, and the clinical picture resembles that of typical CLL. The coexistence of CGL and CLL here may be explained by chance alone. Evidently the histogenesis of two chronic leukemias in our patient took place as an independent evolution of two malignant hematopoietic clones. In spite of the frequent association of chronic leukemias with secondary cancer, no well‐documented cases of two chronic leukemias with a simultaneous presentation have been described previously.
Optogenetic Stimulation of Adrenergic C1 Neurons Causes Sleep State–Dependent Cardiorespiratory Stimulation and Arousal with Sighs in Rats
Authors: Peter G. R. Burke, B. Stephen, Melissa B. Coates, Kenneth E. Viar, Ruth L. Stornetta, Patrice G. Guyenet
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

The rostral ventrolateral medulla (RVLM) contains central respiratory chemoreceptors (retrotrapezoid nucleus, RTN) and the sympathoexcitatory, hypoxia-responsive C1 neurons. Simultaneous optogenetic stimulation of these neurons produces vigorous cardiorespiratory stimulation, sighing, and arousal from non-REM sleep.To identify the effects that result from selectively stimulating C1 cells.A Cre-dependent vector expressing channelrhodopsin 2 (ChR2) fused with enhanced yellow fluorescent protein or mCherry was injected into the RVLM of tyrosine hydroxylase (TH)-Cre rats. The response of ChR2-transduced neurons to light was examined in anesthetized rats. ChR2-transduced C1 neurons were photoactivated in conscious rats while EEG, neck muscle EMG, blood pressure (BP), and breathing were recorded.Most ChR2-expressing neurons (95%) contained C1 neuron markers and innervated the spinal cord. RTN neurons were not transduced. While the rats were under anesthesia, the C1 cells were faithfully activated by each light pulse up to 40 Hz. During quiet resting and non-REM sleep, C1 cell stimulation (20 s, 2-20 Hz) increased BP and respiratory frequency and produced sighs and arousal from non-REM sleep. Arousal was frequency-dependent (85% probability at 20 Hz). Stimulation during REM sleep increased BP, but had no effect on EEG or breathing. C1 cell-mediated breathing stimulation was occluded by hypoxia (12% FIO2), but was unchanged by 6% FiCO2.C1 cell stimulation reproduces most effects of acute hypoxia, specifically cardiorespiratory stimulation, sighs, and arousal. C1 cell activation likely contributes to the sleep disruption and adverse autonomic consequences of sleep apnea. During hypoxia (awake) or REM sleep, C1 cell stimulation increases BP but no longer stimulates breathing.
Role conflict and confidentiality in multidisciplinary athlete support programmes.
Authors: D Collins, P Moore, D Mitchell, F Alpress
Journal: British Journal of Sports Medicine (1999)

As medical and scientific staff have increasingly been called upon to provide multidisciplinary support to elite performers the potential for ethical, professional, and legal conflicts has also increased. Although this has been recognised, little guidance has been provided to help resolve such conflicts. This paper identifies key issues in the provision of effective support and specifically addresses the roles of medical and scientific staff and their relations to coaches and performers. An athlete charter is presented that has successfully been used to resolve ethical conflicts and clarify the lines of communication, confidentiality, and responsibility within a national governing body.
The Diagnosis of Emphysema
Authors: W. M. Thurlbeck
Journal: Thorax (1964)

Pulmonary emphysema is generally defined anatomically. It follows therefore that pathologists have the best opportunity to diagnose emphysema accurately. Whether they take advantage of this opportunity may be doubted by observers interested in lung disease, and Wyatt, Fischer, and Sweet (1961) have called the usual criteria (gross inspection and palpation of the lung and microscopic examination of random sections) 'pathologic chimeras'. There are, however, no investigations concerned specifically with the accuracy of the routine pathological diagnosis of emphysema, such as have been made for its clinical (Fletcher, 1952) and radiological diagnosis (Knott and Christie, 1951). This communication investigates the accuracy of the usual pathological methods in two ways.
C<sub>2</sub>‐ceramide induces apoptosis in a human squamous cell carcinoma cell line
Authors: H. Sugiki, Y. Hozumi, H. Maeshima, Y. Katagata, Y. Mitsuhashi, S. Kondo
Journal: British Journal of Dermatology (2000)

Previous studies have demonstrated that synthetic cell-permeable analogues of ceramide promote differentiation and inhibit proliferation of keratinocytes, and that the vitamin D3 inducible sphingomyelin cycle generates ceramide in keratinocytes. Although it has been suggested that exogenous ceramide induces apoptosis of keratinocytes, which is similar to their effect on other cell types, such as leukaemia cells, only a few studies have reported ceramide-induced apoptosis of keratinocytes.To determine whether ceramide induces apoptosis of keratinocytes, we used the synthetic ceramide analogue, C2-ceramide (N-acetylsphingosine) and a human squamous cell carcinoma cell line, HSC-I.We treated HSC-I cells with C2-ceramide, followed by a viability assay, morphological observations, nick end-labelling (TUNEL), DNA electrophoresis, and electron microscopy.In the viability assay, C2-ceramide was toxic to HSC-I cells in a dose-dependent manner. Manifestations of apoptotic morphology occurred in the ceramide-treated cells, whereas these morphological changes did not occur in cells treated with dihydroceramide (N-acetylsphinganine). TUNEL revealed that many of the ceramide-treated cells showed positive reactivity. DNA electrophoresis demonstrated that C2-ceramide caused internucleosomal fragmentation in a dose- and time-dependent manner. Electron microscopy revealed that the ceramide-treated cells manifested morphological characteristics typical of apoptosis.The present results demonstrate that C2-ceramide induces apoptosis of transformed human keratinocytes, whereas C2-dihydroceramide does not have such an effect. The fact that ceramide induces apoptosis of keratinocyctes raises the possibility that intracellular ceramide, which is increased with differentiation of the epidermis, might be involved in terminal differentiation, a specialized form of apoptosis of keratinocytes.
CYTOTOXICITY MEDIATED BY SOLUBLE ANTIGEN AND LYMPHOCYTES IN DELAYED HYPERSENSITIVITY
Authors: Nancy H. Ruddle, Byron H. Waksman
Journal: The Journal of Experimental Medicine (1968)

The cytopathic effect of lymph node cells from tuberculin-sensitized rats on rat embryo fibroblasts in the presence of PPD was not enhanced by admixture of normal (nonsensitized) lymph node cells. Preincubation studies showed that this in vitro response is initiated by the reaction of lymphocytes with specific antigen, beginning within 30 min, rather than uptake of antigen by the fibroblasts. The supernatant fluids from suspensions of sensitized cells incubated with PPD for 17 hr or more possessed cytotoxic activity. The target fibroblasts showed a marked increase in acid phosphatase content within 48 hr after the addition of sensitized lymph node cells and antigen.
Coexistence of acanthosis nigricans and the sign of Leser-Tr?lat in a patient with gastric adenocarcinoma: A case report and literature review
Authors: James S.M. Yeh, Stephanie E. Munn, Tim A. Plunkett, Peter G. Harper, Deborah J. Hopster, Anthony W. du Vivier
Journal: Journal of the American Academy of Dermatology (2000)
Numbers of acute and stroke consultants rise while other specialties suffer
Authors: A. O'Dowd
Journal: BMJ (2009)

The number of consultants working in acute medicine in the United Kingdom has risen by almost a quarter in a year, but numbers in other specialties have fallen, new figures show.

The latest census of consultant physicians in the UK, published on 25 November, shows that the number in the specialty of acute and general medicine rose to 259, a 23% increase on the previous year’s figure, at a time when the availability of junior doctors has dropped.

The rise reflects the increasing importance of the role of consultant physicians in medical admissions, says the report, published by the Federation of the Royal Colleges of …
Relationships between pressure and flow in the umbilical and uterine circulations of the sheep.
Authors: W Berman, R C Goodlin, M A Heymann, A M Rudolph
Journal: Circulation Research (1976)

We studied the relationship of fetal and maternal vascular pressures to umbilical and uterine blood flow in the unanesthetized ewe and in the sheep fetus in utero by placing electromagnetic flow transducers around both the common umbilical and uterine arteries. Reductions in umbilical arterial pressure or elevations in umbilical venous pressure decreased umbilical blood flow without affecting either the uterine arterial blood flow or other maternal cardiovascular variables which were studied. Elevations in uterine venous pressure or reductions in uterine arterial pressure decreased uterine arterial flow but these interventions had no effect on umbilical blood flow until fetal hypoxemia and bradycardia occurred. When the bradycardia of the fetal hypoxic response was inhibited by atropine, alterations in maternal vascular pressure had no effect on umbilical arterial flow. These data do not support the presence of a "sluice" or "waterfall" effect in the umbilical-placental circulation of the sheep fetus in utero.
How the measurement of residual volume developed after Davy (1800)
Authors: J-C. Yernault, N. Pride, G Laszlo
Journal: European Respiratory Journal (2000)

H. Davy measured the residual volume of his own lungs in 1800, by inhaling a hydrogen mixture contained in a mercurial air holder. Using the same principle, Nestor Grehant determined the functional residual capacity, and the volume of the dead space, in 1864. Both used a forced breathing method, that was substituted by a prolonged dilution method by D.D. Van Slyke and C.A.L. Binger in 1923. It was in 1941 that G.R. Meneely and M.L. Kaltreider replaced hydrogen with helium. The open circuit nitrogen washout method was proposed by R.E. Darling, A. Cournand and D.W. Richards in 1940, and the body plethysmograph by A.B. DuBois et al. in 1956. So the three methods, still in common use today for measuring the static lung volumes, had been described by the mid-1950s.
Research Design Features and Patient Characteristics Associated With the Outcome of Antidepressant Clinical Trials
Authors: Arif Khan, Russell L. Kolts, Michael E. Thase, K. Ranga Rama Krishnan, Walter Brown
Journal: American Journal of Psychiatry (2004)

The authors examined which, if any, research design features and patient characteristics would significantly differ between successful and unsuccessful antidepressant trials.Clinical trial data were reviewed for nine antidepressants approved by the Food and Drug Administration between 1985 and 2000. From the antidepressant research programs on these medications, 52 clinical trials were included in the study. The authors evaluated trial design features, patient characteristics, and difference in response between placebo and antidepressant.Nine trial design features and patient characteristics were present in the research programs for all nine of the antidepressants. The severity of depressive symptoms before patient randomization, the dosing schedule (flexible versus fixed), the number of treatment arms, and the percentage of female patients were significantly associated with the difference in response to antidepressant and placebo. The duration of the antidepressant trial, number of patients per treatment arm, number of sites, and mean age of the patients were similar in successful trials (with a greater antidepressant-placebo difference) and less successful trials (with a smaller antidepressant-placebo difference).These findings may help in the design of future antidepressant trials.
Population Health Impact and Cost-Effectiveness of Tuberculosis Diagnosis with Xpert MTB/RIF: A Dynamic Simulation and Economic Evaluation
Authors: Nicolas A. Menzies, Ted Cohen, Hsien-Ho Lin, Megan Murray, Joshua A. Salomon
Journal: PLoS Medicine (2012)

The Xpert MTB/RIF test enables rapid detection of tuberculosis (TB) and rifampicin resistance. The World Health Organization recommends Xpert for initial diagnosis in individuals suspected of having multidrug-resistant TB (MDR-TB) or HIV-associated TB, and many countries are moving quickly toward adopting Xpert. As roll-out proceeds, it is essential to understand the potential health impact and cost-effectiveness of diagnostic strategies based on Xpert.We evaluated potential health and economic consequences of implementing Xpert in five southern African countries--Botswana, Lesotho, Namibia, South Africa, and Swaziland--where drug resistance and TB-HIV coinfection are prevalent. Using a calibrated, dynamic mathematical model, we compared the status quo diagnostic algorithm, emphasizing sputum smear, against an algorithm incorporating Xpert for initial diagnosis. Results were projected over 10- and 20-y time periods starting from 2012. Compared to status quo, implementation of Xpert would avert 132,000 (95% CI: 55,000-284,000) TB cases and 182,000 (97,000-302,000) TB deaths in southern Africa over the 10 y following introduction, and would reduce prevalence by 28% (14%-40%) by 2022, with more modest reductions in incidence. Health system costs are projected to increase substantially with Xpert, by US$460 million (294-699 million) over 10 y. Antiretroviral therapy for HIV represents a substantial fraction of these additional costs, because of improved survival in TB/HIV-infected populations through better TB case-finding and treatment. Costs for treating MDR-TB are also expected to rise significantly with Xpert scale-up. Relative to status quo, Xpert has an estimated cost-effectiveness of US$959 (633-1,485) per disability-adjusted life-year averted over 10 y. Across countries, cost-effectiveness ratios ranged from US$792 (482-1,785) in Swaziland to US$1,257 (767-2,276) in Botswana. Assessing outcomes over a 10-y period focuses on the near-term consequences of Xpert adoption, but the cost-effectiveness results are conservative, with cost-effectiveness ratios assessed over a 20-y time horizon approximately 20% lower than the 10-y values.Introduction of Xpert could substantially change TB morbidity and mortality through improved case-finding and treatment, with more limited impact on long-term transmission dynamics. Despite extant uncertainty about TB natural history and intervention impact in southern Africa, adoption of Xpert evidently offers reasonable value for its cost, based on conventional benchmarks for cost-effectiveness. However, the additional financial burden would be substantial, including significant increases in costs for treating HIV and MDR-TB. Given the fundamental influence of HIV on TB dynamics and intervention costs, care should be taken when interpreting the results of this analysis outside of settings with high HIV prevalence.