tbuckley/cabot-search huggingface dataset:
Transcriptional Regulation of Estrogen Receptor-α by p53 in Human Breast Cancer Cells
Authors: Stephanie Harkey Shirley, Joyce E. Rundhaug, Jie Tian, Noirin Cullinan-Ammann, Isabel Lambertz, Claudio J. Conti, Robin Fuchs-Young
Journal: Cancer Research (2009)

Estrogen receptor alpha (ER) and p53 are critical prognostic indicators in breast cancer. Loss of functional p53 is correlated with poor prognosis, ER negativity, and resistance to antiestrogen treatment. Previously, we found that p53 genotype was correlated with ER expression and response to tamoxifen in mammary tumors arising in mouse mammary tumor virus-Wnt-1 transgenic mice. These results lead us to hypothesize that p53 may regulate ER expression. To test this, MCF-7 cells were treated with doxorubicin or ionizing radiation, both of which stimulated a 5-fold increase in p53 expression. ER expression was also increased 4-fold over a 24-h time frame. In cells treated with small interfering RNA (siRNA) targeting p53, expression of both p53 and ER was significantly reduced (>60%) by 24 h. Induction of ER by DNA-damaging agents was p53 dependent as either ionizing radiation or doxorubicin failed to up-regulate ER after treatment with p53-targeting siRNA. To further investigate whether p53 directly regulates transcription of the ER gene promoter, MCF-7 cells were transiently transfected with a wild-type (WT) p53 expression vector along with a luciferase reporter containing the proximal promoter of ER. In cells transfected with WT p53, transcription from the ER promoter was increased 8-fold. Chromatin immunoprecipitation assays showed that p53 was recruited to the ER promoter along with CARM1, CBP, c-Jun, and Sp1 and that this multifactor complex was formed in a p53-dependent manner. These data show that p53 regulates ER expression through transcriptional control of the ER promoter, accounting for their concordant expression in human breast cancer.
Disorganised electrical activity in a child with idiopathic intestinal pseudo-obstruction.
Authors: W E Waterfall, G S Cameron, S K Sarna, T D Lewis, E E Daniel
Journal: Gut (1981)

This report presents the findings of investigation of a child with idiopathic intestinal pseudo-obstruction (IIP). Functional abnormalities of the smooth muscle of the gastrointestinal tract were disclosed by electrical recordings from the gut obtained after laparotomy. In vitro analysis of tissue and ultrastructure were undertaken and a possible aetiology of the disorder in this patient based on these findings is presented.
Immunogenicity and safety of the 2009 non-adjuvanted influenza A/H1N1 vaccine in a large cohort of autoimmune rheumatic diseases
Authors: Carla G S Saad, Eduardo F Borba, Nadia E Aikawa, Clovis A Silva, Rosa M R Pereira, Ana Luisa Calich, Julio C B Moraes, Ana C M Ribeiro, Vilma S T Viana, Sandra G Pasoto, Jozelio F Carvalho, Ivan L A França, Lissiane K N Guedes, Samuel K Shinjo, Percival D Sampaio-Barros, Maria T Caleiro, Celio R Goncalves, Ricardo Fuller, Mauricio Levy-Neto, Maria do Carmo S Timenetsky, Alexander R Precioso, Eloisa Bonfa
Journal: Annals of the Rheumatic Diseases (2011)

Background Despite the WHO recommendation that the 2010–2011 trivalent seasonal flu vaccine must contain A/California/7/2009/H1N1-like virus there is no consistent data regarding its immunogenicity and safety in a large autoimmune rheumatic disease (ARD) population. Methods 1668 ARD patients (systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic sclerosis, psoriatic arthritis (PsA), Behçet's disease (BD), mixed connective tissue disease, primary antiphospholipid syndrome (PAPS), dermatomyositis (DM), primary Sjögren's syndrome, Takayasu's arteritis, polymyositis and Granulomatosis with polyangiitis (Wegener's) (GPA)) and 234 healthy controls were vaccinated with a non-adjuvanted influenza A/California/7/2009(H1N1) virus-like strain flu. Subjects were evaluated before vaccination and 21 days post-vaccination. The percentage of seroprotection, seroconversion and the factor increase in geometric mean titre (GMT) were calculated. Results After immunisation, seroprotection rates (68.5% vs 82.9% p&lt;0.0001), seroconversion rates (63.4% vs 76.9%, p&lt;0.001) and the factor increase in GMT (8.9 vs 13.2 p&lt;0.0001) were significantly lower in ARD than controls. Analysis of specific diseases revealed that seroprotection significantly reduced in SLE (p&lt;0.0001), RA (p&lt;0.0001), PsA (p=0.0006), AS (p=0.04), BD (p=0.04) and DM (p=0.04) patients than controls. The seroconversion rates in SLE (p&lt;0.0001), RA (p&lt;0.0001) and PsA (p=0.0006) patients and the increase in GMTs in SLE (p&lt;0.0001), RA (p&lt;0.0001) and PsA (p&lt;0.0001) patients were also reduced compared with controls. Moderate and severe side effects were not reported. Conclusions The novel recognition of a diverse vaccine immunogenicity profile in distinct ARDs supports the notion that a booster dose may be recommended for diseases with suboptimal immune responses. This large study also settles the issue of vaccine safety. ( ClinicalTrials.gov # NCT01151644 )
Scarcity begets addiction
Authors: Giorgio A. Ascoli, Kevin A. McCabe
Journal: Behavioral and Brain Sciences (2006)

As prototypical incentive with biological meaning, food illustrates the distinction between money as tool and money as drug. However, consistent neuroscience results challenge this view of food as intrinsic value and opposite to drugs of abuse. The scarce availability over evolutionary time of both food and money may explain their similar drug-like non-satiability, suggesting an integrated mechanism for generalized reinforcers.
Association Between Urinary Albumin Excretion and Serum Dehydroepiandrosterone Sulfate Concentration in Male Patients With Type 2 Diabetes
Authors: Michiaki Fukui, Yoshihiro Kitagawa, Naoto Nakamura, Mayuko Kadono, Goji Hasegawa, Toshikazu Yoshikawa
Journal: Diabetes Care (2004)

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in patients with type 2 diabetes. Both elevated urinary albumin excretion and low serum concentrations of dehydroepiandrosterone (DHEA) are associated with increased CVD mortality. This raises the possibility of DHEA as a causal intermediate linking urinary albumin excretion to CVD.Relationships of urinary albumin excretion to serum DHEA sulfate (DHEA-S) concentration and to major cardiovascular risk factors, including blood pressure, serum lipid concentration, glycemic control (HbA1c), and BMI, were investigated in 357 consecutive men with type 2 diabetes.Serum DHEA-S concentrations were lower in patients with macroalbuminuria (866.5 +/- 523.8 ng/ml, P <0.0001) and in those with microalbuminuria (1,014.4 +/- 525.3 ng/ml, P=0.0006) than in patients with normoalbuminuria (1,232.6 +/- 542.4 ng/ml). Serum DHEA-S concentration correlated inversely with log (urinary albumin excretion) (r=-0.227, P <0.0001). Multiple regression analysis demonstrated that duration of diabetes (beta=0.147, P=0.0075), HbA1c (beta=0.156, P=0.0048), BMI (beta=0.194, P=0.0007), systolic blood pressure (beta=0.195, P=0.0005), and serum DHEA-S concentration (beta=-0.192, P=0.0010) were independent determinants of log (urinary albumin excretion).Serum DHEA-S concentration, which correlated inversely with degree of urinary albumin excretion, may contribute to the link between elevated urinary albumin excretion and higher CVD mortality in male patients with type 2 diabetes.
Osteomalacia in Asian Immigrants During Pregnancy
Authors: D. J. C. Felton, W. D. Stone
Journal: BMJ (1966)

Rickets and mild osteomalacia have been found in a number of Asian immigrants to the United Kingdom (Dunnigan et al., 1962).Pregnancy can precipitate florid osteomalacia in this group, but in women who speak little English it is not easy to distinguish significant symptoms from the muscular pains common in pregnancy.
Cyproheptadine in the Management of the Galactorrhea-Amenorrhea Syndrome
Authors: JACOBO WORTSMAN
Journal: Annals of Internal Medicine (1979)

We evaluated long-term treatment with the antiserotonergic agent cyproheptadine in the management of the galactorrhea-amenorrhea syndrome. Fifteen women with a mean initial serum prolactin of 37 ±7 ng/mL received 16 to 24 mg of cyproheptadine daily; they had a significant decrease in prolactin concentration at 8 and at 16 weeks (P < 0.01). Gonadotropin responses were variable, but no significant changes were recorded during treatment. Ten of the 15 women had menstrual bleeding while receiving cyproheptadine, seven had decreased galactorrhea, and two had cessation of galactorrhea. The side effects of treatment were transient drowsiness and weight gain. We conclude that long-term treatment of the galactorrhea-amenorrhea syndrome with cyproheptadine is effective in lowering serum prolactin in patients with mildly elevated or normal levels. Its effect on fertility remains to be ascertained.
Is Cytology a Reliable Prognosticator of Radiosensitivity?
Authors: Ruth M. Graham
Journal: JAMA (1965)

In clinics treating large numbers of cases, the five-year survival rate in cancer of the cervix treated by radiation is 50% ± 10. The five-year cure rate for stage II is often quite similar to the overall survival (TAble 4). The stage II case poses a particularly tantalizing problem. About half of the patients have their cancer controlled by radiation therapy and half succumb to their disease. It is tempting to try and determine which patient will die of her disease either before or during treatment, while there is still time to use some other mode of therapy, ie, surgery. In an attempt to solve this problem, we have examined the vaginal smear both before and during radiation treatment. We have focused our attention not on the malignant cells, but on the changes in the benign cells. My remarks will be confined here to the prognostic accuracy of changes in
HISTORY OF A CASE OF RECURRENT NASAL FIBROMA.
Authors: PRICE BROWN
Journal: JAMA (1895)

I must request your forbearance with me, for taking up your valuable time with the report of a single case. We all know how little weight can be attached to individual histories, and that it is only by accumulated evidence that we can be guided to a proper estimate of the value of clinical research. If this is true in reference to surgical practice, it is equally true of a wide range of subjects pertaining to our own special field. Still, there are lesions in which the individual histories are so few and the few so widely spread over time as well as territory that it would seem to behoove every observer to chronicle each instance as it occurs with the hope of adding a fraction, however minute, to the information already possessed. This I am inclined to think is true of nasal fibroma, and as the case I have
Is weighing babies in clinics worth while?
Authors: B. I Johnson
Journal: BMJ (1983)

the diagnoses of only 76 out of the 140 patients with a positive Haemoccult test result, however, these being a colorectal neoplasm, diverticulitis, Crohn's disease, and angiodysplasia.What were the diagnoses in the other 64 patients ?What were the diagnoses and their incidences in the original 802 patients (for comparison) ?What proportion of the latter had no detectable disease ?Incidentally, what were the original presenting symptoms which defined the patients being studied ?
Differential Roles of Cardiac Myosin-Binding Protein C and Cardiac Troponin I in the Myofibrillar Force Responses to Protein Kinase A Phosphorylation
Authors: Julian E. Stelzer, Jitandrakumar R. Patel, Jeffery W. Walker, Richard L. Moss
Journal: Circulation Research (2007)

The heart is remarkably adaptable in its ability to vary its function to meet the changing demands of the circulatory system. During times of physiological stress, cardiac output increases in response to increased sympathetic activity, which results in protein kinase A (PKA)-mediated phosphorylations of the myofilament proteins cardiac troponin (cTn)I and cardiac myosin-binding protein (cMyBP)-C. Despite the importance of this mechanism, little is known about the relative contributions of cTnI and cMyBP-C phosphorylation to increased cardiac contractility. Using engineered mouse lines either lacking cMyBP-C (cMyBP-C −/− ) or expressing a non-PKA phosphorylatable cTnI (cTnI ala2 ), or both (cMyBP-C −/− /cTnI ala2 ), we investigated the roles of cTnI and cMyBP-C phosphorylation in the regulation of the stretch-activation response. PKA treatment of wild-type and cTnI ala2 skinned ventricular myocardium accelerated stretch activation such that the response was indistinguishable from stretch activation of cMyBP-C −/− or cMyBP-C −/− /cTnI ala2 myocardium; however, PKA had no effect on stretch activation in cMyBP-C −/− or cMyBP-C −/− /cTnI ala2 myocardium. These results indicate that the acceleration of stretch activation in wild-type and cTnI ala2 myocardium is caused by phosphorylation of cMyBP-C and not cTnI. We conclude that the primary effect of PKA phosphorylation of cTnI is reduced Ca 2+ sensitivity of force, whereas phosphorylation of cMyBP-C accelerates the kinetics of force development. These results predict that PKA phosphorylation of myofibrillar proteins in living myocardium contributes to accelerated relaxation in diastole and increased rates of force development in systole.
Points: Appropriate use of local resources
Authors: M. McCarthy
Journal: BMJ (1983)

December, p 1617) of a patient in whom atenolol treatment apparently precipitated renal artery thrombosis.Recent reports suggest that the angiotensin converting enzyme inhibitor captopril may cause the same complication in patients with pre-existing renal artery stenosis.Oelkers' has described two patients with renovascular hypertension who developed renal artery occlusion during treatment with captopril, and, according to Hollenberg,' about 10% of patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney developed rapidly progressive renal failure during the first few weeks of treatment with captopril.Half of these patients recovered renal function with a reduction in dosage of captopril.No details of the remaining patients were given, but one might speculate that some or all of them may also have developed renal artery thrombosis.
Cost-Effectiveness of Treating Multidrug-Resistant Tuberculosis
Authors: Stephen C Resch, Joshua A Salomon, Megan Murray, Milton C Weinstein
Journal: PLoS Medicine (2006)

Background Despite the existence of effective drug treatments, tuberculosis (TB) causes 2 million deaths annually worldwide. Effective treatment is complicated by multidrug-resistant TB (MDR TB) strains that respond only to second-line drugs. We projected the health benefits and cost-effectiveness of using drug susceptibility testing and second-line drugs in a lower-middle-income setting with high levels of MDR TB. Methods and Findings We developed a dynamic state-transition model of TB. In a base case analysis, the model was calibrated to approximate the TB epidemic in Peru, a setting with a smear-positive TB incidence of 120 per 100,000 and 4.5% MDR TB among prevalent cases. Secondary analyses considered other settings. The following strategies were evaluated: first-line drugs administered under directly observed therapy (DOTS), locally standardized second-line drugs for previously treated cases (STR1), locally standardized second-line drugs for previously treated cases with test-confirmed MDR TB (STR2), comprehensive drug susceptibility testing and individualized treatment for previously treated cases (ITR1), and comprehensive drug susceptibility testing and individualized treatment for all cases (ITR2). Outcomes were costs per TB death averted and costs per quality-adjusted life year (QALY) gained. We found that strategies incorporating the use of second-line drug regimens following first-line treatment failure were highly cost-effective compared to strategies using first-line drugs only. In our base case, standardized second-line treatment for confirmed MDR TB cases (STR2) had an incremental cost-effectiveness ratio of $720 per QALY ($8,700 per averted death) compared to DOTS. Individualized second-line drug treatment for MDR TB following first-line failure (ITR1) provided more benefit at an incremental cost of $990 per QALY ($12,000 per averted death) compared to STR2. A more aggressive version of the individualized treatment strategy (ITR2), in which both new and previously treated cases are tested for MDR TB, had an incremental cost-effectiveness ratio of $11,000 per QALY ($160,000 per averted death) compared to ITR1. The STR2 and ITR1 strategies remained cost-effective under a wide range of alternative assumptions about treatment costs, effectiveness, MDR TB prevalence, and transmission. Conclusions Treatment of MDR TB using second-line drugs is highly cost-effective in Peru. In other settings, the attractiveness of strategies using second-line drugs will depend on TB incidence, MDR burden, and the available budget, but simulation results suggest that individualized regimens would be cost-effective in a wide range of situations.
Polymorphonuclear cell function in rheumatoid arthritis and in Felty's syndrome.
Authors: G B Howe, J N Fordham, K A Brown, H L Currey
Journal: Annals of the Rheumatic Diseases (1981)

Tests for polymorphonuclear cell (PMN) chemotaxis, adherence, and electrophoretic mobility (EPM) were carried out on blood PMN isolated from 27 normal subjects, 16 patients with uncomplicated rheumatoid arthritis (RA), and 9 patients with Felty9s syndrome. Chemotaxis was measured by a modification of the Boyden chamber technique, adherence by retention of cells on nylon fibre columns, and EPM in a cylindrical electrophoretic assembly. There was no significant difference between the chemotactic migration of normal and rheumatoid PMN as assessed by the leading front measurement. However, PMN from patients with Felty9s syndrome showed significantly reduced chemotaxis (P less than 0.001). Computerised image analysis showed this impaired migration to be due to an overall reduction in cell motility rather than loss of a subset cells. Activated serum from patients with RA and Felty9s syndrome were as good chemoattractants as activated pooled AB serum. There was no significant difference in the adhesiveness of PMN from normal persons and rheumatoid patients, though PMN from patients with Felty9s syndrome did show a trend to lower adhesiveness. Both RA and Felty9s syndrome patients had an increase in the proportion of PMN of lower surface charge than controls. Direct correlations were observed between cells of high surface charge and nonadhesiveness.
Adenosine Receptor Antagonists Including Caffeine Alter Fetal Brain Development in Mice
Authors: Carla G. Silva, Christine Métin, Walid Fazeli, Nuno J. Machado, Sanja Darmopil, Pierre-Serge Launay, Antoine Ghestem, Marie-Pascale Nesa, Emilie Bassot, Eszter Szabó, Younis Baqi, Christa E. Müller, Angelo R. Tomé, Anton Ivanov, Dirk Isbrandt, Yuri Zilberter, Rodrigo A. Cunha, Monique Esclapez, Christophe Bernard
Journal: Science Translational Medicine (2013)

Consumption of certain substances during pregnancy can interfere with brain development, leading to deleterious long-term neurological and cognitive impairments in offspring. To test whether modulators of adenosine receptors affect neural development, we exposed mouse dams to a subtype-selective adenosine type 2A receptor (A2AR) antagonist or to caffeine, a naturally occurring adenosine receptor antagonist, during pregnancy and lactation. We observed delayed migration and insertion of γ-aminobutyric acid (GABA) neurons into the hippocampal circuitry during the first postnatal week in offspring of dams treated with the A2AR antagonist or caffeine. This was associated with increased neuronal network excitability and increased susceptibility to seizures in response to a seizure-inducing agent. Adult offspring of mouse dams exposed to A2AR antagonists during pregnancy and lactation displayed loss of hippocampal GABA neurons and some cognitive deficits. These results demonstrate that exposure to A2AR antagonists including caffeine during pregnancy and lactation in rodents may have adverse effects on the neural development of their offspring.
Respiration of Ascending and Descending Rhythm
Authors: W. J. Mickle
Journal: BMJ (1878)

beladonna extract wAs given every hour; and, after nin-gris's bad 1ei taken, copious alvine evacuation ensued.In two attacks since, the latest being last month, eight grains and nine grains respectively were effectual.No alcohol was prescribed in ay of the above cases, but patient No.x,took about two ounces of port wine before the belladonna treatment was begun.In the after-treatment, and as a preventive' of obstruc- tion, the most effectual remedy I have found has been pulvis glycyi.rhze composita.
643 PEG-IFN-l: ANTIVIRAL ACTIVITY AND SAFETY PROFILE IN A 4-WEEK PHASE 1B STUDY IN RELAPSED GENOTYPE 1 HEPATITIS C INFECTION
Authors: M. Shiffman, E. Lawitz, A. Zaman, J. Vierling, B. Yoffe, J. Freeman, T. Gray, D. Hausman, A. Muir
Journal: Journal of Hepatology (2009)
Effects of Helicobacter pylori eradication on the natural history of lymphocytic gastritis
Authors: M Hayat, D S Arora, M F Dixon, B Clark, S O'Mahony
Journal: Gut (1999)

Lymphocytic gastritis is characterised by an accumulation of lymphocytes in the surface epithelium of the stomach. Lymphocytic gastritis has been linked to coeliac disease and Helicobacter pylori infection.To determine whether H pylori eradication leads to resolution of the lymphocytic infiltrate and clinical improvement in patients with lymphocytic gastritis, and to determine their HLA status.The Leeds Dyspepsia Questionnaire (LDQ) was administered to 13 patients with lymphocytic gastritis. H pylori serology, (13)C urea breath test (UBT), and upper gastrointestinal endoscopy with sampling of the duodenum, antrum, and corpus were done in all cases and the HLA status was determined. Eleven patients had at least one positive test for H pylori. Patients with lymphocytic gastritis and H pylori infection were treated with a one week course of omeprazole, clarithromycin, and metronidazole. Gastric and duodenal intraepithelial lymphocyte (IEL) counts were performed, along with histological assessment of gastric and duodenal biopsies before and after H pylori eradication.Two months after treatment there was a significant reduction in gastric IEL counts in both antrum and corpus. There was no significant change in duodenal IEL counts before and after eradication. According to the Sydney grading there was significant improvement in corpus inflammation after eradication. The patients histologically H pylori positive before treatment became H pylori negative. Dyspepsia scores also improved significantly after treatment.H pylori eradication treatment in patients with lymphocytic gastritis causes significant improvement in the gastric IEL infiltrate, corpus inflammation, and dyspeptic symptoms. H pylori serology is frequently positive when histology and UBT are negative. Lymphocytic gastritis may represent a specific immune response to H pylori infection.