tbuckley/cabot-search huggingface dataset:
Nasal and exhaled nitric oxide in response to occupational latex exposure
Authors: K. Tan, C. Bruce, A. Birkhead, P. S. Thomas
Journal: Allergy (2001)

Background: Latex sensitivity is an increasing problem among health‐care workers. Allergic responses are associated with changes in nitric oxide (NO) generation and the changes secondary to latex have not been described. Methods: A total of 22 subjects comprising equal numbers of control volunteers and subjects with self‐reported latex sensitivity were recruited to undergo latex skin prick testing. Symptom scores, exhaled nitric oxide (eNO), and nasal nitric oxide (nNO) were studied 1) before and after a controlled latex challenge ( n =16), and 2) at the beginning and end of the working week, during exposure to latex ( n =18). Results: Latex challenge caused a significant fall in nNO levels in latex‐sensitive subjects, compared to normal control subjects ( P =0.04). eNO levels also decreased in the latex‐sensitive subjects after latex challenge, but to a lesser degree. There were no significant differences between the beginning and end of the working week in terms of eNO or nNO in either group, although symptom scores showed a nonsignificant increase in latex‐sensitive subjects. Conclusions: Fall in nasal NO after latex challenge is associated with reported symptomatic latex sensitivity, and this corresponds to latex skin prick test positivity. Neither nNO nor eNO showed a clear relationship to routine workplace exposure.
War Against the Weak: Eugenics and America's Campaign to Create a Master Race
Authors: Joff Lelliott
Journal: BMJ (2004)

Eugenics is too frequently overlooked in histories of both the United States and Europe, even though the story is a fascinating and important one. The field to date has remained largely the preserve of academic historians, despite obvious connections to contemporary debates around science and ethics. These were prime motivations for War Against the Weak, Edwin Black's timely look at American eugenics and its impact on Nazism.

Black's earlier book, IBM and the Holocaust , traced the role of the information technology company IBM in creating Nazi Germany's punch-card technology for classifying victims …
Cardiovascular Abnormalities in Transgenic Mice With Reduced Brown Fat
Authors: Antonio Cittadini, Christos S. Mantzoros, Thomas G. Hampton, Kerry E. Travers, Sarah E. Katz, James P. Morgan, Jeffrey S. Flier, Pamela S. Douglas
Journal: Circulation (1999)

A new model of murine obesity has recently been developed through transgenic ablation of brown adipose tissue that manifests typical metabolic complications of obesity, including insulin resistance and non-insulin-dependent diabetes mellitus. The cardiovascular phenotype has not been defined.Transthoracic echocardiography, aortic catheterization, isolated whole-heart studies, and morphometric histology defined cardiac structure and function in 30 transgenic mice with reduced brown fat and 30 matched wild-type controls. Obesity was indicated by a 77% increase in body weight and was accompanied by elevated systemic pressures (mean aortic blood pressure 85+/-1 versus 66+/-2 mm Hg; P<0.01), left ventricular dilation and hypertrophy (mass/body weight 4.0+/-0.2 versus 2.7+/-0.3 mg/g; P<0.01), and high cardiac output (cardiac index 3.2+/-0.4 versus 2.4+/-0.1 mL x kg(-1) x min(-1); P<0.01). Baseline functional parameters assessed in vitro were not different, but after imposition of zero-flow ischemia, significant relaxation impairment developed in obese mice. Although morphometrically determined myocyte diameters were similar, the percentage of interstitial fibrosis was significantly increased in transgenic mice compared with wild-type controls (7.5+/-2% versus 4. 2+/-0.2%; P<0.01).Transgenic ablation of brown adipose tissue is associated not only with obesity but also with systemic hypertension, left ventricular hypertrophy with eccentric remodeling and fibrosis, and high cardiac output, a unique constellation of findings strikingly similar to that seen in human obesity. Mice with reduced brown fat may serve as a new model for the cardiovascular morbid complications associated with obesity in humans.
Calcium uptake by the sarcoplasmic reticulum, high energy content and histological changes in ischemic cardiomyopathy
Authors: Kanigula Mubagwa, Peter Kaplan, Bharati Shivalkar, Marc Miserez, Veerle Leunens, Marcel Borgers, Willem Flameng
Journal: Cardiovascular Research (1998)

Sarcoplasmic reticulum (SR) Ca2+ uptake, myocardial high energy content and histology were examined in different zones of hearts from patients with ischemic cardiomyopathy.Unfractionated homogenates were prepared from left ventricular samples obtained in three zones of each heart: an infarct-remote zone, an outer peri-infarct zone, and an inner peri-infarct zone. Oxalate-supported 45Ca2+ uptake was measured at 37 degrees C using a filtration method. Maximum rate (Vmax) of uptake in absence or in presence of ryanodine was lower in inner peri-infarct (7.4 +/- 0.7 and 9.5 +/- 0.8 nmol min-1 mg-1 of protein, respectively; mean +/- SEM) and outer peri-infarct tissues (8.8 +/- 0.8 and 12.0 +/- 0.8 nmol min-1 mg-1) than in infarct-remote myocardium (12.7 +/- 2.1 and 15.8 +/- 2.2 nmol min-1 mg-1). The apparent affinity constants for Ca2+ (KCa) as well as the Hill coefficients were not different. Homogenate DNA (1.6 +/- 0.1, 1.6 +/- 0.1 and 1.7 +/- 0.1 mg/g of remote, inner peri-infarct and outer peri-infarct myocardium, respectively) and adenine nucleotides contents (ATP: 15 +/- 1.3, 14 +/- 0.8 and 15 +/- 1.0 mumol/g dry weight, respectively) were similar in all tissues. Fibrosis was increased in inner peri-infarct tissue (37 +/- 6%; vs. 13 +/- 2% and 12 +/- 2% in both remote and outer peri-infarct tissues, respectively), but the number of abnormal cells was not significantly different.The decrease of Ca2+ uptake in ischemic cardiomyopathy is not homogeneous in the ventricular wall, and reflects a decreased number/activity of SR Ca(2+)-ATPase, without altered Ca(2+)-affinity or increased Ca2+ leakage through ryanodine receptors.
C57/BL-6 mice produce higher levels of surfactant protein (SP)-D and attenuated airway responses in comparison with balb/c mice following allergic sensitization†
Authors: Elena N Atochina, Angela Haczku, Yaniv Tomer, Hang Chen, Seth T Scanlon, Scott Russo, Reynold A Panetieri, Michael F Beers
Journal: Journal of Allergy and Clinical Immunology (2002)
Antileishmanial defense in macrophages triggered by tumor necrosis factor expressed on CD4+ T lymphocyte plasma membrane.
Authors: J P Sypek, D J Wyler
Journal: The Journal of Experimental Medicine (1991)

In our studies of host defense to the intracellular protozoan Leishmania major, we uncovered a novel mechanism of antileishmanial defense that involves direct cell contact between effector CD4+ lymphocytes and Leishmania-infected macrophages. The mechanism is distinctive because it does not involve lymphokine secretion and induces no cytotoxic effects in the host cells; its expression is antigen-specific and genetically restricted. We now demonstrate that these effector CD4+ cells display tumor necrosis factor (TNF) on their surface and provide evidence that the membrane-associated TNF is involved in the activation of the antileishmanial defense. Using a Leishmania-specific cloned T-T cell hybridoma line (1B6; CD4+, T helper type 1) that activates antileishmanial defense in macrophages through cell contact and does not secrete TNF, we noted that only cells bearing surface TNF (TNF+), but not ones lacking surface TNF (TNF-), exerted these effects. Moreover, the antileishmanial effects excreted by TNF+ 1B6 cells as well as by lymph node CD4+ TNF+ lymphocytes could be blocked with anti-TNF antibody. We propose that membrane-associated TNF on CD4+ T cells may provide a mechanism of targeting activation signals to macrophages in an antigen-specific and genetically restricted manner.
Intestinal absorption of two dipeptides in Hartnup disease
Authors: A. M. Asatoor, B. Cheng, K. D. G. Edwards, A. F. Lant, D. M. Matthews, M. D. Milne, F. Navab, A. J. Richards
Journal: Gut (1970)

The results of oral tolerance tests of two dipeptides and of their constitutent amino acids are compared in normal subjects and in a case of Hartnup disease. In the control subjects the rate of absorption of phenylalanine from phenylalanyl-phenylalanine and of tryptophan from glycyl-tryptophan was slower than after the equivalent amount of the free amino acids. Absorption of the two essential amino acids (tryptophan and phenylalanine) in the patient was almost zero after administration in the free form, but was much greater after the dipeptide. Results of experiments on absorption and hydrolysis of the two peptides in the rat small intestine are also reported. It is suggested that whereas normal subjects absorb essential amino acids by a dual mechanism of mucosal uptake of free amino acids and oligopeptides, nutrition in Hartnup disease is largely dependent on uptake of oligopeptides containing the amino acids affected by the intestinal transport defect of the disease.
Women in Medicine — More Political Pressure — Jerome Cardan's Well
Authors: John Lister
Journal: New England Journal of Medicine (1975)

THE number of women being admitted to British medical schools is increasing steadily. Thus, in 1970 women made up 29 per cent of the total, intake; by 1974 the proportion had risen to 34 per cent, and since there is no longer any quota system restricting the admission of women, the proportion could well rise to 40 per cent or even 50 per cent in the next few years.For many reasons it is essential that when they graduate these women should be able to pursue a satisfactory career in the field of medicine of their choice. For one thing, . . .
Growth dynamics of untreated glioblastomas in vivo
Authors: Anne Line Stensjøen, Ole Solheim, Kjell Arne Kvistad, Asta K. Håberg, Øyvind Salvesen, Erik Magnus Berntsen
Journal: Neuro-Oncology (2015)

Glioblastomas are primary malignant brain tumors with a dismal prognosis. Knowledge of growth rates and underlying growth dynamics is useful for understanding basic tumor biology, developing realistic tumor models, and planning treatment logistics.By using repeated pretreatment contrast-enhanced T1-weighted MRI scans from 106 patients (aged 26-83 years), we studied the growth dynamics of untreated glioblastomas in vivo. Growth rates were calculated as specific growth rates and equivalent volume doubling times. The fit of different possible growth models was assessed using maximum likelihood estimations.There were large variations in growth rates between patients. The median specific growth rate of the tumors was 1.4% per day, and the equivalent volume doubling time was 49.6 days. Exploring 3 different tumor growth models showed similar statistical fit for a Gompertzian growth model and a linear radial growth model and worse fit for an exponential growth model. However, large tumors had significantly lower growth rates than smaller tumors, supporting the assumption that glioblastomas reach a plateau phase and thus exhibit Gompertzian growth.Based on the fast growth rate of glioblastoma shown in this study, it is evident that poor treatment logistics will influence tumor size before surgery and can cause significant regrowth before adjuvant treatment. Since there is a known association between tumor volume, extent of surgical resection, and response to adjuvant therapy, it is likely that waiting times play a role in patient outcomes.
“License to Kill” Reflects Joint Action of CD4 and CD8 T Cells
Authors: Cornelis J.M. Melief
Journal: Clinical Cancer Research (2013)

The spontaneous T-cell responses to the KIF20A cancer-associated antigen found by Tomita and colleagues among peripheral blood mononuclear cells of patients with cancer, but not healthy people, involve both CD4 and CD8 T cells. Synthetic long peptides of KIF20A stimulate synergy between these two T-cell types to promote cancer cell killing.
Value of the electrocardiogram in identifying heart failure due to left ventricular systolic dysfunction
Authors: A P Davie, C M Francis, M P Love, L Caruana, I R Starkey, T R D Shaw, G R Sutherland, J J V McMurray
Journal: BMJ (1996)

Chronic heart failure due to left ventricular systolic dysfunction has a high morbidity and mortality. Angiotensin converting enzyme inhibitors reduce symptomatic deterioration, hospitalisation, and death. Most patients with suspected heart failure present first to general practitioners. Recent studies have emphasised the difficulty of diagnosing heart failure in the community. Fewer than half of patients treated for heart failure by general practitioners have objective evidence of cardiac disease.1 2

To improve diagnosis and treatment Dargie and McMurray suggested that echocardiography should be performed in all patients suspected of having chronic heart failure.3 Screening patients before referral for diagnostic investigation may lessen the considerable resource implications of this approach. We assessed the value of the electrocardiogram in identifying patients with possible chronic heart failure.

An open access echocardiography …
Abstract 2213: Effect of Medical Therapy and Transplantation on the Natural History of Pediatric Dilated Cardiomyopathy: A 25 Year Retrospective Study
Authors: Jonathan R Abraham, Andrew N Redington, Anne I Dipchand, Lee N Benson, Paul F Kantor
Journal: Circulation (2006)

Background: The long term transplant-free survival of infants and children with dilated cardiomyopathy (DCM) has been reported to be poor. We assessed the hypothesis that the introduction of angiot...
The Mll partial tandem duplication: differential, tissue-specific activity in the presence or absence of the wild-type allele
Authors: Adrienne M. Dorrance, Shujun Liu, Anita Chong, Benjamin Pulley, David Nemer, Martin Guimond, Weifeng Yuan, Dennis Chang, Susan P. Whitman, Guido Marcucci, Michael A. Caligiuri
Journal: Blood (2008)
Rapidly Growing Complex Fibroadenoma With Surrounding Ductal Hyperplasia Mimics Breast Malignancy on Serial F-18 FDG PET/CT Imaging
Authors: William Makis, Anthony Ciarallo, Marc Hickeson, Vilma Derbekyan
Journal: Clinical Nuclear Medicine (2011)

A 30-year-old woman was referred for an F-18 fluorodeoxyglucose (FDG) PET/CT to rule out lymphoma, and was found to have an incidental FDG-avid right breast nodule that grew significantly in size and FDG uptake on a subsequent scan, raising suspicion of a growing breast malignancy. Histologic evaluation showed a complex fibroadenoma with adenosis and surrounding ductal hyperplasia. Although variable F-18 FDG uptake in fibroadenomas has been described, a distinction between simple and complex fibroadenomas has not been made in the PET literature, even though complex fibroadenomas have a higher propensity to develop into malignancies. This case shows that a rapidly growing complex fibroadenoma can mimic a breast malignancy on serial F-18 FDG PET/CT scans, showing significant increase in both size and FDG-avidity on follow-up studies.
Morphologic determinants of hemodynamic state after ventricular septal myotomy-myectomy in patients with obstructive hypertrophic cardiomyopathy: M mode and two-dimensional echocardiographic assessment.
Authors: P Spirito, B J Maron, D R Rosing
Journal: Circulation (1984)

To define the morphologic features of the left ventricle after ventricular septal myotomy-myectomy and to elucidate the structural changes associated with a postoperative reduction in the pressure gradient, 28 patients with obstructive hypertrophic cardiomyopathy were studied with M mode and qualitative and quantitative two-dimensional echocardiography. Nine patients with a marked reduction in the pressure gradient (no or small, less than or equal to 25 mm Hg, residual basal gradient) demonstrated a marked reduction in septal thickness after surgery (23 +/- 6 to 13 +/- 4 mm; p less than .01), a concomitant increase in septal to mitral valve distance (20 +/- 2 to 30 +/- 5 mm; p less than .005), and a loss or substantial decrease in the magnitude of systolic anterior motion of the mitral valve. Two-dimensional echocardiographic results demonstrated an increase of over 100% in the cross-sectional area of the left ventricular outflow tract at onset of systole (2.2 +/- 0.6 to 5.5 +/- 3 cm2; p less than .01). In six of the patients postoperative paradoxic septal motion appeared to contribute importantly to the increased size of the outflow tract during ventricular systole. In contrast, nine patients with little or no change in the pressure gradient (residual basal gradient greater than or equal to 40 mm Hg) demonstrated a less marked decrease in septal thickness and no significant change in septal to mitral valve distance or magnitude of mitral systolic anterior motion. Furthermore, the postoperative left ventricular outflow tract area was significantly smaller in patients with residual basal gradients (3.0 +/- 1 cm2) than that in patients with no residual gradient (5.5 +/- 3 cm2; p less than .05). Ten patients with only provocable subaortic gradients after operation showed postoperative left ventricular outflow tract dimensions intermediate between those in patients with either residual basal gradient or no residual gradient. On the basis of this echocardiographic assessment of septal myotomy-myectomy, we conclude that abolition or reduction of the subaortic gradient after operation in patients with obstructive hypertrophic cardiomyopathy is largely the consequence of surgical enlargement of the left ventricular outflow tract area.
Depression of cardiac sarcolemmal phospholipase D activity by oxidant-induced thiol modification.
Authors: J Dai, J T Meij, R Padua, V Panagia
Journal: Circulation Research (1992)

Myocardial phospholipase D (PLD) is primarily localized at the sarcolemmal level and selectively hydrolyzes phosphatidylcholine to form phosphatidic acid as part of the signal transduction mechanisms for regulating Ca2+ movements in the heart. Since the myocardial cell damage induced by oxidative stress is associated with abnormalities in Ca2+ homeostasis and thiol status, we examined the thiol group dependence and the effects of oxidant species on this enzyme. Sarcolemmal membranes isolated from rat heart were exposed to several types of thiol group modifiers. Alkylation with N-ethylmaleimide or methyl methanethiosulfonate, mercaptide formation with p-chloromercuriphenylsulfonic acid, and thiol-disulfide exchange with 5,5'-dithio-bis(2-nitrobenzoate) depressed sarcolemmal PLD activity; in all cases the depression was prevented by dithiothreitol. At different concentrations of N-ethylmaleimide the PLD depression correlated well (r = 0.98) with the decrease in total thiol group content of the membrane. The enzyme activity was not affected by xanthine-xanthine oxidase, a superoxide anion-generating system, but was depressed by hydrogen peroxide (H2O2) in a concentration-dependent manner. This inhibitory effect was prevented by catalase as well as by dithiothreitol, but not by D-mannitol. The effect of a hydroxyl radical-generating system (Fenton reaction) could not be assessed because of an interfering direct inhibition by Fe2+. Dithiothreitol was also able to restore PLD activity in H2O2-pretreated membranes and to prevent a severe deactivation of the enzyme by hypochlorous acid (HOCI). Protection by glutathione and inhibition by its oxidized form were also observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Gene replacement therapy in the central nervous system: Viral vector-mediated therapy of global neurodegenerative disease
Authors: Edward A. Neuwelt, Michael A. Pagel, Alfred Geller, Leslie L. Muldoon
Journal: Behavioral and Brain Sciences (1995)

Abstract This target article describes the current state of global gene replacement in the brain using viral vectors and assesses possible solutions to some of the many problems inherent in gene therapy of the central nervous system (CNS). Gene replacement therapy in the CNS is a potential means of producing a stable expression of normal human proteins in deficient cells and thus curing certain genetically inherited enzyme deficiencies and metabolic diseases as well as cancers. The two major issues to be addressed in CNS gene replacement are the delivery of genetic material to the brain and the expression of recombinant genetic material in target cells within the CNS. Focal inoculation of recombinant virions or other genetic vectors has limitations in global CNS disease. A new approach is the blood-brain barrier (BBB) disruption technique developed in this laboratory, in which hypertonic mannitol transiently shrinks the BBB endothelium, allowing passage of high molecular weight compounds and even viruses. Gene therapy of the CNS will require a viral vector system that allows long-term, nontoxic gene expression in neurons or glial cells. Retroviral vectors have limitations in CNS gene replacement, although they are suitable for expressing recombinant genes in intracerebral grafts, or toxic genes in brain tumors. Using mutant neurotropic viruses with reduced neurotoxicity (such as defective herpes simplex virus type I [HSV-1], the HSV-1 amplicon vector system we have developed, or adenovirus mutants) has potential for direct treatment of neurons. Injecting these vectors into rodent brains can lead to stable expression of foreign genetic material in postmitotic neuronal cells. We discuss our BBB disruption delivery technique, our defective HSV-1 amplicon vector system, and our feline model for the neuronal lysosomal storage disorder Gm 2 -gangliosidosis (Sandhoff disease), which may prove to be a useful model system for CNS gene therapy.
Competing Risks Data Analysis with High-Dimensional Covariates: An Application in Bladder Cancer
Authors: Leili Tapak, Massoud Saidijam, Majid Sadeghifar, Jalal Poorolajal, Hossein Mahjub
Journal: Genomics Proteomics & Bioinformatics (2015)

Abstract Analysis of microarray data is associated with the methodological problems of high dimension and small sample size. Various methods have been used for variable selection in high-dimension and small sample size cases with a single survival endpoint. However, little effort has been directed toward addressing competing risks where there is more than one failure risks. This study compared three typical variable selection techniques including Lasso, elastic net, and likelihood-based boosting for high-dimensional time-to-event data with competing risks. The performance of these methods was evaluated via a simulation study by analyzing a real dataset related to bladder cancer patients using time-dependent receiver operator characteristic (ROC) curve and bootstrap .632+ prediction error curves. The elastic net penalization method was shown to outperform Lasso and boosting. Based on the elastic net, 33 genes out of 1381 genes related to bladder cancer were selected. By fitting to the Fine and Gray model, eight genes were highly significant (P &amp;lt; 0.001). Among them, expression of RTN4, SON, IGF1R, SNRPE, PTGR1, PLEK, and ETFDH was associated with a decrease in survival time, whereas SMARCAD1 expression was associated with an increase in survival time. This study indicates that the elastic net has a higher capacity than the Lasso and boosting for the prediction of survival time in bladder cancer patients. Moreover, genes selected by all methods improved the predictive power of the model based on only clinical variables, indicating the value of information contained in the microarray features.