tbuckley/cabot-search huggingface dataset:
Ultra-Sensitive Detection of Plasmodium falciparum by Amplification of Multi-Copy Subtelomeric Targets
Authors: Natalie Hofmann, Felista Mwingira, Seif Shekalaghe, Leanne J. Robinson, Ivo Mueller, Ingrid Felger
Journal: PLoS Medicine (2015)

Background Planning and evaluating malaria control strategies relies on accurate definition of parasite prevalence in the population. A large proportion of asymptomatic parasite infections can only be identified by surveillance with molecular methods, yet these infections also contribute to onward transmission to mosquitoes. The sensitivity of molecular detection by PCR is limited by the abundance of the target sequence in a DNA sample; thus, detection becomes imperfect at low densities. We aimed to increase PCR diagnostic sensitivity by targeting multi-copy genomic sequences for reliable detection of low-density infections, and investigated the impact of these PCR assays on community prevalence data. Methods and Findings Two quantitative PCR (qPCR) assays were developed for ultra-sensitive detection of Plasmodium falciparum, targeting the high-copy telomere-associated repetitive element 2 (TARE-2, ∼250 copies/genome) and the var gene acidic terminal sequence (varATS, 59 copies/genome). Our assays reached a limit of detection of 0.03 to 0.15 parasites/μl blood and were 10× more sensitive than standard 18S rRNA qPCR. In a population cross-sectional study in Tanzania, 295/498 samples tested positive using ultra-sensitive assays. Light microscopy missed 169 infections (57%). 18S rRNA qPCR failed to identify 48 infections (16%), of which 40% carried gametocytes detected by pfs25 quantitative reverse-transcription PCR. To judge the suitability of the TARE-2 and varATS assays for high-throughput screens, their performance was tested on sample pools. Both ultra-sensitive assays correctly detected all pools containing one low-density P. falciparum–positive sample, which went undetected by 18S rRNA qPCR, among nine negatives. TARE-2 and varATS qPCRs improve estimates of prevalence rates, yet other infections might still remain undetected when absent in the limited blood volume sampled. Conclusions Measured malaria prevalence in communities is largely determined by the sensitivity of the diagnostic tool used. Even when applying standard molecular diagnostics, prevalence in our study population was underestimated by 8% compared to the new assays. Our findings highlight the need for highly sensitive tools such as TARE-2 and varATS qPCR in community surveillance and for monitoring interventions to better describe malaria epidemiology and inform malaria elimination efforts.
Hypertrophic cardiomyopathy: Sudden death is rare in young people with hypertrophic cardiomyopathy
Authors: David S Wald, Malcolm Law
Journal: BMJ (2006)

EDITOR—In their review on the management of hypertrophic cardiomyopathy Spirito and Autore claim that the condition is the most common cause of sudden death in young people without symptoms.1 This is incorrect. The table summarises the results of 12 studies that provided data on the …
Ammonia-induced brain edema and intracranial hypertension in rats after portacaval anastomosis
Authors: Andres T. Blei, Sigurdur Olafsson, Guy Therrien, Roger F. Butterworth
Journal: Hepatology (1994)

Brain edema, leading to intracranial hypertension and brain herniation, is a major cause of death in fulminant liver failure. Astrocyte swelling is a prominent neuropathological feature in experimental fulminant liver failure. It has been postulated that the osmotic effects of glutamine, generated in astrocytes from ammonia and glutamate in a reaction catalyzed by glutamine synthetase, could mediate brain swelling. Normal rats and rats that received a portacaval anastomosis were infused with ammonium acetate or a sodium acetate control; brain water in cerebral cortex was measured with the gravimetry method, intracranial pressure by means of a cisterna magna catheter and cortical amino acids using high-performance liquid chromatography. Although brain edema was detected in both groups receiving ammonia, it was of a greater magnitude in portacaval anastomosis rats (80.94% + 0.17% vs. 80.24% + 0.09%, p < 0.01), resulting in the development of intracranial hypertension. When portacaval anastomosis rats were infused with ammonium acetate and pretreated with 150 mg/kg methionine-sulfoximine, an inhibitor of glutamine synthetase activity, brain edema was ameliorated and intracranial pressure did not rise. A dose-dependent reduction in brain glutamine levels was seen with increasing doses of methionine-sulfoximine; however, brain edema did not decrease beyond the 150 mg/kg dose, suggesting that the increase in brain water was not solely a result of glutamine accumulation. We conclude that brain edema of a magnitude that results in intracranial hypertension is more likely to develop in rats after portacaval anastomosis receiving a continuous ammonia infusion. The osmotic effects of glutamine appear to mediate, but only in part, the increase in brain water seen in this preparation.(ABSTRACT TRUNCATED AT 250 WORDS)
Down's children received "less favourable" hospital treatment
Authors: Z. Kmietowicz
Journal: BMJ (2001)

An inquiry into the way children with heart defects were treated at two “centres of excellence” in England has blamed poor communication between doctors and families and lack of resources for dissatisfaction among parents.

Doctors at the Royal Brompton Hospital in London and the Harefield Hospital in Middlesex failed to put patients first and offered parents a biased view of only some of the treatment options available for children with Down's syndrome, according to the independent inquiry panel's report.

Although it stopped short of accusing doctors of discrimination, the report stated that “children were less favoured in accessing treatment because of their Down's syndrome.”

The inquiry was commissioned by the hospitals 18 months ago after parents whose children had been treated at the hospitals between 1987 and 1999 complained that the results after surgery were worse than elsewhere. An earlier review, however, had found no evidence that this was the case.

Ruth Evans, chairwoman of the inquiry's panel, described the …
Mouse/Human Chimeric Antibodies to a Tumor-Associated Antigen: Biologic Activity of the Four Human IgG Subclasses
Authors: D. R. Shaw, M. B. Khazaeli, A. F. LoBuglio
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Mouse/Human Chimeric Antibodies to a Tumor-Associated Antigen: Biologic Activity of the Four Human IgG Subclasses Get access Denise R. Shaw, Denise R. Shaw Comprehensive Cancer Center, University of Alabama at BirminghamBirmingham, AL Search for other works by this author on: Oxford Academic PubMed Google Scholar M. B. Khazaeli, M. B. Khazaeli Comprehensive Cancer Center, University of Alabama at BirminghamBirmingham, ALVeterans Administration Medical CenterBirmingham, AL Search for other works by this author on: Oxford Academic PubMed Google Scholar Albert F. LoBuglio Albert F. LoBuglio Comprehensive Cancer Center, University of Alabama at BirminghamBirmingham, AL *Correspondence to: Dr. A. F. LoBuglio, Comprehensive Cancer Center. University of Alabama at Birmingham, L B. Wallace Tumor Institute 237, University Station, Birmingham, AL 35294 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 19, 7 December 1988, Pages 1553–1559, https://doi.org/10.1093/jnci/80.19.1553 Published: 07 December 1988 Article history Received: 18 July 1988 Accepted: 16 August 1988 Published: 07 December 1988
936-89 Extent of Coronary Myointimal Proliferation and its Relationship to Resistance Vessel Function in the Cardiac Allograft
Authors: Thomas Wolford, Thomas J. Donohue, John H. Drury, Richard G. Bach, Eugene A. Caracciolo, Andrew S. Potash, Stephen H. Jennison, Morton J. Kern, Pamela S. Pelgh
Journal: Journal of the American College of Cardiology (1995)
The challenge for Beijing: the 10th world conference on tobacco or health
Authors: R. Beaglehole
Journal: BMJ (1997)

Conflicting data on subpopulations of peripheral blood lymphocytes in patients with autoimmune disease largely reflect variations in methods of study. An investigation was therefore conducted aimed at avoiding this difficulty. Serial samples of peripheral blood mononuclear cells from 42 patients with hyperthyroid Graves9 disease were collected at monthly intervals before, during, and for 12 months after a six month course of carbimazole. Samples were stored in liquid nitrogen until completion of the study, when they were thawed and all samples from each patient analysed within the same assay using mouse monoclonal antibodies to human cell subsets and a fluorescence activated cell sorter. Proportions of cytotoxic/suppressor (OKT8) positive cells before treatment (mean 17.4 (SEM 0.8)%) were significantly lower (p less than 0.001) than those in normal controls (29.8 (1.9)%; n = 10) and returned to normal by the end of treatment. In contrast, the proportions of activated T cells (OKIa-OKM1) were significantly raised before treatment as compared with normal (14.4 (0.6)% versus 4.6 (0.8)%; p less than 0.001) and fell to normal by the end of treatment. Proportions of OKT3 and OKT4 positive T cells remained unchanged throughout treatment and in the succeeding 12 months. In patients who relapsed after treatment there was a rise in the proportion of activated T cells and a fall in OKT8 positive T cells, which returned towards normal with retreatment. The explanation for the alterations in numbers of circulating T cells remains to be determined but they may provide a means for predicting more accurately the outcome of Graves9 disease after treatment with carbimazole.
The syndrome of variant angina culminating in acute myocardial infarction.
Authors: J E Madias
Journal: Circulation (1979)

Ten patients 28-54 years old with recurrent attacks of variant angina (chest pain associated with transient ST-segment elevation) culminating in acute myocardial infarction were studied. Systemic blood pressure and heart rate remained unchanged or decreased during chest pain. Diagnosis of myocardial infarction was made on the basis of pathognomonic enzyme changes and T-wave inversions persisting for several weeks (seven patients) or development of Q waves (three patients). Complications were similar to the ones previously observed in conventional myocardial infarction. None of these patients died. Past history was characterized by absence of effort angina. Exercise stress testing after infarction was normal, and coronary arteriography revealed a spectrum of pathology, ranging from normal arteriograms to three-vessel disease. Intraaortic balloon pumping was ineffective in two patients, but subsequent coronary bypass surgery shortly after myocardial infarction was not followed by further attacks of chest pain. Follow-up of these patients revealed a benign course. Alcohol drinking and cigarette smoking appeared to be very prevalent in this group.
Scintigraphic Criteria for the Diagnosis of Obstructive Hepatobiliary Diseases with Tc-99m IDA
Authors: SHAKUNTALA KRISHNAMURTHY, GERBAIL T. KRISHNAMURTHY, DAVID LIEBERMAN, EMMET B. KEEFFE
Journal: Clinical Nuclear Medicine (1988)

The purpose of this study is to define the scintigraphic parameters that reliably predict the presence of obstructive hepatobiliary diseases. Gallbladder and intestinal visualization times noted during cholescintigraphy with Tc-99m IDA were compared to functional and morphologic parameters for their ability to accurately diagnose biliary diseases. One hundred and twenty-five normal subjects and 127 patients with five different types of hepatobiliary diseases were studied. Bile pooling in segmental ducts with minimal prolongation of excretion t-1/2 was the feature most commonly seen in partial common bile duct obstruction, and biliary nonvisualization with marked prolongation of excretion t-1/2 was the primary feature of total obstruction. Sclerosing cholangitis showed band constrictions and beading along bile ducts with regional variation in excretion t-1/2, and primary biliary cirrhosis demonstrated normal bile ducts with uniform prolongation of excretion t-1/2. Patients with cholelithiasis showed normal image patterns of the major ducts. Intestinal visualization by 60 minutes was only 46% sensitive and 77% specific with an overall accuracy of 74% in the detection of biliary obstruction. Delayed gallbladder visualization and reduction in ejection fraction were sensitive but nonspecific indicators of biliary disease. We conclude that Tc-99m-IDA imaging is an accurate test for the diagnosis of obstructive hepatobiliary disease provided both quantitative functional and qualitative morphologic parameters are analyzed. Intestinal nonvisualization at 60 minutes alone is not reliable as a sole parameter for the detection of partial biliary obstruction.
<i>In vitro</i> and <i>In vivo</i> Characterization of 64Cu-Labeled AbegrinTM, a Humanized Monoclonal Antibody against Integrin αvβ3
Authors: Weibo Cai, Yun Wu, Kai Chen, Qizhen Cao, David A. Tice, Xiaoyuan Chen
Journal: Cancer Research (2006)

Abstract AbegrinTM (MEDI-522 or VitaxinTM), a humanized monoclonal antibody against human integrin αvβ3, is in clinical trials for cancer therapy. In vivo imaging using AbegrinTM-based probes is needed for better treatment monitoring and dose optimization. Here, we conjugated AbegrinTM with macrocyclic chelating agent 1,4,7,10-tetra-azacylododecane N,N′,N″,N‴-tetraacetic (DOTA) at five different DOTA/AbegrinTM ratios. The conjugates were labeled with 64Cu (half-life = 12.7 hours) and tested in three human (U87MG, MDA-MB-435, and PC-3) and one mouse (GL-26) tumor models. The in vitro and in vivo effects of these 64Cu-DOTA-AbegrinTM conjugates were evaluated. The number of DOTA per AbegrinTM varied from 1.65 ± 0.32 to 38.53 ± 5.71 and the radiolabeling yield varied from 5.20 ± 3.16% to 88.12 ± 6.98% (based on 2 mCi 64Cu per 50 μg DOTA-AbegrinTM conjugate). No significant difference in radioimmunoreactivity was found among these conjugates (between 59.78 ± 1.33 % and 71.13 ± 2.58 %). Micro-positron emission tomography studies revealed that 64Cu-DOTA-AbegrinTM (1,000:1) had the highest tumor activity accumulation (49.41 ± 4.54% injected dose/g at 71-hour postinjection for U87MG tumor). The receptor specificity of 64Cu-DOTA-Abegrin was confirmed by effective blocking of MDA-MB-435 tumor uptake with coadministration of nonradioactive Abegrin. 64Cu-DOTA-IgG exhibited background level tumor uptake at all time points examined. Integrin αvβ3-specific tumor imaging using 64Cu-DOTA-AbegrinTM may be translated into the clinic to characterize the pharmacokinetics, tumor targeting efficacy, dose optimization, and dose interval of AbegrinTM and/or Abegrin conjugates. Chemotherapeutics or radiotherapeutics using AbegrinTM as the delivering vehicle may also be effective in treating integrin αvβ3-positive tumors. (Cancer Res 2006; 66(19): 9673-81)
Focal Nodular Hyperplasia (FNH): A Potential Cause of False-Positive Positron Emission Tomography
Authors: D L??pez Aznar, Reyes Ojeda, E Uruburu Garcia, F Aparici, P Abreu S??nchez, D Flores, C Mart??nez, R Sopena
Journal: Clinical Nuclear Medicine (2005)

Positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG) has been proven to be a useful tool in the differential diagnosis of liver tumors. Focal nodular hyperplasia (FNH) is an uncommon benign liver lesion, which can be difficult to differentiate from other benign and malignant liver pathologies. FDG PET imaging usually shows uptake similar or even decreased compared to that of the normal liver. We describe a hypermetabolic FNH lesion in a patient with a history of breast cancer. Computed tomography scan, ultrasonography (US), and magnetic resonance imaging were negative. The lesion was resected, and histologic findings were consistent with FNH.
The goals of counterfactual possibilities
Authors: Paolo Legrenzi
Journal: Behavioral and Brain Sciences (2007)

Abstract Why do humans imagine alternatives to reality? The experiments conducted by Byrne explain the mental mechanisms we use when we do just this – that is, imagine one, or more, alternative reality. But why do we do this? The general reason is to give ourselves an explanation of the world, to tell stories; at times to console ourselves, and at times to despair. A good story is not only based on a description of what happened, but also hints at, or explains, what might have happened. Depending on our aim, we construct different kinds of counterfactuals. In all cases, however, we are faced with constraints. These constraints are specific to a given domain of beliefs and use of counterfactuals.
Duodenal metastasis of malignant melanoma observed by magnification endoscopy
Authors: K. Tanaka, H. Toyoda, Y. Hamada, M. Aoki, R. Kosaka, T. Noda, M. Katsurahara, M. Nakamura, K. Ninomiya, H. Inoue, I. Imoto
Journal: Endoscopy (2008)

Although malignant melanoma is the most common source of metastasis to the gastrointestinal tract, the features of these metastases as viewed by magnification endoscopy have not been reported.
Reduced Incidence of Vagally Induced Atrial Fibrillation and Expression Levels of Connexins by n-3 Polyunsaturated Fatty Acids in Dogs
Authors: Jean-Francois Sarrazin, Genevieve Comeau, Pascal Daleau, John Kingma, Isabelle Plante, Dominique Fournier, Franck Molin
Journal: Journal of the American College of Cardiology (2007)
STUDIES ON THE IMMUNE RESPONSE OF THE RHEUMATIC SUBJECT AND ITS RELATIONSHIP TO ACTIVITY OF THE RHEUMATIC PROCESS. V. ACTIVE AND PASSIVE IMMUNIZATION TO HEMOLYTIC STREPTOCOCCUS IN RELATION TO THE RHEUMATIC PROCESS 1
Authors: Alvin F. Coburn, Ruth H. Pauli
Journal: Journal of Clinical Investigation (1935)

There seems to be a close relationship between infection with hemolytic streptococcus, producing skin toxin, and initiation of rheumatic activity in susceptible subjects.The failure of the rheu- matic patient to develop activity of the disease process when infected with a non-erythrogenic strain of hemolytic streptococcus suggests the possibility that toxin may play an important role in the genesis of rheumatic lesions.To test the possibility that an inciease in circulating antitoxin to streptococcus might protect the tissues of the rheumatic subject and modify the disease attack, the authors have made two studies, one on active immunization with scarlatinal (NY5) toxin, the other on passive immunization with NY5 anti- toxin. I. ACTIVE IMMUNIZATION WITH SCARLATINAL TOXINIts relation to streptococcus infection and rheu- matic fever Reports on the effectiveness of active immuni- zation with streptococcus toxin vary widely.Most observers agree that the procedure prevents scarlet fever and many consider it effective in lowering the incidence of throat infections and their complications, such as rheumatic fever and nephritis.The literature has been summarized by the Pickett-Thomson Research Laboratory (1).The present study has been made to deter- mine whether active immunization with strepto- coccus toxin may increase resistance to infection and whether it may modify the host's reactivity.
Prevention of hepatocyte allograft rejection in rats by transferring adenoviral early region 3 genes into donor cells
Authors: Elena V. Mashalova, Chandan Guha, Namita Roy-Chowdhury, Laibin Liu, Ira J. Fox, Jayanta Roy-Chowdhury, Marshall S. Horwitz
Journal: Hepatology (2007)

Abstract Hepatocyte transplantation is being evaluated as an alternative to liver transplantation for metabolic support during liver failure and for definitive treatment of inherited liver diseases. However, as with liver transplantation, transplantation of allogeneic hepatocytes requires prolonged immunosuppression with its associated untoward effects. Therefore, we explored strategies for the genetic modification of donor hepatocytes that could eliminate allograft rejection, obviating the need for immunosuppression. Products of early region 3 ( AdE3 ) of the adenoviral genome are known to protect infected cells from immune recognition and destruction. In the present study we showed that immortalized rat hepatocytes that had been stably transduced with AdE3 before transplantation into fully MHC-mismatched rats are protected from allograft rejection. Quantitative real-time PCR analysis showed that a similar number of engrafted AdE3-transfected hepatocytes had survived in syngeneic and allogeneic recipients. AdE3 expression did not reduce expression of MHC class I on the surfaces of donor hepatocytes. Consistent with this, the in vivo cytotoxic cell–mediated alloresponse was attenuated but not abolished in recipients of AdE3-transfected allogeneic hepatocytes. In contrast, graft survival correlated with a marked reduction in cell-surface localization of Fas receptor in the transplanted cells and inhibition of Fas-mediated apoptosis, which are related to the antiapoptotic functions of the AdE3 proteins. CONCLUSION: AdE3 gene products prevent hepatocyte allograft rejection mainly by protecting the cells from the effector limb of the host immune response and could be used as a tool to facilitate allogeneic hepatocyte transplantation. (Hepatology 2007;45:755–766.)
Heat shock protein 90 in neurodegenerative diseases
Authors: Wenjie Luo, Weilin Sun, Tony Taldone, Anna Rodina, Gabriela Chiosis
Journal: Molecular Neurodegeneration (2010)

Hsp90 is a molecular chaperone with important roles in regulating pathogenic transformation. In addition to its well-characterized functions in malignancy, recent evidence from several laboratories suggests a role for Hsp90 in maintaining the functional stability of neuronal proteins of aberrant capacity, whether mutated or over-activated, allowing and sustaining the accumulation of toxic aggregates. In addition, Hsp90 regulates the activity of the transcription factor heat shock factor-1 (HSF-1), the master regulator of the heat shock response, mechanism that cells use for protection when exposed to conditions of stress. These biological functions therefore propose Hsp90 inhibition as a dual therapeutic modality in neurodegenerative diseases. First, by suppressing aberrant neuronal activity, Hsp90 inhibitors may ameliorate protein aggregation and its associated toxicity. Second, by activation of HSF-1 and the subsequent induction of heat shock proteins, such as Hsp70, Hsp90 inhibitors may redirect neuronal aggregate formation, and protect against protein toxicity. This mini-review will summarize our current knowledge on Hsp90 in neurodegeneration and will focus on the potential beneficial application of Hsp90 inhibitors in neurodegenerative diseases.
Chronic Graft-vs-Host Disease
Authors: Vikas Bhushan
Journal: JAMA (2003)

ALLOGENEIC HEMATOPOIETIC cell transplantation (HCT) is a treatment used increasingly for a variety of malignant and nonmalignant diseases of the bone marrow and immune system. Although the procedure cures many patients with otherwise incurable diseases, it is often associated with serious immunological complications, particularly graft-vs-host disease (GVHD). A chronic form of GVHD afflicts many allogeneic HCT recipients, resulting in dysfunction of numerous organ systems and an oftentimes profound state of immunodeficiency. Chronic GVHD is the most frequent cause of poor longterm outcome and quality of life after allogeneic HCT. The syndrome typically develops several months after transplantation, when the patient may no longer be under the direct care of the transplant team. The patient’s primary physician plays an important role in diagnosis and treatment of the patient with chronic GVHD.