tbuckley/cabot-search huggingface dataset:
<i>Ex Vivo</i> Activation of CD56+ Immune Cells That Eradicate Neuroblastoma
Authors: Piya Rujkijyanont, Wing Keung Chan, Paul W. Eldridge, Timothy Lockey, Martha Holladay, Barbara Rooney, Andrew M. Davidoff, Wing Leung, Queenie Vong
Journal: Cancer Research (2013)

Despite the use of intensive contemporary multimodal therapy, the overall survival of patients with high-risk neuroblastoma is still less than 50%. Therefore, immunotherapy without cross-resistance and overlapping toxicity has been proposed. In this study, we report the development of a novel strategy to specifically activate and expand human CD56(+) (NCAM1) natural killer (NK) immune cells from normal donors and patients with neuroblastoma. Enriched CD56(+) cells from peripheral blood were mixed with CD56(-) fraction at 1:1 ratio and cultured in the presence of OKT3, interleukin (IL)-2, and -15 for five days and then without OKT3 for 16 more days. The final products contained more than 90% CD56(+) cells and could kill neuroblastoma cells effectively that were originally highly resistant to nonprocessed NK cells. Mechanistically, cytolysis of neuroblastoma was mediated through natural cytotoxicity receptor (NCR), DNAX accessory molecule-1 (DNAM-1; CD226), perforin, and granzyme B. Successful clinical scale-up in a good manufacturing practices (GMP)-compliant bioreactor yielded effector cells that in a neuroblastoma xenograft model slowed tumor growth and extended survival without GVHD. Investigation of CD56(+) cells from patients with neuroblastoma revealed a similar postactivation phenotype and lytic activity. Our findings establish a novel and clinically expedient strategy to generate allogeneic or autologous CD56(+) cells that are highly cytotoxic against neuroblastoma with minimal risk of GVHD.
Hydroxyeicosatetraenoic acid metabolism in cultured human skin fibroblasts. Evidence for peroxisomal beta-oxidation.
Authors: J A Gordon, P H Figard, A A Spector
Journal: Journal of Clinical Investigation (1990)

To determine whether the peroxisome is responsible for hydroxyeicosatetraenoic acid (HETE) oxidation, 12- and 15-HETE oxidation was measured in normal and peroxisomal deficient skin fibroblasts from patients with Zellweger's (cerebrohepatorenal) syndrome. When incubated for 1 h with normal fibroblasts, reverse phase HPLC indicated that 24% of the 12-HETE radioactivity was converted to one major polar metabolite. Chemical derivatization followed by reverse phase HPLC and TLC indicated that this metabolite is 8-hydroxyhexadecatrienoic acid [16:3(8-OH)]. Similarly, 33% of the added 15-HETE was also converted to a more polar metabolite. Neither 12- nor 15-HETE were converted to any metabolites by the peroxisomal deficient (Zellweger) cells. No defect in HETE oxidation was found in other human fibroblast cell lines with diverse metabolic abnormalities. Zellweger fibroblasts accumulated increased amounts of 12-HETE, compared with normal fibroblasts. As in the normal cells, most of the 12-HETE incorporated into Zellweger fibroblasts was present in the choline and ethanolamine phosphoglycerides. Protein synthesis, lysosomal acid lipase activity, and mitochondrial butyrate oxidation were not impaired in the Zellweger fibroblasts. Since the Zellweger cells do not convert 12- and 15-HETE to oxidative metabolites, peroxisomes appear to be the cellular organelle responsible for HETE oxidation.
SARCOMA OF OVARY IN A CHILD EIGHT YEARS OLD
Authors: Philip Jaisohn
Journal: JAMA (1930)

Sarcoma of the ovary among children under the age of 10 is quite rare. The available bibliography on the subject in the Surgeon General's Library shows only twenty-four cases between 1888 and 1915, including those reported from Austria, Cuba, France, Great Britain, Germany, Russia, Sweden and the United States. The rarity of the condition warrants my reporting a case that recently came to my observation in this hospital.  Virginia M., aged 8, was admitted to the hospital in the service of Dr. M. Z. Gearhart, Nov. 15, 1929, on the complaint of pain in the lower part of the abdomen and bleeding from the vagina. The physical examination showed that she was quite well nourished and of normal size for her age. There was a mass in the lower part of the left quadrant of the abdomen which was very tender on palpation, and there was some vaginal hemorrhage. This
Spatial and Temporal Heterogeneity in Nucleotide Sequence Evolution
Authors: S. Whelan
Journal: Molecular Biology and Evolution (2008)

Models of nucleotide substitution make many simplifying assumptions about the evolutionary process, including that the same process acts on all sites in an alignment and on all branches on the phylogenetic tree. Many studies have shown that in reality the substitution process is heterogeneous and that this variability can introduce systematic errors into many forms of phylogenetic analyses. I propose a new rigorous approach for describing heterogeneity called a temporal hidden Markov model (THMM), which can distinguish between among site (spatial) heterogeneity and among lineage (temporal) heterogeneity. Several versions of the THMM are applied to 16 sets of aligned sequences to quantitatively assess the different forms of heterogeneity acting within them. The most general THMM provides the best fit in all the data sets examined, providing strong evidence of pervasive heterogeneity during evolution. Investigating individual forms of heterogeneity provides further insights. In agreement with previous studies, spatial rate heterogeneity (rates across sites [RAS]) is inferred to be the single most prevalent form of heterogeneity. Interestingly, RAS appears so dominant that failure to independently include it in the THMM masks other forms of heterogeneity, particularly temporal heterogeneity. Incorporating RAS into the THMM reveals substantial temporal and spatial heterogeneity in nucleotide composition and bias toward transition substitution in all alignments examined, although the relative importance of different forms of heterogeneity varies between data sets. Furthermore, the improvements in model fit observed by adding complexity to the model suggest that the THMMs used in this study do not capture all the evolutionary heterogeneity occurring in the data. These observations all indicate that current tests may consistently underestimate the degree of temporal heterogeneity occurring in data. Finally, there is a weak link between the amount of heterogeneity detected and the level of divergence between the sequences, suggesting that variability in the evolutionary process will be a particular problem for deep phylogeny.
ADULT LIFE COURSE BODY MASS INDEX AND AGE AT FIRST DETECTION OF OVERWEIGHT ARE ASSOCIATED WITH FUTURE INCREASES IN LEFT VENTRICULAR MASS INDEX
Authors: Arjun K. Ghosh, Alun Hughes, Nishi Chaturvedi, Darrel Francis, Diana Kuh, John Deanfield, Denis Pellerin, Jamil Mayet, Rebecca Hardy
Journal: Journal of the American College of Cardiology (2013)
Eosinophil activity markers in peripheral blood have high predictive value for bronchial hyper‐reactivity in patients with
Authors: A. Roquet, G. Halldén, E. Ihre, J. Hed, O. Zetterström
Journal: Allergy (1996)

The present study aimed to evaluate the predictive value of eosinophils and markers of their activity for bronchial hyper‐reactivity (BHR) in a population of patients with recently developed clinical symptoms of asthma. The activation of eosinophils was estimated by measuring eosinophil cationic protein (ECP) in serum. In addition, flow cytometry was used to measure the expression of the EG2‐epitope on intracellular ECP in eosinophils from peripheral blood. Twenty‐eight consecutive patients with clinical history of asthma were studied. Of the 28 patients, 18 had a positive bronchial challenge test measured as PD 20 1600 μg histamine. A significantly higher concentration of eosinophils and a trend to higher ECP in the peripheral blood was found in the hyper‐reactive group than in the nonreactive group. However, the intracellular expression of ECP did not correlate with the PD, value, and no significant difference between the groups was found. With one eosinophil activity marker, either serum ECP or EG2, BHR could be predicted in 70% of the patients. If we combined any two of the activity markers (serum ECP, EG2, or the percentage of eosinophils), the predictive value increased to 100%. We conclude that the blood eosinophil concentration, as well as, to some extent, serum ECP, has a high specificity for BHR in patients with recently developed clinical symptoms of asthma. Despite normal bronchial reactivity, some patients had signs of activated eosinophils, i.e., high serum ECP and increased EG2 expression. Thus, these markers may reflect early stages in the development of BHR. Our results also indicate that a combined evaluation of percentage of eosinophils and of eosinophil activity markers is of clinical value to predict BHR.
Roche Canada stops distributing oseltamivir
Authors: David Spurgeon
Journal: BMJ (2005)

Canadian federal officials are trying to damp down concern about a possible flu pandemic, after reports of Canadians stockpiling the flu treatment oseltamivir (Tamiflu) prompted Roche Canada to cease distribution of the drug to pharmacies until the flu season begins. 

David Butler-Jones, Canada's chief medical officer of health, said that although the government is stockpiling oseltamivir as a …
The NHS in Clacton and the 2014 by-election
Authors: B. F. Sizer
Journal: BMJ (2014)

In The BMJ on Saturday 18 October, Ham wrote that “politicians are understandably reluctant to promise more than they can realistically deliver.”1 Contrastingly, on Sunday, Ed Miliband promised the public cancer diagnoses within seven days. On Monday, the Royal College of Radiologists’ press release said (I paraphrase) “blimey, you will need a lot more radiologists.”

A weekend, let alone a week, is clearly …
Abstract 3569: Transcriptional signatures in human melanoma epitope MART-127-35 specific TCR-engineered T cells
Authors: Prashant Singh, Nitya G. Chakraborty, Umar Farooq, Upendra P. Hegde, Richard Everson, David I. Dorsky, Bijay Mukherji
Journal: Cancer Research (2014)

Abstract Adoptive Cell Therapies (ACT) with T cell receptor-engineered (TCReng) T cells have shown promising results. Unfortunately, for a fuller understanding of their biology, currently available immunological assays have proven inadequate. Given that RNA-Seq using Next Generation Sequencing (NGS) offers substantial opportunities, we carried out NGS of the MART-127-35 specific TCReng human primary CD8+ and CD4+ T-cells following cognate stimulation, to obtain a comprehensive understanding of the transcriptional signatures underlying their biology. Data analyses revealed approximately 30,000 transcripts, a sizeable number of which showing up- or down-regulation covering virtually all relevant aspects of T cell biology (i.e., effector function, differentiation, proliferative activities, apoptosis, etc.) when stimulated by the cognate epitope. The transcriptional profiles of the TCReng CD8+ and CD4+ T cells were found to be remarkably similar. Additionally, 72,000 known isoforms and about 20,000 previously undescribed isoforms were detected. Interestingly, a number of long noncoding RNAs (lncRNA) - some with known functions (e.g., NEAT1 and MALAT1, both implicated in RNA editing, were up-regulated in the two cell types), and others with unknown function (e.g., GAS5, MIAT, and FTX showing modulations in expression), were also detected in both cell types. Although a comprehensive knowledge of the transcriptional signatures and a clear understanding of the spliced variants, the novel isoforms, and the lncRNAs in T cell biology will require further work, our study shows that NGS of specific epitope reactive T cells will be a very useful tool in deciphering the transcriptional controls underlying the function and the fate of epitope specific anti-tumor T cells. Citation Format: Prashant Singh, Nitya G. Chakraborty, Umar Farooq, Upendra P. Hegde, Richard Everson, David I. Dorsky, Bijay Mukherji. Transcriptional signatures in human melanoma epitope MART-127-35 specific TCR-engineered T cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3569. doi:10.1158/1538-7445.AM2014-3569
The relationship between regional myocardial perfusion at rest and arteriographic lesions in patients with coronary atherosclerosis.
Authors: P J Cannon, D H Schmidt, M B Weiss, D L Fowler, R R Sciacca, K Ellis, W J Casarella
Journal: Journal of Clinical Investigation (1975)

Measurements of mean left ventricular (LV) and regional myocardial blood flow rates were made at rest in 161 patients with 133Xe and a multiplecrystal scintillation camera. Myocardial perfusion rates were correlated with assessments of the degree of coronary artery disease made from the arteriograms obtained during the same studies. In patients with normal coronary arteries without heart failure, the presence of hypertension, aortic stenosis, or aortic insufficiency was not associated with changes in mean LV perfusion from the control value of 61+/-7 ml/100 g-min. However, mean LV perfusion was significantly reduced in patients with normal coronary arteries who had cariomyopathy and impaired ventricular performance. Mean LV perfusion was not significantly different from control values in patients with "mild" coronary artery disease (less than 50% obstruction) or in patients with significant isolated disease (greater than 50% obstruction) of the left anterior descending (lad) artery. Significant reductions in mean LV perfusion were found in patients with greater than 50% obstruction of two coronary arteries (LAD + right or LAD + circumflex) and in patients with triple-vessel disease. The average perfusion rate for regions distal to LAD obstructions in patients with isolated LAD disease was not lower than the LAD perfusion in control patients, but was significantly reduced in patients with LAD + right coronary artery disease (43+/-14 ml/100 g-min). In the latter group average perfusion distal to the LAD lesion was significantly lower than the average regional perfusion rate for the remainder of the LV. However, the mean blood flow rate for the remainder of the LV was also significantly lower than control values despite the lack of significant circumflex disease. The data demonstrate that the presence of radiographically "mild" or significant isolated LAD coronary disease is not associated with reductions in mean LV perfusion at rest, but that mean LV perfusion is reduced in the presence of significant disease of two or three coronary artieries. None of the patients experienced angina during the resting studies and most had clinical evidence of ventricular failure. The observation of depressed LV perfusion in this group, as in the patients with cardiomyopathy, raises the possibility that a lowered resting blood supply may be adequate for a reduced level of performance of a diseased ventricle. The lack of selective reductions of regional perfusion at rest in the majority of the patients with LAD lesions suggests that regional myocardial blood flow must be measured during an intervention which increases myocardial oxygen consumption in order to assess the physiological significance of lesions which are observed at coronary arteriography.
Increased prevalence of human parvovirus B19 DNA in systemic sclerosis skin
Authors: T. Ohtsuka, S. Yamazaki
Journal: British Journal of Dermatology (2004)

Human parvovirus B19 is a small, single-stranded DNA virus encoding two structural capsid proteins and a nonstructural protein. It is the aetiological agent of erythema infectiosum and transient aplastic crisis in patients with haemolytic anaemia, and has been associated with fetal death, arthritis and chronic anaemia. In recent years, the possible involvement of parvovirus B19 in systemic sclerosis (SSc) has been reported.To determine whether human parvovirus B19 DNA can be detected in SSc skin tissue specimens.Normal subjects (n = 97) and patients with SSc (n = 48), systemic lupus erythematosus (n = 16), dermatomyositis (n = 8), morphoea (n = 6) and graft-versus-host disease (n = 8) were studied. Crude DNA was extracted from skin tissue specimens. We attempted to determine whether human parvovirus B19 could be detected in the skin of SSc using nested polymerase chain reaction (PCR). PCR amplification was performed with specifically designed first and second primer pairs for parvovirus B19 DNA.After the first PCR, the occurrence rate of parvovirus B19 DNA in SSc skin tissues (36 of 48, 75%) was significantly elevated in comparison with that in normal controls (50 of 97, 52%) (P < 0.01). After the second PCR, the occurrence rate of parvovirus B19 DNA in SSc skin tissues (36 of 48, 75%) was significantly elevated compared with that in normal controls (53 of 97, 55%) (P < 0.02). The occurrence rates in the other diseases showed no significant difference from that in normal controls.The increased prevalence of human parvovirus B19 DNA in SSc skin showed the possibility that the virus may be involved in the formation of skin tissue abnormalities in the disease.
Unspeakably Cruel — Torture, Medical Ethics, and the Law
Authors: George J. Annas
Journal: New England Journal of Medicine (2005)

George Annas reviews international and U.S. laws and U.S. Supreme Court decisions relevant to torture in wartime. He also discusses the controversy over physicians' roles in the torture of prisoners in the prisons at Abu Ghraib and Guantanamo Bay and argues that physicians have a special responsibility to prevent and report torture.
Effect of Kidney Dysfunction on Lung Volume in Patients With Diabetes
Authors: Ian J Gilmour, Jose J Barbosa
Journal: Diabetes Care (1991)

Over several years, one of the authors observed what appeared to be a relationship between a decrease in total lung capacity (TLC) and insulin-dependent diabetes mellitus (IDDM) in patients who were candidates for kidney transplantation.In an effort to define this potential relationship, pulmonary function tests (PFTs) were reviewed on all available kidney transplant candidates between 1983 and 1986. The patients were divided into two groups--those with kidney failure caused by IDDM (group 1) and those with kidney failure from other causes (group 2). A third group (control subjects) of volunteers with IDDM but without evidence of kidney failure was evaluated by PFTs in an attempt to determine whether IDDM without kidney failure was also associated with a decrease in TLC.Demographics of the two groups with kidney failure were similar. However, the duration of IDDM in the volunteers with IDDM was significantly shorter than in group 1 patients (19.6 vs. 25.9 yr). The TLC of group 1 patients was significantly smaller than the TLC of both the group 2 patients and the volunteers with IDDM.We believe that these data suggest that the association between IDDM and decreased TLC is the result of IDDM and not kidney failure. Because our volunteers with IDDM were significantly younger than the patients with IDDM and kidney failure, we can draw no conclusions about any separate contribution of kidney failure to changes in TLC in people with IDDM.
OX40 and other immunoregulatory molecules are highly expressed on tumor infiltrating lymphocytes in oral, head and neck squamous cell carcinoma
Authors: Ryan Montler, Richard B Bell, Rom Leidner, Marka Crittenden, Tuan Bui, Allen Cheng, Ashish Patel, Christopher Tucker, Colin Thalhofer, Andrew Weinberg
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts OX40 is a potent co-stimulatory receptor on the surface of T lymphocytes. An OX40 agonist was recently tested in a Phase I clinical trial and was found to be well tolerated and enhanced both humoral and cellular immunity in patients with metastatic cancer. Both PD-1 and CTLA-4
Topical cidofovir for bowenoid papulosis in an HIV-infected patient
Authors: V. Descamps, X. Duval, M. Grossin, B. Crickx, C. Leport
Journal: British Journal of Dermatology (2001)

Sir, Bowenoid papulosis is an in situ squamous cell carcinoma located in the anogenital region (perianal intraepithelial neoplasia). It is most commonly associated with human papillomavirus (HPV) types 16 and 18. It usually follows a benign course and may spontaneously resolve in immunocompetent patients. In immunocompromised patients it generally persists and may progress to an invasive squamous cell carcinoma.1 Conventional treatments include electrodessication, cryosurgery, surgical or laser removal and topical 5‐fluorouracil. Cidofovir (HPMPC) is a nucleotide analogue that has been shown to be active in vitro against a variety of DNA viruses, including HPV.2 Thus, topical cidofovir was used in a human immunodeficiency virus (HIV) infected patient with severe relapsing perianal bowenoid papulosis. A 40‐year‐old man presented with perianal skin lesions of several years’ duration. He was HIV infected and was persistently immunocompromised despite taking an association of four antiretroviral drugs (stavudine, lamivudine, saquinavir, ritonavir). The patient's viral load and CD4 levels were 26 000 copies mL−1 and 85 mm−3, respectively.
Electrophysiological effect of varied rate and extent of acute in vivo left ventricular load increase
Authors: H. Calkins, J. H Levine, D. A Kass
Journal: Cardiovascular Research (1991)

Study objective — The aim was to determine whether the rate, the magnitude, or both, of increased left ventricular wall stress in vivo has consistent and prominent effects on repolarisation, afterdepolarisations, or arrhythmogenicity. Design — Ten anaesthetised dogs underwent transient proximal aortic occlusion. Wall stress was estimated from pressure-volume data obtained by volume catheter, normalised to preocclusion values, and correlated with simultaneously determined changes in monophasic action potential duration (MAPd). Data were obtained during both fast (>50% rise in wall stress within two beats) and slow occlusions, as well as during innervated and denervated conditions. Experimental material — Adult mongrel dogs (20-25 kg) were used. Measurements and main results — Two- to threefold increases in wall stress resulted in less than 5 ms shortening in MAPd and there was little correlation between wall stress and MAPd shortening. The strongest relation between normalised wall stress (EWSnorm) and MAPd was observed under denervated conditions during rapid aortic occlusion (∆MAPd = −2.5×EWSnorm +2.1, r2 = 0.44, p<0.001). Afterdepolarisations were observed in fewer than 10% of occlusions and were not related to the magnitude or rate of loading change. Ventricular ectopy occurred more frequently during rapid than slow occlusions (87% v 56%, p = 0.01), but was unrelated to the level of wall stress increase or the presence of afterdepolarisations. Conclusions — Marked acute increases in left ventricular loading in vivo minimally alter repolarisation, and rarely lead to afterdepolarisations. The speed rather than magnitude of load change appears more important in the development of ventricular ectopy. These findings suggest that load induced ventricular ectopy is due to stretch induced automaticity rather than triggered activity or re-entry.
LONGEVITY AFTER CORONARY THROMBOSIS
Authors: PAUL D. WHITE
Journal: JAMA (1933)

That acute coronary occlusion is often survived by years of active life has become a fact of common knowledge during the past ten years, but the extent to which recovery is possible and the longevity and strenuous activity that may ensue in some cases are but vaguely realized. I have been led to present herewith important and as yet unique information concerning this problem by the discovery at postmortem examination of a firm scar in the myocardium of a man, aged 80, who suffered a single typical attack of acute coronary occlusion at the age of 63, passed a life insurance examination easily two years later, was in such perfect health at 72 that he climbed mountains at a high rate of speed without symptoms, and finally succumbed to apoplexy without heart failure.  When myocardial infarction from acute coronary occlusion was first described by pathologists, and for many years afterward,