tbuckley/cabot-search huggingface dataset:
Prevalence of human metapneumovirus in adults with acute respiratory tract infection in Beijing, China
Authors: Jianguo Li, Zhong Wang, Richard Gonzalez, Yan Xiao, Hongli Zhou, Jing Zhang, Glaucia Paranhos-Baccala, Guy Vernet, Qi Jin, Jianwei Wang, Tao Hung
Journal: Journal of Infection (2011)

To evaluate the prevalence and clinical manifestations of human metapneumovirus (hMPV) in immunocompetent Chinese adults with acute respiratory tract infections (ARTIs).A reverse transcription PCR (RT-PCR) assay targeting the P gene was developed in this study and used to detect hMPV in nasal and throat swabs collected from 2936 immunocompetent adult patients with ARTIs in Beijing, China between July 2008 and June 2010.Among the 2936 patients studied, 49 (1.7%) were positive for hMPV, of whom 14 (28.6%) were positive for hMPV_A2b, 19 (38.8%) for hMPV_B1, and 16 (32.6%) for hMPV_B2. hMPV_A1 was not detected. An average detection rate of 6.6% was observed in the peak months of the two epidemic seasons studied. The hMPV prevalence was higher in the sampled elderly (>65 years, 3.2%) than in middle aged adults (25-65 years; 2.0%) and teenagers (14-25 years; 0.9%). During the study period, hMPV infections showed a biennial rhythm of seasonality, peaking from November to March in 2008/09 and from March to June in 2010.hMPV infection plays an important role in immunocompetent adults in its epidemic season. The demographic and clinical data presented in this study improves our understanding of the pathogenesis and clinical burden of hMPV infection in adults.
Polymorphism in xeroderma pigmentosum complementation group C codon 939 and aflatoxin B1-related hepatocellular carcinoma in the Guangxi population
Authors: Xi-Dai Long, Yun Ma, Yuan-Feng Zhou, Ai-Min Ma, Guo-Hui Fu
Journal: Hepatology (2010)

Genetic polymorphisms in DNA repair genes may influence individual variations in DNA repair capacity, and this may be associated with the risk and outcome of hepatocellular carcinoma (HCC) related to aflatoxin B1 (AFB1) exposure. In this study, we focused on the polymorphism of xeroderma pigmentosum complementation group C (XPC) codon 939 (rs#2228001), which is involved in nucleotide excision repair. We conducted a case-control study including 1156 HCC cases and 1402 controls without any evidence of hepatic disease to evaluate the associations between this polymorphism and HCC risk and prognosis in the Guangxi population. AFB1 DNA adduct levels, XPC genotypes, and XPC protein levels were tested with a comparative enzyme-linked immunosorbent assay, TaqMan polymerase chain reaction for XPC genotypes, and immunohistochemistry, respectively. Higher AFB1 exposure was observed among HCC patients versus the control group [odds ratio (OR) = 9.88 for AFB1 exposure years and OR = 6.58 for AFB1 exposure levels]. The XPC codon 939 Gln alleles significantly increased HCC risk [OR = 1.25 (95% confidence interval = 1.03-1.52) for heterozygotes of the XPC codon 939 Lys and Gln alleles (XPC-LG) and OR = 1.81 (95% confidence interval = 1.36-2.40) for homozygotes of the XPC codon 939 Gln alleles (XPC-GG)]. Significant interactive effects between genotypes and AFB1 exposure status were also observed in the joint-effects analysis. This polymorphism, moreover, was correlated with XPC expression levels in cancerous tissues ( r = −0.369, P &lt; 0.001) and with the overall survival of HCC patients (the median survival times were 30, 25, and 19 months for patients with homozygotes of the XPC codon 939 Lys alleles, XPC-LG, and XPC-GG, respectively), especially under high AFB1 exposure conditions. Like AFB1 exposure, the XPC codon 939 polymorphism was an independent prognostic factor influencing the survival of HCC. Additionally, this polymorphism multiplicatively interacted with the xeroderma pigmentosum complementation group D codon 751 polymorphism with respect to HCC risk (ORinteraction = 1.71). Conclusion: These results suggest that the XPC codon 939 polymorphism may be associated with the risk and outcome of AFB1-related HCC in the Guangxi population and may interact with AFB1 exposure in the process of HCC induction by AFB1. (Hepatology 2010;)
Diagnosis of Halothane Hepatitis
Authors: Alix Mathieu
Journal: JAMA (1973)

To the Editor.—  The question of how to diagnose halothane hepatitis was asked inThe Journal(222:1192, 1972). From the opinions advanced, a reader unfamiliar with immunology could conclude that the disease is well defined. Thus, I want to comment accurately about the current status of halothane hepatitis. In so doing, I will, by the same token, invalidate the immunological criteria advanced by Dr. Schaffner because they are either nonspecific or have not yet been confirmed. Since most of the evidence proposed is derived from Dr. Paronetto's study, 1 I will refer to several points in his article. The positive lymphocyte transformation test (LTT), in eight out of 15 patients with halothane hepatitis, could not be reproduced by four separate groups as cited by Mathieu et al (unpublished data) and Davies et al and Bruce et al. 2 The patient and control groups in some instances differ marginally in their
A dent in our sobriety
Authors: D. L Shawcross
Journal: BMJ (2009)

It began at last year’s conference of the British Association for the Study of the Liver. As I contemplated during the “symposium on alcohol” on how alcohol has ever so stealthily resulted in 4% of global deaths and disability I couldn’t help but chuckle to myself as I pondered the original meaning of symposium: a forum for men to debate, plot, and boast; in simple terms, an excuse to drink wine and have a party. 

It was difficult to understand why the audience all felt distinctly uncomfortable. After all, rarely a day passes by when, as hepatologists, we don’t see a patient whose psychological or physical wellbeing has been marred by alcohol. We know that the death rate from alcoholic liver disease has doubled in the past 10 years in the United Kingdom and that its incidence has risen eightfold in the under 35s as a culture of binge drinking has evolved among young people. We have all projected that the incidence of cirrhosis will increase exponentially and that there will be a 500% greater need for liver transplantation in the next decade.1 We have heard it all before. Yet as our anxiety was gradually eased by a glass of wine at the end of the symposium, a dent was left in our sobriety.

A …
NT-38 * MerTK AS A TARGET IN GLIOBLASTOMA
Authors: J. Wu, L. Huey, R. E. Bash, S. M. Cohen, M. G. Ewend, X. Wang, D. K. Graham, S. V. Frye, H. S. Earp, C. R. Miller
Journal: Neuro-Oncology (2014)

Glioma-associated macrophages and microglia (GIM) are infiltrating immune cells that modulate the glioblastoma (GBM) micro-environment. Pharmacological targeting of GIM represents a promising therapeutic strategy. MerTK receptor tyrosine kinase triggers macrophage ingestion of apoptotic material and polarizes macrophages to an M2-like, immunosuppressive phenotype that promotes tumor growth. In addition, aberrant MerTK expression in GBM tumor cells can provide pro-survival, pro-invasion and chemo-resistance signals. We examined MerTK expression by double immunofluorescence (IF) in 40 human GBM. Both GFAP+ tumor cells and CD68+ GIM expressed MerTK. Quantification in 12 matched pairs of newly-diagnosed and recurrent GBM showed a 5.5-fold increase in MerTK/CD68+ macrophages (p = 0.002), but no consistent changes in MerTK/GFAP+ tumor cells upon recurrence. Next, we examined the efficacy of a novel UNC-developed small molecule MerTK inhibitor (MerTKI) in a genetically engineered orthotopic allograft model of GBM (TRP). GBM were established for 7 days upon stereotactic injection of luciferase-expressing TRP cells into syngeneic, immune-competent mice. Mice (N = 10-12/group) were then randomized to receive no treatment, daily MerTKI (65mg/kg p.o.), or MerTKI plus fractionated radiation (XRT, 5 Gy q.o.d x3). Median survival was 24, 22, and 41.5 days, respectively (p = 0.003), while historical survival of TRP allograft mice treated with XRT alone was 30 days. Bioluminescence imaging (BLI) showed a significant growth delay in MerTKI + XRT-treated mice (doubling time 14 versus 4-4.5 days, p < 0.0001). Two mice remain alive after 50 days of combination treatment and tumor growth remains stable with 90-99% reduction in pre-treatment BLI. Post-mortem histology and IF are pending. These results suggest that both human GBM tumor cells and GIM express MerTK and that MerTK+ GIM may increase upon disease recurrence. MerTK inhibition in an immune-competent pre-clinical model may potentiate XRT response, providing a rationale for future studies of novel MerTK inhibitors in the treatment of GBM patients.
Comparison of Blood Flow Measured by Plethysmograph and Flowmeter During Steady State Forearm Exercise
Authors: JOHN LONGHURST, ROBERT J. CAPONE, DEAN T. MASON, ROBERT ZELIS
Journal: Circulation (1974)

Forearm blood flow was determined at rest and during steady state grip exercise by the venous occlusion technique with a single strand mercury-in-rubber strain gauge plethysmograph and was compared with blood flow simultaneously determined by an electromagnetic flowmneter around the brachial artery before, during, and after intermittent isotonic grip exercise in eight subjects. The comparison of plethysmographic flow ( y axis) with simultaneously measured flowmeter flow ( x axis) yielded a correlation coefficient of 0.797, a slope of 1.15 and a y intercept of 9.62. When flow was normalized per 100 cc of forearm, the correlation coefficient was 0.823, the slope 1.21, and the y intercept 0.871. The overestimation of the flowmeter blood flow by the plethysmograph could be explained by flow through skin vessels which bypassed the flowmeter. When averaged plethysmographic flow was compared to total planimetered flowmeter flow during exercise, there was a 1.7 times overestimation by the former technique, which was constant over the range of exercise employed.
Treatment of Bleeding Esophageal Varices
Authors: Willard A. Fry
Journal: JAMA (1964)

<h3>To the Editor:—</h3> Edmunds and West in the Sept 14 issue ofThe Journal(<b>189:</b>854, 1964) certainly make a strong plea for shunting operations in the treatment of bleeding esophageal varices. They state that the two groups "were comparable for the purpose of evaluating different types of treatment." However, they do not mention whether theirs is a controlled and/or randomized series and why operation was not performed (although apparently indicated according to their conclusions) on the one group of 21 patients. The medically treated group appears to fulfill the standard criteria for operation. Were there complicating medical disorders, older age ranges, obstinate patients, etc?
Medical Practice Among the Maoris.
Authors: John S. Reekie
Journal: JAMA (1907)

I find an extract from the British Medical Journal on "Phthisis and Superstition Among the Maoris."Perhaps your read- ers may be interested in some observations by myself while acting as local native health officer for four years among these interesting people.All forms of tuberculosis are widespread among them, and even in localities where the conditions are naturally almost ideal for coping with this disease, it is increasing in all its forms.The principal reason for this is their national custom of holding a "tangi" over the dead.This consists of feasting and mourning of all the relatives of the deceased while the body lies in state, surrounded by weeping women and men who rub noses with one another, and cover and uncover the dead to show new arrivals.No matter what the nature of the disease, this custom is not interfered with.The police dare not interfere.I was once called on to perform an autopsy on a native who had died suddenly without any ap¬ parent reason, and when I arrived where the body was lying in state in a tent I was refused permission to do anything and it was only after the police had been called and the tent cleared that I could get to work.Half-way through, the rel¬ atives returned with re-enforcements to drive away the dese¬ City.
A–Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance–Part 34
Authors: D S King, R Baskerville, Y Hellsten, D S Senchina, L M Burke, S J Stear, L M Castell
Journal: British Journal of Sports Medicine (2012)

One of the most concerned problems in neuroscience is how neurons communicate and convey information through spikes. There is abundant evidence in sensory systems to support the use of precise timing of spikes to encode information. However, it remains unknown whether precise temporal patterns could be generated to drive output in the primary motor cortex (M1), a brain area containing ample recurrent connections that may destroy temporal fidelity. Here, we used a novel brain-machine interface that mapped the temporal order and precision of motor cortex activity to the auditory cursor and reward to guide the generation of precise temporal patterns in M1. During the course of learning, rats performed the “temporal neuroprosthetics” in a goal-directed manner with increasing proficiency. Precisely timed spiking activity in M1 was volitionally and robustly produced under this “temporal neuroprosthetics”, demonstrating the feasibility of M1 implementing temporal codes. Population analysis showed that the local network was coordinated in a fine time scale as the overall excitation heightened. Furthermore, we found that the directed connection between neurons assigned to directly control the output (“direct neurons”) was strengthened throughout learning, as well as connections in the subnetwork that contains direct neurons. Network models revealed that excitatory gain and strengthening of subnetwork connectivity transitioned neural states to a more synchronous regime, which improved the sensitivity for coincidence detection and, thus, the precision of spike patterns. Therefore, our results suggested the recurrent connections facilitate the implementation of precise temporal patterns instead of impairing them, which provided new perspectives on the fine-timescale activity and dynamics of M1.
509. Adeno-Associated Vector Mediated Delivery of Anti-HIV Genes
Authors: Mayur C. Tamhane, Ramesh Akkina
Journal: Molecular Therapy (2006)

Recombinant adeno-associated virus serotype 2 (rAAV-2) vectors are being widely used for gene therapy applications. These vectors offer certain advantages for HIV gene therapy since the anti-HIV genes introduced into the vector will not interfere with the vector production as is the case seen with the production of some lentiviral vectors carrying HIV inhibitory genes. In our current studies we introduced three different HIV inhibitory genes with different mechanisms of action into the rAAV vectors and tested their efficacy. These consist of an anti-CCR5 siRNA targeted to the HIV-1 coreceptor CCR5 involved in viral entry, rhesus TRIM5a mediating innate resistance and murine APOBEC that can cause lethal hypermutations in viral genome. These transgenes were introduced into rAAV-2 vectors (Stratagene's helper free system) together with an EGFP reporter. Concentrated vectors were used to transduce a MAGI-CCR5 cell line and peripheral blood mononuclear cells (PBMC's). Transduced cells were sorted for enhanced green fluorescence protein (EGFP) expression and cultured. Down regulation of the CCR5 coreceptor was confirmed by FACS. Expression of TRIM5aRh and murine APOBEC was determined by western blots. The transgenic cells were challenged with HIV-1 to determine viral resistance. Preliminary results showed varying levels of protection with these constructs. The best protection conferred in transduced MAGI-CCR5 cells was seen with murine APOBEC followed by rhesus TRIM5a and then CCR5 shRNA. In PBMC challenges, both murine APOBEC and rhesus TRIM5a showed relatively higher levels of protection compared to that shown by CCR5 shRNA. These results showed the utility of rAAV vectors for gene transduction of different anti-HIV constructs for AIDS gene therapy.
CD4+ T cell lineage integrity is controlled by the histone deacetylases HDAC1 and HDAC2
Authors: Nicole Boucheron, Roland Tschismarov, Lisa Göschl, Mirjam A Moser, Sabine Lagger, Shinya Sakaguchi, Mircea Winter, Florian Lenz, Dijana Vitko, Florian P Breitwieser, Lena Müller, Hammad Hassan, Keiryn L Bennett, Jacques Colinge, Wolfgang Schreiner, Takeshi Egawa, Ichiro Taniuchi, Patrick Matthias, Christian Seiser, Wilfried Ellmeier
Journal: Nature Immunology (2014)
THE DEGREE OF DISPERSION OF THE BACILLUS AS A FACTOR IN INFECTION AND RESISTANCE IN EXPERIMENTAL TUBERCULOSIS
Authors: R. M. Thomas, F. Duran-Reynals
Journal: The Journal of Experimental Medicine (1935)

1. The skin lesions in rabbits and guinea pigs following intradermal injection of tubercle bacilli (5 strains) were greatly increased in size and severity when testicle extract was added to the inoculum. Such enhancement was followed by a more widespread and rapidly progressing disease only when virulent strains were employed. 2. Attempts to suppress the development of skin lesions resulting from the injection of either normal or tuberculous rabbits with very small quantities of tubercle bacilli mixed with testicle extract were unsuccessful. 3. The skin reactions of tuberculous guinea pigs to tuberculo-protein MA 100 were greatly increased in size and markedly reduced in intensity by the addition of testicle extract to the protein solution. The toxic effect of larger quantities of tuberculo-protein was not altered by the addition of testicle extract. 4. The dispersion of tubercle bacilli through the skin of tuberculous rabbits resulted in a marked enhancement of the Koch phenomenon but was not followed by any extension of the new infection to the viscera. Tuberculous rabbits infected on two occasions with dead tubercle bacilli suspended in testicle extract showed an increased resistance to the disease when compared with controls receiving dead bacilli suspended in saline solution. 5. The resistance conferred upon tuberculous guinea pigs by superinfection was greatly increased when the bacilli employed were dispersed through the skin with testicle extract. 6. The parenteral administration of large quantities of testicle extract to recently infected guinea pigs did not result in any increase in the extent of the visceral lesions. 7. The partial immunity conferred upon guinea pigs and rabbits by vaccination with heat-killed tubercle bacilli was increased as a result of dispersion of the vaccine through the skin with testicle extract.
Endothelin at Pathophysiological Concentrations Mediates Coronary Vasoconstriction via the Endothelin-A Receptor
Authors: Charles R. Cannan, John C. Burnett, Roland R. Brandt, Amir Lerman
Journal: Circulation (1995)

Background Endothelin-1 (ET-1) is an endothelium-derived vasoconstrictor peptide. Controversy persists regarding the predominant ET receptor that mediates coronary vasoconstriction at pathophysiological concentrations. The aim of the present study was to test the hypothesis that ET mediates local coronary vasoconstriction via the ET-A receptor at low concentrations of exogenous ET-1 designed to mimic pathophysiological states compared with pharmacological concentrations. Methods and Results ET-1 (group 1, n=5) or sarafotoxin, a specific ET-B receptor agonist (group 3, n=6) (each at 2 ng/kg per minute), was infused into the left circumflex coronary artery in the anesthetized dog. In group 2 dogs (n=5), the same dose of ET-1 was infused with 4 μg/kg per minute of the specific ET-A receptor antagonist FR-139317. In group 4 (n=5), the same dose of sarafotoxin was infused with 50 μg/kg per minute of the specific inhibitor of nitric oxide formation, N G -monomethyl- l -arginine (L-NMMA). No difference in hemodynamics, coronary blood flow (CBF), coronary vascular resistance (CVR), or coronary artery diameter (CAD) was observed at baseline between the groups. In group 1, intracoronary ET-1 significantly decreased CBF and CAD in association with an increase in CVR. The percentage decrease in CBF and CAD in the group that received ET-1 and the ET-A receptor antagonist (group 2) was significantly less than that in the group that received ET-1 alone (group 1) (−12±3% versus −48±6% [ P &lt;.001] and −4.6±0.8 versus 1.0±0.3 [ P &lt;.05], respectively). The administration of the ET-A receptor antagonist (group 2) abolished the ET-mediated increase in CVR (7±5% versus 105±21%, P &lt;.005). There was no significant effect on CBF, CVR, or CAD in the group receiving sarafotoxin alone (group 3). The administration of L-NMMA and sarafotoxin (group 4) resulted in a significant percentage decrease in CBF compared with the group that received sarafotoxin alone (−28±7% versus −8±2% [ P &lt;.05]). Conclusions The present study demonstrates that low concentrations of exogenous ET-1, which may mimic pathophysiological concentrations, result in coronary vasoconstriction mediated predominantly via the ET-A receptor because such vasoconstriction is significantly attenuated by blockade with FR-139317. The ET-B receptor may have a dual vasoconstrictive and vasodilatory effect.
TREATMENT OF LARYNGEAL TUBERCULOSIS AT THE MONTEFIORE HOME FOR CHRONIC INVALIDS (N. Y.)
Authors: W. FREUDENTHAL
Journal: JAMA (1901)

One of the most difficult chapters in the treatment of the upper air-passages is the management and treatment of laryngeal tuberculosis. In fact, to the hospital physician this has been one of the most disagreeable tasks possible. To see these most miserable of sufferers live for months, or even years, with constantly increasing pain, for whom even the swallowing of their own saliva is a dreaded effort, has been an occurrence of every day; and we, as physicians, have been as a rule practically helpless in combatting this disease. Morphin, internally and locally, quickly reached its effectiveness in most cases, and for many patients the cocain spray is extremely disagreeable. For the last ten years I have had to attend to these patients at the Montefiore Home, where we have sometimes as many as twenty or thirty suffering from laryngeal tuberculosis in every stage possible. That under the above condition
Collective Investigation of the Influence of the Silver Nitrate Injections on Phthisis.
Authors: Thomas J. Mays
Journal: JAMA (1901)

Philadelphia, Aug. 15, 1901. <h3>To the Editor:</h3> —In 1892 the undersigned began a collective investigation of the action of cold in the treatment of acute pneumonia and there is reason for believing that this procedure, which resulted in gathering four hundred cases of this disease thus treated, with a death-rate not quite five per cent., was an important factor in calling attention to the utility of that treatment, and in introducing it to the profession of this country. The research was based on the conviction that no remedy can be called truly successful until it has passed the exacting crucible of clinical experience. It is now proposed to apply the same ordeal to the silver-injection treatment of phthisis, which, in a large hospital, dispensary and private practice, reaching over a period of three years, and during which many thousand injections were administered, has given me greater satisfaction than any other
Corrigendum to “Gene expression analysis during dengue virus infection in HepG2 cells reveals virus control of innate immune response” [Journal of Infection 2010;60:65–75]
Authors: Thaís M. Conceição, Tatiana El-Bacha, Camila S.A. Villas-Bôas, Gerardo Coello, Jorge Ramírez, Monica Montero-Lomeli, Andrea T. Da Poian
Journal: Journal of Infection (2010)