tbuckley/cabot-search huggingface dataset:
Response of aldosterone and blood pressure to angiotensin II infusion in anephric man. Effect of sodium deprivation.
Authors: J Deheneffe, V Cuesta, J D Briggs, J J Brown, R Fraser, A F Lever, J J Morton, I S Robertson, M Tree
Journal: Circulation Research (1976)

Angiotensin II, infused intravenously, increased plasma aldosterone concentration in two of six anephric subjects taking their usual dietary quantities of sodium. After 3 days of dietary sodium restriction and weight-reducing hemodialysis, the aldosterone response to infused angiotensin II in the two previously reactive subjects was enhanced, while the four previously unreactive subjects also showed a rise in plasma aldosterone. Before and after sodium depletion the anephric subjects were less responsive than normal subjects. Even when sodium-depleted, the anephrics showed no further rise in plasma aldosterone when arterial plasma angiotensin II was increased by infusion to concentrations greater than 50-199pg/ml, in contrast to sodium-depleted normals who show progressive aldosterone responses with plasma angiotensin II concentrations up to at least 370pg/ml. Before the infusion of angiotensin II, arterial plasma renin, angiotensin II, and aldosterone were detectable in the anephrics, but were unchanged by dietary sodium restriction or weight-reducting hemodialysis. Sodium depletion caused significant falls in weight, plasma sodium, and blood pressure, but no changes in plasma potassium or cortisol. Increases in blood pressure in relation to increments of arterial plasma angiotensin II were unaffected by sodium depletion, as might be expected in the absence of a rise in endogenous angiotensin II.
THE CONCENTRATION OF THE PROTECTIVE BODIES IN ANTIPNEUMOCOCCUS SERUM. SPECIFIC PRECIPITATE EXTRACTS
Authors: Henry T. Chickering
Journal: The Journal of Experimental Medicine (1915)

1. The protective substances contained in specific precipitates from antipneumococcus serum can be extracted by suitable chemical and physical agents, dilute sodium carbonate at 42 degrees C. being especially advantageous as an extractive agent. 2. The resulting water-clear extracts, when made up to the original volume of the serum used for precipitation, protect animals almost as well as does the whole serum. 3. The bacterial extracts used in precipitating the protective substances from the serum act specifically; that is, a bacterial extract of pneumococcus of Type I removes the protective substances from a Type I immune serum only. 4. In a polyvalent serum of Type I and Type II, the protective substances of each type may be removed independently of each other by the successive addition of the homologous antigens. 5. Extracts of specific serum precipitates contain only one-fiftieth to one-sixtieth of the protein in the original serum, and about one-half the protein of the whole precipitate. 6. Extracts contain not only protective substances but agglutinins and precipitins. 7. Extracts and whole precipitates not only confer passive immunity but stimulate the production of active immunity to pneumococcus infection in rabbits and mice.
Properties of cultures of M. tuberculosis isolated from the surfaces of objects TB facilities
Authors: Natalya Eremeeva, Diana Vakhruscheva, Marionella Kravchenco, Kseniya Bobrovskaya, Tatyana Umpeleva
Journal: European Respiratory Journal (2013)

Goal:  determine the degree of contamination of  M. tuberculosis  (MBT) of the surface of objects of TB facilities.   Material and methods.  The specimens from the surfaces were taken by washout method. One part of washout was tested by Real-Time PCR to determine IS6110. If the quantity of DNA was sufficient enough to detecting RIF-, INH-, FQ-resistance mutations determined by TB-Biochip system. The second part of washout was inoculated on medium Lowenstein-Jensen (L-J). Drug susceptibility of MBT cultures to first- and second-line were determined by absolute concentration method. The MBT cultures were genotyped by MIRU-VNTR method. Genetic family was established by comparing MIRU-VNTR isolates profiles obtained with available the data-base «MIRU-VNTRpius» (http//www.miru-vntrplus.org).   Results and discussion.  137 samples of washouts have been obtained. IS6110 of MBT was found in 132 samples. RIF-, INH-, FQ-resistance mutations was found in 44 samples. 15 MBT cultures on L-J were found. All MBT cultures were drug-resistance to first- line of anti-TB drugs and capreomycin, kanamycin. 8 MBT cultures were also resistant to ofloxacin.  The results of genotyping have been were obtained for 13 MBT cultures, in 9 of them having genotype  Beijing . In 4 MBT cultures mix of genotypes such as  Beijing  and  Ural  have been revealed.   Conclusion.  The surfaces in TB facilities are contaminated with MDR and XDR strains of MBT, mainly  Beijing  genotype. So there are very dangerous for staff and patients because there is a high risk of catching of TB.
Relationship between hepatitis C virus subtypes and clinical features of liver disease seen in alcoholics
Authors: Hirokazu Yokoyama, Hiromasa Ishii, Susumu Moriya, Shigeyuki Nagata, Tetsu Watanabe, Kiyotaka Kamegaya, Hisao Takahashi, Katsuya Maruyama, Paul Haber, Masaharu Tsuchiya
Journal: Journal of Hepatology (1995)
Xenotransplantation: where are we today?
Authors: M D Dooldeniya, A N Warrens
Journal: Journal of the Royal Society of Medicine (2003)

Xenotransplantation has retained its topicality since the resurgence of interest in the mid 1990s. Work continues in many scientific fields to overcome the obstacles. However, as old problems are solved, new ones present themselves for solution. In this brief review we discuss the need for xenotransplantation, issues relating to physiological compatibilities, current ideas on how to overcome the initial aggressive hyperacute rejection (HAR) and the later immunological difficulties as well as the risks and ethical issues.
Efficacy and safety of a novel synergistic drug candidate, CRx-102, in hand osteoarthritis
Authors: T K Kvien, E Fjeld, B Slatkowsky-Christensen, M Nichols, Y Zhang, A Proven, K Mikkelsen, O Palm, A A Borisy, J Lessem
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> The novel synergistic drug candidate CRx-102 comprises dipyridamole and low dose prednisolone and is in clinical development for the treatment of immunoinflammatory diseases. The purpose of this clinical study was to examine the efficacy and safety of CRx-102 in patients with hand osteoarthritis (HOA). <h3>Methods:</h3> The study was conducted as a blinded, randomised, placebo-controlled trial at four centres in Norway. Eligibility criteria included being of age 30–70 years, at least one swollen and tender joint, a Kellgren–Lawrence (K–L) score of 2 or higher on radiographs, and a score of at least 30 mm pain on the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) visual analogue pain scale (VAS). The primary endpoint was a reduction in pain from baseline to day 42 on the AUSCAN pain subscale. Two-sided p values for the differences in least squares (LS) means adjusted for baseline are presented. <h3>Results:</h3> The mean age of the 83 patients with HOA was 60 years and 93% were females. CRx-102 was statistically superior to placebo at 42 days for changes in AUSCAN pain (LS mean −14.2 vs −4.0) and for clinically relevant secondary endpoints (joint pain VAS (−18.6 vs −6.3), patient global VAS (−15.9 vs −4.2)) in the intention to treat population. The most frequently reported adverse event during the study was headache (52% in CRx-102 vs 15% in the placebo group). <h3>Conclusions:</h3> The novel synergistic drug candidate CRx-102 demonstrated efficacy by statistically reducing pain compared to placebo in HOA and was generally well tolerated.
Radiation Therapy for Squamous Cell Carcinoma of the Tonsillar Region: A Preferred Alternative to Surgery?
Authors: William M. Mendenhall, Robert J. Amdur, Scott P. Stringer, Douglas B. Villaret, Nicholas J. Cassisi
Journal: Journal of Clinical Oncology (2000)

There are no definitive randomized studies that compare radiotherapy (RT) with surgery for tonsillar cancer. The purpose of this study was to evaluate the results of RT alone and RT combined with a planned neck dissection for carcinoma of the tonsillar area and to compare these data with the results of treatment with primary surgery.Four hundred patients were treated between October 1964 and December 1997 and observed for at least 2 years. One hundred forty-one patients underwent planned neck dissection, and 18 patients received induction (17 patients) or concomitant (one patient) chemotherapy.Five-year local control rates, by tumor stage, were as follows: T1, 83%; T2, 81%; T3, 74%; and T4, 60%. Multivariate analysis revealed that local control was significantly influenced by tumor stage (P =.0001), fractionation schedule (P =.0038), and external beam dose (P =.0227). Local control after RT for early-stage cancers was higher for tonsillar fossa/posterior pillar cancers than for those arising from the anterior tonsillar pillar. Five-year cause-specific survival rates, by disease stage, were as follows: I, 100%; II, 86%; III, 82%; IVa, 63%; and IVb, 22%. Multivariate analysis revealed that cause-specific survival was significantly influenced by overall stage (P =.0001), planned neck dissection (P =.0074), and histologic differentiation (P =.0307). The incidence of severe late complications after treatment was 5%.RT alone or combined with a planned neck dissection provides cure rates that are as good as those after surgery and is associated with a lower rate of severe complications.
INTERNATIONAL COLLABORATION IN RENAL TRANSPLANTATION
Authors: J.A Sachs, H Festenstein, R.T.D Oliver, J.P Blandy, J.R Salaman, I.C Balfour, G.D Pegrum, G.B Williams, J.P Hopewell, J.F Moorhead, A.D Barnes, M Bewick
Journal: The Lancet (1971)
AHT-ChIP-seq: a completely automated robotic protocol for high-throughput chromatin immunoprecipitation
Authors: Sarah Aldridge, Stephen Watt, Michael A Quail, Tim Rayner, Margus Lukk, Michael F Bimson, Daniel Gaffney, Duncan T Odom
Journal: Genome biology (2013)

ChIP-seq is an established manually-performed method for identifying DNA-protein interactions genome-wide. Here, we describe a protocol for automated high-throughput (AHT) ChIP-seq. To demonstrate the quality of data obtained using AHT-ChIP-seq, we applied it to five proteins in mouse livers using a single 96-well plate, demonstrating an extremely high degree of qualitative and quantitative reproducibility among biological and technical replicates. We estimated the optimum and minimum recommended cell numbers required to perform AHT-ChIP-seq by running an additional plate using HepG2 and MCF7 cells. With this protocol, commercially available robotics can perform four hundred experiments in five days.
Lung function decline and outcomes in an elderly population
Authors: D M Mannino
Journal: Thorax (2006)

To determine the risk factors for and outcomes associated with the rapid decline in lung function in a cohort of elderly US adults.Data from 4923 adult participants aged 65 years and older at baseline in the Cardiovascular Health Study were analysed. Subjects were classified using a modification of the GOLD criteria for chronic obstructive pulmonary disease (COPD) and a "restricted" category (FEV1/FVC>or=70% and FVC<80% predicted) was added. Cox proportional hazard models were used to determine the risk of lung function decline over 4 years on subsequent mortality and COPD hospital admissions after adjusting for age, race, sex, smoking status, and other factors.Of the participants in the initial cohort, 3388 (68.8%) had spirometric tests at the year 4 visit. Participants with GOLD stages 3 or 4 COPD at baseline were less likely than normal subjects to have follow up spirometric tests (52.7% v 77.9%, p<0.01) and were more likely to be in the most rapidly declining quartile of FEV1 (28.2% v 21.3%, p<0.01) with an annual loss of FEV1 of at least 3.5%. Overall, being in the most rapidly declining quartile of FEV1 from baseline to year 4 was associated with an increased risk of admission to hospital for COPD (adjusted hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.3 to 2.0) and all-cause death (adjusted HR 1.5, 95% CI 1.2 to 1.7) over an additional 7 years of follow up.More rapid decline in lung function is independently associated with a modest increased risk of hospital admissions and deaths from COPD in an elderly cohort of US participants.
Chronic ETA receptor blockade prevents endothelial dysfunction of small arteries in apolipoprotein E-deficient mice
Authors: Livius V d'Uscio, Matthias Barton, Sidney Shaw, Thomas F Lüscher
Journal: Cardiovascular Research (2002)

Objective: This study investigated whether endothelial dysfunction occurs in mesenteric arteries of apoE-deficient mice and determined the role of endothelin (ET)-1, which is increased in human atherosclerosis, using an orally active endothelin ETA receptor antagonist. Methods: ApoE-deficient and C57BL/6J control mice were fed for 30 weeks with normal chow or high-fat Western-type diet alone or in combination with darusentan (LU135252; 50 mg/kg/day). Vasomotor reactivity of isolated small mesenteric arteries (I.D. 200–250 μm) was studied in vitro under perfused and pressurized conditions. Results: In both mouse strains, about one fourth of the endothelium-dependent relaxant response to acetylcholine was insensitive to inhibition by l-NAME and indomethacin. In mesenteric arteries of apoE-deficient mice on Western-type diet, increased intima-media thickness and levels of endothelin-1 protein were observed. In addition, NO-mediated endothelium-dependent relaxation to acetylcholine was reduced without affecting l-NAME/indomethacin insensitive relaxation and contractions to endothelin-1 and serotonin were enhanced. Treatment with darusentan normalized vascular structure, NO-mediated relaxation to acetylcholine and contractions to endothelin-1 and serotonin without affecting blood pressure or plasma cholesterol levels. Conclusions: Severe hypercholesterolemia in apoE-deficient mice is associated with attenuation of NO-mediated relaxation to acetylcholine and increased vascular endothelin-1 content. Chronic ETA receptor blockade may provide a new therapeutic approach to improve NO-mediated endothelium-dependent vasomotion in small arteries.
Classification of Burn-Care Facilities in the United States
Authors: Irving Feller
Journal: JAMA (1971)

The concept of specialized care facilities for the burned patient is relatively new. The first "burn units" were established in 1947 at the Medical College of Virginia, and at the Army Surgical Research Unit in San Antonio, Tex. These units were organized to provide, within their walls, almost all of the resources required for these severely injured patients. Additional units were established in the next two decades. In 1969, a survey of the short-term general and children's hospitals in the United States was completed, to determine the availability of facilities for the care of the burned patients. Only 32 such facilities could be identified. In addition to the hospitals that provide special facilities for burned patients, 46 others are identified with improved care. These facilities and special programs are not alike, and a classification of them is provided to differentiate the levels of care provided. Of the 6,062 hospitals initially
An Empirical Codon Model for Protein Sequence Evolution
Authors: C. Kosiol, I. Holmes, N. Goldman
Journal: Molecular Biology and Evolution (2007)

In the past, 2 kinds of Markov models have been considered to describe protein sequence evolution. Codon-level models have been mechanistic with a small number of parameters designed to take into account features, such as transition-transversion bias, codon frequency bias, and synonymous-nonsynonymous amino acid substitution bias. Amino acid models have been empirical, attempting to summarize the replacement patterns observed in large quantities of data and not explicitly considering the distinct factors that shape protein evolution. We have estimated the first empirical codon model (ECM). Previous codon models assume that protein evolution proceeds only by successive single nucleotide substitutions, but our results indicate that model accuracy is significantly improved by incorporating instantaneous doublet and triplet changes. We also find that the affiliations between codons, the amino acid each encodes and the physicochemical properties of the amino acids are main factors driving the process of codon evolution. Neither multiple nucleotide changes nor the strong influence of the genetic code nor amino acids' physicochemical properties form a part of standard mechanistic models and their views of how codon evolution proceeds. We have implemented the ECM for likelihood-based phylogenetic analysis, and an assessment of its ability to describe protein evolution shows that it consistently outperforms comparable mechanistic codon models. We point out the biological interpretation of our ECM and possible consequences for studies of selection.
Fight to tackle unhealthy lifestyles has widened gap in health inequalities
Authors: A. O'Dowd
Journal: BMJ (2012)

Efforts to persuade people to follow a healthier lifestyle have worked only for wealthier parts of the population and widened the health inequalities divide.

This is the conclusion of a report from health think tank The King’s Fund, which found that poorer people have been left behind in the fight against unhealthy lifestyles.

The report1 claims to be the first study to examine how patterns of multiple lifestyle behaviours have changed over time in England.

Researchers used data from the Health Survey for England 2 to analyse changes in four key lifestyle behaviours—smoking, excessive drinking, poor diet, and lack of exercise—between 2003 and 2008.

They focused on these four categories of unhealthy …
The Protein Kinase Cβ–Selective Inhibitor, Enzastaurin (LY317615.HCl), Suppresses Signaling through the AKT Pathway, Induces Apoptosis, and Suppresses Growth of Human Colon Cancer and Glioblastoma Xenografts
Authors: Jeremy R. Graff, Ann M. McNulty, Kimberly Ross Hanna, Bruce W. Konicek, Rebecca L. Lynch, Spring N. Bailey, Crystal Banks, Andrew Capen, Robin Goode, Jason E. Lewis, Lillian Sams, Karen L. Huss, Robert M. Campbell, Philip W. Iversen, Blake Lee Neubauer, Thomas J. Brown, Luna Musib, Sandaruwan Geeganage, Donald Thornton
Journal: Cancer Research (2005)

Abstract Activation of protein kinase Cβ (PKCβ) has been repeatedly implicated in tumor-induced angiogenesis. The PKCβ-selective inhibitor, Enzastaurin (LY317615.HCl), suppresses angiogenesis and was advanced for clinical development based upon this antiangiogenic activity. Activation of PKCβ has now also been implicated in tumor cell proliferation, apoptosis, and tumor invasiveness. Herein, we show that Enzastaurin has a direct effect on human tumor cells, inducing apoptosis and suppressing the proliferation of cultured tumor cells. Enzastaurin treatment also suppresses the phosphorylation of GSK3βser9, ribosomal protein S6S240/244, and AKTThr308. Oral dosing with Enzastaurin to yield plasma concentrations similar to those achieved in clinical trials significantly suppresses the growth of human glioblastoma and colon carcinoma xenografts. As in cultured tumor cells, Enzastaurin treatment suppresses the phosphorylation of GSK3β in these xenograft tumor tissues. Enzastaurin treatment also suppresses GSK3β phosphorylation to a similar extent in peripheral blood mononuclear cells (PBMCs) from these treated mice. These data show that Enzastaurin has a direct antitumor effect and that Enzastaurin treatment suppresses GSK3β phosphorylation in both tumor tissue and in PBMCs, suggesting that GSK3β phosphorylation may serve as a reliable pharmacodynamic marker for Enzastaurin activity. With previously published reports, these data support the notion that Enzastaurin suppresses tumor growth through multiple mechanisms: direct suppression of tumor cell proliferation and the induction of tumor cell death coupled to the indirect effect of suppressing tumor-induced angiogenesis.
Enhancement of Hypoxia-Induced Tumor Cell Death <b> <i>In vitro</i> </b> and Radiation Therapy <b> <i>In vivo</i> </b> by Use of Small Interfering RNA Targeted to Hypoxia-Inducible Factor-1α
Authors: Xiuwu Zhang, Takashi Kon, He Wang, Fang Li, Qian Huang, Zahid N. Rabbani, John P. Kirkpatrick, Zeljko Vujaskovic, Mark W. Dewhirst, Chuan-Yuan Li
Journal: Cancer Research (2004)

Abstract Hypoxia-inducible factor-1α (HIF-1α) is an important transcriptional factor that is activated when mammalian cells experience hypoxia, a tumor microenvironmental condition that plays pivotal roles in tumor progression and treatment. In this study, we examined the idea of down-regulating HIF-1α in tumor cells for therapeutic gain. We show that the expression levels of HIF-1α can be significantly attenuated by use of the recently established small interfering RNA technology in combination with adenovirus-mediated gene transfer. Down-regulation of the HIF-1α protein enhanced hypoxia-mediated tumor cell apoptosis in vitro. Subcutaneous tumor growth was also prevented from cells with attenuated HIF-1α expression. In addition, intratumoral injection of adenovirus encoding the HIF-1α-targeted small interfering RNA had a small but significant effect on tumor growth when combined with ionizing radiation. Therefore, our results provide proof of HIF-1α as an effective target for anticancer therapy. They also suggest that an adenovirus-based small interfering RNA gene transfer approach may be a potentially effective adjuvant strategy for cancer treatment.
Correlation between Development of Rash and Efficacy in Patients Treated with the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Erlotinib in Two Large Phase III Studies
Authors: Bret Wacker, Tina Nagrani, Jacqueline Weinberg, Karsten Witt, Gary Clark, Pablo J. Cagnoni
Journal: Clinical Cancer Research (2007)

Data from two large phase III studies were analyzed to characterize the correlation between the occurrence of rash during treatment with the epidermal growth factor receptor inhibitor erlotinib and improved clinical outcomes.Overall survival, progression-free survival (PFS), and tumor response were compared between patients in a rash-evaluable subset who did or did not develop rash in National Cancer Institute of Canada Clinical Trials Group Studies BR.21 (single agent in non-small-cell lung cancer, n = 444 in erlotinib group and n = 229 in placebo group) and PA.3 (combination with gemcitabine in pancreatic cancer, n = 254 in erlotinib plus gemcitabine group and n = 245 in placebo plus gemcitabine group).Presence of rash strongly correlated with overall survival in both studies. In Study BR.21, these correlations increased with rash severity grade: grade 1 versus no rash [hazard ratio (HR), 0.41, P < 0.001] and grade >or=2 versus no rash (HR, 0.29, P < 0.001). Similar results were observed for PFS. Disease control (complete response + partial response + stable disease) seemed to increase with the presence and severity of rash. In Study PA.3, grade >or=2 rash (but not grade 1) strongly correlated with overall survival improvement: grade >or=2 versus no rash (HR, 0.47, P < 0.001). Similarly, grade >or=2 rash was strongly correlated with improvements in PFS and disease control.Physicians and patients should view rash development as a positive event indicative of greater likelihood of clinical benefit. Further studies are required to identify patients most likely to develop rash and to determine if dose escalation to induce rash can improve efficacy.