tbuckley/cabot-search huggingface dataset:
Reduction of Blood Pressure by Puromycin Infused Selectively into the Ischaemic Kidney in Experimental Renal Hypertension
Authors: G. J. Macdonald, R. B. Blacket
Journal: Cardiovascular Research (1967)

In rats made hypertensive by unilateral renal artery constriction, blood pressure could be reduced to normal levels or below by infusion, into the aorta near the origin of the renal arteries, of a solution of puromycin, an inhibitor of protein synthesis. Identical infusions into normal rats, or infusions into hypertensive rats below the origin of the renal arteries, produced no such effect.
Gene Expression Profiling using Nanostring Digital RNA Counting to Identify Potential Target Antigens for Melanoma Immunotherapy
Authors: Rachel E. Beard, Daniel Abate-Daga, Shannon F. Rosati, Zhili Zheng, John R. Wunderlich, Steven A. Rosenberg, Richard A. Morgan
Journal: Clinical Cancer Research (2013)

The success of immunotherapy for the treatment of metastatic cancer is contingent on the identification of appropriate target antigens. Potential targets must be expressed on tumors but show restricted expression on normal tissues. To maximize patient eligibility, ideal target antigens should be expressed on a high percentage of tumors within a histology and, potentially, in multiple different malignancies.A Nanostring probeset was designed containing 97 genes, 72 of which are considered potential candidate genes for immunotherapy. Five established melanoma cell lines, 59 resected metastatic melanoma tumors, and 31 normal tissue samples were profiled and analyzed using Nanostring technology.Of the 72 potential target genes, 33 were overexpressed in more than 20% of studied melanoma tumor samples. Twenty of those genes were identified as differentially expressed between normal tissues and tumor samples by ANOVA analysis. Analysis of normal tissue gene expression identified seven genes with limited normal tissue expression that warrant further consideration as potential immunotherapy target antigens: CSAG2, MAGEA3, MAGEC2, IL13RA2, PRAME, CSPG4, and SOX10. These genes were highly overexpressed on a large percentage of the studied tumor samples, with expression in a limited number of normal tissue samples at much lower levels.The application of Nanostring RNA counting technology was used to directly quantitate the gene expression levels of multiple potential tumor antigens. Analysis of cell lines, 59 tumors, and normal tissues identified seven potential immunotherapy targets for the treatment of melanoma that could increase the number of patients potentially eligible for adoptive immunotherapy.
P299 The Role Of A Multidisciplinary Respiratory Hub In Improving Post-discharge Follow Up Of Patients Receiving Acute Non-invasive Ventilation (niv)
Authors: F. Rauf, A. Oakes, Y. Khan, T. Stuart, B. Chakraborty, A. Turner, R. Mukherjee
Journal: Thorax (2014)

<h3>Introduction</h3> Post-discharge follow up rate is a national audit metric for acute NIV services in the UK [Davies M. Adult NIV Audit report. <i>BTS Reports </i>2012. <b>4</b> (3): 9–10.]. Appropriate respiratory follow up reduces the number of re-admissions [Turner AM <i>et al</i>. <i>Prim Care Respir J</i> 2013; <b>22</b>(1):72–78.] In order to improve post-discharge follow ups, a rapid access one-stop multidisciplinary respiratory outpatient Hub was created at our 709-bedded acute hospital in October 2011. <h3>Methods</h3> From the acute NIV database maintained continuously since 2004, we analysed the proportion of discharges that were offered respiratory follow up within 6 months of discharge after Acute NIV during the calendar year 2009 (pre-Hub) and first 6 months of 2013 (post-Hub). Chi-squared test was performed for statistical significance of the observed differences. <h3>Results</h3> The proportion of unique discharges offered a follow up appointment at the time of discharge improved from 57% (62/107) pre-Hub to 80% (36/45) post-Hub: p = 0.009. The proportion of patients attending follow-up appointments increased from 40% (42/107) pre-Hub to 58% (26/45) post-Hub: p = 0.036, confirming a statistically significant improvement. The number of acute NIV re-admissions dropped between 2009 and 2013 but expectedly not statistically significant, as only 6 months’ data from the post-Hub period was analysed against 12 months of data from the pre-Hub period. <h3>Conclusions</h3> The increase in the number of patients attending post-discharge NIV follow up correlates with the direct increase in the number being offered follow up, an improvement most obviously measuring the impact of the multidisciplinary ‘Hub’. The Hub would also be the most plausible explanation for the drop in acute NIV re-admissions between the 2 periods, not the least because apart from a ‘routine’ follow-up, it supports community teams and provides an alternative to ambulance calls to people with complex respiratory needs in a responsive fashion. Further longitudinal evaluation of the Multidisciplinary Hub is necessary to fully understand its impact on the quality and safety of complex respiratory care.
Depletion of latent HIV-1 infection in vivo: a proof-of-concept study
Authors: Ginger Lehrman, Ian B Hogue, Sarah Palmer, Cheryl Jennings, Celsa A Spina, Ann Wiegand, Alan L Landay, Robert W Coombs, Douglas D Richman, John W Mellors, John M Coffin, Ronald J Bosch, David M Margolis
Journal: The Lancet (2005)
Comparison of Quantitative Sensory-Threshold Measures for Their Association With Foot Ulceration in Diabetic Patients
Authors: Jay M Sosenko, Marta Kato, Ramon Soto, Diane E Bild
Journal: Diabetes Care (1990)

We compared the accuracy of cutaneous pressure perception-threshold measurements with that of other sensory-threshold measurements for detecting diabetic foot ulcer patients. Three hundred fourteen non-insulindependent diabetic patients were studied, of whom 91 had either a current foot ulcer or a history of foot ulceration. Foot ulcer patients had much higher pressure perception thresholds at the hallux than those without foot ulcers (mean ± SE 4.63 ± 0.05 vs. 3.54 ± 0.04 U, P &amp;lt; 0.001). The magnitude of association was higher than that for vibration thresholds and markedlygreater than those for cool and warm thresholds. Pressure thresholds were highly accurate for identifying foot ulcer patients. At a threshold level of 4.21 U, the sensitivity was 0.84, with a specificity of 0.96. At similar sensitivities for vibration and thermal thresholds, specificities were lower. Foot ulceration and cutaneous pressure perception threshold are strongly associated. Pressure-threshold measurements are extremely accurate and perform atleast as well as other quantitative sensory tests in identifying foot ulcer patients. Assessment of the foot pressure threshold may have promise as a simple and inexpensive method for detecting diabetic patients at risk for footulcers.
Renewed Focus on Preventing Gastric Cancer
Authors: S. Jenks
Journal: JNCI Journal of the National Cancer Institute (2015)

Anderson Cancer Center in Houston, who also writes about this topic."Drug companies are increasing drug prices to the extent it is harming our patients.Advocating for lower drug prices is a necessity to save the lives of patients who can't afford them."Elsewhere, Kantarjian, Fojo, and colleagues have endorsed value pricing.In this alternative model, a drug's price reflects the proportional benefit to patients, such as prolonging OS and improving quality of life-concepts that guide price negotiations in Europe and elsewhere. 3-6Drugs with greater benefit may cost more, and those that adversely affect quality of life should compensate by offering more benefits in survival."It requires all of us to agree on benchmarks," Fojo said."For example, a smaller gain could be valued more in pancreatic or rare cancers that currently have no effective therapy."According to Yu, ASCO is developing a framework to compare value of treatments on the basis of clinical benefit, toxic effects, and cost.How much is society pressing to move in this direction?"My patients aren't complaining.They don't actually know what these drugs cost because insurance pays for them," Flaherty said."The groundswell of protest over pricing is among insurance companies, and I can see why," said Lowe, also agreeing with the other
Tuberculosis vaccines: time to reset the paradigm?: Table 1
Authors: Ajit Lalvani, Saranya Sridhar, C Fordham von Reyn
Journal: Thorax (2013)

Development of a more effective tuberculosis vaccine is a global public health priority. The first clinical efficacy trial of a new tuberculosis vaccine candidate in over 45 years recently reported its results. Unfortunately, the vaccine, MVA85A, showed no improved efficacy over BCG in preventing tuberculosis disease or infection in 2797 infants. This disappointing result has far-reaching ramifications because the majority of TB vaccine candidates in clinical trials broadly aim to induce the same type of immune responses as MVA85A. This compels close re-examination of the immunological paradigm underpinning the development of most new tuberculosis vaccines. Progress will require frank appraisal of the gaps in our understanding of protective immunity and appropriate use and interpretation of the available animal models. Identifying correlates of protection by dissecting immune responses induced by existing partially effective vaccines may be a good place to focus renewed efforts.
Intradialytic Blood Volume Monitoring in Ambulatory Hemodialysis Patients
Authors: Donal N. Reddan, Lynda Anne Szczech, Vic Hasselblad, Edmund G. Lowrie, Robert M. Lindsay, Jonathan Himmelfarb, Robert D. Toto, John Stivelman, James F. Winchester, Linda A. Zillman, Robert M. Califf, William F. Owen
Journal: Journal of the American Society of Nephrology (2005)

Complications related to inadequate volume management are common during hemodialysis. This trial tested the hypothesis that availability of an intradialytic blood volume monitoring (IBVM) device improves fluid removal, reducing morbidity. A six-center, randomized trial with 6 mo of intervention comparing IBVM using Crit-Line versus conventional clinical monitoring was conducted. The average rate of non–access-related hospitalizations was compared across treatment groups using Poisson regression. Mortality analysis used the Kaplan Meier method. A total of 227 patients were randomized to Crit-Line, and 216 were randomized to conventional monitoring. Both groups had similar baseline characteristics. During the study, no differences in weight, BP, or number of dialysis-related complications were observed. There were 120 and 81 non–access-related hospitalizations in the Crit-Line and conventional monitoring groups. The adjusted risk ratio for non–access-related and access-related hospitalization was 1.61 (95% confidence interval 1.15 to 2.25; P = 0.01) and 1.52 (95% confidence interval 1.02 to 2.28; P = 0.04) for the Crit-Line monitoring group. Mortality was 8.7% in the Crit-Line monitoring group and 3.3% in the conventional group (P = 0.021). Standardized mortality ratios comparing the Crit-Line and conventional monitoring groups to the prevalent hemodialysis population were 0.77 (NS) and 0.26 (P < 0.001). Hospitalization rates were 1.51 and 1.03 events/yr in the Crit-Line and standard monitoring groups, compared with 2.01 for the prevalent hemodialysis population. IBVM was associated with higher nonvascular and vascular access-related hospitalizations and mortality compared with conventional monitoring. The atypically low hospitalization and mortality rates for the conventional monitoring group suggest that these findings should be generalized to the US hemodialysis population with caution.
Treatment of the Anemia of Chronic Renal Failure with Recombinant Human Erythropoietin
Authors: J W Adamson, J W Eschbach
Journal: Annual Review of Medicine (1990)

Preclinical evidence has firmly established bidirectional interactions among the brain, the gut, and the gut microbiome. Candidate signaling molecules and at least three communication channels have been identified. Communication within this system is ...Read More
Update in Pulmonary Vascular Diseases 2011
Authors: Paul M. Hassoun, Serge Adnot
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Pulmonary arterial hypertension (PAH) and other pulmonary vascular diseases remain a source of great morbidity and mortality because they complicate several primary lung diseases and nonpulmonary syndromes. There has been continuous progress in deciphering the mechanisms involved in the pulmonary vascular remodeling characterizing these diseases, leading to a better understanding of targeted therapy. As in previous years (1), and after a now well established tradition of the Journal, this update summarizes the scientific progress achieved in 2011, linking the work of many investigators under thematic headings. Reading of the primary manuscripts will provide more detailed information on each topic.
The ribosomal protein genes and Minute loci of Drosophila melanogaster
Authors: Steven J Marygold, John Roote, Gunter Reuter, Andrew Lambertsson, Michael Ashburner, Gillian H Millburn, Paul M Harrison, Zhan Yu, Naoya Kenmochi, Thomas C Kaufman, Sally J Leevers, Kevin R Cook
Journal: Genome biology (2007)

Abstract Background Mutations in genes encoding ribosomal proteins (RPs) have been shown to cause an array of cellular and developmental defects in a variety of organisms. In Drosophila melanogaster , disruption of RP genes can result in the 'Minute' syndrome of dominant, haploinsufficient phenotypes, which include prolonged development, short and thin bristles, and poor fertility and viability. While more than 50 Minute loci have been defined genetically, only 15 have so far been characterized molecularly and shown to correspond to RP genes. Results We combined bioinformatic and genetic approaches to conduct a systematic analysis of the relationship between RP genes and Minute loci. First, we identified 88 genes encoding 79 different cytoplasmic RPs (CRPs) and 75 genes encoding distinct mitochondrial RPs (MRPs). Interestingly, nine CRP genes are present as duplicates and, while all appear to be functional, one member of each gene pair has relatively limited expression. Next, we defined 65 discrete Minute loci by genetic criteria. Of these, 64 correspond to, or very likely correspond to, CRP genes; the single non-CRP-encoding Minute gene encodes a translation initiation factor subunit. Significantly, MRP genes and more than 20 CRP genes do not correspond to Minute loci. Conclusion This work answers a longstanding question about the molecular nature of Minute loci and suggests that Minute phenotypes arise from suboptimal protein synthesis resulting from reduced levels of cytoribosomes. Furthermore, by identifying the majority of haplolethal and haplosterile loci at the molecular level, our data will directly benefit efforts to attain complete deletion coverage of the D. melanogaster genome.
THE DETECTION OF POLIOMYELITIS VIRUS IN FLIES COLLECTED DURING EPIDEMICS OF POLIOMYELITIS
Authors: James D. Trask, John R. Paul
Journal: The Journal of Experimental Medicine (1943)

During the summer and fall of 1941, 19 samples of flies were collected in epidemic areas both during and after epidemics of poliomyelitis. Of 8 samples collected for the most part during the latter part of a local epidemic but within 10 days of the onset of a local case of poliomyelitis, 4 yielded the virus; whereas of 8 samples collected more than 10 days from the onset of the last local case, none yielded the virus. In 4 instances there was a potential (though not proven) source of virus (in the form of "exposed" human feces of recent origin) within a few yards or few feet of the site where fly collections were made. Collections of flies from 3 of these sites yielded the virus. No attempt is made in this paper to develop epidemiological implications from this finding.
<b> <i>In vitro</i> </b> Effects of the BH3 Mimetic, (−)-Gossypol, on Head and Neck Squamous Cell Carcinoma Cells
Authors: Christopher L. Oliver, Joshua A. Bauer, Keith G. Wolter, Mathew L. Ubell, Ajita Narayan, Kathleen M. O’Connell, Susan G. Fisher, Shaomeng Wang, Xihan Wu, Min Ji, Thomas E. Carey, Carol R. Bradford
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Bcl-xL overexpression is common in head and neck squamous cell carcinomas (HNSCC) and correlates with resistance to chemotherapy. Thus, a nonpeptidic, cell-permeable small molecule that mimics the BH3 domain of proapoptotic proteins may inhibit Bcl-xL function and have therapeutic potential for HNSCC by overcoming drug-resistance. (−)-Gossypol, the levorotatory isomer of a natural product isolated from cottonseeds and roots, was recently discovered to bind to the BH3 binding groove of Bcl-xL and Bcl-2. Experimental Design: We investigated the in vitro effects of (−)-gossypol on HNSCC cell lines as well as on fibroblast and keratinocyte cultures by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell survival assays and assessed the results with respect to Bcl-2 family protein expression. Results: We observed dose-dependent growth inhibition of 10 HNSCC cell lines at biologically achievable doses (2.5–10 μmol/L). (−)-Gossypol doses required to inhibit the growth of human fibroblast cell lines by 50% were 2- to 10-fold higher than for HNSCC cell lines. To inhibit human oral keratinocyte growth by 50%, (−)-gossypol concentrations were 2-to 3-fold higher than for HNSCC cell lines. Conclusions: There is a direct correlation between Bcl-xL-to-Bcl-xS ratios and sensitivity to (−)-gossypol. This agent induced apoptosis in a much higher proportion of cells with wild-type p53. Importantly, cell lines resistant to cisplatin were very sensitive to (−)-gossypol. These results demonstrate that (−)-gossypol has potent antitumor activity in HNSCC in vitro. This agent may be developed as a novel therapeutic agent for HNSCC, either alone or in combination with existing chemotherapeutic agents.
Use of the English urgent referral pathway for suspected cancer and mortality in patients with cancer: cohort study
Authors: Henrik Møller, Carolynn Gildea, David Meechan, Greg Rubin, Thomas Round, Peter Vedsted
Journal: BMJ (2015)

<b>Objective</b> To assess the overall effect of the English urgent referral pathway on cancer survival. <b>Setting</b> 8049 general practices in England. <b>Design</b> Cohort study. Linked information from the national Cancer Waiting Times database, NHS Exeter database, and National Cancer Register was used to estimate mortality in patients in relation to the propensity of their general practice to use the urgent referral pathway. <b>Participants</b> 215 284 patients with cancer, diagnosed or first treated in England in 2009 and followed up to 2013. <b>Outcome measure</b> Hazard ratios for death from any cause, as estimated from a Cox proportional hazards regression. <b>Results</b> During four years of follow-up, 91 620 deaths occurred, of which 51 606 (56%) occurred within the first year after diagnosis. Two measures of the propensity to use urgent referral, the standardised referral ratio and the detection rate, were associated with reduced mortality. The hazard ratio for the combination of high referral ratio and high detection rate was 0.96 (95% confidence interval 0.94 to 0.99), applying to 16% (n=34 758) of the study population. Patients with cancer who were registered with general practices with the lowest use of urgent referral had an excess mortality (hazard ratio 1.07 (95% confidence interval 1.05 to 1.08); 37% (n=79 416) of the study population). The comparator group for these two hazard ratios was the remaining 47% (n=101 110) of the study population. This result in mortality was consistent for different types of cancer (apart from breast cancer) and with other stratifications of the dataset, and was not sensitive to adjustment for potential confounders and other details of the statistical model. <b>Conclusions</b> Use of the urgent referral pathway could be efficacious. General practices that consistently have a low propensity to use urgent referrals could consider increasing the use of this pathway to improve the survival of their patients with cancer.
SOME PROBLEMS IN THE TREATMENT OF VENEREAL DISEASES
Authors: A. L. McIlroy
Journal: BMJ (1914)

MZD JOUBL 5B79Rnee-jerks.-In one of Dr. Miacnamara's cases the lost linee-jerks not only returned but in an exaagerated degree.uIi another case, thlough the jerks did not return, tlle quadriceps could be felt to contract.Urinary Synlmptoms.-In all cases in which tllese were present tlley slhowed improvement.General Health.-Nearlyall the patieits expressed tliemselves as feeling miuch better as the result of the ti:eatnient.This imrlprovemient in the general lhealthi lhas, indeed, been one of tlle m.ost striking res-ults of the treatment.While it would be inmpossible wlhollyto eliminate the influLence of suggestion in bringing about some -of tlle improvement referred to (for examnple, the dinminuition of the ataxia, alhtnling pains, and urinary disturbances), other effects of the treaetient (for example, the rapicl increase of weighit,' the return of the lost knee-jerks, and the marked changes for tlle better in the cerebro- spinal fliud) obviously cannot be placed to its credit. CONCLUSIONS.In parenchymatous syDhlilis tlhe intrathecal treatment is the onily' one yet devised wlhicll is capable of arresting the morbid process.It acts by destroying tlle spirochlaetes within the central nervous system an(d the cerebro-spinal fluid.The treatment should be beguLn as early as possible.Neur6ns, once destroyed, are incapable of regeneration.Unfortunately, cases of general paralysis anld tabes rarely come before us' until wide tracts of nervous tissue lhave been irretrievably damaged.Tihe iiitrathecal treatmnent. is also indicated in cases of interstitial sypllilis, especially of the spinal cord, wlhich do not readily respond to salvarsan, mercury, or iodide of potassium.The latter drug slhouild be given in not less than draclhimi doses tlhree or eveni four times daily.All tlle details in connexion with the inijectionis were supervised anid carried, out by Mr. H.E. Batten, and to his unremittilng care tlle entire absence of any kind of complication is to be 'attributed.To him I am also inidebted for careful niotes of the cases.Tlle examiination of the blood and cerebro-spinial fluiid were undertaken by Dr. Braxton Hicks with his accustom-ed care and skill.NOTE.-Since this paper was written Mr. Ballance has treatecl two of my patients sufferiing from general' paraly.isbv intro- dulcing salvarsanized serum ilntracrarfially.The operation was well borne, and both patients made a speedy recovery.It is yet too early to speak positively of the thierapeuitic result, though the indications, in one of the cases at least, are distinctly hopeful.