tbuckley/cabot-search huggingface dataset:
A PREALBUMIN ACTIVATOR OF PREKALLIKREIN
Authors: Allen P. Kaplan, A. B. Kay, K. Frank Austen
Journal: The Journal of Experimental Medicine (1972)

Human plasma kallikrein has been shown to directly and selectively attract human neutrophils from a mixed leukocyte population. The capacity of plasma kallikrein to be chemotactic and to generate the nonapeptide bradykinin was maintained during progressive purification. While neither highly purified prekallikrein nor the prealbumin Hageman factor fragments were chemotactic alone, their interaction so as to convert prekallikrein to kallikrein yielded both chemotactic and kinin-generating activity. Both functions of kallikrein were inhibited by treatment with diisopropyl fluorophosphate, indicating an essential role for the active site of the enzyme in the expression of its chemotactic activity.
Inspiratory and skeletal muscle strength and endurance and diaphragmatic activation in patients with chronic airflow limitation.
Authors: S Z Newell, D K McKenzie, S C Gandevia
Journal: Thorax (1989)

To determine whether patients with chronic airflow limitation have a specific alteration in skeletal muscle performance, the strength and endurance of inspiratory and limb muscles were compared in 11 patients with chronic airflow limitation and 11 control subjects during maximal voluntary contractions. Peak inspiratory pressure at observed functional residual capacity (FRC) was significantly less in the patients than in the control subjects (mean 72 (SD 25) v 93 (21) cm H2O), though only two patients had low maximal pressures across a wide volume range. Maximal voluntary torque of the elbow flexor muscles was also reduced in the patients but the difference was not significant (60 (17) v 72 (18) Nm). During the endurance sequence of 18 maximal voluntary contractions (10 s duration, 5 s rest interval) the decline in peak and average force was less for the inspiratory muscles than for the elbow flexors in both groups. Inspiratory muscle endurance was slightly greater in the patients with chronic airflow limitation than in the control subjects, whereas limb muscle endurance was slightly impaired in the patients. In three patients with chronic airflow limitation, two of whom had low maximal inspiratory pressures at FRC, the ability to drive the diaphragm voluntarily was examined by stimulating the phrenic nerves during maximal inspiratory efforts. Each patient was capable of full activation of the diaphragm during the maximal inspiratory efforts. These results suggest that the relative preservation of inspiratory muscle performance in patients with chronic airflow limitation may be an adaptive response to respiratory "loading."
Analysis of Recently Identified Prostate Cancer Susceptibility Loci in a Population-based Study: Associations with Family History and Clinical Features
Authors: Liesel M. FitzGerald, Erika M. Kwon, Joseph S. Koopmeiners, Claudia A. Salinas, Janet L. Stanford, Elaine A. Ostrander
Journal: Clinical Cancer Research (2009)

Two recent genome-wide association studies have highlighted several single nucleotide polymorphisms (SNPs) purported to be associated with prostate cancer risk. We investigated the significance of these SNPs in a population-based study of Caucasian men, testing the effects of each SNP in relation to family history of prostate cancer and the clinicopathologic features of the disease.We genotyped 13 SNPs in 1,308 prostate cancer patients and 1,267 unaffected controls frequency matched to cases by five-year age groups. The association of each SNP with disease risk stratified by family history of prostate cancer and clinicopathologic features of the disease was calculated with the use of logistic and polytomous regression.These results confirm the importance of multiple, previously reported SNPs in relation to prostate cancer susceptibility; 11 of the 13 SNPs were significantly associated with risk of developing prostate cancer. However, none of the SNP associations were of comparable magnitude with that associated with having a first-degree family history of the disease. Risk estimates associated with SNPs rs4242382 and rs2735839 varied by family history, whereas risk estimates for rs10993994 and rs5945619 varied by Gleason score.Our results confirm that several recently identified SNPs are associated with prostate cancer risk; however, the variant alleles only confer a low to moderate relative risk of disease and are generally not associated with more aggressive disease features.
Organophosphate Pesticide Exposure and Neurobehavioral Performance in Agricultural and Nonagricultural Hispanic Workers
Authors: Joan Rothlein, Diane Rohlman, Michael Lasarev, Jackie Phillips, Juan Muniz, Linda McCauley
Journal: Environmental Health Perspectives (2006)

Our understanding of the health risks of farmworkers exposed to pesticides in their work and home environments is rapidly increasing, although studies designed to examine the possible neurobehavioral effects of low-level chronic pesticide exposure are limited. We measured dialkyl phosphate urinary metabolite levels, collected environmental dust samples from a subset of homes, obtained information on work practices, and conducted neurobehavioral tests on a sample of farmworkers in Oregon. Significant correlations between urinary methyl metabolite levels and total methyl organophosphate (azinphos-methyl, phosmet, malathion) house dust levels were observed. We found the neurobehavioral performance of Hispanic immigrant farmworkers to be lower than that observed in a nonagricultural Hispanic immigrant population, and within the sample of agricultural workers there was a positive correlation between urinary organophosphate metabolite levels and poorer performance on some neurobehavioral tests. These findings add to an increasing body of evidence of the association between low levels of pesticide exposure and deficits in neurobehavioral performance.
Spinal and Trigeminal Mechanisms of Nociception
Authors: R Dubner, G J Bennett
Journal: Annual Review of Neuroscience (1983)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Systematic Review: Effects of Resident Work Hours on Patient Safety
Authors: Kathlyn E. Fletcher, Steven Q. Davis, Willie Underwood, Rajesh S. Mangrulkar, Laurence F. McMahon, Sanjay Saint
Journal: Annals of Internal Medicine (2004)

The Accreditation Council for Graduate Medical Education (ACGME) mandated new work hours rules for all residency programs in July 2003.To critically evaluate the evidence that adhering to the ACGME standards will improve patient safety.Searches of electronic databases (MEDLINE, EMBASE, PREMEDLINE, and Current Contents) and other methods to identify the English-language literature for studies on resident work hours for the years 1966 to 2004.Studies that assessed a system change designed to counteract the effects of work hours, fatigue, or sleep deprivation and that included an outcome related to patient safety were included. Seven studies met these criteria.Two investigators abstracted data from all included studies by using a standard data abstraction form; each study was rated according to established criteria to assess study design quality.Interventions used were float systems, other cross-coverage systems, or unspecified schedule changes. Outcomes included mortality, adverse events, and medication errors. The results suggest that introducing such interventions has an unclear effect on selected patient safety indicators. Specifically, some indicators (such as mortality) may not change after interventions, while other indicators may improve or worsen.This analysis is limited by the study designs of the included studies, the diversity of interventions in the studies, and the possibility of publication bias favoring studies that demonstrated statistically significant differences.Evidence on patient safety is insufficient to inform the process of reducing resident work hours.
The Evolutionary History of Kinetoplastids and Their Kinetoplasts
Authors: Alastair G. B. Simpson, Julius Lukeš, Andrew J. Roger
Journal: Molecular Biology and Evolution (2002)

Despite extensive phylogenetic analysis of small subunit ribosomal RNA (SSUrRNA) genes, the deep-level relationships among kinetoplastids remain poorly understood, limiting our grasp of their evolutionary history, especially the origins of their bizarre mitochondrial genome organizations. In this study we examine the SSUrRNA data in the light of a new marker—cytoplasmic heat shock protein 90 (hsp90) sequences. Our phylogenetic analyses divide kinetoplastids into four main clades. Clades 1–3 include the various bodonid kinetoplastids. Trypanosomatids comprise the fourth clade. SSUrRNA analyses give vastly different and poorly supported positions for the root of the kinetoplastid tree, depending on the out-group and analysis method. This is probably due to the extraordinary length of the branch between kinetoplastids and any out-group. In contrast, almost all hsp90 analyses place the root between clade 1 (including Dimastigella, Rhynchomonas, several Bodo spp., and probably Rhynchobodo) and all other kinetoplastids. Maximum likelihood and maximum likelihood distance analyses of hsp90 protein and second codon–position nucleotides place trypanosomatids adjacent to Bodo saltans and Bodo cf. uncinatus (clade 3), as (weakly) do SSUrRNA analyses. Hsp90 first codon– plus second codon–position nucleotide analyses return a slightly different topology. We show that this may be an artifact caused, in part, by the different evolutionary behavior of first- and second-codon positions. This study provides the most robust evidence to date that trypanosomatids are descended from within bodonids and that B. saltans is a close relative of trypanosomatids. A total reevaluation of the high-level systematics within kinetoplastids is needed. We confirm that the interlocking network organization of kinetoplast DNA seen in trypanosomatids is a derived condition within kinetoplastids but suggest that open-conformation minicircles may have arisen early in kinetoplastid evolution. Further understanding of the evolution of kinetoplast structure and RNA editing is hampered by a paucity of data from basal (i.e., clade 1) bodonids.
A randomised, double-blind, placebo-controlled phase IIB clinical trial of repeated application of gene therapy in patients with cystic fibrosis: Table 1
Authors: Eric W F W Alton, A Christopher Boyd, Seng H Cheng, Steve Cunningham, Jane C Davies, Deborah R Gill, Uta Griesenbach, Tracy Higgins, Stephen C Hyde, J Alastair Innes, Gordon D Murray, David J Porteous
Journal: Thorax (2013)

The UK Cystic Fibrosis Gene Therapy Consortium has been working towards clinical gene therapy for patients with cystic fibrosis for several years. We have recently embarked on a large, multi-dose clinical trial of a non-viral, liposome-based formulation powered for the first time to detect clinical benefit. The article describes the details of the protocol.
Comorbidities and Charlson score in resected stage I nonsmall cell lung cancer
Authors: D. Moro-Sibilot, A. Aubert, S. Diab, S. Lantuejoul, P. Fourneret, E. Brambilla, C. Brambilla, P. Y. Brichon
Journal: European Respiratory Journal (2005)

Patients with nonsmall cell lung cancer (NSCLC) have been shown to have a higher prevalence of comorbidity associated with age and tobacco consumption. The objective of the present study was to determine the impact of comorbidity on survival after surgery of stage I NSCLC. In total, 588 consecutive patients operated on for a pathological stage I NSCLC between January 1, 1979 and December 31, 2003 were studied. Comorbidities were analysed individually. Overall comorbidity was assessed using the Charlson index of comorbidity (CCI). Survival data were collected for each patient from the date of operation, with a median duration of follow-up of 104 months. Survival analyses and Cox proportional hazards model analyses were used. The mean age of patients was 62.7 yrs, and 529 (89%) patients were male. The distribution of overall comorbidity severity was as follows. CCI grade 0: 47.1%; grade 1–2: 43.7%; grade 3–4: 8.3%; and grade ≥5: 0.8%. The 2, 3 and 5 yrs survival were 69, 62 and 50%, respectively. Multivariable analysis showed that T stage, age, a concomitant history of moderate-to-severe liver disease, a past history of cured cancer, cerebrovascular disease and CCI were independent predictors of survival (Hazard Ratio for CCI grade &gt;2: 1.81; 95% confidence interval 1.25–2.63). In conclusion, comorbidity has a significant impact on survival after surgical resection of patients with stage I nonsmall cell lung cancer. The use of a validated index of comorbidity in prognostic analyses of resected nonsmall cell lung cancer is recommended.
Antitumoural immunity by virus-mediated immunogenic apoptosis inhibits metastatic growth of hepatocellular carcinoma
Authors: B. Boozari, B. Mundt, N. Woller, N. Struver, E. Gurlevik, P. Schache, A. Kloos, S. Knocke, M. P. Manns, T. C. Wirth, S. Kubicka, F. Kuhnel
Journal: Gut (2010)

<h3>Background and aims</h3> Viral infection of a dying cell dictates the immune response against intracellular antigens, suggesting that virotherapy may be an effective tool to induce immunogenic cell death during systemic cancer treatment. Since viruses and proteasome inhibitors both induce accumulation of misfolded proteins, endoplasmic reticulum (ER) stress and immune responses during treatment of hepatocellular carcinoma (HCC) with bortezomib and the tumour-specifically replicating virus hTert-Ad (human telomerase reverse transcriptase promoter-regulated adenovirus) were investigated. <h3>Methods</h3> Unfolded protein response (UPR) pathways and ER stress-mediated apoptosis were investigated by western blots, caspase-3 assays, 49,6-diamidino-2-phenylindole (DAPI) and Annexin V staining in HCC cells following hTert-Ad/bortezomib treatment. Oncolysis was assessed in subcutaneous HCC mouse models. Antiviral/antitumoural immune responses were characterised in immunocompetent HCC mouse models by ELISA, ELISpot assays and pentamer staining. Systemic efficacy of antitumoural immunity was investigated by determination of lung metastases burden. <h3>Results</h3> Bortezomib and hTert-Ad trigger complementary UPR pathways but negatively interfere with important recovery checkpoints, resulting in enhanced apoptosis of HCC cells in vitro and improved oncolysis in vivo. In immunocompetent mice, bortezomib inhibited antiviral immune responses, whereas ER stress-induced apoptosis of infected HCC resulted in caspase-dependent triggering of antitumoural immunity. In therapeutic settings in immunocompetent, but not in immunodeficient or CD8-depleted mice, virotherapy-induced antitumoural immunity efficiently inhibited outgrowth of non-infected lung metastases. Immunotherapeutic efficacy could be significantly improved by bortezomib in experiments with low viral doses. <h3>Conclusion</h3> Proteasome inhibition during virotherapy disrupts the UPR, leading to enhanced ER stress-induced apoptosis, improved local oncolysis and antitumoural immunity. The results suggest that combining intratumoural virotherapy with adjuvant systemic therapies, which specifically support the function of the virotherapy as an antitumoural vaccine, is a promising immunotherapeutic strategy against HCC.
The Psychotherapy of Schizophrenia: Does It Work?
Authors: JARL E. DYRUD, PHILIP S. HOLZMAN
Journal: American Journal of Psychiatry (1973)

Empirical studies of the treatment of schizophrenia show the unequivocal ameliorative effects of psychoactive drugs. No comparable effects have been claimed for psychotherapy. As a result, psychotherapy has tended to be negated as a viable therapeutic factor in the treatment of schizophrenia. Yet the sophisticated drug evaluation studies are not matched by sophisticated assessments of psychotherapy. Serious methodological errors exist in the latter studies; there have been inappropriate outcome criteria, inadequate assessment procedures to measure change, unsound selection of therapists, and unclear diagnostic appraisals. The issue has been further clouded by the heterogeneous nature of psychotherapeutic interventions, comprising as they do—in contrast to the relatively simple administration of drugs—a congeries of methods, techniques, and goals. This paper examines some of the requirements for appropriate evaluation studies of psychotherapy of schizophrenic patients.
Signalling pathways involved in the contractile response to 5-HT in the human pulmonary artery
Authors: L. Rodat-Despoix, V. Aires, T. Ducret, R. Marthan, J-P. Savineau, E. Rousseau, C. Guibert
Journal: European Respiratory Journal (2009)

Serotonin (5-hydroxytryptamine; 5-HT) is a potent pulmonary vasoconstrictor and mitogenic agent whose plasma level is increased in pulmonary hypertensive patients. Thus, we explored the signalling pathways involved in the contractile response to 5-HT in human pulmonary arteries (HPAs). Intact and β-escin permeabilised rings from HPAs mounted in an organ bath system were used to assess both tension and myofilament Ca 2+ -sensitisation. Microspectrofluorimetry was used for intracellular Ca 2+ recordings in cultured HPA smooth muscle cells. Voltage-operated Ca 2+ channel blockers (nitrendipine and nifedipine) partially reduced the contraction to 5-HT. Thapsigargin or cyclopiazonic acid (CPA), known to deplete sarcoplasmic reticulum Ca 2+ stores, also partially inhibited the contraction, whereas removal of extracellular Ca 2+ under these conditions further inhibited the contraction. Changing from Ca 2+ -free to Ca 2+ containing solution, in the presence of nitrendipine and CPA, a protocol known to stimulate store-operated Ca 2+ channels, induced HPA contractions that were blocked by nickel. Nickel or gadolinium also reduced the contraction to 5-HT. Finally, 5-HT increased intracellular Ca 2+ responses in cultured HPA smooth muscle cells and myofilament Ca 2+ -sensitisation in HPA rings. Collectively, these results indicate that voltage-operated and voltage-independent Ca 2+ channels, as well as Ca 2+ release and myofilament Ca 2+ -sensitisation, participate in 5-HT-induced contraction in HPAs.
Biomarkers of HPV Infection in Oropharyngeal Carcinomas: Can We Find Simplicity in the Puzzle of Complexity?
Authors: Eduardo Méndez
Journal: Cancer Research (2012)

Commentary on Holzinger et al., [p. 4993][1] and Liang et al., [p. 5004][2]

In this issue of Cancer Research , 2 studies by Holzinger and colleagues ([1][3]) and Liang and colleagues ([2][4]) investigate which biomarker(s) of human papillomavirus (HPV) infection are more prognostic in oropharyngeal
Progress Toward HIV Eradication: Case Reports, Current Efforts, and the Challenges Associated with Cure
Authors: Alyssa R. Martin, Robert F. Siliciano
Journal: Annual Review of Medicine (2015)

An estimated 35 million people worldwide are infected with HIV, yet a widely applicable cure strategy remains elusive. Recent case reports have suggested that curing HIV infection is possible, renewing excitement about research efforts. We describe those cases and discuss their relevance to the global HIV epidemic. We also review ongoing cure strategies that are transitioning from the lab to the clinic, and the assays and clinical assessments that can be used to evaluate cure interventions.
Differences in peripheral blood lymphocyte phenotypes between Helicobacter pylori-positive children and adults with duodenal ulcer
Authors: T. Figueiredo Soares, G. Aguiar Rocha, A. M. Camargos Rocha, R. Corrěa-Oliveira, O.A. Martins-Filho, A. S. Teles Carvalho, P. F. Souto Bittencourt, C. Afonso Oliveira, A. M. M. Ferreira Nogueira, M. M. D. Álvares Cabral, A. M. Caetano Faria, D.M.M. Queiroz
Journal: Clinical Microbiology and Infection (2007)
Fever and leucocytosis accompanying asthmatic reactions due to occupational agents: frequency and associated factors
Authors: C Lemiere, D Gautrin, C Trudeau, H Ghezzo, A Desjardins, A Cartier, JL Malo
Journal: European Respiratory Journal (1996)

Fever is sometimes associated with asthmatic reactions following specific inhalation challenges with occupational agents. Our aims were to estimate the prevalence of fever in subjects with occupational asthma confirmed by specific inhalation challenge and to examine the characteristics and clinical correlates of subjects who develop fever on specific inhalation challenge. We performed a retrospective analysis of 317 subjects who had positive specific inhalation challenge to occupational agents and a comparison of subjects who developed fever after specific inhalation challenge with a random sample of those who did not. Fifteen subjects (5%) developed fever associated with positive specific inhalation challenge. They were compared with a random sample of 60 subjects who did not develop fever. The fever group: 1) showed a larger increase in absolute number of blood neutrophils, and a larger decrease both of blood lymphocytes and forced vital capacity after specific inhalation challenge; 2) included fewer atopics; 3) had been exposed more frequently to low rather than high molecular compounds; and 4) always experienced a late reaction and had more atypical reactions. We conclude that after positive specific inhalation challenge; fever occurs infrequently, and is associated with an increase in blood neutrophils and a decrease in blood lymphocytes and forced vital capacity. Such reactions seem more likely to occur in nonatopic subjects exposed to low molecular weight agents.
Surgeon wins court injunction against dismissal
Authors: A. O'Dowd
Journal: BMJ (2009)

A consultant surgeon has won a temporary injunction at the High Court to stop his employer giving him the sack in a case that has been hailed as a strong warning to NHS trusts to follow contractual procedures.

Gideon Lauffer was dismissed by his employer, Barking, Havering and Redbridge University Hospitals NHS Trust, on 25 June, after the trust said it had lost confidence in him over alleged concerns about his capability and conduct as a surgeon.

The High Court, in granting the interim …
Phase I study of highly selective supradose cisplatin infusions for advanced head and neck cancer.
Authors: K T Robbins, A M Storniolo, C Kerber, D Vicario, S Seagren, M Shea, C Hanchett, G Los, S B Howell
Journal: Journal of Clinical Oncology (1994)

PURPOSE To determine the maximum dose-intensity of cisplatin (DDP) that could be administered by selective intraarterial (IA) infusion in combination with systemic sodium thiosulfate neutralization to patients with head and neck carcinoma. PATIENTS AND METHODS Forty-two patients (23 untreated stage III/IV, 19 recurrent) received highly selective IA DDP, rapidly delivered through microcatheters placed angiographically, to a maximum dose-intensity of 200 mg/m2/wk. Concurrently, the systemic effects of DDP were neutralized by intravenous (IV) bolus sodium thiosulfate. RESULTS Problems related to the infusion technique occurred in eight of 140 courses, all of which were inconsequential. The rates of reversible grade I/II and grade III/IV toxicity were 14.8% and 1.1%, respectively. Dose-limiting toxicity, which consisted of severe electrolyte loss, occurred at a dose of 200 mg/m2/wk. The maximum-tolerated dose of DDP was 150 mg/m2 administered weekly for four doses. The overall and complete response rates in 38 assessable patients were 19 of 22 (86%) and nine of 22 (41%) for stage III/IV untreated tumors and 10 of 16 (62%) and four of 16 (25%) for patients with recurrent disease, respectively. CONCLUSION This pharmacologic strategy permits the selective and rapid delivery of extremely high doses of DDP to head and neck carcinomas with minimal procedural complications, low systemic toxicity, and high tumor response rates.