tbuckley/cabot-search huggingface dataset:
Proteases for Processing Proneuropeptides into Peptide Neurotransmitters and Hormones
Authors: Vivian Hook, Lydiane Funkelstein, Douglas Lu, Steven Bark, Jill Wegrzyn, Shin-Rong Hwang
Journal: The Annual Review of Pharmacology and Toxicology (2008)

Peptide neurotransmitters and peptide hormones, collectively known as neuropeptides, are required for cell-cell communication in neurotransmission and for regulation of endocrine functions. Neuropeptides are synthesized from protein precursors (termed proneuropeptides or prohormones) that require proteolytic processing primarily within secretory vesicles that store and secrete the mature neuropeptides to control target cellular and organ systems. This review describes interdisciplinary strategies that have elucidated two primary protease pathways for prohormone processing consisting of the cysteine protease pathway mediated by secretory vesicle cathepsin L and the well-known subtilisin-like proprotein convertase pathway that together support neuropeptide biosynthesis. Importantly, this review discusses important areas of current and future biomedical neuropeptide research with respect to biological regulation, inhibitors, structural features of proneuropeptide and protease interactions, and peptidomics combined with proteomics for systems biological approaches. Future studies that gain in-depth understanding of protease mechanisms for generating active neuropeptides will be instrumental for translational research to develop pharmacological strategies for regulation of neuropeptide functions. Pharmacological applications for neuropeptide research may provide valuable therapeutics in health and disease.
Differences in asthma management between white European and Indian subcontinent ethnic groups living in socioeconomically deprived areas in the Birmingham (UK) conurbation
Authors: H Moudgil, D Honeybourne
Journal: Thorax (1998)

Hospital admission rates for asthma have been higher for Asian (Indian subcontinent, ISC) ethnic minority groups in the UK than for white Europeans (W/E). As this may in part be due to differences in the uptake or delivery of preventative health care strategies, the extent to which targeted education and treatment programmes reach these groups needs to be determined.Six hundred and eighty nine asthmatic subjects (345 W/E, 344 ISC) of mean (SD) age 34.5 (15) years (range 11-59) and mean forced expiratory volume in one second (FEV1) 80% predicted from districts of high ethnicity and socioeconomic deprivation within inner city Birmingham were reviewed in the appropriate dialect (English, Punjabi, Hindi, Urdu) in a community based study.Data adjusted for age and analysed separately for men (M) and women (F) showed no significant differences in the numbers reporting previous asthma education, assessment of delivery techniques, or being taught about medications, but there were significant differences for advice on trigger factors (M: 52% vs 42%; F: 56% vs 42%), recognition of symptoms (M: 51% vs 43%; F: 53% vs 33%), and ownership of peak flow meters (M: 35% vs 22%; F: 36% vs 24%) for W/E and ISC groups, respectively. Anti-inflammatory asthma medications were highly prescribed, but self reported drug compliance (M: 73% vs 62%), understanding medications (F: 59% vs 39%), and self management (F: 23% vs 12%) varied significantly. Asthma follow up in the community was low for both groups with more of the ISC subjects also being followed up by hospital.The management of both ethnic groups has centred on drug prescription, delivery techniques and compliance, but has been deficient, particularly in the ISC group, in developing understanding of the disease and self management.
Metal-on-metal hips: cobalt can induce an endotoxin-like response
Authors: Alison Jane Tyson-Capper, Helen Lawrence, James P Holland, David J Deehan, John A Kirby
Journal: Annals of the Rheumatic Diseases (2012)

Recent studies have highlighted significant risks associated with metal-on-metal (MoM) hip joint replacement,1 leading Smith et al 2 to recommend that research should be ‘focused on understanding the biological consequences of exposure to orthopaedic metals’. One of these consequences may be the development of solid or fluid-filled inflammatory lesions, termed pseudotumours, which have been reported in areas around MoM joints.3 ,4 

The articulating surface of MoM joints is fabricated from a hard alloy containing approximately one part chromium to two of cobalt. Ionic forms of both these metals can be detected at a high level (≤5 mM Cr, ≤0·25 mM Co) in the synovial fluid surrounding MoM joints, with lower levels present in distant body tissues, blood and urine.5 Although …
Clinical significance of early recurrences of atrial fibrillation after pulmonary vein isolation
Authors: Hakan Oral, Bradley P Knight, Mehmet Özaydın, Hiroshi Tada, Aman Chugh, Sohail Hassan, Christoph Scharf, Steve W.K Lai, Radmira Greenstein, Frank Pelosi, S.Adam Strickberger, Fred Morady
Journal: Journal of the American College of Cardiology (2002)
Quality improvement for doctors – it's essential
Authors: Benjamin Lamb
Journal: Journal of the Royal Society of Medicine (2009)

I read Hockey and Marshall's essay on quality improvement with great enthusiasm.1 I agree with the authors about the change in the nature of medicine from a ‘one-to-one relationship behind closed doors’ to one where an appreciation for the wider context in which we practice is essential. Doctors must engage with quality improvement as part of good medical practice.2 Quality in healthcare is not just concerned with outcome targets (of which there are many); quality is primarily concerned with healthcare processes – including education, patient safety, decision-making, partnership with patients and others. While I am a fan of evidence-based medicine (EBM), EBM typically does not offer guidance on what processes one must adopt in order to achieve the goals set out by EBM. Trials often try to define the best medical treatment or surgical intervention. However, the processes that clinicians go through to incorporate evidence into care are equally as critical – so that eventually, evidence is translated into patient outcomes. Quality in healthcare should matter to doctors. Grand technology, like the da Vinci robot3 is great, but reaching a good quality decision about the right treatment for a specific patient, teamwork in theatre, patient safety and the patient's experience are all equally as crucial in achieving a good outcome.4
Acid incubation reverses the polarity of intercalated cell transporters, an effect mediated by hensin
Authors: George J. Schwartz, Shuichi Tsuruoka, Soundarapandian Vijayakumar, Snezana Petrovic, Ayesa Mian, Qais Al-Awqati
Journal: Journal of Clinical Investigation (2002)

Metabolic acidosis causes a reversal of polarity of HCO3– flux in the cortical collecting duct (CCD). In CCDs incubated in vitro in acid media, β-intercalated (HCO3–-secreting) cells are remodeled to functionally resemble α-intercalated (H+-secreting) cells. A similar remodeling of β-intercalated cells, in which the polarity of H+ pumps and Cl–/HCO3– exchangers is reversed, occurs in cell culture and requires the deposition of polymerized hensin in the ECM. CCDs maintained 3 h at low pH ex vivo display a reversal of HCO3– flux that is quantitatively similar to an effect previously observed in acid-treated rabbits in vivo. We followed intracellular pH in the same β-intercalated cells before and after acid incubation and found that apical Cl/HCO3 exchange was abolished following acid incubation. Some cells also developed basolateral Cl–/HCO3– exchange, indicating a reversal of intercalated cell polarity. This adaptation required intact microtubules and microfilaments, as well as new protein synthesis, and was associated with decreased size of the apical surface of β-intercalated cells. Addition of anti-hensin antibodies prevented the acid-induced changes in apical and basolateral Cl–/HCO3– exchange observed in the same cells and the corresponding suppression of HCO3– secretion. Acid loading also promoted hensin deposition in the ECM underneath adapting β-intercalated cells. Hence, the adaptive conversion of β-intercalated cells to α-intercalated cells during acid incubation depends upon ECM-associated hensin.
New insight into the control of the heart beat by intracellular calcium ions
Authors: D. T YUE
Journal: Cardiovascular Research (1988)

Journal Article New insight into the control of the heart beat by intracellular calcium ions Get access DAVID T YUE DAVID T YUE From the Department of Biomedical Engineering, Johns Hopkins University of Medicine, Baltimore, Maryland, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 22, Issue 8, August 1988, Page 587, https://doi.org/10.1093/cvr/22.8.587 Published: 01 August 1988
Association of Fetuin-A With Incident Diabetes Mellitus in Community-Living Older Adults
Authors: Joachim H. Ix, Mary L. Biggs, Kenneth J. Mukamal, Jorge R. Kizer, Susan J. Zieman, David S. Siscovick, Dariush Mozaffarian, Majken K. Jensen, Lauren Nelson, Neil Ruderman, Luc Djousse
Journal: Circulation (2012)

The liver-secreted protein fetuin-A induces peripheral insulin resistance in vitro. In a pilot study, we observed that higher fetuin-A levels were associated with diabetes mellitus in older persons. However, this finding has not been confirmed in large cohorts. We sought to confirm the association of fetuin-A with incident diabetes mellitus in older persons and to determine whether the association differs by age, sex, and race and among persons with cardiovascular disease (CVD).Among 3710 community-living individuals ≥ 65 years of age without diabetes mellitus at baseline, fetuin-A was measured in serum collected in 1992 to 1993. Participants were followed up for 10.6 years (median) for incident diabetes mellitus. Cox regression models evaluated the association of fetuin-A with incident diabetes mellitus. Interaction terms evaluated heterogeneity by age, sex, race, and CVD. Mean age was 75 years; 60 were female; 15 were black; and 16 had CVD. Mean fetuin-A concentrations were 0.47 ± 0.10 g/L. During follow-up, 305 incident diabetes cases occurred. Each 0.10-g/L (SD)-greater fetuin-A was associated with 19 higher risk of diabetes mellitus (hazard ratio, 1.19; 95 confidence interval, 1.06-1.33) after adjustment for demographics, lifestyle factors, albumin, kidney function, and CVD. Further adjustment for potential mediators (body mass index, waist circumference, hypertension, lipids, and C-reactive protein) moderately attenuated the association (hazard ratio, 1.13; 95 confidence interval, 1.00-1.28). Results were similar by sex, race, and CVD status but were stronger in persons <75 years old (P for interaction=0.01).Higher fetuin-A is associated with incident diabetes mellitus in older persons regardless of sex, race, or prevalent CVD status. The association may be attenuated in those ≥ 75 years of age.
<i>In vivo</i> Imaging of Adenovirus Transduction and Enhanced Therapeutic Efficacy of Combination Therapy with Conditionally Replicating Adenovirus and Adenovirus-p27
Authors: Choon-Taek Lee, Yoon-Jin Lee, Sung-Youn Kwon, Jaeho Lee, Kwang Il Kim, Kyung-Ho Park, Joo Hyun Kang, Chul-Gyu Yoo, Young Whan Kim, Sung Koo Han, June-Key Chung, Young-Soo Shim, David T. Curiel, David P. Carbone
Journal: Cancer Research (2006)

Abstract Gene therapy is hampered by poor gene transfer to the tumor mass. We previously proposed a combination adenoviral gene therapy containing a conditionally replicating adenovirus (CRAD) expressing mutant E1 (Δ24RGD) and a replication-defective E1-deleted adenovirus to enhance the efficiency of gene transfer. Mutant E1 expressed by Δ24RGD enables the replication of replication-defective adenoviruses in tumors when cancer cells are co-infected with both viruses. In this study, gene transfer rates in xenografts tumors were monitored by bioluminescence in cells infected with the replication-defective adenovirus-luciferase (ad-luc). Tumor masses treated with CRAD + ad-luc showed dramatically stronger and more prolonged luciferase expression than ad-luc-treated tumors and this expression spread through the entire tumor mass without significant systemic spread. Transduction with CRAD + replication-defective adenovirus-p27 increased the expression of p27 by 24-fold versus transduction with ad-p27 alone. Treatment of a lung cancer cell line and of established lung cancer xenografts with CRAD + adenovirus-p27 also induced stronger growth suppression than treatment with either virus alone. These findings confirm the selective replication of E1-deleted adenovirus containing a therapeutic gene due to the presence of mutant E1 produced by Δ24RGD in tumors. Moreover, this replication increased the therapeutic gene transfer rate and enhanced its antitumor effects. (Cancer Res 2006; 66(1): 372-7)
End-of-Life Discussions, Goal Attainment, and Distress at the End of Life: Predictors and Outcomes of Receipt of Care Consistent With Preferences
Authors: Jennifer W. Mack, Jane C. Weeks, Alexi A. Wright, Susan D. Block, Holly G. Prigerson
Journal: Journal of Clinical Oncology (2010)

Purpose Physicians have an ethical obligation to honor patients' values for care, including at the end of life (EOL). We sought to evaluate factors that help patients to receive care consistent with their preferences. Methods This was a longitudinal multi-institutional cohort study. We measured baseline preferences for life-extending versus symptom-directed care and actual EOL care received in 325 patients with advanced cancer. We also measured associated sociodemographic, health, and communication characteristics, including EOL discussions between patients and physicians. Results Preferences were assessed a median of 125 days before death. Overall, 68% of patients (220 of 325 patients) received EOL care consistent with baseline preferences. The proportion was slightly higher among patients who recognized they were terminally ill (74%, 90 of 121 patients; P = .05). Patients who recognized their terminal illness were more likely to prefer symptom-directed care (83%, 100 of 121 patients; v 66%, 127 of 191 patients; P = .003). However, some patients who were aware they were terminally ill wished to receive life-extending care (17%, 21 of 121 patients). Patients who reported having discussed their wishes for EOL care with a physician (39%, 125 of 322 patients) were more likely to receive care that was consistent with their preferences, both in the full sample (odds ratio [OR] = 2.26; P &lt; .0001) and among patients who were aware they were terminally ill (OR = 3.94; P = .0005). Among patients who received no life-extending measures, physical distress was lower (mean score, 3.1 v 4.1; P = .03) among patients for whom such care was consistent with preferences. Conclusion Patients with cancer are more likely to receive EOL care that is consistent with their preferences when they have had the opportunity to discuss their wishes for EOL care with a physician.
IgE-mediated Cow's Milk Allergy in Brazilian Children: Tolerance Development at five years of age
Authors: A.B.M. Castro, L.A. Watanabe, V.C.Z. Fucci, Â.B.F. Fomin, L.M.A. Ribeiro, A.K. Gushken, G.H. Yonamine, F. Rizzo, U. Doria, A.C. Pastorino
Journal: Journal of Allergy and Clinical Immunology (2009)
IMMUNOLOGICAL STUDIES CONCERNING THE NEPHRITIS OF SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: David Koffler, Peter H. Schur, Henry G. Kunkel
Journal: The Journal of Experimental Medicine (1967)

Antibodies were eluted from the isolated glomeruli prepared from the kidneys of 10 patients with the nephritis of systemic lupus erythematosus. Antibodies reacting primarily with buffer extracts of nuclei were eluted by acid treatment, and antibodies reacting mainly with DNA and nucleoprotein were eluted with deoxyribonuclease. Quantitative immunochemical studies revealed a high concentration of antinuclear antibody per milligram of γ-globulin in glomerular eluates compared with that in the corresponding serums. The γ-globulin of two eluates was found to consist predominantly of antinucleoprotein antibody. The selective elution of antinuclear antibodies was also indicated by the absence of other serum antibodies in the eluates. DNA antigen was demonstrated in the glomeruli of two kidneys with nephritis by means of isolated anti-DNA antibody labeled with fluorescein. In one of these cases, anti-DNA antibodies were also found concentrated in the glomeruli and, in the second, circulating anti-DNA antibodies were demonstrated in the patient's serum. The immunochemical evidence for the high specific activity of antinuclear antibodies and the association of DNA antigen with DNA antibody in glomeruli add further support for the antigen-antibody complex hypothesis for renal injury in systemic lupus erythematosus.
Surgeon-Reported Conflict With Intensivists About Postoperative Goals of Care
Authors: Terrah J. Paul Olson, Karen J. Brasel, Andrew J. Redmann, G. Caleb Alexander, Margaret L. Schwarze
Journal: JAMA Surgery (2013)

<h3>Objective</h3>To examine surgeons' experiences of conflict with intensivists and nurses about goals of care for their postoperative patients.<h3>Design</h3>Cross-sectional incentivized US mail-based survey.<h3>Setting</h3>Private and academic surgical practices.<h3>Participants</h3>A total of 2100 vascular, neurologic, and cardiothoracic surgeons.<h3>Main Outcome Measures</h3>Surgeon-reported rates of conflict with intensivists and nurses about goals of care for patients with poor postsurgical outcomes.<h3>Results</h3>The adjusted response rate was 55.6%. Forty-three percent of surgeons reported sometimes or always experiencing conflict about postoperative goals of care with intensivists, and 43% reported conflict with nurses. Younger surgeons reported higher rates of conflict than older surgeons with both intensivists (57% vs 32%; P = .001) and nurses (48% vs 33%; P = .001). Surgeons practicing in closed intensive care units reported more frequent conflict than those practicing in open intensive care units (60% vs 41%; P = .005). On multivariate analysis, the odds of reporting conflict with intensivists were 2.5 times higher for surgeons with fewer years of experience compared with their older colleagues (odds ratio, 2.5; 95% CI, 1.6-3.8) and 70% higher for reporting conflict with nurses (odds ratio, 1.7; 95% CI, 1.1-2.6). The odds of reporting conflict with intensivists about goals of postoperative care were 40% lower for surgeons who primarily managed their intensive care unit patients than for those who worked in a closed unit (odds ratio, 0.60; 95% CI, 0.40-0.96).<h3>Conclusions</h3>Surgeons regularly experience conflict with critical care clinicians about goals of care for patients with poor postoperative outcomes. Higher rates of conflict are associated with less experience and working in a closed intensive care unit.
Critical role of complex III in the early metabolic changes following myocardial infarction
Authors: L. C. Heather, C. A. Carr, D. J. Stuckey, S. Pope, K. J. Morten, E. E. Carter, L. M. Edwards, K. Clarke
Journal: Cardiovascular Research (2009)

The chronically infarcted rat heart has multiple defects in metabolism, yet the location of the primary metabolic abnormality arising after myocardial infarction is unknown. Therefore, we investigated cardiac mitochondrial metabolism shortly after infarction. Myocardial infarctions (n = 11) and sham operations (n = 9) were performed on Wistar rats, at 2 weeks cardiac function was assessed using echocardiography, and rats were grouped into failing (ejection fraction ≤45%), moderately impaired (46–60%), and sham-operated (>60%). Respiration rates were decreased by 28% in both subsarcolemmal and interfibrillar mitochondria isolated from failing hearts, compared with sham-operated controls. However, respiration rates were not impaired in mitochondria from hearts with moderately impaired function. The mitochondrial defect in the failing hearts was located within the electron transport chain (ETC), as respiration rates were suppressed to the same extent when fatty acids, ketone bodies, or glutamate were used as substrates. Complex III protein levels were decreased by 46% and complex III activity was decreased by 26%, in mitochondria from failing hearts, but all other ETC complexes were unchanged. Decreased complex III activity was accompanied by a three-fold increase in complex III-derived H2O2 production, decreased cardiolipin content, and a 60% decrease in mitochondrial cytochrome c levels from failing hearts. Respiration rates, complex III activity, cardiolipin content, and reactive oxygen species generation rates correlated with ejection fraction. In conclusion, a specific defect in complex III occurred acutely after myocardial infarction, which increased oxidative damage and impaired mitochondrial respiration. The extent of mitochondrial dysfunction in the failing heart was proportional to the degree of cardiac dysfunction induced by myocardial infarction.
Randomized Phase III Trial of Pemetrexed Versus Docetaxel in Patients With Non–Small-Cell Lung Cancer Previously Treated With Chemotherapy
Authors: Nasser Hanna, Frances A. Shepherd, Frank V. Fossella, Jose R. Pereira, Filippo De Marinis, Joachim von Pawel, Ulrich Gatzemeier, Thomas Chang Yao Tsao, Miklos Pless, Thomas Muller, Hong-Liang Lim, Christopher Desch, Klara Szondy, Radj Gervais, None Shaharyar, Christian Manegold, Sofia Paul, Paolo Paoletti, Lawrence Einhorn, Paul A. Bunn
Journal: Journal of Clinical Oncology (2004)

To compare the efficacy and toxicity of pemetrexed versus docetaxel in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with chemotherapy.
CLINICAL REMARKS on CATHETERISATION of the MALE URETERS UNDER ELECTRIC LIGHT
Authors: E. H. Fenwick
Journal: BMJ (1898)

CATHETEBISATION OF MALE URETERS.TM 'R3'doubtedly some examples occur (particularly of dorsal dislo- cation of the index first phalanx) in which great difficulty is met with in reduction.M. Polaillon1' showed three cases two concerning the index and one the ring finger, of dorsal dislocation which resisted all attempts at reduction under anvasthesia and remained out of place.In all such cases it can hardly be doubted that the real difficulty is in the glenoid ligament, and its division may be recommended with confid- ence should the ordinary manipulation fail.Finally, it may be said that with the correct understanding of the part the sesamoid bones And the glenoid ligament play in backward dislocation of the thumb, and with a resort to the simple method of operation already described in cases otherwise irreducible, all the difficulties of this much discussed subject practically disappear.NOTES AND REFERENCES.1A mistaken attempt hae been made in one of the most recent works on aLnatomy to do away with the glenoid ligament of this articulation, and to describe merely " sesamoid bones in place of a glenoid ligament."It is hardly necessary here to combat this view.
Clinical And Laboratorial Findings From Ige Mediated Cow's Milk Allergy (CMA) In Brazilian Pediatric Patients
Authors: A.K.F. Gushken, D.L.A. Pitarello, G.H. Yonamine, E. Ciccone, A.C. Brandão, A.P.B.M. Castro, A.C. Pastorino, C.M.A. Jacob
Journal: Journal of Allergy and Clinical Immunology (2007)