tbuckley/cabot-search huggingface dataset:
Monoclonal antibody characterization of a chymotrypsin-like molecule on neutrophil membrane associated with cellular activation.
Authors: C H King, C H Goralnik, P J Kleinhenz, J A Marino, J R Sedor, A A Mahmoud
Journal: Journal of Clinical Investigation (1987)

Monoclonal antibody 1-15 (Ab 1-15), is a murine anti-human neutrophil (PMN) IgG1 that inhibits PMN effector responses to N-formyl-met-leu-phe (FMLP) and phorbol myristate acetate. In this study, the effects of Ab 1-15 on PMN membrane-related functions were characterized: Ab 1-15 inhibited PMN superoxide (O-2) response to FMLP by 60% (P less than 0.005) without effect on the onset or duration of O-2 production. This inhibition of O-2 response was associated with a significant inhibition of PMN chymotrypsin-like, but not trypsin-like, protease activity. Cell fractionation studies indicated the presence of an Ab 1-15 inhibitable, chymotryptic neutral protease activity in PMN membranes. In studies of Ab 1-15 effects on membrane-related second messenger pathways, Ab 1-15 augmented both FMLP- and isoproterenol-induced intracellular cAMP accumulation, whereas alpha-chymotrypsin decreased PMN cAMP response to these stimuli. Our data suggest that the function-inhibiting, anti-PMN monoclonal Ab 1-15 defines a PMN chymotryptic enzyme on the membrane surface that is involved in regulation of two membrane-related functions, O-2 generation and cAMP generation.
Comparing Physician Workforce Reform Recommendations
Authors: Marc L. Rivo
Journal: JAMA (1993)

LAST year, four respected policymaking bodies released reports calling for physician workforce and medical education reform.<sup>1-4</sup>These reports reflect widespread consensus that the physician workforce, in both numbers and competencies, does not match well with the nation's health care needs. They further point out that the United States has neither a national physician workforce plan nor a health care reimbursement and medical education financing strategy to correct the deficiencies. These independently developed reports also demonstrate striking convergence on the major directions for physician workforce reform (see Table on next page). Each group proposed a series of national goals or targets for the appropriate physician supply, specialty mix, and distribution. They recommended that the proportion of generalist physicians (defined as family physicians, general internists, and general pediatricians) should be significantly increased, the workforce should be better geographically distributed, and the current physician-to-population ratio should be maintained currently at 253 physicians
Pentraxin-3 as a Marker of Disease Activity in Takayasu Arteritis
Authors: Lorenzo Dagna, Fulvio Salvo, Mirta Tiraboschi, Enrica P. Bozzolo, Stefano Franchini, Claudio Doglioni, Angelo A. Manfredi, Elena Baldissera, Maria Grazia Sabbadini
Journal: Annals of Internal Medicine (2011)

Because pentraxin-3 (PTX3) is produced by immune and vascular cells in response to proinflammatory signals, it may be a useful biomarker for defining disease activity in patients with Takayasu arteritis.To compare PTX3 levels in patients who have Takayasu arteritis with those in healthy and infected controls, and to compare accuracy of PTX3 levels with that of C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) for distinguishing active and inactive disease.Cross-sectional, noninterventional study conducted between September 2005 and October 2008.Immunology and rheumatology clinic at a university hospital in Italy.57 consecutive patients with Takayasu arteritis and known disease activity, 57 healthy blood donor controls, and 15 patients with acute infection.Disease activity by clinical criteria; plasma PTX3 and CRP levels and ESR.27 patients had active Takayasu arteritis; 30 had inactive disease. Levels of PTX3 were higher in patients with active disease (median, >2.14 ng/mL [range, 0.57 to 48.18 ng/mL]) than in those with inactive disease (median, 0.63 ng/mL [range, 0.00 to 1.64 ng/mL]) and were higher than in healthy patients (median, 0.11 ng/mL [range, 0 to 1.20 ng/mL]) or those with acute infection (median, 0.26 ng/mL [range, 0 to 0.75 ng/mL]). A plasma PTX3 level greater than 1 ng/mL was more accurate than normal thresholds of CRP or ESR for distinguishing active from inactive disease.The study excluded patients with unknown or equivocal disease status.Plasma levels of PTX3 could help distinguish active from inactive Takayasu arteritis but should not be adopted for clinical use until the findings are confirmed in a broader spectrum of patients whose disease activity is unknown or equivocal before testing.
Site-Specific Integration of Functional Transgenes into the Human Genome by Adeno/AAV Hybrid Vectors
Authors: Alessandra Recchia, Laura Perani, Daniela Sartori, Clelia Olgiati, Fulvio Mavilio
Journal: Molecular Therapy (2004)

Uncontrolled insertion of gene transfer vectors into the human genome is raising significant safety concerns for their clinical use. The wild-type adeno-associated virus (AAV) can insert its genome at a specific site in human chromosome 19 (AAVS1) through the activity of a specific replicase/integrase protein (Rep) binding both the AAVS1 and the viral inverted terminal repeats (ITRs). AAV-derived vectors, however, do not carry the rep gene and cannot maintain site-specific integration properties. We describe a novel hybrid vector carrying an integration cassette flanked by AAV ITRs and a tightly regulated, drug-inducible Rep expression cassette in the framework of a high-capacity, helper-dependent adenoviral (Ad) vector. Rep-dependent integration of ITR-flanked cassettes of intact size and function was obtained in human primary cells and cell lines in the absence of selection. The majority of integrations were site specific and occurred within a 1000-bp region of the AAVS1. Genome-wide sequencing of integration junctions indicates that nonspecific integrations occurred predominantly in intergenic regions. Site-specific integration was obtained also in vivo, in an AAVS1 transgenic mouse model: upon a single tail vein administration of a nontoxic dose of Ad/AAV vectors, AAVS1-specific integrations were detected and sequenced in DNA obtained from the liver of all animals in which Rep expression was induced by drug treatment. Nonrandom integration of double-stranded DNA can therefore be obtained ex vivo and in vivoby the use of hybrid Ad/AAV vectors, in the absence of toxicity and with efficiency compatible with gene therapy applications.
Evolutionary Relationships Among Proteins Encoded by the Regulator of Complement Activation Gene Cluster
Authors: Julia Krushkal, Olga Bat, Irma Gigli
Journal: Molecular Biology and Evolution (2000)

Evolutionary relationships among members of the regulator of complement activation (RCA) gene cluster were analyzed using neighbor-joining and parsimony methods of phylogenetic tree inference. We investigated the structural and functional similarities among short consensus repeats (SCRs) of the following human proteins: the alpha chain of the C4b-binding protein (C4bpalpha), factor H (FH), factor H-related proteins (FHR-1 through FHR-4), complement receptors type 1 (CR1) and type 2 (CR2), the CR1-like protein (CR1L), membrane cofactor protein (MCP), decay accelerating factor (DAF), and the sand bass proteins, the cofactor protein (SBP1) and its homolog, the cofactor-related protein (SBCRP-1). Also included are the beta chain of the human C4b-binding protein (C4bpbeta) and the b subunit of human blood-clotting factor XIII (FXIIIb). Our results indicate that the human plasma complement regulators, FH and C4bpalpha, fall into two distinct groups on the basis of their sequence divergence. Homology among RCA proteins is in agreement with their chromosomal location, with the exception of C4bpbeta. The evolutionary relationships among individual short consensus repeats are confirmed by the exon/intron structure of the RCA members. Structural similarities among repeats of the RCA proteins correlate with their functional activities and demonstrate the importance of the N-terminal SCRs.
Effects of arterial distensibility on left ventricular ejection in the depressed contractile state
Authors: Y. Maruyama, O. Nishioka, E. Nozaki, H. Kinoshita, H. Kyono, Y. Koiwa, T. Takishima
Journal: Cardiovascular Research (1993)

The aim was to evaluate the effects of arterial distensibility on ventricular ejection in various ventricular contractile states: (1) control; (2) a regionally depressed contractile state due to left circumflex coronary artery occlusion (ligation); (3) a globally depressed contractile state induced by lignocaine (lignocaine); and (4) a globally augmented contractile state due to dobutamine infusion (dobutamine).Arterial compliance was decreased from 2.3 x 10(-4) dyne-1.cm5 (C2.3) to 0.4 x 10(-4) dyne-1.cm5 (C0.4), maintaining other afterload components and left ventricular end diastolic pressure constant. Nine excised perfused and paced canine hearts, supported from donor dogs, were used.In control, ligation, lignocaine, and dobutamine groups, the difference in cardiac output between the compliance values of C0.4 and C2.3 was 124(SEM 32), 204(36), 163(33), and 130(24) ml, respectively. Thus cardiac output at C0.4, as a percentage of that at C2.3, was 88(2.8)% (control), 75(2.9)% (ligation), 82(2.9)% (lignocaine), and 88(2.4)% (dobutamine), respectively: control v ligation, and lignocaine v ligation, p < 0.001; control v lignocaine, and dobutamine v ligation, p < 0.01. Stroke work at C0.4 decreased in the ligation group (63%, p < 0.001) and in the lignocaine group (70%, p < 0.001).When cardiac dysfunction is already present, decreased arterial distensibility has a further deleterious effect on cardiac output. This may be due to the fact that the pressure at the end of ejection is higher and as a result the change in dimension during ejection is considerably reduced, especially in cases with depressed cardiac function caused by afterload dependency.
P1-06-26: The EndoPredict Score Is a Response Predictor for Neoadjuvant Chemotherapy in ER-Positive, HER2−Negative Breast Cancer.
Authors: JC Brase, MC Gehrmann, C Petry, KE Weber, M Schmidt, H Kölbl, H Brauch, M Schwab, V Müller, F Jänicke, A Rody, M Kaufmann, M Filipits, M Gnant, C Denkert, S Loibl, Minckwitz G von, R Kronenwett
Journal: Cancer Research (2011)

Abstract Background: The EndoPredict (EP) score is a multigene classifier to predict the likelihood of distant recurrence in ER-positive, HER2−negative breast cancer patients treated with adjuvant endocrine therapy. Two large randomized phase III trials involving endocrine therapy only (n &amp;gt; 1700) demonstrated additional prognostic information of the EP score independent from clinicopathological parameters by classifying 49% as low risk. However, the predictive role of the EP is not clear. Therefore, we examined whether the EP Score also predicts sensitivity towards neoadjuvant chemotherapy in ER-positive, HER2−negative breast cancer patients. Methods: Four publicly available gene expression data sets (Affymetrix HG-U133A) were retrieved from the gene expression omnibus (GEO) data repository. All analyzed breast cancer patients were treated with anthracycline or taxane/anthracycline-based neoadjuvant chemotherapy. Microarray cel files were MAS5 normalized with a global scaling procedure and a target intensity of 500. The analysis was restricted to ER-positive, HER2−negative breast cancer patients according to pre-specified cut-off levels for the respective ESR1/ERBB2 Affymetrix probesets. The EP score was calculated and patients were classified as having low or high risk according to the pre-specified validated cut-off value. Pathological complete response (pCR) — defined as no residual invasive cancer in the breast or lymph nodes — was used as the primary endpoint for the assessment of treatment response. Results: The EP Score was examined in 221 ER-positive, HER2−negative breast cancer patients treated with neoadjuvant therapy. Among the 221 patients, 61 tumors (27.6%) were classified as EP-low-risk, whereas 160 tumors (72.4%) were EP-high-risk. Only one of the EP-low-risk tumors achieved a pCR after neoadjuvant therapy, whereas 24 of the 25 pCR events were classified as EP high risk. The sensitivity of the EP score was 96% and the negative predictive value 98% with an area under the receiver operating characteristic curve of 0.73. Conclusions: The EP Score is a predictor of chemosensitivity in the neoadjuvant setting. The test correctly identified all but one of the patients achieving a pCR suggesting that the benefit of cytotoxic chemotherapy is limited to the EP high risk group. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-06-26.
Factors associated with uptake of measles, mumps, and rubella vaccine (MMR) and use of single antigen vaccines in a contemporary UK cohort: prospective cohort study
Authors: Anna Pearce, Catherine Law, David Elliman, Tim J Cole, Helen Bedford
Journal: BMJ (2008)

To estimate uptake of the combined measles, mumps, and rubella vaccine (MMR) and single antigen vaccines and explore factors associated with uptake and reasons for not using MMR.Nationally representative cohort study.Children born in the UK, 2000-2.14,578 children for whom data on immunisation were available.Immunisation status at 3 years defined as "immunised with MMR," "immunised with at least one single antigen vaccine," and "unimmunised."88.6% (13,013) were immunised with MMR and 5.2% (634) had received at least one single antigen vaccine. Children were more likely to be unimmunised if they lived in a household with other children (risk ratio 1.74, 95% confidence interval 1.35 to 2.25, for those living with three or more) or a lone parent (1.31, 1.07 to 1.60) or if their mother was under 20 (1.41, 1.08 to 1.85) or over 34 at cohort child's birth (reaching 2.34, 1.20 to 3.23, for > or =40), more highly educated (1.41, 1.05 to 1.89, for a degree), not employed (1.43, 1.12 to 1.82), or self employed (1.71, 1.18 to 2.47). Use of single vaccines increased with household income (reaching 2.98, 2.05 to 4.32, for incomes of > or = 52,000 pounds sterling (69,750 euros, $102,190)), maternal age (reaching 3.04, 2.05 to 4.50, for > or =40), and education (reaching 3.15, 1.78 to 5.58, for a degree). Children were less likely to have received single vaccines if they lived with other children (reaching 0.14, 0.07 to 0.29, for three or more), had mothers who were Indian (0.50, 0.25 to 0.99), Pakistani or Bangladeshi (0.13, 0.04 to 0.39), or black (0.31, 0.14 to 0.64), or aged under 25 (reaching 0.14, 0.05 to 0.36, for 14-19). Nearly three quarters (74.4%, 1110) of parents who did not immunise with MMR made a "conscious decision" not to immunise.Although MMR uptake in this cohort is high, a substantial proportion of children remain susceptible to avoidable infection, largely because parents consciously decide not to immunise. Social differentials in uptake could be used to inform targeted interventions to promote uptake.
Can the response of port-wine stains to laser treatment be reliably assessed using subjective methods?
Authors: C.L.A. Currie, B.E. Monk
Journal: British Journal of Dermatology (2000)

Assessing the results of laser treatment of port-wine stains (PWS) is very subjective. Most publications use scoring systems that physically describe the change in PWS after treatment. For results derived from such an analysis to be meaningful, the observers must be able to produce results that not only have a small interobserver variability but are also reproducible. Previous studies have addressed the former but not the latter. The present study was undertaken to investigate this area of concern. Six professionals, experienced in laser work, blindly assessed the response to laser treatment of 20 PWS, on two occasions, 1 month apart. Twenty pairs of comparable clinical photographs (one pretreatment and one post-treatment) were assessed using three different scoring systems commonly used in previous publications. Intrarater concordance between the two sessions was then assessed. Our results demonstrated that the judges could only consistently score results at the extremes of outcome. There was little agreement in the assessment of results lying between these. The judges were, however, consistently able to place a similar proportion of patients in each outcome category. We conclude that, as yet, there is no satisfactory method of monitoring the progress of an individual's PWS following laser treatment. However, the scoring systems examined would seem to be reasonable for presenting the data from patient series.
Case of cobalt poisoning.
Authors: U. O. Schirrmacher
Journal: BMJ (1967)

MEDICLSHORNArequirements of diabetic patients alter with changes in physiological stress without simultaneous alteration in insulin anti- body levels.This does not of course prove that insulin antibodies do not influence the insulin requirements from patient to patient.The studies reported here, showing that the majority of beef-insulin-treated diabetic patients can be maintained on a smaller dose of pork insulin, which can be predetermined by preferential insulin antibody-binding studies, indicate that antibodies to insulin account for a fixed aliquot of the daily insulin requirement.The immediate clinical problem raised by this study is the necessity to exercise caution in changing diabetic patients from a pure beef-insulin preparation to a pure pork-insulin prepara- tion.The theoretical possibility of deliberately inducing bovine-insulin antibodies and subsequently altering to porcine insulin in view of the failure of porcine insulin to produce a primary antibody response under these circumstances (Devlin and Stephenson, 1966) must be considered. SUMMARYThe majority of a beef-insulin-treated diabetic population preferentially bind beef, pork, and human insulins in the order beef>pork>human.The theoretical implications of this observation are briefly discussed.
Priming effect of RANTES on eosinophil oxidative metabolism
Authors: J. Chihara, H. Yamada, T. Yamamoto, D. Kurachi, N. Hayashi‐Kameda, K. Honda, H. Kayaba, O. Urayama
Journal: Allergy (1998)

Background RANTES has been shown to possess chemotactic activity for eosinophils, which have also been considered to play a role in allergic inflammation through reactive oxygen species. Thus, in this study, we examined the effect of RANTES on radical oxygen products from eosinophils. Methods Purified eosinophils by CD16‐negative selection or an eosinophilic cell line (EoL‐1) were incubated with or without RANTES (2.5 x 10 −6 ). To the mixture of eosinophils and luminol, calcium ionophore (A23187) or opsonized zymosan (OZ) was added, and radical oxygen products were determined by luminol‐dependent chemiluminescence for 600 s. Results Eosinophil‐mediated radical oxygen products of untreated eosinophils produced with A23187 gave a peak value of 14.09 + 2.40 (mean±SE, n = 12) relative light units (RLU) and an integrated value of 3232.20 + 513.09 RLU. However, with treatment with RANTES, a peak value of 18.66 + 2.40 RLU and an integrated value of 5301.05 ±561.02 RLU were obtained. Eosinophil oxidative metabolism‐induced A23187 or OZ was apparently augmented by the preincubation with RANTES. In addition, the radical oxygen products of EoL‐1 showed similar results. Conclusions Thus, we concluded that RANTES may play an important role the pathogenesis of allergic inflammation through its involvement in eosinophil activation, as evidenced by oxygen products, as well as in selective eosinophil infiltration as selective eosinophil chemoattractant.
Transcutaneous oxygen tension during exercise in patients with claudication.
Authors: T A Holdich, P J Reddy, R T Walker, J A Dormandy
Journal: BMJ (1986)

Transcutaneous oxygen tension (TcPO2) was monitored during maximal exercise in 10 patients with stable moderate to severe claudication. The TcPO2 fell by 16% at the onset of claudication and 32% at the maximum walking distance. On resting this decrease reached a maximum of 66% roughly four minutes after exercise. This was followed by a steady recovery. The percentage changes were reproducible in each patient and were appreciably different from the TcPO2 exercise profiles of normal healthy volunteers. TcPO2 monitoring during exercise is a simple, reproducible, cheap, and useful technique for assessing claudication and compares favourably with other techniques used to quantify this condition.
The Visible Vessel on the Bleeding Gastric Ulcer: An Endoscopic-Pathological Study
Authors: J.-J. Chen, C.-S. Changchien, C.-C. Lin, W.-C. Chang
Journal: Endoscopy (1997)

The visible vessel is an important endoscopic sign for predicting rebleeding in ulcers. Freeman has described a visible vessel with a high rate of rebleeding as a "pearl" color (whitish) compared with a darkly colored "sentinel" clot with a low rebleeding rate. Clarifying the color of visible vessels helps to distinguish high-risk bleeding ulcers. We conducted a retrospective study that compared pathological findings with endoscopic pictures to determine the significance of the visible vessel's color.From January 1986 to December 1992, 110 patients who underwent endoscopy and received subtotal gastrectomies for ulcer bleeding were included in this study. Of these, 24 received endoscopic therapy before the operation. There were 94 males and 16 females, ranging in age from 30 to 90 years, with a mean age of 62.5 years. According to Freeman's report, a subgroup of visible vessels (IIav +) was defined as having either a "pearl-colored" collar around a red or black protruding mount or a "pearl-colored" mount on the ulcer base. The endoscopic findings were compared with the findings of the pathological specimens.The endoscopic findings on the stigmata of recent hemorrhage in the 110 patients revealed that 31 were of type IIa (including 18 type IIav+ and 13 type IIav-), 56 of type IIb, 18 of type IIc, and 5 of type III. Fifty-four patients (49,1%) were found from their pathological specimen to have an eroded vessel on their ulcer base. Type IIa patients had a higher percentage of eroded vessels. The percentages of eroded vessels in types IIa, IIb, IIc, and III were 67.7%, 46.4%, 33.3%, and 20 %, respectively (P < 0.05, Fisher's exact test). Of the 54 patients with an eroded vessel in their pathological specimen, 13 (24 %) were found to have some vessel wall above the ulcer base (six in type IIa, four in type IIb, two in type IIc, and one in type III). Among the six with vessel wall above the ulcer base in type IIa, five patients (83 %) were identified as type IIav+ under endoscopy. There was a greater frequency of having a vessel wall above the ulcer base in type IIav+ than in type IIav- (38.5% vs. 12.5%) among the 31 endoscopic type IIa patients.From this study, we determined that the wall of an eroded vessel on a gastric ulcer may protrude either above or below the ulcer base. A vessel wall on the ulcer base will appear pearl-colored under endoscopic view.
Laboratory to Study Micronutrients, Cancer Risk as Part of Chemoprevention Efforts
Authors: Timothy F. Kirn
Journal: JAMA (1988)

IF EATING habits can have an impact on cardiovascular risk, some investigators hypothesize, perhaps the same is true for cancer. The National Cancer Institute (NCI), which obviously thinks this hypothesis is worth pursuing, launched a cancer prevention program almost six years ago (<i>JAMA</i>1982;247: 1799-1802) and now is bolstering its commitment. The institute is establishing a 60-person laboratory devoted primarily to researching the role that certain micronutrients such as vitamins and essential minerals play in reducing the risk of cancer. According to Daniel W. Nixon, MD, the newly appointed associate director of the cancer prevention research program, annual funding for the laboratory will be $8 million to $12 million. Previously, the program spent about $5 million annually to support 20 different clinical trials. Nixon says a search of the scientific literature indicates there are at least 200 substances that warrant investigation. Of those, he says, probably about 90 will be