tbuckley/cabot-search huggingface dataset:
In Vivo Near-Infrared Spectroscopy
Authors: Peter Rolfe
Journal: Annual Review of Biomedical Engineering (2000)

▪ Abstract Interrogation of tissue with light offers the potential for noninvasive chemical measurement, and penetration with near-infrared wavelengths (750–1000 nm) is greater than with visible light. Specific absorption by clinically relevant compounds such as oxy- and deoxyhemoglobin and the intracellular respiratory enzyme cytochrome oxidase enable in vivo measurement of these to be performed safely and conveniently. This is the basis of in vivo near-infrared spectroscopy (ivNIRS). Multiple scattering of the interrogating beam by tissues leads to an optical path that is considerably longer than the simple physical pathlength and this complicates the analysis. Modeling of photon propagation through tissues with, for example, finite element and Monte Carlo methods, is assisting in improving the ivNIRS methodology. Instrumentation has advanced from simple continuous wave approaches, through time-resolved methods based on either time-domain or frequency-domain approaches, to spatially resolved measurement based on diffuse reflectance. Initial clinical applications were for monitoring the brain in the neonate and fetus and muscle in adults. Currently, use in adults and children for neurological assessments are of growing interest.
Mitochondrial permeability transition is a central coordinating event of apoptosis.
Authors: P Marchetti, M Castedo, S A Susin, N Zamzami, T Hirsch, A Macho, A Haeffner, F Hirsch, M Geuskens, G Kroemer
Journal: The Journal of Experimental Medicine (1996)

In a number of experimental systems, the early stage of the apoptotic process, i.e., the stage that precedes nuclear disintegration, is characterized by the breakdown of the inner mitochondrial transmembrane potential (delta psi m). This delta psi m disruption is mediated by the opening of permeability transition (PT) pores and appears to be critical for the apoptotic cascade, since it is directly regulated by Bcl-2 and since mitochondria induced to undergo PT in vitro become capable of inducing nuclear chromatinolysis in a cell-free system of apoptosis. Here, we addressed the question of which apoptotic events are secondary to mitochondrial PT. We tested the effect of a specific inhibitor of PT, bongkrekic acid (BA), a ligand of the mitochondrial adenine nucleotide translocator, on a prototypic model of apoptosis glucocorticoid-induced thymocyte death. In addition to abolishing the apoptotic delta psi m disruption, BA prevents a number of phenomena linked to apoptosis: depletion of nonoxidized glutathione, generation of reactive oxygen species, translocation of NF kappa B, exposure of phosphatidylserine residues on the outer plasma membrane, cytoplasmic vacuolization, chromatin condensation, and oligonucleosomal DNA fragmentation. BA is also an efficient inhibitor of p53-dependent thymocyte apoptosis induced by DNA damage. These data suggest that a number of apoptotic phenomena are secondary to PT. In addition, we present data indicating that apoptotic delta psi m disruption is secondary to transcriptional events. These data connect the PT control point to the p53- and ICE/ Ced 3-regulated control points of apoptosis and place PT upstream of nuclear and plasma membrane features of PCD.
Synergistic and suppressive interactions among mouse T lymphocytes in the response to phytohemagglutinin.
Authors: P F Piguet, H K Dewey, P Vassalli
Journal: The Journal of Experimental Medicine (1975)

A synergistic effect in the proliferative response to phytohemagglutinin (PHA) can be observed in cultures containing a mixture of mouse CBA/Ca lymph node cells (LNC) and syngeneic CBA/T6T6 thymocytes (ThC) when compared to cultures containing only one cell type. This effect was analyzed, at various days of culture and in LNC-ThC mixtures of different ratios, by comparing the origin of the cells in mitosis (detected by caryotypic analysis), the stimulation of DNA synthesis, the number of blasts, and the percentage of blasts labeled after pulses of [3H]thymidine (detected by autoradiography). The following conclusions were reached: (a) ThC are induced to proliferate by the presence of LNC, while they are almost unresponsive to PHA when cultured alone; and (b) the strongest "synergistic" effect is exerted on LNC, whose proliferation is markedly enhanced. Evidence is presented that this last effect is not specific to the presence of ThC, but results from a dilution of LNC which retards the time when the culture reaches a critical concentration of blasts, above which proliferation progressively stops. Thus, conditions of culture allowing the response to PHA of a low concentration of LNC leads to the most prolonged T-cell proliferation. These observations may be relevant to the types of T-cell interactions, "synergistic" or "suppressive," occurring during in vitro or in vivo immune responses.
Determinants of change in airway reactivity over 11 years in the SAPALDIA population study
Authors: I. Curjuric, E. Zemp, J. Dratva, U. Ackermann-Liebrich, P.-O. Bridevaux, R. W. Bettschart, M. Brutsche, M. Frey, M. W. Gerbase, B. Knopfli, N. Kunzli, M. Pons, J. Schwartz, C. Schindler, T. Rochat
Journal: European Respiratory Journal (2010)

We investigated determinants of change in bronchial reactivity in the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA), a population-based cohort with wide age range (29–72 yrs at follow-up). The role of sex, age, atopic status, smoking and body mass index (BMI) on percentage change in bronchial reactivity slope from the baseline value was analysed in 3,005 participants with methacholine tests in 1991 and 2002, and complete covariate data. Slope was defined as percentage decline in forced expiratory volume in 1 s from its maximal value per micromole of methacholine. Bronchial hyperreactivity prevalence fell from 14.3 to 12.5% during follow-up. Baseline age was nonlinearly associated with change in reactivity slope: participants aged &lt;50 yrs experienced a decline and those above an increase during follow-up. Atopy was not associated with change, but accentuated the age pattern (p-value for interaction = 0.038). Smoking significantly increased slope by 21.2%, as did weight gain (2.7% increase per BMI unit). Compared with persistent smokers, those who ceased smoking before baseline or during follow-up experienced a significant decrease in slope (-27.7 and -23.9%, respectively). Differing, but not statistically different, age relationships and effect sizes for smoking and BMI between sexes were found. Mean bronchial reactivity increases after 50 yrs of age, possibly due to airway remodelling or ventilation–perfusion disturbances related to cumulative lifetime exposures.
Phase II Study of Recombinant Human Endostatin in Patients With Advanced Neuroendocrine Tumors
Authors: Matthew H. Kulke, Emily K. Bergsland, David P. Ryan, Peter C. Enzinger, Thomas J. Lynch, Andrew X. Zhu, Jeffrey A. Meyerhardt, John V. Heymach, William E. Fogler, Carolyn Sidor, Ann Michelini, Kate Kinsella, Alan P. Venook, Charles S. Fuchs
Journal: Journal of Clinical Oncology (2006)

Endostatin is a 20-kd proteolytic fragment of collagen XVIII that, in preclinical studies, has been shown to have antiangiogenic and antitumor activity. Both preclinical and human phase I studies of recombinant human endostatin (rhEndostatin) suggested activity in neuroendocrine tumors, which are known to be hypervascular. We therefore performed a multicenter phase II study of rhEndostatin in patients with carcinoid or pancreatic neuroendocrine tumors.Forty-two patients with advanced pancreatic endocrine tumors or carcinoid tumors were treated with rhEndostatin administered as a bid subcutaneous injection at a starting dose of 60 mg/m2/d. Steady-state trough levels were obtained after 6 weeks of therapy; patients who did not achieve a target therapeutic level of 300 ng/mL underwent dose escalation to 90 mg/m2/d. Patients were observed for evidence of toxicity, response, and survival.rhEndostatin was associated with minimal toxicity. However, among 40 patients assessable for radiologic response, none experienced partial response to therapy, as defined by WHO criteria. The median steady-state trough level achieved after dose escalation was 331 ng/mL, within the postulated therapeutic range.Treatment with rhEndostatin did not result in significant tumor regression in patients with advanced neuroendocrine tumors.
Public health benefits of strategies to reduce greenhouse-gas emissions: urban land transport
Authors: James Woodcock, Phil Edwards, Cathryn Tonne, Ben G Armstrong, Olu Ashiru, David Banister, Sean Beevers, Zaid Chalabi, Zohir Chowdhury, Aaron Cohen, Oscar H Franco, Andy Haines, Robin Hickman, Graeme Lindsay, Ishaan Mittal, Dinesh Mohan, Geetam Tiwari, Alistair Woodward, Ian Roberts
Journal: The Lancet (2009)
Status Report on Computerized ECG Analysis
Authors: Mario Ariet
Journal: JAMA (1978)

COMPUTER analysis of ECGs has been evolving during the past 15 years. In 1976, an estimated 80 million ECGs were performed in the United States, and approximately 4 million of these were analyzed by computers.<sup>1</sup>In the past two years, three factors have combined to accelerate the rate of utilization of this method: the clinical diagnostic accuracy of some programs has increased to a level at which some clinicians have judged the programs to be useful to them in their care of patients; comprehensive computer systems have been made available that allow users to perform editing of interpretations, organization of reports, and billing; and the price-performance ratio of computer equipment has decreased substantially. <h3>Diagnostic Accuracy</h3> The most important variable in the evaluation of the potential benefits of this method of ECG analysis is the diagnostic accuracy of the computer programs. Unfortunately, this variable is very difficult to measure, and
Therapeutic potential of larval excretory/secretory proteins of the pig whipworm<i>Trichuris suis</i>in allergic disease
Authors: F. Ebner, M. R. Hepworth, S. Rausch, K. Janek, A. Niewienda, A. Kühl, P. Henklein, R. Lucius, E. Hamelmann, S. Hartmann
Journal: Allergy (2014)

Background Gastrointestinal nematodes are currently being evaluated as a novel therapeutic in the treatment of chronic human inflammatory disorders, due to their unique ability to induce immunoregulatory pathways in their hosts. In particular, administration of ova from the pig whipworm Trichuris suis (T. suis; TSO) has been proposed for the treatment of allergic, inflammatory and autoimmune disorders. Despite these advances, the biological pathways through which TSO therapy modulates the host immune system in the context of human disease remain undefined. Methods We characterized the dominant proteins present in the excretory/secretory (E/S) products of first-stage (L1) T. suis larvae (Ts E/S) using LC-MS/MS analysis and examined the immunosuppressive properties of whole larval Ts E/S in vitro and in a murine model of allergic airway disease. Results Administration of larval Ts E/S proteins in vivo during the allergen sensitization phase was sufficient to suppress airway hyperreactivity, bronchiolar inflammatory infiltrate and allergen-specific IgE production. Three proteins in larval Ts E/S were unambiguously identified. The immunomodulatory function of larval Ts E/S was found to be partially dependent on the immunoregulatory cytokine IL-10. Conclusions Taken together, these data demonstrate that the released proteins of larval T. suis have significant immunomodulatory capacities and efficiently dampen allergic airway hyperreactivity. Thus, the therapeutic potential of defined larval E/S proteins should be exploited for the treatment of human allergic disorders.
Image-guided, Lobe-specific Hydrodynamic Gene Delivery to Swine Liver
Authors: Kenya Kamimura, Takeshi Suda, Wei Xu, Guisheng Zhang, Dexi Liu
Journal: Molecular Therapy (2009)

Image-guided, lobe-specific hydrodynamic gene delivery to liver was assessed in pigs. The procedure involved image-guided insertion of a balloon catheter to the hepatic vein of the selected lobe from the jugular vein and hydrodynamic injection of plasmid DNA using a newly developed computer-controlled injection device. We demonstrated that the impact of the procedure was regional with minimal effects on neighboring lobes. Level of gene expression resulted from the procedure was 107 relative light units (RLU)/mg in the targeted lobes and 102–105 RLU/mg in the nontargeted lobes 4 hours after hydrodynamic injection of pCMV-Luc plasmids. Occlusion of blood flow in the inferior vena cava (IVC) or IVC plus portal vein (PV) was effective in elevating hydrodynamic pressure in the targeted vasculature but did not enhance gene delivery efficiency. Physiological examination on pigs with IVC occlusion revealed transient decreases of blood pressure and respiration rate. Removal of occlusion from IVC resulted in a rapid and transient increase in heart rate. Occlusion of the PV and hepatic vein showed no effect on physiological and cardiac activities. No major changes in serum composition were observed. These results suggest that (i) image-guided, lobe-specific hydrodynamic procedure is effective for regional gene delivery to liver, (ii) blockade in IVC should be avoided for hydrodynamic gene delivery to the liver, and (iii) clinical application of hydrodynamic gene delivery to liver is feasible. Image-guided, lobe-specific hydrodynamic gene delivery to liver was assessed in pigs. The procedure involved image-guided insertion of a balloon catheter to the hepatic vein of the selected lobe from the jugular vein and hydrodynamic injection of plasmid DNA using a newly developed computer-controlled injection device. We demonstrated that the impact of the procedure was regional with minimal effects on neighboring lobes. Level of gene expression resulted from the procedure was 107 relative light units (RLU)/mg in the targeted lobes and 102–105 RLU/mg in the nontargeted lobes 4 hours after hydrodynamic injection of pCMV-Luc plasmids. Occlusion of blood flow in the inferior vena cava (IVC) or IVC plus portal vein (PV) was effective in elevating hydrodynamic pressure in the targeted vasculature but did not enhance gene delivery efficiency. Physiological examination on pigs with IVC occlusion revealed transient decreases of blood pressure and respiration rate. Removal of occlusion from IVC resulted in a rapid and transient increase in heart rate. Occlusion of the PV and hepatic vein showed no effect on physiological and cardiac activities. No major changes in serum composition were observed. These results suggest that (i) image-guided, lobe-specific hydrodynamic procedure is effective for regional gene delivery to liver, (ii) blockade in IVC should be avoided for hydrodynamic gene delivery to the liver, and (iii) clinical application of hydrodynamic gene delivery to liver is feasible.
Medical Management Services Ltd
Authors: I. P. Price
Journal: BMJ (1965)

MEDICAL JOURNAFor children in hospital we are amongst the pioneers in co-operating with hospital authorities to introduce play into the wards.The " play lady " does much to alleviate the fears and sense of insecurity attending going to hospital.Paediatric staff are beginning to discover that sick children absorbed in play recover more quickly and suffer less from the emotional upset sometimes following the hospital experience.-Iam, etc.,
Clofarabine Plus Cytarabine Compared With Cytarabine Alone in Older Patients With Relapsed or Refractory Acute Myelogenous Leukemia: Results From the CLASSIC I Trial
Authors: Stefan Faderl, Meir Wetzler, David Rizzieri, Gary Schiller, Madan Jagasia, Robert Stuart, Siddhartha Ganguly, David Avigan, Michael Craig, Robert Collins, Michael Maris, Tibor Kovacsovics, Stuart Goldberg, Karen Seiter, Parameswaran Hari, Jochen Greiner, Norbert Vey, Christian Recher, Farhad Ravandi, Eunice S. Wang, Michael Vasconcelles, Dirk Huebner, Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2012)

To compare the receipt of clofarabine plus cytarabine (Clo+Ara-C arm) with cytarabine (Ara-C arm) in patients ≥ 55 years old with refractory or relapsed acute myelogenous leukemia (AML).Patients were randomly assigned to receive either clofarabine (Clo) 40 mg/m(2) or a placebo followed by Ara-C 1 g/m(2) for five consecutive days. The primary end point was overall survival (OS). Secondary end points included event-free survival (EFS), 4-month EFS, overall remission rate (ORR; complete remission [CR] plus CR with incomplete peripheral blood count recovery), disease-free survival (DFS), duration of remission (DOR), and safety.Among 320 patients with confirmed AML (median age, 67 years), the median OS was 6.6 months in the Clo+Ara-C arm and 6.3 months in the Ara-C arm (hazard ratio [HR], 1.00; 95% CI, 0.78 to 1.28; P = 1.00). The ORR was 46.9% in the Clo+Ara-C arm (35.2% CR) versus 22.9% in the Ara-C arm (17.8% CR; P < .01). EFS (HR: 0.63; 95% CI, 0.49 to 0.80; P < .01) and 4-month EFS (37.7% v 16.6%; P < .01) favored the Clo+Ara-C arm compared with Ara-C arm, respectively. DFS and DOR were similar in both arms. Overall 30-day mortality was 16% and 5% for CLO+Ara-C and Ara-C arms, respectively. In the Clo+Ara-C and Ara-C arms, the most common grade 3 to 4 toxicities were febrile neutropenia (47% v 35%, respectively), hypokalemia (18% v 11%, respectively), thrombocytopenia (16% v 17%, respectively), pneumonia (14% v 10%, respectively), anemia (13% v 0%, respectively), neutropenia (11% v 9%, respectively), increased AST (11% v 2%, respectively), and increased ALT (10% v 3%, respectively).Although the primary end point of OS did not differ between arms, Clo+Ara-C significantly improved response rates and EFS. Study follow-up continues, and the role of clofarabine in the treatment of adult patients with AML continues to be investigated.
A Variant of p22 <sup> <i>phox</i> </sup> , Involved in Generation of Reactive Oxygen Species in the Vessel Wall, Is Associated With Progression of Coronary Atherosclerosis
Authors: Carolyn Cahilly, Christie M. Ballantyne, Do-Sun Lim, Antonio Gotto, Ali J. Marian
Journal: Circulation Research (2000)

Abstract —A series of pro-oxidant and antioxidant enzymes, such as the NADPH oxidase system, maintain the redox state in the vessel wall. A major component of NADPH oxidase is p22 phox , which is implicated in atherosclerosis. We prospectively studied the association of the histidine (H) 72 →tyrosine (Y) mutation in p22 phox with the severity and progression/regression of coronary artery disease (CAD), plasma lipid levels, clinical events, and response to treatment with fluvastatin in a well-characterized population. Genotypes were determined by polymerase chain reaction and restriction digestion with Rsa I enzyme in 368 subjects in the Lipoprotein and Coronary Atherosclerosis Study (LCAS). Fasting plasma lipids and quantitative coronary angiograms were obtained at baseline and 2.5 years after randomization to fluvastatin or placebo. Subjects with CC genotype (n=157) were identified by the presence of 396-bp and 113-bp products on gel electrophoresis. Those with TT (n=39) were identified by the presence of 316-bp, 113-bp, and 80-bp products, and those with CT (n=172) by the presence of 396-bp, 316-bp, 113-bp, and 80-bp products. Baseline and final plasma levels of lipids and the baseline severity of CAD were not significantly different among the genotypes. In the placebo group, subjects with the mutation had a 3- to 5-fold greater loss in mean minimum lumen diameter (MLD) (TT: −0.15±0.15; CT: −0.17±0.26; and CC: −0.03±0.22 mm; P =0.006) and lesion-specific MLD (TT: −0.15±0.06; CT: −0.18±0.03; and CC: −0.06±0.03 mm; P =0.038) than those without. Progression was also more (TT: 8/17 [47%]; CT: 35/73 [48%]; and CC: 17/62 [27%]) and regression less (TT: 0/17 [0%]; CT: 1/73 [1%]; and CC: 11/72 [18%]) common in those with the mutation ( P =0.002). The C 242 T mutation in p22 phox , involved in maintaining the redox state in the vessel wall, is associated with progression of coronary atherosclerosis in the LCAS population.
Identification of the B-cell tumor-specific molecular fingerprint using non-radiolabelled PCR consensus primers
Authors: M Bendandi, R Tonelli, R Maffei, S Botti, C Turi, R Sartini, S Inogés, M R Calvillo, P L Zinzani, A Pession, S A Pileri, G Paolucci
Journal: Annals of Oncology (2001)
Interleukin 1 (IL-1) gene expression, synthesis, and effect of specific IL-1 receptor blockade in rabbit immune complex colitis.
Authors: F Cominelli, C C Nast, B D Clark, R Schindler, R Lierena, V E Eysselein, R C Thompson, C A Dinarello
Journal: Journal of Clinical Investigation (1990)

Interleukin 1 (IL-1) may be a key mediator of inflammation and tissue damage in inflammatory bowel disease (IBD). In rabbits with immune complex-induced colitis, IL-1 alpha and beta mRNA levels were detectable at 4 h, peaked at 12 but were absent at 96 h after the induction of colitis. Colonic IL-1 tissue levels were measured by specific radioimmunoassays. IL-1 alpha was significantly elevated at 4 h (9.4 +/- 1.5 ng/g colon), progressively increased at 48 h (31 +/- 5.8 ng/g) and then decreased by 96 h (11.5 +/- 3.4 ng/g). IL-1 beta levels were 2.0 +/- 0.5 ng/g colon at 4 h, 5.0 +/- 1.6 ng/g at 48 h and undetectable by 96 h. By comparison, colonic levels of PGE2 and LTB4 were unchanged during the first 12 h and did not become elevated until 24 h. IL-1 alpha levels were highly correlated with inflammation (r = 0.885, P less than 0.0001), edema (r = 0.789, P less than 0.0001) and necrosis (r = 0.752, P less than 0.0005). Treatment with a specific IL-1 receptor antagonist (IL-1 ra) before and during the first 33 h after the administration of immune complexes markedly reduced inflammatory cell infiltration index (from 3.2 +/- 0.4 to 1.4 +/- 0.3, P less than 0.02), edema (from 2.2 +/- 0.4 to 0.6 +/- 0.3, P less than 0.01) and necrosis (from 43 +/- 10% to 6.6 +/- 3.2%, P less than 0.03) compared to vehicle-matched colitis animals. These studies demonstrate that (a) IL-1 gene expression and synthesis occur early in the course of immune complex-induced colitis; (b) are significantly elevated for 12 h before the appearance of PGE2 and LTB4; (c) tissue levels of IL-1 correlate with the degree of tissue inflammation and; (d) specific blockade of IL-1 receptors reduces the inflammatory responses associated with experimental colitis.
Risk Factors for Acute Non-A, Non-B Hepatitis in the United States and Association With Hepatitis C Virus Infection
Authors: M J Alter, S C Hadler, F N Judson, A Mares, W J Alexander, P Y Hu, J K Miller, L A Moyer, H A Fields, D W Bradley
Journal: JAMA (1990)

The Centers for Disease Control conducted intensive surveillance for acute non-A, non-B hepatitis in four sentinel counties over a 7-year period. Testing for antibody to hepatitis C virus was performed with the newly developed enzyme immunoassay. The incidence of non-A, non-B hepatitis remained relatively stable (average, 7.1 cases per 100,000, but there were significant changes in disease transmission patterns. The proportion of patients with a history of blood transfusion declined from 17% to 6%, but the proportion with a history of parenteral drug use increased from 21% to 42%. The proportion of patients with histories of sexual exposure (6%), household exposure (3%), occupational exposure to blood (2%), or hemodialysis (0.6%) did not change over time. Antibody to hepatitis C virus was found in 45% of patients within 6 weeks of onset of illness and in 68% of patients followed up for at least 6 months. Patients with no history of transfusions were just as likely to be positive for antibody to hepatitis C virus as patients with transfusion-associated hepatitis, indicating that hepatitis C virus is the major causative agent of all non-A, non-B hepatitis in the United States.