tbuckley/cabot-search huggingface dataset:
Quantitative analysis of the IgG and IgG subclass immune responses to chromosomal Pseudomonas aeruginosa beta-lactamase in serum from patients with cystic fibrosis by western blotting and laser scanning densitometry.
Authors: T. D. Petersen, O. Ciofu, T. Pressler, B. Giwercman, S. S. Pedersen, N. Hoiby
Journal: Thorax (1996)

BACKGROUND: Antibodies against chromosomal beta-lactamase of Pseudomonas aeruginosa (a beta ab) are markers of the development of resistance of P aeruginosa to beta-lactam antibiotics in patients with cystic fibrosis and chronic lung infection. The role of these antibodies in patients with chronic lung infection with P aeruginosa was further investigated by correlating the a beta ab IgG subclasses with pulmonary function in patients with cystic fibrosis. METHODS: Immunoglobulin G (IgG) and IgG subclass a beta ab were investigated by western blotting and quantified by laser scanning densitometry. A longitudinal study on 43 consecutive patients with cystic fibrosis who developed chronic lung infection with P aeruginosa was performed. RESULTS: IgG subclass a beta ab appeared in all patients with chronic infection with P aeruginosa. Eleven years after the onset of infection all the patients had IgG1, 79% had IgG4, 56% IgG2, and only 16% of the patients had IgG3 a beta ab. The IgG1 and IgG4 a beta ab appeared first, and more than 50% of the patients were IgG1 and IgG4 a beta ab positive within 2-3 years of the onset of infection, but IgG2 positivity only appeared after seven years and IgG3 remained absent from most of the patients. The median a beta ab levels increased during chronic infection: 100-fold for IgG1, 22-fold for IgG2, and 45-fold for IgG4. A 16-fold increase in the IgG3 a beta ab levels was detected in the six patients who developed IgG3 a beta ab. In the first four years of the chronic infection the a beta ab titres were higher in patients with good lung function than in those with poor lung function. CONCLUSIONS: The association of a weak IgG3 and a strong IgG4 a beta ab response suggests that the contribution of a beta ab antibodies to lung diseases mediated by immune complexes might be less important than other antipseudomonal antibodies. A beneficial neutralising effect of the a beta ab antibodies on the antibiotic destroying enzymes may be an additional factor.
Unifying cell assembly theory with observations of brain dynamics
Authors: R. Miller
Journal: Behavioral and Brain Sciences (1999)

Empirical evidence suggests that high frequency electrographic activity is involved in active representation of meaningful entities in the cortex. Theoretical work suggests that distributed cell assemblies also represent meaningful entities. However, we are still some way from understanding how these two are related. This commentary also makes suggestions for further investigation of the neural basis of language at the level of both words and sentence planning.
Yet another case of haemochromatosis?
Authors: A. J. Fowell, A. C. Bateman, W. J. Griffiths, K. L. Nash
Journal: Gut (2010)

A 38 year old Caucasian woman whose father and two brothers had been diagnosed with hereditary haemochromatosis was found to have chronic fatigue and a serum ferritin of 1490 μg/l. Her transferrin saturation was 32% and her full blood count, liver biochemistry, international normalised ratio and C-reactive protein were all normal. She had regular menstrual periods and no other medical history of note. She had no specific risk factors for chronic liver disease, her alcohol consumption was less than 5 units a week and there was no history of receipt of blood transfusion. Clinical examination …
Evidence for an association between rheumatoid arthritis and autoimmune endocrine disease.
Authors: D J Thomas, A Young, A N Gorsuch, G F Bottazzo, A G Cudworth
Journal: Annals of the Rheumatic Diseases (1983)

Evidence is presented for the first time of a significantly increased prevalence of type 1 (insulin-dependent) diabetes in the close relatives of patients with rheumatoid arthritis. Thirty-nine (13%) of 295 patients with classical or definite rheumatoid arthritis had a first or second degree relative with type 1 diabetes and 38 (13%) had a close relative with autoimmune thyroid disease. These findings could be compatible with a possible common genetically determined mechanism of susceptibility to both diseases.
Cardiac MyBP-C Regulates the Rate and Force of Contraction in Mammalian Myocardium
Authors: Richard L. Moss, Daniel P. Fitzsimons, J. Carter Ralphe
Journal: Circulation Research (2014)

Cardiac myosin-binding protein-C (cMyBP-C) is a thick filament-associated protein that seems to contribute to the regulation of cardiac contraction through interactions with either myosin or actin or both. Several studies over the past several years have suggested that the interactions of cardiac myosin-binding protein-C with its binding partners vary with its phosphorylation state, binding predominantly to myosin when dephosphorylated and to actin when it is phosphorylated by protein kinase A or other kinases. Here, we summarize evidence suggesting that phosphorylation of cardiac myosin binding protein-C is a key regulator of the kinetics and amplitude of cardiac contraction during β-adrenergic stimulation and increased stimulus frequency. We propose a model for these effects via a phosphorylation-dependent regulation of the kinetics and extent of cooperative recruitment of cross bridges to the thin filament: phosphorylation of cardiac myosin binding protein-C accelerates cross bridge binding to actin, thereby accelerating recruitment and increasing the amplitude of the cardiac twitch. In contrast, enhanced lusitropy as a result of phosphorylation seems to be caused by a direct effect of phosphorylation to accelerate cross-bridge detachment rate. Depression or elimination of one or both of these processes in a disease, such as end-stage heart failure, seems to contribute to the systolic and diastolic dysfunction that characterizes the disease.
A rare diagnosis of pancreatic tumour
Authors: C-S Chung, W-C Liao, H-P Wang
Journal: Gut (2009)

From 1990 to 2000, several effective new treatments were introduced for the prevention of osteoporotic fractures; these treatments were proven effective in large, international, clinical trials. At the same time, there was rapid technologic innovation, with the introduction of new radiologic methods for the noninvasive assessment of patients9 bone density status. These developments led to the publication of guidelines for the clinical use of bone densitometry that include criteria for the referral of patients for investigation as well as recommendations for intervention thresholds for the initiation of preventive treatment of osteoporosis. Dual-energy x-ray absorptiometry scanning of the spine and hip remains the technique of choice for bone densitometry studies, although there is now a wider appreciation of the need for smaller, cheaper devices for scanning the peripheral skeleton if the millions of women most at risk of a fragility fracture are to be identified and treated. This article reviews these developments, concentrating in particular on the advantages and disadvantages of the different types of equipment available for performing bone densitometry investigations, the guidelines for the referral of patients, and the principles for the interpretation of the scan findings.
Vascular Targeted Nanoparticles for Imaging and Treatment of Brain Tumors
Authors: G. Ramachandra Reddy, Mahaveer S. Bhojani, Patrick McConville, Jonathan Moody, Bradford A. Moffat, Daniel E. Hall, Gwangseong Kim, Yong-Eun L. Koo, Michael J. Woolliscroft, James V. Sugai, Timothy D. Johnson, Martin A. Philbert, Raoul Kopelman, Alnawaz Rehemtulla, Brian D. Ross
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Development of new therapeutic drug delivery systems is an area of significant research interest. The ability to directly target a therapeutic agent to a tumor site would minimize systemic drug exposure, thus providing the potential for increasing the therapeutic index. Experimental Design: Photodynamic therapy (PDT) involves the uptake of a sensitizer by the cancer cells followed by photoirradiation to activate the sensitizer. PDT using Photofrin has certain disadvantages that include prolonged cutaneous photosensitization. Delivery of nanoparticles encapsulated with photodynamic agent specifically to a tumor site could potentially overcome the drawbacks of systemic therapy. In this study, we have developed a multifunctional polymeric nanoparticle consisting of a surface-localized tumor vasculature targeting F3 peptide and encapsulated PDT and imaging agents. Results: The nanoparticles specifically bound to the surface of MDA-435 cells in vitro and were internalized conferring photosensitivity to the cells. Significant magnetic resonance imaging contrast enhancement was achieved in i.c. rat 9L gliomas following i.v. nanoparticle administration. Serial magnetic resonance imaging was used for determination of pharmacokinetics and distribution of nanoparticles within the tumor. Treatment of glioma-bearing rats with targeted nanoparticles followed by PDT showed a significant improvement in survival rate when compared with animals who received PDT after administration of nontargeted nanoparticles or systemic Photofrin. Conclusions: This study reveals the versatility and efficacy of the multifunctional nanoparticle for the targeted detection and treatment of cancer.
Should Immunonutrition Become Routine in Critically Ill Patients?
Authors: Daren K. Heyland, Frantisek Novak, John W. Drover, Minto Jain, Xiangyao Su, Ulrich Suchner
Journal: JAMA (2001)

ContextSeveral nutrients have been shown to influence immunologic and inflammatory responses in humans. Whether these effects translate into an improvement in clinical outcomes in critically ill patients remains unclear.ObjectiveTo examine the relationship between enteral nutrition supplemented with immune-enhancing nutrients and infectious complications and mortality rates in critically ill patients.Data SourcesThe databases of MEDLINE, EMBASE, Biosis, and CINAHL were searched for articles published from 1990 to 2000. Additional data sources included the Cochrane Controlled Trials Register from 1990 to 2000, personal files, abstract proceedings, and relevant reference lists of articles identified by database review.Study SelectionA total of 326 titles, abstracts, and articles were reviewed. Primary studies were included if they were randomized trials of critically ill or surgical patients that evaluated the effect of enteral nutrition supplemented with some combination of arginine, glutamine, nucleotides, and omega-3 fatty acids on infectious complication and mortality rates compared with standard enteral nutrition, and included clinically important outcomes, such as mortality.Data ExtractionMethodological quality of individual studies was scored and necessary data were abstracted in duplicate and independently.Data SynthesisTwenty-two randomized trials with a total of 2419 patients compared the use of immunonutrition with standard enteral nutrition in surgical and critically ill patients. With respect to mortality, immunonutrition was associated with a pooled risk ratio (RR) of 1.10 (95% confidence interval [CI], 0.93-1.31). Immunonutrition was associated with lower infectious complications (RR, 0.66; 95% CI, 0.54-0.80). Since there was significant heterogeneity across studies, we examined several a priori subgroup analyses. We found that studies using commercial formulas with high arginine content were associated with a significant reduction in infectious complications and a trend toward a lower mortality rate compared with other immune-enhancing diets. Studies of surgical patients were associated with a significant reduction in infectious complication rates compared with studies of critically ill patients. In studies of critically ill patients, studies with a high-quality score were associated with increased mortality and a significant reduction in infectious complication rates compared with studies with a low-quality score.ConclusionImmunonutrition may decrease infectious complication rates but it is not associated with an overall mortality advantage. However, the treatment effect varies depending on the intervention, the patient population, and the methodological quality of the study.
In Vivo Demonstration of the Cholesterol Feedback System by Means of a Desmosterol Suppression Technique
Authors: Lee A. Bricker, Hans J. Weis, Marvin D. Siperstein
Journal: Journal of Clinical Investigation (1972)

This report describes a "desmosterol suppression" technique with which it has been possible to demostrate the operation of the cholesterol negative feedback system in the intact animal. 0.1% triparanol in the diet causes a virtually complete block in the conversion of desmosterol to cholesterol by liver and intestine. Since desmosterol is not consumed in the diet, the level of plasma desmosterol can be employed as an index of endogenous sterol production and release into the bloodstream. With this technique it was shown that the feeding of cholesterol for 8 days to rats decreases blood desmosterol levels to less than 5% of control values. Very similar results were obtained when cholesterol synthesis was assayed in vivo with acetate-(14)C as a cholesterol precursor. These observations indicate that the cholesterol feedback system operates very effectively in the intact animal in suppressing the endogenous contribution to the circulating cholesterol pool. Since intestinal cholesterol synthesis is only slightly inhibited by exogenous cholesterol, these results also indicate that the intestine does not represent a significant source of plasma sterols in the rat.
Effects of lung volume and thoracic gas compression on maximal and partial flow-volume curves
Authors: R Pellegrino, P Confessore, A Bianco, V Brusasco
Journal: European Respiratory Journal (1996)

Comparing isovolume flows, measured at the mouth during forced expiratory manoeuvres as started from maximal or partial lung inflation, is a means of assessing the effects of deep inhalation on airway calibre. The aim of this study was to investigate whether the assessment of the effect of deep inhalation during induced bronchoconstriction is influenced by the lung volume at which it is determined and by volume differences due to thoracic gas compression that occur during forced expiratory manoeuvres. Four healthy subjects and six subjects with mild-to-moderate asthma subjects performed partial and maximal forced expiratory manoeuvres in a flow-type body plethysmograph at control and during a methacholine (MCh) inhalation challenge. Mouth flow (V1) was plotted against both the expired volume (Vmo) and the simultaneous thoracic volume measured by plethysmography (Vpl) changes (V1-Vmo loop and V1-Vpl loop, respectively). The effects of deep inhalation were quantified by determining 1) the ration of maximal to partial expiratory flows (M/P) at 30, 40 and 50% of control forced vital capacity (FVC) both on V1-Vmo loops (M/Pmo) and V1-Vpl loops (M/Ppl) at control and at MCh end-point; and 2) the slope of the linear regression of maximal vs partial expiratory flows at 30, 40 and 50% of control FVC both on V1-Vmo loops (MPst,mo) and V1-Vpl loops (MPsl,pl) over the entire challenge. At control, M/Pmo and M/Ppl were similar. At MCh end-point, M/Pmo and M/Ppl increased more than twofold (p &lt; 0.002), with M/Pmo consistently exceeding M/Ppl (p &lt; 0.001). In addition, both M/Pmo and M/Ppl varied inversely with lung volume (p &lt; 0.001). By contrast, MPsl,mo and MPsl,pl were not significantly different from each other (p = 0.8), and were also similar at the different lung volumes (p = 0.6). We conclude that during induced bronchoconstriction, the bronchodilation following a deep inhalation, expressed as maximal to partial flow ratio is dependent both on lung volume and volume differences due to thoracic gas compression. The use of expired flow and volume measurements may lead to a small but systematic overestimation of the bronchodilator effect of a deep inhalation. On the contrary, maximal to partial flow slope is insensitive either to lung volume or volume differences due to thoracic gas compression and can, therefore, be fairly determined from expired flow-volume loops.
Identification of objective pathological prognostic determinants and models of prognosis in Dukes' B colon cancer
Authors: V C Petersen, K J Baxter, S B Love, N A Shepherd
Journal: Gut (2002)

<b>Background and aims:</b> There is a need for objective easily determined pathological prognostic parameters in Dukes9 B colon carcinoma to allow selection of such patients for further treatment as the role of adjuvant chemotherapy for these patients remains unclear. This study was initiated to assess the influence of pathological factors on prognosis in an unselected prospective series of Dukes9 B colonic cancer. <b>Methods:</b> The Gloucester Colorectal Cancer study, established in 1988, recruited more than 1000 cases. Meticulous pathological assessment of the 268 Dukes9 B colonic cancer resections in this series included evaluation of all pathological factors that could influence staging and prognosis. All patients entered a comprehensive follow up system. <b>Results:</b> Four pathologically determined factors—peritoneal involvement, venous spread (both submucosal and extramural), spread to involve a surgical margin, and perforation through the tumour—were independent prognostic factors in multivariate analysis. Combining these four factors into a simple cumulative scoring system generated clinically useful prognostic groups. <b>Conclusions:</b> The cumulative prognostic index allows apportionment of patients with Dukes9 B colon cancer into defined prognostic groups, which in turn could allow more objective selection of patients for adjuvant therapy, especially as part of clinical trials.
Diabetes-related emotional distress in Dutch and U.S. diabetic patients: cross-cultural validity of the problem areas in diabetes scale.
Authors: F J Snoek, F Pouwer, G W Welch, W H Polonsky
Journal: Diabetes Care (2000)

OBJECTIVE: To examine the cross-cultural validity of the Problem Areas in Diabetes Scale (PAID) in Dutch and U.S. diabetic patients. RESEARCH DESIGN AND METHODS: A total of 1,472 Dutch people with diabetes completed the PAID along with other self-report measures of affect. Statistics covered Cronbach's alpha, exploratory factor analysis (EFA), and confirmatory factor analysis (CFA), Pearson's product-moment correlation, and t tests. Psychometric properties of PAID were compared for Dutch and U.S. diabetic patients. RESULTS: Internal consistency of the Dutch PAID was high and stable across sex and type of diabetes. Test-retest reliability was high. Principal component analyses confirmed 1 general 20-item factor, whereas EFA identified 4 new subdimensions: negative emotions, treatment problems, food-related problems, and lack of social support. These dimensions were confirmed with CFA and were replicated in the U.S. sample. The PAID and its subscales demonstrated moderate to high associations in the expected direction with other measures of affect. Dutch and U.S. subjects reported having the same problem areas, with U.S. patients reporting higher emotional distress levels both in type 1 and type 2 diabetes. CONCLUSIONS: The Dutch and U.S. 20-item PAID appeared to be psychometrically equivalent, which allowed for cross-cultural comparisons.
Nebulized Liposomal Amphotericin B for Treating <i>Aspergillus</i> Empyema with Bronchopleural Fistula
Authors: Shigeo Hanada, Hironori Uruga, Hisashi Takaya, Atsushi Miyamoto, Nasa Morokawa, Atsuko Kurosaki, Kazuma Kishi
Journal: American Journal of Respiratory and Critical Care Medicine (2014)
Regulation of Smooth Muscle Cell Proliferation by β-Catenin/T-Cell Factor Signaling Involves Modulation of Cyclin D1 and p21 Expression
Authors: Helen Quasnichka, Sadie C. Slater, Cressida A. Beeching, Manfred Boehm, Graciela B. Sala-Newby, Sarah J. George
Journal: Circulation Research (2006)

We previously observed that stimulation of vascular smooth muscle cell (VSMC) proliferation with growth factors is associated with dismantling of cadherin junctions and nuclear translocation of β-catenin. In this study we demonstrate directly that growth factors stimulate β-catenin/T-cell factor (TCF) signaling in primary VSMCs. To determine whether β-catenin/TCF signaling regulates VSMC proliferation via modulation of the β-catenin/TCF responsive cell cycle genes, cyclin D1 and p21, we inhibited β-catenin/TCF signaling by adenoviral-mediated over-expression of N-Cadherin, ICAT (an endogenous inhibitor of β-catenin/TCF signaling), or a dominant negative (dn) mutant of TCF-4. N-cadherin, ICAT or dnTCF-4 over-expression significantly reduced proliferation of isolated human VSMCs by approximately 55%, 80%, and 45% respectively. Similar effects were observed in human saphenous vein medial segments where proliferation was reduced by approximately 55%. Transfection of dnTCF-4 in the ISS10 human VSMC line significantly lowered TCF and cyclin D1 reporter activity but significantly elevated p21 reporter activity, indicating regulation of these genes by β-catenin/TCF signaling. In support of this, over-expression of N-cadherin, ICAT or dnTCF-4 in isolated human VSMCs significantly lowered levels of cyclin D1 mRNA and protein levels. In contrast, over-expression of N-Cadherin, ICAT or dnTCF4 significantly elevated p21 mRNA and protein levels. In summary, we have demonstrated that increasing N-cadherin and inhibiting β-catenin/TCF signaling reduces VSMC proliferation, decreases the expression of cyclin D1 and increases levels of the cell cycle inhibitor, p21. We therefore suggest that the N-cadherin and β-catenin/TCF signaling pathway is a key modulator of VSMC proliferation via regulation of these 2 β-catenin/TCF responsive genes.
Nonmelanoma Skin Cancer in Survivors of Childhood and Adolescent Cancer: A Report From the Childhood Cancer Survivor Study
Authors: Joanna L. Perkins, Yan Liu, Pauline A. Mitby, Joseph P. Neglia, Sue Hammond, Marilyn Stovall, Anna T. Meadows, Ray Hutchinson, ZoAnn E. Dreyer, Leslie L. Robison, Ann C. Mertens
Journal: Journal of Clinical Oncology (2005)

Nonmelanoma skin cancer (NMSC) has become the most common type of cancer in many populations throughout the world. Ultraviolet and ionizing radiation are known risk factors. Because NMSCs are rarely lethal and most cancer registries do not routinely report data regarding these cancers, they have received little attention in studies evaluating long-term effects of cancer therapy. This article reports on the occurrence of secondary NMSC as a long-term effect of cancer therapy in survivors of childhood cancer.The Childhood Cancer Survivor Study (CCSS) is a cohort study of 5-year survivors of childhood and adolescent cancer from 25 participating institutions in North America. NMSC patients were defined by a history of basal cell or squamous cell carcinoma of the skin after primary malignancy treatment. Demographic and treatment data were collected and analyzed.Among the 13,132 eligible CCSS participants, 213 have reported NMSC; 99 patients (46%) have had multiple occurrences. Median age of occurrence was 31 years (range, 7 to 46 years). Location of NMSC included head and neck (43%), back (24%), chest (22%), abdomen and pelvis (5%), extremity (3%), and unknown (4%). Ninety percent of patients had previously received radiation therapy (RT); 90% of tumors occurred within the RT field. RT was associated with a 6.3-fold increase in risk (95% CI, 3.5- to 11.3-fold).Long-term survivors of childhood and adolescent cancer who were treated with RT are at highest risk for developing NMSC. Educational efforts need to be directed to this population to facilitate early diagnosis of NMSC and reduction in sun exposure.