tbuckley/cabot-search huggingface dataset:
Cutaneous immunological activation elicited by a low-fluence pulsed dye laser
Authors: T. Omi, S. Kawana, S. Sato, S. Takezaki, M. Honda, T. Igarashi, R.W. Hankins, P. Bjerring, K. Thestrup-Pedersen
Journal: British Journal of Dermatology (2005)

Three years ago, the nonablative wrinkle reduction laser (a 585-nm laser, Chromogenex V3; Chromogenex Light Technologies, Llanelli, U.K.) was developed, and there have already been several reports about its clinical effectiveness. The Chromogenex V3 laser has also been reported to be effective in treating acne and atopic dermatitis. These results suggest that the Chromogenex V3 laser has some immunological role. In this study, we investigated immunological changes elicited by laser irradiation at the ultrastructural level and by analysis of interleukin (IL)-2 and IL-4 mRNA in skin homing T lymphocytes.Eight healthy adult volunteers (mean age 56.3 years, range 25-66 years) were recruited for this study. Ultrastructural analysis was done 3 h after the laser irradiation, as well as 1 day, 3 days, 1 week, 2 weeks, 4 weeks and 5 weeks later. IL-2 and IL-4 mRNAs in skin homing T cells cultured for 6 weeks were semiquantitatively measured using reverse transcriptase-polymerase chain reaction.Ultrastructural observations revealed that at 3 h after laser therapy, neutrophils, monocytes and mast cells could already be seen in the extravascular dermis. These dermal acute inflammatory changes were observed also at 1 week after laser treatment. Two weeks after laser treatment, the capillaries showed an almost normal structure. Four weeks after laser treatment, many lymphocytes and fibroblasts were observed. The numbers of these lymphocytes increased further at 5 weeks after the laser treatment. One week after the laser irradiation, all subjects were positive for IL-2 mRNA and for IL-4 mRNA. The level of IL-4 mRNA was larger compared with that of IL-2 mRNA in all subjects.The Chromogenex V3 is a 585-nm visible light laser, and it may affect the skin not only by selective photothermolysis but also by direct cutaneous immunological activation.
Bacterial resistance induction with prophylactic antibiotics in COPD
Authors: Simon Brill, Martin Law, James Allinson, Ethaar El-Emir, Timothy McHugh, Gavin Donaldson, Dan Jackson, Michael Sweeting, Wisia Wedzicha
Journal: European Respiratory Journal (2014)

RATIONALE  Prophylactic antibiotic therapy prevents COPD exacerbations but concerns remain about induction of bacterial resistance.  METHOD  During a 13-week single-blind randomised placebo-controlled trial, patients with COPD and FEV1l80% received moxifloxacin 400mg/day on 5 days every 4 weeks, doxycycline 100mg/day, azithromycin 250mg 3x/week or placebo daily. Mean inhibitory concentrations(MIC) were obtained for bacterial isolates cultured from sputum pre- and post-treatment. Analysis was with linear mixed effects models and logistic regression.  RESULTS  237 isolates were detected and tested in 69 patients and dichotomised (resistant/not) where possible. Compared to placebo, post-treatment MIC was 4.79 times higher in patients who received moxifloxacin (95%CI 1.43,16.03, p=0.01), 6.23 for azithromycin (1.66,23.35, p=0.01) and 3.74 for doxycycline (1.46,9.58, p=0.01). Isolates in the doxycycline group were more likely to be resistant post-treatment than placebo (odds ratio 5.77 [1.41,23.66], p=0.01); odds ratios for moxifloxacin and azithromycin were g2 but non-significant. There was no difference in number of isolates cultured between groups post-treatment. Figure 1 shows pre/post-treatment MICs.  CONCLUSION  Each antibiotic was associated with a significant increase in the MIC of cultured isolates; odds of an isolate being clinically resistant also increased with doxycycline. The potential consequences of this observation require further investigation.
Low-dose dobutamine gated SPECT to predict improvement in left ventricular ejection fraction in patients with ischemic cardiomyopathy treated with beta-blocker therapy
Authors: Eric P. Viergever, Ernst E. van der Wall, Geesje Abels, Guido Germano, Daniel S. Berman, Jeroen J. Bax
Journal: Journal of the American College of Cardiology (2003)
Boceprevir for chronic HCV genotype 1 infection in patients with prior treatment failure to peginterferon/ribavirin, including prior null response
Authors: John M. Vierling, Mitchell Davis, Steven Flamm, Stuart C. Gordon, Eric Lawitz, Eric M. Yoshida, Joseph Galati, Velimir Luketic, Jonathan McCone, Ira Jacobson, Patrick Marcellin, Andrew J. Muir, Fred Poordad, Lisa D. Pedicone, Janice Albrecht, Clifford Brass, Anita Y.M. Howe, Lynn Y. Colvard, Frans A. Helmond, Weiping Deng, Michelle Treitel, Janice Wahl, Jean-Pierre Bronowicki
Journal: Journal of Hepatology (2013)
Autism Occurrence by MMR Vaccine Status Among US Children With Older Siblings With and Without Autism
Authors: Anjali Jain, Jaclyn Marshall, Ami Buikema, Tim Bancroft, Jonathan P. Kelly, Craig J. Newschaffer
Journal: JAMA (2015)

<h3>Importance</h3> Despite research showing no link between the measles-mumps-rubella (MMR) vaccine and autism spectrum disorders (ASD), beliefs that the vaccine causes autism persist, leading to lower vaccination levels. Parents who already have a child with ASD may be especially wary of vaccinations. <h3>Objective</h3> To report ASD occurrence by MMR vaccine status in a large sample of US children who have older siblings with and without ASD. <h3>Design, Setting, and Participants</h3> A retrospective cohort study using an administrative claims database associated with a large commercial health plan. Participants included children continuously enrolled in the health plan from birth to at least 5 years of age during 2001-2012 who also had an older sibling continuously enrolled for at least 6 months between 1997 and 2012. <h3>Exposures</h3> MMR vaccine receipt (0, 1, 2 doses) after 1 year of age. <h3>Main Outcomes and Measures</h3> ASD status defined as 2 claims with a diagnosis code in any position for autistic disorder or other specified pervasive developmental disorder (PDD) including Asperger syndrome, or unspecified PDD (<i>International Classification of Diseases, Ninth Revision, Clinical Modification</i>299.0x, 299.8x, 299.9x). <h3>Results</h3> Of 95 727 children with older siblings, 994 (1.04%) were diagnosed with ASD and 1929 (2.02%) had an older sibling with ASD. Of those with older siblings with ASD, 134 (6.9%) had ASD, vs 860 (0.9%) children with unaffected siblings (<i>P</i> &lt; .001). MMR vaccination rates (≥1 dose) were 84% (n = 78 549) at age 2 years and 92% (n = 86 063) at age 5 years for children with unaffected older siblings, vs 73% (n = 1409) at age 2 years and 86% (n = 1660) at age 5 years for children with affected siblings. MMR vaccine receipt was not associated with an increased risk of ASD at any age. For children with older siblings with ASD, at age 2, the adjusted relative risk (RR) of ASD for 1 dose of MMR vaccine vs no vaccine was 0.76 (95% CI, 0.48-1.22;<i>P</i> = .25), and at age 5, the RR of ASD for 2 doses compared with no vaccine was 0.56 (95% CI, 0.30-1.04;<i>P</i> = .07). For children whose older siblings did not have ASD, at age 2, the adjusted RR of ASD for 1 dose was 0.91 (95% CI, 0.68-1.20;<i>P</i> = .50) and at age 5, the RR of ASD for 2 doses was 1.09 (95% CI, 0.76-1.54;<i>P</i> = .65). <h3>Conclusions and Relevance</h3> In this large sample of privately insured children with older siblings, receipt of the MMR vaccine was not associated with increased risk of ASD, regardless of whether older siblings had ASD. These findings indicate no harmful association between MMR vaccine receipt and ASD even among children already at higher risk for ASD.
Fibre and enteral nutrition.
Authors: D B Silk
Journal: Gut (1989)

The recent launch of a number of fibre enriched polymeric diet in the United States and Europe has stimulated considerable interest in the topic of fibre and enteral nutrition, and several commercial concerns appear to be under considerable pressures from their consumers to produce similar products. As a means of identifying areas of potential application of fibre to enteral nutrition some of the recent knowledge gained about the physical properties of dietary fibre and the processes involved in the intestinal assimilation of fibre has been reviewed. Two areas of interest are identifiable. The first relates to the bulking properties of fibre and the application of this to the regulation of bowel function in enterally fed patients. It is clear from the clinical studies that have been reviewed that there remains a paucity of controlled data, and a great deal more research is needed before widespread use of fibre supplemented diets can be supported. Perhaps of greater interest academically is the potentially beneficial effects that appear to be exerted by the VFA9s, liberated as a consequence of colonic bacterial fermentation of fibre, on morphology and function of ileal and colonic mucosa. Although there are a number of potential applications of fibre supplemented enteral diets in this area, more research is required before any firm recommendations can be made about recommending their use. The one exception concerns patients with the nutritionally inadequate short bowel syndrome. There does seem to be sufficient experimental evidence to suggest that clinical studies should be commenced using a pectin supplemented predigested 9elemental9 diet in these patients. Overall therefore, one is forced to conclude that the increasing interest and use of fibre supplemented enteral diets is being driven more by market than scientific forces. Nevertheless, the promotion of these diets has already provided a powerful stimulus to the scientific community, and it remains entirely possible that many of the potential applications of these diets will be realised in the near future.
Mutations in the Human <i>λ5/14.1</i> Gene Result in B Cell Deficiency and Agammaglobulinemia
Authors: Yoshiyuki Minegishi, Elaine Coustan-Smith, Yui-Hsi Wang, Max D. Cooper, Dario Campana, Mary Ellen Conley
Journal: The Journal of Experimental Medicine (1998)

B cell precursors transiently express a pre–B cell receptor complex consisting of a rearranged mu heavy chain, a surrogate light chain composed of λ5/14.1 and VpreB, and the immunoglobulin (Ig)-associated signal transducing chains, Igα and Igβ. Mutations in the mu heavy chain are associated with a complete failure of B cell development in both humans and mice, whereas mutations in murine λ5 result in a leaky phenotype with detectable humoral responses. In evaluating patients with agammaglobulinemia and markedly reduced numbers of B cells, we identified a boy with mutations on both alleles of the gene for λ5/14.1. The maternal allele carried a premature stop codon in the first exon of λ5/14.1 and the paternal allele demonstrated three basepair substitutions in a 33-basepair sequence in exon 3. The three substitutions correspond to the sequence in the λ5/14.1 pseudogene 16.1 and result in an amino acid substitution at an invariant proline. When expressed in COS cells, the allele carrying the pseudogene sequence resulted in defective folding and secretion of mutant λ5/14.1. These findings indicate that expression of the functional λ5/14.1 is critical for B cell development in the human.
Stromal Derived Factor-1–Induced Chemokinesis of Cord Blood CD34+ Cells (Long-Term Culture-Initiating Cells) Through Endothelial Cells Is Mediated by E-Selectin
Authors: Afzal J. Naiyer, Deog-Yeon Jo, Jongcheol Ahn, Robert Mohle, Mario Peichev, George Lam, Roy L. Silverstein, Malcolm A.S. Moore, Shahin Rafii
Journal: Blood (1999)
Quality of life, morbidity, and mortality after low trauma hip fracture in men
Authors: I Pande
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> Osteoporotic hip fractures have been extensively studied in women, but they have been relatively ignored in men. <b>Objective:</b> To study the mortality, morbidity, and impact on health related quality of life of male hip fractures. <b>Methods:</b> 100 consecutive men aged 50 years and over, with incident low trauma hip fracture, admitted to Royal Cornwall Hospital, UK during 1995–97, were studied. 100 controls were recruited from a nearby general practice. Mortality and morbidity, including health status assessed using the SF-36, were evaluated over a 2 year follow up period. <b>Results:</b> Survival after 2 years was 37% in fracture cases compared with 88% in controls (log rank test 62.6, df = 1, p = 0.0001). In the first year 45 patients died but only one control. By 2 years 58 patients but only 8 controls had died. Patients with hip fracture died from various causes, the most common being bronchopneumonia (21 cases), heart failure (9 cases), and ischaemic heart disease (8 cases). Factors associated with increased mortality after hip fracture included older age, residence before fracture in a nursing or residential home, presence of comorbid diseases, and poor functional activity before fracture. Patients with fracture were often disabled with poor quality of life. By 24 months 7 patients could not walk, 12 required residential accommodation, and the mean SF-36 physical summary score was 1.7SD below the normal standards. <b>Conclusions:</b> Low trauma hip fracture in men is associated with a significant increase in mortality and morbidity. Impaired function before fracture is a key determinant of mortality after fracture.
Clinical Pharmacokinetics of High-Dose Leucovorin Calcium After Intravenous and Oral Administration
Authors: R. L. Schilsky, M. J. Ratain
Journal: JNCI Journal of the National Cancer Institute (1990)

The clinical formulation of leucovorin calcium (leucovorin, LV) is a mixture of stereoisomers [(6R,S)-5-formyltetrahydrofolate], which have been shown to differ significantly in plasma clearance and route of elimination after intravenous administration; the (6S) isomer is rapidly converted to 5-CH 3 tetrahydrofolate (5-CH 3 (5-CH 3 THF, and the (6R) isomer is slowly eliminated by renal excretion. The relative importance of (6S) LV and 5-CH 3 THF in expanding reduced folate pools in tumor cells is unknown, but it is known that high concentrations of (6R) LV can support growth of folatedepleted cells and thus have the potential to interfere with the biological activity of the (6S) isomer. To examine the pharmacokinetics of the LV isomers and metabolites, we administered 1,000 mg of LV to five normal subjects as a 2-hour intravenous infusion and in divided oral 100-mg doses given over 24 hours. Plasma and urine samples were analyzed by reverse phase followed by chiral high-performance liquid chromatography. Following intravenous administration, peak plasma concentrations of (6R) LV, (6S) LV, and 5-CH 3 THF were 148 ± 32, 59.1 ± 22, and 17.8 ± 17 μ M , respectively. During oral administration of LV, virtually no (6S) LV appeared in the plasma. Steady-state plasma concentrations of (6R) LV and 5-CH 3 THF were approximately 1.5 ± 0.23 and 2.8 ± 0.41 μM, respectively. Intravenous administration of LV resulted in an area under the curve (AUC) for (6R) LV that was more than four times that of the biologically active (6S) folates, whereas oral administration produced an AUC for (6S) reduced folates [(6S) LV and 5-CH 3 THF] that was approximately twice that of (6R) LV. After administration of high doses of LV intravenously, conversion of (6S) LV to 5-CH 3 THF was saturable, as indicated by the prolonged (6S) LV halflife of 58 minutes and the slow (6S) LV clearance of 119.2 ± 38 mL/min, compared with previously reported data for administration of low doses. This study illustrates that intravenous administration of LV produces equivalent AUCs of (6S) LV and 5-CH 3 THF but a substantially higher AUC for (6R) LV. Oral administration over 24 hours restults in an AUC of 5-CH 3 THF equivalent to that obtained after intravenous dosing in the presence of only small amounts of (6R) LV. The optimal route of LV administration will ultimately be determined by ongoing studies of the cellular pharmacology of LV that will determine if high concentrations of (6R) LV interfere with the biological activity of the (6S) reduced folates. [J Natl Cancer Inst 82:1411–1415, 1990]
Role of phagocytosis in the activation of macrophages
Authors: J Schnyder, M Baggiolini
Journal: The Journal of Experimental Medicine (1978)

Macrophages were obtained by peritoneal lavage from untreated mice or from mice which had received either Brewer's thioglycollate broth or a suspension of streptococcus A cell walls intraperitoneally 4 days before. 3 h after harvesting, adherent cells from untreated mice were allowed to phagocytose zymosan, formaldehyde-treated sheep erythrocytes, or latex beads. Phagocytosis was stopped after 1 h and culture was continued for up to 10 days. Phagocytosis of zymosan or sheep erythrocytes triggered the immediate release of lysosomal glycosidases, stimulated the synthesis of cellular lactate dehydrogenase, and induced the delayed production and secretion of plasminogen activator . No such changes were observed upon phagocytosis of latex. Although all three particles used were phagocytosed, only zymosan and sheep erythrocytes stimulated glucose oxidation via the hexose monophosphate shunt. Similar findings were obtained in macrophages elicited with streptococcus A cell walls after zymosan phagocytosis. Thioglycollate-elicited macrophages, however, which were already secreting lysosomal hydrolases and plasminogen activator, could not be activated further by zymosan. The results of this study show that macrophages become activated after phagocytosis of particles that stimulate the activity of their hexose monophosphate shunt. The triggering event appears to be the burst of shunt activity itself or shunt-related biochemical reactions rather than phagocytic uptake per se or particle-dependent complement activation by the alternative pathway. Once initiated, macrophage activation proceeds independently of the intracellular fate of the ingested material .
Real time, confocal imaging of Ca2+ waves in arterially perfused rat hearts
Authors: A Baader
Journal: Cardiovascular Research (2002)

Objective: The aim of this study was to characterize the spatio-temporal dynamics of slow Ca2+ waves (SCW's) with cellular resolution in the arterially-perfused rat heart. Methods: Wister rat hearts were Langendorff-perfused with Tyrode solution containing bovine-albumine and Dextran. The heart was loaded with the Ca2+ sensitive dye Fluo-3 AM. Intracellular fluorescence changes reflecting changes in [Ca2+]i were recorded from subepicardial tissue layers using a slit hole confocal microscope with an image intensified video camera system at image rates of up to 50/s. Results: SCW's appeared spontaneously during cardiac rest or after trains of electrical stimuli. They were initiated preferentially in the center third of the cell and propagated to the cell borders, suggesting a relation between the cell nucleus and wave initiation. They were suppressed by Ca2+ transients and their probability of occurrence increased with the Ca2+ resting level. Propagation velocity within myocytes (40 to 180 μm/s) decreased with the resting Ca2+ level. Intercellular propagation was mostly confined to two or three cells and occurred bi-directionally. Intercellular unidirectional conduction block and facilitation of SCW's was occasionally observed. On average 10 to 20% of cells showed non-synchronized simultaneous SCW's within a given area in the myocardium. Conclusions: SCW's occurring at increased levels of [Ca2+]i in normoxic or ischemic conditions are mostly confined to two or three cells in the ventricular myocardium. Spatio-temporal summation of changes in membrane potential caused by individual SCW's may underlie the generation of triggered electrical ectopic impulses.
Matrix Metalloproteinase Polymorphisms Are Associated with Bladder Cancer Invasiveness
Authors: A. Karim Kader, Jun Liu, Lina Shao, Colin P. Dinney, Jie Lin, Yunfei Wang, Jian Gu, H. Barton Grossman, Xifeng Wu
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Matrix metalloproteinases (MMP) promote tumor invasion and alter microenvironment. MMP levels are elevated in bladder cancer patients correlating with more advanced stage. We tested whether polymorphisms in MMP genes modify the risk of bladder cancer invasiveness and whether smoke exposure modifies this risk. Experimental Design: Using a case-only study, we examined the association of 11 single-nucleotide polymorphisms and one microsatellite polymorphism in MMP genes MMP1, MMP2, MMP3, MMP8, MMP9, and MMP12 with the risk of invasive bladder cancer in 243 Caucasian patients with muscle invasive compared with 315 Caucasian patients with superficial disease. Results: The MMP9 microsatellite ≥24 CA repeat and MMP12 −82 G alleles were associated with a higher risk of bladder cancer invasiveness [odds ratio (OR), 3.10; 95% confidence interval (95% CI) 1.17-8.23 and OR, 1.50; 95% CI, 1.00-2.28, respectively]. Ever smokers with the MMP9 ≥24 CA repeat allele had a 5.16-fold (95% CI, 1.56-17.1) increased risk of invasiveness compared with wild-type never smokers. Ever smokers with the MMP12 G allele also had an increased risk of bladder cancer invasiveness (OR, 2.32; 95% CI, 1.30-4.12). Conclusions: Our results suggest that genetic changes in MMPs are associated with the development of invasive bladder cancer.
Polζ ablation in B cells impairs the germinal center reaction, class switch recombination, DNA break repair, and genome stability
Authors: Dominik Schenten, Sven Kracker, Gloria Esposito, Sonia Franco, Ulf Klein, Michael Murphy, Frederick W. Alt, Klaus Rajewsky
Journal: The Journal of Experimental Medicine (2009)

Polζ is an error-prone DNA polymerase that is critical for embryonic development and maintenance of genome stability. To analyze its suggested role in somatic hypermutation (SHM) and possible contribution to DNA double-strand break (DSB) repair in class switch recombination (CSR), we ablated Rev3, the catalytic subunit of Polζ, selectively in mature B cells in vivo. The frequency of somatic mutation was reduced in the mutant cells but the pattern of SHM was unaffected. Rev3-deficient B cells also exhibited pronounced chromosomal instability and impaired proliferation capacity. Although the data thus argue against a direct role of Polζ in SHM, Polζ deficiency directly interfered with CSR in that activated Rev3-deficient B cells exhibited a reduced efficiency of CSR and an increased frequency of DNA breaks in the immunoglobulin H locus. Based on our results, we suggest a nonredundant role of Polζ in DNA DSB repair through nonhomologous end joining.