tbuckley/cabot-search huggingface dataset:
Comparative Tumor Imaging and PDT Efficacy of HPPH Conjugated in the Mono- and Di-Forms to Various Polymethine Cyanine Dyes: Part - 2
Authors: Nadine S. James, Tymish Y. Ohulchanskyy, Yihui Chen, Penny Joshi, Xiang Zheng, Lalit N. Goswami, Ravindra K. Pandey
Journal: Theranostics (2013)

Previous reports from our laboratory have shown that a bifunctional agent obtained by conjugating a photosensitizer (HPPH) to a cyanine dye (CD) can be used for fluorescence image-guided treatment of tumor by photodynamic therapy (PDT).However, the resulting HPPH-CD conjugate showed a significant difference between the tumor-imaging and therapeutic doses.It was demonstrated that the singlet oxygen ( 1 O 2 * , a key cytotoxic agent in PDT) produced by the conjugate upon excitation of the HPPH moiety was partially quenched by the CD-moiety; this resulted in a reduced PDT response when compared to HPPH-PDT under similar treatment parameters.To improve the therapeutic potential of the conjugate, we synthesized a series of dual functional agents in which one or two HPPH moieties were separately conjugated to three different dyes (Cypate, modified IR820 or modified IR783).The newly synthesized conjugates were compared with our lead compound HPPH-CD in terms of photophysical properties, in vitro and in vivo PDT efficacy, tumor uptake and imaging potential.Among the analogs investigated, the conjugate, in which two HPPH moieties were linked to the modified IR820 produced enhanced tumor uptake and tumor contrast in both Colon 26 (a murine Colon carcinoma) and U87 (a human glioblastoma) cell lines.The long-term PDT efficacy (cure) of this conjugate in BALB/c mice, bearing Colon 26 tumors was also enhanced; however, its efficacy in Nude mice bearing U87 tumors was slightly reduced.It was also found that in all the conjugates the singlet oxygen generation and, consequently, PDT efficacy were compromised by a competing pathway, whereby an electronic excitation of HPPH, the energy donor, is deactivated through an electronic excitation energy transfer (Forster Resonance Energy Transfer, FRET) to the CD fluorophore, the energy acceptor, resulting in overall reduction of the singlet oxygen production.Conjugates with increased FRET showed reduced singlet oxygen production and PDT efficacy.Among the conjugates investigated, the bifunctional agent in which two HPPH moieties were linked to the benzoindole-based cyanine dye 11 showed superiority over the lead candidate 9 (mono HPPH-cyanine dye).
Extensive analysis of D7S486 in primary gastric cancer supports TESTIN as a candidate tumor suppressor gene
Authors: Haiqing Ma, Desheng Weng, Yibing Chen, Wei Huang, Ke Pan, Hui Wang, Jiancong Sun, Qijing Wang, Zhiwei Zhou, Huiyun Wang, Jianchuan Xia
Journal: Molecular Cancer (2010)

Abstract Background High frequency of loss of heterozygosity (LOH) was found at D7S486 in primary gastric cancer (GC). And we found a high frequency of LOH region on 7q31 in primary GC from China, and identified D7S486 to be the most frequent LOH locus. This study was aimed to determine what genes were affected by the LOH and served as tumor suppressor genes (TSGs) in this region. Here, a high-throughput single nucleotide polymorphisms (SNPs) microarray fabricated in-house was used to analyze the LOH status around D7S486 on 7q31 in 75 patients with primary GC. Western blot, immunohistochemistry, and RT-PCR were used to assess the protein and mRNA expression of TESTIN (TES) in 50 and 140 primary GC samples, respectively. MTS assay was used to investigate the effect of TES overexpression on the proliferation of GC cell lines. Mutation and methylation analysis were performed to explore possible mechanisms of TES inactivation in GC. Results LOH analysis discovered five candidate genes ( ST7 , FOXP2 , MDFIC , TES and CAV1 ) whose frequencies of LOH were higher than 30%. However, only TES showed the potential to be a TSG associated with GC. Among 140 pairs of GC samples, decreased TES mRNA level was found in 96 (68.6%) tumor tissues when compared with matched non-tumor tissues ( p &lt; 0.001). Also, reduced TES protein level was detected in 36 (72.0%) of all 50 tumor tissues by Western blot ( p = 0.001). In addition, immunohistochemical staining result was in agreement with that of RT-PCR and Western blot. Down regulation of TES was shown to be correlated with tumor differentiation ( p = 0.035) and prognosis ( p = 0.035, log-rank test). Its overexpression inhibited the growth of three GC cell lines. Hypermethylation of TES promoter was a frequent event in primary GC and GC cell lines. However, no specific gene mutation was observed in the coding region of the TES gene. Conclusions Collectively, all results support the role of TES as a TSG in gastric carcinogenesis and that TES is inactivated primarily by LOH and CpG island methylation.
Hyperbaric oxygen for children with cerebral palsy: a randomised multicentre trial
Authors: Jean-Paul Collet, Michel Vanasse, Pierre Marois, Maxime Amar, Joanne Goldberg, Jean Lambert, Maryse Lassonde, Paule Hardy, Josée Fortin, Stéphane D Tremblay, David Montgomery, Jacques Lacroix, Ann Robinson, Annette Majnemer
Journal: The Lancet (2001)
Platelet/Endothelial Biomarkers in Depressed Patients Treated With the Selective Serotonin Reuptake Inhibitor Sertraline After Acute Coronary Events
Authors: Victor L. Serebruany, Alexander H. Glassman, Alex I. Malinin, Charles B. Nemeroff, Dominique L. Musselman, Louis T. van Zyl, Mitchell S. Finkel, K. Ranga R. Krishnan, Michael Gaffney, Wilma Harrison, Robert M. Califf, Christopher M. O’Connor
Journal: Circulation (2003)

Depression after acute coronary syndromes (ACSs) has been identified as an independent risk factor for subsequent cardiac death. Enhanced platelet activation has been hypothesized to represent 1 of the mechanisms underlying this association. Selective serotonin reuptake inhibitors (SSRIs) are known to inhibit platelet activity. Whether treatment of depressed post-ACS patients with SSRIs alters platelet function was not known. Accordingly, we serially assessed the release of established platelet/endothelial biomarkers in patients treated with sertraline vs placebo in the Sertraline AntiDepressant Heart Attack Randomized Trial (SADHART).Plasma samples (baseline, week 6, and week 16) were collected from patients randomized to sertraline (n=28) or placebo (n=36). Anticoagulants, aspirin, and ADP-receptor inhibitors were permitted in this study. Platelet factor 4, beta-thromboglobulin (betaTG), platelet/endothelial cell adhesion molecule-1, P-selectin, thromboxane B2, 6-ketoprostaglandin F1a, vascular cell adhesion molecule-1, and E-selectin were measured by ELISA. Treatment with sertraline was associated with substantially less release of platelet/endothelial biomarkers than was treatment with placebo. These differences attained statistical significance for betaTG (P=0.03) at weeks 6 and 16 and for P-selectin (P=0.04) at week 16. Repeated-measures ANOVA revealed a significant advantage for sertraline vs placebo for diminishing E-selectin and betaTG concentrations across the entire treatment period.Treatment with sertraline in depressed post-ACS patients is associated with reductions in platelet/endothelial activation despite coadministration of widespread antiplatelet regimens including aspirin and clopidogrel. The antiplatelet and endothelium-protective properties of SSRIs might represent an attractive additional advantage in patients with depression and comorbid coronary artery and/or cerebrovascular disease.
Use of Audio Computer-assisted Self-Interviews to Assess Tuberculosis-related Risk Behaviors
Authors: ELISE D. RILEY, RICHARD E. CHAISSON, THEODORE J. ROBNETT, JOHN VERTEFEUILLE, STEFFANIE A. STRATHDEE, DAVID VLAHOV
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The objective of this study was to compare self-reported tuberculosis and human immunodeficiency virus (HIV) risk factors obtained from computer-assisted questionnaires and interviewer-assisted questionnaires among participants of a needle exchange program. Between June 1998 and May 1999, needle exchange program participants requesting tuberculosis screening underwent interviews regarding demographics and risk factors for tuberculosis and HIV infection. The first 190 participants underwent traditional interviewer-assisted questionnaires, whereas the remaining 92 underwent computer-assisted questionnaires. Data were analyzed by interview technique using odds ratios (OR) and multiple logistic regression. Among 282 participants, demographic characteristics, health status, HIV serostatus, visits to homeless shelters, alcohol intake, and cigarette smoking were all similar by interview technique. However, respondents receiving computer-assisted questionnaires were more likely than those receiving interviewer-assisted questionnaires to report smoking marijuana (OR = 5.56), crack (OR = 1.88), and heroin (OR = 2.60); as well as sharing cocaine smoking equipment (OR = 4.49), sharing heroin smoking equipment (OR = 2.85), “shotgunning” (OR = 4.48), and visiting crack houses (OR = 4.39). In the final multivariate model, respondents receiving computer-assisted questionnaires were more likely to report “shotgunning” and visiting a crack house relative to respondents receiving interviewer-assisted questionnaires. In conclusion, increased odds of high-risk behaviors for tuberculosis and HIV infection among computer-assisted questionnaire respondents support the use of computer-assisted questionnaires to ascertain risk behavior data for both tuberculosis and HIV.Keywords: tuberculosis; HIV; self-report; drug use; computer-assisted
Allergyprotective effects of Staphylococcus scuiri in a house dust mite (HDM) model of allergic airway inflammation
Authors: Stefanie Hagner, Min Zhao, Hani Harb, Harald Renz, Petra Pfefferle, Holger Garn
Journal: European Respiratory Journal (2012)

Background: Recently, epidemiological studies revealed a specific association between Staphylococcus scuiri exposure and reduced asthma prevalences.  Aim: To investigate the influence and role of S. scuiri, a Gram-positive bacterium, on allergen-induced sensitization and airway inflammation in a murine model with a mixed phenotype (with eosinophil and neutrophil inflammation) using a clinically relevant allergen (HDM model).  Methods: Mice were treated intranasally with S. scuiri three times a week before and during repeated intranasal exposures to HDM extract. Lung function, recruitment of inflammatory cells as well as production of related cytokines and chemokines were measured.  Results: The application of S. scuiri strongly inhibited the generation of HDM extract-induced airway inflammation. Analyses of bronchoalveolar lavages showed a reduction of both, eosinophil and neutrophil numbers, in comparison to control-animals. The reduction of eosinophils correlated with a reduction of IL-5, and of goblet cell hyperplasia. The mRNA expression of eotaxin and KC, the key chemokines in the induction of eosinophils and neutrophils into allergic tissue, was markedly reduced.  Conclusions: Administration of S. scuiri to mice challenged with HDM extracts protects them from the development of airway inflammation and associated pulmonary pathology.
Guidelines for mineral fibre analyses in biological samples: report of the ERS Working Group. European Respiratory Society
Authors: P De Vuyst, A Karjalainen, P Dumortier, JC Pairon, E Monso, P Brochard, H Teschler, A Tossavainen, A Gibbs
Journal: European Respiratory Journal (1998)

Microscopic techniques for analysing asbestos fibres in lung tissue and bronchoalveolar lavage have provided major information in the understanding of asbestos-related diseases. These analyses are increasingly applied for clinical work and medicolegal problems. Differences in sampling, preparation and counting techniques, definitions of reference populations and expression of results have caused major difficulties in comparing results from different laboratories. Therefore it appeared necessary to set a goal to harmonize these analyses between the European laboratories active in this field. This article summarizes the work of a European Respiratory Society working group with participation from nine European laboratories. The five main issues touched upon are: 1) definitions of control populations and reference levels; 2) sampling, preparation and analytical techniques; 3) asbestos fibres in lung tissues in different pathologies; 4) asbestos bodies in lung tissue, bronchoalveolar lavage and sputum; and 5) basis for the interpretation of fibres and asbestos bodies in biological samples. These guidelines indicate the crucial importance of several factors for the interpretation of the results; namely, adequate sampling, comparable analytical procedures and expression of the results, the use of well-defined reference populations, and a comprehensive understanding of the factors affecting the fibre retention and the dose-responses associated with the different asbestos-related diseases.
Acute lymphoblastic leukemia with the phenotype of a putative B‐cell/T‐cell bipotential precursor
Authors: Lee Gong Lau, Lip Kun Tan, Evelyn S.C. Koay, Melvin H.L. Ee, Suat Hoon Tan, Te Chih Liu
Journal: American Journal of Hematology (2004)

Biphenotypic acute leukemias (BALs) are uncommon. Most are of myeloid-B-cell or myeloid-T-cell lineage. We report herein a 70-year-old man with an unusual acute leukemia where the blasts expressed both B- and T-lymphoid markers. He presented to us with an enlarging cutaneous tumor. The presenting peripheral blood and bone marrow aspirate showed 40% and 90% blasts, respectively, which were negative for the usual cytochemical stains. The flow cytometric analysis revealed that the blasts were positive for CD19, CD20, CD22, cytoplasmic (Cyt) CD79a, CD10, Cyt CD3, CD5, CD7, CD4, HLA-DR, TdT, and were negative for myeloid markers. According to the scoring system from the European Group for the Immunological Characterization of Acute Leukaemias (EGIL), this case was an unequivocal B-cell/T-cell BAL. Conventional cytogenetic analysis revealed 46XY [t(4;11)(q31;q13), add(8)(q24), der(9)del(9)(p21)del(9)(q32q34), -13, +mar] in all 25 metaphases analyzed. Fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) for 11q23 rearrangements as well as t(9;22) were negative. PCR for both TCR-gamma and IgH gene analyses revealed polyclonal rearrangements. We postulate that this case of BAL might have arisen from the putative common lymphoid progenitor cell.
Intestinal microbiota in functional bowel disorders: a Rome foundation report
Authors: Magnus Simrén, Giovanni Barbara, Harry J Flint, Brennan M R Spiegel, Robin C Spiller, Stephen Vanner, Elena F Verdu, Peter J Whorwell, Erwin G Zoetendal
Journal: Gut (2012)

It is increasingly perceived that gut host–microbial interactions are important elements in the pathogenesis of functional gastrointestinal disorders (FGID). The most convincing evidence to date is the finding that functional dyspepsia and irritable bowel syndrome (IBS) may develop in predisposed individuals following a bout of infectious gastroenteritis. There has been a great deal of interest in the potential clinical and therapeutic implications of small intestinal bacterial overgrowth in IBS. However, this theory has generated much debate because the evidence is largely based on breath tests which have not been validated. The introduction of culture-independent molecular techniques provides a major advancement in our understanding of the microbial community in FGID. Results from 16S rRNA-based microbiota profiling approaches demonstrate both quantitative and qualitative changes of mucosal and faecal gut microbiota, particularly in IBS. Investigators are also starting to measure host–microbial interactions in IBS. The current working hypothesis is that abnormal microbiota activate mucosal innate immune responses which increase epithelial permeability, activate nociceptive sensory pathways and dysregulate the enteric nervous system. While we await important insights in this field, the microbiota is already a therapeutic target. Existing controlled trials of dietary manipulation, prebiotics, probiotics, synbiotics and non-absorbable antibiotics are promising, although most are limited by suboptimal design and small sample size. In this article, the authors provide a critical review of current hypotheses regarding the pathogenetic involvement of microbiota in FGID and evaluate the results of microbiota-directed interventions. The authors also provide clinical guidance on modulation of gut microbiota in IBS.
How developmental science contributes to theories of future thinking
Authors: Cristina M. Atance, Andrew N. Meltzoff
Journal: Behavioral and Brain Sciences (2007)

Abstract Acting in the present in anticipation of the future is argued to be a behavioral correlate of mental time travel (MTT). Yet, it is important to consider how other future-directed behaviors – including planning, delay of gratification, and acts of prospective memory – figure into a theory of MTT and future thinking more broadly. Developmental science can help in this formulation.
Reactive Oxygen Species (Ros-Induced) Ros Release
Authors: Dmitry B. Zorov, Charles R. Filburn, Lars-Oliver Klotz, Jay L. Zweier, Steven J. Sollott
Journal: The Journal of Experimental Medicine (2000)

We sought to understand the relationship between reactive oxygen species (ROS) and the mitochondrial permeability transition (MPT) in cardiac myocytes based on the observation of increased ROS production at sites of spontaneously deenergized mitochondria. We devised a new model enabling incremental ROS accumulation in individual mitochondria in isolated cardiac myocytes via photoactivation of tetramethylrhodamine derivatives, which also served to report the mitochondrial transmembrane potential, ΔΨ. This ROS accumulation reproducibly triggered abrupt (and sometimes reversible) mitochondrial depolarization. This phenomenon was ascribed to MPT induction because (a) bongkrekic acid prevented it and (b) mitochondria became permeable for calcein (∼620 daltons) concurrently with depolarization. These photodynamically produced “triggering” ROS caused the MPT induction, as the ROS scavenger Trolox prevented it. The time required for triggering ROS to induce the MPT was dependent on intrinsic cellular ROS-scavenging redox mechanisms, particularly glutathione. MPT induction caused by triggering ROS coincided with a burst of mitochondrial ROS generation, as measured by dichlorofluorescein fluorescence, which we have termed mitochondrial “ROS-induced ROS release” (RIRR). This MPT induction/RIRR phenomenon in cardiac myocytes often occurred synchronously and reversibly among long chains of adjacent mitochondria demonstrating apparent cooperativity. The observed link between MPT and RIRR could be a fundamental phenomenon in mitochondrial and cell biology.
Safety and efficacy of interferon-ribavirin combination therapy in HCV-HIV coinfected subjects: an early report
Authors: H Zylberberg
Journal: Gut (2000)

More severe liver disease together with a poor response rate to alpha interferon argue for the use of more potent anti-hepatitis C virus (HCV) therapies in human immunodeficiency virus (HIV)-HCV coinfected patients, but the efficacy and safety of interferon-ribavirin combination therapy in HIV infected subjects are unknown.To retrospectively evaluate the efficacy and safety of anti-HCV combination therapy in 21 HCV-HIV coinfected patients receiving antiretroviral therapy, and to access the clinical relevance of in vitro inhibition of phosphorylation by ribavirin of potent inhibitors of HIV-that is, zidovudine, stavudine, and zalcitabine.Twenty one patients were treated with combined antiretroviral therapy including zidovudine (n=8) or stavudine (n=13) (in association with protease inhibitors in 12). All received ribavirin (1000 or 1200 mg/day) and alpha interferon (3 MU three times/week) for chronic hepatitis C infection. All patients had not responded (n=20) or relapsed (n=1) after a previous six month course of alpha interferon therapy.HIV viral load (Monitor test) and CD4 cells count were measured at the beginning and every three months during and after ribavirin plus alpha interferon therapy over a mean period of 11 (1) months. Clinical and biological adverse effects were recorded.There was no significant variation in HIV viral load or CD4 cell counts after three or six months of ribavirin therapy compared with baseline values. Of the 21 subjects, three (14%) had an increase in HIV viral load of more than 0.5 log leading to discontinuation of ribavirin in one. Eleven of 21 (52.4%) had initial negative HCV viraemia at three (n=10) or six (n=1) months but only six were polymerase chain reaction negative at the end of therapy, leading to rates for primary response and breakthrough of 23.8% and 28.5%, respectively. Six months after completion of therapy, three patients relapsed (14. 3%) and three (14.3%) had sustained virological response. Median haemoglobin concentration decreased significantly after three and six months of ribavirin therapy (p= 0.0002 and p=0.0003, respectively) leading to withdrawal of therapy in one patient.These preliminary results show that: (1) despite in vitro interactions between ribavirin, zidovudine, and stavudine, significant variation in HIV replication does not usually occur in HCV-HIV coinfected patients receiving ribavirin and different antiretroviral regimens, including zidovudine and stavudine; (2) alpha interferon and ribavirin combination therapy induced primary and sustained virological responses in 28.5% and 14.3% of treated subjects (who were previous non-responders to interferon therapy), respectively; (3) anaemia is a frequent adverse event. Such results should be confirmed in larger prospective trials.
Informal Caregiver Burden among Survivors of Prolonged Mechanical Ventilation
Authors: David C. Van Pelt, Eric B. Milbrandt, Li Qin, Lisa A. Weissfeld, Armando J. Rotondi, Richard Schulz, Lakshmipathi Chelluri, Derek C. Angus, Michael R. Pinsky
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Although caregiver burden is well described in chronic illness, few studies have examined burden among caregivers of survivors of critical illness. In existing studies, it is unclear whether the observed burden is a consequence of critical illness or of preexisting patient illness.To describe 1-yr longitudinal outcomes for caregivers of patients who survived critical illness, and to compare depression risk between caregivers of patients with and without pre-intensive care unit (ICU) functional dependency.Prospective, parallel, cohort study of survivors of prolonged (greater than 48 h) mechanical ventilation and their informal caregivers. Caregivers were divided into two cohorts on the basis of whether patients were functionally independent (n = 99, 59%), or dependent (n = 70, 41%) before admission. Functional dependency was defined as dependency in one or more activities of daily living or in three or more instrumental activities of daily living. Patient and caregiver outcomes were measured 2, 6, and 12 mo after mechanical ventilation initiation.We studied three caregiver outcomes: depression risk, lifestyle disruption, and employment reduction. Most patients were male (59.8%), with a mean (SD) age of 56.6 (19.0) yr. Caregivers were mostly female (75.7%), with a mean (SD) age of 54.6 (14.7) yr. Prevalence of caregiver depression risk was high at all time points (33.9, 30.8, and 22.8%; p = 0.83) and did not vary by patient pre-ICU functional status. Lifestyle disruption and employment reduction were also common and persistent.Depression symptoms, lifestyle disruption, and employment reduction were common among informal caregivers of critical illness survivors. Depression risk was high regardless of patient pre-ICU functional status.