tbuckley/cabot-search huggingface dataset:
Randomized Phase III Trial of Dose-Dense Chemotherapy Supported by Whole-Blood Hematopoietic Progenitors in Better-Prognosis Small-Cell Lung Cancer
Authors: Paul Lorigan, Penella J. Woll, M. E. R. O'Brien, Linda F. Ashcroft, Mark R. Sampson, Nick Thatcher
Journal: JNCI Journal of the National Cancer Institute (2005)

Recent dose-intensity studies of small-cell lung cancer (SCLC) have yielded conflicting results. We carried out a phase III randomized trial in patients with better-prognosis SCLC (i.e., prognostic score of 0-1) to investigate whether doubling the dose density of ifosfamide, carboplatin, and etoposide (ICE) chemotherapy with filgrastim and blood-progenitor-cell support improves survival, compared with standard ICE chemotherapy.We studied 318 patients with pathologically proven SCLC who were randomly assigned to receive six cycles of ICE chemotherapy with a 4-week (standard arm) or 2-week (dose-dense arm) interval between cycles. Patients in the dose-dense arm received filgrastim subcutaneously daily on days 4 through 14 and had autologous blood collected before cycles 2 through 6, which was returned 24 hours after treatment. Toxicities, including hematologic toxicity and incidence of neutropenic sepsis, were monitored. Survival was calculated by the Kaplan-Meier method. All statistical tests were two-sided.The delivered median dose intensity was 99% (interquartile range = 96%-100%) for the standard arm and 182% (interquartile range = 163%-196%) for the dose-dense arm. After a median follow-up of 14 months, overall response to treatment was observed in 118 (80%) of the 148 evaluable patients in the standard arm and in 129 (88%) of the 147 evaluable patients in the dose-dense arm, a statistically non-significant difference. Median overall survival was 13.9 months (95% confidence interval [CI] = 12.9 to 15.8 months) in the standard arm and 14.4 months (95% CI = 12.7 to 16.0) in the dose-dense arm, and the 2-year survival was 22% (95% CI = 16% to 29%) and 19% (95% CI = 14% to 27%), respectively--neither difference being statistically significant. The median treatment free time was 286 days (95% CI = 229 to 343 days) for the standard arm and 367 days (95% CI = 321 to 413 days) for the dose-dense arm (difference = 81 days; P = .109). Statistically significantly more hematologic toxicity was reported in the dose-dense arm than in the standard arm, but the number of cycles complicated by neutropenic sepsis was statistically significantly higher in the standard arm than in the dose-dense arm (15.3% versus 11.6%, respectively; difference = 3.7%, 95% CI = -4.1% to 11.5%; P = .03).Dose-dense ICE chemotherapy for SCLC led to shorter treatment duration and less neutropenic sepsis than did standard ICE but did not improve overall survival.
Intraspecific variation of recombination rate in maize
Authors: Eva Bauer, Matthieu Falque, Hildrun Walter, Cyril Bauland, Christian Camisan, Laura Campo, Nina Meyer, Nicolas Ranc, Renaud Rincent, Wolfgang Schipprack, Thomas Altmann, Pascal Flament, Albrecht E Melchinger, Monica Menz, Jesús Moreno-González, Milena Ouzunova, Pedro Revilla, Alain Charcosset, Olivier C Martin, Chris-Carolin Schön
Journal: Genome biology (2013)

In sexually reproducing organisms, meiotic crossovers ensure the proper segregation of chromosomes and contribute to genetic diversity by shuffling allelic combinations. Such genetic reassortment is exploited in breeding to combine favorable alleles, and in genetic research to identify genetic factors underlying traits of interest via linkage or association-based approaches. Crossover numbers and distributions along chromosomes vary between species, but little is known about their intraspecies variation. Here, we report on the variation of recombination rates between 22 European maize inbred lines that belong to the Dent and Flint gene pools. We genotype 23 doubled-haploid populations derived from crosses between these lines with a 50 k-SNP array and construct high-density genetic maps, showing good correspondence with the maize B73 genome sequence assembly. By aligning each genetic map to the B73 sequence, we obtain the recombination rates along chromosomes specific to each population. We identify significant differences in recombination rates at the genome-wide, chromosome, and intrachromosomal levels between populations, as well as significant variation for genome-wide recombination rates among maize lines. Crossover interference analysis using a two-pathway modeling framework reveals a negative association between recombination rate and interference strength. To our knowledge, the present work provides the most comprehensive study on intraspecific variation of recombination rates and crossover interference strength in eukaryotes. Differences found in recombination rates will allow for selection of high or low recombining lines in crossing programs. Our methodology should pave the way for precise identification of genes controlling recombination rates in maize and other organisms.
Heritability of Ambulatory Heart Rate Variability
Authors: Nina H.M. Kupper, Gonneke Willemsen, Mireille van den Berg, Dolf de Boer, Daniëlle Posthuma, Dorret I. Boomsma, Eco J.C. de Geus
Journal: Circulation (2004)

Reduced heart rate variability (HRV) is a prognostic factor for cardiac disease and cardiac mortality. Understanding the sources of individual differences in HRV may increase its diagnostic use and provide new angles for preventive therapy. To date, the contribution of genetic and environmental factors to the variance in HRV has not been investigated during prolonged periods of ambulatory monitoring in a naturalistic setting.In 772 healthy twins and singleton siblings, ambulatory ECG was recorded during 24 hours. Two time domain measures of HRV were used: the standard deviations of all normal-to-normal intervals across 5-minute segments (SDNN index) and the root mean square of successive differences between adjacent normal RR intervals (RMSSD). Multivariate genetic analyses across 4 periods of day (morning, afternoon, evening, night) yielded significant estimates for genetic contribution to the mean ambulatory SDNN index (ranging from 35% to 47%) and the mean ambulatory RMSSD (ranging from 40% to 48%).Ambulatory HRV measures are highly heritable traits that can be used to support genetic association and linkage studies in their search for genetic variation influencing cardiovascular disease risk.
IL-15 induces CD4+ effector memory T cell production and tissue emigration in nonhuman primates
Authors: L. J. Picker
Journal: Journal of Clinical Investigation (2006)

HIV infection selectively targets CD4+ effector memory T (TEM) cells, resulting in dramatic depletion of CD4+ T cells in mucosal effector sites in early infection. Regeneration of the TEM cell compartment is slow and incomplete, even when viral replication is controlled by antiretroviral therapy (ART). Here, we demonstrate that IL-15 dramatically increases in vivo proliferation of rhesus macaque (RM) CD4+ and CD8+ TEM cells with little effect on the naive or central memory T (TCM) cell subsets, a response pattern that is quite distinct from that of either IL-2 or IL-7. TEM cells produced in response to IL-15 did not accumulate in blood. Rather, 5-bromo-2′-deoxyuridine (BrdU) labeling studies suggest that many of these cells rapidly disperse to extralymphoid effector sites, where they manifest (slow) decay kinetics indistinguishable from that of untreated controls. In RMs with uncontrolled SIV infection and highly activated immune systems, IL-15 did not significantly increase CD4+ TEM cell proliferation, but with virologic control and concomitant reduction in immune activation by ART, IL-15 responsiveness was again observed. These data suggest that therapeutic use of IL-15 in the setting of ART might facilitate specific restoration of the CD4+ T cell compartment that is the primary target of HIV with less risk of exhausting precursor T cell compartments or generating potentially deleterious regulatory subsets.
GENETIC CONTROL OF COMBINING SITES OF INSULIN ANTIBODIES PRODUCED BY GUINEA PIGS
Authors: Edward R. Arquilla, Jack Finn
Journal: The Journal of Experimental Medicine (1965)

1. Genetic factors control the configuration of combining sites of guinea pig insulin antibodies. 2. It is possible that the configuration of the combining sites of guinea pig insulin antibodies is controlled by more than one gene and not by multiple alleles at a given gene locus.
Impact of postmenopausal hormone therapy on cardiovascular events and cancer: pooled data from clinical trials
Authors: E. Hemminki, K. McPherson
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objective:</b> To examine the incidence of cardiovascular diseases and cancer from published clinical trials that studied other outcomes of postmenopausal hormone therapy as some surveys have suggested that it may decrease the incidence of cardiovascular diseases and increase the incidence of hormone dependent cancers. <b>Design:</b> Trials that compared hormone therapy with placebo, no therapy, or vitamins and minerals in comparable groups of postmenopausal women and reported cardiovascular or cancer outcomes were searched from the literature. <b>Subjects:</b> 22 trials with 4124 women were identified. In each group, the numbers of women with cardiovascular and cancer events were summed and divided by the numbers of women originally allocated to the groups. <b>Results:</b> Data on cardiovascular events and cancer were usually given incidentally, either as a reason for dropping out of a study or in a list of adverse effects. The calculated odds ratios for women taking hormones versus those not taking hormones was 1.39 (95% confidence interval 0.48 to 3.95) for cardiovascular events without pulmonary embolus and deep vein thrombosis and 1.64 (0.65 to 4.18) with them. It is unlikely that such results would have occurred if the true odds ratio were 0.7 or less. For cancers, the numbers of reported events were too low for a useful conclusion. <b>Conclusions:</b> The results of these pooled data do not support the notion that postmenopausal hormone therapy prevents cardiovascular events. <h3>Key messages</h3> The results of these pooled data do not support the notion that postmenopausal hormone therapy prevents cardiovascular events These results concern only short term effects of postmenopausal hormone therapy, and long term effects may be different There have been hundreds of trials studying the impact of hormones on various physiological phenomena, laboratory values, osteoporosis, symptoms, or various health problems but few fully report adverse effects. Small trials would be useful in studying unintended effects if they were more systematically reported
Weekly paclitaxel as a single agent or in combination with carboplatin or weekly topotecan in patients with resistant ovarian cancer: the CARTAXHY randomized phase II trial from Groupe d’Investigateurs Nationaux pour l’Etude des Cancers Ovariens (GINECO)
Authors: A. Lortholary, R. Largillier, B. Weber, L. Gladieff, J. Alexandre, X. Durando, B. Slama, J. Dauba, D. Paraiso, E. Pujade-Lauraine
Journal: Annals of Oncology (2011)
Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production
Authors: Matthieu Perreau, Anne-Laure Savoye, Elisa De Crignis, Jean-Marc Corpataux, Rafael Cubas, Elias K. Haddad, Laurence De Leval, Cecilia Graziosi, Giuseppe Pantaleo
Journal: The Journal of Experimental Medicine (2012)

In the present study, we have investigated the distribution of HIV-specific and HIV-infected CD4 T cells within different populations of memory CD4 T cells isolated from lymph nodes of viremic HIV-infected subjects. Four memory CD4 T cell populations were identified on the basis of the expression of CXCR5, PD-1, and Bcl-6: CXCR5−PD-1−Bcl-6−, CXCR5+PD-1−Bcl-6−, CXCR5−PD-1+Bcl-6−, and CXCR5+PD-1+Bcl-6+. On the basis of Bcl-6 expression and functional properties (IL-21 production and B cell help), the CXCR5+PD-1+Bcl-6+ cell population was considered to correspond to the T follicular helper (Tfh) cell population. We show that Tfh and CXCR5−PD-1+ cell populations are enriched in HIV-specific CD4 T cells, and these populations are significantly increased in viremic HIV-infected subjects as compared with healthy subjects. The Tfh cell population contained the highest percentage of CD4 T cells harboring HIV DNA and was the most efficient in supporting productive infection in vitro. Replication competent HIV was also readily isolated from Tfh cells in subjects with nonprogressive infection and low viremia (&amp;lt;1,000 HIV RNA copies). However, only the percentage of Tfh cells correlated with the levels of plasma viremia. These results demonstrate that Tfh cells serve as the major CD4 T cell compartment for HIV infection, replication, and production.
Volumetric capnography as a bedside monitoring of thrombolysis in major pulmonary embolism
Authors: Franck Verschuren, Erkki Heinonen, Didier Clause, Jean Roeseler, Fr�d�ric Thys, Philippe Meert, Eric Marion, Abdulwahed El Gariani, Jacques Col, Marc Reynaert, Giuseppe Liistro
Journal: Intensive Care Medicine (2004)
Comparison of the effects of medium and long chain triglyceride containing liquid meals on gall bladder and small intestinal function in normal man.
Authors: S D Ladas, P E Isaacs, G M Murphy, G E Sladen
Journal: Gut (1984)

We investigated the effects of medium (MCT) and long (LCT) chain triglyceride test meals on gall bladder contraction (using ultrasonography) and small intestinal bile acid concentrations and ileal flow rates (using intubation techniques) in normal individuals. Comparing the effects of ingesting medium chain triglyceride and long chain triglyceride meals, the gall bladder volume was reduced by 23.4 +/- 33.6% and 59.0 +/- 17.1% respectively (mean +/- SD, p less than 0.01, n = 13), the jejunal bile acid concentrations increased significantly only after the ingestion of long chain triglyceride (p less than 0.05, n = 5), while the volume of the postprandial jejunal contents was not significantly different (540 +/- 150, 522 +/- 169 ml, medium chain triglyceride vs long chain triglyceride, p = 0.2, n = 5). The postprandial colonic inflow was 48.5 +/- 12.5 and 123.4 +/- 35.2 ml/h (medium chain triglyceride vs long chain triglyceride, p less than 0.01, n = 5). Thus medium chain triglyceride, compared with long chain triglyceride, produces a smaller input of bile acids into the small intestine and a smaller volume of fluid delivered to the colon. These observations may be relevant to the beneficial effects of medium chain triglyceride substitution for long chain triglyceride in the treatment of diarrhoea in patients with small intestinal disease.
Impaired innate immune alveolar macrophage response and the predilection for COPD exacerbations
Authors: Charles S Berenson, Ragina L Kruzel, Ellana Eberhardt, Ree Dolnick, Hans Minderman, Paul K Wallace, Sanjay Sethi
Journal: Thorax (2014)

<h3>Background</h3> Alveolar macrophages (AM) in COPD have fundamentally impaired responsiveness to Toll-like receptor 2 (TLR2) and TLR4 ligands of non-typeable <i>Haemophilus influenzae</i> (NTHI). However, the contribution of innate immune dysfunction to exacerbations of COPD is unexplored. We hypothesised that impaired innate AM responses in COPD extend beyond NTHI to other pathogens and are linked with COPD exacerbations and severity. <h3>Methods</h3> AMs, obtained by bronchoalveolar lavage from 88 volunteers with stable-to-moderate COPD, were incubated with respiratory pathogens (NTHI, <i>Moraxella catarrhalis</i> (MC), <i>Streptococcus pneumoniae</i> (SP) and TLR ligands lipopolysaccharide, Pam<sub>3</sub>Cys) and elicited IL-8 and TNF-α were measured by microsphere flow cytometry. NF-κB nuclear translocation was measured by colorimetric assay. AM TLR2 and TLR4 expression was determined by immunolabeling and quantitation of mean fluorescent indices. Participants were monitored prospectively for occurrence of COPD exacerbations for 1 year following bronchoscopy. Non--parametric analyses were used to compare exacerbation-prone and non-exacerbation-prone individuals. <h3>Results</h3> 29 subjects had at least one exacerbation in the follow-up period (exacerbation-prone) and 59 remained exacerbation-free (non-exacerbation-prone). AMs of exacerbation-prone COPD donors were more refractory to cytokine induction by NTHI (p=0.02), MC (p=0.045) and SP (p=0.046), and to TLR2 (p=0.07) and TLR4 (p=0.028) ligands, and had diminished NF-κB nuclear activation, compared with non-exacerbation-prone counterparts. AMs of exacerbation-prone subjects were more refractory to TLR2 upregulation by MC and SP (p=0.04 each). <h3>Conclusions</h3> Our results support a paradigm of impaired innate responses of COPD AMs to respiratory pathogens, mediated by impaired TLR responses, underlying a propensity for exacerbations in COPD.
Hurtful Words: Association of Exposure to Peer Verbal Abuse With Elevated Psychiatric Symptom Scores and Corpus Callosum Abnormalities
Authors: Martin H. Teicher, Jacqueline A. Samson, Yi-Shin Sheu, Ann Polcari, Cynthia E. McGreenery
Journal: American Journal of Psychiatry (2010)

Objective: Previous studies have shown that exposure to parental verbal abuse in childhood is associated with higher rates of adult psychopathology and alterations in brain structure. In this study the authors sought to examine the symptomatic and neuroanatomic effects, in young adulthood, of exposure to peer verbal abuse during childhood. Method: A total of 848 young adults (ages 18–25 years) with no history of exposure to domestic violence, sexual abuse, or parental physical abuse rated their childhood exposure to parental and peer verbal abuse and completed a self-report packet that included the Kellner Symptom Questionnaire, the Limbic Symptom Checklist–33, and the Dissociative Experiences Scale. Diffusion tensor images were collected for a subset of 63 young adults with no history of abuse or exposure to parental verbal abuse selected for varying degrees of exposure to peer verbal abuse. Images were analyzed using tract-based spatial statistics. Results: Analysis of covariance revealed dose-dependent effects of peer verbal abuse on anxiety, depression, anger-hostility, dissociation, "limbic irritability," and drug use. Peer and parental verbal abuse were essentially equivalent in effect size on these ratings. Path analysis indicated that peer verbal abuse during the middle school years had the most significant effect on symptom scores. Degree of exposure to peer verbal abuse correlated with increased mean and radial diffusivity and decreased fractional anisotropy in the corpus callosum and the corona radiata. Conclusions: These findings parallel results of previous reports of psychopathology associated with childhood exposure to parental verbal abuse and support the hypothesis that exposure to peer verbal abuse is an aversive stimulus associated with greater symptom ratings and meaningful alterations in brain structure.
Pulmonary artery distensibility in pulmonary arterial hypertension: an MRI pilot study
Authors: C. Jardim, C. E. Rochitte, M. Humbert, G. Rubenfeld, D. Jasinowodolinski, C. R. R. Carvalho, R. Souza
Journal: European Respiratory Journal (2006)

Pulmonary arterial hypertension (PAH) is a disease of the small vessels in which there is a substantial increase in pulmonary vascular resistance leading to right ventricle failure and death. Invasive haemodynamic evaluation is mandatory not only for diagnosis confirmation but also to address prognosis and eligibility for the use of calcium-channel blockers through an acute vasodilator challenge. Noninvasive surrogate response markers to the acute vasodilator test have been sought. In the present study, the relationship between pulmonary artery distensibility, assessed using magnetic resonance imaging (MRI), and response to acute vasodilator tests was investigated. In total, 19 patients diagnosed with idiopathic PAH without any specific treatment were evaluated. Within a 48-h window after pulmonary artery catheterisation, patients underwent cardiac MRI. Cardiac index, calculated after the determination (invasively and noninvasively) of cardiac output, showed excellent correlation, as did right atrial pressure and right ventricle ejection fraction. Pulmonary artery distensibility was significantly higher in responders. A receiver operating characteristic curve analysis has shown that 10% distensibility was able to differentiate responders from nonresponders with 100% sensitivity and 56% specificity. The present findings suggest that magnetic resonance imaging and pulmonary artery distensibility may be useful noninvasive tools for the evaluation of patients with pulmonary hypertension.
Histopathologic Features of Idiopathic Macular Holes and Cysts
Authors: David R. Guyer, W. Richard Green, Serge de Bustros, Stuart L. Fine
Journal: Ophthalmology (1990)

The pathogenesis of idiopathic macular holes and cysts is currently debated. The authors studied the histopathologic features of 41 specimens. Of 22 full-thickness holes, 16 (73%) had epiretinal membranes (ERMs), 15 (68%) had cystoid macular edema (CME), and 3 (17%) were sealed by fibroglial and retinal pigment epithelial hyperplasia. Photoreceptors were variably degenerated, for a mean of 480 microns (range, 200-750 microns) from the hole margins. Of 12 lamellar macular holes, 6 (50%) had an ERM exhibiting tangential traction on the internal limiting membrane. Cystoid macular edema was present in five (71%) of seven macular cysts, and an ERM was noted in only one (14%). The authors' results suggest that ERM tangential traction may play a role in the pathogenesis of lamellar macular holes. Macular holes often have associated ERMs and CME, which may be potentially reversible.
Exercise response in 404 young men with asthma: no evidence for a late asthmatic reaction.
Authors: J Karjalainen
Journal: Thorax (1991)

As the existence of a late reaction in exercise induced asthma is controversial, peak expiratory flow (PEF) was measured for up to 13 hours after a running test in 404 consecutive young male army conscripts undergoing assessment of their asthma. In 294 subjects (73%) the immediate post-exercise fall in PEF was 10% or more; the mean (SD) fall in PEF in this group was 27% (15%). Nine patients with exercise induced asthma had a fall in PEF of 20% or more 4-13 hours after the exercise test. In these possible "late responders," however, the change in PEF 4-13 hours after exercise was similar to the change in PEF on control days before and after the exercise day, and the lowest PEF during this period was similar to the lowest measurements on the control days. These nine subjects showed pre-exercise bronchodilatation. Their pre-exercise PEF, from which the percentage fall in PEF was calculated, was 24% (9%) higher than the mean PEF level on control days. This study supports the view that what appears to be a "late asthmatic reaction" after exercise is an artefact. Spontaneous within day fluctuation in pulmonary function, pre-exercise bronchodilatation, and the fact that airflow obstruction persists after the early postexercise response may give a false impression of an exercise induced late asthmatic response in patients with labile airways.