tbuckley/cabot-search huggingface dataset:
Cytokine Complex–expanded Natural Killer Cells Improve Allogeneic Lung Transplant Function via Depletion of Donor Dendritic Cells
Authors: Wolfgang Jungraithmayr, Laura Codarri, Gregory Bouchaud, Carsten Krieg, Onur Boyman, Gabor Gyülvészi, Burkhard Becher, Walter Weder, Christian Münz
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: Natural killer (NK) cells are innate lymphocytes that target virus-infected and tumor cells. Much less is known about their ability to limit adaptive immune responses.Objectives: Thus, we investigated to what extent NK cells can influence mouse lung allograft rejection.Methods: For this purpose, we employed an orthotopic lung transplantation model in mice.Measurements and Main Results: We demonstrate here that NK cells infiltrate mouse lung allografts before T cells and thereby diminished allograft inflammation, and that NK-cell deficiency enhanced allograft rejection. In contrast, expansion of recipient NK cells through IL-15/IL-15Rα complex treatment resulted in decreased T-cell infiltration and alloreactive T-cell priming as well as improved function of the allogeneic lung transplant. Only perforin-competent, but not perforin-deficient, NK cells were able to transfer these beneficial effects into transplanted NK cell–deficient IL-15Rα−/− mice. These NK cells killed allogeneic dendritic cells (DCs) in vitro and significantly decreased the number of allogeneic DCs in transplanted lungs in vivo. Furthermore, DC-depleted lung allografts presented decreased signs of rejection.Conclusions: These results suggest that NK cells favor allograft acceptance by depleting donor-derived DCs, which otherwise would prime alloreactive T-cell responses. Thus, conditioning regimens that augment NK-cell reactivity should be clinically explored to prepare lung allograft recipients.
The Midregional Fragment of Pro-A–Type Natriuretic Peptide, Blood Pressure, and Mortality in a Prospective Cohort Study of Patients With Type 2 Diabetes (ZODIAC-25)
Authors: Kornelis J.J. van Hateren, Gijs W.D. Landman, Nanne Kleefstra, Klaas H. Groenier, Joachim Struck, Gerjan J. Navis, Stephan J.L. Bakker, Sebastiaan T. Houweling, Klaas van der Meer, Henk J.G. Bilo
Journal: Diabetes Care (2012)

Evidence that midregional fragment of pro-A-type natriuretic peptide (MR-proANP) is a marker of mortality in patients with type 2 diabetes is limited. Therefore, we aimed to investigate the capabilities of MR-proANP in predicting mortality. We also investigated whether MR-proANP influences the relationship between blood pressure and mortality in old age.In 1998, 1,143 primary care patients with type 2 diabetes participated in the ZODIAC study. Because blood was drawn for 867 patients (76%) and confounders were missing for 19 patients, the final study sample comprised 848 patients. After a follow-up time of 10 years, we used Cox proportional hazard models to evaluate the relationship between MR-proANP and (cardiovascular) mortality. Harrell C statistic was used to compare models with and without MR-proANP. The regression analyses were repeated without MR-proANP for patients aged older than 75 years.Median MR-proANP in the total study sample was 75 pmol/L (interquartile range, 48-124 pmol/L). During follow-up, 354 (42%) out of 848 patients had died, of whom 152 (43%) deaths were attributable to cardiovascular factors. MR-proANP was independently associated with all-cause and cardiovascular mortality, irrespective of age. During old age, there was a significant inverse relationship between blood pressure and mortality. This relationship did not change after adjustment for MR-proANP.MR-proANP is independently associated with mortality in patients with type 2 diabetes. MR-proANP did not influence the inverse relationship between blood pressure and mortality in elderly patients.
Randomized Phase III Clinical Trial Designs for Targeted Agents
Authors: Antje Hoering, Mike LeBlanc, John J. Crowley
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Cancer therapies with mechanisms of action which are very different from the more conventional chemotherapies are now being developed. In this article, we investigate the performance of several phase III clinical trial designs, both for testing the overall efficacy of a targeted agent and for testing its efficacy in a subgroup of patients with a tumor marker present. We study different designs and different underlying scenarios assuming continuous markers, and assess the trade-off between the number of patients on the study and the effectiveness of treatment in the subgroup of marker-positive patients. Experimental Design: We investigate binary outcomes and use simulation studies to determine sample size and power for the different designs and the various scenarios. We also simulate marker prevalence and marker misclassification and evaluate their effect on power and sample size. Results: In general, a targeted design which randomizes patients with the appropriate marker status performs the best in all scenarios with an underlying true predictive marker. Randomizing all patients regardless of their marker values performs as well as or better in most cases than a clinical trial that randomizes the patient to a treatment strategy based on marker value versus standard of care. Conclusion: If there is the possibility that the new treatment helps marker-negative patients, or that the cutpoint determining marker status has not been well established and the marker prevalence is large enough, we recommend randomizing all patients regardless of marker values, but using a design such that both the overall and the targeted subgroup hypothesis can be tested.
Intravenous ibandronate reduces the incidence of skeletal complications in patients with breast cancer and bone metastases
Authors: J.-J. Body, I.J. Diel, M.R. Lichinitser, E.D. Kreuser, W. Dornoff, V.A. Gorbunova, M. Budde, B. Bergström
Journal: Annals of Oncology (2003)
Docetaxel With Cyclophosphamide Is Associated With an Overall Survival Benefit Compared With Doxorubicin and Cyclophosphamide: 7-Year Follow-Up of US Oncology Research Trial 9735
Authors: Stephen Jones, Frankie Ann Holmes, Joyce O'Shaughnessy, Joanne L. Blum, Svetislava J. Vukelja, Kristi J. McIntyre, John E. Pippen, James H. Bordelon, Robert L. Kirby, John Sandbach, William J. Hyman, Donald A. Richards, Robert G. Mennel, Kristi A. Boehm, Wally G. Meyer, Lina Asmar, Daniel Mackey, Stefan Riedel, Hyman Muss, Michael A. Savin
Journal: Journal of Clinical Oncology (2009)

Purpose We previously reported that four cycles of docetaxel/cyclophosphamide (TC) produced superior disease-free survival (DFS) compared with four cycles of doxorubicin/cyclophosphamide (AC) in early breast cancer. Older women are under-represented in adjuvant chemotherapy trials. In our trial 16% of patients were ≥ 65 years. We now report 7-year results for DFS and overall survival (OS) as well as the impact of age, hormone receptor status, and HER2 status on outcome and toxicity. Patients and Methods Patients were randomly assigned to receive either four cycles of standard-dose AC (60/600 mg/m 2 ; n = 510), or TC (75/600 mg/m 2 ; n = 506), administered by intravenous infusion every 3 weeks. Results The median age in women younger than 65, was 50 years (range, 27 to 64) and for women ≥ 65 was 69 years (range, 65 to 77). Baseline characteristics in the two age subgroups were generally well matched, except that older women tended to have more lymph node involvement. At a median of 7 years follow-up, the difference in DFS between TC and AC was significant (81% TC v 75% AC; P = .033; hazard ratio [HR], 0.74; 95% CI 0.56 to 0.98) as was OS (87% TC v 82% AC; P = .032; HR, 0.69; 95% CI, 0.50 to 0.97). TC was superior in older patients as well as younger patients. There was no interaction of hormone-receptor status or HER-2 status and treatment. Older women experienced more febrile neutropenia with TC and more anemia with AC. Conclusion With longer follow-up, four cycles of TC was superior to standard AC (DFS and OS) and was a tolerable regimen in both older and younger patients.
Slit2 Activity in the Migration of Guidepost Neurons Shapes Thalamic Projections during Development and Evolution
Authors: Franck Bielle, Paula Marcos-Mondejar, Maryama Keita, Caroline Mailhes, Catherine Verney, Kim Nguyen Ba-Charvet, Marc Tessier-Lavigne, Guillermina Lopez-Bendito, Sonia Garel
Journal: Neuron (2011)
Sequence evolution of the CCR5 chemokine receptor gene in primates
Authors: Y. W. Zhang, O. A. Ryder, Y. P. Zhang
Journal: Molecular Biology and Evolution (1999)

The chemokine receptor CCR5 can serve as a coreceptor for M-tropic HIV-1 infection and both M-tropic and T-tropic SIV infection. We sequenced the entire CCR5 gene from 10 nonhuman primates: Pongo pygmaeus, Hylobates leucogenys, Trachypithecus francoisi, Trachypithecus phayrei, Pygathrix nemaeus, Rhinopithecus roxellanae, Rhinopithecus bieti, Rhinopithecus avunculus, Macaca assamensis, and Macaca arctoides. When compared with CCR5 sequences from humans and other primates, our results demonstrate that: (1) nucleotide and amino acid sequences of CCR5 among primates are highly homologous, with variations slightly concentrated on the amino and carboxyl termini; and (2) site Asp13, which is critical for CD4-independent binding of SIV gp120 to Macaca mulatta CCR5, was also present in all other nonhuman primates tested here, suggesting that those nonhuman primate CCR5s might also bind SIV gp120 without the presence of CD4. The topologies of CCR5 gene trees constructed here conflict with the putative opinion that the snub-nosed langurs compose a monophyletic group, suggesting that the CCR5 gene may not be a good genetic marker for low-level phylogenetic analysis. The evolutionary rate of CCR5 was calculated, and our results suggest a slowdown in primates after they diverged from rodents. The synonymous mutation rate of CCR5 in primates is constant, about 1.1 x 10(-9) synonymous mutations per site per year. Comparisons of Ka and Ks suggest that the CCR5 genes have undergone negative or purifying selection. Ka/Ks ratios from cercopithecines and colobines are significantly different, implying that selective pressures have played different roles in the two lineages.
The Mental Health Maze and the Call for Transformation
Authors: John K. Iglehart
Journal: New England Journal of Medicine (2004)

In an early effort to establish his credentials as a “compassionate conservative” during the 2000 presidential campaign, George W. Bush pledged that if he were elected, he would create a commission to conduct a comprehensive review of the care of people with mental illness — the first such examination to be undertaken in almost 25 years. In April 2002, in fulfillment of his campaign pledge, Bush announced the creation of the President's New Freedom Commission on Mental Health, the goal of which was to “recommend improvements to enable adults with serious mental illness and children with serious emotional disturbances to . . .
Comparison of intravenous edrophonium and oesophageal acid perfusion during oesophageal manometry in patients with non-cardiac chest pain.
Authors: J S De Caestecker, A Pryde, R C Heading
Journal: Gut (1988)

Sixty consecutive patients referred for evaluation of non-cardiac chest pain had oesophageal manometry. Motility was assessed basally, after edrophonium 80 micrograms/kg iv and during oesophageal perfusion with 0.1 N HCl at 6 and 14 ml/min for eight and seven minutes respectively. A positive response, defined as symptom reproduction with or without abnormal motility, was present in 21 patients (35%) after acid perfusion and 12 (20%) after edrophonium. Eleven of the 12 patients responding to edrophonium also responded to acid perfusion, including most of the patients with primary motility disorders. Significantly greater increases in peristaltic duration, but not amplitude, were recorded after edrophonium (p less than 0.01) and acid perfusion (p less than 0.05) in positive responders, compared with non-responders. Results indicate that acid perfusion during oesophageal manometry may be a more useful stress test than edrophonium and that the mechanism of symptom production may be similar.
Muscle strength in youth and cardiovascular risk in young adulthood (the European Youth Heart Study)
Authors: Anders Grøntved, Mathias Ried-Larsen, Niels Christian Møller, Peter Lund Kristensen, Karsten Froberg, Søren Brage, Lars Bo Andersen
Journal: British Journal of Sports Medicine (2013)

Background Whether muscle strength in youth is related to cardiovascular risk later in life independent of cardiorespiratory fitness is unclear. Methods We examined the independent association of isometric muscle strength in youth with cardiovascular risk factors in young adulthood using data from the Danish European Youth Heart Study; a population-based prospective cohort study among boys and girls (n=332) followed for up to 12 years. In youth maximal voluntary contractions during isometric back extension and abdominal flexion were determined using a strain-gauge dynamometer and cardiorespiratory fitness was obtained from a maximal cycle ergometer test. Cardiovascular risk factors were obtained in youth and in young adulthood. Associations were examined using multivariable-adjusted regression models including major confounding factors. Results Each 1 SD difference in isometric muscle strength in youth (0.17 N/kg) was inversely associated with body mass index (BMI; −0.60 kg/m 2 , 95% CI −0.97 to −0.22), triglyceride (−0.09 mmol/l, 95% CI −0.16 to −0.02), diastolic blood pressure (BP) (−1.22 mm Hg, 95% CI −2.15 to −0.29) and a composite cardiovascular risk factor score (−0.61 SD, 95% CI −1.03 to −0.20) in young adulthood in multivariable-adjusted analyses including fitness. Associations to triglyceride, diastolic BP and the cardiovascular risk factor score remained with additional adjustment for waist circumference or BMI. Each 1 SD difference in isometric muscle strength in youth was significantly associated with 0.59 (95% CI 0.40 to 0.87) lower odds of general overweight/obesity in young adulthood (p=0.007) and was marginally associated with incident raised BP, raised triglyceride and low high-density lipoprotein cholesterol. Conclusions This study suggests that greater isometric muscle strength in youth is associated with lower levels of cardiovascular risk factors in young adulthood independent of fitness, adiposity and other confounding factors.
Role of Radiation Therapy in Palliative Care of the Patient With Cancer
Authors: Stephen T. Lutz, Joshua Jones, Edward Chow
Journal: Journal of Clinical Oncology (2014)

Radiotherapy is a successful, time-efficient, well-tolerated, and cost-effective intervention that is crucial for the appropriate delivery of palliative oncology care. The distinction between curative and palliative goals is blurred in many patients with cancer, requiring that treatments be chosen on the basis of factors related to the patient (ie, poor performance status, advanced age, significant weight loss, severe comorbid disease), the cancer (ie, metastatic disease, aggressive histology), or the treatment (ie, poor response to systemic therapy, previous radiotherapy). Goals may include symptom relief at the site of primary tumor or from metastatic lesions. Attention to a patient's discomfort and transportation limitations requires hypofractionated courses, when feasible. Innovative approaches include rapid response palliative care clinics as well as the formation of palliative radiotherapy specialty services in academic centers. Guidelines are providing better definitions of appropriate palliative radiotherapy interventions, and bone metastases fractionation has become the first radiotherapy quality measure accepted by the National Quality Forum. Further advances in the palliative radiation oncology subspecialty will require integration of education and training between the radiotherapy and palliative care specialties.
Psychiatric Morbidity and Impact on Hospital Length of Stay Among Hematologic Cancer Patients Receiving Stem-Cell Transplantation
Authors: Jesús M. Prieto, Jordi Blanch, Jorge Atala, Enric Carreras, Montserrat Rovira, Esteve Cirera, Cristóbal Gastó
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To determine the prevalence of psychiatric disorders during hospitalization for hematopoietic stem-cell transplantation (SCT) and to estimate their impact on hospital length of stay (LOS). PATIENTS AND METHODS: In a prospective inpatient study conducted from July 1994 to August 1997, 220 patients aged 16 to 65 years received SCT for hematologic cancer at a single institution. Patients received a psychiatric assessment at hospital admission and weekly during hospitalization until discharge or death, yielding a total of 1,062 psychiatric interviews performed. Psychiatric disorders were determined on the basis of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Univariate and multivariate linear regression analyses were used to identify variables associated with LOS. RESULTS: Overall psychiatric disorder prevalence was 44.1%; an adjustment disorder was diagnosed in 22.7% of patients, a mood disorder in 14.1%, an anxiety disorder in 8.2%, and delirium in 7.3%. After adjusting for admission and in-hospital risk factors, diagnosis of any mood, anxiety, or adjustment disorder (P = .022), chronic myelogenous leukemia (P = .003), Karnofsky performance score less than 90 at hospital admission (P = .025), and higher regimen-related toxicity (P &lt; .001) were associated with a longer LOS. Acute lymphoblastic leukemia (P = .009), non-Hodgkin’s lymphoma (P = .04), use of peripheral-blood stem cells (P &lt; .001), second year of study (P &lt; .001), and third year of study (P &lt; .001) were associated with a shorter LOS. CONCLUSION: Our data indicate high psychiatric morbidity and an association with longer LOS, underscoring the need for early recognition and effective treatment.
Tobacco Use, Body Mass Index, and the Risk of Leukemia and Multiple Myeloma: A Nationwide Cohort Study in Sweden
Authors: Pia Fernberg, Åsa Odenbro, Rino Bellocco, Paolo Boffetta, Yudi Pawitan, Kazem Zendehdel, Johanna Adami
Journal: Cancer Research (2007)

Abstract In a prospective cohort study of more than 330,000 Swedish construction workers, we explored the effect of tobacco smoking, oral moist snuff use, and body mass index (BMI) on the risk of developing leukemia (excluding chronic lymphocytic leukemia) and multiple myeloma (MM). Study subjects were participants of a health surveillance system within the building industry. Record linkage to the nationwide Swedish cancer registry, migration registry, and cause of death registry made a comprehensive follow-up available. A total of 372 incident cases of leukemia and 520 subjects with MM was ascertained. An increase in risk of acute myelogenous leukemia (AML) was observed in current smokers (incidence rate ratio, 1.50; 95% confidence interval, 1.06–2.11). Furthermore, there was an indication of a possible association between smoking intensity and risk of acute lymphocytic leukemia. Results on snuff use as well as BMI showed no association. This study confirms the role of smoking as a risk factor for AML and gives no support to the hypothesis of a role of snuff use or BMI level on the risk of leukemia or MM. [Cancer Res 2007;67(12):5983–6]
MicroRNA Expression Profiles in Serous Ovarian Carcinoma
Authors: Eun Ji Nam, Heejei Yoon, Sang Wun Kim, Hoguen Kim, Young Tae Kim, Jae Hoon Kim, Jae Wook Kim, Sunghoon Kim
Journal: Clinical Cancer Research (2008)

Although microRNAs have recently been recognized as riboregulators of gene expression, little is known about microRNA expression profiles in serous ovarian carcinoma. We assessed the expression of microRNA and the association between microRNA expression and the prognosis of serous ovarian carcinoma.Twenty patients diagnosed with serous ovarian carcinoma and eight patients treated for benign uterine disease between December 2000 and September 2003 were enrolled in this study. The microRNA expression profiles were examined using DNA microarray and Northern blot analyses.Several microRNAs were differentially expressed in serous ovarian carcinoma compared with normal ovarian tissues, including miR-21, miR-125a, miR-125b, miR-100, miR-145, miR-16, and miR-99a, which were each differentially expressed in >16 patients. In addition, the expression levels of some microRNAs were correlated with the survival in patients with serous ovarian carcinoma. Higher expression of miR-200, miR-141, miR-18a, miR-93, and miR-429, and lower expression of let-7b, and miR-199a were significantly correlated with a poor prognosis (P < 0.05).Our results indicate that dysregulation of microRNAs is involved in ovarian carcinogenesis and associated with the prognosis of serous ovarian carcinoma.
Impact of growth hormone therapy on adult height of children with idiopathic short stature: systematic review
Authors: A. Deodati, S. Cianfarani
Journal: BMJ (2011)

<b>Objective</b> To systematically determine the impact of growth hormone therapy on adult height of children with idiopathic short stature. <b>Design</b> Systematic review. <b>Data sources</b> Cochrane Central Register of Controlled Trials, Medline, and the bibliographic references from retrieved articles of randomised and non-randomised controlled trials from 1985 to April 2010. <b>Data extraction</b> Height in adulthood (standard deviation score) and overall gain in height (SD score) from baseline measurement in childhood. <b>Study selection</b> Randomised and non-randomised controlled trials with height measurements for adults. Inclusion criteria were initial short stature (defined as height &gt;2 SD score below the mean), peak growth hormone responses &gt;10 μg/L, prepubertal stage, no previous growth hormone therapy, and no comorbid conditions that would impair growth. Adult height was considered achieved when growth rate was &lt;1.5 cm/year or bone age was 15 years in females and 16 years in males. <b>Results</b> Three randomised controlled trials (115 children) met the inclusion criteria. The adult height of the growth hormone treated children exceeded that of the controls by 0.65 SD score (about 4 cm). The mean height gain in treated children was 1.2 SD score compared with 0.34 SD score in untreated children. A slight difference of about 1.2 cm in adult height was observed between the two growth hormone dose regimens. In the seven non-randomised controlled trials the adult height of the growth hormone treated group exceeded that of the controls by 0.45 SD score (about 3 cm). <b>Conclusions</b> Growth hormone therapy in children with idiopathic short stature seems to be effective in partially reducing the deficit in height as adults, although the magnitude of effectiveness is on average less than that achieved in other conditions for which growth hormone is licensed. The individual response to therapy is highly variable, and additional studies are needed to identify the responders.