bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemoprotective effects of KF41399, a derivative of carbazole compounds, on nimustine-induced thrombocytopenia
Authors: Shiotsu Yukimasa , Yamashita Kinya , Kanai Fumihiko , Ikuina Yoji , Murakata Chikara , Teramura Masanao , Mizoguchi Hideaki , Tamaoki Tatsuya , Akinaga Shiro 
Published: October 2019

AbstractWe examined the chemoprotective effects of KF41399, a novel derivative of carbazole compounds, on severe thrombocytopenia induced by nimustine (ACNU, 45 mg/kg administered for 2 consecutive days intravenously) in mice. Administration schedule studies revealed that pretreatment of mice with KF41399 was necessary to improve thrombocytopenia. Oral administration of KF41399 ameliorated thrombocytopenia induced by ACNU and accelerated the rate of platelet recovery in a dose-dependent fashion. In addition, KF41399 pretreatment improved the decrease in body weight and spleen weight and in the colony-forming activity of bone marrow mononuclear cells (MNC). Oral administration of KF41399 to normal mice induced G0/G1-phase accumulation of MNC as well as hematopoietic progenitor cells (lineage negative cells [Lin−]) and reduced the colony-forming activity of MNC. In Lin− cells derived from KF41399-treated mice, up-regulation of Bcl-2 and down-regulation of cyclin E and cyclin A proteins were observed. In the same cells, a decrease in the phosphorylated form of Rb protein and an increase in the p130 protein were observed without changes in the protein level of cell cycle-dependent kinase 2 (Cdk2), Cdk4, and Cdk6. More important, KF41399 did not affect the antitumor activity of ACNU against mouse Sarcoma180 and human lung cancer LC-6. However, 25-mg/kg KF41399 treatment reduced the antitumor activity of ACNU against human lung cancer Lu-65, and 5 mg/kg KF41399 caused a slight reduction of the antitumor activity of ACNU without inducing thrombocytopenia. These results suggest that KF41399 might be useful as a chemoprotective agent to improve chemotherapy-induced thrombocytopenia and types of other toxicity.
Selective disruption of interleukin 4 autocrine-regulated loop by a tyrosine kinase inhibitor restricts activity of T-helper 2 cells
Authors: Wang Li Hua , Kirken Robert A. , Yang Xiao Yi , Erwin Rebecca A. , DaSilva Luis , Yu Cheng-Rong , Farrar William L. 
Published: October 2019

AbstractInterleukin (IL) 4 is a potent immunomodulatory cytokine secreted by T-helper 2 (Th2) cells and Th2 mast cells that promotes the commitment of cells. However, unregulated production and release of IL-4 can exacerbate allergic reactions and increase susceptibility to infectious organisms and viruses. Here, we present evidence that AG-490, a Janus tyrosine kinase (JAK) 2-JAK3 inhibitor, effectively blocked IL-4 gene expression and secretion in the Th2 cell line D10 that was not occurring after anti-CD3 antibody stimulation, whereas AG-490 had no inhibitory effect on production of other Th2 cytokines or cytokines synthesized by the corresponding Th1 cell line clone 29. AG-490 potently inhibited IL-4–mediated proliferation of both D10 and the IL-4–dependent cell line CT.4S. Moreover, AG-490 markedly inhibited IL-4 activation of JAK3 and blocked the downstream activation of signal transducer and activator of transcription 6, as judged by tyrosine phosphorylation, DNA binding, and transcription assays. In contrast, AG-490 did not affect tumor necrosis factor  activation of NF-κB at similar concentrations of drug. These data suggest that tyrosine kinase inhibitors that inhibit JAK3 may have previously unrecognized and selective clinical potential as immunotherapeutic drugs to treat Th2-mediated diseases driven by IL-4.
Synergistic effects of in vivo depletion of Ly-49A and Ly-49G2 natural killer cell subsets in the rejection of H2b bone marrow cell allografts
Authors: Raziuddin Arati , Bennett Michael , Winkler-Pickett Robin , Ortaldo John R. , Longo Dan L. , Murphy William J. 
Published: October 2019

AbstractSubsets of murine natural killer (NK) cells exist that express the Ly-49 family of molecules that recognize different major histocompatibility complex (MHC) determinants. Bone marrow transplantation studies were performed to examine the in vivo functions of 2 of these subsets. Subsets of Ly-49A and Ly-49G2 NK share specificity for the same MHC class 1 ligand, Dd, binding of which results in an inhibitory signal to the NK cell but allows them to lyse H2b targets in vitro. We therefore examined the ability of these subsets to reject H2b bone marrow cell allografts in lethally irradiated mice. Surprisingly, depletion of Ly-49A+ NK cells in BALB/c or B10.D2 mice (both H2d) had no effect on the rejection of H2b BMC. However, Ly-49A depletion did partially abrogate the ability of B10.BR (H2k) mice to reject H2ballografts. Although depletion of either Ly-49A+ or Ly-49G2+ NK cells alone had no effect on the ability of B10.D2 mice to reject H2b BMC, depletion of both subsets dramatically and synergistically abrogated rejection. Studies with various B10 congenic mice and their F1 hybrids indicate that this synergy between Ly49A and Ly4G2 depletion occurs in every instance. Thus, Ly-49A+ NK cells appear to play a role in the rejection H2b bone marrow allografts, but, in most strains of mice studied, Ly-49G2+ NK cells must also be eliminated. The putative roles of these NK cell subsets in clinical transplantation remains to be elucidated.
A2A receptor dependent and A2A receptor independent effects of extracellular adenosine on murine thymocytes in conditions of adenosine deaminase deficiency
Authors: Apasov Sergey , Chen Jiang-Fan , Smith Patrick , Sitkovsky Michail 
Published: October 2019

AbstractAdenosine deaminase (ADA) deficiency causes severe combined immunodeficiency (SCID) and is accompanied by T-cell depletion and accumulation of both intracellular and extracellular adenosine (extAdo) and deoxyadenosine. To better understand the causes of T-cell depletion in vivo and to discriminate between extracellular and intracellular effects of exogenously added adenosine in vitro, we investigated mechanisms of 2 different effects of adenosine on murine thymocytes. These effects of adenosine include direct induction of apoptosis in about 6% to 15% thymocytes and inhibition of T-cell receptor (TCR)-induced activation of the majority of thymocytes with inhibited ADA. A2A adenosine receptors, but not A2B, A1, or A3 receptors, are shown to be mostly responsible for extAdo-triggered signaling (cyclic adenosine monophosphate [cAMP] accumulation) in murine thymocytes and this prompted studies of the effects of extAdo on thymocytes from A2AR gene-deficient mice. It is found that direct apoptotic effects of extAdo on CD4+CD8+ double positive (DP) thymocytes are completely accounted for by signaling through A2AR, with no contribution of intracellular lymphotoxicity or of compensating A2BRs because only A2AR +/+, but not A2AR −/− thymocytes were susceptible to apoptotic effects of extAdo. Studies of the effects of cAMP-raising agents support observations of extAdo/A2AR/cAMP–triggered apoptosis in DP thymocytes. Unexpectedly, the extAdo strongly inhibited TCR-triggered activation of both A2AR +/+ and A2AR −/− thymocytes in the presence of ADA inhibitors. This was confirmed with thymocytes from ADA gene-deficient mice, suggesting the existence of A2AR-independent effects of extAdo on thymocytes. The presented data raises questions about the identity and functional role of A2AR-expressing thymocytes in T-cell differentiation and of the role of TCR-antagonizing effects of extAdo in conditions of ADA SCID.
Ki-4(scFv)–ETA′, a new recombinant anti-CD30 immunotoxin with highly specific cytotoxic activity against disseminated Hodgkin tumors in SCID mice
Authors: Barth Stefan , Huhn Michael , Matthey Bärbel , Tawadros Samir , Schnell Roland , Schinköthe Timo , Diehl Volker , Engert Andreas 
Published: October 2019

AbstractThe human lymphocyte activation marker CD30 is highly overexpressed on Hodgkin/Reed–Sternberg cells and represents an ideal target for selective immunotherapy. We used the murine anti-CD30 hybridoma Ki-4 to construct a new recombinant immunotoxin (rIT) for possible clinical use in patients with CD30+ lymphoma. Hybridoma V genes were polymerase chain reaction-amplified, assembled, cloned, and expressed as a mini-library for display on filamentous phage. Functional Ki-4 scFv obtained by selection of binding phage on the CD30-expressing Hodgkin lymphoma cell line L540cy was inserted into the bacterial expression vector pBM1.1 and fused to a deletion mutant ofPseudomonas exotoxin A (ETA′). Periplasmically expressed Ki-4(scFv)–ETA′ demonstrated specific activity against a variety of CD30+ lymphoma cells as assessed by different in vitro assays. To evaluate in vivo antitumor activity, severe combined immunodeficient mice challenged with human lymphoma cell lines were treated with the immunotoxin. The blood distribution time t½ of Ki-4(scFv)–ETA′ was 19 minutes, and its serum elimination time t½ was 193 minutes. A single intravenous injection of 40 μg rIT 1 day after tumor inoculation rendered 90% of the mice tumor free, extending the mean survival time to more than 200 days compared with 38.1 days in the phosphate-buffered saline control group (P &lt; .001). This new rIT is a promising candidate for further clinical evaluation in patients with Hodgkin lymphoma or other CD30+malignancies.
Recipient priming to one RBC alloantigen directly enhances subsequent alloimmunization in mice
Authors: Patel Seema R. , Bennett Ashley , Girard-Pierce Kathryn , Maier Cheryl L. , Chonat Satheesh , Arthur Connie M. , Zerra Patricia E. , Mener Amanda , Stowell Sean R. 
Published: October 2019

Key Points
CD4+ T cells primed to one RBC alloantigen promote humoral immunity to a disparate RBC alloantigen when both antigens are on the same RBC. These findings provide a potential explanation for how responses to one antigen may enhance antibody formation to other RBC alloantigens.
The association between motor capacity and mobility performance: frailty as a moderator
Authors: Jansen Carl-Philipp , Toosizadeh Nima , Mohler M. Jane , Najafi Bijan , Wendel Christopher , Schwenk Michael 
Published: October 2019

AbstractBackgroundIn older adults, the linkage between laboratory-assessed ‘motor capacity’ and ‘mobility performance’ during daily routine is controversial. Understanding factors moderating this relationship could help developing more valid assessment as well as intervention approaches. We investigated whether the association between capacity and performance becomes evident with transition into frailty, that is, whether frailty status moderates their association.MethodsWe conducted a cross-sectional analysis of the observational Arizona Frailty Cohort Study (ClinicalTrials.gov identifier: NCT01880229) in a community-dwelling cohort in Tucson, Arizona. Participants wereN = 112 older adults aged 65 years or older who were categorized as non-frail (n = 40), pre-frail (n = 53) or frail (n = 19) based on the Fried frailty index.Motor capacity was quantified as normal (NWS) and fast walking speed (FWS). Mobility performance was quantified as 1) cumulated physical activity (PA) time and 2) everyday walking performance (average steps per walking bout; maximal number of steps in one walking bout), measured by a motion sensor over a 48 h period. Hierarchical linear regression analyses were performed to evaluate moderation effects.ResultsUnlike in non-frail persons, the relationship between motor capacity and mobility performance was evident in pre-frail and frail persons, confirming our hypothesis. A moderating effect of frailty status was found for 1) the relationship between both NWS and FWS and maximal number of steps in one bout and 2) NWS and the average steps per bout. No moderation was found for the association between NWS and FWS with cumulated PA.ConclusionIn pre-frail and frail persons, motor capacity is associated with everyday walking performance, indicating that functional capacity seems to better represent mobility performance in this impaired population. The limited relationship found in non-frail persons suggests that other factors account for their mobility performance. Our findings may help to inform tailored assessment approaches and interventions taking into consideration a person’s frailty status.
Prognoses of different pathological subtypes of colorectal cancer at different stages: A population-based retrospective cohort study
Authors: Wu Xiaoli , Lin Han , Li Shaotang 
Published: October 2019

AbstractBackgroundWhether the prognoses of different pathological subtypes of colorectal cancer (CRC) at different stages are distinct is unclear.MethodsWe extracted data on all cases of CRC from the Surveillance, Epidemiology, and End Results database between 2004 and 2015. The incidence of different pathological subtypes, clinical characteristics, and five-year overall survival (OS) and cause-specific survival (CSS) were analyzed.ResultsA total of 384,996 cases diagnosed as adenocarcinoma (AC), mucinous adenocarcinoma (MAC), and signet ring cell carcinoma (SRCC) were included in this analysis. Compared with AC, MAC and SRCC were more likely to reach T4, N2, M1, stages III and IV, and grades III and IV, and patients were generally of a younger age (P < 0.001). Compared with those with AC, patients with MAC and SRCC showed poorer OS (50.6 and 26.8% vs. 60.2%,P < .001), with corresponding HR values of 1.238 (95% CI, 1.213–1.263,P < .001) and 1.592 (95% CI, 1.558–1.627,P < .001), respectively. The MAC and SRCC groups also showed poorer overall CCS (60.9 and 32.5% vs. 67.8%,P < .001), with corresponding HR values of 1.271 (95% CI, 1.242–1.302,P < .001) and 1.724 (95% CI, 1.685–1.765,P < .001), respectively. Compared with patients with AC, those with MAC showed poor OS at every stage and poor CSS at every stage except stage II (P < .05), while patients with SRCC revealed poor OS and CSS at every stage except stage 0 (P < .05).ConclusionsPatients of different pathological subtypes minimally differed at early stages. However, patients with AC have significantly better prognoses in advanced CRC (stages III and IV) than those with MAC or SRCC. Distinct treatment strategies should be applied depending on a particular histological subtype in advanced CRC.
Prevalence of Potentially Inappropriate Medication use in older drivers
Authors:   The LongROAD Research Team, Li Guohua , Andrews Howard F. , Chihuri Stanford , Lang Barbara H. , Leu Cheng Shiun , Merle David P. , Gordon Abigail , Mielenz Thelma J. , Strogatz David , Eby David W. , Betz Marian E. , DiGuiseppi Carolyn , Jones Vanya C. , Molnar Lisa J. , Hill Linda L. 
Published: October 2019

Abstract

Background
Potentially Inappropriate Medication (PIM) use has been studied in a variety of older adult populations across the world. We sought to examine the prevalence and correlates of PIM use in older drivers.

Methods
We applied the American Geriatrics Society 2015 Beers Criteria to baseline data collected from the “brown-bag” review of medications for participants of the Longitudinal Research on Aging Drivers (LongROAD) study to examine the prevalence and correlates of PIM use in a geographically diverse, community-dwelling sample of older drivers (n = 2949). Proportions of participants who used one or more PIMs according to the American Geriatrics Society 2015 Beers Criteria, and estimated odds ratios (ORs) and 95% confidence intervals (CIs) of PIM use associated with participant characteristics were calculated.

Results
Overall, 18.5% of the older drivers studied used one or more PIM. The most commonly used therapeutic category of PIM was benzodiazepines (accounting for 16.6% of the total PIMs identified), followed by nonbenzodiazepine hypnotics (15.2%), antidepressants (15.2%), and first-generation antihistamines (10.5%). Compared to older drivers on four or fewer medications, the adjusted ORs of PIM use were 2.43 (95% CI 1.68–3.51) for those on 5–7 medications, 4.19 (95% CI 2.95–5.93) for those on 8–11 medications, and 8.01 (95% CI 5.71–11.23) for those on ≥12 medications. Older drivers who were female, white, or living in urban areas were at significantly heightened risk of PIM use.

Conclusion
About one in five older drivers uses PIMs. Commonly used PIMs are medications known to impair driving ability and increase crash risk. Implementation of evidence-based interventions to reduce PIM use in older drivers may confer both health and safety benefits.

Trial registration
Not applicable.
Use of intravoxel incoherent motion imaging to monitor a rat kidney chronic allograft damage model
Authors: Zhang Qiang , Yu Zexing , Zeng Song , Liang Lu , Xu Yue , Zhang Zijian , Tang Hao , Jiao Wenjiao , Xue Wenrui , Wang Wei , Zhang Xiaodong , Jiang Tao , Hu Xiaopeng 
Published: October 2019

Abstract

Background
Chronic allograft damage (CAD) is the leading cause of long-term graft dysfunction. A noninvasive method that can diagnose CAD early and monitor its development is needed.

Methods
Kidneys from Fisher rats were transplanted into Lewis rats to establish a CAD model (n = 20). The control group underwent syngeneic kidney transplantation (n = 20). The serum creatinine of the rats was monitored. At 4, 12, and 20 weeks after modeling, a magnetic resonance imaging (MRI) examination was performed. The apparent diffusion coefficient (ADC), pseudo diffusion coefficient (D*), true diffusion coefficient (D) and perfusion fraction (f) of the two groups were analyzed. Chronic allograft damage index (CADI) scoring was used to evaluate the transplanted kidney specimens. Immunohistochemistry was used to detect the expression of fibrosis markers in the transplanted kidney tissues and to analyze their correlations with all MRI parameters.

Results
The transplanted kidneys in the experimental group developed CAD changes before the appearance of elevated creatinine. The MRI parameters in the experimental group [ADC (1.460 ± 0.109 VS 2.095 ± 0.319, P < 0.001), D (1.435 ± 0.102 VS 1.969 ± 0.305, P < 0.001), and f (26.532 ± 2.136 VS 32.255 ± 4.013, P < 0.001)] decreased, and D* (20.950 ± 2.273 VS 21.415 ± 1.598, P = 0.131) was not significantly different from those in the control group. ADC, D and f were negatively correlated with the CADI and the α-SMA and vimentin expression levels.

Conclusion
Intravoxel incoherent motion (IVIM) imaging could detect CAD earlier than creatinine and reflect the degree of fibrosis in grafts quantitatively.
Assessing the effectiveness of mindfulness-based programs on mental health during pregnancy and early motherhood - a randomized control trial
Authors: Pan Wan-Lin , Chang Chiung-Wen , Chen Shin-Ming , Gau Meei-Ling 
Published: October 2019

Abstract

Background
The process of entering motherhood is highly stressful for women, with 15–85% of new mothers experiencing postpartum blues or depression. This study was designed to evaluate the efficacy of a mindfulness-based childbirth and parenting program in improving psychological health during the postpartum period.

Methods
This research was a randomized controlled trial with single blinding. Recruitment began after the participating hospital granted formal approval. A total of 74 women between 13 and 28-weeks gestation were allocated either to the intervention group or to the comparison group. The intervention program included a series of eight, 3-h classes held once weekly and 1 day of 7-h silent meditation. Psychological health was assessed at baseline and 3-months postpartum.

Results
Significant differences in stress and depression were observed in both groups over time. Stress scores and depression scores were significantly better in the intervention group than in the comparison group at 3-months postpartum (F = 7.19, p = .009 and F = 7.36, p = .008, respectively). No significant difference between the groups was identified for mindfulness scores at 3-months postpartum.

Conclusions
The intervention program effectively reduced postpartum self-perceived stress and depression, suggesting that this program provides acceptable and long-term benefits to women during pregnancy and the postpartum period. The teaching and practice of mindfulness meditation and parenting education during pregnancy may help reduce stress and depression in pregnant women as they transition into parenthood.

Trial registration
The ClinicalTrials.gov identifier for this study is: NCT03185910. The study was retrospectively registered on 14 June 2017.
Intra-arterial EmboCept S® and DC Bead® effectively inhibit tumor growth of colorectal rat liver metastases
Authors: Ziemann Christian , Roller Jonas , Malter Markus M. , Keller Kira , Kollmar Otto , Glanemann Matthias , Menger Michael D. , Sperling Jens 
Published: October 2019

Abstract

Background
Intra-arterial therapy with embolics is established for the treatment of malignancies of the liver. However, there are no studies comparing the different effects of various embolics used in clinical practice. Herein, we analyzed the effect of 3 different embolics on tumor growth in a rat model of colorectal liver metastases.

Methods
Eight days after subcapsular implantation of 5 × 105 colorectal cancer cells (CC531) in the left liver lobe of WAG/Rij rats were randomized into 4 groups (n = 8) and underwent intra-arterial hepatic therapy. Animals received either EmboCept S®, DC Bead® or Lipiodol® Ultra-Fluid. Animals of the control group received a comparable amount of saline. Tumor growth was measured on day 8 and 11 using a three-dimensional 40 MHz ultrasound device. On day 11 tumor and liver tissue were removed for histological and immunohistochemical analyses.

Results
On day 11 animals of the control group showed a tumor growth of ~ 60% compared to day 8. Application of Lipiodol Ultra-Fluid® did not significantly influence tumor growth (~ 40%). In contrast, treatment with EmboCept S® or DC Bead® completely inhibited tumor growth. Of interest, application of EmboCept S® did not only completely inhibit tumor growth but even decreased tumor size. Immunohistochemical analysis showed a significant increase of necrotic areas within the tumors after application of EmboCept S® and DC Bead® compared to Lipiodol® Ultra-Fluid.

Conclusion
The present study demonstrates that an intra-arterial therapy with EmboCept S® and DC Bead®, but not Lipiodol® Ultra-Fluid, results in a complete inhibition of rat colorectal liver metastatic growth.