bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distribution of Granule Channels, Protein, and Phospholipid in Triticale and Corn Starches as Revealed by Confocal Laser Scanning Microscopy
Authors: Naguleswaran Sabaratnam , Li Jihong , Vasanthan Thava , Bressler David 
Published: September 2010

ABSTRACTThe morphology and microstructure of starch granules from two cultivars of triticale and from normal corn were characterized using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Compared to numerous pores distributed randomly on the surfaces of corn starch granules, markedly fewer pores were observed on the surfaces of starch granules isolated from Pronghorn triticale, and even fewer on the surfaces of starch granules isolated from Ultima triticale. CLSM with fluorescence staining revealed that starch‐associated protein was predominately distributed on the granule surface and in the internal channels of both triticale and corn starches. However, after triticale starch was treated with SDS or SO2, the radially oriented, protein‐filled internal channels of the granules were observed more frequently and extended to the central region of granules. Phospholipid was located mainly on the granule surface but also in channels and throughout granules in triticale starches, whereas in corn starch granules, it was mainly in the channels. The amount of protein and phospholipid in chemically and protease‐treated starches varied with starch source and treatment conditions. In treated triticale starches, the nitrogen content was positively correlated with the phosphorus content, indicating a close association between protein and phospholipid within starch granules. Starch‐associated protein and phospholipid may play an important role in maintaining the structural stability of both the granule surface and the internal channels.
Endoplasmic Reticulum Protein Quality Control and Its Relationship to Environmental Stress Responses in Plants
Authors: Liu Jian-Xiang , Howell Stephen H. 
Published: September 2010

AbstractThe endoplasmic reticulum (ER) has a sophisticated quality control (QC) system to eliminate improperly folded proteins from the secretory pathway. Given that protein folding is such a fastidious process and subject to adverse environmental conditions, the ER QC system appears to have been usurped to serve as an environmental sensor and responder in plants. Under stressful conditions, the ER protein folding machinery reaches a limit as the demands for protein folding exceed the capacity of the system. Under these conditions, misfolded or unfolded proteins accumulate in the ER, triggering an unfolded protein response (UPR). UPR mitigates ER stress by upregulating the expression of genes encoding components of the protein folding machinery or the ER-associated degradation system. In Arabidopsis thaliana, ER stress is sensed and stress signals are transduced by membrane-bound transcription factors, which are activated and mobilized under environmental stress conditions. Under acute or chronic stress conditions, UPR can also lead to apoptosis or programmed cell death. Despite recent progress in our understanding of plant protein QC, discovering how different environmental conditions are perceived is one of the major challenges in understanding this system. Since the ER QC system is one among many stress response systems in plants, another major challenge is determining the extent to which the ER QC system contributes to various stress responses in plants.
Treatment of alopecia areata with 308‐nm excimer lamp
Authors: OHTSUKI Akiko , HASEGAWA Toshio , IKEDA Shigaku 
Published: September 2010

AbstractAlopecia areata is considered to be a T‐cell mediated autoimmune disorder. The 308‐nm excimer lamp is thought to be capable of inducing T‐cell apoptosis in vitro, suggesting that the lamp might be effective for the treatment of alopecia areata. We examined the effectiveness of the 308‐nm excimer lamp for the treatment of alopecia areata. We recruited three patients with single alopecia areata lesions that were resistant to conventional treatment. The lesions were exposed to a 308‐nm excimer lamp at 2‐weekly intervals. Hair regrowth was observed in all three patients after approximately 10 treatment sessions. Our study showed that exposure to the 308‐nm excimer lamp effectively induced hair regrowth in solitary alopecia areata lesions. Apart from erythema, there were no significant adverse effects. Therefore, we suggest that it may be considered as a treatment modality for recalcitrant alopecia areata.
Can stand‐alone computer‐based interventions reduce alcohol consumption? A systematic review
Authors: Khadjesari Zarnie , Murray Elizabeth , Hewitt Catherine , Hartley Suzanne , Godfrey Christine 
Published: September 2010

ABSTRACTAim To determine the effects of computer‐based interventions aimed at reducing alcohol consumption in adult populations.Methods The review was undertaken following standard Cochrane and Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidance for systematic reviews. The literature was searched until December 2008, with no restrictions on language. Randomized trials with parallel comparator groups were identified in the form of published and unpublished data. Two authors independently screened abstracts and papers for inclusion. Data extraction and bias assessment was undertaken by one author and checked by a second author. Studies that measured total alcohol consumption and frequency of binge drinking episodes were eligible for inclusion in meta‐analyses. A random‐effects model was used to pool mean differences.Results Twenty‐four studies were included in the review (19 combined in meta‐analyses). The meta‐analyses suggested that computer‐based interventions were more effective than minimally active comparator groups (e.g. assessment‐only) at reducing alcohol consumed per week in student and non‐student populations. However, most studies used the mean to summarize skewed data, which could be misleading in small samples. A sensitivity analysis of those studies that used suitable measures of central tendency found that there was no difference between intervention and minimally active comparator groups in alcohol consumed per week by students. Few studies investigated non‐student populations or compared interventions with active comparator groups.Conclusion Computer‐based interventions may reduce alcohol consumption compared with assessment‐only; the conclusion remains tentative because of methodological weaknesses in the studies. Future research should consider that the distribution of alcohol consumption data is likely to be skewed and that appropriate measures of central tendency are reported.
The CHOICE trial: adalimumab demonstrates safety, fistula healing, improved quality of life and increased work productivity in patients with Crohn’s disease who failed prior infliximab therapy
Authors: Lichtiger S. , Binion D. G. , Wolf D. C. , Present D. H. , Bensimon A. G. , Wu E. , Yu A. P. , Cardoso A. T. , Chao J. , Mulani P. M. , Lomax K. G. , Kent J. D. 
Published: September 2010

Aliment Pharmacol Ther 2010; 32: 1228–1239SummaryBackground  Adalimumab induces and maintains remission in adults with Crohn’s disease.Aim  To evaluate safety, fistula healing, quality of life and work productivity in adalimumab‐treated patients who failed infliximab, including primary nonresponders.Methods  After a ≥8‐week infliximab washout, patients with moderate‐to‐severe Crohn’s disease received open‐label adalimumab as induction (160/80 mg at weeks 0/2) and maintenance (40 mg every other week) therapies. At/after 8 weeks, patients with flare/nonresponse could receive weekly therapy. Minimum study duration was 8 weeks, continuing until the commercial availability of adalimumab for Crohn’s disease.Results  Of 673 patients enrolled, 17% were infliximab primary nonresponders and 83% were initial responders. Three percent of patients had serious infections (mainly abscesses). Complete fistula healing was achieved by 34/88 (39%) patients with baseline fistulas. Improvements in quality of life and work productivity were sustained from week 4 to week 24 for all patients, as well as the subgroup of primary nonresponders.Conclusions  Blinded clinical trials have shown adalimumab to be both an effective first‐line therapy for anti‐TNF‐naïve patients and an important treatment option for infliximab‐refractory or ‐intolerant patients. This trial presents open‐label experience to support further the safety and effectiveness of adalimumab in patients who failed infliximab therapy, including primary nonresponders (NCT00338650).
The effects of dose and timing of esomeprazole administration on 24‐h, daytime and night‐time acid inhibition in healthy volunteers
Authors: Wilder‐Smith C. , Röhss K. , Bokelund Singh S. , Sagar M. , Nagy P. 
Published: September 2010

Aliment Pharmacol Ther 2010; 32: 1249–1256SummaryBackground  Symptoms of gastro‐oesophageal reflux disease (GERD) may persist despite daily treatment with a proton pump inhibitor (PPI).Aim  To compare the pharmacodynamic effect of various esomeprazole dosage and timing regimens in healthy volunteers.Methods  The effect of different esomeprazole dosage regimens [20 mg once daily (od) before breakfast or dinner; 20 mg twice daily (b.d.); 40 mg od before breakfast, dinner or at bedtime; and 40 mg b.d.] on 24‐h, daytime and night‐time acid inhibition was evaluated in a randomized, seven‐way crossover study in healthy volunteers. Each regimen was taken for 5 days.Results  Over the 24‐h period (day 5), esomeprazole 20 mg b.d. was associated with superior acid inhibition vs. all 20 mg and 40 mg od regimens (P < 0.05), but was less effective than esomeprazole 40 mg b.d. (P < 0.05). Dosing with esomeprazole 20 mg or 40 mg od before breakfast gave improved 24‐h and daytime acid inhibition vs. the corresponding administration before dinner or at bedtime (all P < 0.05). Night‐time acid inhibition was improved when esomeprazole 40 mg od was administered before dinner or at bedtime vs. before‐breakfast dosing (P < 0.05).Conclusion  Varying the dose and timing of esomeprazole administration may provide acid inhibition appropriate for the symptom pattern of individual patients with GERD.
Serum HBsAg quantification to predict response to peginterferon therapy of e antigen positive chronic hepatitis B
Authors: Chan H. L.‐Y. , Wong V. W.‐S. , Chim A. M.‐L. , Chan H.‐Y. , Wong G. L.‐H. , Sung J. J.‐Y. 
Published: September 2010

Aliment Pharmacol Ther 2010; 32: 1323–1331SummaryBackground  On‐treatment predictors of response to peginterferon can guide individualization of therapy in chronic hepatitis B virus infection.Aim  To investigate the use of serum hepatitis B surface antigen quantification to predict sustained response.Methods  Hepatitis B e antigen‐positive chronic hepatitis B patients who received peginterferon for 32–48 weeks with or without lamivudine combination were studied. Sustained response was defined as hepatitis B e antigen seroconversion and chronic hepatitis B virus DNA <10 000 copies/mL until 12 months post‐treatment.Results  Twenty‐one of 92 (23%) patients achieved sustained response. At month 6, the area under receiver operating characteristics curve for hepatitis B surface antigen to predict sustained response was 0.77 (95% confidence interval 0.65–0.89, P < 0.001). An hepatitis B surface antigen cutoff at 300 IU/mL at month 6 could give the maximum combination of sensitivity (62%) and specificity (89%) to predict sustained response. Nine of 21 (43%) sustained responders vs. 9 of 71 (13%) nonsustained responders had >1 log hepatitis B surface antigen reduction at month 6 (P < 0.001). Combined hepatitis B surface antigen ≤300 IU/mL and >1 log reduction at month 6 had sensitivity, specificity, positive and negative predictive values of 43%, 96%, 75% and 85% to predict sustained response, respectively.Conclusion  On‐treatment serum hepatitis B surface antigen can predict response to peginterferon therapy in chronic hepatitis B.
The effect of propofol and desflurane anaesthesia on human hepatic blood flow: a pilot study*
Authors: Meierhenrich R. , Gauss A. , Mühling B. , Bracht H. , Radermacher P. , Georgieff M. , Wagner F. 
Published: September 2010

SummaryThis study tested the hypothesis that propofol is associated with a higher hepatic blood flow in humans compared with desflurane. Using a cross over study design, 10 patients received first propofol and then desflurane, and a further 10 patients received desflurane and then propofol. Blood flow index in the right and middle hepatic veins, stroke volume index and cardiac index were assessed by transoesophageal echocardiography. Mean arterial blood pressure, stroke volume index and cardiac index were the same in both groups. Propofol was associated with significantly greater blood flow index in the right hepatic vein (median (IQR [range]) 199 (146–237 [66–388]) vs. 149 (112–189 [42–309]) ml.min−1.m−2; p = 0.005) and middle hepatic vein (150 (122–191 [57–341]) vs. 125 (92–149 [47–362]) ml.min−1.m−2; p < 0.001) compared with desflurane. In routine clinical conditions, propofol anaesthesia was associated with significantly greater hepatic blood flow than desflurane anaesthesia.
Influence of polymorphisms within the methotrexate pathway genes on the toxicity and efficacy of methotrexate in patients with juvenile idiopathic arthritis
Authors: Yanagimachi Masakatsu , Naruto Takuya , Hara Takuma , Kikuchi Masako , Hara Ryoki , Miyamae Takako , Imagawa Tomoyuki , Mori Masaaki , Kaneko Tetsuji , Morita Satoshi , Goto Hiroaki , Yokota Shumpei 
Published: September 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Methotrexate (MTX), which causes adverse effects, such as liver and/or renal dysfunction, is the most common disease‐modifying antirheumatic drug used for the treatment of rheumatoid arthritis and articular‐type juvenile idiopathic arthritis (JIA).• Pharmacogenetic studies analysing the MTX pathway genes would aid in the development of more personalized therapy.• Results regarding the influence of gene polymorphisms on the toxicity and efficacy of MTX are conflicting, and there are marked differences between racial groups in pharmacogenetics. WHAT THIS STUDY ADDS • The non‐TT genotype at γ‐glutamyl hydrolase (GGH) T16C is associated with a high risk of liver dysfunction due to MTX, even after adjustment for duration of MTX treatment.• Longer time interval from disease onset to MTX treatment and rheumatoid factor positivity are associated with lower efficacy of MTX in Japanese patients, as reported previously in Caucasian patients with JIA.AIMS We investigated whether several polymorphisms within the methotrexate (MTX) pathway genes were related to the toxicity and efficacy of MTX in 92 Japanese patients with articular‐type juvenile idiopathic arthritis (JIA).METHODS Eight gene polymorphisms within the MTX pathway genes, namely, RFC, BCRP, MTHFR (two), FPGS, γ‐glutamyl hydrolase (GGH; two) and ATIC, were genotyped using TaqMan assays. Liver dysfunction was defined as an increase in alanine transaminase to five times the normal upper limit. Non‐responders to MTX were defined as patients refractory to MTX and were therefore treated with biologics.RESULTS The non‐TT genotype at GGH T16C was associated with a high risk of liver dysfunction (P = 0.028, odds ratio = 6.90, 95% confidence interval 1.38–34.5), even after adjustment for the duration of MTX treatment. A longer interval from disease onset to treatment (8.5 and 21.3 months, P = 0.029) and rheumatoid factor positivity (P = 0.026, odds ratio = 2.87, 95% confidence interval 1.11–7.39) were associated with lower efficacy of MTX.CONCLUSIONS The non‐TT genotype at GGH T16C was associated with a high risk of liver dysfunction, presumably because the C allele of GGH C16T may reduce the activity of GGH. The time interval before MTX treatment and rheumatoid factor positivity were associated with the efficacy of MTX treatment. The pharmacogenetics of the MTX pathway genes affects the toxicity and efficacy of MTX in Japanese JIA patients.
Weekly versus twice weekly bortezomib given in conjunction with rituximab, in patients with recurrent follicular lymphoma, mantle cell lymphoma and Waldenström macroglobulinaemia
Authors: Agathocleous Agathoclis , Rohatiner Ama , Rule Simon , Hunter Hannah , Kerr Jonathan Paul , Neeson Susan M. , Matthews Janet , Strauss Sandra , Montoto Silvia , Johnson Peter , Radford John , Lister Andrew 
Published: September 2010

SummaryThe combination of bortezomib and rituximab was evaluated in patients with mantle cell lymphoma (MCL), follicular lymphoma (FL) and Waldenström macroglobulinaemia (WM), in a Phase I and later, a randomized Phase II study. In the randomized study, 42 patients with recurrent/refractory disease received either: bortezomib 1·3 mg/m2 on days 1, 4, 8 and 11 of a 3‐week cycle with rituximab 375 mg/m2 on day 1 (21 patients) or: bortezomib 1·6 mg/m2 and rituximab on days 1, 8, 15 and 22 of a 5‐week cycle (with rituximab being given only in cycles 1 and 4).Twenty‐eight patients were withdrawn (toxicity 16, progression 7, and ‘patient choice’ 5). The main toxicities were neurological, gastro‐intestinal and haematological. The overall response rate was 28/42(67%) and by histology: MCL 11/19, FL 8/15, and WM 9/10. Ten of 28 responding patients remained progression‐free at 1–3·5 years. Toxicity and efficacy were equivalent between the two groups. The combination has significant toxicity but is effective, particularly in patients with WM.
The class‐I HDAC inhibitor MGCD0103 induces apoptosis in Hodgkin lymphoma cell lines and synergizes with proteasome inhibitors by an HDAC6‐independent mechanism
Authors: Buglio Daniela , Mamidipudi Vidya , Khaskhely Noor M. , Brady Helen , Heise Carla , Besterman Jeffrey , Martell Robert E. , MacBeth Kyle , Younes Anas 
Published: September 2010

SummaryInhibition of histone deacetylase 6 (HDAC6)‐dependent aggresome function by pan HDAC inhibitors was recently reported to be a key mechanism underlying the synergistic activity between proteasome inhibitors and HDAC inhibitors in a variety of tumour types. Because these combinations induce significant thrombocytopeniain vivo, we examined whether less toxic, isotype‐selective HDAC inhibitors may still synergize with proteasome inhibitors, and if so, by what mechanisms. Here, we showed that the class I HDAC inhibitor, MGCD0103, has a potent antiproliferative activity in Hodgkin lymphoma (HL) cell lines. Furthermore, MGCD0103 induced tumour necrosis factor α (TNF‐α) expression and secretion, which was associated with nuclear factor (NF)‐κB activation. Selective inhibition of TNF‐α expression by short interfering mRNA, or inhibition of MGCD0103‐induced NF‐kB activation by proteasome inhibitors enhanced MGCD0103‐induced cell death. Thus, our results demonstrate that MGCD0103 may synergize with proteasome inhibitors by HDAC6‐independent mechanisms, providing mechanistic rationale for exploring this potentially less toxic combination for the treatment of lymphoma.
Novel interactions between UFH and TFPI in children
Authors: Newall Fiona , Johnston Linda , Summerhayes Robyn , Lane Geoff , Cranswick Noel , Monagle Paul , Ignjatovic Vera 
Published: September 2010

SummaryThe impact of age upon therapeutic response to unfractionated heparin (UFH) in children is proposed to reflect quantitative and potentially qualitative differences in coagulation proteins across childhood. This study explores the UFH‐dependent tissue factor pathway inhibitor (TFPI) release in children compared to previously published data in adults. Children <16 years of age undergoing cardiac angiography formed the population for this prospective cohort study. TFPI release was measured prior to (baseline) and at 15, 30, 45 and 120 min post‐UFH dose. This study demonstrated that, whilst the immediate release of TFPI post‐UFH was similar in children compared to adults, TFPI release in children remained increased and consistent for a significantly longer period post‐UFH administration compared to adults. Plasma TFPI levels in children did not demonstrate an UFH concentration –dependent reduction, as has been previously reported in adults. The prolonged TFPI‐mediated anticoagulant levels observed in children administered UFH may contribute to the increased rate of major bleeding reported in children compared to adults. Furthermore, we postulate that this sustained UFH‐dependent increase in TFPI levels in children may influence the binding of UFH to competitive plasma proteins, such as those involved in the immunological response to UFH associated with heparin‐induced thrombocytopenia.
ASXL1 mutation is associated with poor prognosis and acute transformation in chronic myelomonocytic leukaemia
Authors: Gelsi‐Boyer Véronique , Trouplin Virginie , Roquain Julien , Adélaïde José , Carbuccia Nadine , Esterni Benjamin , Finetti Pascal , Murati Anne , Arnoulet Christine , Zerazhi Hacène , Fezoui Hacène , Tadrist Zoulika , Nezri Meyer , Chaffanet Max , Mozziconacci Marie‐Joëlle , Vey Norbert , Birnbaum Daniel 
Published: September 2010

SummaryChronic myelomonocytic leukaemia (CMML) is a haematological disease currently classified in the category of myelodysplastic syndromes/myeloproliferative neoplasm (MDS/MPN) because of its dual clinical and biological presentation. The molecular biology of CMML is poorly characterized. We studied a series of 53 CMML samples including 31 cases of myeloproliferative form (MP‐CMML) and 22 cases of myelodysplastic forms (MD‐CMML) using array‐comparative genomic hybridisation (aCGH) and sequencing of 13 candidate genes including ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, PTPN11, RUNX1, TET2 and WT1. Mutations in ASXL1 and in the genes associated with proliferation (CBL, FLT3, PTPN11, NRAS) were mainly found in MP‐CMML cases. Mutations of ASXL1 correlated with an evolution toward an acutely transformed state: all CMMLs that progressed to acute phase were mutated and none of the unmutated patients had evolved to acute leukaemia. The overall survival of ASXL1 mutated patients was lower than that of unmutated patients.
Southwest Oncology Group Study S0530: a phase 2 trial of clofarabine and cytarabine for relapsed or refractory acute lymphocytic leukaemia
Authors: Advani Anjali S. , Gundacker Holly M. , Sala‐Torra Olga , Radich Jerald P. , Lai Raymond , Slovak Marilyn L. , Lancet Jeffrey E. , Coutre Steve E. , Stuart Robert K. , Mims Martha P. , Stiff Patrick J. , Appelbaum Frederick R. 
Published: September 2010

SummaryClofarabine and cytarabine target different steps in DNA synthesis and replication, are synergistic in vivo, and have non‐overlapping toxicities, making this combination a potentially promising treatment for acute lymphocytic leukaemia. Thirty‐seven patients were treated. The median age was 41 years, 44% of patients were either in ≥2nd relapse or had refractory disease and 59% of patients had poor risk cytogenetics. Six out of 36 patients (17%) achieved a complete remission with or without complete count recovery; median overall survival was 3 months. Nucleoside transporter expression did not predict outcome. This regimen lacked sufficient activity to warrant further testing.