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  • 1
    Electronic Resource
    Electronic Resource
    Treatment of Rheumatoid Arthritis with Single Dose or Weekly Pulses of Chimaeric Anti-CD4 Monoclonal Antibody (1992)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 36 (1992), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The aetiotogy of rheumatoid arthritis is unknown but CD4+ T eells are known to be involved in its pathogenesis. Because of this, anti-CD4 monoelonal antibody has been used in open studies with clinical benefit in up to 60% of patients. We have used a ehimaeric anti-CD4 monoclonal antibody (cM-T4l2, Centocor) in a randomized, double-blinded, placebo controlled trial as treatment for rheumatoid arthritis. Nine patients with active rheumatoid arthritis resistant to traditional disease-modifying drugs were recruited. Four received an intravenous 50 mg bolus of antibody, and three received 50 mg weekly for four consecutive weeks. Two patients received placebo. Despite a marked reduction (P〈0.001) in peripheral blood CD4+ lymphocytes, there was no significant clinical improvement in any of these patienis. The decrease in CD4+ lymphocyte number lasted one week after a single 50 mg dose of cM-T412 but was more prolonged in the patients who reeeived four infusions. CD8+ T cells. CD16+ cytoloxic cells and CD14+ monoeytes showed only a transient reduction. It may be concluded that the therapeutic efficacy of anti-CD4 therapy is not direetly related to CD4 T-cell lymphopenia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1992.tb03102.x
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  • 2
    Electronic Resource
    Electronic Resource
    Effect of soil temperature on sorghum emergence (1975)
    Springer
    Plant and soil 43 (1975), S. 411-417 
    Details
    ISSN: 1573-5036
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Soil temperature strongly influences both percentage germination and time of emergence of sorghum. Ten hybrids were hand planted in the field. Soil surface was irrigated frequently and emerging plants were counted daily. On three treatments, soil temperature was monitored every hour at five depths. Treatments were designed to achieve a range in surface soil temperature. Results of the study indicated an optimum germination temperature of about 23°C and a heat requirement of 67 degree days. The maturity classifications of the hybrids did not show a consistent trend in their heat requirement for emergence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01928503
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  • 3
    Electronic Resource
    Electronic Resource
    Effect of soil temperature on sorghum emergence (1975)
    Springer
    Plant and soil 43 (1975), S. 411-417 
    Details
    ISSN: 1573-5036
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Soil temperature strongly influences both percentage germination and time of emergence of sorghum. Ten hybrids were hand planted in the field. Soil surface was irrigated frequently and emerging plants were counted daily. On three treatments, soil temperature was monitored every hour at five depths. Treatments were designed to achieve a range in surface soil temperature. Results of the study indicated an optimum germination temperature of about 23°C and a heat requirement of 67 degree days. The maturity classifications of the hybrids did not show a consistent trend in their heat requirement for emergence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01928503
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Standardising joint assessment in rheumatoid arthritis (1996)
    Springer
    Clinical rheumatology 15 (1996), S. 579-582 
    Details
    ISSN: 1434-9949
    Keywords: Rheumatoid Arthritis ; Articular Index ; Joint Assessment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Evaluating joint involvement in rheumatoid arthritis in a key clinical assessment. We investigated the extent of variation in measurement of joint swelling and tenderness and evaluated the impact of training to standardise methods. Eight observers (medical and nursing staff) examined eight rheumatoid patients for joint swelling and tenderness before and after training in clinical methods. The EULAR handbook for joint evaluation was used for training and assessments were based on the 28 joint count. There was extensive variability in both numbers of swollen and tender joints. Coefficients of variation for articular indices recorded by the 8 observers in individual patients were often high (up to a maximum of 204%), indicating considerable differences between observers. Training had an impact on the assessment of the numbers of swollen joints which increased by a mean of 32% (P〈0.05) and the number of tender joints which increased by 41% (p〈0.01). Training had only a limited impact on the variation among observers in determining the number of swollen and number of tender joints. After training, the mean coefficients of variation were still 59% for swollen joints and 65% for tender joints. These results highlight the extent of variation in clinical assessment of rheumatoid arthritis and show the advantages of training. It leads to increased sensitivity of measurement. Standardisation appears essential for clinical studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02238547
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  • 5
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    The role of the adductor muscle as an energy storage organ in the pen shell Atrina japonica (Reeve, 1858) (2015)
    Oxford University Press
    Details
    Publication Date: 2015-10-24
    Description: The biochemical composition and reproductive cycle of the pen shell Atrina japonica were investigated through separate analyses of the adductor muscle, gonad and the remaining tissues over a 1-year cycle. Seasonal variations in condition and gonadosomatic indices reflected those of gross weights of biochemical components of whole tissues. During the spring period, growth was initiated in the gonadal tissues simultaneously with the maximum weight gain in the adductor muscle, in which most of the energy reserves were stored, indicating that gametogenesis occurs at the expense of immediately ingested food energy. The increased energy reserves in the gonad during gametogenic development were exhausted completely during the summer spawning. Protein and carbohydrate reserves in the adductor muscle were used as catabolic substrates during spawning. The interannual shift in the timing of spawning appeared to be related to the changes in energy storage and gamete growth during the spring, probably reflecting changes in nutritional conditions in the ambient environment. Our results suggest that the adductor muscle of the pen shell plays a critical role as a major organ responsible for energy storage and that organ-specific biochemical composition can provide information of general relevance to the processes of energy gain and mobilization in bivalves.
    Print ISSN: 0260-1230
    Electronic ISSN: 1464-3766
    Topics: Biology
    Published by Oxford University Press
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  • 6
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    Protocol for a randomised controlled trial for Reducing Arthritis Fatigue by clinical Teams (RAFT) using cognitive-behavioural approaches (2015)
    BMJ Publishing
    In: BMJ Open
    Details
    Publication Date: 2015-08-08
    Description: Introduction Rheumatoid arthritis (RA) fatigue is distressing, leading to unmanageable physical and cognitive exhaustion impacting on health, leisure and work. Group cognitive–behavioural (CB) therapy delivered by a clinical psychologist demonstrated large improvements in fatigue impact. However, few rheumatology teams include a clinical psychologist, therefore, this study aims to examine whether conventional rheumatology teams can reproduce similar results, potentially widening intervention availability. Methods and analysis This is a multicentre, randomised, controlled trial of a group CB intervention for RA fatigue self-management, delivered by local rheumatology clinical teams. 7 centres will each recruit 4 consecutive cohorts of 10–16 patients with RA (fatigue severity ≥6/10). After consenting, patients will have baseline assessments, then usual care (fatigue self-management booklet, discussed for 5–6 min), then be randomised into control (no action) or intervention arms. The intervention, Reducing Arthritis Fatigue by clinical Teams (RAFT) will be cofacilitated by two local rheumatology clinicians (eg, nurse/occupational therapist), who will have had brief training in CB approaches, a RAFT manual and materials, and delivered an observed practice course. Groups of 5–8 patients will attend 6 x 2 h sessions (weeks 1–6) and a 1 hr consolidation session (week 14) addressing different self-management topics and behaviours. The primary outcome is fatigue impact (26 weeks); secondary outcomes are fatigue severity, coping and multidimensional impact, quality of life, clinical and mood status (to week 104). Statistical and health economic analyses will follow a predetermined plan to establish whether the intervention is clinically and cost-effective. Effects of teaching CB skills to clinicians will be evaluated qualitatively. Ethics and dissemination Approval was given by an NHS Research Ethics Committee, and participants will provide written informed consent. The copyrighted RAFT package will be freely available. Findings will be submitted to the National Institute for Health and Care Excellence, Clinical Commissioning Groups and all UK rheumatology departments. Trial registration number ISRCTN: 52709998; Protocol v3 09.02.2015.
    Keywords: Open access, Health services research, Rheumatology
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 7
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    Expression and Therapeutic Potential of SOX9 in Chordoma (2017)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2017-09-02
    Description: Purpose: Conventional chemotherapeutic agents are ineffective in the treatment of chordoma. We investigated the functional roles and therapeutic relevance of the sex-determining region Y (SRY)-box 9 (SOX9) in chordoma. Experimental Design: SOX9 expression was examined by immunohistochemistry (IHC) using 50 chordoma tissue samples. SOX9 expression in chordoma cell lines was examined by Western blot and immunofluorescent assays. We used synthetic human SOX9 siRNA to inhibit the expression of SOX9. Cell proliferation ability and cytotoxicity of inhibiting SOX9 were assessed by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) and clonogenic assays. The effect of SOX9 knockdown on chordoma cell motility was evaluated by a wound-healing assay and a Transwell invasion chamber assay. Knockdown of SOX9 induced apoptosis, cell-cycle arrest, as well as decreased expression of cancer stem cell markers were determined by Western blot and flow cytometric assays. The effect of the combination of SOX9 siRNA and the chemotherapeutic drug doxorubicin/cisplatin on chordoma cells was assessed by an MTT assay. Results: Tissue microarray and IHC analysis showed that SOX9 is broadly expressed in chordomas and that higher expression levels of SOX9 correlated with a poor prognosis. RNA interference (RNAi)-mediated knockdown of SOX9 inhibited chordoma cell growth, decreased cell motility, and induced apoptosis as well as cell-cycle arrest. Moreover, the combination of SOX9 inhibition and chemotherapeutic drugs had an enhanced anti-cancer effect on chordoma cells. Conclusions: Our results demonstrate that SOX9 plays a crucial role in chordoma. Targeting SOX9 provides a new rationale for treatment of chordoma. Clin Cancer Res; 23(17); 5176–86. ©2017 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
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  • 8
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    Long-term follow-up results of the multicenter phase II trial of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of standard tyrosine kinase inhibitor therapy (2016)
    Oxford University Press
    Details
    Publication Date: 2016-08-27
    Description: Background This investigator-initiated trial provided the justification for the phase III GRID study resulting in worldwide regulatory approval of regorafenib as a third-line therapy for patients with metastatic gastrointestinal stromal tumors (GIST). We report the genotype analyses, long-term safety, and activity results from this initial trial of regorafenib in GIST. Patients and methods The trial was conducted between February 2010 and January 2014, among adult patients with metastatic GIST, after failure of at least imatinib and sunitinib. Patients received regorafenib orally, 160 mg once daily, days 1–21 of a 28-day cycle. Clinical benefit rate (CBR), defined as complete or partial response (PR), or stable disease lasting ≥16 weeks per RECIST 1.1, progression-free survival (PFS), overall survival (OS), long-term safety data, and metabolic response by functional imaging were assessed. Results Thirty-three patients received at least one dose of regorafenib. The median follow-up was 41 months. CBR was documented in 25 of 33 patients [76%; 95% confidence interval (CI) 58% to 89%], including six PRs. The median PFS was 13.2 months (95% CI 9.2–18.3 months) including four patients who remained progression-free at study closure, each achieving clinical benefit for more than 3 years (range 36.8–43.5 months). The median OS was 25 months (95% CI 13.2–39.1 months). Patients whose tumors harbored a KIT exon 11 mutation demonstrated the longest median PFS (13.4 months), whereas patients with KIT/PDGFRA wild-type, non-SDH-deficient tumors experienced a median 1.6 months PFS ( P 〈 0.0001). Long-term safety profile is consistent with previous reports; hand–foot skin reaction and hypertension were the most common reasons for dose reduction. Notably, regorafenib induced objective responses and durable benefit in SDH-deficient GIST. Conclusions Long-term follow-up of patients with metastatic GIST treated with regorafenib suggests particular benefit among patients with primary KIT exon 11 mutations and those with SDH-deficient GIST. Dose modifications are frequently required to manage treatment-related toxicities. Clinical trial number NCT01068769.
    Print ISSN: 0923-7534
    Electronic ISSN: 1569-8041
    Topics: Medicine
    Published by Oxford University Press
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  • 9
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    Response to Comment on "Functional Analysis of a Complement Polymorphism (rs17611) Associated with Rheumatoid Arthritis" [LETTERS TO THE EDITOR] (2015)
    The American Association of Immunologists (AAI)
    Details
    Publication Date: 2015-06-20
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
    Published by The American Association of Immunologists (AAI)
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  • 10
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    CDK11 in Osteosarcoma (2012)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2012-09-01
    Description: Purpose: Identification of new targeted therapies is critical to improving the survival rate of patients with osteosarcoma. The goal of this study is to identify kinase based potential therapeutic target in osteosarcomas. Experimental Design: We used a lentiviral-based shRNA kinase library to screen for kinases which play a role in osteosarcoma cell survival. The cell proliferation assay was used to evaluate cell growth and survival. siRNA assays were applied to confirm the observed phenotypic changes resulting from the loss of kinase gene expression. CDK11 (PITSLRE) was identified as essential for the survival of osteosarcoma cells, and its expression was confirmed by Western blot analysis and immunohistochemistry. Overall patient survival was correlated with the CDK11 expression and its prognosis. The role of CDK11 expression in sustaining osteosarcoma growth was further evaluated in an osteosarcoma xenograft model in vivo . Results: Osteosarcoma cells display high levels of CDK11 expression. CDK11 expression knocked down by either lentiviral shRNA or siRNA inhibit cell growth and induce apoptosis in osteosarcoma cells. Immunohistochemical analysis showed that patients with osteosarcoma with high CDK11 tumor expression levels were associated with significantly shorter survival than patients with osteosarcoma with low level of tumor CDK11 expression. Systemic in vivo administration of in vivo ready siRNA of CDK11 reduced the tumor growth in an osteosarcoma subcutaneous xenograft model. Conclusions: We show that CDK11 signaling is essential in osteosarcoma cell growth and survival, further elucidating the regulatory mechanisms controlling the expression of CDK11 and ultimately develop a CDK11 inhibitor that may provide therapeutic benefit against osteosarcoma. Clin Cancer Res; 18(17); 4580–8. ©2012 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
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