bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human T cell leukaemia virus type 2 tax protein mediates CC-chemokine expression in peripheral blood mononuclear cells via the nuclear factor kappa B canonical pathway
Authors: Barrios C S , Castillo L , Zhi H , Giam C-Z , Beilke M A 
Published: October 2013

Summary
Retroviral co-infections with human immunodeficiency virus type-1 (HIV-1) and human T cell leukaemia virus type 1 (HTLV-1) or type 2 (HTLV-2) are prevalent in many areas worldwide. It has been observed that HIV-1/HTLV-2 co-infections are associated with slower rates of CD4+ T cell decline and delayed progression to AIDS. This immunological benefit has been linked to the ability of Tax2, the transcriptional activating protein of HTLV-2, to induce the expression of macrophage inflammatory protein (MIP)-1α/CCL3, MIP-1β/CCL4 and regulated upon activation normal T cell expressed and secreted (RANTES)/CCL5 and to down-regulate the expression of the CCR5 co-receptor in peripheral blood mononuclear cells (PBMCs). This study aimed to assess the role of Tax2-mediated activation of the nuclear factor kappa B (NF-κB) signalling pathway on the production of the anti-viral CC-chemokines MIP-1α, MIP-1β and RANTES. Recombinant Tax1 and Tax2 proteins, or proteins expressed via adenoviral vectors used to infect cells, were tested for their ability to activate the NF-κB pathway in cultured PBMCs in the presence or absence of NF-κB pathway inhibitors. Results showed a significant release of MIP-1α, MIP-1β and RANTES by PBMCs after the activation of p65/RelA and p50. The secretion of these CC-chemokines was significantly reduced (P &lt; 0·05) by canonical NF-κB signalling inhibitors. In conclusion, Tax2 protein may promote innate anti-viral immune responses through the activation of the canonical NF-κB pathway.
Follicular bronchiolitis as phenotype associated with CD25 deficiency
Authors: Bezrodnik L , Caldirola M S , Seminario A G , Moreira I , Gaillard M I 
Published: October 2013

Summary
Regulatory T cells [Tregs; CD4+CD25+ forkhead box protein 3 (FoxP3+)] are subsets of T cells involved in the maintenance of peripheral self-tolerance by actively suppressing the activation and expansion of autoreactive T cells. Signalling through the interleukin-2 receptor (IL-2R) contributes to T cell tolerance by controlling three important aspects of regulatory T cell (Treg) biology. CD25 is the α-chain of the IL-2R that, in concert with the β-chain and γ-chain, constitutes the complete IL-2R. CD25 contributes only to IL-2 binding affinity but not to the recruitment of signalling molecules. However, its importance in the development of a normal immune response is emphasized by the finding that a truncation mutant of CD25 results in an immunodeficiency in humans characterized by an increased susceptibility to viral, bacterial and fungal infections. In 1997, Sharfe et al. described an infant with severe bacterial, viral and fungal infections. Counts of autologous T lymphocytes were moderately low, T cells displayed a weak proliferative response to mitogens in vitro and the patient displayed no rejection of an allogeneic skin graft. However, unlike children with severe combined immunodeficiency (SCID), besides not having circulating T cells, the patient also developed peripheral lymphocytic proliferation and autoimmune primary biliary cirrhosis. We present the first female Argentine patient with mutation in CD25 associated with chronic and severe inflammatory lung disease (follicular bronchiolitis with lymphocyte hyperplasia), eczema and infections. She has no expression of CD25 on CD4+T cells and an extremely low amount of Tregs. The molecular study confirmed homozygous missense mutation in the alpha subunit of the IL-2 receptor (CD25αR) (c. 122 a &gt; c; p. Y41S).
CD19 as a therapeutic target in a spontaneous autoimmune polyneuropathy
Authors: Abraham P M , Quan S H , Dukala D , Soliven B 
Published: October 2013

SummarySpontaneous autoimmune polyneuropathy (SAP) in B7-2 knock-out non-obese diabetic (NOD) mice is mediated by myelin protein zero (P0)-reactive T helper type 1 (Th1) cells. In this study, we investigated the role of B cells in SAP, focusing on CD19 as a potential therapeutic target. We found that P0-specific plasmablasts and B cells were increased in spleens of SAP mice compared to wild-type NOD mice. Depletion of B cells and plasmablasts with anti-CD19 monoclonal antibody (mAb) led to attenuation of disease severity when administered at 5 months of age. This was accompanied by decreased serum immunoglobulin (Ig)G and IgM levels, depletion of P0-specific plasmablasts and B cells, down-regulation/internalization of surface CD19 and increased frequency of CD4+ regulatory T cells in spleens. We conclude that B cells are crucial to the pathogenesis of SAP, and that CD19 is a promising B cell target for the development of disease-modifying agents in autoimmune neuropathies.
Myasthenia gravis: an update for the clinician
Authors: Sieb J P 
Published: October 2013

Summary
This paper provides a thorough overview of the current advances in diagnosis and therapy of myasthenia gravis (MG). Nowadays the term ‘myasthenia gravis’ includes heterogeneous autoimmune diseases, with a postsynaptic defect of neuromuscular transmission as the common feature. Myasthenia gravis should be classified according to the antibody specificity [acetylcholine, muscle-specific receptor tyrosine kinase (MuSK), low-density lipoprotein receptor-related protein 4 (LRP4), seronegative], thymus histology (thymitis, thymoma, atrophy), age at onset (in children; aged less than or more than 50 years) and type of course (ocular or generalized). With optimal treatment, the prognosis is good in terms of daily functions, quality of life and survival. Symptomatic treatment with acetylcholine esterase inhibition is usually combined with immunosuppression. Azathioprine still remains the first choice for long-term immunosuppressive therapy. Alternative immunosuppressive options to azathioprine include cyclosporin, cyclophosphamide, methotrexate, mycophenolate mofetil and tacrolimus. Rituximab is a promising new drug for severe generalized MG. Emerging therapy options include belimumab, eculizumab and the granulocyte– macrophage colony-stimulating factor. One pilot study on etanercept has given disappointing results. For decades, thymectomy has been performed in younger adults to improve non-paraneoplastic MG. However, controlled prospective studies on the suspected benefit of this surgical procedure are still lacking. In acute exacerbations, including myasthenic crisis, intravenous immunoglobulin, plasmapheresis and immunoadsorption are similarly effective.
Neuroprotection effect of interleukin (IL)-17 secreted by reactive astrocytes is emerged from a high-level IL-17-containing environment during acute neuroinflammation
Authors: Hu M H , Zheng Q F , Jia X Z , Li Y , Dong Y C , Wang C Y , Lin Q Y , Zhang F Y , Zhao R B , Xu H W , Zhou J H , Yuan H P , Zhang W H , Ren H 
Published: October 2013

SummaryAn increase in interleukin (IL)-17A-producing cells, particularly at sites of tissue inflammation, is observed frequently, yet the mechanism is not fully understood. This study aims to dissect the role of IL-17 in autoimmunity-mediated neuroinflammation. The cytokine milieu containing elevated IL-17, which often appears in active states of autoimmunity, was mimicked in vitro by a supernatant obtained from rat peripheral blood monocytes stimulated with phorbol mystistate acetate (PMA)/ionomycin. The application of such inflammatory media on only primary cultured cerebellar granule neurones resulted in significant apoptosis, but the presence of astrocytes largely prevented the effect. The supernatants of the stimulated astrocytes, especially those that contained the highest level of IL-17, achieved the best protection, and this effect could be blocked by anti-IL-17 antibodies. Protein IL-17 inhibited intracellular calcium increase and protected the neurones under inflammatory attack from apoptosis. IL-17, but not interferon (IFN)-γ, in the inflammatory media contributed to astrocyte secretion of IL-17, which depended on the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway activation. The astrocytes that were treated with IL-17 alone or with prolonged treatment of the inflammatory media failed to produce sufficient levels of IL-17. Moreover, confirmatory data were obtained in vivo in a monophasic experimental autoimmune uveitis (EAU) in Lewis rats; in this preparation, the high-level IL-17-containing the cytokine milieu was demonstrated, along with IL-17 secretion by the resident neural cells. The antagonism of IL-17 at a late stage disturbed the disease resolution and resulted in significant neural apoptosis. Our data show a dynamic role of IL-17 in the maintenance of homeostasis and neuroprotection in active neuroinflammation.
Effects of correction of vitamin D insufficiency on serum osteocalcin and glucose metabolism in obese children
Authors: Poomthavorn Preamrudee , Nantarakchaikul Palinee , Mahachoklertwattana Pat , Chailurkit La‐or , Khlairit Patcharin 
Published: October 2013

SummaryObjectivesOsteocalcin (OCN) and vitamin D insufficiency (VDI) have been shown to be associated with abnormal glucose metabolism (GluMet). Whether correction of VDI affects serum OCN is unknown. This study evaluated the effects of correction of VDI on OCN and GluMet, and determined the associations of OCN with 25‐hydroxyvitamin D (25‐OHD) and GluMet.Design, patients and measurementsThis study involved 230 obese children in a cross‐sectional part and 72 participants in a prospective part in which children with VDI were treated with vitamin D2 at a dose of 20 000 IU daily for 28 days. All 230 children underwent an oral glucose tolerance test and had their serum total and undercarboxylated OCNs and 25‐OHD measured. Forty of 72 children were reassessed for the GluMet and serum total and undercarboxylated OCNs and 25‐OHD after the vitamin D2 treatment.ResultsIn the prospective part, correction of VDI by raising mean (SD) 25‐OHD of 51·5 (12·3) to 141·8 (40·8) nmol/l resulted in an improvement of their GluMet and increase in their whole‐body insulin sensitivity index with no changes in their OCN measures. In the cross‐sectional part, after adjustments for age, sex and puberty, the total (β = 0·322) and undercarboxylated OCNs (β = 0·315) were positively associated with insulinogenic index, which is an index of insulin secretion (P = 0·034 and 0·037, respectively) in the group of prediabetic and diabetic children.ConclusionsCorrection of VDI increased insulin sensitivity and improved GluMet, but had no effect on serum OCN measures. OCN was associated with increased insulin secretion in children with abnormal GluMet.
131I‐MIBG therapy for malignant paraganglioma and phaeochromocytoma: systematic review and meta‐analysis
Authors: van Hulsteijn L. T. , Niemeijer N. D. , Dekkers O. M. , Corssmit E. P. M. 
Published: October 2013

SummaryBackground131I‐MIBG therapy can be used for palliative treatment of malignant paraganglioma and phaeochromocytoma. The main objective of this study was to perform a systematic review and meta‐analysis assessing the effect of 131I‐MIBG therapy on tumour volume in patients with malignant paraganglioma/phaeochromocytoma.MethodsA literature search was performed in December 2012 to identify potentially relevant studies. Main outcomes were the pooled proportions of complete response, partial response and stable disease after radionuclide therapy. A meta‐analysis was performed with an exact likelihood approach using a logistic regression with a random effect at the study level. Pooled proportions with 95% confidence intervals (CI) were reported.ResultsSeventeen studies concerning a total of 243 patients with malignant paraganglioma/phaeochromocytoma were treated with 131I‐MIBG therapy. The mean follow‐up ranged from 24 to 62 months. A meta‐analysis of the effect of 131I‐MIBG therapy on tumour volume showed pooled proportions of complete response, partial response and stable disease of, respectively, 0·03 (95% CI: 0·06–0·15), 0·27 (95% CI: 0·19–0·37) and 0·52 (95% CI: 0·41–0·62) and for hormonal response 0·11 (95% CI: 0·05–0·22), 0·40 (95% CI: 0·28–0·53) and 0·21 (95% CI: 0·10–0·40), respectively. Separate analyses resulted in better results in hormonal response for patients with paraganglioma than for patients with phaeochromocytoma.ConclusionsData on the effects of 131I‐MIBG therapy on malignant paraganglioma/phaeochromocytoma suggest that stable disease concerning tumour volume and a partial hormonal response can be achieved in over 50% and 40% of patients, respectively, treated with 131I‐MIBG therapy. It cannot be ruled out that stable disease reflects not only the effect of MIBG therapy, but also (partly) the natural course of the disease.
When would I use medical therapies for the treatment of primary hyperparathyroidism?
Authors: Crowley Rachel K. , Gittoes Neil J. 
Published: October 2013

SummaryAlthough there may be controversy surrounding the indications for parathyroidectomy in primary hyperparathyroidism, it remains the only accepted definitive therapy. However, even if parathyroidectomy is indicated, some patients refuse surgery, are medically unfit or have residual or recurrent disease inaccessible to further surgery. Some of these patients may be suitable for long‐term observation but others require intervention for management of symptomatic or moderate to severe hypercalcaemia, loss of bone mineral density or renal calculi. The selection of a suitable therapy for each patient should be individualized.
The role of ultrasound findings in the management of thyroid nodules with atypia or follicular lesions of undetermined significance
Authors: Yoo Won Sang , Choi Hoon Sung , Cho Sun Wook , Moon Jae Hoon , Kim Kyung Won , Park Hyo Jin , Park So Yeon , Choi Sang Il , Choi Sung Hee , Lim Soo , Yi Ka Hee , Park Do Joon , Jang Hak Chul , Park Young Joo 
Published: October 2013

SummaryBackgroundAtypia or follicular lesions of undetermined significance (AUS/FLUS) is a broad cytological category in the Bethesda system for classifying thyroid cytology. This study investigated the diagnostic accuracy of ultrasound (US) analysis of thyroid nodules with AUS/FLUS.Patients and MethodsOf 5062 subjects with nodules subjected to fine‐needle aspiration cytology (FNACs) at our institution from January 2010 through May 2012, 383 met the Bethesda criteria for AUS/FLUS. After excluding subjects who had a history of thyroid cancer, who only underwent repeat FNA or who underwent no further examinations, we selected 249 subjects who had subsequently undergone a core‐needle biopsy and/or surgery. Of these, 100 were found to have malignant nodules (40·2%), 122 had benign nodules (49%), and 27 had nodules with indeterminate status (10·8%). We compared specific US parameters, including size, location, content, shape, margin, echogenicity, echotexture and calcification across these subject groups.ResultsMultivariate analysis revealed that malignancy was associated with taller‐than‐wide shape (TDW) (OR = 8·43, P = 0·002), ill‐defined margin (OR = 3·23, P = 0·002) and marked hypoechogenicity. (OR = 3·61, P = 0·001). The specificity and positive predictive values of TDW were 98% and 90·6%,respectively. The specificity and positive predictive values of ‘TDW and marked hypoechogenicity’ were both 100%.ConclusionUS findings play a complementary role in the diagnosis of thyroid nodules with AUS/FLUS. In case of highly suspicious US findings such as ‘TDW and marked hypoechogenicity’, could be very helpful in the diagnosis of malignancy.
Socioeconomic factors associated with pediatric diabetic ketoacidosis admissions in Southern West Virginia
Authors: Lewis Kevin R. , Clark Crystal , Velarde Maria C. 
Published: October 2013

SummaryObjectiveDiabetic Ketoacidosis (DKA) is a well‐known complication in children with type 1 diabetes mellitus (T1DM) with a mortality rate estimated at 2%. A previous study identified that T1DM children of non‐Caucasian race with Medicaid insurance had increased incidence of DKA admissions. The aim of this study is to identify the socioeconomic factors associated with DKA admissions in West Virginia (WV).Design and methodsRetrospective chart review of patients admitted to the paediatric intensive care unit with DKA in Charleston, WV from January 2007–December 2010. Included subjects were 1–18 years of age and those with type 1 diabetes of >6 months duration. Admission rates were compared with the normal population distribution in WV. The data collection tool included multiple socioeconomic factors and HbA1c.ResultsWe reviewed a total of 167 patients with an admitting diagnosis of DKA; 57% were female, 43% male. Average age was 13·5 years ± 2·7; 56·4% were covered by Medicaid/Chips (WV state insurance) and 43·6% by commercial payers. 11·9% were African American and 88·1% were Caucasian. The average HbA1c was 10·85 ± 2·36%. Higher risks for DKA included those with HbA1c >14%, African American children (OR 17·4, CI 4–73) and children with Medicaid/Chips insurance (OR 9·3, 95% CI 1·1–76·2).ConclusionsThis study identifies socioeconomic factors associated with children admitted for DKA in WV. Patients at higher risk for DKA include those with elevated HbA1c, African American race and those covered by Medicaid/CHIPS (thereby presumed lower socioeconomic status). Findings can be utilized to identify patients at highest risk for DKA and implementation of prevention strategies.
Twin studies in inherited eye disease
Authors: Nag Abhishek , Hammond Christopher J 
Published: October 2013

AbstractEye diseases represent a significant source of health impairment in humans. Twin studies offer an excellent model to dissect the genetic basis of human diseases. In this review, we discuss the potential advantages of using twin‐based studies in investigating the genetics of eye diseases – from heritability estimation to identifying underlying genetic and epigenetic changes. We also discuss some of the notable findings of twin studies exploring the genetics of eye diseases. Finally, we suggest other novel approaches that can be utilized to tap the potential of twin studies to provide a more complete understanding of genetic factors underlying ocular diseases.
Chromosome 9p21 primary open‐angle glaucoma susceptibility locus: a review
Authors: Ng Soo Khai , Casson Robert J , Burdon Kathryn P , Craig Jamie E 
Published: October 2013

AbstractPrimary open‐angle glaucoma (POAG) is a genetically complex disease. Genome‐wide association study (GWAS) is a particularly useful tool in the search for genetic contributions to glaucoma. Recently, chromosome 9p21 has become a major focus of research endeavour, with multiple genome‐wide association studies suggesting associations to POAG. Herein, we provide a review of the chromosome 9p21 susceptibility locus as a risk factor for POAG.
Clear corneal vitrectomy combined with phacoemulsification and foldable intraocular lens implantation
Authors: Iwase Takeshi , Oveson Brian C , Jo Young‐Joon 
Published: October 2013

AbstractBackgroundWe have developed a technique for the treatment of cataract and epiretinal membrane using a 25‐gauge vitrectomy system through corneal ports.DesignRandomized, prospective study, Toyama Prefectural Central Hospital, Toyama, Japan.ParticipantsTwenty eyes of equal patients scheduled for cataract surgery combined with vitrectomy.MethodsTwenty eyes with cataract and epiretinal membrane were received treatment with our newly developed system (clear corneal vitrectomy) or the standard 25‐gauge pars plana vitrectomy with corneal incision cataract surgery. The newly developed system uses 0.5‐mm wide corneal side ports located at the superonasal, superotemporal and inferotemporal positions. After phacoemulsification using corneal incision, an infusion cannula was inserted from the inferotemporal port. Then core 25‐gauge vitrectomy was performed using the corneal three port. After the epiretinal membrane was removed using forceps, an intraocular lens was implanted into the capsular bag. Finally, all corneal incision wounds were hydrated.Main Outcome MeasurementVisual acuity, intraocular pressure, corneal thickness, corneal endothelial cell and ocular inflammation were examined.ResultsAll procedures were uncomplicated in both groups. There was no leakage of aqueous humour from the corneal wounds in the developed system. There were no significant differences in visual acuity, corneal thickness and endothelial cell density loss.ConclusionsClear corneal vitrectomy would be a good option for selected cases with cataract and vitreoretinal diseases.
Genetic study of diabetic retinopathy: recruitment methodology and analysis of baseline characteristics
Authors: Kaidonis Georgia , Abhary Sotoodeh , Daniell Mark , Gillies Mark , Fogarty Rhys , Petrovsky Nikolai , Jenkins Alicia , Essex Rohan , Chang John H , Pal Bishwanath , Hewitt Alex W , Burdon Kathryn P , Craig Jamie E 
Published: October 2013

AbstractBackgroundDiabetic retinopathy (DR) is a blinding disease of increasing prevalence that is caused by a complex interplay of genetic and environmental factors. Here we describe the patient recruitment methodology, case and control definitions, and clinical characteristics of a study sample to be used for genome‐wide association analysis to detect genetic risk variants of DR.MethodsOne thousand six hundred sixty‐nine participants with either type 1 (T1) or type 2 (T2) diabetes mellitus (DM) aged 18 to 95 years were recruited in Australian hospital clinics. Individuals with T2DM had disease duration of at least 5 years and were taking oral hypoglycaemic medication, and/or insulin therapy. Participants underwent ophthalmic examination. Medical history and biochemistry results were collected. Venous blood was obtained for genetic analysis.ResultsSix hundred eighty‐three diabetic cases (178 T1DM and 505 T2DM participants) with sight‐threatening DR, defined as severe non‐proliferative DR, proliferative DR or diabetic macular oedema were included in this analysis. Eight hundred twelve individuals with DM but no DR or minimal non‐proliferative DR were recruited as controls (191 with T1DM and 621 with T2DM). The presence of sight‐threatening DR was significantly correlated with DM duration, hypertension, nephropathy, neuropathy, HbA1C and body mass index. Diabetic macular oedema was associated with T2DM (P < 0.001), whereas proliferative DR was associated with T1DM (P < 0.001).ConclusionsAdoption of a case‐control study design involving extremes of the DR phenotype makes this a suitable cohort, for a well‐powered genome‐wide association study to detect genetic risk variants for DR.