bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Type 1 Diabetes Is Associated with T Cell Autoimmunity to Zinc Transporter 8
Authors: Dang MyLinh , Rockell Jennifer , Wagner Rebecca , Wenzlau Janet M. , Yu Liping , Hutton John C. , Gottlieb Peter A. , Davidson Howard W. 
Published: April 2011

Abstract
Recently we demonstrated that zinc transporter 8 (ZnT8) is a major target of autoantibodies in human type 1 diabetes (T1D). Because the molecules recognized by T1D autoantibodies are typically also targets of autoreactive T cells, we reasoned that this would likely be the case for ZnT8. To test this hypothesis, IFN-γ–producing T cells specific for ZnT8 in the peripheral blood of 35 patients with T1D (&lt;6 mo after onset at blood draw) and 41 age-matched controls were assayed by ELISPOT using a library of 23 overlapping dipeptide pools covering the entire 369 aa primary sequence. Consistent with our hypothesis, patients showed significantly higher T cell reactivity than the matched controls, manifest in terms of the breadth of the overall response and the magnitude of responses to individual pools. Therefore, the median number of pools giving positive responses (stimulation index ≥ 3) in the control group was 1.0 (range, 0–7) compared with 6.0 (range, 1–20; p &lt; 0.0001) for the patients. Similarly, the median stimulation index of positive responses in controls was 3.1 versus 5.0 in the patients (p &lt; 0.0001). Individually, 7 of 23 pools showed significant disease association (p &lt; 0.001), with several of the component peptides binding the disease associated HLA-DR3 (0301) and -DR4 (0401) molecules in vitro. We conclude that ZnT8 is also a major target of disease-associated autoreactive T cells in human T1D, and we suggest that reagents that target ZnT8-specific T cells could have therapeutic potential in preventing or arresting the progression of this disease.
CD40-Modulated Dual-Specificity Phosphatases MAPK Phosphatase (MKP)-1 and MKP-3 Reciprocally Regulate Leishmania major Infection
Authors: Srivastava Neetu , Sudan Raki , Saha Bhaskar 
Published: April 2011

Abstract
The macrophage-expressed CD40 regulates immune responses to Leishmania major infection by reciprocal signaling through p38 MAPK and ERK1/2. CD40-induced IL-10 or IL-12 plays crucial roles in the promotion or protection from L. major infection, respectively. Because p38 MAPK and ERK1/2 are dephosphorylated by dual-specificity MAPK phosphatases (MKPs), we tested the role of CD40 in the regulation of MKPs in L. major infection. MKP-1 expression and activity increased whereas MKP-3 expression and activity decreased in virulent L. major-infected macrophages. CD40 differentially regulated the expression and activity of MKP-1 and MKP-3, which, in turn, reciprocally regulated CD40-induced p38 MAPK and ERK1/2 phosphorylation and effector functions in macrophages. Triptolide, an inhibitor of MKP-1 expression, and lentivirally expressed MKP-1 short hairpin RNA enhanced CD40-induced anti-leishmanial functions and significantly protected susceptible BALB/c mice from L. major infection. Similarly, lentivirally overexpressed MKP-3 significantly reduced disease progression and parasite burden in susceptible BALB/c mice. Thus, to our knowledge, our data show for the first time that CD40 reciprocally regulates MKP-1 and MKP-3 expression and activity while the MKPs contribute to the reciprocal CD40 signaling-regulated anti-leishmanial functions. The findings reveal a novel parasite-devised immune evasion strategy and an effective target to redirect CD40-regulated immune responses.
Nerve Conduit Enhancement with Vomeronasal Organ Improves Rat Sciatic Functional Index in a Segmental Nerve Defect Model
Authors: Eward William C , Lipton Carter , Barnwell Jonathan , Smith Thomas L , Crowe Matthew , Koman L Andrew 
Published: April 2011

ABSTRACT

Background
Segmental nerve loss presents a challenge to the reconstructive surgeon. The best regenerative results are obtained by using autologous interpositional nerve grafts. While this method can be successful, it necessitates a second surgical step, sacrifices donor nerve function and depends upon a finite supply of potential donor nerves. Collagen nerve conduits are commercially available for reconstruction of segmental nerve defects. However, no conduit-based reconstructive strategy has been as successful as autograft reconstruction. We hypothesized that collagen nerve conduits used to bridge a sciatic nerve defect may be enhanced by grafting with vomeronasal organ (VNO), owing to the unique capacity for regeneration of this mammalian olfactory tissue.

Methods
21 rats underwent resection of a 1.0 cm segment of sciatic nerve. Seven rats underwent repair of the resultant nerve defect using a commercially available collagen nerve conduit (NeuraGen, Integra Life Sciences, Plainsboro NJ, USA). Seven rats underwent immediate repair of the nerve defect using the conduit filled with freshly harvested VNO allograft. An additional Seven rats underwent resection of a 4 mm segment of sciatic nerve and direct epineural repair. At 14 weeks postoperatively, all animals underwent walking track analysis. Toe prints were analyzed morphometrically to permit calculation of sciatic functional index (SFI). At 16 weeks postoperatively, rats were sacrificed and tissues were processed for histomorphometric analysis. This analysis included quantification of the number and diameter of myelinated axons as well as calculation of the axon density.

Results
All animals survived treatment without any serious surgical complications. All sciatic nerves were in continuity at sacrifice. All animals showed signs of sciatic denervation (decubitus ulcers, muscle atrophy) postoperatively. At 14 weeks, the mean sciatic functional index (SFI) was significantly higher in the VNO-enhanced group (p = 0.006) and the epineural repair (ER) groups (p = 0.004) than the conduit-only (CO) group. SFI was equivalent between VNO and ER groups (p = 0.338). Axon density was greater in the VNO (p = 0.013) and ER groups (p = 0.048) than in the CO group. Axon density was equivalent between the VNO and ER groups (p = 0.306).

Conclusions
In a rat sciatic nerve segmental defect model, modification of collagen nerve conduits to contain the pluripotent neuroepitheilial tissue vomeronasal organ (VNO) improves functional recovery and offers increased axon density relative to reconstruction with an empty conduit (CO).
The Cost-Effectiveness of the TriMed Sidewinder Plate for the Treatment of Weber B Ankle Fractures
Authors: Hewitt John D , Haytmanek Craig T , Tennant Joshua N , May Ryan C , Parekh Selene G 
Published: April 2011

ABSTRACT

Background
Ankle fractures are common injuries and many have indications for operative treatment. Newer plate designs have recently been introduced and have the potential to simplify and shorten the operative procedure. This study compares the cost of operative treatment of a lateral malleolar fracture between a novel plate design and a neutralization plate and lag screw approach.

Methods
A retrospective chart review was performed with institutional review board approval. All patients operatively treated for a Weber B lateral malleolar fracture were divided into two cohorts: an experimental group treated with a novel plate and a control group treated with a lag screw and neutralization plate. Cost of implants, operating room costs, and time to healing were compared between the two cohorts.

Results
The average implant cost for the novel plate design ($1,141) was significantly higher than that of the plate and lag screw construct ($208) (p < 0.0001). The average operating room costs were significantly lower for the experimental group ($4,410) compared to the control group ($6,037) (p < 0.01). The average time to union was significantly less in the experimental group (75 days) than in the control group (97 days) (p < 0.04).

Conclusions
Use of a novel plate design in this study was associated with decreased operating room costs and a quicker time to union compared to the use of a traditional construct. This may result from reduced amounts of dissection required to apply the novel plate and a more favorable biological environment for bone healing. The additional cost of new implant designs may be justified by quicker, simpler operative techniques, and enhanced healing.

Level of evidence
Therapeutic Level III.
Tibial Plateau Cysts at the Meniscal Root Insertions: Incidence and Association
Authors: Didolkar Manjiri M , Vinson Emily N 
Published: April 2011

ABSTRACT

Background
The purpose of this study is to identify a possible relationship between high T2-signal cyst-like foci in the tibial plateau at the meniscal root insertions and meniscal pathology.

Methods
Institutional review board approval was obtained for this retrospective study. HIPAA compliance was maintained throughout this study. Two radiologists reviewed 200 knee MRI examinations for tibial plateau cysts at the meniscal root insertion sites; meniscal tears and intrameniscal cysts were also noted. The knee MRI examinations were also evaluated for articular cartilage abnormalities of the medial and lateral tibial plateaus.

Results
Of the 200 knee examinations, 83(41.5%) demonstrated medial meniscal pathology and 47(23.5%) demonstrated lateral meniscal pathology. Twenty (10%) demonstrated cysts in at least one of the described locations; two knees had cysts in two separate locations. four (2%) examinations had cysts at the anterior horn medial meniscal insertion, and all four (100%) had medial meniscal pathology (p = 0.028). Eleven (5.5%) examinations demonstrated cysts at the posterior horn medial meniscal insertion, and eight (72.7%) had medial meniscal pathology (p = 0.031). five (2.5%) examinations demonstrated cysts at the anterior horn lateral meniscal insertion, and one (20%) had lateral meniscal pathology (p = 0.374). Two (1%) examinations demonstrated cysts at the posterior horn lateral meniscal insertion, and one (50%) had lateral meniscal pathology (p = 0.852).

Conclusions
Cysts at the meniscal insertions are often seen on knee MRI. Cysts located at the insertions of the medial meniscus have a statistically significant association with meniscal pathology.

Level of evidence
Level II, retrospective study with development of diagnostic criteria on the basis of consecutive patients.
The Combined Use of the Thermofluor Assay and ThermoQ Analytical Software for the Determination of Protein Stability and Buffer Optimization as an Aid in Protein Crystallization
Authors: Phillips Kevin , de la Peña Andres Hernandez 
Published: April 2011

AbstractThe Thermofluor assay, also referred to as a thermal shift assay or differential scanning fluorescence (DSF), is a fast and simple method that is based upon high‐throughput measurements of protein stability. The Thermofluor method can be performed on nearly all qPCR machines, meaning no special instrumentation is necessary, and can be used to validate the quality of protein preparations, screen for ligands or cofactors, and discover buffers and additives that maximize protein stability. This unit describes how to set up a Thermofluor method on several common models of qPCR instruments, how to prepare the samples for the assay, and how to run and analyze the resulting data. The unit also describes a 96‐well screen to determine optimal buffer conditions for protein stability, which may assist in protein crystallization, and details the use of custom software, developed specifically for the analysis of data from Thermofluor screens. Curr. Protoc. Mol. Biol. 94:10.28.1‐10.28.15. © 2011 by John Wiley & Sons, Inc.
DamIP: Using Mutant DNA Adenine Methyltransferase to Study DNA‐Protein Interactions In Vivo
Authors: Xiao Rui , Moore David D. 
Published: April 2011

AbstractDamIP is a new method for studying DNA‐protein interaction in vivo. A mutant form of DNA adenine methyltransferase (DamK9A) from E. coli is fused to the protein of interest and expressed. The fusion protein will bind to target binding sites and introduce N6‐adenine methylation in nearby sites in the genomic DNA. Methylated DNA fragments are enriched by immunopreciptation with an antibody that recognizes N6‐methyladenine, and can then be used for further analysis, e.g., real‐time PCR, microarray, or high‐throughput sequencing. This method is simple and does not require protein‐DNA crosslinking or a specific antibody to the protein of interest. This unit describes the application of this method for identification of DNA binding sites in vivo. Curr. Protoc. Mol. Biol. 94:21.21.1‐21.21.10. © 2011 by John Wiley & Sons, Inc.
A phase I safety study of enzastaurin plus bortezomib in the treatment of relapsed or refractory multiple myeloma
Authors: Ghobrial Irene M. , Munshi Nikhil C. , Harris Brianna N. , Shi Peipei , Porter Nichole M. , Schlossman Robert L. , Laubach Jacob P. , Anderson Kenneth C. , Desaiah Durisala , Myrand Scott P. , Wooldridge James E. , Richardson Paul G. , Abonour Rafat 
Published: April 2011

AbstractThe purpose of this study was to assess the safety and identify the recommended doses of enzastaurin and bortezomib in combination for future Phase II studies in patients with relapsed or refractory multiple myeloma. Three dose levels (DLs) of oral enzastaurin and intravenous bortezomib were used according to a conventional “3 + 3” design. A loading dose of enzastaurin (250 mg twice/day [BID]) on Day 1 was followed by enzastaurin 125 mg BID for 1 week, after which bortezomib was added (Cycle 1, 28 days, 1.0 mg/m2: Days 8, 11, 15, and 18; seven subsequent 21‐day cycles, 1.3 mg/m2: Days 1, 4, 8, and 11). Twenty‐three patients received treatment; all patients received prior systemic therapy. Most patients received ≥3 regimens; 17 patients were bortezomib‐refractory. A median of four treatment cycles (range 1–24) was completed. No dose‐limiting toxicities were observed; thus, DL 3 was the recommended Phase II dose. The most common drug‐related Grade 3/4 toxicities were thrombocytopenia (n = 6) and anemia (n = 2). No patients died on therapy. One patient (DL 1) achieved a very good partial response; three patients (DLs 2 and 3), a partial response; nine patients, stable disease; and four patients, progressive disease. The recommended Phase II doses in patients with relapsed or refractory multiple myeloma are as follows: enzastaurin loading dose of 375 mg three times/day on Day 1 followed by 250 mg BID, with bortezomib 1.3 mg/m2 on Days 1, 4, 8, and 11 of a 21‐day cycle. The combination was well‐tolerated and demonstrated some antimyeloma activity. Am. J. Hematol. 2011. © 2011 Wiley‐Liss, Inc.
Breast cancer risk by occupation and industry: Analysis of the CECILE study, a population‐based case–control study in France
Authors: Villeneuve Sara , Févotte Joëlle , Anger Antoinette , Truong Thérèse , Lamkarkach Farida , Gaye Oumar , Kerbrat Pierre , Arveux Patrick , Miglianico Laurent , Imbernon Ellen , Guénel Pascal 
Published: April 2011

AbstractBackgroundIt has been suggested that certain occupational exposures may play a role in breast cancer etiology. The recognition of high‐risk occupations may give clues about potential mammary carcinogens in the work place.MethodsWe conducted a population‐based case–control study in France including 1,230 breast cancer cases and 1,315 population controls with detailed information on lifetime work history. Odds ratios for women ever employed in an occupation or industry were adjusted for well‐established risk factors for breast cancer.ResultsAdjusted odds ratios were marginally increased in some white‐collar occupations, as well as in textile workers (2.4; 95% CI [0.9–6.0]), rubber and plastics product makers (1.8; 95% CI [0.9–3.5]), and in women employed for more than 10 years as nurses (1.4; 95% CI [0.9–2.1]) and as tailors/dressmakers (1.5; 95% CI [0.9–2.6]). The incidence of breast cancer was increased among women employed in the manufacture of chemicals, of non‐metallic mineral products, and decreased among women in agriculture.ConclusionsThese findings suggest a possible role of occupational exposures in breast cancer, including night‐shift work, solvents and endocrine disrupting chemicals and require further studies with detailed assessment of occupational exposures. Am. J. Ind. Med. 54:499–509, 2011. © 2011 Wiley‐Liss, Inc.
Wisconsin stillbirth services program: A multifocal approach to stillbirth analysis
Authors: VanderWielen Beth , Zaleski Christina , Cold Christopher , McPherson Elizabeth 
Published: April 2011

AbstractStillbirth accounts for about 26,000 deaths annually in the US. In most previous studies, discrete causes are identified in less than half of all stillbirths. In order to identify causes and non‐causal but potentially contributing abnormalities, we analyzed 416 of the most recent (2004–2010) Wisconsin Stillbirth Service Program (WiSSP) cases from a multifocal approach. In 70% of cases a cause sufficient to independently explain the demise was identified including 40% placental, 21.5% fetal, and 12.7% maternal. Results for stillbirths and second trimester miscarriages did not differ significantly. In 95% of cases at least one cause or non‐causal abnormality was recognizable, and in two‐thirds of cases, more than one cause or non‐causal abnormality was identified. In cases with maternal cause, the placenta was virtually always abnormal. Both placentas (59%) and fetuses (38%) were frequently smaller than expected for gestational age. Previous miscarriage and/or stillbirth were risk factors for second and third trimester losses, with 35% of previous pregnancies ending in fetal demise. Recommendations include complete evaluation of all second and third trimester losses with special attention to placental pathology and thorough investigation for multiple causes or abnormalities whether or not a primary cause is initially recognized. Improved understanding of the causes of late miscarriage and stillbirth may contribute to recognition and management of pregnancies at risk and eventually to prevention of stillbirth. © 2011 Wiley‐Liss, Inc.
The influence of experimental manipulations on chewing speed during in vivo laboratory research in tufted capuchins (Cebus apella)
Authors: Thompson C.L. , Donley E.M. , Stimpson C.D. , Horne W.I. , Vinyard C.J. 
Published: April 2011

AbstractEven though in vivo studies of mastication in living primates are often used to test functional and adaptive hypotheses explaining primate masticatory behavior, we currently have little data addressing how experimental procedures performed in the laboratory influence mastication. The obvious logistical issue in assessing how animal manipulation impacts feeding physiology reflects the difficulty in quantifying mechanical parameters without handling the animal. In this study, we measured chewing cycle duration as a mechanical variable that can be collected remotely to: 1) assess how experimental manipulations affect chewing speed in Cebus apella, 2) compare captive chewing cycle durations to that of wild conspecifics, and 3) document sources of variation (beyond experimental manipulation) impacting captive chewing cycle durations. We find that experimental manipulations do increase chewing cycle durations in C. apella by as much as 152 milliseconds (ms) on average. These slower chewing speeds are mainly an effect of anesthesia (and/or restraint), rather than electrode implantation or more invasive surgical procedures. Comparison of captive and wild C. apella suggest there is no novel effect of captivity on chewing speed, although this cannot unequivocally demonstrate that masticatory mechanics are similar in captive and wild individuals. Furthermore, we document significant differences in cycle durations due to inter‐individual variation and food type, although duration did not always significantly correlate with mechanical properties of foods. We advocate that the significant reduction in chewing speed be considered as an appropriate qualification when applying the results of laboratory‐based feeding studies to adaptive explanations of primate feeding behaviors. Am J Phys Anthropol, 2011. © 2011 Wiley‐Liss, Inc.
Japanese macaque encephalomyelitis: A spontaneous multiple sclerosis–like disease in a nonhuman primate
Authors: Axthelm Michael K. , Bourdette Dennis N. , Marracci Gail H. , Su Weiping , Mullaney Elizabeth T. , Manoharan Minsha , Kohama Steven G. , Pollaro Jim , Witkowski Ellen , Wang Paul , Rooney William D. , Sherman Lawrence S. , Wong Scott W. 
Published: April 2011

AbstractObjective:To describe Japanese macaque encephalomyelitis (JME), a spontaneous inflammatory demyelinating disease occurring in the Oregon National Primate Research Center's (ONPRC) colony of Japanese macaques (JMs, Macaca fuscata).Methods:JMs with neurologic impairment were removed from the colony, evaluated, and treated with supportive care. Animals were humanely euthanized and their central nervous systems (CNSs) were examined.Results:ONPRC's JM colony was established in 1965 and no cases of JME occurred until 1986. Since 1986, 57 JMs spontaneously developed a disease characterized clinically by paresis of 1 or more limbs, ataxia, or ocular motor paresis. Most animals were humanely euthanized during their initial episode. Three recovered, later relapsed, and were then euthanized. There was no gender predilection and the median age for disease was 4 years. Magnetic resonance imaging of 8 cases of JME revealed multiple gadolinium‐enhancing T1‐weighted hyperintensities in the white matter of the cerebral hemispheres, brainstem, cerebellum, and cervical spinal cord. The CNS of monkeys with JME contained multifocal plaque‐like demyelinated lesions of varying ages, including acute and chronic, active demyelinating lesions with macrophages and lymphocytic periventricular infiltrates, and chronic, inactive demyelinated lesions. A previously undescribed gamma‐herpesvirus was cultured from acute JME white matter lesions. Cases of JME continue to affect 1% to 3% of the ONPRC colony per year.Interpretation:JME is a unique spontaneous disease in a nonhuman primate that has similarities with multiple sclerosis (MS) and is associated with a novel simian herpesvirus. Elucidating the pathogenesis of JME may shed new light on MS and other human demyelinating diseases. ANN NEUROL 2011;