bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic approach for the identification of novel, serologically reactive recombinant Varicella-Zoster Virus (VZV) antigens
Authors: Vizoso Pinto Maria G , Pfrepper Klaus-Ingmar , Janke Tobias , Noelting Christina , Sander Michaela , Lueking Angelika , Haas Juergen , Nitschko Hans , Jaeger Gundula , Baiker Armin 
Published: August 2010

Abstract

Background
Varicella-Zoster virus causes chickenpox upon primary infection and shingles after reactivation. Currently available serological tests to detect VZV-specific antibodies are exclusively based on antigens derived from VZV-infected cells.

Results
We present a systematic approach for the identification of novel, serologically reactive VZV antigens. Therefore, all VZV open reading frames were cloned into a bacterial expression vector and checked for small scale recombinant protein expression. Serum profiling experiments using purified VZV proteins and clinically defined sera in a microarray revealed 5 putative antigens (ORFs 1, 4, 14, 49, and 68). These were rearranged in line format and validated with pre-characterized sera.

Conclusions
The line assay confirmed the seroreactivity of the identified antigens and revealed its suitability for VZV serodiagnostics comparable to commercially available VZV-ELISA. Recombinant ORF68 (gE) proved to be an antigen for high-confidence determination of VZV serostatus. Furthermore, our data suggest that a serological differentiation between chickenpox and herpes zoster may be possible by analysis of the IgM-portfolio against individual viral antigens.
Cuticle thickening associated with pyrethroid resistance in the major malaria vector Anopheles funestus
Authors: Wood O R , Hanrahan S , Coetzee M , Koekemoer L L , Brooke B D 
Published: August 2010

Abstract

Background
Malaria in South Africa is primarily transmitted by Anopheles funestus Giles. Resistance to pyrethroid insecticides in An. funestus in northern Kwazulu/Natal, South Africa, and in neighbouring areas of southern Mozambique enabled populations of this species to increase their ranges into areas where pyrethroids were being exclusively used for malaria control. Pyrethroid resistance in southern African An. funestus is primarily conferred by monooxygenase enzyme metabolism. However, selection for this resistance mechanism is likely to have occurred in conjunction with other factors that improve production of the resistance phenotype. A strong candidate is cuticle thickening. This is because thicker cuticles lead to slower rates of insecticide absorption, which is likely to increase the efficiency of metabolic detoxification.

Results
Measures of mean cuticle thickness in laboratory samples of female An. funestus were obtained using scanning electron microscopy (SEM). These females were drawn from a laboratory colony carrying the pyrethroid resistance phenotype at a stable rate, but not fixed. Prior to cuticle thickness measurements, these samples were characterised as either more or less tolerant to permethrin exposure in one experiment, and either permethrin resistant or susceptible in another experiment. There was a significant and positive correlation between mean cuticle thickness and time to knock down during exposure to permethrin. Mean cuticle thickness was significantly greater in those samples characterised either as more tolerant or resistant to permethrin exposure compared to those characterised as either less tolerant or permethrin susceptible. Further, insecticide susceptible female An. funestus have thicker cuticles than their male counterparts.

Conclusion
Pyrethroid tolerant or resistant An. funestus females are likely to have thicker cuticles than less tolerant or susceptible females, and females generally have thicker cuticles than males. In pyrethroid resistant An. funestus, this increase in cuticle thickness is likely to have developed as an auxiliary to the primary mode of pyrethroid resistance which is based on enzyme-mediated detoxification.
Tissue-resident mesenchymal stem cells attract peripheral blood neutrophils and enhance their inflammatory activity in response to microbial challenge
Authors: Brandau Sven , Jakob Mark , Hemeda Hatim , Bruderek Kirsten , Janeschik Sandra , Bootz Friedrich , Lang Stephan 
Published: August 2010

Abstract
Stimulation by LPS elicits proinflammatory functions in MSCs that result in the recruitment and activation of polymorphonuclear granulocytes.
Human MSCs may respond to TLR ligation, and recent research has suggested that many tissues contain tissue-specific MSCs, possibly located in periendothelial and perivascular regions. At present, the functional consequences of these findings are unclear. We hypothesized that tissue-specific MSCs could play an instructional role during early phases of bacterial challenge. To investigate this hypothesis further, we set up a coculture system of glandular MSCs and peripheral blood neutrophils so that we could analyze the cellular interactions of these cells in response to LPS challenge. We found that stimulation with bacterial endotoxin induced chemokine receptor expression and mobility of MSCs. Activated MSCs secreted large amounts of inflammatory cytokines and recruited neutrophils in an IL-8- and MIF-dependent manner. Recruited and activated neutrophils showed a prolonged lifespan, an increased expression of inflammatory chemokines, and an enhanced responsiveness toward subsequent challenge with LPS. Our findings demonstrate a complex, functional interaction between tissue-resident MSCs and peripheral blood neutrophils upon bacterial challenge and suggest a role for MSCs in the early phases of pathogen challenge, when classical immune cells have not been recruited yet.
A Phase II Study of Pazopanib in Patients with Recurrent or Metastatic Invasive Breast Carcinoma: A Trial of the Princess Margaret Hospital Phase II Consortium
Authors: Taylor Sara K. , Chia Stephen , Dent Susan , Clemons Mark , Agulnik Mark , Grenci Pamela , Wang Lisa , Oza Amit M. , Ivy Percy , Pritchard Kathleen I. , Leighl Natasha B. 
Published: August 2010

AbstractPurpose.Angiogenesis is an important hallmark of breast cancer growth and progression. Pazopanib, an oral small molecule inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and KIT, has activity across a range of solid tumors. We evaluated the activity of single-agent pazopanib in recurrent or metastatic breast cancer (MBC).Patients and Methods.Patients with recurrent breast cancer or MBC, treated with up to two prior lines of chemotherapy, were eligible to receive pazopanib, 800 mg daily until progression. The primary endpoint was the objective response rate as measured by Response Evaluation Criteria in Solid Tumors. Secondary endpoints included time to progression, the stable disease rate, and toxicity. Using a two-stage design, confirmed response in three of 18 patients was required to proceed to stage 2.Results.Twenty evaluable patients were treated, with a median age of 56 years; 70% were estrogen receptor positive, all were human epidermal growth factor receptor 2 negative. The majority had one or two prior lines of chemotherapy. One patient (5%) had a partial response, 11 (55%) had stable disease (SD) [four (20%) with SD ≥6 months], and seven (35%) had progressive disease as their best response. One (5%) was not evaluable. The median time to progression was 5.3 months. Pazopanib did not cause significant severe toxicity aside from grade 3–4 transaminitis, hypertension, and neutropenia in three patients each (14% each) and grade 3 gastrointestinal hemorrhage in one patient (5%).Conclusion.Pazopanib provides disease stability in advanced breast cancer. The activity seen is comparable with that of other antiangiogenic agents in this setting. Pazopanib may be of interest for future studies in breast cancer, including in combination with other systemic agents.
Increased Reactive Oxygen Species Production and Lower Abundance of Complex I Subunits and Carnitine Palmitoyltransferase 1B Protein Despite Normal Mitochondrial Respiration in Insulin-Resistant Human Skeletal Muscle
Authors: Lefort Natalie , Glancy Brian , Bowen Benjamin , Willis Wayne T. , Bailowitz Zachary , De Filippis Elena A. , Brophy Colleen , Meyer Christian , Højlund Kurt , Yi Zhengping , Mandarino Lawrence J. 
Published: August 2010

OBJECTIVE
The contribution of mitochondrial dysfunction to skeletal muscle insulin resistance remains elusive. Comparative proteomics are being applied to generate new hypotheses in human biology and were applied here to isolated mitochondria to identify novel changes in mitochondrial protein abundance present in insulin-resistant muscle.

RESEARCH DESIGN AND METHODS
Mitochondria were isolated from vastus lateralis muscle from lean and insulin-sensitive individuals and from obese and insulin-resistant individuals who were otherwise healthy. Respiration and reactive oxygen species (ROS) production rates were measured in vitro. Relative abundances of proteins detected by mass spectrometry were determined using a normalized spectral abundance factor method.

RESULTS
NADH- and FADH2-linked maximal respiration rates were similar between lean and obese individuals. Rates of pyruvate and palmitoyl-dl-carnitine (both including malate) ROS production were significantly higher in obesity. Mitochondria from obese individuals maintained higher (more negative) extramitochondrial ATP free energy at low metabolic flux, suggesting that stronger mitochondrial thermodynamic driving forces may underlie the higher ROS production. Tandem mass spectrometry identified protein abundance differences per mitochondrial mass in insulin resistance, including lower abundance of complex I subunits and enzymes involved in the oxidation of branched-chain amino acids (BCAA) and fatty acids (e.g., carnitine palmitoyltransferase 1B).

CONCLUSIONS
We provide data suggesting normal oxidative capacity of mitochondria in insulin-resistant skeletal muscle in parallel with high rates of ROS production. Furthermore, we show specific abundance differences in proteins involved in fat and BCAA oxidation that might contribute to the accumulation of lipid and BCAA frequently associated with the pathogenesis of insulin resistance.
Acute Stimulation of White Adipocyte Respiration by PKA-Induced Lipolysis
Authors: Yehuda-Shnaidman Einav , Buehrer Ben , Pi Jingbo , Kumar Naresh , Collins Sheila 
Published: August 2010

OBJECTIVE
We examined the effect of β-adrenergic receptor (βAR) activation and cAMP-elevating agents on respiration and mitochondrial uncoupling in human adipocytes and probed the underlying molecular mechanisms.

RESEARCH DESIGN AND METHODS
Oxygen consumption rate (OCR, aerobic respiration) and extracellular acidification rate (ECAR, anaerobic respiration) were examined in response to isoproterenol (ISO), forskolin (FSK), and dibutyryl-cAMP (DB), coupled with measurements of mitochondrial depolarization, lipolysis, kinase activities, and gene targeting or knock-down approaches.

RESULTS
ISO, FSK, or DB rapidly increased oxidative and glycolytic respiration together with mitochondrial depolarization in human and mouse white adipocytes. The increase in OCR was oligomycin-insensitive and contingent on cAMP-dependent protein kinase A (PKA)-induced lipolysis. This increased respiration and the uncoupling were blocked by inhibiting the mitochondrial permeability transition pore (PTP) and its regulator, BAX. Interestingly, compared with lean individuals, adipocytes from obese subjects exhibited reduced OCR and uncoupling capacity in response to ISO.

CONCLUSIONS
Lipolysis stimulated by βAR activation or other maneuvers that increase cAMP levels in white adipocytes acutely induces mitochondrial uncoupling and cellular energetics, which are amplified in the absence of scavenging BSA. The increase in OCR is dependent on PKA-induced lipolysis and is mediated by the PTP and BAX. Because this effect is reduced with obesity, further exploration of this uncoupling mechanism will be needed to determine its cause and consequences.
Antiobesity and Antihyperglycemic Effects of Ginsenoside Rb1 in Rats
Authors: Xiong Ye , Shen Ling , Liu Kristina J. , Tso Patrick , Xiong Yuqing , Wang Guangji , Woods Stephen C. , Liu Min 
Published: August 2010

OBJECTIVE
Obesity and type 2 diabetes are national and worldwide epidemics. Because currently available antiobesity and antidiabetic drugs have limited efficacy and/or safety concerns, identifying new medicinal agents, such as ginsenoside Rb1 (Rb1) as reported here, offers exciting possibilities for future development of successful antiobesity and antidiabetic therapies.

RESEARCH DESIGN AND METHODS
Changes in feeding behavior after acute intraperitoneal administration of Rb1 and the effects of intraperitoneal Rb1 for 4 weeks on body weight, energy expenditure, and glucose tolerance in high-fat diet (HFD)-induced obese rats were assessed. We also examined the effects of Rb1 on signaling pathways and neuropeptides in the hypothalamus.

RESULTS
Acute intraperitoneal Rb1 dose-dependently suppressed food intake without eliciting signs of toxicity. This inhibitory effect on feeding may be mediated by central mechanisms because Rb1 stimulated c-Fos expression in brain areas involved in energy homeostasis. Consistent with this, Rb1 activated the phosphatidylinositol 3-kinase/Akt signaling pathway and inhibited NPY gene expression in the hypothalamus. Four-week administration of Rb1 significantly reduced food intake, body weight gain, and body fat content and increased energy expenditure in HFD-induced obese rats. Rb1 also significantly decreased fasting blood glucose and improved glucose tolerance, and these effects were greater than those observed in pair-fed rats, suggesting that although Rb1's antihyperglycemic effect is partially attributable to reduced food intake and body weight; there may be additional effects of Rb1 on glucose homeostasis.

CONCLUSIONS
These results identify Rb1 as an antiobesity and antihyperglycemic agent.
Detailed Physiological Characterization of the Development of Type 2 Diabetes in Hispanic Women With Prior Gestational Diabetes Mellitus
Authors: Xiang Anny H. , Kjos Siri L. , Takayanagi Miwa , Trigo Enrique , Buchanan Thomas A. 
Published: August 2010

OBJECTIVE
To identify physiological and clinical variables associated with development of type 2 diabetes up to 12 years after pregnancies complicated by gestational diabetes.

RESEARCH DESIGN AND METHODS
Seventy-two islet cell antibody–negative nondiabetic Hispanic women had oral (oGTT) and intravenous (ivGTT) glucose tolerance tests, glucose clamps, and body composition assessed between 15 and 30 months after pregnancies complicated by gestational diabetes mellitus (GDM). They returned for oGTTs at 15-month intervals until they dropped out, developed diabetes, or reached 12 years postpartum. Cox regression analysis was used to identify baseline predictors and changes during follow-up that were associated with development of type 2 diabetes.

RESULTS
At baseline, relatively low insulin sensitivity, insulin response, and β-cell compensation for insulin resistance were independently associated with development of diabetes. During follow-up, weight and fat gain and rates of decline in β-cell compensation were significantly associated with diabetes, while additional pregnancy and use of progestin-only contraception were marginally associated with diabetes risk.

CONCLUSIONS
In Hispanic women, GDM represents detection of a chronic disease process characterized by falling β-cell compensation for chronic insulin resistance. Women who are farthest along at diagnosis and/or deteriorating most rapidly are most likely to develop type 2 diabetes within 12 years after the index pregnancy. Weight gain, additional pregnancy, and progestin-only contraception are potential modifiable factors that increase diabetes risk.
Glucose Excursions Between States of Glycemia With Progression to Type 1 Diabetes in the Diabetes Prevention Trial–Type 1 (DPT-1)
Authors: Sosenko Jay M. , Skyler Jay S. , Krischer Jeffrey P. , Greenbaum Carla J. , Mahon Jeffrey , Rafkin Lisa E. , Cuthbertson David , Cowie Catherine , Herold Kevan , Eisenbarth George , Palmer Jerry P. ,   the Diabetes Prevention Trial–Type 1 Study Group
Published: August 2010

OBJECTIVE
We characterized fluctuations between states of glycemia in progressors to type 1 diabetes and studied whether those fluctuations are related to the early C-peptide response to oral glucose.

RESEARCH DESIGN AND METHODS
Oral glucose tolerance tests (OGTTs) from differing states of glycemia were compared within individuals for glucose and C-peptide. Dysglycemic OGTTs (DYSOGTTs) were compared with normal OGTTs (NLOGTT), while transient diabetic OGTTs (TDOGTTs) were compared with subsequent nondiabetic OGTTs and with OGTTs performed at diagnosis.

RESULTS
Of 135 progressors with four or more OGTTs, 30 (22%) went from NLOGTTs to DYSOGTTs at least twice. Area under the curve (AUC) glucose values from the second NLOGTT were higher (P &lt; 0.001) than values from the first NLOGTT. Among 98 progressors whose DYSOGTTs and NLOGTTs were synchronized for the time before diagnosis, despite higher glucose levels (P &lt; 0.01 at all time points) in the DYSOGTTs, 30- to 0-min C-peptide difference values changed little. Likewise, 30- to 0-min C-peptide difference values did not differ between TDOGTTs and subsequent (within 3 months) nondiabetic OGTTs in 55 progressors. In contrast, as glucose levels increased overall from the first to last OGTTs before diagnosis (P &lt; 0.001 at every time point, n = 207), 30- to 0-min C-peptide difference values decreased (P &lt; 0.001).

CONCLUSIONS
Glucose levels fluctuate widely as they gradually increase overall with progression to type 1 diabetes. As glucose levels increase, the early C-peptide response declines. In contrast, glucose fluctuations are not related to the early C-peptide response. This suggests that changes in insulin sensitivity underlie the glucose fluctuations.
Importance of Time Spent Standing for Those at Risk of Diabetic Foot Ulceration
Authors: Najafi Bijan , Crews Ryan T. , Wrobel James S. 
Published: August 2010

OBJECTIVE
Despite the high cumulative plantar stress associated with standing, previous physical activity reports of diabetic patients at risk of foot ulceration have not taken this activity into account. This study aimed to monitor spontaneous daily physical activity in diabetic peripheral neuropathy (DPN) patients and examine both walking and standing activities as important foot-loading conditions.

RESEARCH DESIGN AND METHODS
Thirteen DPN patients were asked to wear a body-worn sensor for 48 h. Body postures (sitting, standing, and lying) and locomotion (walking, number of steps, and postural transition) were extracted.

RESULTS
Patients daily spent twice as much time standing (13 ± 5%) as walking (6 ± 3%). They spent 37 ± 6% of time sitting and 44 ± 8% lying down. The average number of steps per day was 7,754 ± 4,087, and the number of walking episodes was 357 ± 167 with maximum duration of 3.9 ± 3.8 min.

CONCLUSIONS
The large portion of DPN patients' time spent standing with the feet loaded requires further consideration when treating and preventing foot ulcers.
Spondyloarthritis in a Pediatric Population: Risk Factors for Sacroiliitis
Authors: STOLL MATTHEW L. , BHORE RAFIA , DEMPSEY-ROBERTSON MOLLY , PUNARO MARILYNN 
Published: August 2010

Objective.Pediatric rheumatologists may have an opportunity to diagnose sacroiliitis in its early stages, prior to the development of irreversible radiographic changes. Early diagnosis frequently requires magnetic resonance imaging (MRI), the use of which is limited by expense and requirement for sedation. We set out to identify features of juvenile spondyloarthritis (SpA) associated with the highest risk of sacroiliitis, to identify patients who may be candidates for routine MRI-based screening.Methods.We reviewed the charts of 143 children seen at Texas Scottish Rite Hospital for Children diagnosed with SpA based on the International League of Associations for Rheumatology criteria for enthesitis-related arthritis or the Amor criteria for SpA. We performed logistic regression analysis to identify risk factors for sacroiliitis.Results.A group of 143 children were diagnosed with SpA. Consistent with the diagnosis of SpA, 16% had psoriasis, 43% had enthesitis, 9.8% had acute anterior uveitis, and 70% were HLA-B27+. Fifty-three children had sacroiliitis, of which 11 cases were identified by imaging studies in the absence of suggestive symptoms or physical examination findings. Logistic regression analysis revealed that hip arthritis was a positive predictor of sacroiliitis, while dactylitis was a negative predictor.Conclusion.Children with SpA are at risk for sacroiliitis, which may be present in the absence of suggestive symptoms or physical examination findings. The major risk factor for sacroiliitis is hip arthritis, while dactylitis may be protective. Routine screening by MRI should be considered in patients at high risk of developing sacroiliitis.
Anti-Th/To Are Common Antinucleolar Autoantibodies in Italian Patients with Scleroderma
Authors: CERIBELLI ANGELA , CAVAZZANA ILARIA , FRANCESCHINI FRANCO , AIRÒ PAOLO , TINCANI ANGELA , CATTANEO ROBERTO , PAULEY BRAD A. , CHAN EDWARD K.L. , SATOH MINORU 
Published: August 2010

Objective.Patients with scleroderma (systemic sclerosis; SSc) can be classified into subsets based on autoantibody profile and clinical features. Specificities such as anti-Th/To and anti-fibrillarin (U3RNP) are detectable mainly by immunoprecipitation (IP), which is not widely used in clinical laboratories. We examined the autoantibody profiles and clinical manifestations in a cohort of Italian patients with SSc, focusing on anti-Th/To and anticentromere (ACA) antibodies, associated with limited cutaneous SSc (lcSSc).Methods.Sera from 216 consecutive patients with SSc were tested for ACA (by indirect immunofluorescence), antitopoisomerase I (topo I; by counterimmunoelectrophoresis), and anti-RNA polymerase III (RNAPIII; by ELISA). Forty-one sera negative for these specificities were tested by IP analysis of proteins (35S-methionine labeled K562 cell extract) and RNA (silver staining).Results.Among 216 SSc patients analyzed, anti-topo I, ACA, and anti-RNAPIII were detected in 38% (81/216), 31% (67/216) and 7% (15/216), respectively. Among 41 sera negative for ACA, anti-topo I, and anti-RNAPIII and which were tested by IP, 14 were nucleolar stain-positive. Eight out of 14 (57%) showed anti-Th/To reactivity, but no anti-U3RNP was found. In comparison with ACA-positive patients, anti-Th/To-positive patients were younger (p = 0.0046) and more commonly were male (p = 0.0006). All 8 anti-Th/To-positive and all but one ACA-positive patients had lcSSc. Interstitial lung disease (ILD) and pericarditis were more frequent in anti-Th/To-positive patients.Conclusion.Anti-Th/To are common in antinucleolar antibody-positive Italian patients with SSc. Anti-Th/To and ACA patients had lcSSc, with excellent prognosis. The anti-Th/To group had frequent pericarditis and ILD, although impairment of pulmonary function appeared mild.