bluuebunny/crossref_metadata_2025_split huggingface dataset:
Memories that last forever: strategies for optimizing vaccine T-cell memory
Authors: Ahlers Jeffrey D. , Belyakov Igor M. 
Published: November 2009

Abstract
For acute self-limiting infections a vaccine is successful if it elicits memory at least as good as the natural experience; however, for persistent and chronic infections such as HIV, hepatitis C virus (HCV), human papillomavirus (HPV), and human herpes viruses, this paradigm is not applicable. At best, during persistent virus infection the person must be able to maintain the integrity of the immune system in equilibrium with controlling replicating virus. New vaccine strategies are required that elicit both potent high-avidity CD8+ T-cell effector/memory and central memory responses that can clear the nidus of initial virus-infected cells at mucosal surfaces to prevent mucosal transmission or significantly curtail development of disease. The objective of an HIV-1 T-cell vaccine is to generate functional CD8+ effector memory cells at mucosal portals of virus entry to prevent viral transmission. In addition, long-lived CD8+ and CD4+ central memory cells circulating through secondary lymphoid organs and resident in bone marrow, respectively, are needed to provide a concerted second wave of defense that can contain virus at mucosal surfaces and prevent systemic dissemination. Further understanding of factors which can influence long-lived effector and central memory cell differentiation will significantly contribute to development of effective T-cell vaccines. In this review we will focus on discussing mechanisms involved in T-cell memory and provide promising new approaches toward expanding current vaccine strategies to enhance antiviral memory.
ALK1 signaling regulates early postnatal lymphatic vessel development
Authors: Niessen Kyle , Zhang Gu , Ridgway John Brady , Chen Hao , Yan Minhong 
Published: November 2009

Abstract
In vertebrates, endothelial cells form 2 hierarchical tubular networks, the blood vessels and the lymphatic vessels. Despite the difference in their structure and function and genetic programs that dictate their morphogenesis, common signaling pathways have been recognized that regulate both vascular systems. ALK1 is a member of the transforming growth factor-β type I family of receptors, and compelling genetic evidence suggests its essential role in regulating blood vascular development. Here we report that ALK1 signaling is intimately involved in lymphatic development. Lymphatic endothelial cells express key components of the ALK1 pathway and respond robustly to ALK1 ligand stimulation in vitro. Blockade of ALK1 signaling results in defective lymphatic development in multiple organs of neonatal mice. We find that ALK1 signaling regulates the differentiation of lymphatic endothelial cells to influence the lymphatic vascular development and remodeling. Furthermore, simultaneous inhibition of ALK1 pathway increases apoptosis in lymphatic vessels caused by blockade of VEGFR3 signaling. Thus, our study reveals a novel aspect of ALK1 signaling in regulating lymphatic development and suggests that targeting ALK1 pathway might provide additional control of lymphangiogenesis in human diseases.
A balanced t(5;17) (p15;q22-23) in chondroblastoma: frequency of the re-arrangement and analysis of the candidate genes
Authors: Romeo Salvatore , Szuhai Karoly , Nishimori Isao , Ijszenga Marije , Wijers-Koster Pauline , Taminiau Antonie HM , Hogendoorn Pancras CW 
Published: November 2009

AbstractBackgroundChondroblastoma is a benign cartilaginous tumour of bone that predominantly affects the epiphysis of long bones in young males. No recurrent chromosomal re-arrangements have so far been observed. Methods: We identified an index case with a balanced translocation by Combined Binary Ratio-Fluorescent in situ Hybridisation (COBRA-FISH) karyotyping followed by breakpoint FISH mapping and array-Comparative Genomic Hybridisation (aCGH). Candidate region re-arrangement and candidate gene expression were subsequently investigated by interphase FISH and immunohistochemistry in another 14 cases.ResultsA balanced t(5;17)(p15;q22-23) was identified. In the index case, interphase FISH showed that the translocation was present only in mononucleated cells and was absent in the characteristic multinucleated giant cells. The t(5;17) translocation was not observed in the other cases studied. The breakpoint in 5p15 occurred close to the steroid reductase 5α1 (SRD5A1) gene. Expression of the protein was found in all cases tested. Similar expression was found for the sex steroid signalling-related molecules oestrogen receptor alpha and aromatase, while androgen receptors were only found in isolated cells in a few cases. The breakpoint in 17q22-23 was upstream of the carbonic anhydrase × (CA10) gene region and possibly involved gene-regulatory elements, which was indicated by the lack of CA10 protein expression in the index case. All other cases showed variable levels of CA10 expression, with low expression in three cases.ConclusionWe report a novel t(5;17)(p15;q22-23) translocation in chondroblastoma without involvement of any of the two chromosomal regions in other cases studied. Our results indicate that the characteristic multinucleated giant cells in chondroblastoma do not have the same clonal origin as the mononuclear population, as they do not harbour the same translocation. We therefore hypothesise that they might be either reactive or originate from a distinct neoplastic clone, although the occurrence of two distinct clones is unlikely. Impairment of theCA10gene might be pathogenetically relevant, as low expression was found in four cases. Diffuse expression of SRD5A1 and sex steroid signalling-related molecules confirms their role in neoplastic chondrogenesis.
B7-H4gene polymorphisms are associated with sporadic breast cancer in a Chinese Han population
Authors: Zhang Jie , Zhang Mingyan , Jiang Wei , Wang Lihong , Fu Zhenkun , Li Dalin , Pang Da , Li Dianjun 
Published: November 2009

Abstract

Background
B7-H4, a co-inhibitory molecule of the B7 family, can restrain T cell proliferation, cytokine secretion and the development of cytotoxicity. B7-H4 is expressed in tumor tissues at a higher level than in normal tissues, and has a potential effect to protect tumors from anti-tumor immune responses. This case-control study was carried out to determine the potential influences of B7-H4 gene polymorphisms on the susceptibility and progression of breast cancer in Han women of Northeast China.

Methods
We genotyped three B7-H4 variants (rs10754339, rs10801935 and rs3738414) and tagged all common haplotypes (frequency greater than or equal to 1%) in a Chinese population consisting of 500 breast cancer cases and 504 control individuals matched for age. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to determine the genotypes.

Results
Our data indicated that, compared with the common genotype and allele of each SNP, the rs10754339 AG genotype and G allele showed a significantly increased risk of breast cancer (OR = 1.455, 95% CI 1.119-1.892; OR = 1.325, 95% CI 1.073-1.637, respectively). The rs10801935 CC genotype, the rs3738414 AA genotype and the rs3738414 A allele were associated with a significantly decreased risk of breast cancer (OR = 0.328, 95% CI 0.145-0.739; OR = 0.412, 95% CI 0.203-0.835; OR = 0.698, 95% CI 0.564-0.864, respectively). Additionally, the rs10754339 GG genotype was significantly associated with lymph node metastasis and PR status, and the G allele and the AG genotype were respectively associated with lymph node metastasis and ER status. In haplotype analysis, we observed that compared with the AAG haplotype, the AAA haplotype showed a significantly decreased risk of breast cancer (OR = 0.689, 95% CI 0.539-0.881), but the GAG haplotype was associated with a significantly increased risk of breast cancer (OR = 1.511, 95% CI 1.125-2.031). And the AAA and the GCG haplotypes also respectively have significant influences on tumor size and ER status.

Conclusion
These results suggest that B7-H4 gene polymorphism may contribute to the sporadic breast cancer risk and prognosis in Chinese Han women.
Pharmacologic attenuation of pelvic pain in a murine model of interstitial cystitis
Authors: Rudick Charles N , Schaeffer Anthony J , Klumpp David J 
Published: November 2009

Abstract

Background
Interstitial cystitis/painful bladder syndrome (IC/PBS) is a bladder disease that causes debilitating pelvic pain of unknown origin, and IC/PBS symptoms correlate with elevated bladder lamina propria mast cell counts. Similar to IC/PBS patients, pseudorabies virus (PRV) infection in mice induces a neurogenic cystitis associated with bladder lamina propria mast cell accumulation and pelvic pain. We evaluated several drugs to determine the effectiveness of reducing PRV-induced pelvic pain.

Methods
Neurogenic cystitis was induced by the injection of Bartha's strain of PRV into the abductor caudalis dorsalis tail base muscle of female C57BL/6 mice. Therapeutic modulation of pelvic pain was assessed daily for five days using von Frey filament stimulation to the pelvic region to quantify tactile allodynia.

Results
Significant reduction of PRV-induced pelvic pain was observed for animals treated with antagonists of neurokinin receptor 1 (NK1R) and histamine receptors. In contrast, the H1R antagonist hydroxyzine, proton pump inhibitors, a histamine receptor 3 agonist, and gabapentin had little or no effect on PRV-induced pelvic pain.

Conclusion
These data demonstrate that bladder-associated pelvic pain is attenuated by antagonists of NK1R and H2R. Therefore, NK1R and H2Rrepresent direct therapeutic targets for pain in IC/PBS and potentially other chronic pain conditions.
Attitudes of dermatologists in the southeastern United States regarding treatment of alopecia areata: a cross-sectional survey study
Authors: Mukherjee Niyati , Morrell Dean S , Duvic Madeleine , Stewart Paul W , Goldsmith Lowell A 
Published: November 2009

Abstract

Background
Little evidence exists to guide treatment of alopecia areata (AA). The current practices in treatment of children compared to adults and of progressive stages of hair loss are unknown. The objective of this study was to examine the current practices of southeastern United States dermatologists for the treatment of AA.

Methods
Dermatologists were sent anonymous questionnaires regarding their treatment practices by mail. Respondents' frequencies of treatment in children compared to adults and in patchy hair loss compared to widespread hair loss were compared with Wilcoxon signed-ranks tests and Friedman tests. As a secondary source, the National Alopecia Areata Registry (NAAR) database was analyzed for patients' treatment histories.

Results
Survey results suggested that dermatologists recommend treatment less frequently for children than adults and for more advanced hair loss. NAAR data confirmed that offering no treatment for AA is relatively common.

Conclusion
Dermatologists' treatment of AA is inconsistent. A stronger evidence base will provide more consistent treatment options.
Elevated plasma levels of TNF-alpha and Interleukin-6 in patients with diastolic dysfunction and glucose metabolism disorders
Authors: Dinh Wilfried , Füth Reiner , Nickl Werner , Krahn Thomas , Ellinghaus Peter , Scheffold Thomas , Bansemir Lars , Bufe Alexander , Barroso Michael Coll , Lankisch Mark 
Published: November 2009

Abstract

Background
Diabetes mellitus (DM) has reached epidemic proportions and is an important risk factor for heart failure (HF). Left ventricular diastolic dysfunction (LVDD) is recognized as the earliest manifestation of DM-induced LV dysfunction, but its pathophysiology remains incompletely understood. We sought to evaluate the relationship between proinflammatory cytokine levels (TNF-alpha, IL-6) and tissue Doppler derived indices of LVDD in patients with stable coronary artery disease.

Methods
We enrolled 41 consecutive patients (mean age 65+/-10 years) submitted for coronary angiography. Echocardiographic assessment was performed in all patients. Pulsed tissue Doppler imaging was performed at the mitral annulus and was characterized by the diastolic early relaxation velocity Em. Conventional transmitral flow was measured with pw-doppler. Early (E) transmitral flow velocity was measured. LVDD was defined as E/Em ratio ≥ 15, E/Em 8-14 was classified as borderline. Plasma levels of TNF-alpha and IL-6 were determined in all patients. A standardized oral glucose tolerance test was performed in subjects without diabetes.

Results
Patients with E/Em ratio ≥ 15, classified as LVDD and those with E/Em ratio 8-14 (classified as borderline) had significantly higher IL-6 (P = 0,001), TNF-alpha (P < 0,001) and NT-pro- BNP (P = 0,001) plasma levels compared to those with normal diastolic function. TNF-alpha and IL-6 levels remains significantly elevated after adjustment for sex, age, left ventricular ejection function, body mass index, coronary heart disease, smoking, hypertension and diabetes mellitus with linear regression analysis. Furthermore, in subjects LVDD or borderline LV diastolic function, 75% had diabetes or IGT, respectively. When subjects without diabetes were excluded, both IL-6 (P = 0,006) and TNF-alpha (P = 0,002) remained significantly elevated in subjects with E/Em ratio ≥ 15.

Conclusion
This study reveals that increased plasma levels of IL-6 and TNF-alpha were associated with LVDD. These findings suggest a link between low-grade inflammation and the presence of LVDD. An active proinflammatory process may be of importance in the pathogenesis of diastolic dysfunction.
Influence of cytokine inhibitors on concentration and activity of MMP-1 and MMP-3 in disc herniation
Authors: Genevay Stéphane , Finckh Axel , Mezin Françoise , Tessitore Enrico , Guerne Pierre-André 
Published: November 2009

AbstractIntroductionSpontaneous resorption of disc herniation (DH) after sciatica is well documented. The matrix metalloproteinases (MMP)-1 and MMP-3 are enzymes potentially involved in this process. Glucocorticoid injections are commonly used for treatment, and other anti-inflammatory molecules like tumor necrosis factor (TNF) inhibitors are under clinical investigation. However, little is known about the effect of these molecules on DH resorption.MethodsDH tissue was harvested from patients undergoing surgery for sciatica. Samples were thoroughly washed. Diced explants were cultured ex-vivo in 1) 0.5 ml Dulbecco's modified Eagle's medium (DMEM) 10% fetal calf serum (FCS), (controls), 2) recombinant interleukin 1 receptor antagonist (IL-1Ra), (100 ng/ml), 3) dexamethasone (10E-5 M), or 4) TNF inhibitor monoclonal antibody (10 μg/ml). Supernatants were harvested at 48 hours and frozen. Immunocapture activity assays determined total MMP activity, active MMP levels and pro-MMP levels.ResultsFourteen DH tissue samples were analysed. Levels of all forms of MMP-3 were higher than the respective levels of MMP-1(P< 0.01). In particular, the median (interquartile range [IQR]) total MMP-3 level was 0.97 (0.47 - 2.19) ng/mg of tissue compared to 0.024 (0.01 - 0.07) ng/mg of total MMP-1 level (P< 0.01). Incubation with IL-1Ra, dexamethasone, or TNF inhibitors significantly decreased levels of all forms of MMP-3 (P< 0.05). Dexamethasone significantly decreased the ratio of active MMP-3 to total MMP-3 activity. A significant inhibitory effect of dexamethasone was observed only on active MMP-1, while IL-1 and TNF inhibitor had no significant effect on any form.ConclusionsMMP-3 appears to play a greater role than MMP-1 in DH resorption. Dexamethasone, IL-1-Ra and TNF inhibitor decreased active MMP-3, indicating that the clinical use of these drugs may affect the resorption of DH under certain conditions.
Tissue-Selective Regulation of Aromatase Expression by Calcitriol: Implications for Breast Cancer Therapy
Authors: Krishnan Aruna V. , Swami Srilatha , Peng Lihong , Wang Jining , Moreno Jacqueline , Feldman David 
Published: November 2009

AbstractAromatase, the enzyme that catalyzes estrogen synthesis, is critical for the progression of estrogen receptor-positive breast cancer (BCa) in postmenopausal women. We show that calcitriol, the hormonally active form of vitamin D, regulates the expression of aromatase in a tissue-selective manner. Calcitriol significantly decreased aromatase expression in human BCa cells and adipocytes and caused substantial increases in human osteosarcoma cells (a bone cell model exhibiting osteoblast phenotype in culture) and modest increases in ovarian cancer cells. Calcitriol administration to immunocompromised mice bearing human BCa xenografts decreased aromatase mRNA levels in the tumors and the surrounding mammary adipose tissue but did not alter ovarian aromatase expression. In BCa cells, calcitriol also reduced the levels of prostaglandins (PGs), major stimulators of aromatase transcription, by suppressing the expression of cyclooxygenase-2 (which catalyzes PG synthesis) and increasing that of 15-hydroxyprostaglandin dehydrogenase (which catalyzes PG degradation). The mechanism of aromatase down-regulation by calcitriol in BCa cells is therefore 2-fold: a direct repression of aromatase transcription via promoter II through the vitamin D-response elements identified in this promoter and an indirect suppression by reducing the levels of PGs. Combinations of calcitriol with three different aromatase inhibitors (AIs) caused enhanced inhibition of BCa cell growth. The combination of calcitriol and an AI may have potential benefits for BCa therapy. In addition to augmenting the ability of AIs to inhibit BCa growth, calcitriol acting as a selective aromatase modulator that increases aromatase expression in bone would reduce the estrogen deprivation in bone caused by the AIs, thus ameliorating the AI-induced side effect of osteoporosis.
Freeze-Thaw Performance of Concrete: Reconciling Laboratory-Based Specifications with Field Experience
Authors: Janssen Donald J. 
Published: November 2009

Abstract
Specifications relating to frost resistance of concrete are generally based on laboratory tests of laboratory-produced concrete. Quality control for laboratory-produced concrete is usually significantly better than what can be achieved in the field, and laboratory freeze-thaw tests generally produce conditions that are not close to any real field exposure conditions. Field exposure testing is also problematic. Exposure conditions are not the same from one location to the next and may not even be the same from one year to the next at the same location. This paper attempts to provide guidance for interpreting the results of field tests of concrete exposed to natural freezing and thawing conditions. Types of frost damage as well as types of field test sites are discussed, and recommendations are provided for the use of field test results to modify frost-resistance specifications.
Multimedia Information Retrieval
Authors: Henrich Andreas 
Published: November 2009

Zusammenfassung
Der Umfang, in dem multimediale Daten verfügbar sind, nimmt ständig zu. Dies gilt für das Internet ebenso wie für die Daten auf dem heimischen PC oder auch auf einem PDA. Eine wesentliche Herausforderung stellt dabei die Suche nach Medienobjekten dar. Der vorliegende Artikel geht auf grundlegende Konzepte und Problemstellungen zur Suche nach Medienobjekten und multimedialen Dokumenten ein und gibt einen Überblick über die für verschiedene Medientypen existierenden Ansätze.
Effects of long-term l-thyroxine treatment on endothelial function and arterial distensibility in young adults with congenital hypothyroidism
Authors: Oliviero Ugo , Cittadini Antonio , Bosso Giorgio , Cerbone Manuela , Valvano Antonio , Capalbo Donatella , Apuzzi Valentina , Calabrese Fabrizia , Lettiero Teresa , Salerno Mariacarolina 
Published: November 2009

ObjectivePatients with congenital hypothyroidism (CH) display subclinical abnormalities of the cardiovascular system that are related to unphysiological fluctuations of TSH levels and occur despite careful replacement therapy.DesignThe aim of the present case–control study was to evaluate the effects of long-term levothyroxine (l-T4) replacement therapy on the vascular district in CH patients by assessing endothelial function with flow-mediated dilation (FMD) and brachial artery distensibility with the measurement of the coefficient of distensibility (DC).MethodsThirty-two young adults with CH aged 18.9±0.2 years and 32 age- and sex-matched controls underwent brachial Doppler ultrasound examination to measure FMD and DC at the time of the study. Hypothyroidism was diagnosed by neonatal screening, and l-T4 treatment was initiated within the first month of life.ResultsCompared to healthy controls, CH patients had significantly reduced brachial artery reactivity with lower FMD values (8.9±5.7 vs 14.1±5.1% P=0.003) and decreased vascular distensibility (24.6±1.6 vs 27.3±3 kPa−1×10−3, P<0.0002). Linear regression analysis revealed that both total and pubertal mean TSH and number of episodes of undertreatment were independent determinants of FMD and DC. Pubertal mean TSH was the best predictor of both FMD and DC (r=0.81 and r=0.87 respectively, P<0.001).ConclusionsYoung adults with CH treated with long-term l-T4 replacement therapy may have significant impairment of both FMD and DC. Our data suggest that high TSH levels, inadequately corrected by l-T4 replacement therapy in CH patients especially during puberty, can exert significant effects on the elastic and functional vessel properties.
Herpesvirus type 7 infection may play an important role in individuals with a genetic profile of susceptibility to Graves' disease
Authors: Leite Janaina Luisa , Bufalo Natassia Elena , Santos Roberto Bernardo , Romaldini João Hamilton , Ward Laura Sterian 
Published: November 2009

ObjectiveAn inherited profile of genes related to the response to aggressive environmental factors such as viruses and chemicals may be related to an increased susceptibility to Graves' disease (GD).Design and methodsThis prospective case–control study was designed to examine the relationship between human herpesviruses (HHV) infection, determined by circulating DNA; tumour protein p53 (TP53) apoptotic ability; and detoxification system genes, and GD. We studied 280 confirmed GD patients paired to 284 controls with respect to environmental exposure. Exclusion criteria included medications that could interfere with thyroid function evaluation and a recent history of viral and bacterial infections.ResultsA stepwise regression analysis adjusted for age, gender, and ethnicity established the inheritance of glutathione S-transferase pi 1 (GSTP1) (odds ratio (OR)=3.423; 95% confidence interval (CI)=2.120–5.527; P<0.001) and cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) variants (OR=1.649; 95% CI=1.012–2.686; P=0.0445) as significant risk factors for the disease. HHV-7 infection was much more common in GD patients (64.64%) than in controls (38.73%; χ2, P<0.0001), and it increased the risk for GD more than three times (OR=3.133; 95% CI=1.959–5.011; P<0.0001). The inheritance of less efficient Pro/Pro TP53 gene variants significantly increased the risk of GD development (OR=5.196; 95% CI=2.112–12.783; P<0.0001) and also favored HHV-7 infection (OR=2.835; 95% CI=1.100–7.310; P=0.0275). In addition, 72TP53 variants augmented the risk of GD relapse (OR=1.860; 95% CI=1.015–3.410; P=0.0446).ConclusionsWe suggest that an inherited genetic profile involving TP53 may favor HHV-7 infection and maintenance, which, in turn, may initiate and perpetuate GD autoimmune process.