bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intratumoral delivery of IL-18 naked DNA induces T-cell activation and Th1 response in a mouse hepatic cancer model
Authors: Chang Chi-Young , Lee Jienny , Kim Eun-Young , Park Hae-Jung , Kwon Choon-Hyuck , Joh Jae-Won , Kim Sung-Joo 
Published: May 2007

AbstractBackgroundThe novel cytokine, interleukin (IL)-18, is a strong interferon-γ inducer and costimulatory factor in Th1 cell activation. IL-18 triggers IFN-γ production and enhances cytolytic activity in both T and NK cells. However, the exact mechanism of antitumor action of IL-18 remains to be clarified. To determine the effects of IL-18 plasmid DNA on hepatic cancer in mice, CT26 murine colon adenocarcinoma cells were established in mouse liver.MethodsPlasmid vectors encoding IL-18 were transferred directly into the liver 7 days after tumor injection to restrict IL-18 expression within the tumor site. The IL-18 protein level was increased in the liver 4 days after plasmid injection, and a marked antitumoral effect was observed at day 7. Antitumor effects were evaluated by measuring tumor regression, immune cell population, and IFN-γ production.ResultsThe IL-18 plasmid controlled the growth of hepatic tumors and proliferation of splenic immune cells. Moreover, treatment of CT26 tumors with the IL-18 plasmid significantly enhanced the population of the effector T and NK cells in the spleen and peripheral blood. In spleen, the population of CD4+CD62Lowcells was augmented in response to IL-18 on day 7. These results are consistent with the increase in CD4+T cells secreting IFN-γ, but not CD8+T cells. The marked reduction of tumor growth in tumor-bearing mice was associated with the maintenance of IFN-γ production in spleen in response to IL-18. These antitumoral effects were maintained until 14 days after plasmid injection.ConclusionOur results suggest that direct plasmid DNA transfer of IL-18 with no accompanying reagents to augment transfection efficiency may be useful in tumor immunotherapy.
Association between 5-HT2A, TPH1 and GNB3 genotypes and response to typical neuroleptics: a serotonergic approach
Authors: Anttila Sami , Kampman Olli , Illi Ari , Rontu Riikka , Lehtimäki Terho , Leinonen Esa 
Published: May 2007

Abstract

Background
Schizophrenia is a common psychiatric disease affecting about 1% of population. One major problem in the treatment is finding the right the drug for the right patients. However, pharmacogenetic results in psychiatry can seldom be replicated.

Methods
We selected three candidate genes associated with serotonergic neurotransmission for the study: serotonin 2A (5-HT2A) receptor gene, tryptophan hydroxylase 1 (TPH1) gene, and G-protein beta-3 subunit (GNB3) gene. We recruited 94 schizophrenia patients representing extremes in treatment response to typical neuroleptics: 43 were good responders and 51 were poor responders. The control group consisted of 392 healthy blood donors.

Results
We do, in part, replicate the association between 5-HT2A T102C polymorphism and response to typical neuroleptics. In female patients, C/C genotype was significantly more common in non-responders than in responders [OR = 6.04 (95% Cl 1.67–21.93), p = 0.005] or in the control population [OR = 4.16 (95% CI 1.46–11.84), p = 0.005]. TPH1 A779C C/A genotype was inversely associated with good treatment response when compared with non-responders [OR = 0.59 (95% Cl 0.36–0.98), p = 0.030] or with the controls [OR = 0.44 (95% CI 0.23–0.86, p = 0.016], and GNB3 C825T C/T genotype showed a trend-like positive association among the male patients with a good response compared with non-responders [OR = 3.48 (95% Cl 0.92–13.25), p = 0.061], and a clearer association when compared with the controls [OR = 4.95 (95% CI 1.56–15.70), p = 0.004].

Conclusion
More findings on the consequences of functional polymorphisms for the role of serotonin in the development of brain and serotonergic neurotransmission are needed before more detailed hypotheses regarding susceptibility and outcome in schizophrenia can be formulated. The present results may highlight some of the biological mechanisms in different courses of schizophrenia between men and women.
Evaluating the organisational climate in Italian public healthcare institutions by means of a questionnaire
Authors: Wienand Ulrich , Cinotti Renata , Nicoli Augusta , Bisagni Miriam 
Published: May 2007

AbstractBackgroundBy means of the ICONAS project, the Healthcare Agency of an Italian Region developed, and used a standardised questionnaire to quantify the organisational climate. The aims of the project were (a) to investigate whether the healthcare institutions were interested in measuring climate, (b) to estimate the range of applicability and reliability of the instrument, (c) to analyse the dimensions of climate among healthcare personnel, (d) to assess the differences among employees with different contractual positions.MethodsThe anonymous questionnaire containing 50 items, each with a scale from 1 to 10, was offered to the healthcare organisations, to be compiled during ad hoc meetings. The data were sent to the central project coordinator. The differences between highly specialised staff (mostly physicians) and other employees were assessed after descriptive statistical analysis of the single items. Both Principal Component Analysis and Factor Analysis were used.ResultsTen healthcare organisations agreed to partecipate. The questionnaire was completed by 8691 employees out of 13202. The mean value of organisational climate was 4.79 (range 1–10). There were significant differences among single items and between the 2 groups of employees. Multivariate methods showed: (a) one principal component explained > 40% of the variance, (b) 7 factors summarised the data.ConclusionItalian healthcare institutions are interested in assessing organisational phenomena, especially after the reforms of the nineties. The instrument was found to be applicable and suitable for measuring organisational climate. Administration of the questionnaire leads to an acceptable response rate. Climate can be discribed by means of 7 underlying dimensions.
Larvicidal effects of a neem (Azadirachta indica) oil formulation on the malaria vector Anopheles gambiae
Authors: Okumu Fredros O , Knols Bart GJ , Fillinger Ulrike 
Published: May 2007

Abstract

Background
Larviciding is a key strategy used in many vector control programmes around the world. Costs could be reduced if larvicides could be manufactured locally. The potential of natural products as larvicides against the main African malaria vector, Anopheles gambiae s.s was evaluated.

Methods
To assess the larvicidal efficacy of a neem (Azadirachta indica) oil formulation (azadirachtin content of 0.03% w/v) on An. gambiae s.s., larvae were exposed as third and fourth instars to a normal diet supplemented with the neem oil formulations in different concentrations. A control group of larvae was exposed to a corn oil formulation in similar concentrations.

Results
Neem oil had an LC50 value of 11 ppm after 8 days, which was nearly five times more toxic than the corn oil formulation. Adult emergence was inhibited by 50% at a concentration of 6 ppm. Significant reductions on growth indices and pupation, besides prolonged larval periods, were observed at neem oil concentrations above 8 ppm. The corn oil formulation, in contrast, produced no growth disruption within the tested range of concentrations.

Conclusion
Neem oil has good larvicidal properties for An. gambiae s.s. and suppresses successful adult emergence at very low concentrations. Considering the wide distribution and availability of this tree and its products along the East African coast, this may prove a readily available and cheap alternative to conventional larvicides.
Deletion mutagenesis of large areas in Plasmodium falciparum genes: a comparative study
Authors: Williams Marni , Louw Abraham I , Birkholtz Lyn-Marie 
Published: May 2007

Abstract

Background
The increasing emergence of Plasmodium falciparum parasites resistant to most of the cost-effective drugs has necessitated the identification of novel leads and drug targets. Parasite-specific inserts in enzymes that are essential for the differentiation and proliferation of malarial parasites have received considerable interest since it distinguishes these proteins from their human counterparts. The functions of these inserts, which include mediations of protein activities or protein-protein interactions, are being investigated by several strategies including deletion mutagenesis. A comparative study of five widely used PCR-based mutagenesis methods identified a modified inverse PCR method as particularly suitable for the deletion of large areas (>100 bp) in malaria parasite genes.

Methods
The restriction enzyme-mediated inverse PCR method described here incorporates unique restriction enzyme sites at the 5'-ends of inverse tail-to-tail primers. The entire gene-containing vector is amplified except the desired region to be deleted and cloned using the unique restriction sites to increase ligation efficiency. This method was compared in its efficiency to delete a ~400 bp parasite-specific insert in malarial S-adenosylmethionine decarboxylase/ornithine decarboxylase (PfAdoMetDC/ODC) to existing PCR-based site-directed deletion mutagenesis methods including the QuickChange™ site-directed mutagenesis, ExSite™, overlapping primer and inverse PCR. In addition, the modified method was applied in the deletion of a >600 bp parasite-specific insert in another malarial gene, pyridoxal kinase (PfPdxK).

Results
The modified and optimized restriction enzyme-mediated inverse PCR method resulted in 80% compared to 40% deletion mutagenesis efficiency of the overlapping primer method in the deletion of a large area (411 bp) from a large malaria gene (PfAdoMetDC/ODC, gene size 4257 bp). In contrast, deletion mutagenesis methods such as the well-known QuickChange™ site-directed mutagenesis, ExSite™ and inverse PCR methods produced insignificant results. A 100% mutagenesis efficiency was obtained with the restriction enzyme-mediated inverse PCR method to delete 618 bp from a smaller gene (PfPdxK, gene size 1536 bp).

Conclusion
An efficient method was developed for the deletion of large areas (>100 bp) in significantly sized genes such as those of the A+T-rich P. falciparum genome.
In vitro activities of 18 antimicrobial agents against Staphylococcus aureus isolates from the Institut Pasteur of Madagascar
Authors: Randrianirina Frédérique , Soares Jean-Louis , Ratsima Elisoa , Carod Jean-François , Combe Patrice , Grosjean Pierre , Richard Vincent , Talarmin Antoine 
Published: May 2007

Abstract

Background

Staphylococcus aureus, one of the most frequently isolated pathogens in both hospitals and the community, has been particularly efficient at developing resistance to antimicrobial agents. In developed countries, as methicillin-resistant S. aureus (MRSA) has prevailed and, furthermore, as S. aureus with reduced susceptibility to vancomycin has emerged, the therapeutic options for the treatment of S. aureus infections have become limited. In developing countries and especially African countries very little is known concerning the resistance of S. aureus to antibiotics. In Madagascar no data exist concerning this resistance.

Objective
To update the current status of antibiotic resistance of S. aureus in Antananarivo, Madagascar.

Methods
Clinical S. aureus isolates were collected from patients at the Institut Pasteur of Madagascar from January 2001 to December 2005. Susceptibility tests with 18 antibiotics were performed by the disk diffusion method.

Results
Among a total of 574 isolates, 506 were from community-acquired infections and 68 from nosocomial infections. There was no significant difference in the methicillin resistance rate between community-acquired strains (33 of 506; 6.5%) and nosocomial strains (3 of 68, 4.4%). Many MRSA isolates were resistant to multiple classes of antibiotics. Resistance to tetracyclin, trimethoprim-sulfamethoxazole and erythromycin was more common. Among MRSA isolates resistance rates to rifampicin, fusidic acid, gentamicin and ciprofloxacin were lower than that observed with other drugs easily available in Madagascar. No isolates were resistant to glycopeptides.

Conclusion
The rate of methicillin-resistant S. aureus is not different between community-acquired and nosocomial infections and is still rather low in Madagascar.
Correlating metabolic and anatomic responses of primary lung cancers to radiotherapy by combined F-18 FDG PET-CT imaging
Authors: Wong Ching-yee O , Schmidt Joseph , Bong Jeffery S , Chundru Suyra , Kestin Larry , Yan Di , Grills Inga , Gaskill Marianne , Cheng Vincent , Martinez Alvaro A , Fink-Bennett Darlene 
Published: May 2007

Abstract
Background
To correlate the metabolic changes with size changes for tumor response by concomitant PET-CT evaluation of lung cancers after radiotherapy.

Methods
36 patients were studied pre- and post-radiotherapy with18FDG PET-CT scans at a median interval of 71 days. All of the patients were followed clinically and radiographically after a mean period of 342 days for assessment of local control or failure rates. Change in size (sum of maximum orthogonal diameters) was correlated with that of maximum standard uptake value (SUV) of the primary lung cancer before and after conventional radiotherapy.

Results
There was a significant reduction in both SUV and size of the primary cancer after radiotherapy (p < 0.00005). Among the 20 surviving patients, the sensitivity, specificity, and accuracy using PET (SUV) were 94%, 50%, 90% respectively and the corresponding values using and CT (size criteria) were 67%, 50%, and 65% respectively. The metabolic change (SUV) was highly correlated with the change in size by a quadratic function. In addition, the mean percentage metabolic change was significantly larger than that of size change (62.3 ± 32.7% vs 47.1 ± 26.1% respectively, p = 0.03)

Conclusion
Correlating and incorporating metabolic change by PET into size change by concomitant CT is more sensitive in assessing therapeutic response than CT alone.
High synovial expression of the inhibitory FcγRIIb in rheumatoid arthritis
Authors: Magnusson Sofia E , Engström Marianne , Jacob Uwe , Ulfgren Ann-Kristin , Kleinau Sandra 
Published: May 2007

AbstractActivating Fc gamma receptors (FcγRs) have been identified as having important roles in the inflammatory joint reaction in rheumatoid arthritis (RA) and murine models of arthritis. However, the role of the inhibitory FcγRIIb in the regulation of the synovial inflammation in RA is less known. Here we have investigated synovial tissue from RA patients using a novel monoclonal antibody (GB3) specific for the FcγRIIb isoform. FcγRIIb was abundantly expressed in synovia of RA patients, in sharp contrast to the absence or weak staining of FcγRIIb in synovial biopsies from healthy volunteers. In addition, the expression of FcγRI, FcγRII and FcγRIII was analyzed in synovia obtained from early and late stages of RA. Compared with healthy synovia, which expressed FcγRII, FcγRIII but not FcγRI, all activating FcγRs were expressed and significantly up-regulated in RA, regardless of disease duration. Macrophages were one of the major cell types in the RA synovium expressing FcγRIIb and the activating FcγRs. Anti-inflammatory treatment with glucocorticoids reduced FcγR expression in arthritic joints, particularly that of FcγRI. This study demonstrates for the first time that RA patients do not fail to up-regulate FcγRIIb upon synovial inflammation, but suggests that the balance between expression of the inhibitory FcγRIIb and activating FcγRs may be in favour of the latter throughout the disease course. Anti-inflammatory drugs that target activating FcγRs may represent valuable therapeutics in this disease.
Analysis of 14 BAC sequences from the Aedes aegyptigenome: a benchmark for genome annotation and assembly
Authors: Lobo Neil F , Campbell Kathy S , Thaner Daniel , deBruyn Becky , Koo Hean , Gelbart William M , Loftus Brendan J , Severson David W , Collins Frank H 
Published: May 2007

Abstract
Background
Aedes aegypti is the principal vector of yellow fever and dengue viruses throughout the tropical world. To provide a set of manually curated and annotated sequences from the Ae. aegypti genome, 14 mapped bacterial artificial chromosome (BAC) clones encompassing 1.57 Mb were sequenced, assembled and manually annotated using a combination of computational gene-finding, expressed sequence tag (EST) matches and comparative protein homology. PCR and sequencing were used to experimentally confirm expression and sequence of a subset of these transcripts.

Results
Of the 51 manual annotations, 50 and 43 demonstrated a high level of similarity to Anopheles gambiae and Drosophila melanogaster genes, respectively. Ten of the 12 BAC sequences with more than one annotated gene exhibited synteny with the A. gambiae genome. Putative transcripts from eight BAC clones were found in multiple copies (two copies in most cases) in the Aedes genome assembly, which point to the probable presence of haplotype polymorphisms and/or misassemblies.

Conclusion
This study not only provides a benchmark set of manually annotated transcripts for this genome that can be used to assess the quality of the auto-annotation pipeline and the assembly, but it also looks at the effect of a high repeat content on the genome assembly and annotation pipeline.
Altered Activity of 11β-Hydroxysteroid Dehydrogenase Types 1 and 2 in Skeletal Muscle Confers Metabolic Protection in Subjects with Type 2 Diabetes
Authors: Jang Christina , Obeyesekere Varuni R. , Dilley Rodney J. , Krozowski Zygmunt , Inder Warrick J. , Alford Frank P. 
Published: May 2007

AbstractContext: There is little information regarding the regulation of 11β-hydroxysteroid dehydrogenase (11β-HSD) enzymes in skeletal muscle in the setting of type 2 diabetes.Objective: Our objective was to investigate whether there is differential mRNA expression and enzyme activity of 11β-HSD1 and 11β-HSD2 in the skeletal muscle of diabetic subjects compared with controls at baseline and in response to dexamethasone.Design: Participants underwent muscle biopsy of vastus lateralis at baseline and after dexamethasone.Setting: The study took place at a university teaching hospital.Participants: Twelve subjects with type 2 diabetes and 12 age- and sex-matched controls participated.Intervention: Subjects were given oral dexamethasone, 4 mg/d for 4 d.Main Outcome Measures: We assessed 11β-HSD1, 11β-HSD2, and H6PDH mRNA levels by quantitative RT-PCR and enzyme activity by percent conversion of [3H]cortisone and [3H]cortisol, respectively.Results: At baseline, mRNA levels were similar in diabetic and control subjects for 11β-HSD1, 11β-HSD2, and H6PDH. 11β-HSD1 activity was reduced in diabetic subjects (percent conversion of [3H]cortisone to [3H]cortisol was 11.4 ± 2.5% vs. 18.5 ± 2.2%; P = 0.041), and 11β-HSD2 enzyme activity was higher in diabetic subjects (percent conversion of [3H]cortisone to [3H]cortisol was 17.2 ± 2.6% vs. 9.2 ± 1.3%; P = 0.012). After dexamethasone, 11β-HSD1 mRNA increased in both groups (P &lt; 0.001), whereas 11β-HSD2 mRNA decreased (P = 0.002). 11β-HSD1 activity increased in diabetic subjects (P = 0.021) but not in controls, whereas 11β-HSD2 activity did not change in either group. At baseline, there was a significant negative correlation between 11β-HSD1 and 11β-HSD2 enzyme activity (r = −0.463; P = 0.026).Conclusions: The activities of skeletal muscle 11β-HSD1 and 11β-HSD2 are altered in diabetes, which together may reduce intracellular cortisol generation, potentially conferring metabolic protection.
Sleep Loss Alters Basal Metabolic Hormone Secretion and Modulates the Dynamic Counterregulatory Response to Hypoglycemia
Authors: Schmid Sebastian M. , Hallschmid Manfred , Jauch-Chara Kamila , Bandorf Nadine , Born Jan , Schultes Bernd 
Published: May 2007

Abstract
Context: Sleep loss has immediate effects on metabolic function that in the long run may contribute to the development of obesity and type 2 diabetes.
Objective: Our objective was to explore the neuroendocrine mechanisms mediating the acute effects of sleep deprivation on blood glucose regulation under basal and hypoglycemic conditions.
Methods: In a randomized, crossover study in 10 healthy young men, plasma concentrations of relevant hormones were examined during basal rest, a subsequent stepwise hypoglycemic clamp after one night of total sleep deprivation (SD) and one night of regular sleep.
Results: Basal glucagon concentrations were decreased (P = 0.022) and C-peptide levels were slightly reduced after SD (P = 0.085), compared with regular sleep. During hypoglycemia after SD, the glucagon increase relative to baseline was enhanced (P = 0.034) and the relative decrease in C-peptide was reduced (P = 0.013). Also, the relative increase in norepinephrine was reduced (P = 0.031). SD did not affect epinephrine, ACTH, cortisol, lactate, β-hydroxybutyrate, or nonesterified fatty acids during hypoglycemia, but overall, plasma nonesterified fatty acid levels were reduced after SD (P = 0.009). SD markedly increased rated hunger during basal rest (P &lt; 0.008), resulting in a dampened relative increase during hypoglycemia (P &lt; 0.009). Unexpectedly, despite distinct alterations in basal secretory activity, the absolute amplitude of hormonal counterregulation and hunger responses to hypoglycemia was not affected by SD.
Conclusion: Short-term SD distinctly alters hormonal glucose regulation, affecting especially pancreatic islet secretion, and also increases hunger. Immediate perturbations in the dynamic regulation of energy metabolism caused by acute sleep curtailment may contribute to the association between chronic sleep loss and metabolic disorders.
Growth Hormone Treatment in Adolescent Males with Idiopathic Short Stature: Changes in Body Composition, Protein, Fat, and Glucose Metabolism
Authors: Hannon Tamara S. , Danadian Kapriel , Suprasongsin Chittiwat , Arslanian Silva A. 
Published: May 2007

Abstract
Context: Cross-sectional observations show an inverse relationship between pubertal increase in GH and insulin sensitivity, suggesting that pubertal insulin resistance may be mediated by GH.
Objective: Our objective was to assess longitudinally the effects of short-term GH supplementation in adolescent males with non-GH-deficient idiopathic short stature (ISS) on body composition, substrate metabolism, and insulin sensitivity. Children with ISS were studied to simulate the pubertal increase in GH secretion.
Participants and Setting: Eight males with ISS (10.8–16.5 yr) were recruited from pediatric endocrinology clinics at an academic medical center.
Study Design: Participants were evaluated in the General Clinical Research Center before and after 4 months of GH supplementation (0.3 mg/kg·wk). Body composition was assessed with dual-energy x-ray absorptiometry. Whole-body glucose, protein, and fat turnover were measured using stable isotopes. In vivo insulin action was assessed during a 3-h hyperinsulinemic (40 mU/m2·min) euglycemic clamp.
Results: GH supplementation led to 1) increase in hepatic glucose production and fasting insulin levels, 2) increase in lean body mass and decrease in fat mass, and 3) improvement in cardiovascular lipid risk profile. Plasma IGF-I levels correlated positively with insulin levels.
Conclusions: Four months of GH supplementation in adolescent males with ISS is associated with significant body composition changes and hepatic insulin resistance.