bluuebunny/crossref_metadata_2025 huggingface dataset:
Pre-gastrula expression of zebrafish extraembryonic genes
Authors: Hong Sung-Kook , Levin Carly S , Brown Jamie L , Wan Haiyan , Sherman Brad T , Huang Da Wei , Lempicki Richard A , Feldman Benjamin
Published: May 2010

Background

Many species form extraembryonic tissues during embryogenesis, such as the placenta of humans and other viviparous mammals. Extraembryonic tissues have various roles in protecting, nourishing and patterning embryos. Prior to gastrulation in zebrafish, the yolk syncytial layer - an extraembryonic nuclear syncytium - produces signals that induce mesoderm and endoderm formation. Mesoderm and endoderm precursor cells are situated in the embryonic margin, an external ring of cells along the embryo-yolk interface. The yolk syncytial layer initially forms below the margin, in a domain called the external yolk syncytial layer (E-YSL).

Results

We hypothesize that key components of the yolk syncytial layer's mesoderm and endoderm inducing activity are expressed as mRNAs in the E-YSL. To identify genes expressed in the E-YSL, we used microarrays to compare the transcription profiles of intact pre-gastrula embryos with pre-gastrula embryonic cells that we had separated from the yolk and yolk syncytial layer. This identified a cohort of genes with enriched expression in intact embryos. Here we describe our whole mount in situ hybridization analysis of sixty-eight of them. This includes ten genes with E-YSL expression (camsap1l1, gata3, znf503, hnf1ba, slc26a1, slc40a1, gata6, gpr137bb, otop1 and cebpa), four genes with expression in the enveloping layer (EVL), a superficial epithelium that protects the embryo (zgc:136817, zgc:152778, slc14a2 and elovl6l), three EVL genes whose expression is transiently confined to the animal pole (elovl6l, zgc:136359 and clica), and six genes with transient maternal expression (mtf1, wu:fj59f04, mospd2, rftn2, arrdc1a and pho). We also assessed the requirement of Nodal signaling for the expression of selected genes in the E-YSL, EVL and margin. Margin expression was Nodal dependent for all genes we tested, including the concentrated margin expression of an EVL gene: zgc:110712. All other instances of EVL and E-YSL expression that we tested were Nodal independent.

Conclusion

We have devised an effective strategy for enriching and identifying genes expressed in the E-YSL of pre-gastrula embryos. To our surprise, maternal genes and genes expressed in the EVL were also enriched by this strategy. A number of these genes are promising candidates for future functional studies on early embryonic patterning.
Effects of Alu elements on global nucleosome positioning in the human genome
Authors: Tanaka Yoshiaki , Yamashita Riu , Suzuki Yutaka , Nakai Kenta
Published: May 2010

Background

Understanding the genome sequence-specific positioning of nucleosomes is essential to understand various cellular processes, such as transcriptional regulation and replication. As a typical example, the 10-bp periodicity of AA/TT and GC dinucleotides has been reported in several species, but it is still unclear whether this feature can be observed in the whole genomes of all eukaryotes.

Results

With Fourier analysis, we found that this is not the case: 84-bp and 167-bp periodicities are prevalent in primates. The 167-bp periodicity is intriguing because it is almost equal to the sum of the lengths of a nucleosomal unit and its linker region. After masking Alu elements, these periodicities were greatly diminished. Next, using two independent large-scale sets of nucleosome mapping data, we analyzed the distribution of nucleosomes in the vicinity of Alu elements and showed that (1) there are one or two fixed slot(s) for nucleosome positioning within the Alu element and (2) the positioning of neighboring nucleosomes seems to be in phase, more or less, with the presence of Alu elements. Furthermore, (3) these effects of Alu elements on nucleosome positioning are consistent with inactivation of promoter activity in Alu elements.

Conclusions

Our discoveries suggest that the principle governing nucleosome positioning differs greatly across species and that the Alu family is an important factor in primate genomes.
NADase as a target molecule of in vivo suppression of the toxicity in the invasive M-1 group A Streptococcal isolates
Authors: Tatsuno Ichiro , Isaka Masanori , Minami Masaaki , Hasegawa Tadao
Published: May 2010

Background

NAD-glycohydrolase (NADase) secreted by M-1 group A streptococcal (GAS) isolates are suspected as one of the virulence factors to cause severe invasive disease including streptococcal toxic shock-like syndrome (STSS). M-1 GAS strains were divided into three groups based on NADase activity: high activity, low activity and no activity in our previous report.

Results

The representative high activity isolates taken from STSS patients showed higher virulence compared with isolates from the low activity group, when used to infect mice. The knockout mutant of the nga gene, which encodes NADase also showed reduced virulence in a mouse infection study. The cloned nga gene was able to significantly complement the lost virulence. In addition, the solution containing purified recombinant IFS, which is an inhibitor of NADase, partially rescued mice infected with S. pyogenes.

Conclusions

These results indicate that NADase is important for the virulence of S. pyogenes in vivo and is the potential target to suppress the virulence.
Wheat gene bank accessions as a source of new alleles of the powdery mildew resistance gene Pm3: a large scale allele mining project
Authors: Bhullar Navreet K , Zhang Zhiqing , Wicker Thomas , Keller Beat
Published: May 2010

Background

In the last hundred years, the development of improved wheat cultivars has led to the replacement of landraces and traditional varieties by modern cultivars. This has resulted in a decline in the genetic diversity of agriculturally used wheat. However, the diversity lost in the elite material is somewhat preserved in crop gene banks. Therefore, the gene bank accessions provide the basis for genetic improvement of crops for specific traits and and represent rich sources of novel allelic variation.

Results

We have undertaken large scale molecular allele mining to isolate new alleles of the powdery mildew resistance gene Pm3 from wheat gene bank accessions. The search for new Pm3 alleles was carried out on a geographically diverse set of 733 wheat accessions originating from 20 countries. Pm3 specific molecular tools as well as classical pathogenicity tests were used to characterize the accessions. Two new functional Pm3 alleles were identified out of the eight newly cloned Pm3 sequences. These new resistance alleles were isolated from accessions from China and Nepal. Thus, the repertoire of functional Pm3 alleles now includes 17 genes, making it one of the largest allelic series of plant resistance genes. The combined information on resistant and susceptible Pm3 sequences will allow to study molecular function and specificity of functional Pm3 alleles.

Conclusions

This study demonstrates that molecular allele mining on geographically defined accessions is a useful strategy to rapidly characterize the diversity of gene bank accessions at a specific genetic locus of agronomical importance. The identified wheat accessions with new resistance specificities can be used for marker-assisted transfer of the Pm3 alleles to modern wheat lines.
Dosage effect on uropathogenic Escherichia coli anti-adhesion activity in urine following consumption of cranberry powder standardized for proanthocyanidin content: a multicentric randomized double blind study
Authors: Howell Amy B , Botto Henry , Combescure Christophe , Blanc-Potard Anne-Béatrice , Gausa Lluis , Matsumoto Tetsuro , Tenke Peter , Sotto Albert , Lavigne Jean-Philippe
Published: May 2010

Background

Ingestion of cranberry (Vaccinium macrocarpon Ait.) has traditionally been utilized for prevention of urinary tract infections. The proanthocyanidins (PACs) in cranberry, in particular the A-type linkages have been implicated as important inhibitors of primarily P-fimbriated E. coli adhesion to uroepithelial cells. Additional experiments were required to investigate the persistence in urine samples over a broader time period, to determine the most effective dose per day and to determine if the urinary anti-adhesion effect following cranberry is detected within volunteers of different origins.

Methods

Two separate bioassays (a mannose-resistant hemagglutination assay and an original new human T24 epithelial cell-line assay) have assessed the ex-vivo urinary bacterial anti-adhesion activity on urines samples collected from 32 volunteers from Japan, Hungary, Spain and France in a randomized, double-blind versus placebo study. An in vivo Caenorhabditis elegans model was used to evaluate the influence of cranberry regimen on the virulence of E. coli strain.

Results

The results indicated a significant bacterial anti-adhesion activity in urine samples collected from volunteers that consumed cranberry powder compared to placebo (p < 0.001). This inhibition was clearly dose-dependent, prolonged (until 24 h with 72 mg of PAC) and increasing with the amount of PAC equivalents consumed in each cranberry powder regimen. An in vivo Caenorhabditis elegans model showed that cranberry acted against bacterial virulence: E. coli strain presented a reduced ability to kill worms after a growth in urines samples of patients who took cranberry capsules. This effect is particularly important with the regimen of 72 mg of PAC.

Conclusions

Administration of PAC-standardized cranberry powder at dosages containing 72 mg of PAC per day may offer some protection against bacterial adhesion and virulence in the urinary tract. This effect may offer a nyctohemeral protection.
Co-existence of Phenylketonuria and Fabry disease on a 3 year-old boy: case report
Authors: Concolino Daniela , Rapsomaniki Maria , Disabella Eliana , Sestito Simona , Pascale Maria G , Moricca Maria T , Bonapace Giuseppe , Arbustini Elisea , Strisciuglio Pietro
Published: May 2010

Background

The co-existence of two genetically distinct metabolic disorders in the same patient has rarely been reported. Phenylketonuria (PKU) is an inborn error of the metabolism resulting from a phenylalanine hydroxylase deficiency. Fabry disease (FD) is an X-linked lysosomal storage disorder due to a deficiency of the enzyme alpha-galactosidase A.

Case presentation

We report a case of a 3 year- old boy affected by classic PKU and FD, both confirmed by molecular data. The FD was suspected at the age of 21 months on the presence of non-specific GI symptoms (severe abdominal pain and periodically appearance of not specific episodes of gastroenteritis) apparently non related to PKU.

Conclusion

This is the first report of co-existence of FD and PKU, two different congenital inborn of metabolism and in consideration of the prevalence of each disease this chance association is a very unusual event. The co-existence of this diseases made very difficult the correct interpretation of clinical symptoms as lack of appetite, severe abdominal pain and non-specific gastroenteritis episodes. Furthermore, this case report helps to define the early clinical phenotype of FD.
Attributable mortality to radon exposure in Galicia, Spain. Is it necessary to act in the face of this health problem?
Authors: Pérez-Ríos Mónica , Barros-Dios Juan M , Montes-Martínez Agustín , Ruano-Ravina Alberto
Published: May 2010

Background

Radon is the second risk factor for lung cancer after tobacco consumption and therefore it is necessary to know the burden of disease due to its exposure. The objective of this study is to estimate radon-attributable lung cancer mortality in Galicia, a high emission area located at the Northwest Spain.

Methods

A prevalence-based attribution method was applied. Prevalence of tobacco use and radon exposure were obtained from a previously published study of the same area. Attributable mortality was calculated for each of six possible risk categories, based on radon exposure and smoking status. Two scenarios were used, with 37 Bq/m3 and 148 Bq/m3 as the respective radon exposure thresholds. As the observed mortality we used lung cancer mortality for 2001 from the Galician mortality registry.

Results

Mortality exclusively attributable to radon exposure ranged from 3% to 5% for both exposure thresholds, respectively. Attributable mortality to combined exposure to radon and smoking stood at around 22% for exposures above 148 Bq/m3. Applying the United States Environmental Protection Agency (EPA) action level, radon has a role in 25% of all lung cancers.

Conclusions

Although the estimates have been derived from a study with a relatively limited sample size, these results highlight the importance of radon exposure as a cause of lung cancer and its effect in terms of disease burden. Radon mitigation activities in the study area must therefore be enforced.
Predicting growth and curve progression in the individual patient with adolescent idiopathic scoliosis: design of a prospective longitudinal cohort study
Authors: Busscher Iris , Wapstra Frits Hein , Veldhuizen Albert G
Published: May 2010

Background

Scoliosis is present in 3-5% of the children in the adolescent age group, with a higher incidence in females. Treatment of adolescent idiopathic scoliosis is mainly dependent on the progression of the scoliotic curve. There is a close relationship between curve progression and rapid (spinal) growth of the patient during puberty. However, until present time no conclusive method was found for predicting the timing and magnitude of the pubertal growth spurt in total body height, or the curve progression of the idiopathic scoliosis.

The goal of this study is to determine the predictive value of several maturity indicators that reflect growth or remaining growth potential, in order to predict timing of the peak growth velocity of total body height in the individual patient with adolescent idiopathic scoliosis. Furthermore, different parameters are evaluated for their correlation with curve progression in the individual scoliosis patient.

Methods/design

This prospective, longitudinal cohort study will be incorporated in the usual care of patients with adolescent idiopathic scoliosis. All new patients between 8 and 17 years with adolescent idiopathic scoliosis (Cobb angle >10 degrees) visiting the outpatient clinic of the University Medical Center Groningen are included in this study. Follow up will take place every 6 months. The present study will use a new ultra-low dose X-ray system which can make total body X-rays. Several maturity indicators are evaluated like different body length dimensions, secondary sexual characteristics, skeletal age in hand and wrist, skeletal age in the elbow, the Risser sign, the status of the triradiate cartilage, and EMG ratios of the paraspinal muscle activity.

Correlations of all dimensions will be calculated in relationship to the timing of the pubertal growth spurt, and to the progression of the scoliotic curve. An algorithm will be made for the optimal treatment strategy in the individual patient with adolescent idiopathic scoliosis.

Discussion

This study will determine the value of many maturity indicators and will be useful as well for other clinicians treating children with disorders of growth. Since not all clinicians have access to the presented new 3D X-ray system or have the time to make EMG's, for example, all indicators will be correlated to the timing of the peak growth velocity of total body height and curve progression in idiopathic scoliosis. Therefore each clinician can chose which indicators can be used best in their practice.

Trial registration number

NTR2048
Isolation of an Escherichia coli K4 kfoC mutant over-producing capsular chondroitin
Authors: Zanfardino Anna , Restaino Odile F , Notomista Eugenio , Cimini Donatella , Schiraldi Chiara , De Rosa Mario , De Felice Maurilio , Varcamonti Mario
Published: May 2010

Background

Chondroitin sulphate is a complex polysaccharide having important structural and protective functions in animal tissues. Extracted from animals, this compound is used as a human anti-inflammatory drug. Among bacteria, Escherichia coli K4 produces a capsule containing a non-sulphate chondroitin and its development may provide an efficient and cheap fermentative production of the polysaccharide.

Results

A random N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis was performed on E. coli K4 to isolate mutants showing an increased production of chondroitin. Several mutants were isolated, one of which, here named VZ15, produced about 80% more chondroitin than the wild type E. coli. We found that the mutant has a missense mutation in the codon 313 of kfoC, the gene encoding chondroitin polymerase (K4CP), with a change from arginine to glutamine. A docking analysis to explain the increased productivity of the K4CP enzyme is presented.

Conclusion

The enhanced chondroitin production by the E. coli K4 mutant reported here shows the validity of the strain improvement strategy for more cost-friendly fermentative processes in the production of this pharmaceutically important but so-far expensive polysaccharide.
Global sequence variation in the histidine-rich proteins 2 and 3 of Plasmodium falciparum: implications for the performance of malaria rapid diagnostic tests
Authors: Baker Joanne , Ho Mei-Fong , Pelecanos Anita , Gatton Michelle , Chen Nanhua , Abdullah Salim , Albertini Audrey , Ariey Frederic , Barnwell John , Bell David , Cunningham Jane , Djalle Djibrine , Echeverry Diego F , Gamboa Dionicia , Hii Jeffery , Kyaw Myat Phone , Luchavez Jennifer , Membi Christopher , Menard Didier , Murillo Claribel , Nhem Sina , Ogutu Bernhards , Onyor Pamela , Oyibo Wellington , Wang Shan Qing , McCarthy James , Cheng Qin
Published: May 2010

Background

Accurate diagnosis is essential for prompt and appropriate treatment of malaria. While rapid diagnostic tests (RDTs) offer great potential to improve malaria diagnosis, the sensitivity of RDTs has been reported to be highly variable. One possible factor contributing to variable test performance is the diversity of parasite antigens. This is of particular concern for Plasmodium falciparum histidine-rich protein 2 (PfHRP2)-detecting RDTs since PfHRP2 has been reported to be highly variable in isolates of the Asia-Pacific region.

Methods

The pfhrp2 exon 2 fragment from 458 isolates of P. falciparum collected from 38 countries was amplified and sequenced. For a subset of 80 isolates, the exon 2 fragment of histidine-rich protein 3 (pfhrp3) was also amplified and sequenced. DNA sequence and statistical analysis of the variation observed in these genes was conducted. The potential impact of the pfhrp2 variation on RDT detection rates was examined by analysing the relationship between sequence characteristics of this gene and the results of the WHO product testing of malaria RDTs: Round 1 (2008), for 34 PfHRP2-detecting RDTs.

Results

Sequence analysis revealed extensive variations in the number and arrangement of various repeats encoded by the genes in parasite populations world-wide. However, no statistically robust correlation between gene structure and RDT detection rate for P. falciparum parasites at 200 parasites per microlitre was identified.

Conclusions

The results suggest that despite extreme sequence variation, diversity of PfHRP2 does not appear to be a major cause of RDT sensitivity variation.
Alterations in early cytokine-mediated immune responses to Plasmodium falciparum infection in Tanzanian children with mineral element deficiencies: a cross-sectional survey
Authors: Mbugi Erasto V , Meijerink Marjolein , Veenemans Jacobien , Jeurink Prescilla V , McCall Matthew , Olomi Raimos M , Shao John F , Verhoef Hans , Savelkoul Huub FJ
Published: May 2010

Background

Deficiencies in vitamins and mineral elements are important causes of morbidity in developing countries, possibly because they lead to defective immune responses to infection. The aim of the study was to assess the effects of mineral element deficiencies on early innate cytokine responses to Plasmodium falciparum malaria.

Methods

Peripheral blood mononuclear cells from 304 Tanzanian children aged 6-72 months were stimulated with P. falciparum-parasitized erythrocytes obtained from in vitro cultures.

Results

The results showed a significant increase by 74% in geometric mean of TNF production in malaria-infected individuals with zinc deficiency (11% to 240%; 95% CI). Iron deficiency anaemia was associated with increased TNF production in infected individuals and overall with increased IL-10 production, while magnesium deficiency induced increased production of IL-10 by 46% (13% to 144%) in uninfected donors. All donors showed a response towards IL-1β production, drawing special attention for its possible protective role in early innate immune responses to malaria.

Conclusions

In view of these results, the findings show plasticity in cytokine profiles of mononuclear cells reacting to malaria infection under conditions of different micronutrient deficiencies. These findings lay the foundations for future inclusion of a combination of precisely selected set of micronutrients rather than single nutrients as part of malaria vaccine intervention programmes in endemic countries.
Genetic polymorphism of merozoite surface protein-1 and merozoite surface protein-2 in Plasmodium falciparum field isolates from Myanmar
Authors: Kang Jung-Mi , Moon Sung-Ung , Kim Jung-Yeon , Cho Shin-Hyeong , Lin Khin , Sohn Woon-Mok , Kim Tong-Soo , Na Byoung-Kuk
Published: May 2010

Background

Merozoite surface protein-1 (MSP-1) and MSP-2 of Plasmodium falciparum are potential vaccine candidate antigens for malaria vaccine development. However, extensive genetic polymorphism of the antigens in field isolates of P. falciparum represents a major obstacle for the development of an effective vaccine. In this study, genetic polymorphism of MSP-1 and MSP-2 among P. falciparum field isolates from Myanmar was analysed.

Methods

A total of 63 P. falciparum infected blood samples, which were collected from patients attending a regional hospital in Mandalay Division, Myanmar, were used in this study. The regions flanking the highly polymorphic characters, block 2 for MSP-1 and block 3 for MSP-2, were genotyped by allele-specific nested-PCR to analyse the population diversity of the parasite. Sequence analysis of the polymorphic regions of MSP-1 and MSP-2 was also conducted to identify allelic diversity in the parasite population.

Results

Diverse allelic polymorphism of MSP-1 and MSP-2 was identified in P. falciparum isolates from Myanmar and most of the infections were determined to be mixed infections. Sequence analysis of MSP-1 block 2 revealed that 14 different alleles for MSP-1 (5 for K1 type and 9 for MAD20 type) were identified. For MSP-2 block 3, a total of 22 alleles (7 for FC27 type and 15 for 3D7 type) were identified.

Conclusion

Extensive genetic polymorphism with diverse allele types was identified in MSP-1 and MSP-2 in P. falciparum field isolates from Myanmar. A high level of mixed infections was also observed, as was a high degree of multiplicity of infection.
Pharmacokinetics of Linezolid and Ertapenem in experimental parapneumonic pleural effusion
Authors: Saroglou Maria , Tryfon Stavros , Ismailos Georgios , Liapakis Ioannis , Tzatzarakis Manolis , Tsatsakis Aristidis , Papalois Apostolos , Bouros Demosthenes
Published: May 2010

Objective

To determine the extent of linezolid and ertapenem penetration into the empyemic fluid using a rabbit model of empyema.

Methods

An empyema was created via the intrapleural injection of Escherichia coli bacteria (ATCC 35218) into the pleural space of New Zealand white rabbits. After an empyema was verified by thoracocentesis, 24 hours post inoculation, linezolid (10 mg/kg) and ertapenem (60 mg/kg) were administered intravenously into 10 and 8 infected empyemic rabbits, respectively. Antibiotic levels were determined in samples of pleural fluid and blood serum, collected serially at 1, 2, 4, 6 and 8 hours, after administration each of the two antibiotics.

Results

Linezolid as well as ertapenem penetrate well into the empyemic pleural fluid, exhibiting a slower onset and decline compared to the corresponding blood serum levels. Equilibration between blood serum and pleural fluid compartments seems to occur at 1.5 hours for both linezolid and ertapenem, with peak pleural fluid levels (Cmaxpf of 2.02 ± 0.73 «mu»g/ml and Cmaxpf of 3.74 ± 1.39 «mu»g/ml, correspondingly) occurring 2 hours post antibiotics administration and decreasing very slowly thereafter. The serum concentrations for both antibiotics were significantly lower from the corresponding pleural fluid ones during the 8 hours collecting data, with the exception of samples collected at the 1st hour (Cmaxserum of 2.1 ± 1.2 «mu»g/ml for linezolid and Cmaxserum of 6.26 ± 2.98 «mu»g/ml for ertapenem).

Conclusion

Pleural fluid levels of both antibiotics are inhibitory for common specified pathogens causing empyema.
Spawning seasons of Rasbora tawarensis (Pisces: Cyprinidae) in Lake Laut Tawar, Aceh Province, Indonesia
Authors: Muchlisin ZA , Musman Musri , Azizah MN Siti
Published: May 2010

Background

Rasbora tawarensis is an endemic freshwater fish in Lake Laut Tawar, Aceh Province, Indonesia. Unfortunately, its status is regarded as critical endangered with populations decreasing in recent years. To date no information on the spawning activities of the fish are available. Therefore, this study provides a contribution to the knowledge on reproductive biology of R. tawarensis especially on spawning seasons as well as basic information for conservation of the species.

Methods

Monthly sampling was conducted from April 2008 to March 2009 by using selective gillnets. The gonadosomatic index, size composition and sex ratio were assessed. The gonadal development was evaluated based on macroscopic and microscopic examinations of the gonads.

Results

The gonadosomatic index (GSI) varied between 6.65 to 18.16 in female and 4.94 to 8.56 for male. GSI of the female R. tawarensis was higher in March, September and December indicating the onset of reproductive seasons, the GSI and oocyte size being directly correlated with gonadal development stages. Although, a greater proportion of mature male than female was detected during the study, the sex ratio showed that the overall number of female was higher than male. The ovaries had multiple oocyte size classes at every stage of gonadal development, thus R. tawarensis can be classified as a group synchronous spawner or a fractional multiple spawner.

Conclusion

The spawning seasons of R. tawarensis were three times a year and September being the peak of the reproductive season and the female was the predominant sex. This species is classified as a group synchronous spawner.
Sexual dysfunctions in patients with diabetes: a study from Iran
Authors: Ziaei-Rad Marzieh , Vahdaninia Mariam , Montazeri Ali
Published: May 2010

Background

Diabetes mellitus is a chronic disease that causes short and long-term complications. This study aimed to investigate the prevalence of sexual dysfunctions (SD) among diabetic patients in Iran and to examine whether glycemic control has a role in SD.

Methods

A consecutive sample of diabetic women and men who were registered in the Isfahan Endocrine and Metabolism Center, Iran were studied. Sexual dysfunction was evaluated using the Female Sexual Function Index (FSFI) in women and the International Index of Erectile Function (IIEF) in men. In addition the level of glycosylated hemoglobin was assessed to classify the diabetes status in patients.

Results

In all 200 patients (100 male and 100 female) were entered into the study. The mean age of patients was 48.6 (SD = 7.3) years and most had type 2 diabetes (91.0%). The results showed that sexual dysfunctions were widespread in both gender and 165 (82.5%) patients reported that experienced at least one sexual dysfunction. There were significant associations between sexual dysfunctions and gender and type of diabetes (P = 0.04). Women and patients with type 1 diabetes had higher rates of SD. No major differences were found between SD and age, diabetes status, duration of diabetes and hypertension. In addition, glycemic control did not show a significant association with SD in both genders.

Conclusion

The findings of this study showed that SD prevalence was high in diabetic patients of both genders and the glycemic control did not correlate with the frequency of SD in the study population. It is recommended that SD should be addressed more precisely in health care practice in Iran.
Immunotherapy with Allergen Peptides
Authors: Larché Mark
Published: May 2010

Specific allergen immunotherapy (SIT) is disease-modifying and efficacious. However, the use of whole allergen preparations is associated with frequent allergic adverse events during treatment. Many novel approaches are being designed to reduce the allergenicity of immunotherapy preparations whilst maintaining immunogenicity. One approach is the use of short synthetic peptides which representing dominant T cell epitopes of the allergen. Short peptides exhibit markedly reduced capacity to cross link IgE and activate mast cells and basophils, due to lack of tertiary structure. Murine pre-clinical studies have established the feasibility of this approach and clinical studies are currently in progress in both allergic and autoimmune diseases.
Airways Disease: Phenotyping Heterogeneity Using Measures of Airway Inflammation
Authors: Siddiqui Salman , Brightling Christopher E.
Published: May 2010

Despite asthma and chronic obstructive pulmonary disease being widely regarded as heterogeneous diseases, a consensus for an accurate system of classification has not been agreed. Recent studies have suggested that the recognition of subphenotypes of airway disease based on the pattern of airway inflammation may be particularly useful in increasing our understanding of the disease. The use of non-invasive markers of airway inflammation has suggested the presence of four distinct phenotypes: eosinophilic, neutrophilic, mixed inflammatory and paucigranulocytic asthma. Recent studies suggest that these subgroups may differ in their etiology, immunopathology and response to treatment. Importantly, novel treatment approaches targeted at specific patterns of airway inflammation are emerging, making an appreciation of subphenotypes particularly relevant. New developments in phenotyping inflammation and other facets of airway disease mean that we are entering an era where careful phenotyping will lead to targeted therapy.
Nonsteroidal Anti-Inflammatory Drug Hypersensitivity in Preschool Children
Authors: Kidon Mona Iancovici , Kang Liew Woei , Chin Chiang Wen , Hoon Lim Siok , Hugo Van Bever
Published: May 2010

Although extensively studied in adults, nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity in children, especially in young children, remains poorly defined. Pediatricians, prescribing antipyretics for children, rarely encounter significant problems, but the few epidemiologic studies performed show conflicting results. Although it is clear that some patients with acetylsalicylic acid (ASA)-sensitive asthma have their clinical onset of disease in childhood and bronchoconstriction after ASA challenge is seen in 0 to 22% of asthmatic children so challenged, ibuprofen at antipyretic doses may cause acute respiratory problems only in a very small number of mild to moderate asthmatics. The recently elucidated mechanism of action of acetaminophen may explain some occurrences of adverse reactions in patients with cross-reactive NSAID hypersensitivity on the basis of its inhibitory activity on the newly described enzyme, cyclooxygenase (COX)-3. This nonspecific sensitivity to inhibition of COX is most likely genetically determined and shows a remarkable association with atopic disease even in the very young age group and possibly an increased predilection in specific ethnic groups. This review summarizes state-of-the-art published data on NSAID hypersensitivity in preschool children.
Interleukin-12 Peripheral Blood Levels in Asthmatic Children
Authors: Soferman Ruth , Rosenzwig Idit , Fireman Elizabeth
Published: May 2010

Interleukin-12 (IL-12) was measured in 45 asthmatic children aged 3 to 16 years. The assessments were performed on 20 children during an episode of acute exacerbation and on 25 children during remission. There was no significant difference between the mean IL-12 level during exacerbation (1.63 ± 2.08 pg/mL) and during remission (0.88 ± 0.56 pg/mL) (p= .83). A positive, but insignificant, correlation was found between forced expiratory volume in 1 second and IL-12 (p= .634). IL-12 levels were significantly lower in children with a positive family history of asthma (1.13 ± 1.78 pg/mL) compared with those without (1.31 ± 1.06 pg/mL) (p< .012), supporting the theory that the gene-environment interactions affect the immune responses. IL-12 peripheral blood levels had no detectable impact on the course of established asthma in the study population.
Concurrent radiochemotherapy in advanced hypopharyngeal cancer
Authors: Krstevska Valentina , Stojkovski Igor , Lukarski Dusko
Published: May 2010

Background

Concurrent platinum-based radiochemotherapy has been recommended as a standard of care in patients with locally advanced squamous cell head and neck carcinomas. Unfortunately, there is a lack of level one evidence on best treatment approach for advanced hypopharyngeal cancer. This report aims to summarize the results of our study on concurrent radiochemotherapy in patients with advanced hypopharyngeal cancer.

Methods

A retrospective analysis of 41 patients with stage III-IV hypopharyngeal cancer was performed. All patients were treated with three dimensional conformal radiotherapy and received 70 Gy in 35 fractions (2 Gy per fraction, 5 fractions per week). In dependence of the period when radiotherapy was realized, two different treatment techniques were used. Concurrent chemotherapy consisted of cisplatin 30 mg/m2 given on a weekly basis.

Results

The median age was 52 years (range 29-70). Stage IV disease was recognized in 73.2% of the patients. Complete response rates at the primary site and at the metastatic neck lymph nodes were 68.3% and 36.6%, respectively. A complete composite response was present in 27 patients (65.9%). Median follow-up was 13 months (range 7-36). Distant metastases as initial failure occurred in 7 patients (46.7%). The 2-year local relapse-free survival and regional relapse-free survival rates were 55.2% and 75.8%, respectively. The 2-year locoregional relapse-free survival rate was 51.3%. The 2-year disease-free survival and overall survival rates were 29.3% and 32.8%, respectively. Confluent mucositis was developed in 46.3% of patients. Leucopenia grade 1 was the most frequent hematological toxicity. The median weight loss at the end of treatment was 12% (range 5-21). The worst grade of late toxicity was most commonly pronounced in the skin and in the subcutaneous tissue.

Conclusions

Based on unsatisfactory results in our study we suggest that the use of sequential radiochemotherapy or chemotherapy given concomitantly with altered fractionation radiotherapy with the implementation of intensity-modulated radiotherapy as radiotherapy technique could represent treatment approaches able to improve outcome in patients with advanced hypopharyngeal cancer.
Mapping the potential distribution of high artemisinin-yielding Artemisia annua L. (Qinghao) in China with a geographic information system
Authors: Huang Linfang , Xie Caixiang , Duan Baozhong , Chen Shilin
Published: May 2010

Background

Artemisia annua L. is an important source for artemisinin, a potent drug for treating malaria. This study aims to map and predict the potential geographic distribution of A. annua L. in China.

Methods

The Geographic Information System for traditional Chinese medicine (TCM-GIS) was developed and used to map the potential geographic distribution of A. annua L.

Results

Climatic, edaphic and topographic characteristics of A. annua L. microhabitats in Youyang County were mapped to find distribution patterns. The maps identified that certain habitats in the Chongqing region and some potential regions, especially in Guizhou Province, possess similarity indices of ≥98%. In particular, high quality microhabitats A. annua L. were found in the Wuling mountains region.

Conclusion

The present study demonstrates a GIS approach to predict potential habitats for A. annua L. TCM-GIS is a powerful tool for assessing bioclimatic suitability for medicinal plants.
Endocytic pathways mediating oligomeric Aβ42 neurotoxicity
Authors: Yu Chunjiang , Nwabuisi-Heath Evelyn , Laxton Kevin , LaDu Mary Jo
Published: May 2010

Background

One pathological hallmark of Alzheimer's disease (AD) is amyloid plaques, composed primarily of amyloid-β peptide (Aβ). Over-production or diminished clearance of the 42 amino acid form of Aβ (Aβ42) in the brain leads to accumulation of soluble Aβ and plaque formation. Soluble oligomeric Aβ (oAβ) has recently emerged to be as a likely proximal cause of AD.

Results

Here we demonstrate that endocytosis is critical in mediating oAβ42-induced neurotoxicity and intraneuronal accumulation of Aβ. Inhibition of clathrin function either with a pharmacological inhibitor, knock-down of clathrin heavy chain expression, or expression of the dominant-negative mutant of clathrin-assembly protein AP180 did not block oAβ42-induced neurotoxicity or intraneuronal accumulation of Aβ. However, inhibition of dynamin and RhoA by expression of dominant negative mutants reduced neurotoxicity and intraneuronal Aβ accumulation. Pharmacologic inhibition of the dynamin-mediated endocytic pathway by genistein also reduced neurotoxicity.

Conclusions

These data suggest that dynamin-mediated and RhoA-regulated endocytosis are integral steps for oligomeric Aβ42-induced neurotoxicity and intraneuronal Aβ accumulation.
Inhibitory effects of ZSTK474, a novel phosphoinositide 3-kinase inhibitor, on osteoclasts and collagen-induced arthritis in mice
Authors: Toyama Shoko , Tamura Naoto , Haruta Kazuhiko , Karakida Takeo , Mori Shigeyuki , Watanabe Tetsuo , Yamori Takao , Takasaki Yoshinari
Published: May 2010

Introduction

Targeting joint destruction induced by osteoclasts (OCs) is critical for management of patients with rheumatoid arthritis (RA). Since phosphoinositide 3-kinase (PI3-K) plays a critical role in osteoclastogenesis and bone resorption, we examined the effects of ZSTK474, a novel phosphoinositide 3-kinase (PI3-K)-specific inhibitor, on murine OCs in vitro and in vivo.

Methods

The inhibitory effect of ZSTK474 on OC formation was determined and compared with other PI3-K inhibitors by counting tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells after culturing murine bone marrow monocytic OC precursors, and RAW264.7 cells. Activation of Akt and expression of nuclear factor of activated T cells (NFAT) c1 in cultured RAW264.7 cells were examined. The suppressing effect of ZSTK474 on bone resorption was assessed by the pit formation assay. The in vivo effects of ZSTK474 were studied in collagen-induced arthritis (CIA) in the mouse. Oral daily administration of ZSTK474 was started either when more than half or when all mice developed arthritis. Effects of ZSTK474 were evaluated using the arthritis score and histological score of the hind paws.

Results

ZSTK474 inhibited the differentiation of bone marrow OC precursors and RAW264.7 cells in a dose-dependent manner. The inhibitory effect of ZSTK474 was much stronger than that of LY294002, the most commonly used PI3-K inhibitor. In addition, ZSTK474 suppressed the bone resorbing activity of mature OCs. Moreover, oral daily administration of ZSTK474, even when begun after the development of arthritis, ameliorated CIA in mice without apparent toxicity. Histological examination of the hind paw demonstrated noticeable reduction of inflammation and of cartilage destruction in ZSTK474-treated mice. ZSTK474 also significantly decreased OC formation adjacent to the tarsal bone of the hind paw.

Conclusions

These findings suggest that inhibition of PI3-K with ZSTK474 may potentially suppress synovial inflammation and bone destruction in patients with RA.
Incorporating tumour pathology information into breast cancer risk prediction algorithms
Authors: Mavaddat Nasim , Rebbeck Timothy R , Lakhani Sunil R , Easton Douglas F , Antoniou Antonis C
Published: May 2010

Introduction

Mutations in BRCA1 and BRCA2 confer high risks of breast cancer and ovarian cancer. The risk prediction algorithm BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) may be used to compute the probabilities of carrying mutations in BRCA1 and BRCA2 and help to target mutation screening. Tumours from BRCA1 and BRCA2 mutation carriers display distinctive pathological features that could be used to better discriminate between BRCA1 mutation carriers, BRCA2 mutation carriers and noncarriers. In particular, oestrogen receptor (ER)-negative status, triple-negative (TN) status, and expression of basal markers are predictive of BRCA1 mutation carrier status.

Methods

We extended BOADICEA by treating breast cancer subtypes as distinct disease end points. Age-specific expression of phenotypic markers in a series of tumours from 182 BRCA1 mutation carriers, 62 BRCA2 mutation carriers and 109 controls from the Breast Cancer Linkage Consortium, and over 300,000 tumours from the general population obtained from the Surveillance Epidemiology, and End Results database, were used to calculate age-specific and genotype-specific incidences of each disease end point. The probability that an individual carries a BRCA1 or BRCA2 mutation given their family history and tumour marker status of family members was computed in sample pedigrees.

Results

The cumulative risk of ER-negative breast cancer by age 70 for BRCA1 mutation carriers was estimated to be 55% and the risk of ER-positive disease was 18%. The corresponding risks for BRCA2 mutation carriers were 21% and 44% for ER-negative and ER-positive disease, respectively. The predicted BRCA1 carrier probabilities among ER-positive breast cancer cases were less than 1% at all ages. For women diagnosed with breast cancer below age 50 years, these probabilities rose to more than 5% in ER-negative breast cancer, 7% in TN disease and 24% in TN breast cancer expressing both CK5/6 and CK14 cytokeratins. Large differences in mutation probabilities were observed by combining ER status and other informative markers with family history.

Conclusions

This approach combines both full pedigree and tumour subtype data to predict BRCA1/2 carrier probabilities. Prediction of BRCA1/2 carrier status, and hence selection of women for mutation screening, may be substantially improved by combining tumour pathology with family history of cancer.
Activated protein C ameliorates coagulopathy but does not influence outcome in lethal H1N1 influenza: a controlled laboratory study
Authors: Schouten Marcel , van der Sluijs Koenraad F , Gerlitz Bruce , Grinnell Brian W , Roelofs Joris JTH , Levi Marcel M , van 't Veer Cornelis , Poll Tom van der
Published: May 2010

Introduction

Influenza accounts for 5 to 10% of community-acquired pneumonias and is a major cause of mortality. Sterile and bacterial lung injuries are associated with procoagulant and inflammatory derangements in the lungs. Activated protein C (APC) is an anticoagulant with anti-inflammatory properties that exert beneficial effects in models of lung injury. We determined the impact of lethal influenza A (H1N1) infection on systemic and pulmonary coagulation and inflammation, and the effect of recombinant mouse (rm-) APC hereon.

Methods

Male C57BL/6 mice were intranasally infected with a lethal dose of a mouse adapted influenza A (H1N1) strain. Treatment with rm-APC (125 μg intraperitoneally every eight hours for a maximum of three days) or vehicle was initiated 24 hours after infection. Mice were euthanized 48 or 96 hours after infection, or observed for up to nine days.

Results

Lethal H1N1 influenza resulted in systemic and pulmonary activation of coagulation, as reflected by elevated plasma and lung levels of thrombin-antithrombin complexes and fibrin degradation products. These procoagulant changes were accompanied by inhibition of the fibrinolytic response due to enhanced release of plasminogen activator inhibitor type-1. Rm-APC strongly inhibited coagulation activation in both plasma and lungs, and partially reversed the inhibition of fibrinolysis. Rm-APC temporarily reduced pulmonary viral loads, but did not impact on lung inflammation or survival.

Conclusions

Lethal influenza induces procoagulant and antifibrinolytic changes in the lung which can be partially prevented by rm-APC treatment.
Hypofractionated Stereotactic Radiation Therapy: An Effective Therapy for Recurrent High-Grade Gliomas
Authors: Fogh Shannon E. , Andrews David W. , Glass Jon , Curran Walter , Glass Charles , Champ Colin , Evans James J. , Hyslop Terry , Pequignot Edward , Downes Beverly , Comber Eileen , Maltenfort Mitchell , Dicker Adam P. , Werner-Wasik Maria
Published: May 2010

Purpose

Salvage options for recurrent high-grade gliomas (HGGs) are limited by cumulative toxicity and limited efficacy despite advances in chemotherapeutic and radiotherapeutic techniques. Previous studies have reported encouraging survival results and favorable toxicity with fractionated stereotactic radiotherapy, and small studies have shown similar benefit using a shortened course of hypofractionated stereotactic radiation therapy (H-SRT). We sought to determine the efficacy and toxicity profile of H-SRT alone or in addition to repeat craniotomy or concomitant chemotherapy.

Patients and Methods

Between 1994 and 2008, 147 patients with recurrent HGG were treated with H-SRT (median dose, 35 Gy in 3.5-Gy fractions). Cox regression models were used to analyze survival outcomes. Variables included age, surgery before H-SRT, time to first recurrence, reirradiation dose, inclusion of chemotherapy with H-SRT, and gross tumor volume (GTV).

Results

Younger age (P = .001), smaller GTV (P = .025), and shorter time between diagnosis and recurrence (P = .034) were associated with improvement in survival from H-SRT. Doses of radiation ≥ 35 Gy approached significance (P = .07). There was no significant benefit of surgical resection or chemotherapy in this population when analysis was controlled for other prognostic factors.

Conclusion

H-SRT was well tolerated and resulted in a median survival time of 11 months after H-SRT, independent of re-operation or concomitant chemotherapy. Patients who experienced recurrence within 6 months after initial treatment had an excellent response and should not be disqualified from H-SRT. This is the largest series to examine the efficacy and tolerability of H-SRT in recurrent HGG.