bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation of the Continuous AutoTransfusion System (C.A.T.S) in Open Abdominal Aortic Aneurysm Repair: An Observational Comparative Cohort Study
Authors: Tawfick Wael A. , O'Connor Martina , Hynes Niamh , Sultan Sherif
Published: January 2008

The use of the Continuous AutoTransfusion System (C.A.T.S; Fresenius Hemotechnology, Bad Homburg v.d.H., Germany), which conserves allogenic blood, is reported in 187 patients having abdominal aortic aneurysm repair during a 9-year period. Patients were allocated to C.A.T.S if a Haemovigilance technician was available. A mean of 685 mL of retrieved blood was reinfused in 101 patients receiving C.A.T.S; 61% required 2 U or less. All control patients required 3 U or more of allogenic blood. Allogenic transfusion in C.A.T.S patients decreased significantly ( P < .0001). Mean intensive care unit stay was significantly reduced in C.A.T.S patients ( P = .042). Mean postoperative hospital stay was 18 days for C.A.T.S group and 25 days in control patients ( P = .014). The respective 30-day mortality was 12% versus 19% ( P = .199). The C.A.T.S markedly reduced the amount of blood transfused, was associated with reduced intensive care unit and postoperative hospital stay, and was cost-effective.
Endovascular Repair of a Common Iliac Artery Aneurysm Using the Cook Zenith Abdominal Aortic Aneurysm Endovascular Graft Converter
Authors: Crago Aimee M. , Singh Niten , Deaton David H. , Neville Richard F. , Laredo James
Published: January 2008

Isolated common iliac artery aneurysm is a rare condition that is treated aggressively because of its high risk of rupture. Endovascular abdominal aortic aneurysm (AAA) repair has recently been extended to the clinical management of the iliac artery aneurysm. Stent grafts have been used successfully to exclude iliac artery aneurysms. Successful graft deployment and aneurysm exclusion require adequate seal and fixation at the proximal and distal attachment sites. This article presents a high-risk surgical patient whose 6.8-cm-diameter iliac artery aneurysm was repaired with a Zenith AAA Endovascular Graft Converter (Cook, Bloomington, Indiana). This device is normally used to convert an aortobiiliac endograft to an aortouniiliac endograft during AAA repair. The tapered 80-mm-long graft has diameters of 24 mm proximally and 12 mm distally. Completion arteriogram demonstrated exclusion of the iliac artery aneurysm with no evidence of endoleak. No postoperative complications occurred. No endoleak was seen on the follow-up abdominal computed tomography scan.
Prospective Randomized Trials of Carotid Artery Stenting Versus Carotid Endarterectomy: An Appraisal of the Current Literature
Authors: Lin Peter H. , Barshes Neal R. , Annambhotla Suman , Huynh Tam T.
Published: January 2008

Carotid artery stenting has emerged as a treatment alternative in patients at high risk for carotid endarterectomy. Recent technological advances in catheter-based intervention have both facilitated the procedure and possibly improved the clinical outcome of this percutaneous intervention. The reduction in device profile of introducer sheaths and stents, as well as the ubiquitous use of neuroprotection devices, has resulted in a greater application of this treatment modality in patients with carotid bifurcation disease. The efficacy of carotid artery stenting must be carefully evaluated against carotid endarterectomy in a prospective randomized manner, as the latter treatment has long been considered the standard treatment of carotid occlusive disease. Several recent clinical trials comparing carotid artery stenting versus carotid endarterectomy have yielded mixed results with regard to the efficacy of this percutaneous intervention. This article analyzed the results of these prospective randomized trials comparing carotid artery stenting and carotid endarterectomy. Critical appraisal of these trials, as well as relevant methodological issues of these investigations, is discussed in this article.
The Complexities of Teachers' Commitment to Environmental Education
Authors: Sosu Edward M. , McWilliam Angus , Gray Donald S.
Published: January 2008

This article argues that a mixed methods approach is useful in understanding the complexity that underlies teachers' commitment to environmental education. Using sequential and concurrent procedures, the authors demonstrate how different methodological approaches highlighted different aspects of teacher commitment. The quantitative survey examined significant factors that determine teachers' commitment, whereas the qualitative approach used a soft systems methodology to expand understanding and to explore ways of increasing teacher commitment to environmental education. Results indicate a complex range of factors affecting commitment, and different layers of reality discovered by the different methods provide a holistic understanding of teacher commitment to environmental education. The article also demonstrates how a mixed methods approach can serve the dual role of confirming and elaborating findings.
PRDM1 is involved in chemoresistance of T-cell lymphoma and down-regulated by the proteasome inhibitor
Authors: Zhao Wei-Li , Liu Yan-Yan , Zhang Qun-Ling , Wang Li , Leboeuf Christophe , Zhang Yi-Wen , Ma Jie , Garcia José-Francisco , Song Yong-Ping , Li Jun-Min , Shen Zhi-Xiang , Chen Zhu , Janin Anne , Chen Sai-Juan
Published: January 2008

The positive regulatory domain I (PRDM1) is a master regulator of terminal B-cell differentiation. However, PRDM1 is not B-cell specific. To determine its role in T-cell lymphoma, PRDM1 expression was investigated in 60 patients. PRDM1α and PRDM1β transcripts were detected in laser-microdissected T-lymphoma cells in 27 and 14 patients, respectively, mostly in cases with IRF4 expression. PRDM1β was associated with increased c-MYC expression. PRDM1β-positive patients displayed advanced Ann Arbor stage and high-risk International Prognostic Index and were linked to short survival times. In vitro, PRDM1β was related to resistance to chemotherapeutic agents and could be down-regulated by the proteasome inhibitor bortezomib. Kinetic studies showed that bortezomib down-regulation of PRDM1β preceded decreased IRF4 and c-MYC expression. An earlier retaining of cytoplasmic IκBα in bortezomib-treated cells was revealed, concomitant with blockade of NF-κB nuclear translocation. These results demonstrate the involvement of PRDM1β in T-cell lymphoma, with possible therapeutic interference by the proteasome inhibitor.
Platelet larceny: spurious hypoxaemia due to extreme thrombocytosis
Authors: Mehta A. , Lichtin A. E. , Vigg A. , Parambil J. G.
Published: January 2008

Rapid oxygen consumption by markedly increased numbers of hypermetabolic leukocytes in leukaemic patients resulting in the apparent diagnosis of hypoxaemia on arterial blood gas analyses is termed leukocyte larceny.

In the present report, a case of polycythaemia vera, extreme thrombocytosis, normal leukocyte counts and arterial hypoxaemia in the absence of clinical, radiological or physiological evidence of lung disease is described.

This pseudohypoxaemia case was established by pulse oximetry, as well as by incubation of a blood specimen with potassium cyanide, and became less significant after the use of cytoreductive agents showed a proportionate increase in arterial oxygen tension as platelet counts decreased on serial arterial blood gas analyses.

The present case report demonstrates spurious hypoxaemia due to extreme thrombocytosis and shows that, beside significant leukocytosis, even markedly elevated platelet counts can cause larceny of arterial blood oxygen.
Cannabis use and risk of lung cancer: a case–control study
Authors: Aldington S. , Harwood M. , Cox B. , Weatherall M. , Beckert L. , Hansell A. , Pritchard A. , Robinson G. , Beasley R.
Published: January 2008

The aim of the present study was to determine the risk of lung cancer associated with cannabis smoking.

A case–control study of lung cancer in adults ≤55 yrs of age was conducted in eight district health boards in New Zealand. Cases were identified from the New Zealand Cancer Registry and hospital databases. Controls were randomly selected from the electoral roll, with frequency matching to cases in 5-yr age groups and district health boards. Interviewer-administered questionnaires were used to assess possible risk factors, including cannabis use. The relative risk of lung cancer associated with cannabis smoking was estimated by logistic regression.

In total, 79 cases of lung cancer and 324 controls were included in the study. The risk of lung cancer increased 8% (95% confidence interval (CI) 2–15) for each joint-yr of cannabis smoking, after adjustment for confounding variables including cigarette smoking, and 7% (95% CI 5–9) for each pack-yr of cigarette smoking, after adjustment for confounding variables including cannabis smoking. The highest tertile of cannabis use was associated with an increased risk of lung cancer (relative risk 5.7 (95% CI 1.5–21.6)), after adjustment for confounding variables including cigarette smoking.

In conclusion, the results of the present study indicate that long-term cannabis use increases the risk of lung cancer in young adults.
Mucosal inflammation in idiopathic bronchiectasis: cellular and molecular mechanisms
Authors: Fuschillo S. , De Felice A. , Balzano G.
Published: January 2008

Bronchiectasis is a chronic and debilitating lung disease, characterised by irreversible dilatation of the bronchi as consequence of airway injury and remodelling due to recurrent or chronic airway inflammation and infection. The underlying aetiologies include autoimmune diseases, severe infections, genetic abnormalities and acquired disorders.

The pathogenesis of bronchiectasis is poorly understood. Three distinct pathogenetic elements, namely infection, inflammation and enzymatic actions, which interact with each other, have been implicated in the pathophysiology of bronchiectasis.

Some recent observations indicate that airway inflammation in bronchiectasis comes from a deregulated cytokine network independent of bacterial airway colonisation.

In the present review, current knowledge about cellular and molecular inflammatory events in the dynamic process of host–pathogen interaction that are thought to play a relevant role in the pathogenic mechanisms of airway wall destruction leading to bronchiectasis are discussed.
Endothelin receptor antagonists in pulmonary arterial hypertension
Authors: Dupuis J. , Hoeper M. M.
Published: January 2008

The endothelin (ET) system, especially ET-1 and the ETAand ETBreceptors, has been implicated in the pathogenesis of pulmonary arterial hypertension (PAH). Together with prostanoids and phosphodiesterase 5 inhibitors, ET receptor antagonists have become mainstays in the current treatment of PAH.

Three substances are currently available for the treatment of PAH. One of these substances, bosentan, blocks both ETAand ETBreceptors, whereas the two other compounds, sitaxsentan and ambrisentan, are more selective blockers of the ETAreceptor.

There is ongoing debate as to whether selective or nonselective ET receptor blockade is advantageous in the setting of PAH, although there is no clear evidence that receptor selectivity is relevant with regard to the clinical effects of these drugs.

For the time being, other features, such as safety profiles and the potential for pharmacokinetic interactions with other drugs used in the treatment of PAH, may be more important than selectivity or nonselectivity when selecting treatments for individual patients.
Nontypeable Haemophilus influenzae induces COX-2 and PGE2 expression in lung epithelial cells via activation of p38 MAPK and NF-kappa B
Authors: Xu Feng , Xu Zhihao , Zhang Rong , Wu Zuqun , Lim Jae-Hyang , Koga Tomoaki , Li Jian-Dong , Shen Huahao
Published: January 2008

Background

NontypeableHaemophilus influenzae(NTHi) is an important respiratory pathogen implicated as an infectious trigger in chronic obstructive pulmonary disease, but its molecular interaction with human lung epithelial cells remains unclear. Herein, we tested that the hypothesis that NTHi induces the expression of cyclooxygenase (COX)-2 and prostaglandin E2 (PGE2) via activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappa B in pulmonary alveolar epithelial cells.

Methods

Human alveolar epithelial A549 cells were infected with different concentrations of NTHi. The phosphorylation of p38 MAPK was detected by Western blot analysis, the DNA binding activity of NF-kappa B was assessed by electrophoretic mobility shift assay (EMSA), and the expressions of COX-1 and 2 mRNA and PGE2 protein were measured by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA), respectively. The roles of Toll-like receptor (TLR) 2 and TLR4, well known NTHi recognizing receptor in lung epithelial cell and gram-negative bacteria receptor, respectively, on the NTHi-induced COX-2 expression were investigated in the HEK293 cells overexpressing TLR2 and TLR4in vitroand in the mouse model of NTHi-induced pneumonia by using TLR2 and TLR4 knock-out micein vivo. In addition, the role of p38 MAPK and NF-kappa B on the NTHi-induced COX-2 and PGE2 expression was investigated by using their specific chemical inhibitors.

Results

NTHi induced COX-2 mRNA expression in a dose-dependent manner, but not COX-1 mRNA expression in A549 cells. The enhanced expression of PGE2 by NTHi infection was significantly decreased by pre-treatment of COX-2 specific inhibitor, but not by COX-1 inhibitor. NTHi induced COX-2 expression was mediated by TLR2 in the epithelial cellin vitroand in the lungs of micein vivo. NTHi induced phosphorylation of p38 MAPK and up-regulated DNA binding activity of NF-kappa B. Moreover, the expressions of COX-2 and PGE2 were significantly inhibited by specific inhibitors of p38 MAPK and NF-kappa B. However, NTHi-induced DNA binding activity of NF-kappa B was not affected by the inhibition of p38 MAPK.

Conclusion

NTHi induces COX-2 and PGE2 expression in a p38 MAPK and NF-kappa B-dependent manner through TLR2 in lung epithelial cellsin vitroand lung tissuesin vivo. The full understanding of the role of endogenous anti-inflammatory PGE2 and its regulation will bring new insight to the resolution of inflammation in pulmonary bacterial infections.
Response projected clustering for direct association with physiological and clinical response data
Authors: Yi Sung-Gon , Park Taesung , Lee Jae K
Published: January 2008

Background

Microarray gene expression data are often analyzed together with corresponding physiological response and clinical metadata of biological subjects, e.g. patients' residual tumor sizes after chemotherapy or glucose levels at various stages of diabetic patients. Current clustering analysis cannot directly incorporate such quantitative metadata into the clustering heatmap of gene expression. It will be quite useful if these clinical response data can be effectively summarized in the high-dimensional clustering display so that important groups of genes can be intuitively discovered with different degrees of relevance to target disease phenotypes.

Results

We introduced a novel clustering analysis approach,response projected clustering(RPC), which uses a high-dimensional geometrical projection of response data to the gene expression space. The projected response vector, which becomes the origin in the projected space, is then clustered together with the projected gene vectors based on their different degrees of association with the response vector. A bootstrap-counting based RPC analysis is also performed to evaluate statistical tightness of identified gene clusters. Our RPC analysis was applied to thein vitrogrowth-inhibition and microarray profiling data on the NCI-60 cancer cell lines and the microarray gene expression study of macrophage differentiation in atherogenesis. These RPC applications enabled us to identify many known and novel gene factors and their potential pathway associations which are highly relevant to the drug's chemosensitivity activities and atherogenesis.

Conclusion

We have shown that RPC can effectively discover gene networks with different degrees of association with clinical metadata. Performed on each gene's response projected vector based on its degree of association with the response data, RPC effectively summarizes individual genes' association with metadata as well as their own expression patterns. Thus, RPC greatly enhances the utility of clustering analysis on investigating high-dimensional microarray gene expression data with quantitative metadata.
Characterization of a newly developed chicken 44K Agilent microarray
Authors: Li Xianyao , Chiang Hsin-I , Zhu James , Dowd Scot E , Zhou Huaijun
Published: January 2008

Background

The development of microarray technology has greatly enhanced our ability to evaluate gene expression. In theory, the expression of all genes in a given organism can be monitored simultaneously. Sequencing of the chicken genome has provided the crucial information for the design of a comprehensive chicken transcriptome microarray. A long oligonucleotide microarray has been manually curated and designed by our group and manufactured using Agilent inkjet technology. This provides a flexible and powerful platform with high sensitivity and specificity for gene expression studies.

Results

A chicken 60-mer oligonucleotide microarray consisting of 42,034 features including the entire Marek's disease virus, two avian influenza virus (H5N2 and H5N3), and 150 chicken microRNAs has been designed and tested. In an important validation study, total RNA isolated from four major chicken tissues: cecal tonsil (C), ileum (I), liver (L), and spleen (S) were used for comparative hybridizations. More than 95% of spots had high signal noise ratio (SNR > 10). There were 2886, 2660, 358, 3208, 3355, and 3710 genes differentially expressed between liver and spleen, spleen and cecal tonsil, cecal tonsil and ileum, liver and cecal tonsil, liver and ileum, spleen and ileum (P < 10-7), respectively. There were a number of tissue-selective genes for cecal tonsil, ileum, liver, and spleen identified (95, 71, 535, and 108, respectively; P < 10-7). Another highlight of these data revealed that the antimicrobial peptides GAL1, GAL2, GAL6 and GAL7 were highly expressed in the spleen compared to other tissues tested.

Conclusion

A chicken 60-mer oligonucleotide 44K microarray was designed and validated in a comprehensive survey of gene expression in diverse tissues. The results of these tissue expression analyses have demonstrated that this microarray has high specificity and sensitivity, and will be a useful tool for chicken functional genomics. Novel data on the expression of putative tissue specific genes and antimicrobial peptides is highlighted as part of this comprehensive microarray validation study. The information for accessing and ordering this 44K chicken array can be found at http://people.tamu.edu/~hjzhou/TAMUAgilent44KArray/
Measuring the financial burden of acute cough in pre-school children: a cost of illness study
Authors: Hollinghurst Sandra , Gorst Catherine , Fahey Tom , Hay Alastair D
Published: January 2008

Background

Context:Acute cough is a very common symptom presentation among children in primary care and is usually due to respiratory infection, yet its cost is unknown. An estimate of the cost to healthcare providers and parents would aid budgetary decision-making, and provide an insight into the need for interventions to reduce the burden.Purpose:To estimate the cost per child per episode, and the annual population cost in the UK, of acute cough in pre-school children presenting to primary care.

Methods

Design: Incidence and prevalence-based cost-of-illness study from the perspectives of the UK NHS and of parents and caregivers.Setting:11 general practices in Bristol, UK.Subjects:121 children without known asthma aged 3 to 59 months presenting for the first time with an acute (≤ 28 days) cough.

Results

Mean cost per episode to the NHS: £27.43 (95% CI: £24.38 – £30.49). Mean cost per episode to parents and carers: £14.77 (£4.90 – £24.65). Annual cost to the NHS in the UK: at least £31.5 m (95% CI: £28.0 m – £35.0 m).

Conclusion

The cost burden on the healthcare provider of acute cough in pre-school children is substantial; the majority of this cost arises from consultations with general practitioners. Parents experience some personal cost through travel and expenditure on over-the-counter preparations, and may suffer significantly if loss of earnings is experienced. There is scope for evaluating interventions designed to reduce this burden.
Acquisition of new infection and clearance of type-specific human papillomavirus infections in female students in Busan, South Korea: a follow-up study
Authors: Oh Jin-Kyoung , Ju Young-Hee , Franceschi Silvia , Quint Wim , Shin Hai-Rim
Published: January 2008

Background

Little is known about the natural history of human papillomavirus (HPV) infection in Asian women.

Methods

A follow-up study was conducted, with exfoliated cervicovaginal cells self-collected from, and questionnaires administered to 197 female students, aged 17–26 years, who had been already examined one and half years before. The presence of 25 HPV types was evaluated by a polymerase chain reaction-based assay.

Results

The acquisition of new infection for any HPV type among 171 female students at risk who were negative at baseline, 60% of whom had remained as virgins, was 17.5% (95% confidence interval [CI]: 11.8–23.2). Among individual types, HPV16, 18 and 35 showed the highest rate of new infection. Women who had had first sexual intercourse (OR = 2.9; 95% CI: 1.0–8.8), or had changed sexual partners (OR = 2.9; 95% CI: 0.9–9.3) during the follow-up period showed a higher risk of new HPV infection than women who had remained virgins since baseline. The rate of new infection also tended to be higher in those who started, or continued smoking during the follow-up period, than in nonsmokers. Clearance of HPV infections since baseline examination was 80.6% (95% CI: 67.6–93.5), and did not differ between high-risk and low-risk HPV types or between single- and multiple-type infections.

Conclusion

This study shows that the acquisition of new HPV infection among young women in the Republic of Korea is high and also the clearance is frequent. Self-collection of cervicovaginal cells is applicable to follow-up studies that include virgins.
Heterozygous CAV1 frameshift mutations (MIM 601047) in patients with atypical partial lipodystrophy and hypertriglyceridemia
Authors: Cao Henian , Alston Lindsay , Ruschman Jennifer , Hegele Robert A.
Published: January 2008

Background

Mice with a deleted Cav1 gene encoding caveolin-1 develop adipocyte abnormalities and insulin resistance. From genomic DNA of patients with atypical lipodystrophy and hypertriglyceridemia who had no mutations in any known lipodystrophy gene, we used DNA sequence analysis to screen the coding regions of human CAV1 (MIM 601047).

Results

We found a heterozygous frameshift mutation in CAV1, designated I134fsdelA-X137, in a female patient who had atypical partial lipodystrophy, with subcutaneous fat loss affecting the upper part of her body and face, but sparing her legs, gluteal region and visceral fat stores. She had severe type 5 hyperlipoproteinemia, with recurrent pancreatitis. In addition, she had some atypical features, including congenital cataracts and neurological findings. Her father was also heterozygous for this mutation, and had a similar pattern of fat redistribution, hypertriglyceridemia and congenital cataracts, with milder neurological involvement. An unrelated patient had a different heterozygous frameshift mutation in the CAV1 gene, designated -88delC. He also had a partial lipodystrophy phenotype, with subcutaneous fat loss affecting the arms, legs and gluteal region, but sparing his face, neck and visceral fat stores. He also had severe type 5 hyperlipoproteinemia, with recurrent pancreatitis; however he had no clinically apparent neurological manifestations. The mutations were absent from the genomes of 1063 healthy individuals.

Conclusion

Thus, very rare CAV1 frameshift mutations appear to be associated with atypical lipodystrophy and hypertriglyceridemia.
Differential regulation of insulin-like growth factor binding protein-1 and -2 by insulin in the baboon (Papio anubis) endometrium
Authors: Fleming Steven D , Fazleabas Asgerally T , Bell Stephen C
Published: January 2008

Background

The purpose of this study was to examine the effect of insulin on expression and synthesis of IGFBP-1 and IGFBP-2 in the baboon endometrium in vitro.

Methods

Baboon endometrial explants collected from cycling, ovariectomized, steroid-treated, simulated-pregnant and pregnant animals were cultured for 48 h in the presence or absence of insulin, with or without estradiol, progesterone and hCG.

Results

Insulin clearly inhibited IGFBP-1 production and mRNA expression in a time- and dose-dependent manner, whereas IGFBP-2 synthesis was not significantly affected. The inhibitory effects of insulin on IGFBP-1 were more evident in explants of non-pregnant tissue or tissue away from the implantation site. In the absence of insulin, synthesis of IGFBP-1 was induced in explants with low levels of de novo synthesis whereas IGFBP-2 synthesis was inhibited. This effect was potentiated by steroids and hCG in the explant cultures.

Conclusion

Insulin differentially regulates endometrial IGFBP-1 and IGFBP-2 secretion in the baboon.
Mortality after infection with methicillin-resistant Staphylococcus aureus(MRSA) diagnosed in the community
Authors: Delaney JA 'Chris' , Schneider-Lindner Verena , Brassard Paul , Suissa Samy
Published: January 2008

Background

Outbreak reports suggest that community-acquired methicillin-resistantStaphylococcus aureus(MRSA) infections can be life-threatening. We conducted a population based cohort study to assess the magnitude of mortality associated with MRSA infections diagnosed in the community.

Methods

We used the United Kingdom's General Practice Research Database (GPRD) to form a cohort of all patients with MRSA diagnosed in the community from 2001 through 2004 and up to ten patients without an MRSA diagnosis. The latter were frequency-matched with the MRSA patients on age, GPRD practice and diagnosis date. All patients were older than 18 years, had no hospitalization in the 2 years prior to cohort entry and medical history information of at least 2 years prior to cohort entry. The cohort was followed up for 1 year and all deaths and hospitalizations were identified. Hazard ratios of all-cause mortality were estimated using the Cox proportional hazards model adjusted for patient characteristics.

Results

The cohort included 1439 patients diagnosed with MRSA and 14,090 patients with no MRSA diagnosis. Mean age at cohort entry was 70 years in both groups, while co-morbid conditions were more prevalent in the patients with MRSA. Within 1 year, 21.8% of MRSA patients died as compared with 5.0% of non-MRSA patients. The risk of death was increased in patients diagnosed with MRSA in the community (adjusted hazard ratio 4.1; 95% confidence interval: 3.5–4.7).

Conclusion

MRSA infections diagnosed in the community are associated with significant mortality in the year after diagnosis.
Differential inhibition of human cytomegalovirus (HCMV) by toll-like receptor ligands mediated by interferon-beta in human foreskin fibroblasts and cervical tissue
Authors: Harwani Sailesh C , Lurain Nell S , Zariffard M Reza , Spear Gregory T
Published: January 2008

Human cytomegalovirus (HCMV) can be acquired sexually and is shed from the genital tract. Cross-sectional studies in women show that changes in genital tract microbial flora affect HCMV infection and/or shedding. Since genital microbial flora may affect HCMV infection or replication by stimulating cells through Toll-like receptors (TLR), we assessed the effects of defined TLR-ligands on HCMV replication in foreskin fibroblasts and ectocervical tissue. Poly I:C (a TLR3-ligand) and lipopolysaccharide (LPS, a TLR4-ligand) inhibited HCMV and induced secretion of IL-8 and Interferon-beta (IFNβ) in both foreskin fibroblasts and ectocervical tissue. The anti-HCMV effect was reversed by antibody to IFNβ. CpG (TLR9 ligand) and lipoteichoic acid (LTA, TLR2 ligand) also inhibited HCMV infection in ectocervical tissue and this anti-HCMV effect was also reversed by anti-IFNβ antibody. In contrast, LTA and CpG did not inhibit HCMV infection in foreskin fibroblasts. This study shows that TLR ligands induce an HCMV-antiviral effect that is mediated by IFNβ suggesting that changes in genital tract flora may affect HCMV infection or shedding by stimulating TLR. This study also contrasts the utility of two models that can be used for assessing the interaction of microbial flora with HCMV in the genital tract. Clear differences in the response to different TLR ligands suggests the explant model more closely reflects in vivo responses to genital infections.
Redundancy and compensation in axon guidance: genetic analysis of the Drosophila Ptp10D/Ptp4E receptor tyrosine phosphatase subfamily
Authors: Jeon Mili , Nguyen Huong , Bahri Sami , Zinn Kai
Published: January 2008

Background

Drosophila has six receptor protein tyrosine phosphatases (RPTPs), five of which are expressed primarily in neurons. Mutations in all five affect axon guidance, either alone or in combination. Highly penetrant central nervous system (CNS) and motor axon guidance alterations are usually observed only when specific combinations of two or more RPTPs are removed. Here, we examine the sixth RPTP, Ptp4E, which is broadly expressed.

Results

Ptp4E and Ptp10D are closely related type III RPTPs. Non-drosophilid insect species have only one type III RPTP, which is closest to Ptp10D. We found that Ptp4E mutants are viable and fertile. We then examined Ptp4E Ptp10D double mutants. These die before the larval stage, and have a mild CNS phenotype in which the outer longitudinal 1D4 bundle is frayed. Ptp10D Ptp69D double mutants have a strong CNS phenotype in which 1D4 axons abnormally cross the midline and the outer and middle longitudinal bundles are fused to the inner bundle. To examine if Ptp4E also exhibits synthetic phenotypes in combination with Ptp69D, we made Ptp4E Ptp69D double mutants and Ptp4E Ptp10D Ptp69D triple mutants. No phenotype was observed in the double mutant. The triple mutant phenotype differs from the Ptp10D Ptp69D phenotype in two ways. First, the longitudinal tracts appear more normal than in the double mutant; two or three bundles are observed, although they are disorganized and fused. Second, axons labelled by the SemaIIB-τMyc marker often cross in the wrong commissure. We also examined motor axon guidance, and found that no phenotypes are observed in any Ptp4E double mutant combination. However, triple mutants in which Ptp4E Ptp10D was combined with Ptp69D or Ptp52F exhibited stronger phenotypes than the corresponding Ptp10D double mutants.

Conclusion

Type III RPTPs are required for viability in Drosophila, since Ptp4E Ptp10D double mutants die before the larval stage. Unlike Ptp10D, Ptp4E appears to be a relatively minor player in the control of axon guidance. Strong phenotypes are only observed in triple mutants in which both type III RPTPs are eliminated together with Ptp69D or Ptp52F. Our results allow us to construct a complete genetic interaction matrix for all six of the RPTPs.
Tuberculous peritonitis in a German patient with primary biliary cirrhosis: a case report
Authors: Vogel Yilin , Bous Jan C , Winnekendonk Guido , Henning Bernhard F
Published: January 2008

Background

The number of cases of tuberculosis as a complication in people with immunodeficiency, people on immunosuppressive therapy and among the immigrant population is increasing in Germany. However, tuberculous peritonitis rarely occurs without these risks, particularly in Germans. The incidence of tuberculous peritonitis in Germany is very low; tuberculosis of the intestinal tract was found in approximately 0.8 % of tuberculosis cases in 2004. The diagnosis of tuberculous peritonitis is often delayed on account of non-specific clinical symptoms. The absence of specific biological markers, long incubation times for cultures and non-specific radiographic or ultrasonographic signs increase the morbidity associated with this treatable condition.

Case presentation

We report a case of tuberculous peritonitis in a 73-year-old female German patient. Her medical history revealed primary biliary cirrhosis (PBC) since 1992. On admission, she complained of abdominal pain, vomiting, ascites and peripheral edema. The patient has been in a seriously reduced general condition and had fever up to 39.6°C. A few weeks earlier, the patient was in another hospital with the same complaint. Inflammatory parameters were elevated, but the procalcitonin level was normal. Blood culture was always negative, as was the tuberculin test. Ultrasonography of the abdomen showed massive ascites with multiple septa. The patient underwent a computed tomography (CT) scan of the abdomen which showed a thickened intestinal wall in the sigmoid colon and a pronounced enhancement of the peritoneum. Computed tomography scans of the lung showed only slight bilateral pleural effusion. Because of the anaesthetic and bleeding risk due to thrombocytopenia, laparoscopy was not immediately undertaken. The culture from ascites was positive for M.tuberculosis after three weeks.

Conclusion

In primary biliary cirrhosis patients with non-specific clinical symptoms, such as vomiting, abdominal pain, ascites, weight loss, and fever, tuberculous peritonitis must be considered in the initial differential diagnosis, although these symptoms may be attributed to cirrhosis of the liver with spontaneous bacterial peritonitis. Ultrasonographic and CT scab findings are not specific for tuberculous peritonitis, but an awareness of the ultrasonographic features and the features of the CT scan may help in the diagnosis of tuberculous peritonitis and avoid clinical mismanagement.
Microarray analysis in B cells among siblings with/without MS - role for transcription factor TCF2
Authors: Avasarala Jagannadha R , Chittur Sridar V , George Ajish D , Tine John A
Published: January 2008

Background

We investigated if global gene expression and transcription networks in B-lymphocytes of siblings with multiple sclerosis (MS) were different from healthy siblings.

Results

Using virus-transformed immortalized B cells and human whole genome bioarrays with validation using RT-qPCR, we found that in siblings with MS, genes for CXCL10, serpin B1 and FUT4 were up regulated whereas CDC5L, TNFRSF19 and HLA-DR were down regulated, among others; transcription analysis showed two intersecting clusters of transcriptional factors - the larger, governed by the upregulated transcription factor 2 (TCF2) and the smaller network regulated by the downregulated CDC5L.

Conclusion

No study has linked TCF2 to MS and to better understand the role of TCF2 in MS, studies in larger cohorts are required.
Robust SNP genotyping by multiplex PCR and arrayed primer extension
Authors: Podder Mohua , Ruan Jian , Tripp Ben W , Chu Zane E , Tebbutt Scott J
Published: January 2008

Background

Arrayed primer extension (APEX) is a microarray-based rapid minisequencing methodology that may have utility in 'personalized medicine' applications that involve genetic diagnostics of single nucleotide polymorphisms (SNPs). However, to date there have been few reports that objectively evaluate the assay completion rate, call rate and accuracy of APEX. We have further developed robust assay design, chemistry and analysis methodologies, and have sought to determine how effective APEX is in comparison to leading 'gold-standard' genotyping platforms. Our methods have been tested against industry-leading technologies in two blinded experiments based on Coriell DNA samples and SNP genotype data from the International HapMap Project.

Results

In the first experiment, we genotyped 50 SNPs across the entire 270 HapMap Coriell DNA sample set. For each Coriell sample, DNA template was amplified in a total of 7 multiplex PCRs prior to genotyping. We obtained good results for 41 of the SNPs, with 99.8% genotype concordance with HapMap data, at an automated call rate of 94.9% (not including the 9 failed SNPs). In the second experiment, involving modifications to the initial DNA amplification so that a single 50-plex PCR could be achieved, genotyping of the same 50 SNPs across each of 49 randomly chosen Coriell DNA samples allowed extremely robust 50-plex genotyping from as little as 5 ng of DNA, with 100% assay completion rate, 100% call rate and >99.9% accuracy.

Conclusion

We have shown our methods to be effective for robust multiplex SNP genotyping using APEX, with 100% call rate and >99.9% accuracy. We believe that such methodology may be useful in future point-of-care clinical diagnostic applications where accuracy and call rate are both paramount.
Mental health policy reforms and case complexity in CMHTs in England: replication study
Authors: Huxley Peter , Evans Sherrill , Munroe Maria , Cestari Leticia
Published: January 2008

Aims and Method

Community mental health team (CMHT) services in many Western countries have been remodelled to focus on people with the most severe illnesses and complex problems. Complexity scores using the Matching Resource to Care (MARC2) measure from CMHT cases in 2004–2005 (n=1481) are compared with scores in 1997–1998 (n=3178) in the same locations, before the introduction of the National Service Framework, and before the impact of the creation of integrated mental health trusts in England.

Results

The 2004–2005 baseline complexity scores are all worse than those in 1997–1998.

Clinical Implications

If increased targeting brought about by the National Service Framework and other reforms has led to a greater proportion of people with complex problems in case-loads, what care services, if any, are now being received by people who were in receipt of CMHT services before the reforms?
Insight and treatment attitude in schizophrenia: comparison of patients on depot and atypical antipsychotics
Authors: Mahadun P. N. , Marshall M.
Published: January 2008

Aims and Method

To establish if participants with schizophrenia receiving depot antipsychotics had less insight than similar participants receiving oral atypical antipsychotics. We assessed the difference between these two groups.

Results

Participants on oral antipsychotics had greater insight than those on depot antipsychotics (ITAQ, P=0.01). In the multiple regression analysis, only receiving depot antipsychotics contributed significantly to explaining variance in insight (adjusted R2=0.135, F=8.99, P=0.004).

Clinical Implications

Depot antipsychotics seem to be prescribed to a subgroup of people with schizophrenia who are likely to be less adherent because of lower levels of insight. These individuals are on significantly higher doses of antipsychotic medication. Clinicians should review their patients on depot antipsychotics at regular intervals.
New Ways of Working: time to get off the fence
Authors: Vize Christine , Humphries Stephen , Brandling Janet , Mistral Willm
Published: January 2008

New Ways of Working is about developing new, enhanced and changed roles for mental health staff, and redesigning systems and processes to support staff to deliver effective, person-centred care in a way that is personally, financially and organisationally sustainable. It is about developing capable teams attuned to the needs of their users, supported by good systems (particularly information systems) and adequate resources, embedded within a values-driven organisational culture with leadership and effective team working modelled at all levels. New Ways of Working is what it says – new ways of working – rather than a single service model or structure that has to be adopted. It recognises that services catering for the different types of needs of service users across their lifespan and differing demographics and geography will need different configurations to manage their task most effectively. However, the underlying principles relating to using the skills of the workforce in the most productive way are common. It is about achieving cultural change; a shift in the way teams think about themselves, the skills of the individuals within them, and the reasons they are there. However, cultural change is difficult to achieve and it is difficult to measure the extent to which it has been achieved.
Oscillatory lunatic fringe activity is crucial for segmentation of the anterior but not posterior skeleton
Authors: Shifley Emily T. , VanHorn Kellie M. , Perez-Balaguer Ariadna , Franklin John D. , Weinstein Michael , Cole Susan E.
Published: January 2008

The Notch pathway plays multiple roles during vertebrate somitogenesis,functioning in the segmentation clock and during rostral/caudal (R/C) somite patterning. Lunatic fringe (Lfng) encodes a glycosyltransferase that modulates Notch signaling, and its expression patterns suggest roles in both of these processes. To dissect the roles played by Lfng during somitogenesis, a novel allele was established that lacks cyclic Lfngexpression within the segmentation clock, but that maintains expression during R/C somite patterning (LfngΔFCE1). In the absence of oscillatory Lfng expression, Notch activation is ubiquitous in the PSM of LfngΔFCE1 embryos. LfngΔFCE1 mice exhibit severe segmentation phenotypes in the thoracic and lumbar skeleton. However, the sacral and tail vertebrae are only minimally affected in LfngΔFCE1mice, suggesting that oscillatory Lfng expression and cyclic Notch activation are important in the segmentation of the thoracic and lumbar axial skeleton (primary body formation), but are largely dispensable for the development of sacral and tail vertebrae (secondary body formation). Furthermore, we find that the loss of cyclic Lfng has distinct effects on the expression of other clock genes during these two stages of development. Finally, we find that LfngΔFCE1 embryos undergo relatively normal R/C somite patterning, confirming that Lfngroles in the segmentation clock are distinct from its functions in somite patterning. These results suggest that the segmentation clock may employ varied regulatory mechanisms during distinct stages of anterior/posterior axis development, and uncover previously unappreciated connections between the segmentation clock, and the processes of primary and secondary body formation.
Proposals forPalisada poiteauivar.gemmiferacomb. nov. andPalisada corallopsiscomb. nov. (Rhodomelaceae, Rhodophyta)
Authors: Sentíes Abel , Díaz-Larrea Jhoana
Published: January 2008

SinceChondrophycus poiteauivar.gemmiferusandC. corallopsisfall within the new recently validated segregate genusPalisadaK.W. Nam, two new nomenclatural combinations are proposed:Palisada poiteauivar.gemmiferaandP. corallopsis.
Sand-to-Concrete Interface Response to Complex Load Paths in a Large Displacement Shear Box
Authors: Gómez Jesús E. , Filz George M. , Ebeling Robert M. , Dove Joseph E.
Published: January 2008

The large displacement shear box (LDSB) allows testing of interfaces as large as 711 by 406 mm (28 by 16 in.) with maximum interface displacements of 305 mm (12 in.). This device has been used to investigate the response of a variety of interfaces, including clay-geomembrane interfaces for which large displacements are important. The most recent application of the LDSB was to study the response of several sand-to-concrete interfaces under complex loading paths. In this application, the relevant characteristics of the LDSB are its geometry, which reduces the significance of end effects, its ability to apply monotonic and cyclic loading, and its ability to apply simultaneous changes in shear and normal stresses so that complex loading paths can be followed. This paper describes the main features of the LDSB, as well as the testing procedures and results of the sand-to-concrete interface tests that were performed. A procedure for normalizing the interface shear test data is also presented. This procedure facilitates comparative evaluations of interface response to different types of loading. The test results formed the basis for development of an extended hyperbolic model for interfaces that has been implemented in finite element analyses of soil-structure interaction problems.
Differentiation of the bovine dominant follicle from the cohort upregulates mRNA expression for new tissue development genes
Authors: Mihm M , Baker P J , Fleming L M , Monteiro A M , O'Shaughnessy P J
Published: January 2008

This study was designed to identify genes that regulate the transition from FSH- to LH-dependent development in the bovine dominant follicle (DF). Serial analysis of gene expression (SAGE) was used to compare the transcriptome of granulosa cells isolated from the most oestrogenic growing cohort follicle (COH), the newly selected DF and its largest subordinate follicle (SF) which is destined for atresia. Follicle diameter, follicular fluid oestradiol (E) and E:progesterone ratio confirmed follicle identity. Results show that there are 93 transcript species differentially expressed in DF granulosa cells, but only 8 of these encode proteins known to be involved in DF development. Most characterised transcripts upregulated in the DF are from tissue development genes that regulate cell differentiation, proliferation, apoptosis, signalling and tissue remodelling. Semiquantitative real-time PCR analysis confirmed seven genes with upregulated (P≤0.05) mRNA expression in DF compared with both COH and SF granulosa cells. Thus, the new genes identified by SAGE and real-time PCR, which show enhanced mRNA expression in the DF, may regulate proliferation (cyclin D2;CCND2), prevention of apoptosis or DNA damage (growth arrest and DNA damage-inducible, β;GADD45B), RNA synthesis (splicing factor, arginine/serine rich 9;SFRS9) and unknown processes associated with enhanced steroidogenesis (ovary-specific acidic protein; DQ004742) in granulosa cells of DF at the onset of LH-dependent development. Further studies are required to show whether the expression of identified genes is dysregulated when abnormalities occur during DF selection or subsequent development.
Genes involved in conceptus–endometrial interactions in ruminants: insights from reductionism and thoughts on holistic approaches
Authors: Spencer Thomas E , Sandra Olivier , Wolf Eckhard
Published: January 2008

This review summarizes new knowledge on expression of genes and provides insights into approaches for study of conceptus–endometrial interactions in ruminants with emphasis on the peri-implantation stage of pregnancy. Conceptus–endometrial interactions in ruminants are complex and involve carefully orchestrated temporal and spatial alterations in gene expression regulated by hormones from the ovary and conceptus. Progesterone is the hormone of pregnancy and acts on the uterus to stimulate blastocyst survival, growth, and development. Inadequate progesterone levels or a delayed rise in progesterone is associated with pregnancy loss. The mononuclear trophectoderm cells of the elongating blastocyst synthesize and secrete interferon-τ (IFNT), the pregnancy recognition signal. Trophoblast giant binucleate cells begin to differentiate and produce hormones including chorionic somatomammotropin 1 (CSH1 or placental lactogen). A number of genes, induced or stimulated by progesterone, IFNT, and/or CSH1 in a cell-specific manner, are implicated in trophectoderm adhesion to the endometrial luminal epithelium and regulation of conceptus growth and differentiation. Transcriptional profiling experiments are beginning to unravel the complex dynamics of conceptus–endometrial interactions in cattle and sheep. Future experiments should incorporate physiological models of pregnancy loss and be complemented by metabolomic studies of uterine lumen contents to more completely define factors required for blastocyst survival, growth, and implantation. Both reduction and holistic approaches will be important to understand the multifactorial phenomenon of recurrent pregnancy loss and provide a basis for new strategies to improve pregnancy outcome and reproductive efficiency in cattle and other domestic animals.