bluuebunny/crossref_metadata_2025 huggingface dataset:
Human T-cell leukemia virus type 2 produces a spliced antisense transcript encoding a protein that lacks a classic bZIP domain but still inhibits Tax2-mediated transcription
Authors: Halin Marilène , Douceron Estelle , Clerc Isabelle , Journo Chloé , Ko Nga Ling , Landry Sébastien , Murphy Edward L. , Gessain Antoine , Lemasson Isabelle , Mesnard Jean-Michel , Barbeau Benoît , Mahieux Renaud
Published: July 2009

Human T-cell leukemia virus type 1 (HTLV-1) and type 2 (HTLV-2) retroviruses infect T lymphocytes. The minus strand of the HTLV-1 genome encodes HBZ, a protein that could play a role in the development of leukemia in infected patients. Herein, we demonstrate that the complementary strand of the HTLV-2 genome also encodes a protein that we named APH-2 for “antisense protein of HTLV-2.” APH-2 mRNA is spliced, polyadenylated, and initiates in the 3′-long terminal repeat at different positions. This transcript was detected in all HTLV-2–infected cell lines and short-term culture of lymphocytes obtained from HTLV-2 African patients tested and in 4 of 15 HTLV-2–infected blood donors. The APH-2 protein is 183 amino acids long, is localized in the cell nucleus, and is detected in vivo. Despite the lack of a consensus basic leucine zipper domain, APH-2 interacts with cyclic adenosine monophosphate-response element binding protein (CREB) and represses Tax2-mediated transcription in Tax2-expressing cells and in cells transfected with an HTLV-2 molecular clone. Altogether, our results demonstrate the existence of an antisense strand–encoded protein in HTLV-2, which could represent an important player in the development of disorders, such as lymphocytosis, which is frequently observed in HTLV-2 patients.
First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia
Authors: Eichhorst Barbara F. , Busch Raymonde , Stilgenbauer Stephan , Stauch Martina , Bergmann Manuela A. , Ritgen Matthias , Kranzhöfer Nicole , Rohrberg Robert , Söling Ulrike , Burkhard Oswald , Westermann Anne , Goede Valentin , Schweighofer Carmen D. , Fischer Kirsten , Fink Anna-Maria , Wendtner Clemens M. , Brittinger Günter , Döhner Hartmut , Emmerich Bertold , Hallek Michael ,   the German CLL Study Group (GCLLSG)
Published: July 2009

Although chronic lymphocytic leukemia (CLL) is a disease of elderly patients, subjects older than 65 years are heavily underrepresented in clinical trials. The German CLL study group (GCLLSG) initiated a multicenter phase III trial for CLL patients older than 65 years comparing first-line therapy with fludarabine with chlorambucil. A total of 193 patients with a median age of 70 years were randomized to receive fludarabine (25 mg/m2 for 5 days intravenously, every 28 days, for 6 courses) or chlorambucil (0.4 mg/kg body weight [BW] with an increase to 0.8 mg/kg, every 15 days, for 12 months). Fludarabine resulted in a significantly higher overall and complete remission rate (72% vs 51%, P = .003; 7% vs 0%, P = .011). Time to treatment failure was significantly shorter in the chlorambucil arm (11 vs 18 months; P = .004), but no difference in progression-free survival time was observed (19 months with fludarabine, 18 months with chlorambucil; P = .7). Moreover, fludarabine did not increase the overall survival time (46 months in the fludarabine vs 64 months in the chlorambucil arm; P = .15). Taken together, the results suggest that in elderly CLL patients the first-line therapy with fludarabine alone does not result in a major clinical benefit compared with chlorambucil. This trial is registered with www.isrctn.org under identifier ISRCTN 36294212.
Insertion of FLT3 internal tandem duplication in the tyrosine kinase domain-1 is associated with resistance to chemotherapy and inferior outcome
Authors: Kayser Sabine , Schlenk Richard F. , Londono Martina Correa , Breitenbuecher Frank , Wittke Kerstin , Du Juan , Groner Silja , Späth Daniela , Krauter Jürgen , Ganser Arnold , Döhner Hartmut , Fischer Thomas , Döhner Konstanze ,   for the German-Austrian AML Study Group (AMLSG)
Published: July 2009

To evaluate internal tandem duplication (ITD) insertion sites and length as well as their clinical impact in younger adult patients with FLT3-ITD–positive acute myeloid leukemia (AML), sequencing after DNA-based amplification was performed in diagnostic samples from 241 FLT3-ITD–mutated patients. All patients were treated on 3 German-Austrian AML Study Group protocols. Thirty-four of the 241 patients had more than 1 ITD, leading to a total of 282 ITDs; the median ITD length was 48 nucleotides (range, 15-180 nucleotides). ITD integration sites were categorized according to functional regions of the FLT3 receptor: juxtamembrane domain (JMD), n = 148; JMD hinge region, n = 48; beta1-sheet of the tyrosine kinase domain-1 (TKD1), n = 73; remaining TKD1 region, n = 13. ITD length was strongly correlated with functional regions (P < .001). In multivariable analyses, ITD integration site in the beta1-sheet was identified as an unfavorable prognostic factor for achievement of a complete remission (odds ratio, 0.22; P = .01), relapse-free survival (hazard ratio, 1.86; P < .001), and overall survival (hazard ratio, 1.59; P = .008). ITD insertion site in the beta1-sheet appears to be an important unfavorable prognostic factor in young adult patients with FLT3-ITD–positive AML. The clinical trials described herein have been registered as follows: AML HD93 (already published in 2003), AML HD98A (NCT00146120; http://www.ClinicalTrials.gov), and AMLSG 07-04 (NCT00151242; http://www.ClinicalTrials.gov).
A compartmentalized approach to the assembly of physical maps
Authors: Bozdag Serdar , Close Timothy J , Lonardi Stefano
Published: July 2009

Background

Physical maps have been historically one of the cornerstones of genome sequencing and map-based cloning strategies. They also support marker assisted breeding and EST mapping. The problem of building a high quality physical map is computationally challenging due to unavoidable noise in the input fingerprint data.

Results

We propose a novel compartmentalized method for the assembly of high quality physical maps from fingerprinted clones. The knowledge of genetic markers enables us to group clones into clusters so that clones in the same cluster are more likely to overlap. For each cluster of clones, a local physical map is first constructed using FingerPrinted Contigs (FPC). Then, all the individual maps are carefully merged into the final physical map. Experimental results on the genomes of rice and barley demonstrate that the compartmentalized assembly produces significantly more accurate maps, and that it can detect and isolate clones that would induce "chimeric" contigs if used in the final assembly.

Conclusion

The software is available for download at http://www.cs.ucr.edu/~sbozdag/assembler/
Phylogenetic analysis of the true water bugs (Insecta: Hemiptera: Heteroptera: Nepomorpha): evidence from mitochondrial genomes
Authors: Hua Jimeng , Li Ming , Dong Pengzhi , Cui Ying , Xie Qiang , Bu Wenjun
Published: July 2009

Background

The true water bugs are grouped in infraorder Nepomorpha (Insecta: Hemiptera: Heteroptera) and are of great economic importance. The phylogenetic relationships within Nepomorpha and the taxonomic hierarchies of Pleoidea and Aphelocheiroidea are uncertain. Most of the previous studies were based on morphological characters without algorithmic assessment. In the latest study, the molecular markers employed in phylogenetic analyses were partial sequences of 16S rDNA and 18S rDNA with a total length about 1 kb. Up to now, no mitochondrial genome of the true water bugs has been sequenced, which is one of the largest data sets that could be compared across animal taxa. In this study we analyzed the unresolved problems in Nepomorpha using evidence from mitochondrial genomes.

Results

Nine mitochondrial genomes of Nepomorpha and five of other hemipterans were sequenced. These mitochondrial genomes contain the commonly found 37 genes without gene rearrangements. Based on the nucleotide sequences of mt-genomes, Pleoidea is not a member of the Nepomorpha and Aphelocheiroidea should be grouped back into Naucoroidea. Phylogenetic relationships among the superfamilies of Nepomorpha were resolved robustly.

Conclusion

The mt-genome is an effective data source for resolving intraordinal phylogenetic problems at the superfamily level within Heteroptera. The mitochondrial genomes of the true water bugs are typical insect mt-genomes. Based on the nucleotide sequences of the mt-genomes, we propose the Pleoidea to be a separate heteropteran infraorder. The infraorder Nepomorpha consists of five superfamilies with the relationships (Corixoidea + ((Naucoroidea + Notonectoidea) + (Ochteroidea + Nepoidea))).
Inconsistencies of genome annotations in apicomplexan parasites revealed by 5'-end-one-pass and full-length sequences of oligo-capped cDNAs
Authors: Wakaguri Hiroyuki , Suzuki Yutaka , Sasaki Masahide , Sugano Sumio , Watanabe Junichi
Published: July 2009

Background

Apicomplexan parasites are causative agents of various diseases including malaria and have been targets of extensive genomic sequencing. We generated 5'-EST collections for six apicomplexa parasites using our full-length oligo-capping cDNA library method. To improve upon the current genome annotations, as well as to validate the importance for physical cDNA clone resources, we generated a large-scale collection of full-length cDNAs for several apicomplexa parasites.

Results

In this study, we used a total of 61,056 5'-end-single-pass cDNA sequences from Plasmodium falciparum, P. vivax, P. yoelii, P. berghei, Cryptosporidium parvum, and Toxoplasma gondii. We compared these partially sequenced cDNA sequences with the currently annotated gene models and observed significant inconsistencies between the two datasets. In particular, we found that on average 14% of the exons in the current gene models were not supported by any cDNA evidence, and that 16% of the current gene models may contain at least one mis-annotation and should be re-evaluated. We also identified a large number of transcripts that had been previously unidentified. For 732 cDNAs in T. gondii, the entire sequences were determined in order to evaluate the annotated gene models at the complete full-length transcript level. We found that 41% of the T. gondii gene models contained at least one inconsistency. We also identified and confirmed by RT-PCR 140 previously unidentified transcripts found in the intergenic regions of the current gene annotations. We show that the majority of these discrepancies are due to questionable predictions of one or two extra exons in the upstream or downstream regions of the genes.

Conclusion

Our data indicates that the current gene models are likely to still be incomplete and have much room for improvement. Our unique full-length cDNA information is especially useful for further refinement of the annotations for the genomes of apicomplexa parasites.
Genomic Resources of Magnaporthe oryzae (GROMO): A comprehensive and integrated database on rice blast fungus
Authors: Thakur Shalabh , Jha Sanjay , Roy-Barman Subhankar , Chattoo Bharat
Published: July 2009

Background

Magnaporthe oryzae, rice blast fungus, is the most devastating pathogen of rice. It has emerged as a model phytopathogen for the study of host-pathogen interactions. A large body of data has been generated on different aspects of biology of this fungus and on host-pathogen interactions. However, most of the data is scattered and is not available as a single resource for researchers in this field.

Description

Genomic Resources of Magnaporthe oyzae (GROMO), is a specialized, and comprehensive database for rice blast fungus, integrating information from several resources. GROMO contains information on genomic sequence, mutants available, gene expression, localization of proteins obtained from a variety of repositories, as primary data. In addition, prediction of domains, pathways, protein-protein interactions, sumolyation sites and biochemical properties that were obtained after computational analysis of protein sequences have also been included as derived data. This database has an intuitive user interface that shall prompt the user to explore various possible information resources available on a given gene or a protein, from a single source.

Conclusion

Currently, information on M. oryzae is available from different resources like BROAD MIT Magnaporthe database, Agrobacterium tumefaciens-mediated transformation (ATMT) M. oryzae database, Magnaporthe grisea – Oryza sativa (MGOS) and Massive Parallel Signature Sequencing (MPSS) databases. In the GROMO project, an effort has been made to integrate information from all these databases, derive some new data based on the available information analyzed by relevant programs and make more insightful predictions to better understand the biology of M. oryzae. The database is currently available at: http://gromo.msubiotech.ac.in/
Estrous cycle influences the expression of neuronal nitric oxide synthase in the hypothalamus and limbic system of female mice
Authors: Sica Monica , Martini Mariangela , Viglietti-Panzica Carla , Panzica GianCarlo
Published: July 2009

Background

Nitric oxide plays an important role in the regulation of male and female sexual behavior in rodents, and the expression of the nitric oxide synthase (NOS) is influenced by testosterone in the male rat, and by estrogens in the female. We have here quantitatively investigated the distribution of nNOS immunoreactive (ir) neurons in the limbic hypothalamic region of intact female mice sacrificed during different phases of estrous cycle.

Results

Changes were observed in the medial preoptic area (MPA) (significantly higher number in estrus) and in the arcuate nucleus (Arc) (significantly higher number in proestrus). In the ventrolateral part of the ventromedial nucleus (VMHvl) and in the bed nucleus of the stria terminalis (BST) no significant changes have been observed. In addition, by comparing males and females, we observed a stable sex dimorphism (males have a higher number of nNOS-ir cells in comparison to almost all the different phases of the estrous cycle) in the VMHvl and in the BST (when considering only the less intensely stained elements). In the MPA and in the Arc sex differences were detected only comparing some phases of the cycle.

Conclusion

These data demonstrate that, in mice, the expression of nNOS in some hypothalamic regions involved in the control of reproduction and characterized by a large number of estrogen receptors is under the control of gonadal hormones and may vary according to the rapid variations of hormonal levels that take place during the estrous cycle.
Tissue culture-induced transpositional activity of mPing is correlated with cytosine methylation in rice
Authors: Ngezahayo Frédéric , Xu Chunming , Wang Hongyan , Jiang Lily , Pang Jinsong , Liu Bao
Published: July 2009

Background

mPingis an endogenous MITE in the rice genome, which is quiescent under normal conditions but can be induced towards mobilization under various stresses. The cellular mechanism responsible for modulating the activity ofmPingremains unknown. Cytosine methylation is a major epigenetic modification in most eukaryotes, and the primary function of which is to serve as a genome defense system including taming activity of transposable elements (TEs). Given that tissue-culture is capable of inducing both methylation alteration andmPingtransposition in certain rice genotypes, it provides a tractable system to investigate the possible relationship between the two phenomena.

Results

mPingtransposition and cytosine methylation alteration were measured in callus and regenerated plants in three rice (ssp.indica) genotypes, V14, V27 and R09. All three genotypes showed transposition ofmPing, though at various frequencies. Cytosine methylation alteration occurred both at themPing-flanks and at random loci sampled globally in callus and regenerated plants of all three genotypes. However, a sharp difference in the changing patterns was noted between themPing-flanks and random genomic loci, with a particular type of methylation modification, i.e., CNG hypermethylation, occurred predominantly at themPing-flanks. Pearson's test on pairwise correlations indicated thatmPingactivity is positively correlated with specific patterns of methylation alteration at random genomic loci, while the element's immobility is positively correlated with methylation levels of themPing's 5'-flanks. Bisulfite sequencing of twomPing-containing loci showed that whereas for the immobile locus loss of CG methylation in the 5'-flank was accompanied by an increase in CHG methylation, together with an overall increase in methylation of all three types (CG, CHG and CHH) in themPing-body region, for the active locus erasure of CG methylation in the 5'-flank was not followed by such a change.

Conclusion

Our results documented that tissue culture-inducedmPingactivity in rice ssp.indicais correlated with alteration in cytosine methylation patterns at both random genomic loci and the elements' flanks, while the stability ofmPingpositively correlates with enhanced methylation levels of both the flanks and probably the elementsper se. Thus, our results implicate a possible role of cytosine methylation in maintainingmPingstability under normal conditions, and in releasing the element's activity as a consequence of epigenetic perturbation in a locus-specific manner under certain stress conditions.
Anti-fibrinolytic agents in post partum haemorrhage: a systematic review
Authors: Ferrer Pili , Roberts Ian , Sydenham Emma , Blackhall Karen , Shakur Haleema
Published: July 2009

Background

Post partum haemorrhage is a leading cause of maternal death worldwide. It also contributes to maternal morbidity as women may require a hysterectomy to control bleeding, or may require a blood transfusion, which can transmit viral infections. Anti-fibrinolytic agents have been proposed as a treatment for post partum haemorrhage. We conducted a systematic review to assess the effectiveness and safety of anti-fibrinolytic agents in post partum bleeding.

Methods

All randomised controlled trials of anti-fibrinolytic agents given for bleeding during the postpartum period were included in this review. We searched Medline, PubMed, EMBASE, Cochrane Central Register of Controlled trials, Web of Science, metaRegister of controlled trials, LILACS, Reproductive Health Library, African healthline, POPLINE, MedCarib, CINAHL, Clinicaltrials.gov and the reference lists of eligible trials. Two authors extracted data. Methodological quality was assessed by evaluating allocation concealment. The primary outcome was maternal mortality. Secondary outcomes were blood loss, blood transfusion, hysterectomy, mean haemoglobin concentration, thrombo-embolic events and other adverse effects.

Results

We identified three randomised controlled trials involving 461 participants. The trials compared tranexamic acid with no treatment and reported blood loss after delivery. In all three trials, allocation concealment was either inadequate or unclear. The administration of tranexamic acid was associated with a reduction in blood loss of 92 millilitres (95%CI 76 to 109). The most frequently reported adverse effect of tranexamic acid was nausea, although the increase was easily compatible with the play of chance (RR 4.63, 95%CI 0.23 to 95.14).

Conclusion

Tranexamic acid may reduce blood loss in post partum haemorrhage. However, the quality of the currently available evidence is poor. Adequately powered, high quality randomised controlled trials are needed.
Expression of ezrin is associated with invasion and dedifferentiation of hepatitis B related hepatocellular carcinoma
Authors: Yeh Chun-Nan , Pang See-Tong , Chen Tsung-Wen , Wu Ren-Ching , Weng Wen-Hui , Chen Miin-Fu
Published: July 2009

Background

Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world and constitutes the leading cause of cancer-related death among men, and second among women in Taiwan. Liver cirrhosis and HCC are relatively prevalent, and 80% to 85% of the patients with these conditions have positive results for hepatitis B surface antigen in Taiwan. Only 5% of the general population is seronegative for all hepatititis B virus (HBV) markers. This is the first study to determine the role of ezrin upon HBV HCC cell and patients with HBV HCC undergoing hepatectomy

Methods

Immunohistochemical study with ezrin in 104 human HBV-HCC cases were carried out to investigate its association with the clinicopathological features and the outcomes of 104 HBV-HCC patients undergoing hepatetomy. In addition, DNA constructs including the wild type ezrin (wt-ezrin) and mutant ezrin Tyr353 (Y353) were transfected into Hep3B cell to study its role in tumor invasion and differentiation.

Results

HBV HCC patients with ezrin over-expression independently have smaller tumor size, cirrhotic liver background, poor tumor differentiation, and more vascular invasion. Ezrin expression status has no impact on survival for HBV-HCC patients undergoing hepatectomy. The in vitro assay showed that wt-ezrin Hep3B cells have a significant higher level of AFP secretion and higher invasion ability as compared with the control and Y353- ezrin Hep3B cells.

Conclusion

Ezrin over-expression contributed to de-differentiation and invasion of HBV-HCC cell. HBV-HCC patients with ezrin over-expression were independently associated with tumor with smaller size, cirrhotic liver background, poor differentiation, and vascular invasion.
Breast cancer cells stimulate osteoprotegerin (OPG) production by endothelial cells through direct cell contact
Authors: Reid Penny E , Brown Nicola J , Holen Ingunn
Published: July 2009

Background

Angiogenesis, the sprouting of capillaries from existing blood vessels, is central to tumour growth and progression, however the molecular regulation of this process remains to be fully elucidated. The secreted glycoprotein osteoprotegerin (OPG) is one potential pro-angiogenic factor, and clinical studies have demonstrated endothelial cells within a number of tumour types to express high levels of OPG compared to those in normal tissue. Additionally, OPG can increase endothelial cell survival, proliferation and migration, as well as induce endothelial cell tube formation in vitro. This study aims to elucidate the processes involved in the pro-angiogenic effects of OPG in vitro, and also how OPG levels may be regulated within the tumour microenvironment.

Results

It has previously been demonstrated that OPG can induce tube formation on growth factor reduced matrigel. In this study, we demonstrate that OPG enhances the pro-angiogenic effects of VEGF and that OPG does not stimulate endothelial cell tube formation through activation of the VEGFR2 receptor. We also show that cell contact between HuDMECs and the T47D breast cancer cell line increases endothelial cell OPG mRNA and protein secretion levels in in vitro co-cultures. These increases in endothelial cell OPG secretion were dependent on ανβ3 ligation and NFκB activation. In contrast, the pro-angiogenic factors VEGF, bFGF and TGFβ had no effect on HuDMEC OPG levels.

Conclusion

These findings suggest that the VEGF signalling pathway is not involved in mediating the pro-angiogenic effects of OPG on endothelial cells in vitro. Additionally, we show that breast cancer cells cause increased levels of OPG expression by endothelial cells, and that direct contact between endothelial cells and tumour cells is required in order to increase endothelial OPG expression and secretion. Stimulation of OPG secretion was shown to involve ανβ3 ligation and NFκB activation.
Malaria ookinetes exhibit multiple markers for apoptosis-like programmed cell death in vitro
Authors: Arambage Shashini C , Grant Karen M , Pardo Ian , Ranford-Cartwright Lisa , Hurd Hilary
Published: July 2009

Background

A wide range of unicellular eukaryotes have now been shown to undergo a form of programmed cell death (PCD) that resembles apoptosis; exhibiting morphological and, in some cases, biochemical markers typical of metazoans. However, reports that sexual and asexual stages of malaria parasites exhibit these markers have been challenged. Here we use a rodent malaria model, Plasmodium berghei, to determine whether, and what proportion of cultured ookinetes show signs of apoptosis-like death and extend the study to examine ookinetes of Plasmodium falciparum in vivo.

Results

Ookinetes displayed the following markers of PCD: loss of mitochondrial membrane potential, nuclear chromatin condensation, DNA fragmentation, translocation of phosphatidylserine to the outer surface of the cell membrane and caspase-like activity. The proportion of parasites expressing apoptosis markers rose with time, particularly when cultured in phosphate buffered saline. Some ookinetes positive for apoptosis markers also had compromised membranes, which could represent a late stage in the process. When these are included a similar proportion of ookinetes display each marker. Over 50% of P. falciparum ookinetes, removed from the mosquito midgut lumen 24 h post-infection, had nuclei containing fragmented DNA.

Conclusion

We have confirmed previous reports that Plasmodium ookinetes display multiple signs that suggest they die by a mechanism resembling apoptosis. This occurs in vivo and in vitro without experimental application of triggers. Our findings support the hypothesis that non-necrotic mechanisms of cell death evolved before the advent of multicellular organisms.
The change and effect of endothelial progenitor cells in pig with multiple organ dysfunction syndromes
Authors: Luo Tian Hang , Wang Yao , Lu Zheng Mao , Zhou Hong , Xue Xu Chao , Bi Jian Wei , Ma Li Ye , Fang Guo En
Published: July 2009

Introduction

The dysfunction and decrease of endothelial progenitor cells (EPCs) may play a very important role in the initiation of organ dysfunction caused by trauma or severe sepsis. We aim to measure the number and function of EPCs in the progression of multiple organ dysfunction syndromes (MODS) caused by severe sepsis, which may help to understand the pathogenesis of MODS by the changing of EPCs.

Methods

A total of 40 pigs were randomly divided into two groups, which were subjected to hemorrhagic shock, resuscitation and endotoxemia (experimental group, n = 20) or acted as a control (control group, n = 20). The number and function of EPCs including adhesive, migratory and angiogenesis capacities were analyzed at different times in both groups.

Results

All the animals in the experimental group developed MODS (100%) and 17 of 20 animals (85%) died due to MODS; the incidence of MODS and death of the animals in the control group were 0% (P < 0.01). The number, migratory and adhesive capacities of EPCs decreased sharply in the animals of the experimental group corresponding to the increasing severities of MODS, but the angiogenesis function increased gradually until death. The decrease in function of EPCs preceded the decrease in number of EPCs. The decrease in number and function of EPCs occurred prior to the occurrence of MODS.

Conclusions

For the first time, it was observed that the number and function of EPCs decreased sharply in the progression of MODS and that it was prior to the occurrence of MODS. The decrease in number and function of EPCs may be one of the main pathogenic factors of MODS.
Alcohol abuse and pulmonary disease
Authors: Boé Darren M , Vandivier R William , Burnham Ellen L , Moss Marc
Published: July 2009

Review on alcohol abuse increasing the risk for acute respiratory distress syndrome through alterations in pulmonary function, and implications to potential therapeutic targets.

ARDS is a severe form of lung injury characterized by increased permeability of the alveolar capillary membrane, diffuse alveolar damage, the accumulation of proteinaceous interstitial and intra-alveolar edema, and the presence of hyaline membranes. These pathological changes are accompanied by physiological alterations, including severe hypoxemia, an increase in pulmonary dead space, and decreased pulmonary compliance. Approximately 200,000 individuals develop ARDS in the United States each year [1], and nearly 50% of these patients have a history of alcohol abuse. We have identified alcohol abuse as an independent risk factor for the development of ARDS [2–5], and more recent studies have validated these findings in patients following lung resection and blood transfusion [2, 3]. In ARDS survivors, alcohol abuse is also associated with an increased duration of mechanical ventilation and prolonged ICU length of stay [5]. Despite studies aimed at improving outcomes in patients with ARDS, the mortality remains high at >40% [6]. For those who abuse alcohol, the mortality is even higher, at 65% [4]. In this review, we will discuss the relationship between alcohol abuse and ARDS, the effects of alcohol abuse on pulmonary function, and future directions and potential therapeutic targets for patients at risk for ARDS as a result of alcohol abuse, which impairs immune function, decreases pulmonary antioxidant capacity, decreases alveolar epithelial cell function, alters activation of the renin angiotensin system, and impairs GM-CSF signaling. These pathways represent potential therapeutic targets for patients at risk for ARDS as a result of alcohol abuse.
Impaired osteoclastogenesis by staphylococcal lipoteichoic acid through Toll-like receptor 2 with partial involvement of MyD88
Authors: Yang Jihyun , Ryu Young Hee , Yun Cheol-Heui , Han Seung Hyun
Published: July 2009

Staphylococcal LTA inhibits osteoclast differentiation primarily through TLR2; and in part through MyD88 signaling, which in turn inhibits activation of ERK, JNK, and AP-1.

Degenerative bone disease, marked by excessive loss of calcified matrix, is often associated with bacterial infections. Osteoclasts, which mediate the bone-resorptive process, are derived mainly from myeloid precursor cells of the monocyte/macrophage lineage, from which cells with phagocytic and inflammatory capacities may alternatively arise. Here, we investigated the effect of LTA, a major cell-wall virulence factor of Gram-positive bacteria, on osteoclast differentiation. Osteoclast precursors were prepared from C57BL/6 mouse BM using M-CSF and RANKL. When osteoclastogenesis was induced in the presence of staphylococcal LTA, LTA dose-dependently inhibited the differentiation of osteoclast precursors to mature osteoclasts. A corresponding inhibition of bone-resorptive function was observed in the reduced resorption area on calcium phosphate-coated culture plates. In contrast, the phagocytic and inflammatory potential of the osteoclast precursors increased in the presence of LTA. TLR2, known to recognize LTA, might be essential for the LTA inhibition of osteoclastogenesis, as the inhibition did not occur in the precursors from TLR2-deficient mice. Importantly, MyD88-dependent and MyD88-independent pathways would participate in the inhibition, as determined using MyD88-deficient cells. Moreover, LTA inhibited phosphorylation of ERK and JNK in osteoclast precursors stimulated with M-CSF and RANKL, concomitantly with a decreased DNA-binding activity of AP-1. These results suggest that staphylococcal LTA inhibits osteoclast differentiation primarily through TLR2 but also in part through MyD88 signaling, which in turn, inhibits activation of ERK, JNK, and AP-1.
Stanniocalcin-1 suppresses superoxide generation in macrophages through induction of mitochondrial UCP2
Authors: Wang Yanlin , Huang Luping , Abdelrahim Maen , Cai Qingsong , Truong Anh , Bick Roger , Poindexter Brian , Sheikh-Hamad David
Published: July 2009

Mammalian stanniocalcin-1, a secreted phosphogylcoprotein that targets the mitochondria, suppresses superoxide and may function as an LPS antagonist in macrophages.

Mammalian STC1 decreases the mobility of macrophages and diminishes their response to chemokines. In the current experiments, we sought to determine the impact of STC1 on energy metabolism and superoxide generation in mouse macrophages. STC1 decreases ATP level in macrophages but does not affect the activity of respiratory chain complexes I–IV. STC1 induces the expression of mitochondrial UCP2, diminishing mitochondrial membrane potential and superoxide generation; studies in UCP2 null and gp91phox null macrophages suggest that suppression of superoxide by STC1 is UCP2-dependent yet is gp91phox-independent. Furthermore, STC1 blunts the effects of LPS on superoxide generation in macrophages. Exogenous STC1 is internalized by macrophages within 10 min and localizes to the mitochondria, suggesting a role for circulating and/or tissue-derived STC1 in regulating macrophage function. STC1 induces arrest of the cell cycle at the G1 phase and reduces cell necrosis and apoptosis in serum-starved macrophages. Our data identify STC1 as a key regulator of superoxide generation in macrophages and suggest that STC1 may profoundly affect the immune/inflammatory response.
Growth Hormone and Sex Steroid Effects on Serum Glucose, Insulin, and Lipid Concentrations in Healthy Older Women and Men
Authors: Münzer Thomas , Harman S. Mitchell , Sorkin John D. , Blackman Marc R.
Published: July 2009

Context: With aging, GH, IGF-I, and sex steroid concentrations and glucose tolerance decrease, and body fat and serum lipids increase.

Objective: The aim of the study was to assess GH and/or sex steroid administration effects on serum glucose, insulin, insulin sensitivity, and lipids in older individuals.

Design: A double-masked, 2 × 2 factorial, placebo-controlled, double-dummy design was used for the study.

Intervention: GH and/or sex steroid [transdermal estradiol plus oral medroxyprogesterone acetate in women (HRT); testosterone enanthate (T) in men] were administered for 6 months.

Participants: Healthy, community-dwelling women (n = 57) and men (n = 74) ages 65–88 yr (mean, 72 yr) participated in the study.

Main Outcome Measures: We measured serum glucose, insulin, and insulin sensitivity [quantitative insulin sensitivity check index (QUICKI) and insulin sensitivity index (ISI)] before and during an oral glucose tolerance test and lipid profiles.

Results: In women, GH did not alter oral glucose tolerance test 120 min or 2-h area under the curve (AUC) glucose values, but it increased 120 min insulin and AUC insulin. There were no significant effects of HRT or GH+HRT. ISI and QUICKI decreased after GH. In men, GH increased 120 min and AUC glucose and insulin AUC. GH+T increased 120 min glucose and glucose and insulin AUCs. T alone did not affect glucose or insulin. ISI decreased after GH and GH+T, whereas QUICKI decreased after GH. GH in women and men and GH+T in men decreased QUICKI by 4 wk. In women, HRT decreased total cholesterol and low-density lipoprotein (LDL)-cholesterol, and GH decreased LDL-cholesterol. In men, total cholesterol decreased after T and GH+T. LDL-cholesterol decreased after GH and GH+T. GH increased serum triglycerides.

Conclusions: GH administration to healthy older individuals for 6 months increased insulin resistance with moderately beneficial effects on lipids.

Chronic GH administration to healthy older individuals increases insulin resistance with moderately beneficial effects on lipids.
The Clinical, Radiological and Pathological Aspects of Pulmonary Hæmosiderosis
Authors: Park S. D. Scott
Published: July 2009

The first radiological recognition of pulmonary hæmosiderosis was apparently by Rosenhagen, in 1928. Since then recorded cases have been few and the condition is generally regarded as being rare. Most of the cases described are in mitral stenosis, but more recently some of a different etiology have been recognised, usually in children with a fairly severe anæmia. In many of the recorded cases of both types, miliary tuberculosis has been diagnosed on the X-ray film, even in those where the patient had mitral stenosis, and usually the diagnosis was not corrected until post-mortem.
The Radiological Anatomy of the Labyrinth
Authors: Pygott F.
Published: July 2009

By sectioning a disarticulated temporal bone in two parallel planes I was able to wire the labyrinth and catheterise the canal of the facial nerve from the internal auditory meatus to the stylomastoid foramen. The first section passed vertically through the external auditory meatus and the Eustachian canal. The second ran along the ridge of the petrous and vertically throught the tip of the mastoid.

The bone was radiographed with its fellow of the opposite side in positions as nearly as possible corresponding to those used in the Law, Granger, Stenvers, and Mayer projections.

The Law projection is obtained by positioning the head so that the orbito-meatal line is at right angles to the centre line of the couch, with the Sagittal plane parallel to the table top. The central ray is directed through the external meatus at an angle of 15° to the face and 15° downwards to the feet. I find in practice that this is unnecessarily complicated; the double tilt prevents the use of Bucky or grid and increases the difficulty of securing corresponding views of the opposite mastoid on the same film. I allow the patient's head to rest naturally on its side on the table with the orbito-meatal line at right angles to the centre line of the table and the Sagittal plane rotated from the horizontal. The position is best assumed with the body in the Sims' semi-prone position, with the arm of the corresponding side lying by the side of the body.
Medical Members' Meeting
Authors: A. M. R.
Published: July 2009

This meeting took place in the Reid Knox Hall of the Institute, on Friday, January 17, 1947, and was attended by about thirty members. Dr. J. Duncan White was in the Chair.

Dr. R. Connell showed films of a case. A man, aged 27 years, a professional footballer, with a history of epileptiform fits. Subject to minor accidents on the football field, but no definite history of fracture. First seen after a football accident in which he sustained a cut over the eyebrow. There was no clinical sign of fracture.

A X ray of the skull was taken and revealed a roughly rounded hiatus in the left temporo-parietal region of the vault. The margins of the hole were smooth and not sclerosed, and the both tables of the bone appeared to be deficient. No sign of fracture was evident. There was, in addition, hyperostosis frontales interna.
Dr. H. Courtney Gage
Authors: Williams Rohan
Published: July 2009

It is given to few men of determined character and of high principles to pass through life and yet to make no enemies, to be regarded by all with sincere and deep affection. Courtney Gage was such a man. After a life devoted to the service of others, Gage died a few days before his sixty-second birthday on October 4, 1947. His death leaves a gap in British radiology that will not be filled.

Before 1914, Gage worked with Sir James Mackenzie Davidson, one of the great pioneer radiologists; he went to France in 1914 with the Essex Yeomanry, was wounded early in the war, and was invalided out of the army. But before long he was back in France with the American Red Cross as an X-ray Technician and was responsible for a great volume of radiographic work for war casualties at Ris Orangis, near Paris; he also covered the work of two large French civil hospitals in that area. His work was recognised by the French Government when he was made “Officier de l'Instruction publique”. He originated a number of techniques for the adequate investigation of spinal injuries and the localisation of foreign bodies, which were published in the French Journal de Radiologie in 1916–1918.

Courtney Gage joined St. Mary's Hospital Medical School in 1919 and qualified in 1924. Thus, on achieving his medical qualification, he came to medical radiology with an unrivalled technical experience behind him.
Carcinoma of the Bronchus with Especial Reference to its Treatment by Radiotherapy
Authors: Shorvon L. M.
Published: July 2009

1. The incidence, ætiology, pathology, symptomatology and diagnosis of carcinoma of the bronchus are briefly described, and the extreme importance of early diagnosis emphasised.

2. Although pneumonectomy is the treatment of choice in suitable cases, it is pointed out that the number of operable cases is small, not more than about 10 per cent.

3. The contradictory opinions as to the value of radiotherapy are referred to.

4. The techniques of treatment by deep X-rays, which I have employed, are described, and the value of penicillin during the course of treatment stressed.

5. A series of 213 cases of carcinoma of the bronchus, seen in Mount Vernon Hospital during the years 1942–6, is analysed.

6. The results of radiotherapy are evaluated under the headings of possibility of cure, prolongation of life, and relief of symptoms.
The Inhibition of Ribo-and Thymo-Nucleic Acid Synthesis in Tumour Tissue by Irradiation with X rays
Authors: Holmes Barbara E.
Published: July 2009

1. The uptake of radioactive phosphorus in the thymonucleic acid fraction of rat tumour tissue is markedly inhibited by X rays.

2. The uptake of radioactive phosphorus in the ribonucleic acid fraction is also inhibited, but to a smaller extent.

3. Nembutal inhibits the uptake of radioactive phosphorus in both these fractions and should, therefore, not be used as a sedative during the irradiation.

4. The observation of Hevesy, that irradiation of one tumour can affect the nucleic acid metabolism of another tumour in the same animal, has been confirmed.
Tendinitis of Flexor Carpi Ulnaris
Authors: Winchester J. W. , Mekie E. C.
Published: July 2009

The deposition of calcium salts in tendons and bursæ has been recognised for many years. The commonest sites at which this occurs are in relation to the capsule and tendons about the shoulder. Painter (1907) was the first to report a case of periarticular calcification at the shoulder, diagnosed prior to operation on radiological findings. Numerous papers have appeared since that date illustrating lesions about the shoulder joint, stressing the radiological findings and describing the pathology, but recently attention has been focused upon the occurrence of lesions of a similar pathological character occurring at other sites. Lapidus (1943) has described a series of cases of tendinitis with calcification occurring at the shoulder, elbow, hip, knee, foot, and wrist.

The recognition of the condition at sites other than the shoulder is perhaps inadequately stressed, and the following case is reported as an example in relation to the flexor carpi ulnaris tendon at its insertion into the pisiform bone.
Editorial: The Biological Effects of Penetrating Radiations
Authors: Spear F. G.
Published: July 2009

The demonstration that penetrating radiation produced recognisable changes in living tissues by which they were absorbed resulted in the biological effects of radiation being widely studied, in part to satisfy a natural curiosity, but also to determine how the rays might be usefully employed in medicine. The whole subject has a greatly increased importance today in consequence of recent discoveries in the field of atomic energy (cf. Plutonium Project Symposium, 1947).

For roughly twenty-five years biological observations were mainly qualitative, and by seemingly haphazard methods many facts of fundamental importance were learnt. From about 1920 biological response was, in the laboratory at least, much more frequently measured quantitatively, though all tissues were not equally convenient for experiments of this kind, and unwarrantable generalisations were sometimes attempted. Meanwhile, work on the physical measurement of dose culminated in an international unit of measurement for X rays, the röntgen, now applicable to γ radiation as well.

Experimental radiobiology has thus grown to a science in which physical dose and biological response can be measured with reasonable accuracy. Its development has been greatly influenced by its relation to medicine, and while attempts are sometimes made to distinguish those investigations which have obvious application to medical practice (“applied radiology”) from those which have not (“pure research”), opinion would often be divided as to which category any particular investigation should be assigned.
VI. The Statistical Approach to Gastric Cancer
Authors: Jennings Denys
Published: July 2009

Statistics throw no light on the etiology of gastric cancer. On the contrary, they suggest that its incidence is much the same in widely differing environments.

There are no carefully planned statistical experiments to prove that one form of treatment is better than another.

Only a small proportion of cases of gastric cancer are ever submitted to gastrectomy.

The long-term survival rates of the survivors of gastrectomy compare favourably with the results from radical operation in other forms of malignant disease.

Earlier and repeated X-ray and gastroscopical examinations would probably save a considerable number of lives.
Wessex Branch
Authors: Buckley G. L.
Published: July 2009

The Wessex Branch has recently held its eighty-ninth Meeting, and is, in fact, slightly older than the Institute.

The members consist of nearly all the radiologists in an area extending from Portsmouth to Torquay, and from Cheltenham to the Isle of Wight. The radiologists from Netley and Haslar Hospitals have also been temporary members. There have never been any non-medical members.
Microradiography applied to Botany
Authors: Barclay A. E. , Leatherdale Donald
Published: July 2009

With the exceptions of Dauviller's work (1930) and experiments by Flower (1948), the possibilities of employing radiological methods in botanical fields have been little explored. Both of these workers succeeded in making radiographs of flowers by using very much softer X rays than are available from a normal X-ray tube. Flower, in conjunction with H. C. Mayle, used Grenz rays for his later beautiful work. So far as we are aware, this work was never followed up, nor was any attempt made to obtain finer detail. With the development of micro-arteriography (Barclay, 1947), techniques have been evolved whereby radiographs of specimens may be enlarged by many hundreds of diameters. Such techniques are by no means limited to medical and zoological fields, and this short note is an indication of one of these applications to the realm of botany.

Using the technique applied in microarteriography, a leaflet of a climbing Mermaid rose was radiographed, and upon subsequent magnification under the microscope it showed that either in or closely related to the veins were large numbers of “spots” (Fig. 1); for want of a more scientific description, we shall use this simple word. These bodies clearly possessed a much higher atomic weight than that of the leaf structure, for the densities of shadows cast by substances are roughly in direct proportion to the atomic numbers of the elements of which those substances are composed.
Correspondence
Authors: Brevet W. K.
Published: July 2009

In the June issue of this year of your journal I read “Some Aspects of Radiology in War-time Germany” by G. E. Donovan. The author writes about X-ray stereofluoroscopy. The device is not new. I saw it demonstrated on the congress of the German Radiological Society in Wiesbaden in 1927.