bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Teaching Improves with Resident Evaluation and Feedback
Authors: Baker Keith
Published: August 2010

Background

The literature is mixed on whether evaluation and feedback to clinical teachers improves clinical teaching. This study sought to determine whether resident-provided numerical evaluation and written feedback to clinical teachers improved clinical teaching scores.

Methods

Anesthesia residents anonymously provided numerical scores and narrative comments to faculty members who provided clinical teaching. Residents returned 19,306 evaluations between December 2000 and May 2006. Faculty members received a quantitative summary report and all narrative comments every 6 months. Residents also filled out annual residency program evaluations in which they listed the best and worst teachers in the department.

Results

The average teaching score for the entire faculty rose over time and reached a plateau with a time constant of approximately 1 yr. At first, individual faculty members had average teaching scores that were numerically diverse. Over time, the average scores became more homogeneous. Faculty members ranked highest by teaching scores were also most frequently named as the best teachers. Faculty members ranked lowest by teaching scores were most frequently named as the worst teachers. Analysis of ranks, differential improvement in scores, and a decrease in score diversity effectively ruled out simple score inflation as the cause for increased scores. An increase in teaching scores was most likely due to improved teaching.

Conclusions

A combination of evaluation and feedback, including comments on areas for improvement, was related to a substantial improvement in teaching scores. Clinical teachers are able to improve by using feedback from residents.
Mycobacterium marinum MMAR_2380, a predicted transmembrane acyltransferase, is essential for the presence of the mannose cap on lipoarabinomannan
Authors: Driessen Nicole N. , Stoop Esther J. M. , Ummels Roy , Gurcha Sudagur S. , Mishra Arun K. , Larrouy-Maumus Gérald , Nigou Jérôme , Gilleron Martine , Puzo Germain , Maaskant Janneke J. , Sparrius Marion , Besra Gurdyal S. , Bitter Wilbert , Vandenbroucke-Grauls Christina M. J. E. , Appelmelk Ben J.
Published: August 2010

Lipoarabinomannan (LAM) is a major glycolipid in the mycobacterial cell envelope. LAM consists of a mannosylphosphatidylinositol (MPI) anchor, a mannan core and a branched arabinan domain. The termini of the arabinan branches can become substituted with one to threeα(1→2)-linked mannosyl residues, the mannose cap, producing ManLAM. ManLAM has been associated with a range of different immunomodulatory properties ofMycobacterium tuberculosisduring infection of the host. In some of these effects, the presence of the mannose cap on ManLAM appears to be crucial for its activity. So far, in the biosynthesis of the mannose cap on ManLAM, two enzymes have been reported to be involved: a mannosyltransferase that adds the first mannosyl residue of the mannose caps to the arabinan domain of LAM, and another mannosyltransferase that elongates the mannose cap up to three mannosyl residues. Here, we report that a third gene is involved,MMAR_2380, which is theMycobacterium marinumorthologue ofRv1565c.MMAR_2380encodes a predicted transmembrane acyltransferase. InM. marinumΔMMAR_2380, the LAM arabinan domain is still intact, but the mutant LAM lacks the mannose cap. Additional effects of mutation ofMMAR_2380on LAM were observed: a higher degree of branching of both the arabinan domain and the mannan core, and a decreased incorporation of [1,2-14C]acetate into the acyl chains in mutant LAM as compared with the wild-type form. This latter effect was also observed for related lipoglycans, i.e. lipomannan (LM) and phosphatidylinositol mannosides (PIMs). Furthermore, the mutant strain showed increased aggregation in liquid cultures as compared with the wild-type strain. All phenotypic traits ofM. marinumΔMMAR_2380, the deficiency in the mannose cap on LAM and changes at the cell surface, could be reversed by complementing the mutant strain withMMAR_2380. Strikingly, membrane preparations of the mutant strain still showed enzymic activity for the arabinan mannose-capping mannosyltransferase similar to that of the wild-type strain. Although the exact function of MMAR_2380 remains unknown, we show that the protein is essential for the presence of a mannose cap on LAM.
Reproduction without sex: conidiation in the filamentous fungus Trichoderma
Authors: Steyaert Johanna M. , Weld Richard J. , Mendoza-Mendoza Artemio , Stewart Alison
Published: August 2010

Trichodermaspp. have served as models for asexual reproduction in filamentous fungi for over 50 years. Physical stimuli, such as light exposure and mechanical injury to the mycelium, trigger conidiation; however, conidiogenesis itself is a holistic response determined by the cell's metabolic state, as influenced by the environment and endogenous biological rhythms. Key environmental parameters are the carbon and nitrogen status and the C : N ratio, the ambient pH and the level of calcium ions. Recent advances in our understanding of the molecular biology of this fungus have revealed a conserved mechanism of environmental perception through the White Collar orthologues BLR-1 and BLR-2. Also implicated in the molecular regulation are the PacC pathways and the conidial regulator VELVET. Signal transduction cascades which link environmental signals to physiological outputs have also been revealed.
Genes required for the synthesis of heptose-containing oligosaccharide outer core extensions in Haemophilus influenzae lipopolysaccharide
Authors: Hood Derek W. , Deadman Mary E. , Engskog Mikael K. R. , Vitiazeva Varvara , Makepeace Katherine , Schweda Elke K. H. , Moxon Richard
Published: August 2010

Heptose-containing oligosaccharides (OSs) are found in the outer core of the lipopolysaccharide (LPS) of a subset of non-typable Haemophilus influenzae (NTHi) strains. Candidate genes for the addition of either l-glycero-d-manno-heptose (ld-Hep) or d-glycero-d-manno-heptose (dd-Hep) and subsequent hexose sugars to these OSs have been identified from the recently completed genome sequences available for NTHi strains. losA1/losB1 and losA2/losB2 are two sets of related genes in which losA has homology to genes encoding glycosyltransferases and losB to genes encoding heptosyltransferases. Each set of genes is variably present across NTHi strains and is located in a region of the genome with an alternative gene organization between strains that contributes to LPS heterogeneity. Dependent upon the strain background, the LPS phenotype, structure and serum resistance of strains mutated in these genes were altered when compared with the relevant parent strain. Our studies confirm that losB1 and losB2 usually encode dd-heptosyl- and ld-heptosyl transferases, respectively, and that losA1 and losA2 encode glycosyltransferases that play a role in OS extensions of NTHi LPS.
The rkpU gene of Sinorhizobium fredii HH103 is required for bacterial K-antigen polysaccharide production and for efficient nodulation with soybean but not with cowpea
Authors: Hidalgo Ángeles , Margaret Isabel , Crespo-Rivas Juan C. , Parada Maribel , Murdoch Piedad del Socorro , López Abigail , Buendía-Clavería Ana M. , Moreno Javier , Albareda Marta , Gil-Serrano Antonio M. , Rodríguez-Carvajal Miguel A. , Palacios Jose M. , Ruiz-Sainz José E. , Vinardell José M.
Published: August 2010

In this work, the role of the rkpU and rkpJ genes in the production of the K-antigen polysaccharides (KPS) and in the symbiotic capacity of Sinorhizobium fredii HH103, a broad host-range rhizobial strain able to nodulate soybean and many other legumes, was studied. The rkpJ- and rkpU-encoded products are orthologous to Escherichia coli proteins involved in capsule export. S. fredii HH103 mutant derivatives were contructed in both genes. To our knowledge, this is the first time that the role of rkpU in KPS production has been studied in rhizobia. Both rkpJ and rkpU mutants were unable to produce KPS. The rkpU derivative also showed alterations in its lipopolysaccharide (LPS). Neither KPS production nor rkpJ and rkpU expression was affected by the presence of the flavonoid genistein. Soybean (Glycine max) plants inoculated with the S. fredii HH103 rkpU and rkpJ mutants showed reduced nodulation and clear symptoms of nitrogen starvation. However, neither the rkpJ nor the rkpU mutants were significantly impaired in their symbiotic interaction with cowpea (Vigna unguiculata). Thus, we demonstrate for the first time to our knowledge the involvement of the rkpU gene in rhizobial KPS production and also show that the symbiotic relevance of the S. fredii HH103 KPS depends on the specific bacterium–legume interaction.
A ToxR-dependent role for the putative phosphoporin VCA1008 in bile salt resistance in Vibrio cholerae El Tor N16961
Authors: Goulart Carolina Lage , dos Santos Guilherme Garcia , Barbosa Livia Carvalho , Lery Letícia Miranda Santos , Bisch Paulo Mascarello , von Krüger Wanda Maria Almeida
Published: August 2010

The putative phosphoporin encoded by vca1008 of Vibrio cholerae O1 is expressed in vivo during infection and is essential for the intestinal colonization of infant mice. In vitro, its expression is induced under inorganic phosphate (Pi) limitation in a PhoB/R-dependent manner. In this work we demonstrated that VCA1008 has a strain-specific role in the physiology and pathogenicity of V. cholerae O1. Disruption of vca1008 led to a growth defect, an inability to colonize and a high susceptibility to sodium deoxycholate (DOC; the major bile compound) in the El Tor biotype strain N16961, but did not affect the classical strain O395 in the same way. Furthermore, vca1008 promoter activity was higher in N16961 cells grown under a low Pi supply in the presence of DOC than in the absence of the detergent. In the Pi-limited cells, vca1008 was positively regulated by PhoB, but when DOC was added to the medium, it negatively affected the PhoB-mediated activation of the gene, and enhanced vca1008 expression in a ToxR-dependent manner. These findings reveal for the first time a complex strain-specific interplay between ToxR and PhoB/R systems to control porin genes, as well as the influence of DOC on the expression of PhoB- and ToxR-regulated genes and pathogenesis in pandemic strains of V. cholerae.
Genome-wide mapping of nuclear mitochondrial DNA sequences links DNA replication origins to chromosomal double-strand break formation in Schizosaccharomyces pombe
Authors: Lenglez Sandrine , Hermand Damien , Decottignies Anabelle
Published: August 2010

Chromosomal double-strand breaks (DSBs) threaten genome integrity and repair of these lesions is often mutagenic. How and where DSBs are formed is a major question conveniently addressed in simple model organisms like yeast. NUMTs, nuclear DNA sequences of mitochondrial origin, are present in most eukaryotic genomes and probably result from the capture of mitochondrial DNA (mtDNA) fragments into chromosomal breaks. NUMT formation is ongoing and was reported to cause de novo human genetic diseases. Study of NUMTs is likely to contribute to the understanding of naturally occurring chromosomal breaks. We show that Schizosaccharomyces pombe NUMTs are exclusively located in noncoding regions with no preference for gene promoters and, when located into promoters, do not affect gene transcription level. Strikingly, most noncoding regions comprising NUMTs are also associated with a DNA replication origin (ORI). Chromatin immunoprecipitation experiments revealed that chromosomal NUMTs are probably not acting as ORI on their own but that mtDNA insertions occurred directly next to ORIs, suggesting that these loci may be prone to DSB formation. Accordingly, induction of excessive DNA replication origin firing, a phenomenon often associated with human tumor formation, resulted in frequent nucleotide deletion events within ORI3001 subtelomeric chromosomal locus, illustrating a novel aspect of DNA replication-driven genomic instability. How mtDNA is fragmented is another important issue that we addressed by sequencing experimentally induced NUMTs. This highlighted regions of S. pombe mtDNA prone to breaking. Together with an analysis of human NUMTs, we propose that these fragile sites in mtDNA may correspond to replication pause sites.
Susceptibility to chronic pain following nerve injury is genetically affected by CACNG2
Authors: Nissenbaum Jonathan , Devor Marshall , Seltzer Ze'ev , Gebauer Mathias , Michaelis Martin , Tal Michael , Dorfman Ruslan , Abitbul-Yarkoni Merav , Lu Yan , Elahipanah Tina , delCanho Sonia , Minert Anne , Fried Kaj , Persson Anna-Karin , Shpigler Hagai , Shabo Erez , Yakir Benjamin , Pisanté Anne , Darvasi Ariel
Published: August 2010

Chronic neuropathic pain is affected by specifics of the precipitating neural pathology, psychosocial factors, and by genetic predisposition. Little is known about the identity of predisposing genes. Using an integrative approach, we discovered that CACNG2 significantly affects susceptibility to chronic pain following nerve injury. CACNG2 encodes for stargazin, a protein intimately involved in the trafficking of glutamatergic AMPA receptors. The protein might also be a Ca2+ channel subunit. CACNG2 has previously been implicated in epilepsy. Initially, using two fine-mapping strategies in a mouse model (recombinant progeny testing [RPT] and recombinant inbred segregation test [RIST]), we mapped a pain-related quantitative trait locus (QTL) (Pain1) into a 4.2-Mb interval on chromosome 15. This interval includes 155 genes. Subsequently, bioinformatics and whole-genome microarray expression analysis were used to narrow the list of candidates and ultimately to pinpoint Cacng2 as a likely candidate. Analysis of stargazer mice, a Cacng2 hypomorphic mutant, provided electrophysiological and behavioral evidence for the gene's functional role in pain processing. Finally, we showed that human CACNG2 polymorphisms are associated with chronic pain in a cohort of cancer patients who underwent breast surgery. Our findings provide novel information on the genetic basis of neuropathic pain and new insights into pain physiology that may ultimately enable better treatments.
The Metabolic and Developmental Roles of Carotenoid Cleavage Dioxygenase4 from Potato
Authors: Campbell Raymond , Ducreux Laurence J.M. , Morris Wayne L. , Morris Jenny A. , Suttle Jeffrey C. , Ramsay Gavin , Bryan Glenn J. , Hedley Pete E. , Taylor Mark A.
Published: August 2010

The factors that regulate storage organ carotenoid content remain to be fully elucidated, despite the nutritional and economic importance of this class of compound. Recent findings suggest that carotenoid pool size is determined, at least in part, by the activity of carotenoid cleavage dioxygenases. The aim of this study was to investigate whether Carotenoid Cleavage Dioxygenase4 (CCD4) activity affects potato (Solanum tuberosum) tuber carotenoid content. Microarray analysis revealed elevated expression of the potato CCD4 gene in mature tubers from white-fleshed cultivars compared with higher carotenoid yellow-fleshed tubers. The expression level of the potato CCD4 gene was down-regulated using an RNA interference (RNAi) approach in stable transgenic lines. Down-regulation in tubers resulted in an increased carotenoid content, 2- to 5-fold higher than in control plants. The increase in carotenoid content was mainly due to elevated violaxanthin content, implying that this carotenoid may act as the in vivo substrate. Although transcript level was also reduced in plant organs other than tubers, such as leaves, stems, and roots , there was no change in carotenoid content in these organs. However, carotenoid levels were elevated in flower petals from RNAi lines. As well as changes in tuber carotenoid content, tubers from RNAi lines exhibited phenotypes such as heat sprouting, formation of chain tubers, and an elongated shape. These results suggest that the product of the CCD4 reaction may be an important factor in tuber heat responses.
Helping the police with their inquiries: the development of special care questioning techniques
Authors: TULLY BRYAN , TAM KAM‐OI
Published: August 2010

SUMMARY. When children are dealt with in the justice system, by the police or the courts, the results are often highly emotionally distressing, and damaging to the true purpose of testimony. This paper describes a training programme of ‘special care questioning’ developed by a police force which employs clinical pychologists. An outline rationale is described, and the results discussed. It concludes that the task of protecting children cannot be the exclusive domain of either Clinical* social service practitioners or legal officers. Creative and ethical cooperation is possible and necessary.

The special care questioning programme was developed from experimental work previously carried out with the Metropolitan Police with funding from the Police Foundation, UK.
Close encounters of the utilitarian kind: mediated reparation for young offenders
Authors: WATSON DAVID
Published: August 2010

SUMMARY. The proposal that reparation be added to the range of disposals available in our systems of juvenile justice has generally been resisted. In looking at both English and Scottish systems, it is stressed that decision‐makers are legally required to give priority to the welfare of the child. However, where reparation warrants rehabilitation that requirement is satisfied. Rehabilitation is more likely to be achieved when young offenders are diverted to programmes which support the development of appropriate attitudes to rights in property or person. Mediated encounters between victims and offenders may be programmes of the right type
After Cleveland: a crisis of confidence
Authors: GREENWOOD MARY , WAGTENDONK JAN VAN
Published: August 2010

SUMMARY. The article argues that social work is experiencing a crisis of confidence about child abuse. This lack of confidence is examined from various points of view; the social work skills needed to work with abused children and their families; the theoretical framework underpinning assessment and intervention; public confidence in social work; the legal processes; and departmental policy and practice. It suggests ways of overcoming the problems associated with the crisis of confidence including increased and better quality training, a more open approach to the community and an acceptance of professional independence
Evaluation of an easy to read parent‐held information and record booklet of child health
Authors: POLNAY LEON , ROBERTS HEATHER
Published: August 2010

SUMMARY. An evaluation of the Nottingham parent‐held record and information booklet is presented. The book was well used by the majority of parents with 80 per cent of the parents having read all the booklet by the time their babies were three months old. 70 per cent of the parents had retained the booklet when their children had reached the age of one year
Use of pre‐school daycare and education 1979–86
Authors: MOSS PETER , OWEN CHARLIE
Published: August 2010

SUMMARY. Using General Household Survey data, this paper considers attendance by children under five at public and private services providing non‐parental daycare and education in 1986 and compares it with 1979. Attendance of children under five rose from 32 per cent in 1979 to 42 per cent in 1986. The services included are primary schools, nursery schools and classes, playgroups, day nurseries and child minders. Playgroups are most used for two and three year olds and schools for four year olds with the majority of children attending on apart time basis. Children from higher social class backgrounds are more likely to receive care and/or education with 50 per cent of such children using pre‐school services, as compared to 3 7 per cent of children with fathers in manual occupations
Care fit for children
Authors: COLTON MATTHEW
Published: August 2010

SUMMARY. Following on from articles in Children and Society (3.1), this article discusses issues raised by recent research on foster and residential care practices, and centres on the question of whether children's homes should seek to provide child oriented day‐to‐day care. The role performed by children's homes in substitute child care is considered in order to highlight the dangers inherent in the notion that it may be appropriate to trade off child oriented care for the rather abstract notion of the ‘wider function’ of children's homes
Sudden death in infancy
Authors: BRYANT GILL
Published: August 2010

SUMMARY. Sudden death in infancy is now one of the commonest cause of death in young children in the United Kingdom affecting two to three per 1,000 livebirths. A number of background factors are associated with an increased risk of sudden death and the aetiology is likely to be multifactional. Some of these background factors are reviewed together with possible causes. The relationship with child abuse is discussed. While the aetiology and therefore methods of prevention remain uncertain, it is clear that families who suffer this form of bereavemem need support and counselling. The response of one health authority to the challenge of cot death is described.
Provision for the under‐fives: one council's response 1980–87
Authors: HAMILTON DOREEN
Published: August 2010

SUMMARY. Coordination of services for under‐fives is a major concern in efforts to achieve a reasonable level of services with low levels of resources. This article relates the history of one attempt to develop such a coordinated approach in one local authority — Leeds. A specially appointed Council Committee led the way to breaking down many barriers between services, to improving training, and to using scarce professional skills to best advantage.
Foster families and residential care for older children: some interpersonal dynamics
Authors: ALDGATE JANE
Published: August 2010

This paper compares the interpersonal dynamics of the family and residential care for older children within the context of ecologically based permanency planning where the birth family will be the preferred source of permanence in most cases. The author argues, on the basis of a review of the research, that foster care has a great deal to offer many children and is undoubtedly preferable for young children, but residential care is a genuine and important alternative for some older children. She concludes that the decision for placement should rest on a comprehensive assessment, taking into account consumer views.
Prisoners' children and politics: an aetiology of victimisation
Authors: SHAW ROGER
Published: August 2010

SUMMARY. Very little attention has been paid to the needs of prisoners' children, in spite of the large numbers involved. Whilst to some extent this is due to the hidden nature of the problem, it is also influenced significantly by the fact that the justice system ‐ based on concepts of acquitting the innocent and punishing the guilty ‐ cannot afford to accept publicly that many tens of thousands of children are punished more by the sentence than is their imprisoned parent. Often the prisoner's child may also suffer more than the victim of the parent's crime. Media attention to the sentencing of a mother by Judge Pickles brought into the open a subject which is mostly hidden or ignored. This article explores the issues and argues for a new approach
Under Fives: Thirty Years of No Progress?
Authors: Jackson Sonia
Published: August 2010

SUMMARY. The value of preschool education was already well recognised 30 years ago but the UK, unlike other European countries, has never developed a coherent system of public provision for young children. Reliance on private, voluntary and self‐help facilities to fill the gaps has produced diversity but variable quality and little real choice. Over the same period attitudes and family structures have changed and there have been great advances in our understanding of how children's development can be supported and enhanced. The Children Act 1989 provides a legal framework for translating this knowledge into action. Yet at a time when a remarkable degree of professional consensus has been achieved on what is needed, we seem as far as ever from an adequate level of good quality provision. The article suggests that the reason is to be found in the marginalisation of our youngest children as the concern only of their parents and not of society as a whole.
New Vocational Qualifications in Child Care and Education in the UK
Authors: Calder Pamela
Published: August 2010

SUMMARY: This paper explores the implications of the introduction of the new system of National Vocational Qualifications (NVQs) in Child Care and Education.

The historical context of provision and the dual system of training of early childhood workers in Britain, split between care and education, is briefly described to show why pressures for change have come about. The background to the development of the qualifications is examined to see what light this throws on their current implementation.

The paper argues that, compared with Europe where most countries are moving towards graduate status for early childhood education workers and many are thinking about an integration between care and education, with the introduction of our new child care NVQs we are moving in the opposite direction. Their introduction is likely to entrench the current split and does nothing to encourage the development of higher level qualifications which integrate care and education.
The Community Mothers Programme—Empowerment of parents by parents
Authors: Johnson Zachary , Molloy Brenda
Published: August 2010

SUMMARY: An innovative directed support intervention programme using lay people aimed at improving the quality of parenting during the first year of life was introduced on a pilot basis in Dublin in 1983 for parents of children living in working class communities. It involved experienced mothers who delivered a programme focusing on healthcare, nutritional improvement and overall child development to new parents. Support, encouragement and guidance were used rather than advice. The programme was evaluated in 1989 using a randomised controlled approach and was found to be effective in terms of health, nutrition and developmental stimulation. It has since expanded to incorporate breastfeeding support, mother and toddler groups and attention to the special needs of travellers, and the potential for applying this approach to other areas of healthcare and social development is large.
Researching Children: Methods and Ethics
Authors: Mahon Ann , Glendinning Caroline , Clarke Karen , Craig Gary
Published: August 2010

The appropriateness and desirability of researching children have been issues of some debate. Children may be perceived as non‐competent or vulnerable, and proxies have been used as children's representatives. Increasingly researchers are speaking to children directly. Why is this so and what are the methodological and ethical implications of researching children's views? In this paper the authors draw on their own experiences of researching children in the fields of child carers and the impact of the Child Support Act 1991. A number of social, political and legal trends are identified which form a background to the growing interest in children as potential and actual participants in the research process. The theoretical, methodological, ethical and practical issues involved are then identified and described, using examples from two separate studies conducted by the authors.
Parents Dilemmas in Sharing Donor Insemination Conception Stories with their Children
Authors: Hargreaves Katrina , Daniels Ken
Published: August 2010

Parents of children conceived by gamete (sperm or egg) donation often find it challenging to share donor conception stories with their children. This study reports findings of a qualitative study of families with children conceived by donor insemination in New Zealand, a country where the policy and practice of sharing information in donor insemination is advanced. Almost all parents had told, or planned to tell, their children about their origins, but some parents faced considerable dilemmas around disclosure. Parents need to be given support and guidance as they inform their children about their donor family history. © 2007 The Author(s). Journal compilation © 2007 National Children's Bureau.
let‐7 and miR‐17‐92: Small‐sized major players in lung cancer development
Authors: Osada Hirotaka , Takahashi Takashi
Published: August 2010

MicroRNA (miRNA)‐encoding small non‐coding RNA have been recognized as important regulators of a number of biological processes that inhibit the expression of hundreds of genes. Accumulating evidence also indicates the involvement of miRNA alterations in various types of human cancer, including lung cancer, which has long been the leading cause of cancer death in economically well‐developed countries, including Japan. We previously found that downregulation of members of the tumor‐suppressive let‐7 miRNA family and overexpression of the oncogenic miR‐17‐92 miRNA cluster frequently occur in lung cancers, and molecular insight into how these miRNA alterations may contribute to tumor development has been rapidly accumulating. The present review summarizes recent advances in elucidation of the molecular functions of these miRNA in relation to their roles in the pathogenesis of lung cancer. Given the crucial roles of miRNA alterations, additional studies are expected to provide a better understanding of the underlying molecular mechanisms of disease development, as well as a foundation for novel strategies for cancer diagnosis and treatment of this devastating disease. (Cancer Sci 2011; 102: 9–17)
Failure to improve cigarette smoking abstinence with transdermal selegiline + cognitive behavior therapy
Authors: Killen Joel D. , Fortmann Stephen P. , Murphy Greer M. , Hayward Chris , Fong Dalea , Lowenthal Kimberly , Bryson Susan W. , Killen Diana T. , Schatzberg Alan F.
Published: August 2010

Aims  To examine the effectiveness of transdermal selegiline for producing cigarette smoking abstinence.

Design  Adult smokers were randomly assigned to receive selegiline transdermal system (STS) or placebo given for 8 weeks. All participants received cognitive behavior therapy (CBT). Follow‐ups were conducted at 25 and 52 weeks.

Setting  Community smoking cessation clinic.

Participants  243 adult smokers (≥18 years of age; ≥10 cigarettes/day).

Measures  Expired‐air carbon monoxide confirmed 7‐day point prevalence abstinence.

Findings  STS was not superior to placebo. More women than men were abstinent at 52 week follow‐up (28% vs 16%, P < 0.05). Behavioral activation (BAS) moderated treatment response (P = 0.01). The survival rate through week 52 for those with high ‘drive’ scores on the BAS was 47% if assigned to selegiline and 34% if assigned to placebo. The survival rate for those with low ‘drive scores’ on the BAS was 35% if assigned to selegiline compared to 53% if assigned to placebo.

Conclusion  Transdermal selegiline does not appear generally effective in aiding smoking cessation though there may be a selective effect in those smokers with low ‘behavioral activation’.
Genetic polymorphisms of proteins in different breeds and different populations of chickens
Authors: Stratil A.
Published: August 2010

Six polymorphic protein systems in 15 chicken breeds have been investigated. In the Silkie breed another variant of G3 proteins (G3 AF Silkie) has been observed characterized by higher electrophoretic mobility than G3 A. The frequencies of individual alleles in various lines and different generations have been determined in two breeds (White Leghorn and White Cornish).
Polymorphism in glucose‐6‐phosphate dehydrogenase in the German Large‐White
Authors: Verhorst D.
Published: August 2010

Glucose‐6‐phosphate dehydrogenase was tested in haemolysed swine erythrocytes by starch gel electrophoresis. In the German Large‐White this system is genetically controlled by two alleles, G‐6‐PDA and G‐6‐PDB.
The AB blood group system of cats
Authors: Auer L. , Bell K.
Published: August 2010

Holmes (1950) and Eyquem. Podliachouk & Milot (1962) classified feline erythrocytes into two types according to their reactions with naturally occurring antibodies in cats' plasmas. Eyquem et al. (1962) designated the two antigens, A and B. and this nomenclature has been retained in the present study. The blood group system. AB. was investigated in more detail, both genetically and serologically. Frequencies of 73.3 % A and 26.3 % B were found in a survey of 1895 Brisbane cats and in addition, a new phenotype. AB. was discovered with a low incidence of 0.4 %.The results of the serological testing and limited family information suggested that the AB phenotype is inherited and not due to blood chimaerism. Preliminary genetic studies indicated that the A gene is dominant to the B in the usual situation and hypotheses to explain the occurrence of the AB phenotype are discussed.

The incidence of naturally occurring antibodies was investigated in cats, with 1895 of blood type B having anti‐A and only 35 % of type A having anti‐B. No subgroups of the A and B antigens were detected and no blood group substances were found in the salivas of 37 cats. There was no evidence of any serological relationship of the feline A and B antigens with the human ABO antigens.
The swine histo compatibility system SLA: serological studies in the common Swiss and Danish swine breeds
Authors: Kristensen Birte , Philipsen Merete , Lazary S. , Renard Christine , de Weck A. L.
Published: August 2010

Alloantisera were produced in common Swiss and Danish swine breeds by immunization with leucocytes or skin‐grafts. Out of the 126 antisera, 66 were chosen for further study based on titrations employing lymphocytes from unrelated pigs typed with French SLA antisera (Vaiman, Chardon & Renard, 1979). The 66 selected antisera and the French reagents defining 26 SLA specificities were used to type lymphocytes from 595 unrelated pigs of the common Swiss and Danish breeds. The reaction‐patterns of the French, Swiss and Danish antisera were adequately correlated for the French SLA specificities Nos FJ 2, 3, 6, 7, 8, 9, 11, 14, 19, 20 and 24 and for the haplotypes FJ 15.1.18 and FJ 5.4. In addition, a cluster of correlated Danish and Swiss antisera characterized a new specificity, provisionally designated CPH 31. This specificity was frequent in the Danish Landrace pigs.

Using the reagents identified in this report, the segregation of SLA markers was studied. Back‐cross families demonstrated segregation of 15 distinct SLA haplotypes of which 14 are common in French Landrace or Large White. Differences were found in haplotype frequencies in both the Swiss and the Danish Landrace and Large White breeds.
Advances in understanding the pulmonary infiltration in acute promyelocytic leukaemia
Authors: Luesink Maaike , Jansen Joop H.
Published: August 2010

In acute promyelocytic leukaemia (APL), differentiation therapy can be complicated by the development of a differentiation syndrome (DS). Pulmonary infiltration of differentiating leukaemic cells is a key event in the development of DS. Several mediators have been identified that may promote migration and extravasation of differentiating APL cells from the bloodstream into the tissue. Adhesion of APL cells to each other and to the endothelium is induced by upregulation of the expression of adhesion molecules and constitutively active β2‐integrins during differentiation therapy. The expression of chemokines and their receptors is significantly upregulated as well. Pulmonary chemokine production can trigger transendothelial migration of differentiating APL cells from the bloodstream into the underlying tissue (initiation phase of DS). Massive production of chemokines by infiltrated APL cells can further enhance transendothelial migration of differentiating APL cells, causing an uncontrollable hyperinflammatory reaction in the lung (aggravation phase), which is not efficiently switched‐off by corticosteroids.
Thrombopoietic effect of VPAC1 inhibition during megakaryopoiesis
Authors: Peeters Karen , Loyen Serena , Van kerckhoven Soetkin , Stoffels Katinka , Hoylaerts Marc F. , Van Geet Chris , Freson Kathleen
Published: August 2010

Megakaryocytes and platelets express the stimulatory G protein (Gs)‐coupled VPAC1 receptor, for which the pituitary adenylyl cyclase‐activating peptide (PACAP) and vasoactive intestinal peptide (VIP) are agonists. The neuropeptide PACAP and VPAC1 were previously found to negatively regulate megakaryopoiesis, and inhibition of their physiological pathway was found to have a thrombopoietic effect in conditions where megakaryo‐poiesis and thrombopoiesis were impaired, such as chemotherapy‐induced thrombocytopenia and congenital thrombocytopenia. The present study explored the thrombopoietic effect of VPAC1 inhibition in a murine model of syngeneic bone marrow transplantation (BMT) and in passive immune thrombocytopenia. Treatment of donor mice with a neutralizing anti‐VPAC1 antibody stimulated the initial, most critical recovery of the platelets in irradiated mice. In the passive immune thrombocytopenia model, we observed a thrombopoietic effect, resulting in a less severe platelet drop after induction of their removal in the spleen by an anti‐platelet antibody. We concluded that inhibition of the physiological PACAP/VPAC1 pathway could stimulate in vivo megakaryopoiesis. This inhibition can be applied to attenuate thrombocytopenia in conditions where platelets are destroyed as the major pathogenetic mechanism, e.g. immune thrombocytopenia purpura, or need to be produced de novo, e.g. after irradiation and BMT.
Prospective study of a therapeutic regimen with all‐trans retinoic acid and anthracyclines in combination of cytarabine in children with acute promyelocytic leukaemia: the Japanese childhood acute myeloid leukaemia cooperative study
Authors: Imaizumi Masue , Tawa Akio , Hanada Ryoji , Tsuchida Masahiro , Tabuchi Ken , Kigasawa Hisato , Kobayashi Ryoji , Morimoto Akira , Nakayama Hideki , Hamamoto Kazuko , Kudo Kazuko , Yabe Hiromasa , Horibe Keizo , Tsuchiya Shigeru , Tsukimoto Ichiro
Published: August 2010

In childhood acute promyelocytic leukaemia (APL), the efficacy of therapy combining cytarabine with all‐trans retinoic acid (ATRA) and anthracyclines remains unclear in terms of long‐term prognosis. Between August 1997 and March 2004, 58 children with APL (median age: 11 years) were enrolled into an acute myeloid leukaemia (AML) study (AML99‐M3) and followed up for a median time of 86 months. The regimen included ATRA and anthracyclines combined with cytarabine in both induction and consolidation. In induction, two patients died of haemorrhage and four patients developed retinoic acid syndrome. Of 58 patients, 56 (96·6%) achieved complete remission, two of whom relapsed in the bone marrow after 15 and 19 months respectively. Sepsis was a major complication, with an incidence of 5·6–10·9% in the consolidation blocks, from which all but one of patients recovered. Consequently, 7‐year overall and event‐free survival rates were 93·1% and 91·4% respectively, and cumulative incidence of relapse plateaued at 3·6% after 2 years. Follow‐up survey of 54 patients revealed no patients with late cardiotoxicity or secondary malignancy, except one with asymptomatic prolongation of QTc interval. This study suggests that the combination of cytarabine with ATRA and anthracycline‐based therapy may have useful implications in the perspective of long‐term prognosis and late adverse effects for childhood APL.
A comparison of anti-lymphocyte immunotoxins containing different ribosome-inactivating proteins and antibodies
Authors: BOLOGNESI A , TAZZARI P L , TASSI C , GROMO G , GOBBI M , STIRPE F
Published: August 2010

Immunotoxins were prepared with several single-chain ribosome-inactivating proteins (RIPs type 1) and with the A-chain of ricin linked to the F(ab′)2 fragment of sheep anti-mouse IgG. The cytotoxic activity of these conjugates was tested on human lymphocytes pretreated with an anti-CD3 murine MoAb. The immunotoxins inhibited DNA synthesis in phytohaemagglutinin (PHA)-stimulated lymphocytes with IC50S (concentrations causing 50% inhibition) ranging from 8·9 × 10−13 to 5·7 × 10−11m (immunotoxins containing dianthin 32, saporin, pokeweed antiviral protein from seeds (PAP-S), bryodin, momordin, momorcochin, and trichokirin), 1 × 10−8m (immunotoxin containing gelonin) and 5 × 10−9m (immunotoxin containing ricin A-chain). The immunotoxin containing saporin linked to the anti-mouse IgG F(ab′)2 fragment was also highly toxic to human lymphocytes pretreated with anti-CD2, -CD3, -CD5 and -CD45 MoAbs, with IC50s ≤ 10−11m. Immunotoxins were prepared also with saporin linked to MoAbs against various CD antigens. The immunotoxin prepared with the anti-CD3 antibody had the highest specific cytotoxicity to human lymphocytes.
Effects of tumour necrosis factor-alpha (TNF-α), IL-1β and monocytes on lymphokine-activated killer (LAK) induction from natural killer (NK) cells and T lymphocytes
Authors: YONEDA K , OSAKI T , YAMAMOTO T , UETA E
Published: August 2010

Roles of monocytes and cytokines were investigated on LAK induction from T and NK cells. Monocytes augmented more T-LAK induction than did NK-LAK. Expression of IL-β, TNF-α and interferon-gamma (IFN-γ)-mRNA and their cytokine production were superior in NK cells compared with T cells in parallel with their LAK activities. An increase of TNF-α, IL-1β and IFN-γ production was induced by co-culturing NK or T cells with autologous monocytes. The augmentation of T cell cytokine production and T-LAK activity by monocytes was more prominent than that of NK cells. TNF-α and IL-1β were generated 24 h after IL-2 stimulation, and these cytokines were able to almost substitute for monocytes in LAK induction. Conversely, LAK induction was almost completely suppressed by both anti-IL-1β and anti-TNF-α antibodies, if they were added within 24 h after the start of the LAK induction. IFN-γ, which was produced at a later stage, scarcely affected LAK induction in spite of the cooperation with TNF-α. The results obtained indicate conclusively that the superiority of NK-LAK depends on their superior productivity of both IL-1β and TNF-α, and that the up-regulation of LAK induction by monocytes is largely due to the enhanced generation of both cytokines.
HIV-1 infection of monocyte-derived macrophages reduces Fc and complement receptor expression
Authors: KENT S J , STENT G , SONZA S , HUNTER S D , CROWE S M
Published: August 2010

Fc receptor (FcR) and complement receptor (CR) expression on HIV-infectcd monocyte-derived macrophages may be an important determinant of immune function. We studied the effects of HIV-1 infection of macrophages in vitro on FcR and CR expression. Macrophages were infected with HlV-lpv 7 days following isolation, and the expression of FcgI-III and CR3 were measured at intervals thereafter by flow cytometry. We found a reduction in receptor expression with the percentage of cells expressing FcRI 14 days post infection declining from 77% to 13%, FcRII fell from 96% to 85%. FcRIII from 45%, to 9%. and CR3 from 91%. to 67& 14 days following infection. As these receptors are important for macrophage function, their down-modulation muy contribute to the pathogenesis of HIV-related disease.
Quantitative analysis of C4Ab and C4Bb binding to the C3b/C4b receptor (CR1, CD35)
Authors: REILLY B D , MOLD C
Published: August 2010

Complement-dependent clearance of immune complexes in humans is dependent on the activation and binding of the early components of the classical complement cascade. This prevents immune complex precipitation and promotes binding of the complexes by the C4b/C3b complement receptor CR1 (CD35) found on erythrocytes. The fourth component of human complement is encoded by two closely linked genes within the MHC. These genes give rise to the isotypic forms C4A and C4B, and recent studies suggest that CR1 binds activated C4A (C4Ab) to a greater extent than activated C4B (C4Bb). To study this difference in a more quantitative way the binding reactions between CR1 and C4Ab- and C4Bb-coated immune complexes and between CR1 and soluble dimers of C4Ab (C4Ab2) and C4Bb (C4Bb2) were analysed using the native receptor on human erythrocytes. The binding reaction between immune complexes with equivalent amounts of covalently bound C4Ab or C4Bb and erythrocyte CR1 showed a two-fold higher binding of complexes coated with C4A. Furthermore, erythrocyte CR1 bound C4Ab2 with an apparent four-fold higher affinity (Kd= 1·4 × 10−7m) than C4Bb2 (Kd=4·8×10−7m), indicating a preferential binding of CR1 for C4A.
Txk, a member of the non-receptor tyrosine kinase of the Tec family, forms a complex with poly(ADP-ribose) polymerase 1 and elongation factor 1α and regulates interferon-γ gene transcription in Th1 cells
Authors: Maruyama T , Nara K , Yoshikawa H , Suzuki N
Published: August 2010

We have found previously that Txk, a member of the Tec family tyrosine kinases, is involved importantly in T helper 1 (Th1) cytokine production. However, how Txk regulates interferon (IFN)-γ gene transcription in human T lymphocytes was not fully elucidated. In this study, we identified poly(ADP-ribose) polymerase 1 (PARP1) and elongation factor 1α (EF-1α) as Txk-associated molecules that bound to the Txk responsive element of the IFN-γ gene promoter. Txk phosphorylated EF-1α and PARP1 formed a complex with them, and bound to the IFN-γ gene promoter in vitro. In particular, the N terminal region containing the DNA binding domain of PARP1 was important for the trimolecular complex formation involving Txk, EF-1α and PARP1. Several mutant Txk which lacked kinase activity were unable to form the trimolecular complex. A PARP1 inhibitor, PJ34, suppressed IFN-γ but not interleukin (IL)-4 production by normal peripheral blood lymphocytes (PBL). Multi-colour confocal analysis revealed that Txk and EF-1α located in the cytoplasm in the resting condition. Upon activation, a complex involving Txk, EF-1α and PARP1 was formed and was located in the nucleus. Collectively, Txk in combination with EF-1α and PARP1 bound to the IFN-γ gene promoter, and exerted transcriptional activity on the IFN-γ gene.
BY55/CD160 cannot be considered a cytotoxic marker in cytomegalovirus-specific human CD8+ T cells
Authors: Merino J , Ramírez N , Moreno C , Toledo E , Fernández M , Sánchez-Ibarrola A
Published: August 2010

CD160/BY55 is a glucosyl-phosphatidylinositol (GPI)-anchored cell membrane receptor that is expressed primarily in natural killer (NK) cells. Its presence in CD8+ T lymphocytes is considered to be a marker of cytotoxic activity, although there are few data in this regard. In the present work, we analysed the expression of CD160 in subpopulations of cytomegalovirus (CMV)-specific CD8+ T cells. Subpopulations were defined by CD28 and CD57 expression and exhibited varying degrees of differentiation and cytotoxic potential, as evaluated by the expression of perforin, interferon (IFN)-γ and interleukin (IL)-7Rα/CD127. We included subjects with different intensities of anti-viral immune response. Results showed that the terminally differentiated CD28– CD57+ subset displaying the highest level of perforin expressed CD160 at a level similar to that of memory CD28+ CD57–perforin– cells. A comparison of the expression of perforin in CD160+ cells versus CD160– cells showed that expression was significantly higher in the absence of CD160. Interestingly, the CMV-specific CD8+ T cell subset from a patient with ongoing CMV reactivation did not begin to express CD160 until day +92 of the follow-up period. Taken together, our data show that CD160 cannot be considered a cytotoxic marker in CMV-specific CD8+ T cells.