bluuebunny/crossref_metadata_2025 huggingface dataset:
Mycobacterium tuberculosis induces high production of nitric oxide in coordination with production of tumour necrosis factor‐α in patients with fresh active tuberculosis but not in MDR tuberculosis
Authors: Sharma Sadhna , Sharma Monika , Roy Sugata , Kumar Praveen , Bose Mridula
Published: July 2004

Mycobacterium tuberculosis is an intracellular pathogen that readily survives and replicates in human macrophages. Host cells have developed various mycobactericidal and immunoregulatory mechanisms, such as the production of nitric oxide and inflammatory cytokines to control intracellular replication of M. tuberculosis. Inducible nitric oxide synthase (iNOS) is transcriptionally under the control of IFN‐γ and TNF‐α. IL‐12 provides a crucial link between activated mononuclear phagocytes and T cells by regulating the production of IFN‐γ. In this study, we investigated the production of nitric oxide (NO), TNF‐α and IL‐12 by the peripheral blood monocytes (PB Mn) of patients suffering from multidrug‐resistant tuberculosis (MDR‐TB). The cells were infected with M. tuberculosis and stimulated with IFN‐γ or activated with mycobacterial subcellular components. The results were compared with those from cases of newly diagnosed TB and healthy controls. Nitric oxide production was significantly depressed in PB Mn from MDR‐TB patients. Infected monocytes from newly diagnosed TB patients produced significantly higher levels of NO as compared to those from MDR‐TB patients or normal controls. The subcellular fraction of M. tuberculosis‐like whole cell lysate (WCL), culture filtrate protein (CFP) and lipoarabinomannan (LAM) induced higher concentrations of NO release in PB Mn from newly diagnosed TB patients as compared to those from MDR‐TB patients. Cell culture supernatant from PB Mn assayed at 48 h after infection or stimulation demonstrated significantly depressed release of TNF‐α and IL‐12 from MDR‐TB cases as compared to the fresh cases. We observed a definite correlation between nitric oxide release and TNF‐α production, irrespective of low or high production in MDR‐TB or fresh cases, respectively. The present data suggest that peripheral blood monocytes of MDR‐TB patients typically show signs of immunosuppression. Whether such immunodepression is the cause or the effect of MDR‐TB merits further investigation.
Pseudomonas aeruginosa‐induced production of free radicals by IFNγ plus TNFα‐activated human endothelial cells: mechanism of host defense or of bacterial pathogenesis?
Authors: De Assis Maria‐Cristina , Saliba Alessandra M , Vidipó Luciana A , De Salles João B , Plotkowski Maria‐Cristina
Published: July 2004

We have previously shown that human umbilical vein endothelial cells (HUVEC) can be activated by IFNγ plus TNFα to kill intracellular (IC) Pseudomonas aeruginosa through production of reactive oxygen intermediate, but the cumulative effects of cytokine activation and bacterial infection on host cells has not been extensively addressed. In this study we investigated the fate of IFNγ plus TNFα‐activated HUVEC that have harboured IC bacteria for up to 24 h. At 10 h, the endothelial cell killing of P. aeruginosa isolates exceeded 90%. IC bacteria enhanced the expression of inducible nitric oxide synthase (iNOS) and induced overproduction of NO and superoxide by infected HUVEC. P. aeruginosa IC infection also induced a slight decrease in the cellular level of reduced glutathione (GSH). Overproduction of NO correlated with a marked peroxidation of plasma membrane lipids and decline in HUVEC viability. Treatment of cells with the antioxidant α‐lipoic acid significantly increased the survival of infected cells. Our data suggest that with the failure of adequate scavenger mechanisms, oxidant radicals overproduced in response to bacterial infection were highly toxic to host cells. Therefore, instead of contributing to defence against infectious agents, the upregulation of free radicals production by endothelial cells in response to cytokine activation would be detrimental to the host.
Therapeutic efficacy of pooled buffy‐coat platelet components prepared and stored with a platelet additive solution
Authors: Van Rhenen D. J. , Gulliksson H. , Cazenave J. P. , Pamphilon D. , Davis K. , Flament J. , Corash L.
Published: July 2004

Summary.  Despite the introduction of platelet additive solutions for the preparation of pooled platelet components, only a few studies of limited scope have evaluated the clinical efficacy of platelets stored in these solutions. The current report presents an analysis of data to evaluate the response to the transfusion of pooled buffy‐coat components suspended in storage solution with reduced (35%) plasma content in comparison with 100% plasma products.

During the euroSPRITE clinical trial of platelet components treated with a pathogen inactivation process, control treatment group platelet components were prepared in 100% allogeneic donor plasma (plasma control) or in platelet additive solution (T‐Sol™) mixed with plasma (T‐Sol control). Control group thrombocytopenic patients received either plasma control or T‐Sol control platelet components. One‐hour and 24‐h platelet count increments (CIs) and corrected count increments (CCIs) were analysed for these two types of preparation. In addition, haemostatic assessments were conducted for each transfusion.

One‐hour and 24‐h mean platelet CIs and post‐transfusion haemostatic scores were not significantly different for patients receiving platelet components suspended in 100% plasma and T‐Sol plasma mixtures.

Pooled buffy‐coat platelet components prepared in reduced plasma content mixtures provided therapeutic platelet CIs with effective haemostasis.
Plasma quality after whole‐blood filtration depends on storage temperature and filter type
Authors: Heiden M. , Salge U. , Henschler R. , Pfeiffer H.‐U. , Volkers P. , Hesse J. , Sireis W. , Seitz R.
Published: July 2004

Summary.  The study evaluated the quality of plasma obtained after whole‐blood filtration with four different polyester filters and one polyurethane filter. The activities of coagulation factors and proteinase inhibitors were not or only negligibly affected by filtration, in all experiments. Filtration did not increase markers of clotting and fibrinolysis. Only a strong neutrophil and complement activation was observed, which depended on the type of filter and whole‐blood storage conditions. However, as neutrophil elastase‐specific degradation products did not increase and the complement‐derived anaphylatoxin C3a was found in its inactivated form, C3a‐desArg, these filtration‐dependent changes apparently have little impact on the therapeutic quality of whole‐blood‐filtered fresh frozen plasma for transfusion.
SERF: a new antigen in the Cromer blood group system
Authors: Banks J. , Poole J. , Ahrens N. , Seltsam A. , Salama A. , Hue‐Roye K. , Storry J. R. , Palacajornsuk P. , Ma B‐W. , Lublin D. M. , Reid M. E.
Published: July 2004

Summary.  The Cromer blood group system consists of eight high incidence and three low incidence antigens carried on decay‐accelerating factor (DAF). This report describes the identification and characterization of a new Cromer high incidence antigen, named SERF.

Sequence analyses of DNA from a Thai female whose serum contained the alloantibody to a high incidence antigen in the Cromer blood group system (anti‐SERF) and from her two children were performed. Reverse transcriptase‐polymerase chain reaction (RT‐PCR) and sequence analysis on cDNA from the proband and PCR‐restriction fragment length polymorphism analysis on DNA from Thais were also performed. To map the epitope, DAF deletion mutants were tested by immunoblotting with anti‐SERF.

Sequence analysis revealed a substitution of 647C>T in exon 5 DAF in the proband. The proband's two children and two of 100 Thais were heterozygotes 647C/T. Analysis using DAF deletion mutants revealed the antigenic determinant to be within short consensus repeat 3 (SCR3), which is encoded by exon 5.

This study describes a novel high incidence antigen (SERF) in the Cromer blood group system characterized by the amino acid proline at position 182 in SCR3 of DAF. The SERF‐negative proband has a substitution mutation that predicts for leucine at this position. SERF has been provisionally assigned the International Society of Blood Transfusion number 021·012 (CROM 12).
Controlling the release and production of renin
Authors: Persson P. B. , Skalweit A. , Thiele B. J.
Published: July 2004

The renin–angiotensin system (RAS) plays a pivotal role for a variety of cardiovascular functions. The diversity of renin actions is reflected by its complex control. The major stimulus for the release of renin from the vesicles in juxtaglomerular cells is determined by stretch, as induced by changes in arterial pressure. The production of renin underlies a vastly complex control network, which takes place at different levels, such as transcription and translation. With regard to transcription, important regions for binding transcription factors have been identified several years ago, but the conservation of nucleotide sequences throughout different species suggests that there might be additional binding regions of importance. At the post‐transcriptional level, the modulation of renin mRNA stability is seems pivotal. The half‐life of renin mRNA appears to be controlled by the interaction between several regulatory proteins, most of which are well known in other systems. Moreover, in addition to the modulation of mRNA stability, the translation efficiency seems to play a key role in determining the amount of renin to be produced.
Structure of renal afferent arterioles in the pathogenesis of hypertension
Authors: Skov K. , Mulvany M. J.
Published: July 2004

Renal vascular resistance is increased in essential hypertension, as in genetic models of hypertension. Here we review the evidence that this is at least in part due to structural changes in the afferent arterioles. Rat studies show that the renal afferent arteriole is structurally narrowed in young and adult spontaneously hypertensive rats (SHR). Furthermore, in the second generation of crossbred SHRs/normotensive rats (SHR/WKY F2‐hybrids), a narrowed afferent arteriole lumen diameter at 7 weeks is a predictor of later development of high blood pressure. The reduced lumen diameter of resistance vessels is accompanied by a decrease in media cross‐sectional area in SHR and could therefore be due to inhibited growth. Evidence from a primate model of hypertension has shown a negative correlation between left ventricular hypertrophy and afferent arteriole diameter, but apparently no relation to blood pressure. In SHR, the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors is mediated through renal vascular mechanisms, while ACE inhibitors (like AT1 antagonists) have a more persistent effect on blood pressure after treatment withdrawal compared with other antihypertensive drugs. Taken together, the evidence suggests that structural narrowing of the renal afferent arteriole could be an important link in the pathogenesis of primary hypertension, at least in the SHR.
Nitric oxide counteracts angiotensin II induced contraction in efferent arterioles in mice
Authors: Patzak A. , Kleinmann F. , Lai E. Y. , Kupsch E. , Skelweit A. , Mrowka R.
Published: July 2004

Aim:  Efferent arterioles (Ef) are one of the final control elements in glomerular haemodynamics. The influence of nitric oxide (NO) on Ef remains ambiguous.

Methods:  To test the hypothesis that endothelial NO plays an important role in this context, afferent arterioles (Af) and Ef of wild‐type mice (WT), and Ef of mice lacking the endothelial NO synthetase [eNOS(−/−)] were perfused. Perfusion was performed in Ef via Af (orthograde) as well as from the distal end of Ef (retrograde), which provides an estimate for the importance of substances derived from the glomerulus. Angiotensin II (Ang II) was added in doses ranging from 10−12 to 10−6 mol L−1 to the bath solution.

Results:  Ang II reduced the luminal diameter of Af to 68 ± 7 and in Ef to 55 ± 8% during orthograde, and to 35 ± 6% during retrograde perfusion (10−6 mol L−1 Ang II) in WT. Pre‐treatment with NG‐Nitro‐l‐arginine‐methylester (l‐NAME) (10−4 mol L−1) increased the Ang II sensitivity in retrograde (17 ± 9%) and orthograde perfused Ef (19 ± 9%). The Ang II sensitivity was enhanced in eNOS(−/−) mice compared with WT, too. Already at a dose of Ang II 10−9 mol L−1, luminal diameters diminished to 8 ± 7 and 7 ± 4%.

Conclusion:  The increased Ang II sensitivity during l‐NAME pre‐treatment and in eNOS(−/−) mice indicates a strong counteraction of endothelial derived NO on Ang II induced contraction in Ef. Moreover, Ef are similarly sensitive to Ang II during either retrograde or orthograde perfusion in the absence of NO effects, suggesting that NO mediates, at least in part, the action of potential vasodilatory substances from the glomerulus.
Renal autoregulation in P2X1 knockout mice
Authors: Inscho E. W. , Cook A. K. , Imig J. D. , Vial C. , Evans R. J.
Published: July 2004

Autoregulation of renal blood flow is an established physiological phenomenon, however the signalling mechanisms involved remain elusive. Autoregulatory adjustments in preglomerular resistance involve myogenic and tubuloglomerular feedback (TGF) influences. While there is general agreement on the participation of these two regulatory pathways, the signalling molecules and effector mechanisms have not been identified. Currently, there are two major hypotheses being considered to explain the mechanism by which TGF signals are transmitted from the macula densa to the afferent arteriole. The adenosine hypothesis proposes that the released adenosine triphosphate (ATP) is hydrolysed to adenosine and this product stimulates preglomerular vasoconstriction by activation of A1 receptors on the afferent arteriole. Alternatively, the P2 receptor hypothesis postulates that ATP released from the macula densa directly stimulates afferent arteriolar vasoconstriction by activation of ATP‐sensitive P2X1 receptors. This hypothesis has emerged from the realization that P2X1 receptors are heavily expressed along the preglomerular vasculature. Inactivation of P2X1 receptors impairs autoregulatory responses while afferent arteriolar responses to A1 adenosine receptor activation are retained. Autoregulatory behaviour is markedly attenuated in mice lacking P2X1 receptors but responses to adenosine A1 receptor activation remain intact. More recent experiments suggest that P2X1 receptors play an essential role in TGF‐dependent vasoconstriction of the afferent arteriole. Interruption of TGF‐dependent influences on afferent arteriolar diameter, by papillectomy or furosemide treatment, significantly attenuated pressure‐mediated afferent arteriolar vasoconstriction in wild‐type mice but had no effect on the response in P2X1 knockout mice. Collectively, these observations support an essential role for P2X1 receptors in TGF‐mediated afferent arteriolar vasoconstriction.
The role of the RAS in programming of adult hypertension
Authors: Rasch R. , Skriver E. , Woods L. L.
Published: July 2004

The aetiology of cardiovascular disease originally included two components: a genetic component and an environmental or lifestyle component. Increasing epidemiologic evidence has been accumulating during the last decades indicating the importance of a third component: the influence of the environment during foetal development. Poor living conditions resulted in a high infant mortality and influenced the incidence of cardiovascular diseases in adulthood despite better living conditions (A. Forsdahl. Br J Prev Soc Med 1977; 31, 91–95). An association between pre‐natal growth pattern and the rate of death from cardiovascular disease in adulthood was reported (D.J. Barker, P.D. Winter, C. Osmond, B. Margetts & S.J. Simmonds. Lancet 1989; 2, 577–580). Men from Hartfordshire (UK), born between 1911 and 1930 were investigated. The investigations showed that men with the lowest weight at birth and at 1 year of age had the highest risks of death from cardiovascular disease (D.J. Barker, P.D. Winter, C. Osmond, B. Margetts & S.J. Simmonds. Lancet 1989; 2, 577–580). These findings suggested that factors in the perinatal environment could programme an individual for later risk of development of cardiovascular disease compared with someone born with a normal weight. Numerous studies have since confirmed these initial findings of an inverse relationship between early growth pattern and cardiovascular disease in adulthood.
Exploring type I angiotensin (AT1) receptor functions through gene targeting
Authors: Crowley S. D. , Tharaux P.‐L. , Audoly L. P. , Coffman T. M.
Published: July 2004

The renin–angiotensin system (RAS) modulates a diverse set of physiological processes including development, blood pressure, renal function and inflammation. The principal effector molecule of this system, angiotensin II, mediates most of these actions. The classically recognized functions of the RAS are triggered via the type 1 (AT1) class of angiotensin receptors. Pharmacological blockade of the AT1 receptor lowers blood pressure and slows the progression of cardiovascular and renal diseases. Gene‐targeting technology provides an experimental approach for precisely dissecting the physiological functions of the RAS. Here, we review how gene‐targeting experiments have elucidated AT1 receptor functions.
Consomic rat model systems for physiological genomics
Authors: Cowley A. W. , Liang M. , Roman R. J. , Greene A. S. , Jacob H. J.
Published: July 2004

A consomic rat strain is one in which an entire chromosome is introgressed into the isogenic background of another inbred strain using marker‐assisted selection. The development and physiological screening of two inbred consomic rat panels on two genetic backgrounds (44 strains) is well underway. Consomic strains enable one to assign traits and quantitative trait loci (QTL) to chromosomes by surveying the panel of strains with substituted chromosomes. They enable the rapid development of congenic strains over a narrow region and enable one to perform F2 linkage studies to positionally locate QTL on a single chromosome with a fixed genetic background. These rodent model systems overcome many of the problems encountered with segregating crosses where even if linkage is found, each individual in the cross is genetically unique and the combination of genes cannot be reproduced or studied in detail. For physiologists, consomics enable studies to be performed in a replicative or longitudinal manner to elucidate in greater detail the sequential expression of genes responsible for the observed phenotypes of these animals. They often provide the best available inbred control strains for physiological comparisons with the parental strains and they enable one to assess the impact of a causal gene region in a genome by allowing comparisons of the effect of replacement of a specific chromosome on a disease susceptible or a resistant genomic background. Consomic rat strains are proving to be a unique scientific resource that can greatly extend our understanding of genes and their role in the regulation of complex function and disease.
Hormones and pregnancy: thromboembolic risks for women
Authors: Kujovich Jody L.
Published: July 2004

During their lifetimes, women face several unique situations with an increased risk of venous thromboembolism (VTE). Doctors in a variety of specialties must advise women on the risks of oral contraceptives (OC), hormone replacement or pregnancy. Modern ‘low dose’ OC are associated with a three to sixfold increased relative risk of VTE. Hormone replacement and selective oestrogen receptor modulators confer a similar two to fourfold increase in thrombotic risk. However, because the baseline incidence of thrombosis is higher in older postmenopausal women, the absolute risk is higher than in younger OC users. The risk of venous thrombosis is six to 10‐fold higher during pregnancy than in non‐pregnant women of similar age. Thrombophilic disorders increase the thrombotic risk of OC, hormone replacement and pregnancy, especially in women with homozygous or combined defects. This review focuses on recent data estimating the thrombotic risk of hormonal therapies and pregnancy in women with and without other thrombotic risk factors.
CD34+ cell selection of peripheral blood progenitor cells using the CliniMACS device for allogeneic transplantation: clinical results in 102 patients
Authors: Ringhoffer Mark , Wiesneth Markus , von Harsdorf Stephanie , Schlenk Richard F. , Schmitt Anita , Reinhardt Peter P. , Moessner Margit , Grimminger Wolfgang , Mertens Thomas , Reske Sven N. , Döhner Hartmut , Bunjes Donald
Published: July 2004

The present study investigated the effects of CD34+ cell selection in 102 patients using the CliniMACS device. Patients were at high risk for the development of graft versus host disease (GvHD) because of age, or the use of a haploidentical, mismatched or unrelated donor (UD). The median age of the patients was 44 years. The CliniMACS procedure yielded 8·0 × 106 CD34+ cells/kg and the number of residual T cells was 1·3 × 104/kg (median). The median follow up was 20·6 months. The probability of graft failure was 7%. The rate of acute GvHD was low (compatible family donors 10%, UDs 17%, and haploidentical donors 26%) with no patient enduring more than grade II disease. The cumulative incidence of chronic GvHD at the median follow up after transplant was 15% for the compatible family donor group, 40% for the UD group and 78% in the group transplanted from a haploidentical donor Treatment failure was mainly because of transplant‐related mortality, especially aspergillus infection, and not due to relapse. The probability of disease‐free survival, stratified for the risk of treatment failure, was 27% for the high risk, 46% for the intermediate risk and 83% for the low risk group.
Compound heterozygous mutations in the γ‐glutamyl carboxylase gene cause combined deficiency of all vitamin K‐dependent blood coagulation factors
Authors: Rost Simone , Fregin Andreas , Koch Dieter , Compes Markus , Müller Clemens R. , Oldenburg Johannes
Published: July 2004

Hereditary combined deficiency of the vitamin K‐dependent coagulation factors II, VII, IX, X, protein C, S and protein Z (VKCFD) is a very rare autosomal recessive inherited bleeding disorder. The phenotype may result from functional deficiency of either the γ‐glutamyl carboxylase (GGCX) or the vitamin K epoxide reductase (VKOR) complex. We report on the third case of VKCFD1 with mutations in the γ‐glutamyl carboxylase gene, which is remarkable because of compound heterozygosity. Two mutations were identified: a splice site mutation of exon 3 and a point mutation in exon 11, resulting in the replacement of arginine 485 by proline. Screening of 100 unrelated normal chromosomes by restriction fragment length polymorphism and denaturing high‐performance liquid chromatography analysis excluded either mutation as a frequent polymorphism. Substitution of vitamin K could only partially normalize the levels of coagulation factors. It is suggested that the missense mutation affects either the propeptide binding site or the vitamin K binding site of GGCX.
Human γδ T cells as mediators of chimaeric‐receptor redirected anti‐tumour immunity
Authors: Rischer Markus , Pscherer Sibylle , Duwe Susanne , Vormoor Josef , Jürgens Heribert , Rossig Claudia
Published: July 2004

Human peripheral blood γδ T cells (Vγ9+ Vδ2+) can be selectively expanded in vivo by the systemic administration of aminobisphosphonates without prior antigen priming. To assess the potential of human γδ T cells to serve as effector cells of specific anti‐tumour immunity, we expanded peripheral blood‐derived γδ T cells and transduced them with recombinant retrovirus encoding GD2‐ or CD19‐specific chimaeric receptors. Flow cytometric analysis of T cells from four individual donors cultured in the presence of zoledronate at day 14 of culture showed selective enrichment of the γδ T cell population (Vγ9+ Vδ2+ CD3+ CD4− CD8−) to 73–96% of total CD3+ T cells. Retroviral gene transfer resulted in chimaeric receptor surface expression in 73 ± 12% of the population. Transduced γδ T cells efficiently recognized antigen‐expressing tumour cell targets, as demonstrated by target‐specific upregulation of CD69 and secretion of interferon‐α. Moreover, transduced γδ T cells efficiently and specifically lysed the antigen‐expressing tumour targets. They could be efficiently expanded in vitro and maintained in culture for prolonged periods. Zoledronate‐activated human γδ T cells expressing chimaeric receptors may thus serve as potent and specific anti‐tumour effector cells. Their responsiveness to stimulation with aminobisphosphonates may enable the selective re‐expansion of adoptively transferred T cells in vivo, permitting long lasting anti‐tumour immune control.
Translocations involving 6p22 in acute myeloid leukaemia at relapse: breakpoint characterization using microarray‐based comparative genomic hybridization
Authors: Tchinda Joëlle , Dijkhuizen Trijnie , Vlies Pieter van der , Kok Klaas , Horst Jürgen
Published: July 2004

The detection of chromosomal aberrations is essential for the diagnosis and therapy of acute myeloid leukaemia (AML). We report two cases of de novo AML with translocations involving the breakpoint 6p22 first detected at relapse. Chromosomes were identified by conventional and molecular cytogenetics. At diagnosis, one patient presented a normal karyotype and the other one a trisomy 11 and a del(7)(q31q36). In the first case, cytogenetic analyses at relapse revealed a t(3;6)(q21;p22). The second patient showed a t(1;6)(q21;p22) at relapse. Detailed characterization of the breakpoints on the short arm of chromosome 6 was performed using array comparative genomic hybridization (CGH) on a platform specific for chromosome 6. In both cases, array CGH showed a terminal deletion and a small internal duplication of the short arm of chromosome 6. The region 6p22 is involved in several aberrations in tumours. Translocation partners are distributed throughout the human genome. We identified 3q21, a recurrent breakpoint in AML, for the first time as a translocation partner. The fragile site FRA6C, located in 6p22.2, and possibly the genes that reside within it, may play a role in tumorigenesis. The occurrence of translocations involving 6p22 after chemotherapy or radiation therapy suggests that one or more therapeutic agents might play a role in their origin.
Reversal of established CD4+ type 2 T helper‐mediated allergic airway inflammation and eosinophilia by therapeutic treatment with DNA vaccines limits progression towards chronic inflammation and remodelling
Authors: Jarman Elizabeth R. , Lamb Jonathan R.
Published: July 2004

Immunostimulatory DNA‐based vaccines can prevent the induction of CD4+ type 2 T helper (Th2) cell‐mediated airway inflammation in experimental models, when administered before or at the time of allergen exposure. Here we demonstrate their efficacy in limiting the progression of an established response to chronic pulmonary inflammation and airway remodelling on subsequent allergen challenge. Mice exhibiting Th2‐mediated airway inflammation induced following sensitization and challenge with group 1 allergen derived from Dermatophagoides pteronyssinus group species (Der p 1), a major allergen of house dust mite, were treated with pDNA vaccines. Their airways were rechallenged and the extent of inflammation assessed. In plasma DNA (pDNA)‐vaccinated mice, infiltration of inflammatory cells, goblet cell hyperplasia and mucus production were reduced and subepithelial fibrosis attenuated. The reduction in eosinophil numbers correlated with a fall in levels of the profibrotic mediator transforming growth factor (TGF)‐β1 in bronchoalveolar lavage (BAL) and lung tissue. In addition to lung epithelial cells and resident alveolar macrophages, infiltrating eosinophils, the principle inflammatory cells recruited following allergen exposure, were a major source of TGF‐β1. Protection, conferred irrespective of the specificity of the pDNA construct, did not correlate with a sustained increase in systemic interferon (IFN)‐γ production but in a reduction in levels of the Th2 pro‐inflammatory cytokines. Notably, there was a reduction in levels of interleukin (IL)‐5 and IL‐13 produced by systemic Der p 1 reactive CD4+ Th2 cells on in vitro stimulation as well as in IL‐4 and IL‐5 levels in BAL fluid. These data suggest that suppression of CD4+ Th2‐mediated inflammation and eosinophilia were sufficient to attenuate progression towards airway remodelling. Immunostimulatory DNA may therefore have a therapeutic application in treatment of established allergic asthma in patients.
Identification of the Rf gene conferring fertility restoration of the CMS Dian‐type 1 in rice by using simple sequence repeat markers and advanced inbred lines of restorer and maintainer
Authors: Tan X. L. , Tan Y. L. , Zhao Y. H. , Zhang X. M. , Hong R. K. , Jin S. L. , Liu X. R. , Huang D. J.
Published: July 2004

Cytoplasmic male sterility of Dian‐type 1 (CMS‐D1) was developed 30 years ago in Yunnan. A major gene conferring fertility restoration for the CMS‐D1 system was detected by microsatellite markers in advanced inbred lines consisting of 196 maintainers and 62 restorers developed in breeding programmes of hybrid rice involving the CMS‐D1 system. The gene was mapped between two simple sequence repeat markers, OSR33 and RM228, on chromosome 10, and was temporarily designated as Rf‐D1(t). The genetic distances of the gene to the two microsatellite markers were 3.4 and 5.0 cM, respectively. This linkage was confirmed by using an F2 population derived from a cross between a CMS‐D1 line and a restorer. This study also demonstrated that using OSR33 was reliable and efficient for identification of restoring lines in hybrid rice breeding with the CMS‐D1 system.
Risk factors in past histories and familial episodes related to development of testicular germ cell tumor
Authors: KANTO SATORU , HIRAMATSU MASAYOSHI , SUZUKI KENICHI , ISHIDOYA SHIGETO , SAITO HIDEO , YAMADA SHIGEYUKI , SATOH MAKOTO , SAITO SEIICHI , FUKUZAKI ATSUSHI , ARAI YOICHI
Published: July 2004

Abstract  Background:  A retrospective study was conducted to examine the host factors of 240 testicular germ cell tumor patients. This study was performed to address a new theory proposed by Skakkebaek called testicular dysgenesis syndrome which claims that cryptorchism, hypospadias, poor semen quality and testicular germ cell tumors are symptoms of an underlying testicular dysgenesis in uterus.

Methods:  The past health histories and familial episodes of 240 testicular germ cell tumor patients were examined. The past health histories included cryptorchism, hypospadias, infertility, atrophic testis and inguinal hernia.

Results:  Of the 240 patients, 13 (5.4%) had a history of cryptorchism or orchidopexy. Two (0.8%) showed existence of hypospadias or had experienced urethroplasty. Among 129 married couples, 104 (80.6%) couples were fertile. Three (1.3%) patients developed testicular tumors after they were diagnosed as infertile or came to the hospital with the complaints of infertility. Four (1.7%) had contralateral atrophic testis. 19 (7.9%) had experienced inguinal herniorrhaphy before age 15. Three (1.3%) had testicular germ cell tumor patients among their family or relatives.

Conclusions:  The testicular germ cell tumor patients showed a considerable incidence of complications such as cryptorchism, hypospadias and incomplete closure of processus vaginalis. Cryptorchism, perinatal factors and familial factors could be risks for developing testicular germ cell tumors.
Extracorporeal magnetic innervation treatment for urinary incontinence
Authors: YOKOYAMA TERUHIKO , FUJITA OSAMU , NISHIGUCHI JUN , NOZAKI KUNIHIRO , NOSE HIROYUKI , INOUE MIYABI , OZAWA HIDEO , KUMON HIROMI
Published: July 2004

Abstract  Background:  Extracorporeal magnetic innervation (ExMI) is a new technology used for pelvic muscle strengthening for the treatment of stress urinary incontinence. We explored whether this new technology is effective for patients with urge incontinence, as well as those with stress urinary incontinence.

Methods:  We studied 20 patients with urge incontinence and 17 patients with stress urinary incontinence. The Neocontrol system (Neotonus Inc., Marietta, GA) was used. Treatment sessions were for 20 min, twice a week for 8 weeks. Evaluations were performed by bladder diaries, one‐hour pad weight testing, quality‐of‐life surveys and urodynamic studies.

Results:  Of the urge incontinence cases, five patients were cured (25.0%), 12 patients improved (60.0%) and three patients did not show any improvement (15.0%). Leak episodes per day reduced from 5.6 times to 1.9 times at 8 weeks (P < 0.05). Eight patients with urge incontinence recurred within 24 weeks after the last treatment (47.1%). Of the stress incontinence cases, nine patients were cured (52.9%), seven patients improved (41.1%) and one patient did not show any improvement (6%). In one‐hour pad weight testing, the mean pad weight reduced from 7.9 g to 1.9 g at 8 weeks (P < 0.05). Three patients returned to the baseline values within 24 weeks after the last treatment (17.6%). No side‐effects were experienced by any of the patients.

Conclusion:  Although the results for urge incontinence were less effective than for stress urinary incontinence, ExMI therapy offers a new option for urge incontinence as well as stress urinary incontinence.
Basic study on velocity‐flow urodynamics using Doppler sonography: Simultaneous detection of cavitation and Doppler signals in an artificial urethral model
Authors: KUMON HIROMI , OZAWA HIDEO , NOSE HIROYUKI , OHTA HIDEKUNI , NISHIGAKI KAZU
Published: July 2004

Abstract  Background:  We have developed velocity‐flow urodynamics using Doppler sonography based on the hypothesis that microbubbles formed in the urethra are responsible for Doppler signals. In order to confirm this hypothesis derived from Bernoulli's principle, we investigated the simultaneous detection of cavitation noise and Doppler signals in an experimental system.

Methods:  An experimental circuit was built in which a stenosis was created using a glass or silicon tube with tap water used as the sample fluid. Doppler signals, pressure before and after the stenosis, flow rate, flow velocity and cavitation noise were measured. Direct detection of cavitation with a high‐speed charged‐coupled device (CCD) camera was conducted in the glass tube. The relationship between cross‐sectional area and flow velocity in terms of the detection of Doppler signals was analyzed in the silicon tube study.

Results:  In the glass tube study, a high‐speed CCD camera clearly detected masses of microbubbles associated with cavitation. The range of flow rates creating cavitation completely corresponded with those producing Doppler signals detected by ultrasonography. A similar correlation was observed in the silicon tube study, which showed that a low flow velocity of 41.5 cm/sec through a stenosis with a cross‐sectional area of 20 mm2 created Doppler signals at a flow rate of 8.3 mL/sec.

Conclusion:  The results of the present study confirmed that microbubbles created in flowing urine are responsible for Doppler signals. Measurement of velocity‐flow urodynamics has great potential to become a non‐invasive and reliable alternative to conventional pressure‐ flow urodynamic studies.
Xanthogranulomatous orchitis with scrotal fistulas
Authors: DEMİRCİ DENIZ , EKMEKÇİOǦLU OǦUZ , SOYUER IŞIN , EMİRDOǦAN MUSTAFA
Published: July 2004

Abstract  Xanthogranulomatous orchitis is an extremely rare inflammatory change of testis which is difficult to distinguish from testicular tumor. We report on a 21‐year‐old man who presented with left testicular swelling and pyogenic discharge from the scrotum. Testicular tumor markers were normal. Scrotal ultrasonography showed a testicular tumor in the left testis. Because of severe adhesion between the scrotum and intrascrotal structures, radical orchiectomy combined with hemiscrotectomy was performed to exclude possible malignancy. Histopathological findings showed xanthogranulomatous orchitis.
Resection of pulmonary metastases following chemotherapy for high stage testicular tumors
Authors: ESKICORAPCI SAADETTIN Y , EKICI SINAN , ATSU M NECMETTIN , DOGAN RIZA , OZEN HALUK
Published: July 2004

Abstract  Background:  Our objective was to analyze retrospectively our experience with 19 patients who had metastatic germ cell testicular tumor and had undergone resection of pulmonary metastases following chemotherapy. We wished to determine the necessity of thoracic surgery on these patients.

Methods:  Of 103 patients in need of postchemotherapeutic surgery for metastatic germ cell testicular tumors, 19 patients (mean age 31) underwent surgery for thoracic masses following cis‐platin based chemotherapy. Resection of pulmonary metastases was performed on patients with normal tumor markers after chemotherapy, who did not achieve complete radiological remission. Histopathological findings, correlation with the pathology of abdominal surgery and probable prognostic factors for disease‐free and overall survivals were evaluated.

Results:  Disease‐free and overall survival rates were 14/19 (73%) and 16/19 (84%), respectively, within a median follow‐up time of 30 months (15–212 months). Patients with and without viable tumor cells in their thoracic histopathological specimen had 40% and 85% disease‐free survival rates, respectively (P < 0.05). Eight patients had both abdominal and thoracic postchemotherapy surgery. Only two (25%) of these patients had the same histopathological features at both sites.

Conclusions:  All patients with residual thoracic masses must be considered candidates for surgery, because there are no predictive factors to determine the thoracic pathology without surgery. With the resection of the pulmonary metastases only, surgery can be performed without significant morbidity and is essential to select patients for further chemotherapy, to remove all visible masses and to provide histopathological confirmation. Patients with viable tumor cells in the thoracic surgical specimen have a poor prognosis.
Minimum effective dose of dexamethasone after tonsillectomy
Authors: Çeliker Varol , Çelebi Nalan , Canbay Özgür , Başgül Elif , Aypar Ülkü
Published: July 2004

Background : The minimum effective dose of dexamethasone in conjunction with 50 μg·kg−1 ondansetron was evaluated in the treatment for vomiting after elective tonsillectomy or adenotonsillectomy.

Methods : A total of 102 healthy children between 2 and 12 years of age participated in this prospective, randomized, double‐blind study. A single intravenous (i.v.) dose of dexamethasone (50, 100, 150 μg·kg−1, maximum dose 8 mg) with ondansetron (50 μg·kg−1) was administered just before the end of surgery. Equal volumes of normal saline were given to the control group. General anaesthesia was induced and maintained by inhalation of N2O/O2 and sevoflurane. All other preoperative and postoperative medications (including a supplementary dose of antiemetics if necessary), anaesthesia and surgical techniques were standardized.

Results : No significant differences were observed between groups in postoperative vomiting on the day of surgery and the next day, or in the need for postoperative pain medication and supplementary doses of antiemetics (P > 0.05).

Conclusions : These results indicate that surgical technique and anaesthetic management used in this study could be the cause of the lower incidence of nausea and vomiting. Assessment of nausea and vomiting in a prospective study with larger groups of patients may reflect different results.
The use of recalcified citrated whole blood – a pragmatic approach for thromboelastography in children
Authors: Rajwal Sanjay , Richards Mike , O'Meara Moira
Published: July 2004

Background : Thromboelastography (TEG) is an established way of monitoring the coagulation status of children and adults requiring blood products during surgery. Serial measurements are performed using a nearside machine and blood product prescription may be titrated against changes in TEG. There may also be useful applications when the patient is remote from the TEG machine but these are limited because TEG is usually performed on fresh native whole blood within 6 min of venepuncture. Citrated whole blood can be used for TEG if transport time is more than 6 min. We wished to establish whether TEG parameters for citrated whole blood were comparable with those of native whole blood in healthy children.

Methods : Blood was obtained from 14 healthy children undergoing minor surgical procedures, at the time of intravenous cannula insertion for anaesthesia. Each sample was divided: TEG was performed on part of the sample in its fresh native state at 6 min and second portion of the sample was citrated, kept at room temperature and TEG was performed at 30 min after recalcification.

Results : There was a significant difference in TEG parameters (r, k, α, MA and LY30) for fresh native whole blood and recalcified citrated whole blood (paired t‐test).

Conclusions : The normal range for fresh native whole blood TEG parameters is well established, which is routinely used in practice. There was a significant difference between TEG parameters for fresh native whole blood and citrated whole blood. We recommend that a specific normal range be established for citrated whole blood to enable it to be used in clinical practice.
Anesthetic management of a patient with myotonic dystrophy for a Nissen fundoplication and gastrostomy
Authors: Jenkins J.A. , Facer E.K.
Published: July 2004

A 16‐month‐old baby with myotonic dystrophy underwent an open Nissen fundoplication and gastrostomy insertion under general anesthesia with an epidural. Postoperative care was managed on the pediatric intensive care unit for the first 6 h. She was then discharged to the ward, where she continued to make an uncomplicated recovery. Other anesthetic management that has been used in children with myotonic dystrophy is discussed.
Political Externalities, Nondiscrimination, and a Multilateral World
Authors: Ethier Wilfred J.
Published: July 2004

During the past half century, multilateral trade liberalization has reduced tariffs to historically low levels. The “Received Theory” of multilateral trade agreements, based solely on terms‐of‐trade externalities between national governments, offers an explanation that has become the conventional wisdom. But it is dramatically inconsistent with actual trade agreements. This paper offers an alternative explanation, based on intergovernmental political externalities, consistent with what we actually observe. With remarkably little necessary formal structure—in particular, no formal bargaining model—this framework (chosen to parallel actual experience) gives an immediate and transparent role to the basic characteristics of contemporary trade agreements: gradual liberalization, reciprocity, nondiscrimination, and multilateralism.
Semi‐Nonparametric Estimates of Currency Substitution: the Demand for Sterling in Europe
Authors: Drake Leigh , Fleissig Adrian R.
Published: July 2004

The paper presents new evidence of significant substitution between European domestic monetary assets and foreign holdings of sterling. The finding of significant cross‐country currency substitution implies reduced costs of transition towards monetary union and easier European policy convergence. Elasticities of substitution, using the Morishima measure, are estimated from the semi‐nonparametric Fourier flexible form.
Pricing in Segmented Markets, Arbitrage Barriers, and the Law of One Price: Evidence from the European Car Market
Authors: Lutz Matthias
Published: July 2004

The paper uses micro‐level price data from the European car market to examine why there are deviations from the law of one price. The absolute law of one price is strongly rejected, but there is convergence to its relative version. Two sets of explanations are considered: (i) price‐setting in segmented markets, and (ii) arbitrage barriers. Overall, the determinants of arbitrage costs have more explanatory power. The single most important factor is the distance between markets. Evidence for Belgium and Luxembourg suggests that a single currency lowers price differences significantly.
The Bundesbank's Inflation Policy and Asymmetric Behavior of the German Term Structure
Authors: Bohl Martin T. , Siklos Pierre L.
Published: July 2004

The paper analyzes the influence of the Bundesbank's inflation targeting policy on the behavior of the spread between long‐term and short‐term German interest rates. The term spread is considered to be a key indicator of future inflation and economic activity. The application of a momentum threshold autoregressive cointegration model enables the authors to study the adjustment process of the spread toward equilibrium in greater detail than heretofore possible, and permits relaxation of the linear and symmetric adjustment assumption underlying conventional cointegration and error correction investigations on the expectations hypothesis. The empirical findings are consistent with the hypothesized asymmetric adjustment behavior of the spread and can be explained by the Bundesbank's inflation targeting policy during the period from 1975 to 1998.
Tariff Wars and Trade Deals with Costly Government
Authors: Burbidge John , Myers Gordon
Published: July 2004

The authors study a simple model of tariff wars and trade deals in which government revenue collection and disbursement uses resources. The introduction of costly governments leads to lower non‐cooperative tariffs, the possibility that a less costly government may win a tariff war, and fully cooperative trade deals where countries lower tariffs but do not eliminate them, even with lump‐sum taxes and transfers.
Effect of Prior Information on String Length Estimates
Authors: Franklin Christine A. , Mulekar Madhuri S.
Published: July 2004

This article describes an activity through which students collect data and explore ways to display them through graphs and charts. It also motivates various summary measures for location, spread and shape. Finally, it gives an introduction to concepts of validity, reliability and unbiasedness.
Great Expectations?
Authors: Sheldon Neil
Published: July 2004

This article introduces the concept of a prediction interval in a gambling context.
A Lower Bound for the Most Deviant Z Score
Authors: Hayes Kevin
Published: July 2004

This article demonstrates that the lower bound for the most deviant Z score and the upper bound for the sample standard deviation are attained simultaneously.
Dopamine and cyclic AMP‐regulated phosphoprotein‐32 phosphorylation pattern in cocaine and morphine‐sensitized rats
Authors: Scheggi S. , Rauggi R. , Gambarana C. , Tagliamonte A. , De Montis M. G.
Published: July 2004

This study reports some of the modifications in dopaminergic signalling that accompany cocaine and morphine behavioural sensitization. Cocaine‐sensitized rats showed increased phosphorylation of dopamine‐ and cyclic AMP‐regulated phosphoprotein Mr 32 kDa (DARPP‐32) at threonine‐75 (Thr75) and decreased DARPP‐32 phosphorylation at Thr34, in the caudate–putamen (CPu) and nucleus accumbens (NAc) 7 days after sensitization assessment. Conversely, in morphine‐sensitized rats, no apparent modifications in DARPP‐32 phosphorylation pattern were observed. Morphine‐sensitized rats have increased binding and coupling of µ‐opioid receptors and increased dopaminergic transmission in striatal areas and, upon morphine challenge, exhibit dopamine D1 receptor‐dependent stereotypies. Thus, the DARPP‐32 phosphorylation pattern was studied in morphine‐sensitized rats at different times after morphine challenge. Morphine challenge increased levels of phospho‐Thr75 DARPP‐32 and decreased levels of phospho‐Thr34 DARPP‐32 in a time‐dependent manner in the CPu and NAc. In order to assess whether these modifications were related to modified cyclic AMP‐dependent protein kinase (PKA) activity, the phosphorylation levels of two other PKA substrates were examined, the GluR1 and NR1 subunits of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate and NMDA receptors respectively. The phosphorylation levels of GluR1 and NR1 subunits decreased in parallel with those of phospho‐Thr‐34 DARPP‐32, supporting the hypothesis that morphine challenge elicited a decrease in PKA activity in morphine‐sensitized rats.