bluuebunny/crossref_metadata_2025 huggingface dataset:
Does soluble triggering receptor expressed on myeloid cells-1 play any role in the pathogenesis of septic shock?
Authors: Routsi C , Giamarellos-Bourboulis E J , Antonopoulou A , Kollias S , Siasiakou S , Koronaios A , Zakynthinos S , Armaganidis A , Giamarellou H , Roussos C
Published: September 2005

In order to define the significance of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) upon progression from sepsis or severe sepsis to septic shock a prospective study was designed with 90 enrolled patients with septic syndrome due to ventilator-associated pneumonia. Blood was sampled on seven consecutive days upon initiation of symptoms and concentrations of tumour necrosis factor-alpha (TNFα), interleukin-6 (IL-6), IL-8 and sTREM-1 were estimated in serum by an enzymeimmunoassay. No differences in concentrations of TNFα, IL-6 and IL-8 were found between patients with sepsis, severe sepsis and septic shock on the first day of presentation of symptoms. Patients presenting with septic shock had concentrations of sTREM-1 significantly higher than both patients with sepsis and severe sepsis on the first day; no difference was found between patients with sepsis and severe sepsis. A positive correlation was detected between sTREM-1 and the white blood cell count. Serum levels of sTREM-1 were significantly lower in patients where VAP resolved compared to those where VAP did not resolve; similar findings were noted between patients who eventually survived and those who died. IL-6 followed the kinetics of sTREM-1 in correlation to patients's prognosis; levels of TNFα and IL-8 were unrelated to prognosis. It is concluded that sTREM-1 is particularly increased upon evolution from sepsis or severe sepsis to septic shock. Its sustained increase is an indication of poor outcome. The underlined pathophysiological role of sTREM-1 for the transition from sepsis or severe sepsis to septic shock might constitute a novel target for immunomodulatory therapy.
Mechanisms dependent on tryptophan catabolism regulate immune responses in primary Sjögren's syndrome
Authors: Pertovaara M , Raitala A , Uusitalo H , Pukander J , Helin H , Oja S S , Hurme M
Published: September 2005

To investigate the possible role of tryptophan metabolism in immune regulation of primary Sjögren's syndrome (pSS) the serum concentrations of tryptophan and its metabolite kynurenine were measured by reverse-phase high-performance liquid chromatography (HPLC) in 103 patients with pSS, 56 patients with sicca symptoms and 309 healthy blood donors. The kynurenine per tryptophan ratio (kyn/trp), which reflects the activity of the indoleamine-pyrrole 2,3-dioxygenase (IDO) enzyme involved in tryptophan catabolism, was calculated. Both female and male patients with pSS had significantly higher serum kynurenine concentrations and kyn/trp than subjects with sicca symptoms or healthy blood donors. The median (quartile range) concentration of kynurenine in female patients with pSS was 2·41 µmol/l (1·86–3·26) compared with 1·85 µmol/l (1·58–2·38, P < 0·0001) in subjects with sicca symptoms and 1·96 µmol/l (1·65–2·27, P < 0·0001) in healthy blood donors. Their kyn/trp × 1000 was 34·0 (25·1–44·3) compared with 25·3 (21·1–31·5, P < 0·0001) in subjects with sicca symptoms and 24·3 (21·0–28·9, P < 0·0001) in healthy blood donors. Female pSS patients with high IDO activity (kyn/trp × 1000 ≥ 34·0) had significantly higher ESR, serum C-reactive protein, serum IgA and serum beta-2 microglobulin concentrations as well as higher serum creatinine levels, and they had positive antinuclear antibodies more frequently and presented with more American-European consensus group criteria than those with low IDO activity (kyn/trp × 1000 < 34·0). These data suggest that mechanisms dependent on tryptophan catabolism regulate immune responses in pSS. Tryptophan degradation is enhanced in patients with pSS, and high IDO activity is associated with severity of pSS.
Association between atopy and recurrent vaginal candidiasis
Authors: Neves N A , Carvalho L P , De Oliveira M A M , Giraldo P C , Bacellar O , Cruz Á A , Carvalho E M
Published: September 2005

To determine whether there is an association between atopy and recurrent vaginal candidiasis (RVC) and to evaluate the type-2 immune response in patients with RVC. Evaluation of immediate hypersensitivity skin tests to aeroallergens, measurement of total IgE and Candida albicans specific IgE and levels of IL-5 in 44 women with RVC and 26 with sporadic vaginal candidiasis (SVC). Statistical analyses were performed by Mann–Whitney test and χ2 test with Yates correction. History of atopy (68%) and positive skin test (42%) were higher (P < 0·05) in RVC than in patients with SVC. No significant difference was found in total IgE, C. albicans specific IgE and IL-5 levels. There was a strong association between atopy and RVC, but type-2 immune response to C. albicans antigen was absent or similar in the two groups of patients.
Absence of reuptake of serotonin influences susceptibility to clinical autoimmune disease and neuroantigen-specific interferon-gamma production in mouse EAE
Authors: Hofstetter H H , Mössner R , Lesch K P , Linker R A , Toyka K V , Gold R
Published: September 2005

Serotonin (5-hydroxytryptamine, 5-HT) is one of the most extensively studied neurotransmitters of the central nervous system. It also has been identified in constituents of the immune system. Therefore serotonin has been suggested to serve as a mediator of bidirectional interactions between the nervous system and the immune system. We investigated this interaction in experimental autoimmune encephalomyelitis (EAE), a well-defined animal model of autoimmune disease of the central nervous system (CNS) mimicking features of the human disease multiple sclerosis. EAE was induced by immunization with the autoantigens myelin basic protein (MBP) or the immunodominant peptide of myelin oligodendrocyte glycoprotein (MOG) spanning amino acids 35–55 (MOGp 35–55). We studied EAE in knockout (KO) mice lacking the 5-HT transporter (5-HTT) on a C57.BL/6 background, in comparison with wild-type C57.BL/6 animals. After immunization with MOGp 35–55, or with rat MBP, the disease courses of the 5-HTT knockout mice were attenuated as compared to wildtype control mice. This difference was more pronounced in female animals. To dissect potential immune mechanisms underlying this phenomenon, histological studies of the CNS and cytokine measurements in mononuclear cells from the spleens of 5-HTT KO mice and wild-type controls were performed. We found a reduction of the inflammatory infiltrate in the CNS and of the neuroantigen-specific production of IFN-γ in splenocytes, again accompanied by a gender difference. These findings suggest a potential role of extracellular 5-HT homeostasis in the fine-tuning of neuroantigen-specific immune responses.
MHC class I chain-related gene A-A5·1 allele is associated with ulcerative colitis in Chinese population
Authors: Ding Yijuan , Xia Bing , Lü Min , Zhang Yan , Li Jin , Ye Mei , Luo Hesheng , Yu Jieping , Zhang Xiaolian , Tan Jingquan
Published: September 2005

The human MHC class I chain-related gene A (MICA) plays a role in regulating protective responses by intestinal epithelial Vδ1 γ δ T cells and the polymorphism of MICA were reported to be related to several autoimmune diseases. The present study aimed to investigate the association of the microsatellite polymorphisms of TM region of MICA gene with the susceptibility to ulcerative colitis (UC) in Chinese population. The microsatellite polymorphisms of the MICA were genotyped in unrelated 86 Chinese patients with UC and 172 ethnically matched healthy controls by a semiautomatic fluorenscently labelled PCR method. All the subjects were the Chinese with Han nationality. The frequency of MICA-A5·1 homozygous genotype and A5·1 allele were significantly increased in UC patients compared with healthy controls (22·1%versus 7%, P = 0·0009, Pc = 0·0126, OR = 3·781, 95%CI: 1·738–8·225 and 30·2%versus 17·4%, P = 0·0014, Pc = 0·007, OR = 2·051, 95%CI: 1·336–3·148, respectively). Adjusted the effects of gender and age at onset, MICA-A5·1 homozygous genotype and A5·1 allele were also increased in the UC patients. Moreover MICA-A5·1 allele was significantly increased in frequency in the female UC patients (38·2%versus 21·0%, P = 0·0095, Pc = 0·0475, OR = 2·326, 95%CI: 1·234–4·382). Logistic regression analysis also revealed that gender was independently associated with UC patients carried MICA-A5·1 allele (P = 0·046, OR (male) = 0·511, 95% CI: 0·264–0·987). Although the UC patients with extensive colitis (32·5%versus 17·4% in the healthy controls, P = 0·005, Pc = 0·025) and the UC patients with extraintestinal manifestations (36%versus 17·4% in the healthy controls, P = 0·0039, Pc = 0·0195) were more likely to carry the MICA-A5·1 allele, EIMs was associated with extent of disease (P < 0·0001, OR (with EIMs) = 3·511, 95% CI 1·747–7·056) and MICA-A5·1 allele was not associated with UC patients with extensive colitis or with EIMs in the logistic regression analysis. Therefore, the MICA-A5·1 homozygous genotype and A5·1 allele were closely associated with UC and the MICA-A5·1 allele was positively associated with the female UC patients in Chinese population.
Fishing rights auctions in the fisheries of Lake Peipsi‐Pihkva, Estonia
Authors: VETEMAA M. , EERO M. , HANNESSON R.
Published: September 2005

Abstract  To deal with excessive fishing capacity, a part of the fishing rights, both volume quotas and gear use rights, in all Estonian fisheries was allocated each year during 2001–2003 through auctions while the remainder was allocated on the basis of the recent fishing rights use history. All fishing rights depreciated in a geometric manner by 10% annually. This was carried out for the first time in 2001, but the system was abandoned for political reasons in 2003. In this paper, the development of the small‐scale Estonian inland fisheries, as well as the results of the auctions of fishing rights in those fisheries, are discussed. The auctions led to some increase in the number of owners of fishing rights. In most cases, however, new enterprises were formed on the basis of fishers active up to 2001 as employees of other enterprises. The auctions did not lead to a concentration of ownership of fishing rights in large enterprises. On the contrary, the share of smaller owners increased. According to the Fishing Act, in Estonia there is a fishing fee for all professional fishing gears. The official fishing fee was always used as the starting price in bidding, and this increased greatly during the bidding. Finally, the auction system served as a real incentive for fishers to cooperate more than they did during the previous management system based only on earlier rights.
Effect of fishing regulation on the occurrence of repeat spawners and age distribution of Atlantic salmon in a northern Baltic river
Authors: JOKIKOKKO E. , JUTILA E.
Published: September 2005

Abstract  Upstream migrating Atlantic salmon, Salmo salar L., were trapped annually between 1990 and 2003 at the mouth of the River Simojoki in the northern part of the Gulf of Bothnia, the Baltic Sea, to collect hatchery brood fish. They were also collected between 1996 and 1998 in the river to estimate the number of ascending salmon. These data on spawners were used to study the effect of changing fishing regulations in the Finnish coastal fishery in the mid‐1990s on the structure of the spawning stock. In total, 1.9% of 2290 multi‐sea‐winter adults had previously spawned. The average annual proportion of repeat spawners was 0.5% between 1990 and 1996, but significantly higher (2.8%) between 1997 and 2003. The age distribution also changed significantly, as 4SW and 5SW salmon appeared in the population in the latter years. These changes were most probably due to the application of stricter fishing regulations. The potential of salmon to spawn repeatedly was thus preserved, despite a severe decline in natural production in the 1980s and early 1990s.
Thermal reaction norms in two Coenagrion damselfly species: contrasting embryonic and larval life‐history traits
Authors: VAN DOORSLAER W. , STOKS R.
Published: September 2005

1. We studied the temperature‐dependence of important life‐history traits both at the embryonic (egg hatching success, embryonic development time and hatchling size) and the larval stage (larval growth rate, larval survival and larval size after 100 days) using full‐sib families of two congeneric damselflies, Coenagrion hastulatum and Coenagrion puella, that differ in latitudinal distribution. Larvae were reared in the laboratory from the egg stage at four temperatures (12, 17, 22 and 27 °C).

2. The observed patterns of thermal plasticity in embryonic traits showed that the northern species was more successful than the southern species at lower temperatures, in line with the pattern of temperature adaptation in thermal reaction norms.

3. At the larval stage, we found no consistent pattern of latitudinal compensation. The thermal family reaction norms indicate, however, the potential for latitudinal compensation to evolve. We observed an ontogenetic shift in thermal optima for larval growth rate, with a higher optimal temperature for growth rate during the first 2 weeks of the larval stage.

4. This is the first indication of the existence of latitudinal compensation at the interspecific level in an invertebrate; it is stage‐specific, being present only in the embryonic stage. We argue that compensation in the embryonic stage may be much more likely than in the larvae and stress the importance of including more then one life‐history stage when drawing conclusions about the adaptiveness of patterns in thermal reaction norms.
Differential effects of CpG‐DNA in Toll‐like receptor‐2/‐4/‐9 tolerance and cross‐tolerance
Authors: Dalpke Alexander H. , Lehner Martin D. , Hartung Thomas , Heeg Klaus
Published: September 2005

Lipopolysaccharide (LPS) tolerance is a state of refractoriness towards a second stimulation by LPS after a preceding stimulation. LPS is recognized by Toll‐like receptor‐4 (TLR‐4), which belongs to a group of pattern recognition receptors mediating activation of innate immunity by microbial components. To date, it is not known in detail to what extent other TLR‐dependent stimuli also induce tolerance and whether preceding and challenging stimuli are interchangeable. We have examined tolerance induction in detail for lipoteichoic acid (LTA), LPS and CpG‐DNA, which are recognized by TLR‐2, ‐4 and ‐9, respectively. In RAW264·7 macrophages, all three stimuli induced tolerance towards a subsequent challenge with the same stimulus used for priming, as well as cross‐tolerance towards subsequent challenge with other stimuli signalling via different TLRs. However, whereas LPS/LTA cross‐tolerance was also functional in an in vivo model of galactosamine (GalN)‐primed liver damage, pretreatment with CpG only protected against GalN/CpG challenge and failed to induce cross‐tolerance for LPS and LTA. CpG‐DNA pretreatment even enhanced tumour necrosis factor (TNF)‐α production and liver damage upon subsequent challenge with LPS or LTA. Stimulation with CpG‐DNA resulted in a peculiar sensitization for interferon (IFN)‐γ secretion. The data indicate that, in contrast to in vitro macrophage desensitization, the in vivo consequences of repeated TLR stimulation greatly differ amongst different TLR ligands.
Tyrosine kinase activity and remodelling of the actin cytoskeleton are co‐temporally required for degranulation by cytotoxic T lymphocytes
Authors: Shen Aimee , Puente Lawrence G. , Ostergaard Hanne L.
Published: September 2005

In this study, we examined the contribution of the actin cytoskeleton to T‐cell receptor (TCR)‐initiated signalling in cytotoxic T lymphocytes (CTLs). We demonstrate that cytoskeletal remodelling is required for sustaining TCR‐stimulated signals that lead to degranulation by CTLs. Disruption of the actin cytoskeleton in CTLs already undergoing signalling responses results in an almost immediate loss of essentially all protein tyrosine phosphorylation. This signal reversal is not restricted to tyrosine phosphorylation, as disruption of the actin cytoskeleton also reverses the phosphorylation of the more downstream serine/threonine kinase extracellular signal regulated kinase (Erk). An intact cytoskeleton and cell spreading are not sufficient for maintaining signals, as stabilization of actin filaments, at a point when peak tyrosine phosphorylation is occurring, also leads to the rapid loss of protein tyrosine phosphorylation. Disruption of tyrosine kinase activity after TCR signals are maximally induced causes the immediate reversal of tyrosine phosphorylation as well as cytoskeletal disruption, as indicated by loss of cell spreading, adhesion and CTL degranulation. Taken together, our results indicate that actin remodelling occurs co‐temporally with ongoing tyrosine kinase activity, leading to CTL degranulation. We hypothesize that continuous actin remodelling is important for sustaining productive signals, even after downstream signalling molecules such as Erk have been activated, and that the actin cytoskeleton is not solely required for initiating and maintaining the T cell in contact with its stimulus.
Quality of life and its measurement: important principles and guidelines
Authors: Verdugo M. A. , Schalock R. L. , Keith K. D. , Stancliffe R. J.
Published: September 2005

Background  The importance of the valid assessment of quality of life (QOL) is heightened with the increased use of the QOL construct as a basis for policies and practices in the field of intellectual disability (ID).

Method  This article discusses the principles that should guide the measurement process, the major interrogatories (i.e. who, what, when, where, why, and how) of QOL measurement, issues and procedures in the cross‐cultural measurement of QOL, and the current uses of QOL data.

Results  Based on the above methods, the article presents a number of important guidelines regarding QOL measurement.

Conclusion  From a measurement perspective the use of the QOL construct is changing. Initially it was used as a sensitizing notion, social construct, and unifying theme. Increasingly, it is being used as conceptual framework for assessing quality outcomes, a social construct that guides quality enhancement strategies, and a criterion for assessing the effectiveness of those strategies. This new role places additional emphasis on the valid assessment of one's QOL.
Conceptual principles of quality of life: an empirical exploration
Authors: Bramston P. , Chipuer H. , Pretty G.
Published: September 2005

Background  Quality of life is a popular measure of outcomes and its widespread use has led to recent calls for a better understanding of the construct, emphasizing the need to build a substantial body of knowledge around what determines perceptions of life quality. Three widely reported and used conceptual principles are examined in this study.

Methods  Self‐ratings of life quality and three likely determinants at an individual level (stress), an interactional level (social support) and a community level (neighbourhood belonging) were used. The study involved two groups of young adults from an urban community, one identified as having an intellectual disability (ID).

Results  Young adults with ID rated their satisfaction with health significantly higher and intimacy and community involvement lower than the comparison group. Social support emerged as the strongest predictor of life satisfaction across both groups.

Conclusion  The conceptual principles of subjective quality of life provide a useful framework to discuss findings and to stimulate further research.
Quality of life for people with intellectual disabilities in China: a cross‐culture perspectives study
Authors: Xu J. , Wang M. , Xiang Y. , Hu X.
Published: September 2005

Background  The concept of quality of life (QOL) is explained on the basis of traditional Chinese culture and contemporary social and cultural trends.

Method  The importance of internationally recognized QOL domains and indicators was determined for three respondent groups: consumers, parents of the consumers, and teachers and rehabilitation professionals working with the clients.

Results  Principal component analysis confirmed seven factors influencing QOL for people with intellectual disabilities (ID) in China. These seven components are conceptually equivalent to the eight domains found in the international QOL literature.

Conclusion  The concept of QOL has become one of the most sensitive issues in present Chinese society and peoples’ lives, and an important theoretical framework for the education and rehabilitation for people with ID in several ways: curriculum development, service delivery models, education and rehabilitation practices, and employment models.
Variables influencing the ratings of importance and use of quality of life domains and indicators by Polish professionals
Authors: Otrębski W.
Published: September 2005

Background  Interest in the concept of quality of life (QOL) as a category guiding the development and provision of services for individuals with intellectual disabilities (ID) in Poland is increasingly being observed. Its presence in rehabilitation and care is strongly associated with the assessment of importance and use of QOL domains and indicators by Polish professionals.

Method  The present study examined the differences related to selected demographic variables in the assessment of importance and use of eight QOL domains made by professionals in Poland working with persons with ID.

Results  The evaluation of the importance and use of eight QOL domains and their indicators is related significantly to professionals’ level of education, place of work, and total years of work.

Conclusions  The perception of professionals cannot be overlooked when considering the development and provision of QOL‐related services and supports.
The effect of different types of employment on quality of life
Authors: Kober R. , Eggleton I. R. C.
Published: September 2005

Background Despite research that has investigated whether the financial benefits of open employment exceed the costs, there has been scant research as to the effect sheltered and open employment have upon the quality of life of participants. The importance of this research is threefold: it investigates outcomes explicitly in terms of quality of life; the sample size is comparatively large; and it uses an established and validated questionnaire.

Method One hundred and seventeen people with intellectual disability (ID) who were employed in either open or sheltered employment by disability employment agencies were interviewed. Quality of life was assessed using theQuality of Life Questionnaire. After making an initial assessment to see whether the outcomes achieved depended on type of employment, quality of life scores were analyzed controlling for participants’ level of functional work ability (assessed via the Functional Assessment Inventory).

Results The results showed that participants placed in open employment reported statistically significant higher quality of life scores. When the sample was split based upon participants’ functional work ability, the type of employment had no effect on the reported quality of life for participants with a low functional work ability. However, for those participants with a high functional work ability, those in open employment reported statistically significantly higher quality of life.

Conclusions The results of this study support the placement of people with ID with high functional work ability into open employment. However, a degree of caution needs to be taken in interpreting the results presented given the disparity in income levels between the two types of employment.
Conceptualizing and measuring family quality of life
Authors: Summers J. A. , Poston D. J. , Turnbull A. P. , Marquis J. , Hoffman L. , Mannan H. , Wang M.
Published: September 2005

Background  Increasing emphasis on family‐centred approaches to services and supports for families of children with disabilities has surfaced the issue of accountability for family outcomes. We present a review of literature about the impacts of children with disabilities on families as a backdrop to proposing family quality of life as a concept that encompasses impacts of disability and one that can be used to assess the impact of supports and services on families.

Method  We briefly introduce the Beach Center Family Quality of Life Scale, providing information about its factor structure, reliability and convergent validity.

Results  The Beach Center Family Quality of Life Scale contains 25 items assessing family ratings of importance and satisfaction with five domains: Family interaction, Parenting, Emotional well‐being, Physical/material well‐being and Disability‐related supports.

Conclusion  We present a framework for utilizing a measure of family quality of life as a long‐term outcome in concert with other short‐term measures of service outcomes for families.
A self‐evaluation instrument for support plans
Authors: Schippers A. P.
Published: September 2005

Background  Actual practice in the Netherlands has shown the need of an instrument to evaluate the quality of support plans. This article describes the development of an instrument for such evaluation.

Method  The concept of quality of life (QOL) domains were used to develop an instrument to evaluate the quality of support plans within a QOL conceptual and measurement model. Information from the literature and client files was used along with expert judgement.

Results  Views on support can be divided in two dimensions: an emphasis on the person and an emphasis on relationships. With this information an instrument was developed for self‐evaluation and one that is intended for the drafters of support plans.

Conclusion  Data from 268 respondents demonstrated the instruments reliability and validity.
Left ventricular function and calcium phosphate plasma levels in uraemic patients
Authors: GALETTA F. , CUPISTI A. , FRANZONI F. , FEMIA F. R. , ROSSI M. , BARSOTTI G. , SANTORO G.
Published: September 2005

Background.  Recent investigations have focused on the pathogenetic role of disturbances of calcium phosphate metabolism in causing cardiovascular morbidity and mortality in haemodialysis patients. The aim of the present study was to assess left ventricular function and its relationship to phosphate and calcium plasma levels in stable uraemic patients on haemodialysis treatment.

Methods.  Twenty uraemic patients (mean age 51 ± 13 years) on maintenance haemodialysis and free from overt cardiac dysfunction, and 20 healthy volunteers underwent standard echocardiography, tissue Doppler‐derived early (Em) and late (Am) diastolic velocities, tissue characterization with cyclic variations of integrated backscatter (CV‐IBS), and serum biochemistry.

Results.  With respect to tissue Doppler imaging (TDI), uraemic patients showed a lower Em peak, a higher Am peak, and a reduced Em/Am ratio of both interventricular septum and lateral wall (0.01 > P < 0.001) than controls. CV‐IBS of both septum and posterior wall was significantly smaller in uraemic patients than in the control subjects (P < 0.001). Moreover, the Em/Am ratio of septum and lateral wall were negatively related to serum phosphorus and to calcium phosphate product (P < 0.001 for all). Accordingly, an inverse relationship was also found between CV‐IBS of septum and lateral wall and calcium phosphate product and phosphorus (P < 0.05 for all).

Conclusions.  These results showed early cardiac impairment of diastolic myocardial function evaluated by TDI and IBS analysis, and a close relationship between these changes and the calcium‐phosphate plasma levels. These findings are well in keeping with the important role of hyperphosphataemia as a risk factor for cardiovascular damage, and justify the effort for optimal control of calcium phosphate metabolism in uraemic patients.
Effects of smoking, obesity and physical activity on the risk of type 2 diabetes in middle‐aged Finnish men and women
Authors: PATJA K. , JOUSILAHTI P. , HU G. , VALLE T. , QIAO Q. , TUOMILEHTO J.
Published: September 2005

Objective.  To examine the association of cigarette smoking with the risk of type 2 diabetes and to find out whether the association is modified by obesity and physical activity.

Design and subjects.  A prospective study comprising 41 372 men and women aged 25–64 years without a history of diabetes, coronary heart disease or stroke at baseline. Data on incident cases of diabetes were ascertained through the nationwide Drug Register and the Hospital Discharge Register. During the mean follow‐up of 21 years 2770 subjects were diagnosed with type 2 diabetes. The Cox proportional hazards model was used to estimate the effect of smoking and other factors on the risk of type 2 diabetes.

Results.  Smoking had a graded association with the risk type 2 diabetes, and it remained significant after controlling for age and major risk factors. The multifactorial‐adjusted (age, study year, education, body mass index (BMI), systolic blood pressure, physical activity and coffee and alcohol drinking) hazard ratio was 1.22 [95% confidence interval (CI) 1.04–1.43] amongst men smoking less than 20 cigarettes per day and 1.57 (95% CI 1.34–1.84) amongst men smoking 20 cigarettes per day or more. In women the corresponding hazard ratios were 1.46 (95% CI 1.21–1.76) and 1.87 (95% CI 1.36–2.59) respectively. Smoking increased the risk of type 2 diabetes at all levels of BMI and physical activity.

Conclusion.  Smoking is a risk factor for type 2 diabetes independently of BMI and physical activity. Prevention of smoking should be encouraged as a part of efforts to reduce the risk of type 2 diabetes, and it will result in other health benefits, too.
Hypotensive shock and angio‐oedema from angiotensin II receptor blocker: a class effect in spite of tripled tryptase values
Authors: NIELSEN E. W.
Published: September 2005

In adverse reactions with shock, tripled tryptase values can support a diagnosis of anaphylaxis. A 51‐year old physically fit woman experienced angio‐oedema and hypotensive shock after irbesartan ingestion requiring noradrenaline infusion. Serum tryptase rose to three times the normal value. Total immunoglobulin E and skin prick tests were normal, however. As nonallergic increases in tryptase have been observed, e.g. during angio‐oedema from angiotensin‐converting enzyme inhibitors, and bradykinin itself can degranulate mast cells acutely, we interpret the reaction as a class effect. To our knowledge, our report is one of the first on shock and angio‐oedema from irbesartan.
Abnormal angiopoietins 1&2, angiopoietin receptor Tie‐2 and vascular endothelial growth factor levels in hypertension: relationship to target organ damage [a sub‐study of the Anglo‐Scandinavian Cardiac Outcomes Trial (ASCOT)]
Authors: NADAR S. K. , BLANN A. , BEEVERS D. G. , LIP G. Y. H.
Published: September 2005

Background.  The increased risk of target organ damage (TOD) in hypertension may be related to a prothrombotic or hypercoagulable state, with abnormalities in platelet activation. Altered angiogenesis, possibly related to increased plasma vascular endothelial growth factor (VEGF) is also a feature of hypertension. We hypothesized a link between altered angiogenesis and TOD in hypertension. Accordingly, the angiogenic growth factors VEGF, angiopoietin 1 and 2 (Ang 1 & 2) and soluble angiopoietin receptor Tie‐2 in plasma and in platelets were assessed in terms of the presence or absence of hypertensive TOD.

Methods.  We studied 199 patients (75% men; mean age 68 years) with hypertension. Of these, 125 had evidence of hypertensive TOD (stroke, previous myocardial infarction, angina, left ventricular hypertrophy and mild renal failure). Patients were compared with 74 healthy normotensive controls (69% men; mean age 68 years). Plasma VEGF, Ang 1 & 2 and Tie‐2, and total platelet levels of VEGF and Ang‐1 (obtained by lysing a known number of platelets with 0.5% Tween) were measured by an enzyme‐linked immunosorbent assay.

Results.  Hypertensive patients had higher levels of plasma VEGF, Ang‐1, Ang‐2, Tie‐2 and platelet VEGF (all P ≤ 0.01), but not platelet Ang‐1, when compared with normotensive controls. Patients with TOD had higher levels of platelet VEGF and Ang‐1 (both P < 0.001), and plasma Ang‐1 (P < 0.001). Amongst the hypertensives, plasma levels of VEGF correlated significantly with Ang‐1, Ang‐2, Tie‐2 and platelet VEGF, whilst platelet VEGF correlated strongly with plasma levels of VEGF and Ang‐1 (all P < 0.05).

Conclusion.  Patients with hypertension have evidence of changes in plasma angiogenic growth factors that correlate with the platelet levels of these molecules. Platelets may be involved in the abnormal angiogenesis seen in hypertension.
Favourable trends in the incidence and outcome of myocardial infarction in nondiabetic, but not in diabetic, subjects: findings from the MONICA myocardial infarction registry in northern Sweden in 1989–2000
Authors: RAUTIO A. , LUNDBERG V. , MESSNER T. , NASIC S. , STEGMAYR B. , ELIASSON M.
Published: September 2005

Background: The aim of this study was to compare time trends in incidence, case fatality and mortality due to myocardial infarction (MI) in patients with or without diabetes.

Methods: This study was based on the Northern Sweden MONICA Project MI registry with a target population of about 200 000 inhabitants in the age group 35–64 years in the two northernmost counties of Sweden. During 1989–2000, 6254 patients who had had an MI according to MONICA criteria were included in this study: 4569 patients had a first MI and 1685 had a recurrent MI. Sixteen per cent of the men and 20% of the women had had diabetes mellitus diagnosed prior the MI.

Results: Over the 12‐year period, there was a declining trend in incidence and case fatality in first MI. Also, the event rates (first ever and recurrent MI) declined in men without diabetes. In women without diabetes favourable time trends were seen in first ever MI, recurrent MI and in case fatality. There were no favourable time trends for any of these outcomes in patients with diabetes.

Conclusion: In nondiabetic subjects below the age of 65, the incidence of, and case‐fatality in, MI declined. This led to a decreased mortality over the 12‐year period. These favourable trends over time were not observed in diabetic subjects.
Brain regulation of food intake and appetite: molecules and networks
Authors: BROBERGER C.
Published: September 2005

In the clinic, obesity and anorexia constitute prevalent problems whose manifestations are encountered in virtually every field of medicine. However, as the command centre for regulating food intake and energy metabolism is located in the brain, the basic neuroscientist sees in the same disorders malfunctions of a model network for how integration of diverse sensory inputs leads to a coordinated behavioural, endocrine and autonomic response. The two approaches are not mutually exclusive; rather, much can be gained by combining both perspectives to understand the pathophysiology of over‐ and underweight. The present review summarizes recent advances in this field including the characterization of peripheral metabolic signals to the brain such as leptin, insulin, peptide YY, ghrelin and lipid mediators as well as the vagus nerve; signalling of the metabolic sensors in the brainstem and hypothalamus via, e.g. neuropeptide Y and melanocortin peptides; integration and coordination of brain‐mediated responses to nutritional challenges; the organization of food intake in simple model organisms; the mechanisms underlying food reward and processing of the sensory and metabolic properties of food in the cerebral cortex; and the development of the central metabolic system, as well as its pathological regulation in cancer and infections. Finally, recent findings on the genetics of human obesity are summarized, as well as the potential for novel treatments of body weight disorders.
The potential costs of accounting for genotypic errors in molecular parentage analyses
Authors: MORRISSEY MICHAEL B. , WILSON ALASTAIR J.
Published: September 2005

Genotypic errors, whether due to mutation or laboratory error, can cause the genotypes of parents and their offspring to appear inconsistent with Mendelian inheritance. As a result, molecular parentage analyses are expected to benefit when allowances are made for the presence of genotypic errors. However, a cost of allowing for genotypic errors might also be expected under some analytical conditions, primarily because parentage analyses that assume nonzero genotypic error rates can neither assign nor exclude parentage with certainty. The goal of this work was therefore to determine whether or not such costs might be important under conditions relevant to parentage analyses, particularly in natural populations. Simulation results indicate that the costs may often outweigh the benefits of accounting for nonzero error rates, except in situations where data are available for many marker loci. Consequently, the most powerful approach to handling genotypic errors in parentage analyses might be to apply likelihood equations with error rates set to values substantially lower than the rates at which genotypic errors occur. When applying molecular parentage analyses to natural populations, we advocate an increased consideration of optimal strategies for handling genotypic errors. Currently available software packages contain procedures that can be used for this purpose.
The frequency and rate of pilin antigenic variation in Neisseria gonorrhoeae
Authors: Criss Alison K. , Kline Kimberly A. , Seifert H. Steven
Published: September 2005

The pilin antigenic variation (Av) system of Neisseria gonorrhoeae (Gc) mediates unidirectional DNA recombination from silent gene copies into the pilin expression locus. A DNA sequencing assay was developed to accurately measure pilin Av in a population of Gc strain FA1090 arising from a defined pilin progenitor under non‐selective culture conditions. This assay employs a piliated parental Gc variant with a recA allele whose promoter is replaced by lac‐regulatory elements, allowing for controlled induction of pilin Av. From this assay, the frequency of pilin Av was measured as 0.13 recombination events per cell, with a corresponding rate of pilin Av of 4 × 10−3 events per cell per generation. Most pilin variants retained the parental piliation phenotype, providing the first comprehensive analysis of piliated variants arising from a piliated progenitor. Sequence analysis of pilin variants revealed that a subset of possible recombination events predominated, which differed between piliated and non‐piliated progeny. Pilin Av exhibits the highest reported frequency of any pathogenic gene conversion system and can account for the extensive pilin variation detected during human infection.
The solute‐binding component of a putative Mn(II) ABC transporter (MntA) is a novel Bacillus anthracis virulence determinant
Authors: Gat Orit , Mendelson Itai , Chitlaru Theodor , Ariel Naomi , Altboum Zeev , Levy Haim , Weiss Shay , Grosfeld Haim , Cohen Sara , Shafferman Avigdor
Published: September 2005

Here we describe the characterization of a lipoprotein previously proposed as a potential Bacillus anthracis virulence determinant and vaccine candidate. This protein, designated MntA, is the solute‐binding component of a manganese ion ATP‐binding cassette transporter. Coupled proteomic‐serological screen of a fully virulent wild‐type B. anthracis Vollum strain, confirmed that MntA is expressed both in vitro and during infection. Expression of MntA is shown to be independent of the virulence plasmids pXO1 and pXO2. An mntA deletion, generated by allelic replacement, results in complete loss of MntA expression and its phenotypic analysis revealed: (i) impaired growth in rich media, alleviated by manganese supplementation; (ii) increased sensitivity to oxidative stress; and (iii) delayed release from cultured macrophages. The ΔmntA mutant expresses the anthrax‐associated classical virulence factors, lethal toxin and capsule, in vitro as well as in vivo, and yet the mutation resulted in severe attenuation; a 104‐fold drop in LD50 in a guinea pig model. MntA expressed in trans allowed to restore, almost completely, the virulence of the ΔmntA B. anthracis strain. We propose that MntA is a novel B. anthracis virulence determinant essential for the development of anthrax disease, and that B. anthracisΔmntA strains have the potential to serve as platform for future live attenuated vaccines.
Regulation of AmtR‐controlled gene expression in Corynebacterium glutamicum: mechanism and characterization of the AmtR regulon
Authors: Beckers Gabriele , Strösser Julia , Hildebrandt Ulrich , Kalinowski Jörn , Farwick Mike , Krämer Reinhard , Burkovski Andreas
Published: September 2005

AmtR, the master regulator of nitrogen control in Corynebacterium glutamicum, represses transcription of a number of genes during nitrogen surplus. Repression is released by an interaction of AmtR with signal transduction protein GlnK. As shown by pull‐down assays and gel retardation experiments, only adenylylated GlnK, which is present in the cells during nitrogen limitation, is able to bind to AmtR.

The AmtR regulon was characterized in this study by a combination of bioinformatics, transcriptome and proteome analyses. At least 33 genes are directly controlled by the repressor protein including those encoding transporters and enzymes for ammonium assimilation (amtA, amtB, glnA, gltBD), urea and creatinine metabolism (urtABCDE, ureABCEFGD, crnT, codA), a number of biochemically uncharacterized enzymes and transport systems (NCgl1099, NCgl1100, NCgl 1915–1918) as well as signal transduction proteins (glnD, glnK). For the AmtR regulon, an AmtR box has been defined which comprises the sequence tttCTATN6AtAGat/aA. Furthermore, the transcriptional organization of AmtR‐regulated genes and operons was characterized.
Comparison of extraction procedures and determination of the detection threshold for Clavibacter michiganensis ssp. michiganensis in tomato seeds
Authors: Hadas R. , Kritzman G. , Klietman F. , Gefen T. , Manulis S.
Published: September 2005

Several seed extraction procedures, used for detection of Clavibacter michiganensis ssp. michiganensis (Cmm) in naturally infected and artificially infested tomato seed lots were evaluated. Extraction methods that included grinding the seeds were significantly better at detecting the pathogen in three different seed lots than methods that used only soaking. The detection threshold of Cmm in relation to seed sample size was determined by adding naturally infected seeds into samples of three different sizes. Cmm was detected by agar plating assay, on three media (CNS, mSCM, D2ANX), and by direct PCR from seeds and Bio‐PCR (bacteria cultured on agar media prior to PCR). In samples of 10 000 seeds containing one infected seed, Cmm could be detected only by Bio‐PCR and in only one replicate out of five. In samples containing five or 10 infected seeds per 10 000 seeds, three of five and five of five replicates, respectively, were detected by the three detection methods. In samples of 5000 seeds, one infected seed could be detected in all five replicates only after adding a concentration step. A high correlation (R2 = 0·9448) between artificially infested seeds and the disease incidence was found. Seed lots infested with less than 58 colony‐forming units (CFU) per g did not cause disease under glasshouse conditions, whereas lots with about 1000 CFU g−1 caused disease in 78 plants out of 2000.
Distinctions between phytoplasmas at the subgroup level detected by heteroduplex mobility assay
Authors: Wang K. , Hiruki C.
Published: September 2005

A total of 62 phytoplasma isolates were collected from North America, Europe and Asia and analysed by heteroduplex mobility assay (HMA) of the 16/23S spacer region amplified by the polymerase chain reaction. The results revealed wide genetic diversity among the phytoplasmas studied and a number of new phytoplasma strains were identified from known or new plant hosts in Alberta, Canada. Two distinctive subgroups were revealed by HMA in phytoplasmas associated with canola yellows, Chinese aster yellows, dandelion yellows and monarda yellows. In Alberta, two subgroups of the aster yellows group of phytoplasmas, I‐A and I‐B, were prevalent in naturally infected field crops and ornamentals in open gardens. The results indicated that HMA is a simple, but rapid and accurate, alternative method for the detection and estimation of genetic divergence of phytoplasmas when finer molecular characterization of phytoplasmas is required at the subgroup level.
Effect of a nonhost‐selective toxin from Alternaria alternata on chloroplast‐electron transfer activity in Eupatorium adenophorum
Authors: Chen S. , Dai X. , Qiang S. , Tang Y.
Published: September 2005

AAC‐toxin, a putative nonhost‐selective phytotoxin, was obtained from Alternaria alternata causing a brown leaf spot disease of Crofton weed (Eupatorium adenophorum). The effect of AAC‐toxin on the electron transfer reaction of chloroplasts showed that the activity of photosystem II, but not photosystem I, was completely inhibited by the toxin. AAC‐toxin affected the following chlorophyll fluorescence parameters: coefficient of photochemical quenching (qP), the half‐time value of fluorescence rise, and the O–J–I–P fluorescence induction kinetics curve, but not the ratio values of Fv/Fm (the quantum yield of photosystem II) and the half‐time value of fluorescence quenching. It was concluded that the toxin inhibited electron transfer from QA to QB (primary and secondary quinine acceptors of photosystem II) in photosystem II by competing with QB for the binding site in D1 protein on the thylakoid membrane.
Methods for studying population structure, including sensitivity to the fungicide silthiofam, of the cereal take‐all fungus, Gaeumannomyces graminis var. tritici
Authors: Freeman J. , Ward E. , Gutteridge R. J. , Bateman G. L.
Published: September 2005

Field isolates (n = 144) of the wheat take‐all fungus Gaeumannomyces graminis var. tritici (Ggt) were tested for sensitivity to silthiofam, a take‐all‐specific fungicide used as a seed treatment, and identified as A‐ or B‐type by PCR–RFLP analysis of nuclear rDNA. A possible association was identified between polymorphisms in ITS2 of the nuclear rDNA and sensitivity to silthiofam. A Ggt‐specific PCR assay was developed which simultaneously identified isolates of Ggt as A‐ or B‐type, based on the polymorphisms in the nuclear rDNA. A highly significant correlation between Ggt type using the PCR assay and sensitivity to silthiofam was demonstrated in a collection of 358 isolates from three field experiments designed to test the effects of seed‐treatment fungicides on take‐all and Ggt populations in winter wheat. In one experiment the percentages of silthiofam‐sensitive and B‐type isolates were significantly less in populations from plots sown with silthiofam‐treated seed in two consecutive years than in populations from plots sown with nontreated seed. However, silthiofam still provided a significant amount of control of take‐all. The natural occurrence of fungicide‐insensitive isolates, up to about 30% in soils in which the fungicide had never been used, is unusual. The new PCR assay provides a useful tool for studying the population structure of Ggt, and may provide a novel method for assessing the incidence of insensitivity to silthiofam (the target site for which has not yet been identified) in field populations of Ggt.