bluuebunny/crossref_metadata_2025 huggingface dataset:
γ-Tubulin Is Essential for Microtubule Organization and Development inArabidopsis
Authors: Pastuglia Martine , Azimzadeh Juliette , Goussot Magali , Camilleri Christine , Belcram Katia , Evrard Jean-Luc , Schmit Anne-Catherine , Guerche Philippe , Bouchez David
Published: May 2006

The process of microtubule nucleation in plant cells is still a major question in plant cell biology. γ-Tubulin is known as one of the key molecular players for microtubule nucleation in animal and fungal cells. Here, we provide genetic evidence that in Arabidopsis thaliana, γ-tubulin is required for the formation of spindle, phragmoplast, and cortical microtubule arrays. We used a reverse genetics approach to investigate the role of the two Arabidopsis γ-tubulin genes in plant development and in the formation of microtubule arrays. Isolation of mutants in each gene and analysis of two combinations of γ-tubulin double mutants showed that the two genes have redundant functions. The first combination is lethal at the gametophytic stage. Disruption of both γ-tubulin genes causes aberrant spindle and phragmoplast structures and alters nuclear division in gametophytes. The second combination of γ-tubulin alleles affects late seedling development, ultimately leading to lethality 3 weeks after germination. This partially viable mutant combination enabled us to follow dynamically the effects of γ-tubulin depletion on microtubule arrays in dividing cells using a green fluorescent protein marker. These results establish the central role of γ-tubulin in the formation and organization of microtubule arrays in Arabidopsis.
ArabidopsisPASTICCINO2 Is an Antiphosphatase Involved in Regulation of Cyclin-Dependent Kinase A
Authors: Da Costa Marco , Bach Liên , Landrieu Isabelle , Bellec Yannick , Catrice Olivier , Brown Spencer , De Veylder Lieven , Lippens Guy , Inzé Dirk , Faure Jean-Denis
Published: May 2006

PASTICCINO2 (PAS2), a member of the protein Tyr phosphatase-like family, is conserved among all eukaryotes and is characterized by a mutated catalytic site. The cellular functions of the Tyr phosphatase-like proteins are still unknown, even if they are essential in yeast and mammals. Here, we demonstrate that PAS2 interacts with a cyclin-dependent kinase (CDK) that is phosphorylated on Tyr and not with its unphosphorylated isoform. Phosphorylation of the conserved regulatory Tyr-15 is involved in the binding of CDK to PAS2. Loss of the PAS2 function dephosphorylated Arabidopsis thaliana CDKA;1 and upregulated its kinase activity. In accordance with its role as a negative regulator of the cell cycle, overexpression of PAS2 slowed down cell division in suspension cell cultures at the G2-to-M transition and early mitosis and inhibited Arabidopsis seedling growth. The latter was accompanied by altered leaf development and accelerated cotyledon senescence. PAS2 was localized in the cytoplasm of dividing cells but moved into the nucleus upon cell differentiation, suggesting that the balance between cell division and differentiation is regulated through the interaction between CDKA;1 and the antiphosphatase PAS2.
The role of supraspinal vasopressin and glutamate neurones in an increase in renal sympathetic activity in response to mild haemorrhage in the rat
Authors: Yang Zhou , Coote J. H.
Published: May 2006

This study investigated the importance of supraspinal vasopressin and glutamate neurones in regulating renal sympathetic activity as part of the response to an acute reduction in blood volume. Wistar rats anaesthetized with chloralose and urethane were instrumented to record arterial blood pressure, heart rate and left renal sympathetic nerve activity. Pharmacological agonists and antagonists to glutamate and vasopressin were applied to the renal outflow of the spinal cord via an intrathecal catheter inserted at the foramen magnum and with the tip at the level of T10. Both glutamate and vasopressin increased renal sympathetic activity, and these actions were shown to be selectively blocked by their respective antagonists. Removing 1 ml of venous blood from a femoral venous catheter elicited an increase of 26 ± 2% in renal sympathetic activity. This response to mild haemorrhage was halved to 13 ± 4% by prior intrathecal application of a selective V1a antagonist. Similarly, prior intrathecal application of kynurenic acid reduced the response to the mild haemorrhage from 28 ± 2 to 12.6 ± 2.8%. Intrathecal application of both antagonists together reduced the haemorrhage response even further to 8 ± 3%. All the changes were statistically significant at P < 0.01. It is concluded that a small reduction in blood volume induces an increase in renal sympathetic activity dependent on vasopressin and glutamate release from terminals of supraspinal neurones. It is suggested that the vasopressin neurones most probably originate from the paraventricular nucleus of the hypothalamus.
Nuclear and cytoplasmic Maspin expression in primary non-small cell lung cancer
Authors: Woenckhaus Matthias , Bubendorf Lukas , Dalquen Peter , Foerster Julia , Blaszyk Hagen , Mirlacher Martina , Soler Markus , Dietmaier Wolfgang , Sauter Guido , Hartmann Arndt , Wild Peter J
Published: May 2006

Aim:To investigate whether nuclear and cytoplasmic Maspin expression is associated with distinct clinicopathological parameters and TP53 expression in a representative series of primary non-small cell lung cancer (NSCLC).

Methods:Tissue microarrays (n = 487) were used to immunohistochemically analyse expression of Maspin and TP53. Cytoplasmic and nuclear expression of Maspin was scored on the basis of the percentage of positive tumour cells. Univariate analysis of clinicopathological variables potentially affecting tumour-specific survival was performed.

Results:Immunohistochemical Maspin expression (nuclear and cytoplasmic) was informative in 72.3% (352/487) of cases. Cytoplasmic and nuclear Maspin immunoreactivity in ⩾10% of tumour cells was detected in 37.8% (133/352) and 65.3% (230/352) of informative cases, respectively. Nuclear and cytoplasmic Maspin staining was observed more frequently in primary squamous cell carcinomas than in other lung cancer types. Only nuclear Maspin immunoreactivity was significantly associated with positive TP53 staining. Cytoplasmic or nuclear Maspin expression was not associated with tumour-specific survival.

Conclusion:Maspin expression was found both in the nucleus and the cytoplasm of NSCLC, more frequently in squamous cell carcinomas. However, no association with tumour-specific survival could be demonstrated.
My approach to pancreatic fine needle aspiration
Authors: Leiman Gladwyn
Published: May 2006

Pancreatic fine needle aspiration cytopathology has earned a reputation as a rapid, safe, accurate and cost-beneficial modality of investigation of pancreatic mass lesion. Optimal results can be expected only if these procedures are undertaken regularly in gastroenterology departments processing large numbers of patients; occasional aspirators cannot exploit the technique to full potential. Professional teams following a dedicated approach to patient selection and management develop requisite expertise over time. Cytodiagnosis rests as much on morphological examination as on the milieu in which is it practised, and as much on sample quality as on cellular criteria. This article focuses attention on specimen handling, with particular reference to rapid on-site evaluation. The significance of particular cytodiagnoses in patient care is evaluated, and tumour types that may be encountered are enumerated and illustrated.
Examination of peripheral blood films using automated microscopy; evaluation of Diffmaster Octavia and Cellavision DM96
Authors: Ceelie H , Dinkelaar R B , van Gelder W
Published: May 2006

Background:Differential counting of peripheral blood cells is an important diagnostic tool. Yet, this technique requires highly trained staff, is labour intensive and has limited statistical reliability. A recent development in this field was the introduction of automated peripheral blood differential counting systems. These computerised systems provide an automated morphological analysis of peripheral blood films, including a preclassification of both red and white cells (RBCs and WBCs, respectively).

Aims:To investigate the ability of two automated microscopy systems to examine peripheral blood smears.

Methods:Two automated microscopy systems, the Cellavision Diffmaster Octavia (Octavia) and Cellavision DM96 (DM96), were evaluated.

Results:The overall preclassification accuracy values for the Octavia and the DM96 systems were 87% and 92%, respectively. Evaluation of accuracy (WBC analysis) showed good correlation for both automated systems when compared with manual differentiation. Total analysis time (including post classification) was 5.4 min/slide for the Octavia and 3.2 min/slide for the DM96 (100 WBC/slide) system. The DM96 required even less time than manual differentiation by an experienced biomedical scientist.

Conclusions:The Octavia and the DM96 are automated cell analysis systems capable of morphological classification of RBCs and WBCs in peripheral blood smears. Classification accuracy depends on the type of pathological changes in the blood sample. Both systems operate most effectively in the analysis of non-pathological blood samples.
Expression of peroxisome proliferator activated receptor γ and cyclo-oxygenase 2 in primary and recurrent ovarian carcinoma
Authors: Stadlmann Sylvia , Gueth Uwe , Wight Edward , Kunz-Schughart Leoni A , Hartmann Arndt , Singer Gad
Published: May 2006

Aim:Peroxisome proliferator-activated receptor γ (PPARγ) has emerged as a potential therapeutic target in several types of cancer. In ovarian carcinomas, limited and conflicting data on PPARγ protein expression have been reported.

Methods:The immunoexpression of PPARγ and its putative target cyclo-oxygenase 2 (COX2) was investigated in tumour tissues from 80 patients with primary and corresponding recurrent ovarian serous carcinomas after conventional platinum-based chemotherapy.

Results:PPARγ expression was observed in 29% of primary and recurrent carcinomas. In the recurrent tumours, PPARγ expression inversely correlated with COX2 overexpression in both chemosensitive (p = 0.02) and chemoresistant (p = 0.04) carcinomas.

Conclusions:The data indicate that PPARγ may represent a potential target for second-line treatment in ovarian cancers.
Construction and validation of a bone marrow tissue microarray
Authors: Zimpfer Annette , Schönberg Sharon , Lugli Alessandro , Agostinelli Claudio , Pileri Stefano A , Went Philip , Dirnhofer Stephan
Published: May 2006

Background:The use of tissue microarrays (TMAs) is now a generally accepted method for the investigation of solid tumours. However, little is known about the applicability of the TMA technique for analysis of patients with acute leukaemia. A bone marrow (BM)-TMA analysis with 15 different immunohistochemical markers was performed. The TMA was validated by comparison with the corresponding full tissue sections.

Materials and methods:A BM-TMA comprising 148 cases of acute leukaemia, including 115 acute myeloid leukaemia (AML) and 33 acute lymphoblastic leukaemia (ALL) cases, was constructed. Expression of CD3, CD10, CD15, CD20, CD34, CD61, CD68, CD79a, CD99, CD117, CD138, myeloperoxidase, haemoglobin A1, glycophorin and terminal deoxynucleotidyl transferase was immunohistochemically analysed. 50 cases of the TMA were directly compared with the corresponding full tissue section to validate the results.

Results:Morphologically and immunohistochemically, 6 (4%) of 148 cases and 765 (11%) cores of 6912 individual analyses were not evaluable. A direct comparison of TMA cases with conventional full sections showed a concordance of the results of 100%.

Conclusions:The small size of bone-marrow biopsies and the presence of bony trabeculae do not preclude construction and analysis of acute leukaemia TMAs. Acute leukaemia cases on TMA displayed the characteristic phenotypic profiles expected in different AML and ALL subtypes. Therefore, the TMA technique is also a promising method for high-throughput analysis of combined marker expression and clinicopathological correlations in patients with leukaemia.
Presence of mouse mammary tumour-like virus gene sequences may be associated with morphology of specific human breast cancer
Authors: Lawson J S , Tran D D , Carpenter E , Ford C E , Rawlinson W D , Whitaker N J , Delprado W
Published: May 2006

Background:Mouse mammary tumour virus (MMTV) has a proven role in breast carcinogenesis in wild mice and genetically susceptible in-bred mice. MMTV-likeenvgene sequences, which indicate the presence of a replication-competent MMTV-like virus, have been identified in some human breast cancers, but rarely in normal breast tissues. However, no evidence for a causal role of an MMTV-like virus in human breast cancer has emerged, although there are precedents for associations between specific histological characteristics of human cancers and the presence of oncogenic viruses.

Aim:To investigate the possibility of an association between breast cancer and MMTV-like viruses.

Methods:Histological characteristics of invasive ductal human breast cancer specimens were compared with archival MMTV-associated mammary tumours from C3H experimental mice. The presence of MMTV-likeenvDNA sequences in the human breast cancer specimens was determined by polymerase chain reaction and confirmed by Southern hybridisation.

Results:MMTV-likeenvgene sequences were identified in 22 of 59 (37.3%) human breast cancer specimens. Seventeen of 43 (39.5%) invasive ductal carcinoma breast cancer specimens and 4 of 16 (25%) ductal carcinoma in situ specimens had some histological characteristics, which were similar to MMTV-associated mouse mammary tumours. However, these similarities were not associated with the presence or absence of MMTV-like gene sequences in the human breast tumour specimens. A significant (p = 0.05) correlation was found between the grade of the human breast cancer and similarity to the mouse mammary tumours. The lower the grade, the greater the similarity.

Conclusion:Some human breast cancer specimens, in which MMTV-likeenvDNA sequences have been identified, were shown to have histological characteristics (morphology) similar to MMTV-associated mouse mammary tumours. These observations are compatible with, but not conclusive of, an association between the presence of MMTV-likeenvDNA sequences and some human breast cancers.
Variability of grade and stage in simultaneous paired liver biopsies in patients with hepatitis C
Authors: Skripenova Silvia , Trainer Thomas D , Krawitt Edward L , Blaszyk Hagen
Published: May 2006

Background:Grading and staging of liver biopsies in patients with chronic hepatitis remains an inexact “gold standard” that is influenced by variabilities in scoring systems, sampling, observer agreement and expertise. Spatial disease variability relative to markers of the adequacy of biopsy has not been studied previously.

Methods:Paired liver biopsy specimens were obtained from the right and left hepatic lobes of 60 patients with chronic hepatitis C. Histological grade and disease stage were assessed according to the Ludwig scoring system, and scores were evaluated in relation to differences in size and number of portal tracts in all paired samples.

Results:The relative difference (%) in aggregate biopsy size and number of portal tracts was similar between paired samples with and without a difference in grade. Paired samples with a difference in stage showed a larger relative difference in biopsy size (p = 0.09) and in the number of portal tracts (p = 0.016).

Conclusions:Our study shows a difference of one grade or one stage in 30% of paired liver biopsies, due to a combination of sampling variability and observer variability. Acknowledgment of “built-in” variability in grading and staging chronic hepatitis C by both clinicians and pathologists is essential for managing the individual patient with chronic hepatitis C.
Value of ezrin, maspin and nm23-H1 protein expressions in predicting outcome of patients with head and neck squamous-cell carcinoma treated with radical radiotherapy
Authors: Mhawech-Fauceglia Paulette , Dulguerov Pavel , Beck Amy , Bonet Marta , Allal Abdelkarim S
Published: May 2006

Background:Prognostic factors in predicting outcomes in patients with head and neck squamous-cell carcinoma (HNSCC) are limited to the clinical–pathological parameters, including lymph node metastasis, location, grade and stage of the disease.

Aim:To determine whether the expression of these proteins has a value in predicting patient outcome.

Methods:Ezrin, maspin and nm23-H1 immunohistochemistry in tissue samples of 120 patients with HNSCC were evaluated using the microarray technique.

Results:In determining the association among each of the three proteins and the clinical–pathological parameters, low maspin expression was the only one found to be significantly associated with high tumour grade (p = 0.007); all others showed no significant associations. In univariate analysis, patients with tumours expressing high ezrin had a shorter disease-free survival (DFS) of 51% than those with low ezrin expression (DFS 84%; p = 0.08). In multivariate analysis, tumours with the combination of loss of maspin and low histological grade had longer DFS (83%) compared with those with high maspin and high histological grade (DFS 42%; p = 0.08).

Conclusion:Our study is the first to determine the value of ezrin and maspin in HNSCC in a large series of patients with long follow-up. Ezrin and maspin seem to have a potential prognostic value in patients with HNSCC but results should be confirmed with further studies.
Expression of KAI1 and tenascin, and microvessel density are closely correlated with liver metastasis of gastrointestinal adenocarcinoma
Authors: Zheng Huachuan , Tsuneyama Koichi , Cheng Chunmei , Takahashi Hiroyuki , Cui Zhengguo , Nomoto Kazuhiro , Murai Yoshihiro , Takano Yasuo
Published: May 2006

Aim:To seek good markers to predict invasion and metastasis of gastrointestinal adenocarcinoma (GIA).

Methods:Expression of KAI1 and tenascin were examined on tissue microarrays containing gastric adenocarcinoma (n = 98), colorectal adenocarcinoma (n = 125), gastric adjacent non-cancerous mucosa (n = 95) and colorectal adjacent non-cancerous mucosa (n = 112) by immunostaining. Microvessel density (MVD) in GIA was labelled using anti-CD34 antibody by immunostaining. Expression of KAI1 and tenascin, and MVD were compared with clinicopathological features of tumours, including PTEN (phosphatase and tensin homology deleted from human chromosome 10) and EMMPRIN (extracellular matrix metalloproteinase inducer) expression.

Results:KAI1 expression was higher in GIAs than in their adjacent non-cancerous mucosa (p<0.05). KAI1 and tenascin expression showed a significantly negative association with liver metastasis of GIA (p<0.05), but not with depth of invasion, venous invasion or lymph node metastasis (p>0.05). A significantly negative relationship was observed between EMMPRIN and tenascin expression in GIA (p<0.05). MVD was positively correlated with depth of invasion, venous invasion, lymph node metastasis and liver metastasis of tumours (p<0.05), whereas it was negatively correlated with PTEN expression (p<0.05).

Conclusions:Up-regulated KAI1 expression may play an important part in malignant transformation of gastrointestinal epithelial cells. Reduced expression of KAI1 and tenascin might underlie the molecular basis of liver metastasis of GIA. Angiogenesis is a key event in the invasion and metastasis of GIA. These markers might be used to indicate liver metastasis of GIA in clinicopathological practice.
The role of immunohistochemistry for smooth-muscle actin, p63, CD10 and cytokeratin 14 in the differential diagnosis of papillary lesions of the breast
Authors: Tse G M K , Tan P-H , Lui P C W , Gilks C B , Poon C S P , Ma T K F , Law B K B , Lam W W M
Published: May 2006

Background:Histological differentiation of mammary papillary lesions can be difficult. The evaluation of myoepithelial cells can be helpful, with benign papilloma showing a continuous myoepithelial cell layer, which becomes attenuated or absent in malignant papillary lesions.

Methods:A large series of 100 papillomas (28 papillomas with florid epithelial hyperplasia) and 68 papillary carcinomas (9 invasive, 44 in situ, and 15 ductal carcinomas in situ (DCIS) involving papillomas) of the breast were stained for myoepithelial cells by immunohistochemistry using antibodies to smooth-muscle actin (SMA), p63, CD10 and cytokeratin (CK) 14.

Results:In the papillomas, using these four antibodies, myoepithelial cells were positive in 88%, 99%, 91% and 95% of cases, respectively, with SMA showing marked stromal component cell staining and CD10 showing epithelial and stromal staining. CK14 also showed epithelial staining in 71% of papillomas and 96% of papillomas with florid epithelial hyperplasia. In the papillary carcinomas, 36 (53%) cases showed staining of myoepithelial cells that were scattered, discontinuous and diminished in number and the remaining 32 (47%) cases did not show myoepithelial cells. Invasive papillary carcinoma has the lowest proportion (33%) with myoepithelial cells, and DCIS involving papillomas had the highest proportion (87%).

Conclusions:p63 had the highest sensitivity and did not cross-react with stromal cells and only rarely with epithelial cells. CK14 has the added ability to distinguish between florid epithelial hyperplasia involving papilloma and DCIS involving papillomas. CK14 and p63 may be used as an adjunct in assessing difficult papillary lesions of the breast.
Spatial organisation of microbiota in quiescent adenoiditis and tonsillitis
Authors: Swidsinski A , Göktas Ö , Bessler C , Loening-Baucke V , Hale L P , Andree H , Weizenegger M , Hölzl M , Scherer H , Lochs H
Published: May 2006

Background:The reasons for recurrent adenotonsillitis are poorly understood.

Methods:The in situ composition of microbiota of nasal (5 children, 25 adults) and of hypertrophied adenoid and tonsillar tissue (50 children, 20 adults) was investigated using a broad range of fluorescent oligonucleotide probes targeted to bacterial rRNA. None of the patients had clinical signs of infection at the time of surgery.

Results:Multiple foci of ongoing purulent infections were found within hypertrophied adenoid and tonsillar tissue in 83% of patients, including islands and lawns of bacteria adherent to the epithelium, with concomitant marked inflammatory response, fissures filled with bacteria and pus, and diffuse infiltration of the tonsils by bacteria, microabscesses, and macrophages containing phagocytosed microorganisms.Haemophilusinfluenzaemainly diffusely infiltrated the tissue,StreptococcusandBacteroideswere typically found in fissures, andFusobacteria,PseudomonasandBurkholderiawere exclusively located within adherent bacterial layers and infiltrates. The microbiota were always polymicrobial.

Conclusions:Purulent processes persist during asymptomatic periods of adenotonsillitis. Most bacteria involved in this process are covered by a thick inflammatory infiltrate, are deeply invading, or are located within macrophages. The distribution of the bacteria within tonsils may be responsible for the failure of antibiotic treatment.
Fertility and exposure to solvents among families in the Agricultural Health Study
Authors: Sallmén M , Baird D D , Hoppin J A , Blair A , Sandler D P
Published: May 2006

Background:Several studies have reported associations between solvent exposure and reduced female fertility, but the evidence is inconclusive for male fertility.

Objectives:To investigate the impact of solvent exposure on subfertility among families of male licensed pesticide applicators in the Agricultural Health Study cohort.

Methods:The couples enrolled between 1993 and 1997. Cross-sectional questionnaire information on work tasks was used to assess exposure to solvents. The data were limited to couples (wife aged less than 40 years) with an attempt at pregnancy in the last four years (n = 2112).

Results:Twenty eight per cent of the couples were defined as subfertile (not conceiving a pregnancy after at least 12 months of unprotected intercourse, regardless of whether or not a pregnancy ultimately occurred). Adjusted subfertility odds ratios (OR) for exposure to solvents were calculated with logistic regression. Female (OR 1.42, 95% CI 1.15 to 1.75) and male exposure to solvents (OR 1.21 (95% CI 0.93 to 1.57) for monthly exposure and 1.40 (95% CI 0.97 to 2.03) for daily or weekly exposure) were associated with subfertility. In farming, spouses may share or exchange jobs. To account for potential dual exposure, variables for parental exposure (either parent exposed or both parents exposed) were also defined. Both were strongly associated with subfertility (OR 1.62 (95% CI 1.20 to 2.17) and OR 2.10 (95% CI 1.22 to 3.60), respectively).

Conclusions:Solvents may impair fertility of either gender, though the evidence for female effects is stronger than for male effects.
Injustice at work and incidence of psychiatric morbidity: the Whitehall II study
Authors: Ferrie J E , Head J , Shipley M J , Vahtera J , Marmot M G , Kivimäki M
Published: May 2006

Background:Previous studies of organisational justice and mental health have mostly examined women and have not examined the effect of change in justice.

Aim:To examine effects of change in the treatment of employees by supervisors (the relational component of organisational justice) on minor psychiatric morbidity, using a cohort with a large proportion of men.

Methods:Data are from the Whitehall II study, a prospective cohort of 10 308 white-collar British civil servants (3143 women and 6895 men, aged 35–55 at baseline) (Phase 1, 1985–88). Employment grade, relational justice, job demands, job control, social support at work, effort–reward imbalance, physical illness, and psychiatric morbidity were measured at baseline. Relational justice was assessed again at Phase 2 (1989–90). The outcome was cases of psychiatric morbidity by Phases 2 and 3 (1991–93) among participants case-free at baseline.

Results:In analyses adjusted for age, grade, and baseline physical illness, women and men exposed to low relational justice at Phase 1 were at higher risk of psychiatric morbidity by Phases 2 and 3. Adjustment for other psychosocial work characteristics, particularly social support and effort–reward imbalance, partially attenuated these associations. A favourable change in justice between Phase 1 and Phase 2 reduced the immediate risk (Phase 2) of psychiatric morbidity, while an adverse change increased the immediate and longer term risk (Phase 3).

Conclusion:This study shows that unfair treatment by supervisors increases risk of poor mental health. It appears that the employers’ duty to ensure that employees are treated fairly at work also has benefits for health.
Chronic fatigue syndrome-like caseness as a predictor of work status in fatigued employees on sick leave: four year follow up study
Authors: Huibers M J H , Leone S S , Kant IJ , Knottnerus J A
Published: May 2006

Objective:To assess whether CFS-like caseness (meeting the criteria for chronic fatigue syndrome (CFS)) predicts work status in the long term.

Methods:Prospective study in a sample of fatigued employees absent from work. Data were collected at baseline and four years later, and included CFS-like caseness and work status (inactive work status and full work incapacity).

Results:CFS-like cases at baseline were three times more likely to be unable to work at follow up than fatigued employees who did not meet CFS criteria at baseline (ORs 3–3.3). These associations grew even stronger when demographic and clinical confounders were controlled for (ORs 3.4–4.4).

Conclusion:A CFS-like status (compared to non-CFS fatigue) proved to be a strong predictor of an inactive work status and full work incapacity in the long term. Since little is known about effective interventions that prevent absenteeism and work incapacity or facilitate return to work in subjects with chronic fatigue, there is a great need for powerful early interventions that restore or preserve the ability to work, especially for workers who meet criteria for CFS.
Association of ventricular arrhythmias detected by implantable cardioverter defibrillator and ambient air pollutants in the St Louis, Missouri metropolitan area
Authors: Rich D Q , Kim M H , Turner J R , Mittleman M A , Schwartz J , Catalano P J , Dockery D W
Published: May 2006

Background:It has previously been reported that the risk of ventricular arrhythmias is positively associated with ambient air pollution among patients with implantable cardioverter defibrillators (ICD) in Boston.

Aims:To assess the association of community exposures to air pollution with ventricular arrhythmias in a cohort of ICD patients in metropolitan St Louis, Missouri.

Methods:ICD detected episodes reported during clinical follow up were abstracted and reviewed by an electrophysiologist to identify ventricular arrhythmias. A total of 139 ventricular arrhythmias were identified among 56 patients. A case-crossover design was used with control periods matched on weekday and hour of the day within the same calendar month. Conditional logistic regression models were adjusted for temperature, barometric pressure, and relative humidity in the 24 hours preceding the event.

Results:There was a significant (24%, 95% CI 7% to 44%) increase in risk of ventricular arrhythmias associated with each 5 ppb increase in mean sulphur dioxide and non-significantly increased risk (22%, 95% CI −6% to 60%; and 18%, 95% CI −7% to 50%) associated with increases in nitrogen dioxide (6 ppb) and elemental carbon (0.5 μg/m3), respectively in the 24 hours before the arrhythmia.

Conclusions:These results provide evidence of an association between ventricular arrhythmias and ambient air pollutants in St Louis. This is consistent with previous results from Boston, although the pollutants responsible for the increased risk are different.
Update of mortality and cancer incidence in the Australian petroleum industry cohort
Authors: Gun R T , Pratt N , Ryan P , Roder D
Published: May 2006

Objectives:To update the analysis of the cohort mortality and cancer incidence study of employees in the Australian petroleum industry.

Methods:Employees of Australian Institute of Petroleum member companies were enrolled in the cohort in four industry-wide surveys between 1981 and 1999. Mortality of 16 547 males and 1356 females was determined up to 31 December 2001 and cancer incidence to 31 December 2000. Cause specific mortality and cancer incidence were compared with those of the Australian population by means of standardised mortality ratios (SMRs) and standardised incidence ratios (SIRs). Associations between increased incidence of specific cancers and employment in the petroleum industry were tested by trends according to period of first employment, duration of employment, latency, and hydrocarbon exposure, adjusting for personal smoking history where appropriate.

Results:There was a significant elevation of the incidence of mesothelioma (SIR 1.77, 95% CI 1.05 to 2.79), melanoma (SIR 1.37, 95% CI 1.19 to 1.58), and prostate cancer (SIR 1.18, 95% CI 1.04 to 1.34). The SIRs of all leukaemias and of acute non-lymphocytic leukaemia (ANLL) were not significantly different from unity, but all 11 ANLL cases were clustered in the middle to high hydrocarbon exposure categories. Tanker drivers had a significantly elevated incidence of kidney cancer (12 casesv5.84 expected, SIR 2.05, 95% CI 1.06 to 3.59). Lung cancer incidence was significantly reduced (SIR 0.69, 95% CI 0.57 to 0.83)

Conclusions:Most cases of mesothelioma are probably related to past exposure to asbestos in refineries. No occupational cause has been identified for the excess of melanoma, or prostatic or bladder cancer. The possibility of a causal relationship between cancer of the kidney and hydrocarbon exposure warrants further study. It is uncertain whether benzene exposures, particularly past levels of exposure, have been high enough to cause ANLL.
Prediction of sickness absence: development of a screening instrument
Authors: Duijts S F A , Kant I J , Landeweerd J A , Swaen G M H
Published: May 2006

Objectives:To develop a concise screening instrument for early identification of employees at risk for sickness absence due to psychosocial health complaints.

Methods:Data from the Maastricht Cohort Study on “Fatigue at Work” were used to identify items to be associated with an increased risk of sickness absence. The analytical procedures univariate logistic regression, backward stepwise linear regression, and multiple logistic regression were successively applied. For both men and women, sum scores were calculated, and sensitivity and specificity rates of different cut-off points on the screening instrument were defined.

Results:In women, results suggested that feeling depressed, having a burnout, being tired, being less interested in work, experiencing obligatory change in working days, and living alone, were strong predictors of sickness absence due to psychosocial health complaints. In men, statistically significant predictors were having a history of sickness absence, compulsive thinking, being mentally fatigued, finding it hard to relax, lack of supervisor support, and having no hobbies. A potential cut-off point of 10 on the screening instrument resulted in a sensitivity score of 41.7% for women and 38.9% for men, and a specificity score of 91.3% for women and 90.6% for men.

Conclusions:This study shows that it is possible to identify predictive factors for sickness absence and to develop an instrument for early identification of employees at risk for sickness absence. The results of this study increase the possibility for both employers and policymakers to implement interventions directed at the prevention of sickness absence.
Work–family conflict as a risk factor for sickness absence
Authors: Jansen N W H , Kant IJ , van Amelsvoort L G P M , Kristensen T S , Swaen G M H , Nijhuis F J N
Published: May 2006

Objectives:(1) To study both cross-sectional and prospective relationships between work–family conflict and sickness absence from work; (2) to explore the direction of the relationships between the different types of conflict (work–home interference and home–work interference) and sickness absence; and (3) to explore gender differences in the above relationships.

Methods:Data from the Maastricht Cohort Study were used with six months of follow up (5072 men and 1015 women at T6). Work–family conflict was measured with the Survey Work–Home Interference Nijmegen (SWING). Sickness absence was assessed objectively through individual record linkage with the company registers on sickness absence.

Results:In the cross-sectional analyses, high levels of work–family conflict, work–home interference, and home–work interference were all associated with a higher odds of being absent at the time of completing the questionnaire, after controlling for age and long term disease. Differences in average number of absent days between cases and non-cases of work–home interference were significant for men and most pronounced in women, where the average number of absent days over six months follow up was almost four days higher in women with high versus low–medium work–home interference.

Conclusions:A clear relation between work–family conflict and sickness absence was shown. Additionally, the direction of work–family conflict was associated with a different sickness absence pattern. Sickness absence should be added to the list of adverse outcomes for employees struggling to combine their work and family life.
Cardiac ischemia-reperfusion injury induces matrix metalloproteinase-2 expression through the AP-1 components FosB and JunB
Authors: Alfonso-Jaume Maria Alejandra , Bergman Marina R. , Mahimkar Rajeev , Cheng Sunfa , Jin Zhu Q. , Karliner Joel S. , Lovett David H.
Published: May 2006

Matrix metalloproteinase-2 (MMP-2) is a central component of the response to injury in the heart. During ischemia, MMP-2 influences ventricular performance and is a determinant of postinfarction remodeling. Elevation of MMP-2 during reperfusion after ischemia suggests that new protein is synthesized, but the molecular regulation of MMP-2 generation during ischemia-reperfusion (I/R) injury has not been studied. Using the MMP-2 promoter linked to a β-galactosidase reporter in transgenic mice, we investigated the transcriptional regulation and cellular sources of MMP-2 in isolated, perfused mouse hearts subjected to acute global I/R injury. I/R injury induced a rapid activation of MMP-2 promoter activity with the appearance of β-galactosidase antigen in cardiomyocytes, fibroblasts, and endothelial cells. Activation of intrinsic MMP-2 transcription and translation was confirmed by real-time PCR and quantitative Western blot analyses. MMP-2 transcription and translation were inhibited by perfusion with 1.0 mM hydroxyl radical scavenger N-(-2-mercaptopropionyl)-glycine. Nuclear extracts demonstrated increased abundance of two activator proteins-1 (AP-1) components JunB and FosB following I/R injury. Immunohistochemical staining localized JunB and FosB proteins to the nuclei of all three cardiac cell types following I/R injury, consistent with enhanced nuclear transport of these transcription factors. Chromatin immunoprecipitation (ChIP) of the AP-1 binding site in the intrinsic murine MMP-2 promoter yielded only JunB under control conditions, whereas ChIP following I/R injury recovered both JunB and FosB, consistent with a change in occupancy from JunB homodimers in controls to JunB/FosB heterodimers following I/R injury. We conclude that enhanced MMP-2 transcription and translation following I/R injury are mediated by induction, via oxidant stress, of discrete AP-1 transcription factor components.
Ventricular-arterial coupling in a rat model of reduced arterial compliance provoked by hypervitaminosis D and nicotine
Authors: Jegger David , da Silva Rafaela , Jeanrenaud Xavier , Nasratullah Mohammad , Tevaearai Hendrik , von Segesser Ludwig K. , Segers Patrick , Gaillard Virginie , Atkinson Jeffrey , Lartaud Isabelle , Stergiopulo Nikolaos
Published: May 2006

The vitamin D3 and nicotine (VDN) model is one of isolated systolic hypertension (ISH) in which arterial calcification raises arterial stiffness and vascular impedance. The effects of VDN treatment on arterial and cardiac hemodynamics have been investigated; however, a complete analysis of ventricular-arterial interaction is lacking. Wistar rats were treated with VDN (VDN group, n = 9), and a control group ( n = 10) was included without the VDN. At week 8, invasive indexes of cardiac function were obtained using a conductance catheter. Simultaneously, aortic pressure and flow were measured to derive vascular impedance and characterize ventricular-vascular interaction. VDN caused significant increases in systolic (138 ± 6 vs. 116 ± 13 mmHg, P < 0.01) and pulse (42 ± 10 vs. 26 ± 4 mmHg, P < 0.01) pressures with respect to control. Total arterial compliance decreased (0.12 ± 0.08 vs. 0.21 ± 0.04 ml/mmHg in control, P < 0.05), and pulse wave velocity increased significantly (8.8 ± 2.5 vs. 5.1 ± 2.0 m/s in control, P < 0.05). The arterial elastance and end-systolic elastance rose significantly in the VDN group ( P < 0.05). Wave reflection was augmented in the VDN group, as reflected by the increase in the wave reflection coefficient (0.63 ± 0.06 vs. 0.52 ± 0.05 in control, P < 0.05) and the amplitude of the reflected pressure wave (13.3 ± 3.1 vs. 8.4 ± 1.0 mmHg in control, P < 0.05). We studied ventricular-arterial coupling in a VDN-induced rat model of reduced arterial compliance. The VDN treatment led to development of ISH and provoked alterations in cardiac function, arterial impedance, arterial function, and ventricular-arterial interaction, which in many aspects are similar to effects of an aged and stiffened arterial tree.
KCa+ channels contribute to exercise-induced coronary vasodilation in swine
Authors: Merkus Daphne , Sorop Oana , Houweling Birgit , Hoogteijling Bas A. , Duncker Dirk J.
Published: May 2006

Coronary blood flow is controlled via several vasoactive mediators that exert their effect on coronary resistance vessel tone through activation of K+ channels in vascular smooth muscle. Because Ca2+-activated K+ (KCa+) channels are the predominant K+ channels in the coronary vasculature, we hypothesized that KCa+ channel activation contributes to exercise-induced coronary vasodilation. In view of previous observations that ATP-sensitive K+ (KATP+) channels contribute, in particular, to resting coronary resistance vessel tone, we additionally investigated the integrated control of coronary tone by KCa+ and KATP+ channels. For this purpose, the effect of KCa+ blockade with tetraethylammonium (TEA, 20 mg/kg iv) on coronary vasomotor tone was assessed in the absence and presence of KATP+ channel blockade with glibenclamide (3 mg/kg iv) in chronically instrumented swine at rest and during treadmill exercise. During exercise, myocardial O2 delivery increased commensurately with the increase in myocardial O2 consumption, so that myocardial O2 extraction and coronary venous Po2 ([Formula: see text]) were maintained constant. TEA (in a dose that had no effect on KATP+ channels) had a small effect on the myocardial O2 balance at rest and blunted the exercise-induced increase in myocardial O2 delivery, resulting in a progressive decrease of [Formula: see text] with increasing exercise intensity. Conversely, at rest glibenclamide caused a marked decrease in [Formula: see text] that waned at higher exercise levels. Combined KCa+ and KATP+ channel blockade resulted in coronary vasoconstriction at rest that was similar to that caused by glibenclamide alone and that was maintained during exercise, suggesting that KCa+ and KATP+ channels act in a linear additive fashion. In conclusion, KCa+ channel activation contributes to the metabolic coronary vasodilation that occurs during exercise. Furthermore, in swine KCa+ and KATP+ channels contribute to coronary resistance vessel control in a linear additive fashion.
Regulation of α1-adrenoceptor-mediated contractions of uterine arteries by PKC: effect of pregnancy
Authors: Zhang Hongying , Xiao DaLiao , Longo Lawrence D. , Zhang Lubo
Published: May 2006

Protein kinase C (PKC) plays an important role in the regulation of uterine artery contractility and its adaptation to pregnancy. The present study tested the hypothesis that PKC differentially regulates α1-adrenoceptor-mediated contractions of uterine arteries isolated from nonpregnant (NPUA) and near-term pregnant (PUA) sheep. Phenylephrine-induced contractions of NPUA and PUA sheep were determined in the absence or presence of the PKC activator phorbol 12,13-dibutyrate (PDBu). In NPUA sheep, PDBu produced a concentration-dependent potentiation of phenylephrine-induced contractions and shifted the dose-response curve to the left. In contrast, in PUA sheep, PDBu significantly inhibited phenylephrine-induced contractions and decreased their maximum response. Simultaneous measurement of contractions and intracellular free Ca2+concentrations ([Ca2+]i) in the same tissues revealed that PDBu inhibited phenylephrine-induced [Ca2+]iand contractions in PUA sheep. In NPUA sheep, PDBu increased phenylephrine-induced contractions without changing [Ca2+]i. Western blot analysis showed six PKC isozymes, α, βI, βII, δ, ε, and ζ, in uterine arteries, among which βI, βII, and ζ isozymes were significantly increased in PUA sheep. In contrast, PKC-α was decreased in PUA sheep. In addition, analysis of subcellular distribution revealed a significant decrease in the particulate-to-cytosolic ratio of PKC-ε in PUA compared with that in NPUA sheep. The results suggest that pregnancy induces a reversal of PKC regulatory role on α1-adrenoceptor-mediated contractions from a potentiation in NPUA sheep to an inhibition in PUA sheep. The differential expression of PKC isozymes and their subcellular distribution in uterine arteries appears to play an important role in the regulation of Ca2+mobilization and Ca2+sensitivity in α1-adrenoceptor-mediated contractions and their adaptation to pregnancy.
Vascular endothelial growth factor promotes cardiomyocyte differentiation of embryonic stem cells
Authors: Chen Yu , Amende Ivo , Hampton Thomas G. , Yang Yinke , Ke Qingen , Min Jiang-Yong , Xiao Yong-Fu , Morgan James P.
Published: May 2006

Embryonic stem cells (ESCs) overexpressing the vascular endothelial growth factor (VEGF) improve cardiac function in mouse models of myocardial ischemia and infarction by mechanisms that are poorly understood. Here we studied the effects of VEGF on cardiomyocyte differentiation of mouse ESCs in vitro. We used flow cytometry to determine the expression of α-myosin heavy chain (α-MHC), cardiac troponin I (cTn-I), and Nkx2.5 in differentiated ESCs. VEGF (20 ng/ml) significantly enhanced α-MHC, cTn-I, and Nkx2.5 expression in differentiated ESCs. Western blot analysis confirmed these findings. We found that VEGF receptor FMS-like tyrosine kinase-1 (Flt-1) and fetal liver kinase-1 (Flk-1) expression increased during ESC differentiation. Antibodies against Flk-1 totally blocked and against Flt-1 partially blocked VEGF-induced NKx2.5-positive-stained cells. The ERK inhibitor PD-098059 abolished VEGF-induced cardiomyocyte differentiation of ESCs. Our results suggest that VEGF promotes cardiomyocyte differentiation predominantly by ERK-mediated Flk-1 activation and, to a lesser extent, by Flt-1 activation. These findings may be of significance for stem cell and growth factor therapies to regenerate failing cardiomyocytes.
Competitive displacement of phosphoinositide 3-kinase from β-adrenergic receptor kinase-1 improves postinfarction adverse myocardial remodeling
Authors: Curcio Antonio , Noma Takahisa , Naga Prasad Sathyamangla V. , Wolf Matthew J. , Lemaire Anthony , Perrino Cinzia , Mao Lan , Rockman Howard A.
Published: May 2006

Adverse remodeling after myocardial infarction (MI) determines the progression of heart failure. Failing hearts are characterized by downregulation of β-adrenergic receptor (β-AR) signaling in part because of increased β-AR kinase 1 activity. Our previous studies have shown that overexpression of the phosphoinositide kinase (PIK) domain of phosphoinositide 3-kinase (PI3K), prevents β-AR downregulation and enhances adrenergic agonist responsiveness by inhibiting the targeting of PI3K to the β-AR complex. To investigate whether preventing β-AR downregulation in the heart ameliorates cardiac function post-MI, transgenic mice with cardiac-specific overexpression of the PIK domain peptide (TgPIK) underwent left coronary artery ligation and were subsequently followed by serial echocardiography at 4, 8, 12, 16, and 20 wk. Despite having similar infarction sizes, TgPIK mice showed better systolic function, less cardiac dilatation, and improved hemodynamic response to dobutamine compared with littermate controls after MI. To test that displacement of PI3K from the β-AR complex, but not the total loss of PI3K-γ, is critical for amelioration of cardiac function, mice lacking the PI3K-γ (PI3K-γ-KO) underwent MI, and their cardiac function was assessed 20 wk post-MI. Serial echocardiographic measurements showed severe reduction in contractile performance in PI3K-γ-KO compared with TgPIK mice. Furthermore, significant β-AR downregulation and desensitization were only seen in infarcted wild-type and PI3K-γ-KO mice and not in TgPIK mice. Together, these results demonstrate that adverse remodeling of the ventricle after MI can be attenuated by a strategy that prevents recruitment of PI3K to the plasma membrane and restores normal β-AR function.