bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in smoking behaviour between 1985 and 2000 in nine European countries by education
Authors: Giskes K , Kunst A E , Benach J , Borrell C , Costa G , Dahl E , Dalstra J A A , Federico B , Helmert U , Judge K , Lahelma E , Moussa K , Ostergren P O , Platt S , Prattala R , Rasmussen N K , Mackenbach J P
Published: April 2005

Objective:To examine whether trends in smoking behaviour in Western Europe between 1985 and 2000 differed by education group.

Design:Data of smoking behaviour and education level were obtained from national cross sectional surveys conducted between 1985 and 2000 (a period characterised by intense tobacco control policies) and analysed for countries combined and each country separately. Annual trends in smoking prevalence and the quantity of cigarettes consumed by smokers were summarised for each education level. Education inequalities in smoking were examined at four time points.

Setting:Data were obtained from nine European countries: Norway, Sweden, Denmark, Finland, the United Kingdom, the Netherlands, Germany, Italy, and Spain.

Participants:451 386 non-institutionalised men and women 25–79 years old.

Main outcome measures:Smoking status, daily quantity of cigarettes consumed by smokers.

Results:Combined country analyses showed greater declines in smoking and tobacco consumption among tertiary educated men and women compared with their less educated counterparts. In country specific analyses, elementary educated British men and women, and elementary educated Italian men showed greater declines in smoking than their more educated counterparts. Among Swedish, Finnish, Danish, German, Italian, and Spanish women, greater declines were seen among more educated groups.

Conclusions:Widening education inequalities in smoking related diseases may be seen in several European countries in the future. More insight into effective strategies specifically targeting the smoking behaviour of low educated groups may be gained from examining the tobacco control policies of the UK and Italy over this period.
Physical functioning in elderly Europeans: 10 year changes in the north and south: the HALE project
Authors: Äijänseppä Sinikka , Notkola Irma-Leena , Tijhuis Marja , van Staveren Wija , Kromhout Daan , Nissinen Aulikki
Published: April 2005

Objectives:To examine age related changes in physical functioning in elderly men and women.

Design:Prospective, population based study.

Setting:Population of 15 rural and urban centres in 10 European countries.

Participants:Altogether 3496 men and women born between 1900 and 1920 who participated in the baseline survey of the HALE project in 1988–1991. The study population was examined again about five (in 1993–1995) and 10 (in 1999–2001) years after the baseline examination.

Main outcome measures:Physical functioning was measured by means of a self administered questionnaire of activities of daily living (ADL). Dichotomised prevalence of disability and need for help in self care and mobility ADL were used as dependent variables in the analyses.

Results:Prevalence of disability and need for help tended to be higher in women than in men and in mobility abilities than in self care activities. Disability and need for help increased with advancing age but ameliorated over time from one birth cohort to another. In longitudinal analyses this beneficial time trend was independent of the effect of age, study, and region in self care disability in men and women (OR 0.85, 95% CI 0.75 to 0.97 and OR 0.64, 95% CI 0.43 to 0.97, respectively) and self care need for help in men (OR 0.83, 95% CI 0.70 to 0.96). Mobility disability among men and self care disability among women decreased more in the south than in the north.

Conclusion:While European populations are aging, the proportions of elderly people with disability are decreasing. These results suggest that dynamics of functioning may differ across cultures. Future studies are needed to clarify which potentially modifiable and culturally determined factors protect against functional decline.
Proton-sensing G protein-coupled receptor mobilizes calcium in human synovial cells
Authors: Christensen Burgess N. , Kochukov Mikhail , McNearney Terry A. , Taglialatela Giulio , Westlund Karin N.
Published: April 2005

Lowered extracellular pH in a variety of tissues is associated with increased tissue destruction and initiation of inflammatory processes. Although the acid-sensing receptors described previously are ion channels, we describe a G protein-coupled proton-sensitive receptor that stimulates Ca2+ release from intracellular stores in a tumor-derived synoviocyte cell line (SW982) and in primary cultures of human synovial cells from patients with inflammatory arthropathies. We established a link between proton-dependent receptor activation and intracellular Ca2+ mobilization by demonstrating 1) dependence on the integrity of the intracellular Ca2+ store, 2) independence from extracellular Ca2+, and 3) proton-induced production of inositol phosphate and 4) by abolishing the effect with GTPase inhibitors. We propose that this G protein-coupled acid-sensing receptor linked to intracellular Ca2+ mobilization in synoviocytes can contribute to downstream inflammatory and cellular proliferative processes in synovial fibroblasts. The acid-sensing receptor has distinct characteristics as a metabotropic G protein-coupled receptor on human synoviocytes in this emerging new class of receptors.
PYK2 regulates SERCA2 gene expression in neonatal rat ventricular myocytes
Authors: Heidkamp Maria C. , Scully Brian T. , Vijayan Kalpana , Engman Steven J. , Szotek Erika L. , Samarel Allen M.
Published: April 2005

The nonreceptor protein tyrosine kinase (PTK) proline-rich tyrosine kinase 2 (PYK2) has been implicated in cell signaling pathways involved in left ventricular hypertrophy and heart failure, but its exact role has not been elucidated. In this study, replication-defective adenoviruses (Adv) encoding green fluorescent protein (GFP)-tagged, wild-type (WT), and mutant forms of PYK2 were used to determine whether PYK2 overexpression activates MAPKs, and downregulates SERCA2 mRNA levels in neonatal rat ventricular myocytes (NRVM). PYK2 overexpression significantly decreased SERCA2 mRNA (as determined by Northern blot analysis and real-time RT-PCR) to 54 ± 4% of Adv-GFP-infected cells 48 h after Adv infection. Adv-encoding kinase-deficient (KD) and Y402F phosphorylation-deficient mutants of PYK2 also significantly reduced SERCA2 mRNA (WT>KD>Y402F). Conversely, the PTK inhibitor PP2 (which blocks PYK2 phosphorylation by Src-family PTKs) significantly increased SERCA2 mRNA levels. PYK2 overexpression had no effect on ERK1/2, but increased JNK1/2 and p38MAPK phosphorylation from fourfold to eightfold compared with GFP overexpression. Activation of both “stress-activated” protein kinase cascades appeared necessary to reduce SERCA2 mRNA levels. Adv-mediated overexpression of constitutively active (ca)MKK6 or caMKK7, which activated only p38MAPK or JNKs, respectively, was not sufficient, whereas combined infection with both Adv reduced SERCA2 mRNA levels to 45 ± 12% of control. WTPYK2 overexpression also significantly reduced SERCA2 promoter activity, as determined by transient transfection of a 3.8-kb SERCA2 promoter-luciferase construct. Thus a PYK2-dependent signaling cascade may have a role in abnormal cardiac Ca2+ handling in left ventricular hypertrophy and heart failure via downregulation of SERCA2 gene transcription.
Inhibition of signal termination-related kinases by membrane-permeant bitter and sweet tastants: potential role in taste signal termination
Authors: Zubare-Samuelov Meirav , Shaul Merav E. , Peri Irena , Aliluiko Alexander , Tirosh Oren , Naim Michael
Published: April 2005

Sweet and bitter taste sensations are believed to be initiated by the tastant-stimulated T1R and T2R G protein-coupled receptor (GPCR) subfamilies, respectively, which occur in taste cells. Although such tastants, with their significantly diverse chemical structures (e.g., sugar and nonsugar sweeteners), may share the same or similar T1Rs, some nonsugar sweeteners and many bitter tastants are amphipathic and produce a significant delay in taste termination (lingering aftertaste). We report that such tastants may permeate rat taste bud cells rapidly in vivo and inhibit known signal termination-related kinases in vitro, such as GPCR kinase (GRK)2, GRK5, and PKA. GRK5 and perhaps GRK2 and GRK6 are present in taste cells. A new hypothesis is proposed in which membrane-permeant tastants not only interact with taste GPCRs but also interact intracellularly with the receptors' downstream shutoff components to inhibit signal termination.
Angiotensin depolarizes parvocellular neurons in paraventricular nucleus through modulation of putative nonselective cationic and potassium conductances
Authors: Latchford Kevin J. , Ferguson Alastair V.
Published: April 2005

Neurosecretory parvocellular neurons in the hypothalamic paraventricular nucleus (PVN) exercise considerable influence over the adenohypophysis and thus play a critical role in neuroendocrine regulation. ANG II has been demonstrated to act as a neurotransmitter in PVN, exerting significant impact on neuronal excitability and also influencing corticotrophin-releasing hormone secretion from the median eminence and, therefore, release of ACTH from the pituitary. We have used whole cell patch-clamp techniques in hypothalamic slices to examine the effects of ANG II on the excitability of neurosecretory parvocellular neurons. ANG II application resulted in a dose-dependent depolarization of neurosecretory neurons, a response that was maintained in tetrodotoxin (TTX), suggesting a direct mechanism of action. The depolarizing actions of this peptide were abolished by losartan, demonstrating these effects are AT1 receptor mediated. Voltage-clamp analysis using slow voltage ramps revealed that ANG II activates a voltage-independent conductance with a reversal potential of −37.8 ± 3.8 mV, suggesting ANG II effects on a nonselective cationic current. Further, a sustained potassium current characteristic of IK was significantly reduced (29.1 ± 4.7%) by ANG II. These studies identify multiple postsynaptic modulatory sites through which ANG II can influence the excitability of neurosecretory parvocellular PVN neurons and, as a consequence of such actions, control hormonal secretion from the anterior pituitary.
In Vivo Analysis of Proprioceptive Coding and Its Antidromic Modulation in the Freely Behaving Crayfish
Authors: Le Ray Didier , Combes Denis , Déjean Cyril , Cattaert Daniel
Published: April 2005

Although sensory nerves in vitro are known to convey both orthodromic (sensory) and antidromic (putatively modulating) action potentials, in most cases very little is known about their bidirectional characteristics in intact animals. Here, we have investigated both the sensory coding properties and antidromic discharges that occur during real walking in the freely behaving crayfish. The activity of the sensory nerve innervating the proprioceptor CBCO, a chordotonal organ that monitors both angular movement and position of the coxo-basipodite (CB) joint, which is implicated in vertical leg movements, was recorded chronically along with the electromyographic activity of the muscles that control CB joint movements. Two wire electrodes placed on the sensory nerve were used to discriminate orthodromic from antidromic action potentials and thus allowed for analysis of both sensory coding and antidromic discharges. A distinction is proposed between 3 main classes of sensory neuron, according to their firing in relation to levator muscle activity during free walking. In parallel, we describe 2 types of antidromic activity: one produced exclusively during motor activity and a second produced both during and in the absence of motor activity. A negative correlation was found between the activity of sensory neurons in each of the 3 classes and identified antidromic discharges during walking. Finally, a state-dependent plasticity of CBCO nerve activity has been found by which the distribution of sensory orthodromic and antidromic activity changes with the physiological state of the biomechanical apparatus.
Rehabilitation versus Control: An Organizational Theory of Prison Management
Authors: Craig Susan Clark
Published: April 2005

Traditionally, the organizational effectiveness of prisons has been seen in terms of control, rather than rehabilitation, of inmates. Consequently, control-oriented organizational models have been presumed to be the most effective. Historical and contemporary prison management models are discussed. It is suggested that control-oriented models have had an inhibitory effect on the performance of other organizational goals of prisons, notably those of rehabilitation and treatment. Implications of control-oriented organizational models for the management of personnel working in the prison are examined, as are the potential impacts of such models on the delivery of rehabilitation services by private-sector providers.
Tissue Penetration of Cefpodoxime and Cefixime in Healthy Subjects
Authors: Liu Ping , Müller Markus , Grant Maria , Obermann Bernd , Derendorf Hartmut
Published: April 2005

Microdialysis is a technique that allows the measurement of free antibiotic concentrations in different tissues, which are responsible for the antibacterial activity at the infection site. In an open, randomized, 2‐way crossover study in healthy volunteers, the muscle penetration of orally administered cefpodoxime (400 mg) and cefixime (400 mg) was compared using microdialysis. The results show that the total plasma concentration‐time profiles of each antibiotic were similar; the area under the curve for cefpodoxime was 22.4 ± 8.7 versus 25.6 ± 8.5 mg/L•h for cefixime. However, tissue penetration was twice as high for cefpodoxime (area under the curve 15.4 ± 5.1 mg/L•h) as for cefixime (area under the curve 7.3 mg/L•h). This degree of tissue distribution is consistent with their protein binding of 21% for cefpodoxime and 65% for cefixime. After equilibration, the unbound tissue concentrations of both antibiotics were similar to their unbound plasma concentrations. Pharmacokinetic modeling was applied to describe the pharmacokinetic profiles in plasma and muscle. The study demonstrates that cefpodoxime shows greater tissue penetration than cefixime.
Pharmacokinetics of an Oral Drug (Acetaminophen) Administered at Various Times in Relation to Subcutaneous Injection of Exenatide (Exendin‐4) in Healthy Subjects
Authors: Blase Erich , Taylor Kristin , Gao Hong‐ye , Wintle Matthew , Fineman Mark
Published: April 2005

Exenatide is an incretin mimetic with potential glucoregulatory activity in type 2 diabetes. This randomized, single‐blind, placebo‐controlled 6‐way crossover study assessed exenatide's effect on acetaminophen pharmacokinetics. Of 40 randomized healthy subjects, 39 completed the study. On the placebo day, acetaminophen (1000 mg) was ingested and placebo injected subcutaneously at 0 hours. On exenatide days, acetaminophen was ingested at −1, 0, +1, +2, and +4 hours, relative to the 10 μg exenatide injected subcutaneously at 0 hours. With exenatide injection, mean plasma acetaminophen AUC0–12 h values were reduced by 11% to 24% (vs placebo). Peak plasma acetaminophen concentrations were similar for the −1‐hour and placebo groups and reduced by 37% to 56% at other times. The most frequent adverse events were generally mild to moderate nausea and vomiting. Exenatide treatment concurrent with or preceding acetaminophen ingestion slowed acetaminophen absorption but had minimal effect on the extent of absorption.
Pharmacokinetic Profile of the Oral Direct Thrombin Inhibitor Dabigatran Etexilate in Healthy Volunteers and Patients Undergoing Total Hip Replacement
Authors: Stangier Joachim , Eriksson Bengt I. , Dahl Ola E. , Ahnfelt Lennart , Nehmiz Gerhard , Stähle Hildegard , Rathgen Karin , Svärd Robbyna
Published: April 2005

Dabigatran etexilate is an oral low‐molecular‐weight direct thrombin inhibitor. Following oral administration, dabigatran etexilate is rapidly converted to its active form, dabigatran. The authors investigated the absorption, distribution, and elimination of a single 150‐mg dose capsule formulation of dabigatran etexilate in healthy volunteers and patients undergoing total hip replacement. In an open‐label, 3‐way crossover study, dabigatran etexilate was administered to 18 male volunteers in the fasted state, after administration of food and with coadministration of the proton pump inhibitor, pantoprazole. In a subsequent multicenter, open‐label study, 59 patients received a single dose of dabigatran etexilate, administered 1 to 3 hours following total hip replacement. In healthy volunteers, food had no effect on the extent of absorption of dabigatran etexilate, although there was reduced interindividual variability for dabigatran maximum plasma concentration and AUC0‐∞. A decrease in the mean dabigatran AUC0‐∞ (904 to 705 ng•h/mL) occurred with coadministration of pantoprazole. In patients undergoing total hip replacement, immediate onset of absorption was seen with the maximum plasma concentration of dabigatran occurring after 6 hours. The AUC0–24 of dabigatran was 88% of the steady‐state AUC using a preliminary tablet formulation and 106% of that seen in the healthy volunteer study. Compared with healthy volunteers, the postoperative profile was flattened with delayed peak concentrations. In summary, administration of the dabigatran etexilate capsule with food has no effect on the extent of dabigatran absorption, with a moderate decrease when coadministered with pantoprazole. Adequate plasma concentrations of dabigatran were seen with early postoperative administration of the dabigatran etexilate capsule. These pharmacokinetic characteristics confirm the suitability of this oral solid dosage form for use in future clinical trials.
Politics of Intraexecutive Conflict in Semipresidential Regimes in Eastern Europe
Authors: Protsyk Oleh
Published: April 2005

This article analyzes the patterns of intraexecutive conflict and cooperation in East European democracies that adopted semipresidential constitutional frameworks. It explores how the coexistence of popularly elected presidents and prime ministers is shaped by constitutional provisions, parliamentary fragmentation, and party system characteristics. The article emphasizes a critical role that party systems play in the evolution of intraexecutive relations across the region. It argues that variations in the political status of the cabinet, in the character of parliamentary composition, and in the constitutional powers of the president affect both the type and frequency of intraexecutive conflict experienced by semipresidential regimes.
“Democracy” without a Demos? The Bosnian Constitutional Experiment and the Intentional Construction of Nonfunctioning States
Authors: Hayden Robert M.
Published: April 2005

The social science literature on ethnically divided states is huge and varied, but suggestions for constitutional solutions are strangely uniform: “loose federations” of ethnically defined ministates, with minimal central authority that must act by consensus and thus cannot act at all on issues that are contested rather than consented. In Bosnia, the political system mandated by the international High Representative suffer the same structural flaws that were used to make the former Yugoslav federation and the Socialist Republic of Bosnia and Herzegovina unworkable. Similarly nonviable systems were proposed in 1994 to 1995 for Croatia and in 1998 to 1999 for Kosovo and recently for Cyprus and for Iraq. This article analyzes the paradox of mandating consensus-based politics in ethnically divided states, inclusion in which does not have the consent of most members of at least one group.
Titanium dioxide particle – induced goblet cell hyperplasia : association with mast cells and IL-13
Authors: Ahn Mi-Hyun , Kang Chun-Mi , Park Choon-Sik , Park Sang-Jun , Rhim Taiyoun , Yoon Pyeong-Oh , Chang Hun Soo , Kim Soo-Ho , Kyono Hiroko , Kim Kwang Chul
Published: April 2005

Background

Inhalation of particles aggravates respiratory symptoms including mucus hypersecretion in patients with chronic airway disease and induces goblet cell hyperplasia (GCH) in experimental animal models. However, the underlying mechanisms remain poorly understood.

Methods

To understand this, the numbers of goblet cells, Muc5ac (+) expressing epithelial cells and IL-13 expressing mast cells were measured in the trachea of sham or TiO2 particles – treated rats using periodic acid-Schiff, toluidine blue and immunohistochemical staining. RT-PCR for Muc-1, 2 and 5ac gene transcripts was done using RNA extracted from the trachea. Differential cell count and IL-13 levels were measured in bronchoalveolar lavage (BAL) fluid. In pretreatment groups, cyclophosphamide (CPA) or dexamethasone (DEX) was given before instillation of TiO2. TiO2 treatment markedly increased Muc5ac mRNA expression, and Muc5ac (+) or PAS (+) epithelial cells 48 h following treatment.

Results

The concentration of IL-13 in BAL fluids was higher in TiO2 treated – rats when compared to those in sham rats (p < 0.05). Pretreatment with cyclophosphamide (CPA) decreased the number of neutrophils and eosinophils in BAL fluid of TiO2 treated – rats (p < 0.05), but affected neither the percentage of PAS (+) cells, nor IL-13 levels in the BAL fluids (p > 0.05). In contrast, pretreatment with dexamethasone (DEX) diminished the percentage of PAS (+) cells and the levels of IL-13 (p < 0.05). TiO2 treatment increased the IL-13 (+) mast cells (p < 0.05) in the trachea, which was suppressed by DEX (p < 0.05), but not by CPA pretreatment (p > 0.05). In addition there were significant correlations of IL-13 (+) rate of mast cells in the trachea with IL-13 concentration in BAL fluid (p < 0.01) and with the percentage of Muc5ac (+) cells in the sham and TiO2 treated rats (p < 0.05).

Conclusion

In conclusion, TiO2 instillation induces GCH and Muc5ac expression, and this process may be associated with increased production of IL-13 by mast cells.
Good old days?
Authors: Greenberg Charles J
Published: April 2005

Alternative models of subsidizing scholarly publishing and dissemination have germinated and gathered momentum in the fertile soil of dissatisfaction. Like the stubborn spring dandelion that needs but a small crack in the sidewalk to flower boldly, the first flowers of Open Access in library literature, including Biomedical Digital Libraries, have sensed their opportunity to change the existing paradigm of giving away our scholarship and intellectual property, only to buy it back for the privilege of knowing it can be read. Will biomedical digital library and informatics researchers understand their role in a new era of Open Access simply by desiring an immediate uninhibited global audience and recognizing the necessity of open access peer-reviewed literature to become self-sufficient?
Differentiation- and maturation-dependent content, localization, and secretion of cystatin C in human dendritic cells
Authors: Zavašnik-Bergant Tina , Repnik Urška , Schweiger Ana , Romih Rok , Jeras Matjaž , Turk Vito , Kos Janko
Published: April 2005

Antigen-presenting cells (APC) play a pivotal role in the initiation of the T cell-mediated and antigen-specific immune response. The suggested role of endogenous inhibitor cystatin C (CyC) is to modulate cysteine proteases (cathepsins) present in human APC. To test this hypothesis, dendritic cells (DC) were generated in vitro from isolated monocytes, and changes in content, localization, and secretion of CyC and cathepsins S, L, and H (CatS, -L, and -H, repsectively) were followed in response to interleukin-4, enabling monocyte differentiation, and to tumor necrosis factor α (TNF-α), enabling DC maturation. A large increase in intracellular CyC accompanied the differentiation of monocytes to immature DC, also shown by strong immunolabeling of Golgi in immature DC. On DC maturation, intracellular CyC levels decreased, and CyC was mostly absent from the Golgi. On prolonged incubation of mature DC with TNF-α, CyC was found located in the proximity of the plasma membrane, indicating that the transport of CyC from Golgi was not blocked as the result of the arrested exocytosis in mature DC. The secretion of CyC ceased, consistent with the peak of the surface expression of phenotypic markers (CD40, CD54, CD80, CD83, CD86, and major histocompatibility complex class II), characteristic for the mature DC stage, whereas the secretion of cathepsins did not correlate with the maturation stage. The difference in localization of CyC and of CatS, -L, and -H in immature and mature DC shows that the regulatory potential of CyC toward CatS, -L, and -H inside DC is limited. However, these interactions may occur extracellularly in lymph, as suggested by the large excess of CyC over secreted CatS, -L, and -H, and they may facilitate DC migration to lymph nodes.
Two-person red-and-black with bet-dependent win probabilities
Authors: Pontiggia Laura
Published: April 2005

We present two variations of a two-person, noncooperative stochastic game, inspired by the famous red-and-black gambling problem presented by Dubins and Savage. Two players each hold an integer amount of money and they each aim to win the other player's fortune. At every stage of the game they simultaneously bid an integer portion of their current fortune, and their probabilities of winning depend on these bids. We describe two different laws of motion specifying this dependency. In one version of the game, the players' probabilities of winning are proportional to their bets. In the other version, the probabilities of winning depend on the size of their bets and a weight parameter w. For each version we give a Nash equilibrium, in which the player for which the game is subfair (w ≤ ½) plays boldly and the player for which the game is superfair (w ≥ ½) plays timidly.
Fractional random fields associated with stochastic fractional heat equations
Authors: Kelbert M. Ya. , Leonenko N. N. , Ruiz-Medina M. D.
Published: April 2005

This paper introduces a convenient class of spatiotemporal random field models that can be interpreted as the mean-square solutions of stochastic fractional evolution equations.
Gbx2is required for the morphogenesis of the mouse inner ear: a downstream candidate of hindbrain signaling
Authors: Lin Zhengshi , Cantos Raquel , Patente Maria , Wu Doris K.
Published: April 2005

Gbx2 is a homeobox-containing transcription factor that is related to unplugged in Drosophila. In mice, Gbx2 and Otx2 negatively regulate each other to establish the mid-hindbrain boundary in the neural tube. Here, we show that Gbx2 is required for the development of the mouse inner ear. Absence of the endolymphatic duct and swelling of the membranous labyrinth are common features in Gbx2-/- inner ears. More severe mutant phenotypes include absence of the anterior and posterior semicircular canals, and a malformed saccule and cochlear duct. However, formation of the lateral semicircular canal and its ampulla is usually unaffected. These inner ear phenotypes are remarkably similar to those reported in kreisler mice, which have inner ear defects attributed to defects in the hindbrain. Based on gene expression analyses, we propose that activation of Gbx2 expression within the inner ear is an important pathway whereby signals from the hindbrain regulate inner ear development. In addition, our results suggest that Gbx2 normally promotes dorsal fates such as the endolymphatic duct and semicircular canals by positively regulating genes such as Wnt2b and Dlx5. However, Gbx2 promotes ventral fates such as the saccule and cochlear duct, possibly by restricting Otx2 expression.
The ubiquitin ligaseDrosophilaMind bomb promotes Notch signaling by regulating the localization and activity of Serrate and Delta
Authors: Lai Eric C. , Roegiers Fabrice , Qin Xiaoli , Jan Yuh Nung , Rubin Gerald M.
Published: April 2005

The receptor Notch and its ligands of the Delta/Serrate/LAG2 (DSL) family are the central components in the Notch pathway, a fundamental cell signaling system that regulates pattern formation during animal development. Delta is directly ubiquitinated by Drosophila and Xenopus Neuralized,and by zebrafish Mind bomb, two unrelated RING-type E3 ubiquitin ligases with common abilities to promote Delta endocytosis and signaling activity. Although orthologs of both Neuralized and Mind bomb are found in most metazoan organisms, their relative contributions to Notch signaling in any single organism have not yet been assessed. We show here that a Drosophilaortholog of Mind bomb (D-mib) is a positive component of Notch signaling that is required for multiple Neuralized-independent, Notch-dependent developmental processes. Furthermore, we show that D-mib associates physically and functionally with both Serrate and Delta. We find that D-mib uses its ubiquitin ligase activity to promote DSL ligand activity, an activity that is correlated with its ability to induce the endocytosis and degradation of both Delta and Serrate (see also Le Borgne et al., 2005). We further demonstrate that D-mib can functionally replace Neuralized in multiple cell fate decisions that absolutely require endogenous Neuralized, a testament to the highly similar activities of these two unrelated ubiquitin ligases in regulating Notch signaling. We conclude that ubiquitination of Delta and Serrate by Neuralized and D-mib is an obligate feature of DSL ligand activation throughout Drosophiladevelopment.
The influence of postmenopausal hormone replacement therapy on cognitive functioning: results from an observational study
Authors: King Robert , Travers Catherine , O'Neill Sheila , Byrne Gerard , Khoo Soo Keat
Published: April 2005

Objectives: The aim of this study was to evaluate the impact of hormone replacement therapy (HRT) upon memory deficit in a group of urban Australian women.

Participants and setting: A cohort of 493 women aged 40-80 years was tested as part of the Longitudinal Study of Ageing in Women (LAW study) at the Royal Brisbane and Women's Hospital, Brisbane, Australia.

Main outcome measures: The current memory functioning of participants was evaluated using the Wechsler Memory Scale – version three (WMS-III) while pre-morbid cognitive functioning was estimated from scores on the National Adult Reading Test (NART). Memory deficit was estimated by comparing NART scores with the age-corrected scale scores of the WMS-III.

Results: Overall, NART scores correlated with WMS-III scores, consistent with the expected relationship between pre-morbid functioning and current functioning. For the sample as a whole, memory deficit was evident but mostly, age appropriate. There was considerable variation as to the extent of memory deficit within the sample. When memory functioning for women with a history of five or more years of combined oestrogen plus progestogen HRT or oestrogen replacement therapy (ERT) was compared with that of women who had never used HRT or ERT there was no evidence of any effect for either HRT or ERT on memory deficit.

Conclusions: The use of HRT or ERT had neither a protective nor an adverse effect on memory deficit.
Clinical nurse specialists and the psychosexual needs of patients with gynaecological cancer
Authors: Parkinson Nancy , Pratt Heather
Published: April 2005

Due to improved survival rates many women have been left with chronic problems following treatment for a gynaecological cancer. These include psychosexual issues, premature menopause and infertility. Common sexual problems may result from low self-esteem, loss of femininity, vaginal stenosis and dryness. In the UK, clinical nurse specialists are recognized as key members of the multidisciplinary teams required to care for women diagnosed with a gynaecological cancer. Their role in providing information and support with special reference to psychosexual problems is examined.
Vertebroplasty and kyphoplasty
Authors: Suresh Sri Priya , Whitehouse Richard W
Published: April 2005

Vertebral compression fractures are common in elderly populations and in particular in postmenopausal women as a consequence of osteoporosis. Percutaneous vertebroplasty and kyphoplasty are minimally invasive procedures that are increasingly used to treat persistent or severe acute pain from these fractures. Vertebroplasty works by augmenting the weak osteopenic vertebrae with polymethylmethacrylate (PMMA) bone cement and thus preventing further microfractures and associated pain. The aim of kyphoplasty is pain relief combined with restoration of vertebral body height and reduction in kyphosis. This is achieved by 'expanding' the fractured vertebra with a balloon and then filling of the resultant cavity with PMMA cement. Vertebroplasty and kyphoplasty are undertaken under local and general anaesthesia, respectively. Both procedures have a very low complication rate if properly performed by well trained clinicians using appropriate cement and technique and highquality imaging. Patient selection and the selection of the level at which the percutaneous vertebroplasty is to be done are of utmost importance for maximal therapeutic benefit. Additional trials are required to establish conclusively the effectiveness of both procedures compared with conservative medical therapy and each other.
Conjugated linoleic acid suppresses the secretion of atherogenic lipoproteins from human HepG2 liver cells
Authors: Pal Sebely , Takechi Ryusuke , Ho Suleen S.
Published: April 2005

Studies in healthy humans have shown that consumption of conjugated linoleic acid (CLA) significantly reduced very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) blood concentrations. We propose that decreased concentrations are due to the inhibition of VLDL production and secretion [measured by apolipoprotein B100 (apoB100)] from the liver. To investigate the effects of a mixture of CLA isomers on VLDL metabolism, HepG2 liver cells were incubated for 24h with 50μmol/L of the different fatty acids. Effects of CLA were compared to a saturated fatty acid (palmitic acid), an n-6 fatty acid (linoleic acid) and no treatment (control). HepG2-cell apoB100 levels were measured using Western blotting. ApoB100 secretion was significantly decreased in cells treated with CLA (44%, p<0.005) compared to control cells and those enriched with palmitic acid. Treatment of cells with CLA also decreased intracellular cholesterol levels. Collectively, these results demonstrate that CLA reduces apoB100 production and secretion compared to saturated and polyunsaturated fatty acids, possibly by limiting the availability of free cholesterol (required for apoB100 production). A reduction in apoB100 production in the body would decrease the levels of VLDL and atherogenic LDL and thus reduce the risk of developing cardiovascular disease.
Advanced oxidation protein products (AOPP) for monitoring oxidative stress in critically ill patients: a simple, fast and inexpensive automated technique
Authors: Selmeci László , Seres Leila , Antal Magda , Lukács Júlia , Regöly-Mérei Andrea , Acsády György
Published: April 2005

Oxidative stress is known to be involved in many human pathological processes. Although there are numerous methods available for the assessment of oxidative stress, most of them are still not easily applicable in a routine clinical laboratory due to the complex methodology and/or lack of automation. In research into human oxidative stress, the simplification and automation of techniques represent a key issue from a laboratory point of view at present. In 1996 a novel oxidative stress biomarker, referred to as advanced oxidation protein products (AOPP), was detected in the plasma of chronic uremic patients. Here we describe in detail an automated version of the originally published microplate-based technique that we adapted for a Cobas Mira Plus clinical chemistry analyzer. AOPP reference values were measured in plasma samples from 266 apparently healthy volunteers (university students; 81 male and 185 female subjects) with a mean age of 21.3years (range 18–33). Over a period of 18months we determined AOPP concentrations in more than 300 patients in our department. Our experiences appear to demonstrate that this technique is especially suitable for monitoring oxidative stress in critically ill patients (sepsis, reperfusion injury, heart failure) even at daily intervals, since AOPP exhibited rapid responses in both directions. We believe that the well-established relationship between AOPP response and induced damage makes this simple, fast and inexpensive automated technique applicable in daily routine laboratory practice for assessing and monitoring oxidative stress in critically ill or other patients.
Quality control in urinary stone analysis: results of 44 ring trials (1980–2001)
Authors: Hesse Albrecht , Kruse Rolf , Geilenkeuser Wolf-Jochen , Schmidt Matthias
Published: April 2005

Urinary stone analysis is the most important diagnostic step after stone removal from the body. The methods employed for these analyses are based on diverse analytical principles. Chemical methods are used for detecting individual ions. Infrared spectroscopy is used for examining molecular structures, and X-ray diffraction for determination of the crystalline structure of a substance. Since 1980, a twice-yearly ring trials quality control survey has been on offer to examine the quality of urinary stone analyses. A summary of the results of 44 ring trials (1980–2001) has been compiled for individual pure substances and binary (two-component) mixtures. On average, 100 laboratories have participated in these ring trials. Initially, over 80% of the participants carried out their analyses using chemical methods. In 2001, this figure decreased to a mere 13%. In contrast, a progressive increase in the use of infrared spectroscopy was observed, up to 79% of all participants employed this method. X-Ray diffraction was only employed in a small number of specialised laboratories (5–9%). The chemical methods produced a very high proportion of errors (6.5–94%) with both the pure substances and binary mixtures, whereas high error rates for infrared spectroscopy and X-ray diffraction were confined to individual substances only. Due to the poor results in the ring trials, the majority of laboratories stopped using chemical analysis, which is now considered to be obsolete. Regarding mixtures, error rates of over 10% also occurred with infrared spectroscopy and X-ray diffraction. Ring trials are indispensable for the quality management of urinary stone analysis.
The number of consultant clinical chemists in the 15-nation European Union
Authors: Smit Erik , Beastall Graham , Bjorses Ulla-Maj , Candito Mirande , Fiorentini Piero
Published: April 2005

The number of consultant clinical chemists (NCCC) in the 15-nation European Union (EU) (Austria, Belgium, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, The Netherlands, Portugal, Spain, Sweden, United Kingdom) has been ascertained. These data were analysed in relation to several established national parameters, including demographics, gross domestic product (GDP), cost of healthcare, cost of in vitro diagnostic (IVD) testing and the number of physicians and pharmacists. Large differences in the population-corrected costs of IVD testing (range ∼2.4-fold) and NCCC (range ∼30-fold) were observed between the countries, which could not be satisfactorily explained by any of the parameters assessed. The differences in IVD testing and NCCC might reflect different practices in laboratory medicine across the EU, but could not be estimated independently. In recognition of the different scope of laboratory medicine practised under the title of clinical chemistry, a simple staffing model was derived in an attempt to give a better estimate of the appropriate number of consultant laboratory medicine specialists. This model allocated a fixed number of laboratory specialists per million inhabitants for the five disciplines: clinical chemistry, 10; haematology, 10; serology, 7.5; microbiology, 12.5; and blood banking, 2. The staffing model also allowed for the contribution of the primary care sector by including one full-time consultant laboratory medicine specialist for each small private laboratory and two extra consultant laboratory specialists per million inhabitants where there are not large numbers of private laboratories. Application of the model to the available data helped to reduce the variation observed in the primary analysis of NCCC (range ∼9-fold) but still revealed important differences between countries. These differences could arise from the poor quality of published data as much as from true differences in laboratory medicine practice. We conclude that a more sophisticated analysis of laboratory practice and of all professionals working in laboratory medicine disciplines would be required before any conclusions could be drawn about relative staffing, efficiency or cost effectiveness. The staffing model derived is a first step towards objective estimation of the number of consultant laboratory specialists in the EU.
Estimativa de biomassa de sistemas agroflorestais das várzeas do rio juba, Cametá, Pará
Authors: Santos Silvio Roberto Miranda dos , Miranda Izildinha de Souza , Tourinho Manoel Malheiros
Published: April 2005

Este trabalho apresenta uma estimativa da biomassa seca (BS) acima do solo e estoque de carbono (EC) de sistemas agroflorestais (SAF) estudados nas várzeas do rio Juba, Cametá, Pará. A BS foi estimada pelo método indireto a partir dos dados de um inventário florestal realizado em sete parcelas de 0,25 ha (50 m x 50 m). Foram inventariados em média 2594 indivíduos/ha com DAP >5 cm. Euterpe oleracea Mart.(açaí) e Theobroma cacao L. (cacau), foram as espécies mais importantes e representaram 80 % dos indivíduos (54 % e 26 %, respectivamente) e as outras espécies (árvores) 20 %. Em média a BS dos SAF foi de 298,44 t/ha. O açaí apresentou BS de 4,47 t/ha (43 % nas folhas e 57 % nos estipes), o cacau 1,45 t/ha (18 % nas folhas e 82 % na madeira) e as árvores 292,52 t/ha (1 % nas folhas e 99 % na madeira). O EC contido na BS total média foi de 134,30 t/ha; as árvores estocaram 131,63 t/ha (98 %), o açaí 2,01 t/ha (1,5 %) e o cacau 0,65 t/ha (0,5 %). O EC médio dos SAF estudados (idade média de 12 anos) representou, em média, cerca de 96 % do carbono que é estocado numa floresta primária de terra firme; cerca de 62 % a mais do estocado em florestas secundárias enriquecidas (idade média de 26 meses) e 23 % a mais do estocado em florestas de várzeas na Amazônia brasileira.
Structure and composition of the ground-herb community in a terra-firme Central Amazonian forest
Authors: Costa Flávia Regina Capellotto
Published: April 2005

The herb community of tropical forests is very little known, with few studies addressing its structure quantitatively. Even with this scarce body of information, it is clear that the ground herbs are a rich group, comprising 14 to 40% of the species found in total species counts in tropical forests. The present study had the objective of increasing the knowledge about the structure and composition of the ground-herb community and to compare the sites for which there are similar studies. The study was conducted in a tropical non-inundated and evergreen forest 90 km north of Manaus, AM. Ground herbs were surveyed in 22 transects of 40 m², distributed in five plots of 4 ha. The inventoried community was composed of 35 species, distributed in 24 genera and 18 families. Angiosperms were represented by 8 families and Pteridophytes by 10 families. Marantaceae (12 sp) and Cyperaceae (4 sp) were the richest families. Marantaceae and Poaceae were the families with greatest abundance and cover. Marantaceae, Poaceae, Heliconiaceae and Pteridophytes summed 96% of total herb cover, and therefore were responsible for almost all the cover of the community. The 10 most important species had 83.7% of the individuals. In general, the most abundant species were also the most frequent. Richness per transect varied from 7 to 19 species, and abundance varied from 30 to 114 individuals. The community structure was quite similar to 3 other sites in South America and one site in Asia.
Screening of plants found in the State of Amazonas, Brazil for activity against Aedes aegypti larvae
Authors: Pohlit Adrian Martin , Quinard Etienne Louis Jacques , Nunomura Sergio Massayoshi , Tadei Wanderli Pedro , Hidalgo Ari de Freitas , Pinto Ana Cristina da Silva , Santos Elba Vieira Mustafa dos , Morais Sabrina Kelly Reis de , Saraiva Rita De Cássia Guedes , Ming Lin Chau , Alecrim Alexandre Mascarenhas , Ferraz Alfeu de Barros , Pedroso Andreza Cristiana da Silva , Diniz Elisangela Vieira , Finney Ellen Kathryn , Gomes Erika de Oliveira , Dias Hercules Bezerra , Souza Katiuscia dos Santos de , Oliveira Laura Cristina Pereira de , Don Luciana de Castro , Queiroz Maria Mireide Andrade , Henrique Marycleuma Campos , Santos Mirian dos , Lacerda Júnior Orivaldo da Silva , Pinto Patrícia de Souza , Silva Suniá Gomes , Graça Yara Rodrigues
Published: April 2005

Ethanol, methanol and water extracts representing mostly native plant species found in the Amazon region were prepared, respectively, by maceration, continuous liquid-solid extraction and infusion, followed by evaporation and freeze-drying. The freeze-dried extracts were tested for lethality toward Aedes aegypti larvae at test concentrations of 500 mg / mL. In general, methanol extracts exhibited the greatest larvicidal activity. The following 7 methanol extracts of (the parts of) the indicated plant species were the most active, resulting in 100% mortality in A. aegypti larvae: Tapura amazonica Poepp. (root), Piper aduncum L. (leaf and root), P. tuberculatum Jacq. (leaf, fruit and branch). and Simaba polyphylla (Cavalcante) W.W. Thomas (branch).
Reavaliação taxonômica de Colletotrichum guaranicola Albuq. agente causal da antracnose do guaranazeiro
Authors: Bentes Jânia Lília da Silva , Barreto Robert Weingart
Published: April 2005

Foi realizada uma reavaliação morfológica de estruturas reprodutivas e de infecção do agente causal da antracnose do guaranazeiro (Paullinia cupana var. sorbilis), visando confirmar a identidade do patógeno. Os resultados reforçam o reconhecimento da espécie Colletotrichum guaranicola Albuq., como um novo taxon dentro do gênero Colletotrichum.
O efeito da floresta alagada na alimentação de três espécies de peixes onívoros em lagos de várzea da Amazônia Central, Brasil
Authors: Claro-Jr Luiz , Ferreira Efrem , Zuanon Jansen , Araujo-Lima Carlos
Published: April 2005

As enchentes anuais dos rios na Amazônia alagam extensas áreas de floresta conhecidas como várzeas ou igapós. Estas áreas têm papel importante na vida dos peixes da região, pois são fontes de alimento e de abrigo. Acreditamos que o desmatamento destas áreas ocasiona prejuízos à ictiofauna principalmente pela diminuição da quantidade e diversidade de alimento disponível. O estudo da relação entre a quantidade de floresta e a dieta de Parauchenipterus galeatus (Auchenipteridae, Siluriformes), Mylossoma duriventre (Characidae, Characiformes)e Triportheus elongatus (Characidae, Characiformes)permitiu registrar pela primeira vez a influência direta da floresta alagada na ecologia alimentar de peixes na Amazônia Central.