bluuebunny/crossref_metadata_2025 huggingface dataset:
Barrier-to-Autointegration Factor Phosphorylation on Ser-4 Regulates Emerin Binding to Lamin A In Vitro and Emerin Localization In Vivo
Authors: Bengtsson Luiza , Wilson Katherine L.
Published: December 2005

Barrier-to-autointegration factor (BAF) is a conserved 10-kDa chromatin protein essential in proliferating cells. BAF dimers bind double-stranded DNA, histone H3, histone H1.1, lamin A, and transcription regulators, plus emerin and other LEM-domain nuclear proteins. Two-dimensional gel analysis showed that endogenous human and Xenopus BAF are posttranslationally modified by phosphorylation and potentially other modifications and that they are hyperphosphorylated during mitosis. The invariant Ser-4 residue on BAF is a major site of phosphorylation during both interphase and mitosis. In HeLa cells that overexpressed the phosphomimetic BAF missense mutant S4E, but not S4A, emerin mislocalized from the nuclear envelope, suggesting Ser-4-nonphosphorylated BAF normally promotes emerin localization at the nuclear envelope. Supporting this model, wild-type BAF but not mutant S4E enhanced emerin binding to lamin A in vitro. Thus, Ser-4-unphosphorylated BAF has a positive role in localizing emerin; this role may be disease relevant because loss or mislocalization of emerin causes Emery–Dreifuss muscular dystrophy. Our findings further suggest Ser-4 phosphorylation inhibits BAF binding to emerin and lamin A, and thereby weakens emerin–lamin interactions during both mitosis and interphase.
LEARNING BY ASSOCIATION: MICRO CREDIT IN CHIAPAS, MEXICO
Authors: BARBOZA GUSTAVO A. , BARRETO HUMBERTO
Published: December 2005

Micro credit programs provide institutional arrangements for low‐income people to transit from nonmarket to market‐oriented settings. This article develops a data set of payment records to determine micro credit participants' behavior on repayment performance. The findings shed new light strongly supporting micro credit as a feasible alternative to successfully provide financial resources to the poor, when controlling for asymmetric information. The empirical evidence indicates that learning by association through peer mentoring is a significant determinant in explaining high repayment rates, whereas peer monitoring is not. (JEL O1, O17, L31, J15)
Pneumothorax in the Intensive Care Unit
Authors: de Lassence Arnaud , Timsit Jean-François , Tafflet Muriel , Azoulay Élie , Jamali Samir , Vincent François , Cohen Yves , Garrouste-Orgeas Maïté , Alberti Corinne , Dreyfuss Didier
Published: December 2005

Background

The risk factors and outcomes of critically ill patients with iatrogenic pneumothorax (IP) have not been studied in a large unselected intensive care unit (ICU) population.

Methods

The authors studied a prospective cohort of adults admitted for more than 24 h. Data were collected at ICU admission and daily by senior physicians until ICU discharge. Risk factors for IP were identified in the entire cohort. A matched nested case-control study was used to evaluate the excess risk of IP in decedents.

Results

Of the 3,499 patients, 69 with pneumothorax before ICU admission were excluded. Of the remaining 3,430 patients, 94 experienced IP within 30 days (42 due to barotrauma and 52 due to invasive procedures). The cumulative incidence of IP was 1.4% (95% confidence interval [CI], 1.0-1.8) on day 5 and 3.0% (95% CI, 2.4-3.6) on day 30. Risk factors for IP (hazard ratio [95% CI]) were body weight less than 80 kg (2.4 [1.3-4.2]), history of adult immunodeficiency syndrome (2.8 [1.2-6.4]), diagnosis of acute respiratory distress syndrome (5.3 [2.6-11]) or cardiogenic pulmonary edema at admission (2.0 [1.1-3.6]), central vein or pulmonary artery catheter insertion (1.7 [1.0-2.7]), and use of inotropic agents during the first 24 h (2.1 [1.3-3.4]). Excess risk of IP in decedents was 2.6 (95% CI, 1.3-4.9; P = 0.004).

Conclusion

Iatrogenic pneumothorax is a life-threatening complication seen in 3% of ICU patients. Incorporating risk factors for IP into preventive strategies should reduce the occurrence of IP.
Effects of Increasing Concentrations of Propofol on Jugular Venous Bulb Oxygen Saturation in Neurosurgical Patients under Normothermic and Mildly Hypothermic Conditions
Authors: Iwata Masato , Kawaguchi Masahiko , Inoue Satoki , Takahashi Masahiro , Horiuchi Toshinori , Sakaki Toshisuke , Furuya Hitoshi
Published: December 2005

Background

Recent evidence suggested that propofol can deteriorate the cerebral oxygen balance compared with inhalational anesthetics. However, dose-related influences of propofol on cerebral oxygen balances were not clearly investigated. In the current study, the authors investigated the effects of increasing concentrations of propofol on jugular venous bulb oxygen saturation (Sj(O2)) in neurosurgical patients under normothermic and mildly hypothermic conditions.

Methods

After institutional approval and informed consent were obtained, 30 adult patients undergoing elective craniotomy were studied. Patients were randomly allocated to either normothermic or hypothermic group (n = 15 in each group). In the normothermic and hypothermic groups, tympanic membrane temperature was maintained at 36.5 degrees and 34.5 degrees C, respectively. Sj(O2) was measured at predicted propofol concentrations of 3, 5, and 7 microg/ml using a target-controlled infusion system in both groups.

Results

At a predicted propofol concentration of 3 microg/ml, there were no significant differences in Sj(O2) values between the normothermic and hypothermic groups, although the incidence of desaturation (Sj(O2) < 50%) was significantly higher in the normothermic group than in the hypothermic group (30% vs. 13%; P < 0.05). Sj(O2) values and the incidence of desaturation remained unchanged during the changes in predicted propofol concentration from 3 to 7 microg/ml both in the normothermic and hypothermic groups.

Conclusion

The results indicated that the increasing concentrations of propofol did not affect Sj(O2) values in neurosurgical patients under normothermic and mildly hypothermic conditions.
Comparison of Two Techniques for Retrograde Tracheal Intubation in Human Fresh Cadavers
Authors: Lenfant François , Benkhadra Mehdi , Trouilloud Pierre , Freysz Marc
Published: December 2005

Background

During retrograde tracheal intubation, the short distance existing between the cricothyroid membrane and vocal cords may be responsible for accidental extubation. The insertion of a catheter into the trachea before the removal of the guide wire may help to cope with this problem. This work was conducted to study the impact of such a modification on the success rate and the duration of the procedure.

Methods

Procedures of retrograde tracheal intubation following the classic and modified techniques were randomly performed in cadavers (n = 70). The duration of the procedure from the puncture of the cricothyroid membrane to the inflation of the balloon of the endotracheal tube was measured, and, at the end of the procedure, the position of the endotracheal tube was checked under laryngoscopy. The procedure was considered to have failed if it had taken more than 5 min or when the endotracheal tube was not positioned in the trachea.

Results

The mean time to achieve tracheal intubation was similar in both groups (123 +/- 51 vs. 127 +/- 41 s; not significant), but intubation failed significantly more frequently with the classic technique (22 vs. 8 failures; P < 0.05). All failures were related to incorrect positioning of the endotracheal tube. In four cases, both techniques failed.

Conclusions

This efficient, simple modification of the technique significantly increases the success rate of the procedure, without prolonging its duration. These data should be confirmed in clinical conditions but may encourage a larger use of the retrograde technique in cases of difficult intubation.
Ultralong Peripheral Nerve Block by Lidocaine:Prilocaine 1:1 Mixture in a Lipid Depot Formulation
Authors: Söderberg Lars , Dyhre Henrik , Roth Bodil , Björkman Sven
Published: December 2005

Background

The aim of this study was to develop stable and easily injectable lipid depot preparations of local anesthetics in which the drug concentration can be varied according to desired duration of action.

Methods

The formulations contained a 2.0, 5.0, 10, 20, 40, 60, 80, or 100% eutectic mixture of lidocaine and prilocaine base in medium-chain triglyceride. Duration of sciatic nerve block and local neurotoxicity was investigated in rats with 2.0% lidocaine:prilocaine HCl solution and 99.5% ethanol as controls. The rate of release of local anesthetic from the site of administration and the possibility to predict in vivo depot characteristics from in vitro release data were investigated for the 20 and 60% formulations.

Results

The duration of sensory sciatic block was prolonged 3 times with the 20% formulation and approximately 180 times with the 60% formulation, in comparison with the 2% aqueous solution. With the 80 and 100% formulations, all animals still showed nerve block after 2 weeks. The in vivo release of local anesthetic could be approximately predicted from in vitro data for the 20% but not for the 60% formulation. The formulations of 60% or greater and ethanol showed neurotoxic effects.

Conclusions

The pharmaceutical properties of these formulations compare favorably with those of other depot preparations. The high-percentage ones showed the longest duration of action yet reported for sciatic nerve block in rats. The possibility of using a high-concentration local anesthetic depot formulation as an alternative to ethanol or phenol for long-term nerve blocks in chronic pain merits further investigation.
Increased Susceptibility to Ventilator-associated Lung Injury Persists after Clinical Recovery from Experimental Endotoxemia
Authors: Schreiber Torsten , Hueter Lars , Schwarzkopf Konrad , Hohlstein Sylvia , Schmidt Barbara , Karzai Waheedullah
Published: December 2005

Background

Endotoxin, when delivered shortly before or during mechanical ventilation, increases susceptibility to ventilation-associated lung injury. However, it is unclear whether increased susceptibility to ventilator-associated lung injury is still present after clinical recovery from a transient endotoxin challenge.

Methods

Anesthetized rats were submitted to a 4-h period of mechanical ventilation with low (8 ml/kg) or high (24, 27, or 30 ml/kg) tidal volumes (VTs) 24 h after transient illness had been provoked by a single nonlethal intravenous injection of Escherichia coli endotoxin. Control animals were injected with phosphate-buffered saline and underwent the same protocol.

Results

At 24 h, endotoxin-treated nonventilated animals showed no symptoms of clinical illness, and oxygenation was comparable with that of controls, but lung neutrophil counts were increased. Compared with controls, mechanical ventilation with high VT induced a stronger pulmonary inflammatory response and more severe lung injury in endotoxin-treated animals, as indicated by impaired oxygenation, increased lung wet-to-dry weight ratio, and increased levels of protein, neutrophils, and cytokines in lung lavage fluid. In addition, the highest VT resulted in increased mortality in endotoxin-treated animals. Low VT after endotoxin treatment did not cause functional pulmonary impairment but induced an inflammatory response.

Conclusions

In this animal model, a 24-h delay after a single systemic injection of endotoxin resulted in clinical recovery and preserved pulmonary function but did not prevent increased susceptibility to ventilator-associated lung injury provoked by high VT. Residual pulmonary inflammation and neutrophilic infiltration at initiation of mechanical ventilation probably contribute to these findings.
Thoracic Epidural versus Intravenous Patient-controlled Analgesia after Cardiac Surgery
Authors: Hansdottir Vigdis , Philip Julia , Olsen Monika Fagevik , Eduard Christina , Houltz Erik , Ricksten Sven-Erik
Published: December 2005

Background

Perioperative thoracic epidural analgesia reduces stress response and pain scores and may improve outcome after cardiac surgery. This prospective, randomized trial was designed to compare the effectiveness of patient-controlled thoracic epidural analgesia with patient-controlled analgesia with intravenous morphine on postoperative hospital length of stay and patients' perception of their quality of recovery after cardiac surgery.

Methods

One hundred thirteen patients undergoing elective cardiac surgery were randomly assigned to receive either combined thoracic epidural analgesia and general anesthesia followed by patient-controlled thoracic epidural analgesia or general anesthesia followed by to patient-controlled analgesia with intravenous morphine. Postoperative length of stay, time to eligibility for hospital discharge, pain and sedation scores, degree of ambulation, lung volumes, and organ morbidities were evaluated. A validated quality of recovery score was used to measure postoperative health status.

Results

Length of stay and time to eligibility for hospital discharge were similar between the groups. Study groups differed neither in postoperative global quality of recovery score nor in five dimensions of quality of recovery score. Time to extubation was shorter (P < 0.001) and consumption of anesthetics was lower in the patient-controlled thoracic epidural analgesia group. Pain relief, degree of sedation, ambulation, and lung volumes were similar between the study groups. There was a trend for lower incidences of pneumonia (P = 0.085) and confusion (P = 0.10) in the patient-controlled thoracic epidural analgesia group, whereas cardiac, renal, and neurologic outcomes were similar between the groups.

Conclusions

In elective cardiac surgery, thoracic epidural analgesia combined with general anesthesia followed by patient-controlled thoracic epidural analgesia offers no major advantage with respect to hospital length of stay, quality of recovery, or morbidity when compared with general anesthesia alone followed by to patient-controlled analgesia with intravenous morphine.
Gravity, the Belly, and the Diaphragm
Authors: Froese Alison B. , Raja Srinivasa N.
Published: December 2005

Using a radiologic technique, the position and pattern of movement of the diaphragm have been evaluated in three adult volunteers, both awake and anesthetized, during spontaneous ventilation and with muscle paralysis and mechanical ventilation. Studies were made with the subjects in supine and left lateral decubitus positions with tidal and large-volume breaths. Positive end-expiratory pressure (PEEP) was added in studies of two subjects. During spontaneous ventilation awake or anesthetized, because of regional mechanical advantages, the dependent part of the diaphragm had the greatest displacement despite the higher intraabdominal pressure in this region. Paralysis, awake or anesthetized, caused a cephalad shift of the end-expiratory position of the diaphragm that was disproportionately large in dependent regions. It also reversed the pattern of diaphragmatic displacement. The passive diaphragm was displaced preferentially in nondependent zones where abdominal pressure is least. Consequently, PEEP could not restore the diaphragm to its awake functional residual capacity position, and large breaths also could not duplicate the pattern of displacement achieved spontaneously.
Chromosomal mapping of 170 BAC clones in the ascidian Ciona intestinalis
Authors: Shoguchi Eiichi , Kawashima Takeshi , Satou Yutaka , Hamaguchi Makoto , Sin-I Tadasu , Kohara Yuji , Putnam Nik , Rokhsar Daniel S. , Satoh Nori
Published: December 2005

The draft genome (∼160 Mb) of the urochordate ascidian Ciona intestinalis has been sequenced by the whole-genome shotgun method and should provide important insights into the origin and evolution of chordates as well as vertebrates. However, because this genomic data has not yet been mapped onto chromosomes, important biological questions including regulation of gene expression at the genome-wide level cannot yet be addressed. Here, we report the molecular cytogenetic characterization of all 14 pairs of C. intestinalis chromosomes, as well as initial large-scale mapping of genomic sequences onto chromosomes by fluorescent in situ hybridization (FISH). Two-color FISH using 170 bacterial artificial chromosome (BAC) clones and construction of joined scaffolds using paired BAC end sequences allowed for mapping of up to 65% of the deduced 117-Mb nonrepetitive sequence onto chromosomes. This map lays the foundation for future studies of the protochordate C. intestinalis genome at the chromosomal level.
Identification of transposable elements using multiple alignments of related genomes
Authors: Caspi Anat , Pachter Lior
Published: December 2005

Accurate genome-wide cataloging of transposable elements (TEs) will facilitate our understanding of mobile DNA evolution, expose the genomic effects of TEs on the host genome, and improve the quality of assembled genomes. Using the availability of several nearly completeDrosophilagenomes and developments in whole genome alignment methods, we introduce a large-scale comparative method for identifying repetitive mobile DNA regions. These regions are highly enriched for transposable elements. Our method has two main features distinguishing it from other repeat-finding methods. First, rather than relying on sequence similarity to determine the location of repeats, the genomic artifacts of the transposition mechanism itself are systematically tracked in the context of multiple alignments. Second, we can derive bounds on the age of each repeat instance based on the phylogenetic species tree. We report results obtained using both complete and draft sequences of four closely relatedDrosophilagenomes and validate our results with manually curated TE annotations in theDrosophila melanogastereuchromatin. We show the utility of our findings in exploring both transposable elements and their host genomes: In the study of TEs, we offer predictions for novel families, annotate new insertions of known families, and show data that support the hypothesis that all known TE families inD. melanogasterwere recently active; in the study of the host, we show how our findings can be used to determine shifts in the eu-heterochromatin junction in the pericentric chromosome regions.
Capture of monomeric refolding intermediate of human muscle creatine kinase
Authors: Li Sen , Bai Ji‐Hong , Park Yong‐Doo , Zhou Hai‐Meng
Published: December 2005

Human muscle creatine kinase (CK) is an enzyme that plays an important physiological role in the energy metabolism of humans. It also serves as a typical model for studying refolding of proteins. A study of the refolding and reactivation process of guanidine chloride–denatured human muscle CK is described in the present article. The results show that the refolding process can be divided into fast and slow folding phases and that an aggregation process competes with the proper refolding process at high enzyme concentration and high temperature. An intermediate in the early stage of refolding was captured by specific protein molecules: the molecular chaperonin GroEL and αs‐casein. This intermediate was found to be a monomer, which resembles the “molten globule” state in the CK folding pathway. To our knowledge, this is the first monomeric intermediate captured during refolding of CK. We propose that aggregation is caused by interaction between such monomeric intermediates. Binding of GroEL with this intermediate prevents formation of aggregates by decreasing the concentration of free monomeric intermediates, whereas binding of αs‐casein with this intermediate induces more aggregation.
Parasitoids use herbivore‐induced information to adapt patch exploitation behaviour
Authors: Tentelier Cédric , Wajnberg Eric , Fauvergue Xavier
Published: December 2005

Abstract.  1. Optimal foraging models ultimately predict that female parasitoids should exploit rich host patches for longer than poorer ones. At the proximate level, mechanistic models and experimental studies show that parasitoids use both chemicals produced by their hosts and direct encounters with their hosts to estimate patch quality. Although it has been extensively studied in the context of host location, the use of herbivore‐induced plant response by insect parasitoids has never been considered in the context of patch time allocation.

2. In this study, the respective roles of herbivore‐induced plant response and direct contact with hosts on the foraging behaviour of Lysiphlebus testaceipes females on an aphid patch were quantified. For this, the level of herbivore‐induced plant response and the number of aphids on the leaf bearing the patch were manipulated independently. Different levels of plant response were obtained by varying the duration of infestation on another leaf.

3. Parasitoid residence time and number of attacks increased with both the level of plant response and the number of aphids.

4. These results suggest that L. testaceipes females use the combination of herbivore‐induced response of plants and direct encounters with hosts to assess patch quality and adjust their patch use behaviour.
Selection for discontinuous life‐history traits along a continuous thermal gradient in the butterflyAricia agestis
Authors: Burke Steve , Pullin Andrew S. , Wilson Robert J. , Thomas Chris D.
Published: December 2005

Abstract. 1. Voltinism may be conceptualised as the product of development rate and the timing of diapause – two components that together translate gradual environmental variation, through periods of growth and development, into ‘generational units’. This may result in very different selection pressures on diapause induction and development time in populations with different numbers of generations per year.

2. Developmental data from univoltine and bivoltine populations of the butterflyAricia agestis(Lepidoptera: Lycaenidae) in North Wales were used to examine larval development time and the timing of diapause, and their contribution towards voltinism in populations that occur at the same latitude and in geographic proximity to one another along a thermal gradient.

3. The critical photoperiod for diapause induction in univoltines and bivoltines from the same latitude differed by more than 1.5 h.

4. Development time also differed significantly between these populations, in line with predictions that bivoltines would need to exhibit shorter development times in order to achieve two complete generations per year. Shorter development times for bivoltines result in lower pupal weights, suggesting a trade‐off exists between generation number and body size that may dictate the position of the transition zone between the two life‐history strategies. Analysis of development times in a third population, from southern England, with greater thermal availability than those from North Wales, further supports this hypothesised trade‐off.

5. To achieve the conversion of a continuous thermal gradient into the binary biological response from univoltism to bivoltism, bivoltines speed up development, reduce adult body size and shift their diapause induction response.
Phenotypic plasticity in host‐plant specialisation in Aphis fabae
Authors: Gorur Gazi , Lomonaco Cecilia , Mackenzie Aulay
Published: December 2005

Abstract.  1. The study of phenotypic plasticity in host utilisation is crucial for predicting evolutionary patterns of insect – plant interactions. The presence of sufficient variation in plasticity may facilitate host race formation and sympatric speciation.

2. Aphis fabae genotypes showed high levels of phenotypic plasticity in the intrinsic rate of natural increase (rm), relative growth rate (RGR), birth weight (BW), adult weight (AW), fecundity (F), and development time (1/d).

3. Thirteen A. fabae genotypes reared both on broad bean and nasturtium exhibited statistically significant genotypic variability in phenotypic plasticity.

4. Some genotypes displayed fitness improvement on novel host plants.

5. Differences in genotypic correlation among fitness components between the two hosts and increased variance on nasturtium indicated different genomic expression on nasturtium.

6. The results indicated that phenotypic plasticity in a novel environment may be a major determinant of the evolutionary trajectory of a parasitic species and might support the idea that speciation starts with phenotypic plasticity.
Thermal biology of the meadow grasshopper, Chorthippus parallelus, and the implications for resistance to disease
Authors: Springate Simon , Thomas Matthew B.
Published: December 2005

Abstract.  1. The thermal biology of the meadow grasshopper, Chorthippus parallelus, a common, habitat generalist acridid species found in the U.K., was characterised and the influence of thermoregulatory behaviour for resistance against a temperate (Beauveria bassiana) and tropical (Metarhizium anisopliae var. acridum) fungal pathogen was determined.

2. Chorthippus parallelus was found to be an active behavioural thermoregulator, with a preferred temperature range of 32–35 °C.

3. Both pathogens proved lethal to fifth instar and adult grasshoppers. No evidence of behavioural fever in response to infection by either pathogen was found, but normal thermoregulation was found to reduce virulence and spore production of B. bassiana. Normal thermoregulation did not appear to affect M. anisopliae var. acridum.

4. These results suggest that the effects of temperature on host resistance depend on the thermal sensitivity of the pathogen and, in this case, derive from direct effects of temperature on pathogen growth rather than indirect effects mediated by host immune response.

5. The implications for possible risks of exotic pathogens and influence of climate change are discussed.
The effect of a probiotic drink with Lactobacillus plantarum 299v on the bacterial composition in faeces and mucosal biopsies of rectum and ascending colon
Authors: GOOSSENS D. A. M. , JONKERS D. M. A. E. , RUSSEL M. G. V. M. , STOBBERINGH E. E. , STOCKBRÜGGER R. W.
Published: December 2005

Background  Studies on probiotics mainly base their results on faecal samples, which may not represent the situation in the mucosa of distal and proximal colon.

Aim  In a placebo‐controlled study, to assess the effect of Lactobacillus plantarum 299v on the bacterial composition of faecal vs. mucosal samples.

Methods  Twenty‐nine patients undergoing colonoscopic examination for polyps consumed a twice‐daily drink with or without L. plantarum 299v (1011 CFU/day) for 2 weeks. Faecal samples were collected before and after consumption. During colonoscopy, biopsies were collected from the ascending colon and rectum. The faecal and mucosal bacterial concentrations and prevalence were determined.

Results  L. plantarum 299v significantly increased the concentration of faecal lactic acid bacteria, lactobacilli and clostridia, and was identified in two rectal biopsies but not in the ascending colon biopsies of probiotic‐treated subjects. Concentrations and prevalence in ascending colon and rectum biopsies were comparable, but were significantly lower compared with faecal samples.

Conclusions  After probiotic consumption, a significant increase in the faecal concentration of lactobacilli was found but concentrations were low in biopsies. The bacterial composition in biopsies of the ascending colon and rectum did not differ based on culture techniques. To further elucidate the modes of action of probiotics, it might be necessary to study differences in colonization with molecular techniques.
Upper gastrointestinal bleeding associated with antiplatelet drugs
Authors: IBÁÑEZ L. , VIDAL X. , VENDRELL L. , MORETTI U. , LAPORTE J. R. ,   THE SPANISH–ITALIAN COLLABORATIVE GROUP FOR THE EPIDEMIOLOGY OF GASTROINTESTINAL BLEEDING
Published: December 2005

Background  The risk of major upper gastrointestinal bleeding associated with various antiplatelet drugs and the protection conferred by gastroprotective agents are not well defined.

Aim  To estimate the risk of upper gastrointestinal bleeding associated with the use of antiplatelet drugs and its prevention by gastroprotective agents.

Methods  In a case‐control study, we compared all cases of upper gastrointestinal bleeding from a gastric or duodenal lesion in patients over 18 years of age (2813 cases), with 7193 matched controls. Odds ratios of upper gastrointestinal bleeding for individual antiplatelet drugs with adjustment for potential confounders were estimated.

Results  The individual risks of upper gastrointestinal bleeding were cardiovascular acetylsalicylic acid 4.0 (3.2–4.9), clopidogrel 2.3 (0.9–6.0), dipyridamole 0.9 (0.4–2.0), indobufen 3.8 (1.2–12.2), ticlopidine 3.1 (1.8–5.1) and triflusal 1.6 (0.9–2.7). Concomitant proton pump inhibitors decreased all risk estimates. For acetylsalicylic acid plus a proton pump inhibitor, the odds ratio was 1.1 (0.5–2.6). As a group, antiplatelet drugs accounted for 14.5% of all cases of upper gastrointestinal bleeding, i.e. 58 per million per year (334 per million per year among those older than 70 years).

Conclusions  The risk of upper gastrointestinal bleeding is substantially decreased by the concomitant use of proton pump inhibitors. The risk of acetylsalicylic acid plus a proton pump inhibitor seems lower than that of ticlopidine or clopidogrel.
Meta‐analysis: Smectite in the treatment of acute infectious diarrhoea in children
Authors: SZAJEWSKA H. , DZIECHCIARZ P. , MRUKOWICZ J.
Published: December 2005

Background  Although not currently recommended, dioctahedral smectite (smectite) is commonly used to treat acute infectious diarrhoea in many countries.

Aim  To evaluate systematically the effectiveness of smectite in treating acute infectious diarrhoea in children.

Methods  Using medical subject headings and free‐language terms, the following electronic databases were searched for studies relevant to acute infectious diarrhoea and smectite: MEDLINE, EMBASE, CINAHL and The Cochrane Library; additional references were obtained from reviewed articles. Only randomized‐controlled trials were included.

Results  Nine randomized‐controlled trials (1238 participants) met the inclusion criteria. Combined data from six randomized‐controlled trials showed that smectite significantly reduced the duration of diarrhoea compared with placebo. The pooled weighted mean difference was (−22.7 h, 95% CI: −24.8 to −20.6) with a fixed model and remained significant in a random effect model (−24.4 h, 95% CI: −29.8 to −19.1). The chance of cure on intervention day 3 was significantly increased in the smectite vs. the control group (RR 1.64, 95% CI: 1.36–1.98; number needed to treat 4, 95% CI: 3–5). Adverse effects were similar in both groups.

Conclusions  Smectite may be a useful adjunct to rehydration therapy in treating acute paediatric gastroenteritis. However, the results of this meta‐analysis should be interpreted with caution as most of the included studies had important limitations. Cost‐effectiveness analyses should be undertaken before routine pharmacological therapy with smectite is recommended.
Multiple cardiac arrests following an overdose of caffeine complicated by penetrating trauma
Authors: Emohare O. , Ratnam V.
Published: December 2005

A 28‐year‐old man was admitted following a massive caffeine overdose and a self inflicted gunshot wound in an apparent suicide attempt. Although initially stable on admission, he subsequently suffered multiple cardiac arrests and generalised seizures within 23 h of admission; over the next 48 h, he developed rhabdomyolysis. The importance of early management in caffeine overdose is highlighted.
Is influenza vaccination in asthmatic children helpful?
Authors: Bueving H. J.
Published: December 2005

The rationale for influenza vaccination in asthmatic children theoretically lies in prevention of exacerbations and serious complications like pneumonia. Solid evidence from randomized clinical trials of its preventive effects on these clinical endpoints is, however, lacking. Nevertheless, most Western guidelines advise to vaccinate these children. In the real life situation this advice isn't very well followed: vaccine coverage for this indication is low.

To assess the usefulness of influenza vaccination in children with asthma a set of fundamental questions regarding this activity is presented and answered. This leads to the conclusion that, given the evidence, influenza vaccination in children with mild to moderate disease should be reconsidered.
Lipoprotein lipase activity/mass ratio is higher in omental than in subcutaneous adipose tissue
Authors: Ruge T. , Sukonina V. , Myrnäs T. , Lundgren M. , Eriksson J. W. , Olivecrona G.
Published: December 2005

Background  Lipoprotein lipase (LPL) is important for lipid deposition in adipose tissue (AT) and responds rapidly to changes in the nutritional state. Animal experiments indicate that short‐term regulation of LPL is mainly post‐translational. Different processing of LPL in different AT depots may play a role in the distribution of lipids in the body.

Materials and methods  Lipoprotein lipase mRNA, mass and activity were measured in pieces of omental adipose tissue (OAT) and subcutaneous adipose tissue (SAT) from 15 subjects undergoing gastrointestinal surgery (four male and 11 female subjects, mean age 54 ± 5 years, BMI 28 ± 2 kg m−2).

Results  Lipoprotein lipase activity was higher in OAT than in SAT (18 ± 2.1 compared with 12 ± 1·6 mU g−1, P < 0·01), whereas LPL mass was lower in OAT than in SAT (100 ± 9 compared with 137 ± 16 mU g−1, P < 0·05). Consequently, the specific LPL activity (ratio of activity over mass) was approximately twofold greater in OAT compared with SAT. There was correlation between LPL mRNA and LPL activity in SAT (P < 0·05) and a similar tendency in OAT (P = 0·08). There were strong correlations (P < 0·01) for mRNA abundance as well as for LPL activity between the two depots. In contrast there was no correlation between the LPL mass and LPL mRNA or activity in any of the depots.

Conclusions  These results indicate that long‐term regulation, as reflected in the mRNA abundance, is similar in the two types of adipose tissue. The displayed activity reflects the mRNA abundance and the fraction of newly synthesized LPL molecules which the post‐translational mechanism allows to become/remain active. This fraction was on average twofold greater in OAT compared with SAT.
Impaired β‐cell function in lean normotolerant former gestational diabetic women
Authors: Tura A. , Mari A. , Winzer C. , Kautzky‐Willer A. , Pacini G.
Published: December 2005

Background  Former gestational diabetes (fGDM) constitutes a risk condition for the development of Type 2 diabetes. Former gestational diabetes is often characterized by obesity and hyperglycaemia, which may be concomitant and independent risk factors.

Materials and methods  To assess insulin sensitivity and β‐cell function in fGDM uncomplicated by obesity and hyperglycaemia, we studied 24 lean fGDM women and 23 control women matched for age (30·7 ± 0·7 years, whole cohort), body mass index (22·2 ± 0·3 kg m−2), and indistinguishable for plasma glucose both at fasting and at 120 min. Several insulin sensitivity and β‐cell function indices were computed: homeostasis model assessment insulin resistance index (HOMA‐R), insulin sensitivity index derived from an oral glucose tolerance test (OGIS), insulinogenic index, other empirical indices of insulin secretion and β‐cell function, and indices obtained using a β‐cell model.

Results  Though the majority of indices, and in particular insulin sensitivity (HOMA‐R: 1·35 ± 0·13 vs. 1·65 ± 0·14; OGIS: 492·7 ± 6·3 vs. 496·4 ± 9·4 mL min−1 m−2), were not significantly different in the two groups, the β‐cell glucose sensitivity obtained by modelling analysis was lower in fGDM (108 ± 14 vs. 165 ± 22 pmol min−1 m−2 mM−1, P = 0·031).

Conclusions  Impairment of β‐cell glucose sensitivity may be an intrinsic risk factor in fGDM independently of obesity and hyperglycaemia. Furthermore, we have shown that modelling analysis, in contrast to the empirical parameters, may be able to detect early β‐cell alterations in fGDM women.
CTLA‐4 interacts with STAT5 and inhibits STAT5‐mediated transcription
Authors: Srahna M. , Van Grunsven L. A. , Remacle J. E. , Vandenberghe P.
Published: December 2005

Cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4; CD152) is a member of the immunoglobulin gene superfamily with strong homology to the receptor CD28 with which it shares the ligands CD80 and CD86. Unlike CD28, a potent costimulator of T‐cell responses, CTLA‐4 is transiently expressed on the cell surface of activated T cells and appears to operate predominantly as a negative regulator of T‐cell proliferation. Signal transduction mechanisms utilized by CTLA‐4 remain unclear although several mechanisms have been implicated. In this study, we show that the cytoplasmic domain of CTLA‐4, but not of CD28, binds to STAT5 in yeast two‐hybrid assay and in coimmunoprecipitation assays. Mutations of Tyr165 and Tyr182 in CTLA‐4 did not abrogate the interaction of STAT5 with CTLA‐4. Finally, the overexpression of CTLA‐4 in Jurkat T cells inhibits STAT‐mediated activation of STAT5 responsive elements. These results suggest that CTLA‐4 and STAT5 interact in T cells and that this interaction is important for CTLA‐4 signalling.
Imbalance of regulatory T cells in human autoimmune diseases
Authors: Dejaco Christian , Duftner Christina , Grubeck‐Loebenstein Beatrix , Schirmer Michael
Published: December 2005

The breakdown of mechanisms assuring the recognition of self and non‐self is a hallmark feature of autoimmune diseases. In the past 10 years, there has been a steadily increasing interest in a subpopulation of regulatory T cells, which exert their suppressive function in vitro in a contact‐dependent manner and preferentially express high levels of CD25 and forkhead and winged‐helix family transcription factor forkhead box P3 (FOXP3) (TREGs). Recent findings of changed prevalences and functional efficiencies indicate that these TREGs play a unique role in autoimmune diseases. Clinical findings in patients with mutated FOXP3 genes and a specific polymorphism in the promotor region of FOXP3 also support the role of FOXP3 as a ‘master control gene’ in the development and functioning of TREGs. Both altered generation of TREGs and insufficient suppression of inflammation in autoimmune diseases are considered to be crucial for the initiation and perpetuation of disease. TREG‐related somatic cell therapy is considered as an intriguing new intervention to approach autoimmune diseases.
Double‐blind placebo‐controlled study of testosterone patch therapy on bone turnover in men with borderline hypogonadism
Authors: Merza Z. , Blumsohn A. , Mah P. M. , Meads D. M. , McKenna S. P. , Wylie K. , Eastell R. , Wu F. , Ross R. J. M.
Published: December 2005

Clinical studies suggest there may be a threshold concentration of serum testosterone below which replacement will result in skeletal and psychological benefit. We evaluated the response to testosterone in men with borderline hypogonadism. A randomized double‐blind placebo‐controlled trial in 39 men over age 40 years presenting with sexual dysfunction and a borderline low testosterone level (total testosterone <10 nmol/L or free androgen index <30%). Patients were randomized to Testoderm®TTS body patch (5 mg/day, n = 20) or a placebo patch (n = 19) for 6 months, followed by open‐label testosterone replacement for a further 6 months in all patients. During the placebo‐controlled phase of the study serum testosterone increased significantly on testosterone vs. placebo treatment (p = 0.004); this was associated with a decrease in total body fat mass (p = 0.019) and increase in haemoglobin level (p = 0.036). There were no significant changes in lean body mass, markers of bone turnover, and measures of bone mineral density (BMD). There was evidence of difference in quality of life according to the Male Erectile Dysfunction Quality of Life questionnaire (MEDQoL score, p = 0.017), mainly accounted for by deterioration in the placebo arm. When the active treatment period was combined for placebo and testosterone groups, the within‐patient analysis showed a significant effect of testosterone to decrease markers of bone resorption (uNTX/Cr, p = 0.007; iFDPD/Cr, p = 0.0006) and to increase lean body mass (p = 0.001). There was little convincing evidence from this study that testosterone replacement is likely to have major benefit in men over age 40 years with borderline hypogonadism and sexual dysfunction. However, there was evidence of suppression in bone resorption and hence longer and larger studies are needed to examine its effect on BMD.
Expression of SpanX proteins in normal testes and in testicular germ cell tumours
Authors: SALEMI MICHELE , CALOGERO ALDO E. , CASTIGLIONE ROBERTO , TRICOLI DARIO , ASERO PAOLA , ROSA ROMEO , RAPPAZZO GIANCARLO , VICARI ENZO
Published: December 2005

We investigated the expression of the SpanX protein family in cells of normal testes and in testicular germ cell tumours, mainly seminomas and embryonal carcinomas, using an immunohistochemical approach. Most of the normal germ cells, belonging to spermatogonial and primary spermatocytic classes, showed a strong nuclear positivity. In contrast, post‐meiotic germ cells showed diffused cytoplasmic and sometimes also perinuclear localization of the signal. The vast majority of cells were also positive in eight seminomas, six embryonal cell carcinomas and one teratocarcinoma. In all seminomas, nuclei were either exclusively or preferentially labelled; whereas, the nuclear signal intensity decreased in parallel with the appearance of some cytoplasmic staining in embryonal carcinomas. In conclusion, these data suggest that the SpanX protein family is not exclusively expressed post‐meiotically and that seminomas and embryonal carcinomas may originate from SpanX‐positive carcinoma‐in‐situ cell.
Dynamic expression of the prion‐like protein Doppel in ovine testicular tissue
Authors: Espenes Arild , Harbitz Ingrid , Skogtvedt Susan , Fuglestveit Ragnhild , Berg Kjell A. , Dick Gunnar , Krogenaes Anette , Tranulis Michael A.
Published: December 2005

Transgenic knockout of the gene encoding the prion‐like protein Doppel (Dpl) leads to male infertility in mice. The precise role of Dpl in male fertility is still unclear, but sperm from Dpl‐deficient mice appear to be unable to undergo the normal acrosome reaction that is necessary to penetrate the zona pellucida of the ovum. We have investigated the expression pattern and some biochemical properties of Dpl in sheep testicular tissue and spermatozoa. Neither the Dpl protein nor its mRNA was detected in pre‐pubertal sheep testis. This was in contrast to the findings in adult rams where both Dpl mRNA and protein were present. The molecular mass and glycosylation pattern of sheep Dpl were similar to that of mice Dpl. The Dpl protein was detected in the seminiferous epithelium during the two final (7 and 8) and the two initial (1 and 2) stages of the spermatogenic cycle in a characteristic pattern. In stage 8, an intense brim of granular Dpl‐immunoreactivity associated with maturation phase spermatids was observed, while after the release of spermatozoa in stages 1 and 2, the Dpl‐staining was disseminated more diffusely in the epithelium, reaching the basal lamina. From stage 3 to stage 6, Dpl‐immunoreactivity could not be detected, indicating that the Dpl protein had disappeared between stages 2 and 3. Dpl was not detected on ejaculated spermatozoa. These patterns of staining indicate that Dpl is enriched in residual bodies, which are phagocytosed and destroyed by Sertoli cells after release of sperm into the lumen of the seminiferous tubule.
Habitat selection by chironomid larvae: fast growth requires fast food
Authors: DE HAAS ELSKE M. , WAGNER COEN , KOELMANS ALBERT A. , KRAAK MICHIEL H. S. , ADMIRAAL WIM
Published: December 2005

Sediments have been considered as a habitat, a cover from predators and a source of food, but also as a source of potential toxic compounds. Therefore, the choice of a suitable substrate is essential for the development of chironomids.

For the midge Chironomus riparius (Meigen 1804) the growth rate of larvae has often been related to the food quality in sediments rather than to the amount of toxicants in the sediment. Both food quality and sediment‐bound toxicants have been reported to determine the field distribution of chironomid larvae.

We therefore studied the habitat selection by C. riparius larvae of floodplain lake sediments, differing in both food quality and concentrations of sediment‐bound toxicants. We offered the different sediments pairwise to the chironomid larvae in a choice experiment and their settlement in the paired sediments was determined after 10 days.

It was observed that larvae showed a clear preference for sediments with higher food quality, which also provided better growth conditions, and that the food quality overruled avoidance of the sediments with higher toxicant concentrations.

Our observations correspond with the persistence of this fast growing opportunistic chironomid species in organically enriched aquatic ecosystems independent of the contamination level.
Targeting of two effector protein classes to the type III secretion system by a HpaC‐ and HpaB‐dependent protein complex from Xanthomonas campestris pv. vesicatoria
Authors: Büttner Daniela , Lorenz Christian , Weber Ernst , Bonas Ulla
Published: December 2005

The Gram‐negative plant pathogenic bacterium Xanthomonas campestris pv. vesicatoria translocates effector proteins via a specialized type III secretion (TTS) system into the host cell cytosol. The efficient secretion of many effector proteins depends on the global TTS chaperone HpaB. Here, we identified a novel export control protein, HpaC, which significantly contributes to bacterial pathogenicity. Deletion of hpaC leads to a severe reduction in secretion of effector proteins and the putative type III translocon proteins HrpF and XopA. By contrast, secretion of the TTS pilus protein HrpE is not affected. We provide experimental evidence that HpaC differentiates between two classes of effector proteins. Using an in vivo reporter assay, we found that HpaC specifically promotes the translocation of the effector proteins XopJ and XopF1 into the plant cell, whereas AvrBs3 and XopC are efficiently translocated even in the absence of HpaC. Similar findings were obtained for HpaB. Inhibition of protein synthesis suggests that HpaB is involved in the secretion of stored effector proteins. Furthermore, protein–protein interaction studies revealed that HpaB and HpaC form an oligomeric protein complex and that they interact with members of both effector protein classes and the conserved TTS system component HrcV. Taken together, our data indicate that HpaB and HpaC play a central role in recruiting TTS substrates to the secretion apparatus.