bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of pollen‐related food allergens on pollen allergy
Authors: Bohle B.
Published: December 2006

Patients with birch pollen allergy frequently develop hypersensitivity reactions to certain foods, e.g. apples, celery, carrots and hazelnuts. These reactions are mainly caused by IgE‐antibodies specific for the major birch pollen allergen, Bet v 1, which cross‐react with homologous proteins in these foods. Analyzing the T‐cell response to Bet v 1‐related food allergens revealed that these dietary proteins contain several distinct T‐cell epitopes and activate Bet v 1‐specific T cells to proliferate and produce cytokines. Several of these cross‐reactive T‐cell epitopes were not destroyed by simulated gastrointestinal digestion of food allergens and stimulated Bet v 1‐specific T cells despite nonreactivity with IgE antibodies. Similarly, cooked food allergens did not elicit IgE‐mediated symptoms (oral allergy syndromes) but caused T‐cell‐mediated late‐phase reactions (deterioration of atopic eczema) in birch pollen‐allergic patients with atopic dermatitis because thermal processing affected their conformational structure and not the primary amino acid sequence. Thus, T‐cell cross‐reactivity between Bet v 1 and related food allergens occurs independently of IgE‐cross‐reactivity in vitro and in vivo. We speculate that symptom‐free consumption of pollen‐related food allergens may have implications for the pollen‐specific immune response of allergic individuals.
Combined mediator blockade or topical steroid for treating the unified allergic airway
Authors: Barnes M. L. , Menzies D. , Fardon T. C. , Burns P. , Wilson A. M. , Lipworth B. J.
Published: December 2006

Background:  Asthma and allergic rhinitis are manifestations of a single unified allergic airway, for which the best treatment is uncertain.

Objective:  To compare the anti‐inflammatory efficacy in the unified allergic airway of combined oral mediator antagonism and combined topical steroid.

Methods:  Subjects with asthma and perennial allergic rhinitis entered a randomized double blind crossover study comparing montelukast 10 mg and cetirizine 10 mg to extra‐fine inhaled beclomethasone 400 mcg/day and intranasal beclomethasone 200 mcg/day, each taken once daily for 2 months, after 2‐week placebo washouts. Measurements were made after each washout and randomized treatment, comprising: methacholine PC20, exhaled and nasal nitric oxide, blood eosinophils and eosinophilic cationic protein, symptoms, lung and nasal function tests.

Results:  Seventeen patients completed per protocol. For PC20 and exhaled nitric oxide, only combined topical steroid produced improvements (P < 0.005) from placebo baseline. Combined steroid was superior by a 0.93 (95% CI 0.14–0.93, P < 0.05) doubling dilution difference for PC20 and a 0.99 (95% CI 0.9–15.1, P < 0.01) doubling difference for exhaled nitric oxide. Both treatments attenuated eosinophils and eosinophilic cationic protein, and reduced nasal symptoms (P < 0.05). Only steroid improved nasal nitric oxide (P = 0.05) and asthma symptoms (P < 0.05). Neither treatment affected lung or nasal function tests.

Conclusion:  Combined topical steroid and combined mediator antagonism both attenuated systemic inflammation in the unified allergic airway, but only the former reduced bronchial and nasal inflammatory markers. The relevance of this to exacerbations and airway remodelling needs to be defined.
Thunderstorm‐asthma and pollen allergy
Authors: D'Amato G. , Liccardi G. , Frenguelli G.
Published: December 2006

Thunderstorms have been linked to asthma epidemics, especially during the pollen seasons, and there are descriptions of asthma outbreaks associated with thunderstorms, which occurred in several cities, prevalently in Europe (Birmingham and London in the UK and Napoli in Italy) and Australia (Melbourne and Wagga Wagga). Pollen grains can be carried by thunderstorm at ground level, where pollen rupture would be increased with release of allergenic biological aerosols of paucimicronic size, derived from the cytoplasm and which can penetrate deep into lower airways. In other words, there is evidence that under wet conditions or during thunderstorms, pollen grains may, after rupture by osmotic shock, release into the atmosphere part of their content, including respirable, allergen‐carrying cytoplasmic starch granules (0.5–2.5 μm) or other paucimicronic components that can reach lower airways inducing asthma reactions in pollinosis patients. The thunderstorm‐asthma outbreaks are characterized, at the beginning of thunderstorms by a rapid increase of visits for asthma in general practitioner or hospital emergency departments. Subjects without asthma symptoms, but affected by seasonal rhinitis can experience an asthma attack. No unusual levels of air pollution were noted at the time of the epidemics, but there was a strong association with high atmospheric concentrations of pollen grains such as grasses or other allergenic plant species. However, subjects affected by pollen allergy should be informed about a possible risk of asthma attack at the beginning of a thunderstorm during pollen season.
A comparison of the performance of two penicillin reagent kits in the diagnosis ofβ‐lactam hypersensitivity
Authors: Romano A. , Viola M. , Bousquet P. J. , Gaeta F. , Valluzzi R. , Caruso C. , Demoly P.
Published: December 2006

Background: Skin testing with penicilloyl polylysine (PPL) and minor determinant mixture (MDM) represents the first‐line method for diagnosingβ‐lactam hypersensitivity. However, in 2004, Allergopharma and Hollister‐Stier announced their decision to stop the production of penicillin reagents (Allergopen®and PrePen®, respectively) within 1 year. Therefore, we decided to compare PPL and MDM from Allergopharma (Allergopen) with those from Diater (DAP®).

Methods: We skin‐tested 195 subjects with both Allergopen and DAP reagents, as well as with otherβ‐lactams; 74 (group A) had had immediate reactions toβ‐lactams and 74 (group B) nonimmediate reactions, while 47 (group C) underwent prophylactic tests.

Results: One hundred two patients (52.3%) had positive skin tests; 29 (14.9%) were positive to PPL and/or MDM. Of the 102 skin‐test‐positive patients, 44 belonged to group A, 57 to B and 1 to C; the last was positive only to Allergopen PPL (PPL‐A) and tolerated the benzylpenicillin challenge. Minor determinant mixture reagents produced identical results in the 148 patients of groups A and B, 22 (14.9%) of which were positive. Both PPL reagents produced negative results in 139 of these 148 patients and positive ones in 5; one subject was positive to DAP PPL (PPL‐D) and negative to PPL‐A, while three patients were positive to PPL‐A and negative to PPL‐D; two of the latter tolerated benzylpenicillin challenges.

Conclusions: Minor determinant mixture reagents produced identical results in all 195 patients. Results of skin testing with PPL reagents were concordant in 190 (97.4%) of them. Therefore, DAP reagents are a reliable alternative to Allergopen ones.
Etoricoxib pre‐medication combined with intra‐operative subacromial block for pain after arthroscopic acromioplasty
Authors: Toivonen J. , Pitko V.‐M. , Rosenberg P. H.
Published: December 2006

Background: Arthroscopic shoulder surgery under general anaesthesia is often associated with severe post‐operative pain which may delay discharge and the start of rehabilitation. Etoricoxib is a new cyclo‐oxygenase‐2 inhibitor with a long duration of action and a lack of a deteriorating effect on platelet function. Therefore, the effect of pre‐operative etoricoxib combined with local anaesthesia on post‐operative pain and the discharge profile was studied in day‐surgery patients undergoing arthroscopic shoulder surgery under general anaesthesia.

Methods: Thirty ASA I–II adult patients scheduled for arthroscopic shoulder surgery were enrolled in this randomized prospective study. Half of the patients received etoricoxib 120 mg orally (group E) and the other half received placebo tablet orally (group C) 1 h before surgery. All patients received 20 ml of bupivacaine 2.5 mg/ml solution with epinephrine at the start of surgery and 20 ml of bupivacaine 5.0 mg/ml solution with epinephrine at the end of surgery into the subacromial space. All patients received general anaesthesia with spontaneous breathing via a laryngeal mask. In the post‐anaesthesia care unit, pain was assessed on a scale from 0 to 10 (visual analogue scale, VAS) and intravenous fentanyl 25 μg was administered as scheduled (VAS ≥ 3). In the day‐surgery unit and at home, the analgesic was a tablet containing paracetamol 500 mg + codeine 30 mg (VAS ≥ 3), as needed.

Results: Patients in group E reported lower post‐operative pain scores at 30, 60, 120 (P< 0.01) and 180 min (P< 0.05) after surgery, and longer time to first analgesic use (P< 0.05). Patients in group E required less fentanyl (P< 0.05) and were discharged more quickly (P< 0.05) than patients in group C. Patients in group E had a lower cumulative consumption of paracetamol + codeine tablets (P< 0.05) and lower pain scores (P< 0.05) during 7 days at home than patients in group C. Adverse events were rare in both groups.

Conclusion: In patients having arthroscopic shoulder surgery under general anaesthesia combined with intra‐operative subacromial regional analgesia, etoricoxib 120 mg reduced immediate and late post‐operative pain, and facilitated early post‐operative discharge.
Efficacy of ribavirin plus interferon‐α in patients aged ≥60 years with chronic hepatitis C
Authors: Honda Takashi , Katano Yoshiaki , Urano Fumihiro , Murayama Mutsumi , Hayashi Kazuhiko , Ishigami Masatoshi , Nakano Isao , Yoshioka Kentaro , Toyoda Hidenori , Kumada Takashi , Goto Hidemi
Published: December 2006

Background:  In Japan, patients with hepatitis C virus (HCV)‐associated liver disease are getting older, and thus the number of deaths due to such disease is increasing. The efficacy of combination therapy with ribavirin and interferon for chronic HCV infection in elderly patients has not been fully clarified. The aim of the present study was to evaluate the efficacy and tolerability of combination therapy in such patients.

Methods:  Two hundred and twenty consecutive patients with chronic hepatitis C were treated with combination therapy. These patients were divided into two groups according to age: patients ≥ 60 years (n = 66) and patients < 60 years (n = 154). Clinical characteristics, the sustained virologic response (SVR) rate obtained by intention‐to‐treat analysis, and the rate of reduction or discontinuation of ribavirin were compared between the two groups.

Results:  The ribavirin discontinuation rate was significantly higher in the patients aged ≥60 years than in the patients aged <60 years. However, the SVR rates did not differ significantly between patients aged ≥60 years and those aged <60 years (31.8% vs 38.3% by intention‐to‐treat analysis). According to multivariate analysis, genotype and HCV viral load were significantly associated with SVR while patient age did not affect SVR.

Conclusions:  Treatment of chronic hepatitis C with combination therapy was comparably effective between patients aged ≥60 years and those aged <60 years, although the ribavirin discontinuation rate was higher among the older patients than the younger patients.
Living donor liver transplantation for hepatitis B cirrhosis
Authors: Karasu Zeki , Akyildiz Murat , Kilic Murat , Zeytunlu Murat , Aydin Unal , Tekin Fatih , Yilmaz Funda , Ozacar Tijen , Akarca Ulus , Ersoz Galip , Gunsar Fulya , Ilter Tankut , Lucey Michael R
Published: December 2006

Background and Aim:  Living donor liver transplantation (LDLT) has particular advantages for Turkey where hepatitis B virus (HBV) infection is the most common cause of cirrhosis, both because LDLT circumvents the difficulties encountered in the emerging world in providing deceased donor organs, and because it allows preemptive antiviral therapy. The aim of this study was to review one institution's experience with LDLT in patients with chronic HBV infection.

Methods:  A total of 109 patients with chronic HBV infection underwent LDLT between September 1999 and June 2005, of whom 40 were coinfected with hepatitis D virus and 23 had hepatocellular carcinoma. Antiviral prophylaxis was attempted in all, beginning prior to transplantation with lamivudine or adefovir, and continuing after transplantation with low dose intramuscular hyperimmune B immunoglobulin (HBIg) plus lamivudine or adefovir.

Results:  In a median follow up of 20 months (range 1–66 months), there was no donor mortality. One‐year recipient survival was 90%, and in total 16 recipients died. None of the deaths was related to HBV. Recurrence of HBV infection was detected by reappearance of serum hepatitis B surface antigen in six patients (5.5%) at 5, 8, 12, 17, 34 and 46 months after transplantation, respectively. There was no influence of donor hepatitis B core antibody status on the likelihood of recurrence of HBV in the allograft.

Conclusion:  The results indicate that LDLT with antiviral treatment and low dose HBIg provides excellent results for donors and recipients.
EVALUATION OF GASTRIC ULCER AFTER ENDOSCOPIC INJECTION SCLEROTHERAPY FOR ESOPHAGEAL VARICES
Authors: Sato Takahiro , Yamazaki Katsu , Toyota Jouji , Karino Yoshiyasu , Ohmura Takumi , Akaike Jun , Kuwata Yasuaki , Arakawa Tomohiro , Suga Toshihiro
Published: December 2006

Background:  Endoscopic injection sclerotherapy (EIS) is an effective procedure for the treatment of esophageal varices. In the present study, the pathogenesis of gastric ulcer after EIS for esophageal varices was investigated.

Methods:  EIS for esophageal varices was performed for 610 patients in our department, and the frequency and clinical course of gastric ulcer after EIS were investigated retrospectively. EIS was performed using 5% ethanolamine oleate with iopamidol, which was injected intermittently under fluoroscopy.

Results:  Gastric ulcer after EIS for esophageal varices was observed in 14 of the 610 (2.3%) patients. These were located around the cardia of the stomach from the fornix to the gastric body. Gastric ulcer extended from the stomach lining into the esophagus in 11 of the 14 cases. Severe chest pain was observed, and dark purple mucosal changes of the esophagus and stomach were detected endoscopically at the time of injection in all 14 cases. All cases received dripping therapy, and prescription of a proton pump inhibitor. Gastric ulcer after EIS was refractory, and almost 2 months was required until the healing stage was reached.

Conclusion:  Gastric ulcer after EIS for esophageal varices is a rare but important complication of EIS.
ANALYSIS OF BURIED BUMPER SYNDROME AFTER PERCUTANEOUS ENDOSCOPIC GASTROSTOMY DUE TO USE OF A BUTTON‐TYPE KIT
Authors: Usuba Teruyuki , Suzuki Yutaka , Kuramochi Akira , Tajiri Hisao , Yanaga Katsuhiko
Published: December 2006

Background:  Buried bumper syndrome (BBS) is a rare complication of percutaneous endoscopic gastrostomy (PEG). Along with the widespread use of the button‐type kit, BBS is encountered frequently.

Methods:  In the present study, we examined causes and treatments for BBS among 1400 patients who had undergone PEG.

Results:  The causes of BBS after PEG were classified into two categories: early causes consisted of wound infection, inappropriate size of kit and severe lordosis, while late causes were inappropriate exchange of kit, rough management or weight gain. The treatments for BBS could be determined by the degree of wound infection, fistula and burial of the bumper.

Conclusion:  We prepared a flowchart for replacement, by which BBS can be managed safely and quickly without surgical or endoscopic intervention.
MECKEL’S DIVERTICULUM WITH ULCERATION DIAGNOSED BY DOUBLE BALLOON ENTEROSCOPY
Authors: Hotta Kinichi , Oyama Tsuneo , Tomori Akihisa , Miyata Yoshinori
Published: December 2006

A 31‐year‐old man was referred to our hospital for an evaluation of recurrent episodes of melena. Esophagogastroduodenoscopy, total colonoscopy, computed tomography and Tc‐99 m scintigraphy were performed at a previous hospital, but the bleeding source remained unidentified. Double balloon enteroscopy (DBE) was performed with the use of an anal approach at our hospital. DBE was inserted into the ileum approximately 100 cm from the ileocecal valve, and then Meckel’s diverticulum was discovered. There was a circular ulceration in the middle part of the diverticulum without adherent blood clots, visible vessels nor heterotopic gastric mucosa. Meckel’s diverticulum was identified as the bleeding source, but an immediate risk of rebleeding was considered relatively low. The patient chose conservative therapy without surgery. Two years later, he is well, without further bleeding episodes. DBE made it possible not only to diagnose the existence of the Meckel’s diverticulum but also to assess the risk of rebleeding.
Chemosensory and steroid‐responsive regions of the medial amygdala regulate distinct aspects of opposite‐sex odor preference in male Syrian hamsters
Authors: Maras Pamela M. , Petrulis Aras
Published: December 2006

In rodent species, such as the Syrian hamster, the expression of sexual preference requires neural integration of social chemosensory signals and steroid hormone cues. Although anatomical data suggest that separate pathways within the nervous system process these two signals, the functional significance of this separation is not well understood. Specifically, within the medial amygdala, the anterior region (MEa) receives input from the olfactory bulbs and other chemosensory areas, whereas the posterodorsal region (MEpd) contains a dense population of steroid receptors and receives less substantial chemosensory input. Consequently, the MEa may subserve a primarily discriminative function, whereas the MEpd may mediate the permissive effects of sex steroids on sexual preference. To test these hypotheses, we measured preference and attraction to female and male odors in males with lesions of either the MEa or MEpd. In Experiment 1, lesions of either region eliminated opposite‐sex odor preferences. Importantly, MEpd‐lesioned males displayed decreased attraction toward female odors, suggesting decreased sexual motivation. In contrast, MEa‐lesioned males displayed high levels of investigation of both male and female odors, suggesting an inability to categorize the relevance of the odor stimuli. In Experiment 2, we verified that both MEa‐ and MEpd‐lesioned males could discriminate between female and male odors, thereby eliminating the possibility that the observed lack of preference reflected a sensory deficit. Taken together, these results suggest that both the MEa and MEpd are critical for the expression of opposite‐sex odor preference, although they appear to mediate distinct aspects of this behavior.
Monoamine oxidase A rather than monoamine oxidase B inhibition increases nicotine reinforcement in rats
Authors: Guillem Karine , Vouillac Caroline , Azar Marc R. , Parsons Loren H. , Koob George F. , Cador Martine , Stinus Luis
Published: December 2006

Although nicotine is considered to be responsible for the addictive properties of tobacco, growing evidence underlines the importance of non‐nicotine components in smoking reinforcement. It has been shown that tobacco smoke contains monoamine oxidase (MAO) A and B inhibitors and decreases MAO‐A and MAO‐B activity in smokers. Here, we investigated the effects of clorgyline hydrochloride (irreversible MAO‐A inhibitor; 2 mg/kg/day), selegiline (irreversible MAO‐B inhibitor; 4 mg/kg) and the beta‐carboline norharmane hydrochloride (reversible MAO‐B inhibitor; 5 mg/kg/day) treatments on nicotine self‐administration (30 µg/kg/infusion, free base) in rats. Independent of the responsiveness to novelty and locomotor activity stimulation, only clorgyline hydrochloride treatment increased the intake of nicotine in a fixed‐ratio schedule (FR5) of reinforcement. When a progressive‐ratio schedule was implemented, both clorgyline hydrochloride and norharmane hydrochloride treatments potentiated the reinforcing effects of nicotine, whereas selegiline had no effect. Taken together, these results indicate that MAO‐A inhibition interacts with nicotine to enhance its rewarding effects in rats and suggest that other compounds present in tobacco, such as beta‐carboline, may also play an important role in sustaining smoking behavior in humans.
Riluzole promotes cell survival and neurite outgrowth in rat sensory neuronesin vitro
Authors: Shortland Peter J. , Leinster Veronica H. L. , White William , Robson Lesley G.
Published: December 2006

This study explored the effects of riluzole administration on cell survival and neurite growth in adult and neonatal rat dorsal root ganglion (DRG) neuronesin vitro. Neuronal survival was assessed by comparing numbers of remaining neurones in vehicle‐ and riluzole‐treated cultures. A single dose of 0.1 µmriluzole was sufficient to promote neuronal survival in neonatal DRG cultures, whereas repeated riluzole administration was necessary in adult cultures. However, a single administration of riluzole was sufficient to induce neuritogenesis, promote neurite branching and enhance neurite outgrowth in both neonatal and adult DRG cultures. The effects of a single dose of riluzole on adult DRG neurones after peripheral nerve or dorsal root injury were also studiedin vitroat 48 h. For both types of injury, riluzole enhanced neurite outgrowth in terms of number, length and branch pattern significantly more on the injured side as compared with the contralateral side. No effect was seen on cell survival. The results suggest that, in addition to its cell survival effects, riluzole has novel growth‐promoting effects on sensory neuronesin vitroand that riluzole may offer a new way to promote sensory afferent regeneration following peripheral injury.
Evidence for time‐variant decision making
Authors: Ditterich Jochen
Published: December 2006

Computational models based on diffusion processes have been proposed to account for human decision‐making behaviour in a variety of tasks. The basic idea is that the brain keeps accumulating noisy sensory evidence until a critical level is reached. This study explores whether such models account for the speed and accuracy of perceptual decisions in a reaction‐time random dot motion direction discrimination task, and whether they explain the decision‐related activity of neurons recorded from the parietal cortex (area LIP) of monkeys performing the task. While a simple diffusion model can explain the psychometric function and the mean response times of correct responses, it fails to account for the longer response times observed for errors and for the response time distributions. Here I demonstrate that a time‐variant version of the diffusion model can explain the psychometric function, the mean response times and the shape of the response time distributions. Such a time‐variant mechanism could be implemented in different ways, but the best match between the physiological data and model predictions is provided by a diffusion process with a gain of the sensory signals, which increases over time. It can be shown that such a time‐variant decision process allows the monkey to perform optimally (in the sense of maximizing reward rate) given the risk of aborting a trial by breaking fixation before a choice can be reported. The results suggest that the brain trades off speed and accuracy not only by adjusting parameters between trials but also by dynamic adjustments during an ongoing decision.
Degeneration of noradrenergic fibres from the locus coeruleus causes tight‐junction disorganisation in the rat brain
Authors: Kalinin Sergey , Feinstein Douglas L. , Xu Hao‐Liang , Huesa Gema , Pelligrino Dale A. , Galea Elena
Published: December 2006

Although functional studies demonstrate that noradrenaline controls the permeability of the blood–brain barrier, it has never been determined whether this neurotransmitter regulates the tight junction (TJ) assembly that confers the barrier property to brain microvessels. We thus tested in rats the effect of pharmacological depletion of noradrenaline with the noradrenergic toxin DSP4 (5 mg/kg) on the expression of the TJ proteins zonula occludens‐1 (ZO1) and occludin. The effectiveness of the lesion was confirmed by tyrosine hydroxylase immunoreactivity, which showed noradrenergic fibre reduction accompanied by debris and swollen fibres in DSP4‐treated brains. Noradrenergic fibre degeneration caused: (i) gliosis; (ii) disappearance of TJ proteins in vascular cell‐to‐cell contacts (49.9 and 38.3% reductions for occludin and ZO1, respectively); (iii) a 49.2% decrease in total ZO1 protein, measured by Western blot analysis, parallel to a 39.5% decrease in ZO1 mRNA, measured by real‐time PCR; and (iv) a relative increase in the beta occludin isoform (62.9%), with no change in total occludin protein or mRNA. The expression of endothelial brain antigen, a marker of a functionally competent brain endothelium, was also reduced. We conclude that damage to the ascending fibres from the locus coeruleus caused TJ disruption and gliosis, a sign of inflammation. These results imply that the locus coeruleus degeneration reported in Alzheimer's and Parkinson's diseases may contribute to these disorders by causing blood–brain barrier dysfunction. Whether the vascular damage is the result of impaired noradrenergic transmission or secondary to the inflammatory reaction remains to be determined.
Cytosolic phospholipase A2alpha modulates NMDA neurotoxicity in mouse hippocampal cultures
Authors: Brady Ken M. , Texel Sarah J. , Kishimoto Koji , Koehler Raymond C. , Sapirstein Adam
Published: December 2006

The arachidonic acid‐specific cytosolic phospholipase A2alpha (cPLA2α) has been implicated in the generation of neurological injuries. cPLA2α‐dependent neurological injury has been postulated to be mediated through inflammatory and eicosanoid pathways. We determined if cPLA2α amplifies the injury of a non‐inflammatory, excitotoxic stimulus by modifying a well‐described toxicity assay to measure the toxicity ofN‐methyl‐d‐aspartate (NMDA) in the CA1 region of organotypic, mouse hippocampal cultures. Hippocampal cultures from wild‐type and cPLA2α knockout mice were exposed to 5, 7.5 or 10 µmNMDA for 1 h. Toxicity was measured 23 h later. Cultures derived from cPLA2α–/–mice and cultures treated with the selective inhibitor AACOCF3were significantly protected from NMDA toxicity, as compared with wild‐type cultures. To determine if cPLA2α‐dependent toxicity is cyclooxygenase (COX)‐2 dependent, COX‐2 and PGE2levels were measured 7 and 25 h after NMDA treatment. NMDA treatment failed to induce COX‐2 protein or increase PGE2in the culture media in either genotype at either time. In contrast, phorbol 12‐myristate 13‐acetate and ionophore treatment caused robust induction of COX‐2 and PGE2in both genotypes. We conclude that cPLA2α may have a hitherto unrecognized direct effect on excitatory neurotoxicity, suggesting that cPLA2α inhibition is a therapeutic candidate for treatment of the early, excitotoxic injury observed in stroke.
Urinary pheromones promote ERK/Akt phosphorylation, regeneration and survival of vomeronasal (V2R) neurons
Authors: Xia Jing , Sellers Lynda A. , Oxley David , Smith Trevor , Emson Piers , Keverne Eric B.
Published: December 2006

The G protein‐coupled pheromone receptor neurons (V1R and V2R) of the vomeronasal organ (VNO) are continually replaced throughout the lifetime of the mouse. Moreover, active signalling of V2Rs via the transient receptor potential 2(TRPC2) channel is necessary for regeneration of receptors, as the TRPC2 null mutant mouse showed a 75% reduction of V2Rs by the age of two months. Here we describe V2R mediated signalling in a neuronal line established from vomeronasal stem cells taken from postnatal female mice. Cells were immunoreactive for Gαo and V2R, whereas V1R and Gαi immunoreactivity could not be detected. Biological ligands (dilute urine and its protein fractions) were found to increase proliferation and survival of these neurons. Dilute mouse urine but not artificial urine also induced ERK, Akt and CREB signalling in a dose dependent way. The volatile fraction of male mouse urine alone was without effect while the fraction containing peptides (> 5 kDa) also stimulated ERK and Akt phosphorylation. The ERK, Akt and CREB phosphorylation response was sensitive to pertussis toxin, confirming the involvement of V2R linked Gαo. Dilute mouse urine or its high molecular weight protein fraction increased survival and proliferation of these neurons. Hence, urinary pheromones, which signal important social information via mature neurons, also promote survival and proliferation of their regenerating precursors. These data show that regenerating V2Rs respond to urine and the urinary peptides by activation of the Ras‐ERK and PI3‐Akt pathways, which appear to be important for vomeronasal neural survival and proliferation.
Export of nitrogenous compounds due to incomplete cycling within biological soil crusts of arid lands
Authors: Johnson Shannon L. , Neuer Susanne , Garcia‐Pichel Ferran
Published: December 2006

Second only to water among limiting factors, nitrogen controls the fertility of most arid regions. Where dry and wet depositions are weak, as in the western US deserts, N inputs rely heavily on biological N2 fixation. Topsoil cyanobacterial communities known as biological soil crusts (BSCs) are major N2 fixation hot spots in arid lands, but the fate of their fixed N remains controversial. Using a combination of microscale and mesoscale process rate determinations, we found that, in spite of theoretically optimal conditions, denitrification rates in BSCs were paradoxically immaterial for nitrogen cycling. Denitrifier populations within BSCs were extremely low. Because of this absence of denitrification, and because of the limitation of respiration and ammonia oxidation by diffusive O2 supply, we could demonstrate that BSCs function as net exporters of ammonium, nitrate and organic N to the soils they cover, in approximately stoichiometrically equal proportions. Overall export rates during periods of biological activity are in the range of tens to hundreds of μmol‐N m−2 h−1, commensurate with those of N2 fixation. These results explain the long‐term dependence of BSCs on N2 fixation, confirm their role in landscape fertility, and provide a robust argument for conservation of these endangered communities.
Sequence diversity of the OprD protein of environmental Pseudomonas strains
Authors: Chevalier Sylvie , Bodilis Josselin , Jaouen Thomas , Barray Sylvie , Feuilloley Marc G. J. , Orange Nicole
Published: December 2006

OprD has been widely described for Pseudomonas aeruginosa at both structural and functional levels. Here, we describe the sequence diversity of the OprD proteins from other fluorescent Pseudomonads. We analysed the sequence of the oprD gene in each of the 49 Pseudomonas isolates, mostly putida and fluorescens species, obtained from various environmental sources, including soil, rhizosphere and hospitals. Phylogeny based on OprD sequences distinguished three well‐separated clusters in the P. fluorescens species whereas P. putida isolates formed only one cluster. The OprD sequences were generally well conserved within each cluster whereas on the opposite, they were highly variable from one cluster to another and particularly with regards to the cluster of P. aeruginosa. Predicted secondary structures, based on the topological model elaborated for P. aeruginosa, suggest signatures in the large extracellular loops of OprD, which are linked to the OprD‐based clusters. Correlations between these OprD‐based clusters and ecological niches, growth on various carbon sources and antibiotic sensitivity were investigated.
Risk of dysplasia and adenocarcinoma following restorative proctocolectomy for ulcerative colitis
Authors: Das P. , Johnson M. W. , Tekkis P. P. , Nicholls R. J.
Published: December 2006

Objective  Restorative proctocolectomy (RPC) with or without mucosectomy is the treatment of choice for most patients with ulcerative colitis (UC) requiring surgery. The ileal mucosa in the reservoir and the anorectal columnar epithelium below the ileo‐anal anastomosis are at risk of neoplastic transformation.

Method  The literature has been reviewed to identify patients developing this complication and an attempt has been made to develop a rational follow‐up policy based on the data available.

Results  Dysplasia in the ileal reservoir is rare. It is associated with histological type C changes, sclerosing cholangitis and unremitting pouchitis in the ileal mucosa and to the presence of sclerosing cholangitis. Nine patients who have developed adenocarcinoma in the residual anorectal mucosa and seven in the reservoir have been reported in the literature. A further hitherto unreported patient treated by the authors brings the total to 17 patients. Twelve of these had histopathological data on either dysplasia or carcinoma in the original operative specimen. The time intervals from the onset of UC and from the RPC to the development of cancer were 120–528 (median 246) and 16–216 (median 60) months respectively. Cancer appeared to be related to the duration of disease rather than to the interval from RPC. In all the reported patients the interval from the onset of UC was 10 years.

Conclusion  Based on these data a surveillance programme should begin at 10 years from the onset of disease. Patients with dysplasia or carcinoma in the original specimen, those with type C ileal mucosal changes and patients with sclerosing cholangitis should be selected for surveillance. This will involve multiple biopsies of the ileal reservoir and the anorectal mucosa below the ileo‐anal anastomosis.
The effects of cyclical oestrogen on bladder and urethral structure and function
Authors: Palmieri Katherine , Mannikarottu Anita S. , Chichester Paul , Kogan Barry , Leggett Robert E. , Whitbeck Catherine , Levin Robert M.
Published: December 2006

OBJECTIVE

To determine the effects of cycling oestrogen in rabbits, as oestrogen is essential for physiological maintenance and integrity of the female urogenital tract.

MATERIALS AND METHODS

Changes in circulating oestrogen have marked effects on the bladder of experimental animals, with ovariectomy (Ovx) inducing smooth muscle (SM) and mucosal atrophy, increasing collagen synthesis and deposition, decreasing contractile function, mucosal and SM blood flow; oestrogen reverses these effects and increases bladder mass and SM density, primarily by stimulating angiogenesis and increasing blood flow. Twenty adult female New Zealand White rabbits were divided into five equal groups; group 1 served as the control group, and groups 2–5 had a bilateral Ovx. Group 2 received no oestradiol and was assessed 2 weeks after Ovx; groups 3–5 received 17‐β oestradiol from a subcutaneous slow‐release tablet 2 weeks after Ovx, which remained in place for a subsequent 2‐week period. Group 3 was then assessed after the 2 weeks on oestradiol. Groups 4 and 5 then had their oestradiol tablets removed for 2 weeks and group 4 was assessed after this period off oestradiol. Group 5 then received a new oestradiol tablet that was left in place for an additional 2 weeks.

RESULTS

Both groups receiving oestrogen (3 and 5) had a statistically significantly greater bladder weight than both the control group and group 2. The volume fraction of SM paralleled the bladder weight, showing that oestrogen increased the volume fraction of SM whereas Ovx and low oestrogen decreased the SM fraction. The cross‐sections of the urethra from groups 3 and 5 were significantly wider than those of either the control or group 1, also being consistent with the structural effects of oestrogen. Intra‐arterial phenylephrine increased urethral pressure to a similar level in all groups. The urethral pressure response to intra‐arterial acetylcholine shifted from contraction in the control to relaxation in the oestrogen‐treated groups. Ovx resulted in a lower vascular density, whereas oestrogen resulted in a significant increase in vascular density (angiogenesis).

CONCLUSIONS

Cyclical oestrogen had pronounced structural and pharmacological effects. Low oestrogen decreased the volume fraction of SM, increased collagen, and decreased vasculature, whereas oestrogen mediated a marked hypertrophy of the SM components, decreased the collagen component, and stimulated angiogenesis. Cyclical oestrogen also had marked effects on the responses to intra‐arterial acetylcholine, shifting the response from contraction to relaxation.
Early effects of pharmacological androgen deprivation in human prostate cancer
Authors: Mercader Maria , Sengupta Shomik , Bodner Barbara K. , Manecke Ryan G. , Cosar Ediz F. , Moser Michael T. , Ballman Karla V. , Wojcik Eva M. , Kwon Eugene D.
Published: December 2006

OBJECTIVES

To assess the early histological effects of pharmacological androgen deprivation (AD), which have been assessed only over longer periods, as surgical castration leads rapidly to diminished cell proliferation and enhanced cell death within the prostate.

PATIENTS AND METHODS

With Institutional Review Board approval, 35 patients were randomly assigned (seven in each group) to receive 0, 7, 14, 21 and 28 days of AD (flutamide, 250 mg orally three times/day, and one injection with leuprolide acetate 7.5 mg) before radical prostatectomy. The surgical specimens were assessed by conventional histology and immunohistochemistry, while macroarray analysis and quantitative real‐time polymerase chain reaction (QRT‐PCR) were used to examine gene expression.

RESULTS

There were morphological changes within the prostatic tissues as early as 7 days after initiating AD, similar to the response to castration. There was tumour cell vacuolization indicating cellular injury, glandular atrophy and mononuclear cell infiltration as prominent and progressive effects but, by contrast with castration studies, there were no changes in epithelial proliferation or apoptosis. Macroarray analysis, validated by QRT‐PCR and immunohistochemistry, showed up‐regulation of numerous and potentially counter‐effective genes involved in the cell cycle and apoptosis.

CONCLUSIONS

Pharmacological AD induces significant involution within prostatic tissues over 7–28 days, but allows the persistence of some viable tumour cells capable of proliferation.
Transdermal oestrogen therapy as a second‐line hormonal intervention in prostate cancer: a bad experience
Authors: Kandola Sandhir , Anyamene Nicola , Payne Heather , Harland Stephen
Published: December 2006

OBJECTIVE

To compare transdermal oestrogen with oral diethylstilbestrol (DES) as a second‐ or third‐line hormonal therapy in the treatment of prostate cancer.

PATIENTS AND METHODS

In all, 32 assessable patients who, having already had a relapse on at least one line of hormonal therapy, received transdermal oestrogen therapy as an alternative to oral DES, when DES became unavailable.

RESULTS

Whereas DES had controlled the prostate‐specific antigen (PSA) level for a median of 29 weeks in a group of 15 patients in remission, all but one had an increase in PSA level (median 86% increase above the starting PSA level) within a median of 8 weeks after introducing transdermal therapy. This increase was reversed in seven of the 12 patients who recommenced DES therapy.

CONCLUSION

Although the use of transdermal oestrogen is currently attracting enthusiasm as a first‐line treatment for prostate cancer, these results show that for second‐ or third‐line therapy further cautious research with careful monitoring is necessary.
Correlation between risk factors for vascular disease and the American Urological Association Symptom Score
Authors: Gibbons Erin P. , Colen John , Nelson Joel B. , Benoit Ronald M.
Published: December 2006

OBJECTIVE

To evaluate the correlation between risk factors for vascular disease and the American Urological Association Symptom Score (AUA‐SS), by comparing the presence of these risk factors with the degree of lower urinary tract symptoms (LUTS).

PATIENTS AND METHODS

We retrospectively reviewed the medical history, AUA‐SS, and prostate volume of men who had a radical prostatectomy. The degree of LUTS in men with and without risk factors for cardiovascular disease was compared.

RESULTS

The mean AUA‐SS was 7.2 for the entire cohort, 5.6 in men with no risk factors, and 7.9 in men with at least one risk factor (P < 0.05). In men with one to four risk factors, the mean AUA‐SS was 6.9, 7.9, 10.7, and 19.5, respectively. There was no correlation between the AUA‐SS and prostate size in the entire cohort or among any groups.

CONCLUSIONS

Men with risk factors for vascular disease are more likely to have a higher AUA‐SS than men without these risk factors. These findings suggest the possibility of an association between vascular disease and the development and severity of LUTS in men.
Vertical rectus abdominis flap reconstruction in patients with advanced penile squamous cell carcinoma
Authors: Kayes Oliver J. , Durrant Charles A. , Ralph David , Floyd David , Withey Simon , Minhas Suks
Published: December 2006

OBJECTIVES

To evaluate the role of radical surgical debridement and excision with a vertical rectus abdominis myocutaneous (VRAM) flap reconstruction in patients with advanced penile cancer and subcutaneous metastatic disease, as the quality of life in such patients is extremely poor, multimodal treatments often fail and the outlook for the patient is limited with the development of uncontrollable disease.

PATIENTS AND METHODS

Four patients with advanced penile cancer presenting with fungating, cutaneous tumour deposits received palliative surgical resections for abdominal and inguinal disease. A VRAM flap was used in all cases to achieve tissue coverage.

RESULTS

All grafts were viable and the mean inpatient stay was 14 days. There were no immediate complications after surgery; patient satisfaction and symptom relief was excellent.

CONCLUSIONS

Aggressive palliative resection with a VRAM can dramatically improve the patients’ quality of life in advanced penile cancer, permitting disease control with satisfactory cosmesis. However, a multidisciplinary approach involving both the urological reconstructive and plastic surgeon is essential.
Complexity of Outsourcing Contracts and Ex Post Transaction Costs: An Empirical Investigation*
Authors: Barthélemy Jérôme , Quélin Bertrand V.
Published: December 2006

abstract In this article, we use Transaction Cost Economics (TCE) and the Resource‐Based View (RBV) of the firm to study outsourcing agreements. We develop an original approach of contract complexity and analyse the links among exchange hazards (i.e. specificity and environmental uncertainty), the contractual aspects of outsourcing (control, incentives, penalties, price and flexibility clauses) and the level of ex post transaction costs. Both contract complexity and ex post transaction costs are operationalized and measured. Our empirical research analyses 82 outsourcing contracts. This article uses three different dimensions (proximity to the core business, switching costs and adaptation costs) to assess the strategic importance of an outsourced activity. Our findings extend TCE's validity for the outsourcing of activities with a strategic value. Finally, this study offers an indirect measurement of ex post transaction costs. In short, to restrict vendor opportunism, contracts must contain incentives and penalties, as well as pricing and monitoring clauses.
Exploring the Political Side of Board Involvement in Strategy: A Study of Mixed‐Ownership Institutions*
Authors: Ravasi Davide , Zattoni Alessandro
Published: December 2006

abstractThis article reports on a comparative study of strategic decision‐making and board functioning in nine firms. Findings indicate that the heterogeneity of interests represented on the board, members' possession of relevant knowledge, and the presence of ex‐ante conflict resolution mechanisms combine in shaping if and how board members engage in strategy‐related activities and how strategic decisions are taken. Findings extend current understandings about the strategic functions of the board (monitoring, advice, and resource‐dependence), suggesting how, under certain conditions, boards may act as negotiation forums where directors search for a reconciliation between diverging shareholders' interests and views.
Encouraging Best Practice in Quantitative Management Research: An Incomplete List of Opportunities*
Authors: Echambadi Raj , Campbell Benjamin , Agarwal Rajshree
Published: December 2006

abstract The paper identifies some common problems encountered in quantitative methodology and provides information on current best practice to resolve these problems. We first discuss issues pertaining to variable measurement and concerns regarding the underlying relationships among variables. We then highlight several advances in estimation methodology that may circumvent issues encountered in common practice. Finally, we discuss approaches that move beyond existing research designs, including the development and use of datasets that embody linkages across levels of analysis, or combine qualitative and quantitative methods.
Finding a Working Balance Between Competitive and Communal Strategies*
Authors: Barnett Michael L.
Published: December 2006

abstractThis paper presents a dynamic framework that describes how firms allocate limited resources between improving their competitive position relative to rivals and their communal position shared with rivals. This dynamic framework outlines how organizational field‐level dynamics influence industry attractiveness and thereby alter a firm's incentive to engage in communal strategy relative to competitive strategy. Communal strategy, in turn, can influence the institutions governing an organizational field and thereby shape industry attractiveness. Overall, the interplay between factors exogenous and endogenous to an industry cause change in an organizational field and so determine the nature of the communal environment shared by a firm and its rivals over time. Analysis of this interplay provides insight into the micro‐level drivers of macro‐level change and furthers understanding of the conditions under which rivalrous firms voluntarily contribute to collective betterment of their industry despite collective rationality.
Building Better Theory by Bridging the Quantitative–Qualitative Divide*
Authors: Shah Sonali K. , Corley Kevin G.
Published: December 2006

abstract Qualitative methods for data collection and analysis are not mystical, but they are powerful, particularly when used to build new or refine existing theories. This article provides an introduction to qualitative methods and an overview of tactics for ensuring rigor in qualitative research useful for the novice researcher, as well as more experienced researchers interested in expanding their methodological repertoire or seeking guidance on how to evaluate qualitative research. We focus our discussion on the qualitative analytical technique of grounded theory building, and suggest that organizational research has much to gain by coupling of use of qualitative and quantitative research methods.
SIGNPOSTS OF INVENTION: ARTISTS' SIGNATURES IN ITALIAN RENAISSANCE ART
Authors: RUBIN PATRICIA
Published: December 2006

The opening lines of Dante Alighieri's Divine Comedy provide the starting point for a consideration of the ways that artists inscribed themselves within their works during the Renaissance. This is a matter both of signatures and of authorial complicity. This article examines how signatures were defined in the period and how they were used in a process of artistic definition. Conventions of inscription are outlined, and four particularly inventive instances (Fra Filippo Lippi, Donatello, Michelangelo and Titian) are considered in greater detail to show how artists' names could be used to direct the viewer's experience of their works and appreciation of their authorship.