bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors analysis for hepatocellular carcinoma in patients with and without cirrhosis: A case–control study of 213 hepatocellular carcinoma patients from India
Authors: Kumar Manoj , Kumar Rakesh , Hissar Syed S , Saraswat Manoj Kumar , Sharma Barjesh Chander , Sakhuja Puja , Sarin Shiv Kumar
Published: June 2007

Aim:  To assess the role of hepatitis B virus (HBV), hepatitis C virus (HCV) and alcohol intake as risk factors for hepatocellular carcinoma (HCC) in the presence or absence of cirrhosis in Indian population.

Methods:  A total of 213 patients with HCC and 254 control subjects not affected with hepatic diseases or neoplasm were recruited. Odds ratios (ORs) were estimated for each risk factor and synergism among various risk factors was also studied.

Results:  The ORs and 95% confidence intervals (CI) of HCC were 48.02 (25.06–91.98) for any HBV marker, 38.98 (19.55–77.71) for HBsAg positivity, 12.34 (2.84–53.61) for HBsAg negative and antibody positive (either of anti‐HBe or total anti‐HBc), 5.45 (2.02–14.71) for anti‐HCV positive and HCV RNA positive, and 2.83 (1.51–5.28) for heavy alcohol use. No significant risk increase was evident for subjects who were anti‐HCV positive and HCV RNA negative. Synergism between alcohol and HCV infection in causing HCC was found, but not between alcohol and HBV. Overall, conclusive evidence of the presence or absence of cirrhosis was reached in 189 (88.73%) HCC patients; cirrhosis was present in 137 (72.48%) of them. ORs with 95% CI of HCC in the presence and absence of cirrhosis, respectively, for HBV were as follows: (i) 48.90 (24.61–97.19) and 35.03 (15.59–78.66) for any HBV marker; (ii) 39.88 (19.41–81.97) and 24.40 (10.60–56.18) for HBsAg positivity; and (iii) 12.10 (2.67–54.88) and 19.60 (3.94–97.39) for HBsAg negativity and antibody positivity. Significantly increased risk was found among cirrhotic patients for anti‐HCV positivity and HCV RNA positivity [OR = 7.53 (2.73–20.78)] and for heavy alcohol use [OR = 3.32 (1.70–6.47)]; however, in the absence of cirrhosis, no significant risk increase was evident for subjects who were anti‐HCV positive and HCV RNA positive [OR = 0.97 (0.11–8.54)], or who had history of heavy alcohol use [OR = 1.58 (0.55–4.53)].

Conclusions:  Infection with HBV and HCV are the major risk factors for the development of HCC in Indian patients. Presence of HBV antibodies even in the absence of HBsAg conferred increased risk for HCC in the presence or absence of cirrhosis. Anti‐HCV positivity in the absence of HCV RNA conferred no increased risk. HCV RNA positivity and heavy alcohol use significantly increased the risk of HCC among cirrhotic patients, but not non‐cirrhotic patients.
Relevance of ineffective esophageal motility and hyperactive acid sensitization in patients with gastroesophageal reflux
Authors: Hong Su Jin , Ko Bong Min , Jung In Seop , Ryu Chang Beom , Moon Jong Ho , Cho Joo Young , Kim Jin Oh , Lee Joon Seong , Lee Moon Sung , Shim Chan Sup , Kim Boo Sung
Published: June 2007

Background and Aim:  Esophageal motor abnormalities including ineffective esophageal motility (IEM) and visceral hypersensitivity have been frequently observed in patients with gastroesophageal reflux. The aim of this study was to observe the incidences of hypersensitivity to acid infusion and motor abnormalities in non‐erosive reflux disease (NERD) compared with erosive esophagitis.

Methods:  We performed upper GI endoscopy, an acid perfusion test and esophageal manometry on 113 NERD patients and 37 erosive esophagitis patients.

Results:  The frequency of acid sensitization was 69.9% in NERD and 67.6% in erosive esophagitis. The frequency of esophageal motor abnormality in patients with erosive esophagitis (48.6%) was higher than in patients with NERD (25.7%, P = 0.014). The most frequent esophageal motor abnormality was IEM. The frequency of IEM was 15.9% in NERD patients, 42.9% in Los Angeles grade A, 53.8% in Los Angeles grade B and 66.7% in Los Angeles grade C esophagitis (χ2 = 16.67, P < 0.0001).

Conclusion:  Our results suggest that no difference exists between visceral hypersensitivity in patients with NERD and those with erosive esophagitis, and that IEM occurs in NERD as well as erosive esophagitis patients. The occurrence of IEM is associated with the endoscopic severity of gastroesophageal reflux disease.
Prognostication in severe acute respiratory syndrome: A retrospective time‐course analysis of 1312 laboratory‐confirmed patients in Hong Kong
Authors: CHAN Jane C.K. , TSUI Eva L.H. , WONG Vivian C.W. ,   The Hospital Authority SARS Collaborative Group
Published: June 2007

Background and objective:  The temporal importance of prognostic indicators for severe acute respiratory syndrome (SARS) has not been studied. This study identified the various clinical prognostic factors for SARS and described the temporal evolution of these factors in the course of the SARS illness in Hong Kong in 2003.

Methods:  A retrospective analysis of the entire Hong Kong cohort of 1312 laboratory‐confirmed SARS patients aged 15–74 years was undertaken. Demographic, clinical and laboratory data at presentation and investigative data during the first 10 days of illness from the time of symptom onset were compiled. Two adverse outcomes were examined: hospital mortality and the development of oxygenation failure based on the estimated PaO2/FiO2 ratio of <200 mm Hg. Logistic regression was used to identify the association between these prognostic factors and outcomes.

Results:  Based on adjusted odds ratios with a P‐value of <0.05, older age, male gender, elevated pulse rate and elevated neutrophil count were all predictive of oxygenation failure and death during the 10‐day illness. Raised serum albumin and creatinine phosphokinase (CPK) levels were predictive of hospital mortality during this period. The presenting ALT and CPK level and the day 7 and day 10 platelet counts were predictive of oxygenation failure while the day 7 LDH was predictive of death. Contact exposure outside health‐care institutions also appeared to carry higher risk of death.

Conclusion:  This large‐scale analysis identified important discriminatory parameters related to the patients’ demographic profile (age and gender), severity of illness (pulse rate and neutrophil count), and multisystem derangement (platelet count, CPK, ALT and LDH), all of which prognosticated adverse outcomes during the SARS episode. While age, pulse rate and neutrophil count consistently remained significant prognosticators during the first 10 days of illness, the prognostic impact of other derangements was more time‐course dependent. Clinicians should be aware of the time‐course evolution of these prognosticators.
Prevalence of coronary artery abnormality in incomplete Kawasaki disease
Authors: SONOBE TOMOYOSHI , KIYOSAWA NOBUYUKI , TSUCHIYA KEIJI , ASO SEIJIRO , IMADA YOSHIO , IMAI YOKO , YASHIRO MAYUMI , NAKAMURA YOSHIKAZU , YANAGAWA HIROSHI
Published: June 2007

Background: The aim of the present study was to determine the prevalence of coronary artery abnormality (CAA) and other clinical features in patients with incomplete Kawasaki disease (iKD) using the data from the 17th Japanese nationwide survey of KD.

Methods: iKD was defined as the presence of four or fewer of the principal symptoms of the Japanese diagnostic guidelines, regardless of whether the patient had CAA. A total of 15 857 cases were analyzed.

Results: Among 15 857 cases, 83.9% of patients had five to six principal symptoms (complete KD: cKD), and 16.1% had iKD. The prevalence of CAA in cKD was 14.2%, and 18.4% in iKD. The prevalence of CAA in patients with four principal symptoms was 18.1%, which was higher than in cKD cases (14.2%). Although the reliability of the data has some limitations, the prevalence of CAA among patients with one to three symptoms was 19.3%. Among all CAA patients, 14% had four symptoms, and 6% had only one to three symptoms.

Conclusion: Incomplete KD should not be equated with mild KD. Patients with four principal symptoms were comparable to cKD with respect to CAA occurrence. In patients with one to three symptoms also, especially in those under 1 year and older than 4 years of age, other significant symptoms and laboratory findings of the guidelines are very important in making a correct and early diagnosis of iKD so as to prevent CAA.
Is varicocelectomy indicated in subfertile men with clinical varicoceles who have asthenospermia or teratospermia and normal sperm density?
Authors: Okeke Linus , Ikuerowo Odunayo , Chiekwe Ifeanyi , Etukakpan Blessing , Shittu Olayiwola , Olapade‐Olaopa Olubunmi
Published: June 2007

Objective:  Varicocele is the most common treatable cause of male infertility and is associated with progressive decline in testicular function. Varicocelectomy, a commonly performed operation, is indicated in infertile males with varicoceles who have oligospermia, asthenospermia, teratospermia or a combination of these factors. It is not clear if varicocelectomy is indicated if the patients have normal sperm density associated with asthenospermia or teratospermia.

Methods:  We reviewed 167 patients with varicocele‐associated male infertility over a 7‐year period (December 1999–November 2005). Pre‐ and post‐varicocelectomy seminal fluid analyses, assessed using the World Health Organization criteria, were obtained at intervals of 4–6 months. Wilcoxon signed rank tests were used to evaluate for statistical significance and P ≤ 0.05 was considered significant.

Results:  The mean age of the patients and their spouses were 35 and 28 years, respectively. The mean duration of infertility was 3.2 years (range, 1.5–7.5). Oligospermia, teratospermia, asthenospermia, oligospermia, asthenospermia and teratospermia (OAT) syndrome and azoospermia were found preoperatively in 106 (63.5%), 58 (34.7%), 154 (92%), 118 (71%) and 15 (9%) patients, respectively. Overall, significant improvements in semen volume (P < 0.001), sperm density (P < 0.001), sperm motility (P < 0.001) and sperm vitality (P < 0.001) were obtained after varicocelectomy. There was, however, no significant improvement in sperm morphology after varicocelectomy (P = 0.220). When patients with preoperative oligospermia (sperm density, <20 million/mL) were considered separately, varicocelectomy led to significant improvement in all the semen parameters except the sperm morphology (P = 0.183). Conversely, when varicocele patients with a sperm density of ≥20 million/mL (normospermia) associated with asthenospermia and/or teratospermia were considered separately, they did not show significant improvement in any of the semen parameters after varicocelectomy (P > 0.05). In addition, azoospermic patients did not show significant improvement in any of the semen parameters (P > 0.05)

Conclusion:  No significant improvement in semen parameters may be obtained in patients with clinical varicocele and preoperative normospermia. It is possible that only patients with preoperative oligospermia may benefit from varicocelectomy. Larger multi‐institutional studies are needed to determine more definitively if asthenospermia or teratospermia in normospermic subfertile males with clinical varicoceles are in fact indications for varicocelectomy.
Reverse transcriptase‐polymerase chain reaction and immunohistochemical studies for detection of prostate stem cell antigen expression in prostate cancer: Potential value in molecular staging of prostate cancer
Authors: Joung Jae Young , Yang Seung Ok , Jeong In Gab , Han Kyung Suk , Seo Ho Kyung , Chung Jinsoo , Park Weon Seo , Lee Kang Hyun
Published: June 2007

Objectives:  To determine whether detection of prostate stem cell antigen (PSCA) expression has potential for molecular staging in prostate cancer (PCa), we examined the relationship between established prognostic factors, biochemical recurrence (BCR) and PSCA expression.

Methods:  This study was comprised of 66 patients who underwent radical prostatectomy for the treatment of PCa. We employed reverse transcriptase‐polymerase chain reaction (RT‐PCR) to detect PSCA mRNA‐bearing cells in peripheral blood, and used immunohistochemical (IHC) techniques to identify PSCA protein expression in microarrayed tissue.

Results:  PSCA‐mRNA was detected in the peripheral blood of nine (13.6%) patients by RT‐PCR. Whereas 3.2% of patients with low‐grade disease were PSCA positive, 22.9% of patients with high‐grade disease were PSCA positive (P = 0.030). There was also a significant relationship of RT‐PCR PSCA positivity to whether or not the tumor was confined to the prostate. Whereas only 6.8% of patients with prostate‐confined disease were RT‐PCR PSCA positive, 27.3% of extraprostatic diseases were RT‐PCR PSCA positive (P = 0.022). IHC studies of tumor tissue microarrays demonstrated that PSCA expression intensity was related to both extraprostatic extension (P = 0.014) and positive surgical margin (P = 0.053). Whereas 23.8% of prostate‐confined diseases were high intensity, 54.5% of extraprostatic diseases were high intensity. BCR developed in seven patients (10.6%) during the follow‐up period (median, 16.2 months; range, 9–25 months). Prognostic factors increasing the risk of BCR included: seminal vesicle invasion (P = 0.004), extraprostatic disease (P = 0.019), lymphovascular emboli (P = 0.036) and RT‐PCR PSCA positivity (P = 0.004) in univariate analysis.

Conclusions:  We were able to detect PSCA mRNA‐bearing cells in peripheral blood by RT‐PCR, and also identify PSCA protein expression in tumors by IHC analysis of tissue microarrays. RT‐PCR PSCA positivity in peripheral blood may be a potential modality for molecular staging of PCa.
NEDD4L protein truncating variant (v13[G/A]: rs4149601) is associated with essential hypertension in a sample of the Japanese population
Authors: Ishigami Tomoaki , Umemura Masanari , Araki Naomi , Hirawa Nobuhito , Tamura Koichi , Uchino Kazuaki , Umemura Satoshi , Rohrwasser Andreas , Lalouel Jean‐Marc
Published: June 2007

The ubiquitin ligase, NEDD4L, participates in plasma volume and blood pressure regulation by controlling cell surface expression of kidney epithelial sodium channel (ENaC). Impairment of ENaC internalization with disrupting Nedd4L binding PY motif in the C‐terminal of the protein showed rare Mendelian human hypertension disorder, Liddle syndrome. Therefore, possible involvements of ENaC‐Nedd4L system abnormalities were suggested in development of human hypertension. Previously, we discovered a common variant, named v13(G/A), that affects the formation of an evolutionally new C2‐encoding isoform of the Nedd4L gene in humans. The aim of this study was to test a hypothesis whether this variant is involved in essential hypertension; we performed the association study in a sample of the Japanese population. We found a gender‐specific genotypic and allelic association with statistical significance achieved only in males. Our data suggest that this genetic variation may contribute to essential hypertension in Japanese male patients through the mechanism of disrupting the C2 encoding isoform in vivo. Furthermore, molecular and functional studies will be required to elucidate the mechanism by which genetic variation in NEDD4L contributes to the development of essential hypertension.
Identifying interacting predictors of falling among hospitalized elderly in Japan: A signal detection approach
Authors: Nabeshima Atsuko , Hagihara Akihito , Hayashi Kazuo , Nabeshima Shigeki , Okochi Jiro
Published: June 2007

Falling is a complex phenomenon that involves interaction of multiple risk factors. The authors analyzed factors related to falls in a geriatric hospital to elucidate interaction of multiple risk factors for falls in elderly inpatients. Subjects were 364 patients (mean age, 81.7; women 76.7%) who were aged 60 years and over and had been hospitalized for more than 6 months between April 2000 and March 2001. A signal detection model was used to identify baseline variables that best divided the sample into subgroups using incidence of falling as an outcome variable. During a follow‐up period, 91 patients (25%) had at least one incident of fall. Out of 14 independent variables, a higher‐order interaction consisting of six significant variables was identified. Consequently, the subjects were categorized into seven subgroups whose fall rate varied 5.7–80.9%. We found that the combination of non‐bedridden state, dementia, and medication of tranquilizers or sleeping drugs was the highest fall rate (80.9%). Signal detection analysis is useful to identify the combination of multiple risk factors of falling, and applicable to develop prevention programs for each subgroups.
Coupled elastoplasticity and viscoplasticity under thermomechanical loading
Authors: NAGODE M. , FAJDIGA M.
Published: June 2007

This paper is a contribution to material behaviour modelling. Total strain is decomposed into elastoplastic and viscoplastic strains. Both parts are analysed separately and put together by the principle of superposition. The spring‐slider model controlled by either stress or strain enables elastoplasticity modelling under constant or variable temperature with the Prandtl operators. Viscoplasticity is taken into account, if temperature exceeds creep temperature, by adding a nonlinear damper to existing spring‐slider models, otherwise just elastoplasticity is considered. The material parameters result from isothermal strain‐controlled low cycle fatigue (LCF) tests. Hysteresis loops are assumed to be stabilized. The high speed of computation that is characteristic of Masing and memory rules is retained. Solving of differential equations is not required. The model developed so far is uniaxial, but a multiaxial extension is possible.
Brittle fracture of high‐strength steels at very low temperatures
Authors: RODRÍGUEZ‐MARTÍN R. , OCAÑA I. , MARTÍN‐MEIZOSO A.
Published: June 2007

High‐strength steels are used to increase the load carrying capacity of components. However, to guarantee a safe design, it is also necessary to combine high strength with adequate fracture toughness. In this paper, fracture toughness of three high‐strength steels with yield strengths ranging from 460 to 890 MPa has been studied at very low temperatures. Taking into account experimental evidence, a new mechanism of cleavage at very low temperatures is proposed. This mechanism considers the possibility of reaching the ideal strength (the stress at which the lattice of a single crystal losses its stability) in the immediate vicinity of the fatigue crack tip. Moreover, a computational model able to calculate the external load needed to produce a catastrophic failure of these steels has been developed.
Nigrostriatal cell firing action on the dopamine transporter
Authors: Rodriguez Manuel , Gonzalez Sergio , Morales Ingrid , Sabate Magdalena , Gonzalez‐Hernandez Tomas , Gonzalez‐Mora Jose Luis
Published: June 2007

The influence of nigrostriatal cell firing on the dopamine transporter (DAT) activity of the rat striatum was studiedin vivowith amperometric methods. Data were obtained after preventing dopamine (DA) release with α‐methyl‐l‐tyrosine and replenishing extracellular DA with local injections. The DA cell stimulation, which under basal conditions increased extracellular DA, decreased DA after this pre‐treatment, suggesting that firing activity facilitates the DA cell uptake of DA under these circumstances (drain response). Cocaine and GBR13069 markedly decreased the drain response, suggesting that it is dependent on DAT activation. Data obtained after haloperidol and apomorphine administration showed that the drain response was facilitated by pre‐synaptic DA receptor stimulation but that receptors are not a necessary requirement. Two components in the drain response were observed, one with a short latency and duration that needed high‐frequency stimuli, and the other with a long latency and duration that was even induced by low‐frequency stimuli. This is the first evidence showing that DAT can be activated by the firing activity in nigrostriatal cells in a direct way and without the participation of pre‐synaptic DA receptors.
Striatal dysfunction increases basal ganglia output during motor cortex activation in parkinsonian rats
Authors: Belluscio Mariano A. , Riquelme Luis A. , Murer M. Gustavo
Published: June 2007

During movement, inhibitory neurons in the basal ganglia output nuclei show complex modulations of firing, which are presumptively driven by corticostriatal and corticosubthalamic input. Reductions in discharge should facilitate movement by disinhibiting thalamic and brain stem nuclei while increases would do the opposite. A proposal that nigrostriatal dopamine pathway degeneration disrupts trans‐striatal pathways' balance resulting in sustained overactivity of basal ganglia output nuclei neurons and Parkinson's disease clinical signs is not fully supported by experimental evidence, which instead shows abnormal synchronous oscillatory activity in animal models and patients. Yet, the possibility that variation in motor cortex activity drives transient overactivity in output nuclei neurons in parkinsonism has not been explored. In Sprague–Dawley rats with 6‐hydroxydopamine (6‐OHDA)‐induced nigrostriatal lesions, approximately 50% substantia nigra pars reticulata (SNpr) units show abnormal cortically driven slow oscillations of discharge. Moreover, these units selectively show abnormal responses to motor cortex stimulation consisting in augmented excitations of an odd latency, which overlapped that of inhibitory responses presumptively mediated by the trans‐striatal direct pathway in control rats. Delivering D1 or D2 dopamine agonists into the striatum of parkinsonian rats by reverse microdialysis reduced these abnormal excitations but had no effect on pathological oscillations. The present study establishes that dopamine‐deficiency related changes of striatal function contribute to producing abnormally augmented excitatory responses to motor cortex stimulation in the SNpr. If a similar transient overactivity of basal ganglia output were driven by motor cortex input during movement, it could contribute to impeding movement initiation or execution in Parkinson's disease.
Spontaneous glutamate release controls NT‐3‐dependent development of hippocampal calbindin–D28kphenotype through activation of sodium channelsex vivo
Authors: Pieraut Simon , Boukhaddaoui Hassan , Scamps Frédérique , Dayanithi Govindan , Sieso Victor , Valmier Jean
Published: June 2007

Functional NMDA and AMPA ionotropic glutamate receptors are expressed in embryonic hippocampal glutamatergic pyramidal neurons prior to synapse formation but their function and mechanisms of action are still unclear. At the same time, these neurons develop their calbindin–D28kphenotype through an activity‐dependent NT‐3 autocrine loop. Using single‐neuron microcultures, we show here that immature pyramidal neurons spontaneously secreted glutamate and that chronic blockade of either NMDA or AMPA receptors down‐regulated the number of calbindin–D28k‐positive pyramidal neurons without affecting neuronal survival. This antagonistic effect of glutamate ionotropic receptors was mimicked by anti‐TrkC antibodies and reversed by the application of NT‐3. Similar results were obtained inex vivoembryonic hippocampal slice cultures. Moreover, glutamate receptor blockade inhibited the generation of spontaneous sodium‐driven action potentials which, in turn, regulate both the endogenous secretion of NT‐3 and the calbindin–D28kphenotype acquisition. Altogether, these results suggest an unexpected role for glutamate in the development of the physiological and biochemical properties of hippocampal pyramidal neurons and support the idea that glutamate may underlie an activity‐dependent mode of differentiation prior to synapse formation.
Voluntary attention changes the speed of perceptual neural processing
Authors: Noguchi Yasuki , Tanabe Hiroki C. , Sadato Norihiro , Hoshiyama Minoru , Kakigi Ryusuke
Published: June 2007

While previous studies in psychology demonstrated that humans can respond more quickly to the stimuli at attended than unattended locations, it remains unclear whether attention also accelerates the speed of perceptual neural activity in the human brain. One possible reason for this unclarity would be an insufficient spatial resolution of previous electroencephalography (EEG) and magnetoencephalography (MEG) techniques in which neural signals from multiple brain regions are merged with each other. Here, we addressed this issue by combining MEG with a novel stimulus‐presentation technique that can focus on neural signals from higher visual cortex where the magnitude of attentional modulation is prominent. Results revealed that the allocation of spatial attention induces both an increase in neural intensity (attentional enhancement) and a decrease in neural latency (attentional acceleration) to the attended compared to unattended visual stimuli (Experiment 1). Furthermore, an attention‐induced behavioural facilitation reported in previous psychological studies (Posner paradigm) was closely correlated with the neural ‘acceleration’ rather than ‘enhancement’ in the visual cortex (Experiment 2). In addition to bridging a gap between previous psychological and neurological findings, our results demonstrated a temporal dynamics of attentional modulation in the human brain.
The phagocytic capacity of neurones
Authors: Bowen Samantha , Ateh Davidson D. , Deinhardt Katrin , Bird Margaret M. , Price Karen M. , Baker Cathy S. , Robson Joanna C. , Swash Michael , Shamsuddin Wassim , Kawar Shalini , El‐Tawil Tariq , Roos Jesper , Hoyle Andrew , Nickols Carole D. , Knowles Charles H. , Pullen Anthony H. , Luthert Phillip J. , Weller Roy O. , Hafezparast Majid , Franklin Robin J. M. , Revesz Tamas , King Rosalind H. M. , Berninghausen Otto , Fisher Elizabeth M. C. , Schiavo Giampietro , Martin Joanne E.
Published: June 2007

Phagocytosis is defined as the ingestion of particulates over 0.5 µm in diameter and is associated with cells of the immune system such as macrophages or monocytes. Neurones are not generally recognized to be phagocytic. Using light, confocal, time‐lapse and electron microscopy, we carried out a wide range of in‐vitro and in‐vivo experiments to examine the phagocytic capacity of different neuronal cell types. We demonstrated phagocytosis of material by neurones, including cell debris and synthetic particles up to 2.8 µm in diameter. We showed phagocytosis in different neuronal types, and demonstrated that debris can be transported from neurite extremities to cell bodies and persist within neurones. Flow cytometry analysis demonstrated the lack of certain complement receptors on neurones but the presence of others, including integrin receptors known to mediate macrophage phagocytosis, indicating that a restricted set of phagocytosis receptors may mediate this process. Neuronal phagocytosis occurs in vitro and in vivo, and we propose that this is a more widespread and significant process than previously recognized. Neuronal phagocytosis may explain certain inclusions in neurones during disease, cell‐to‐cell spread of disease, neuronal death during disease progression and provide a potential mechanism for therapeutic intervention through the delivery of particulate drug carriers.
Acute stress‐mediated increases in extracellular glutamate levels in the rat amygdala: differential effects of antidepressant treatment
Authors: Reznikov Leah R. , Grillo Claudia A. , Piroli Gerardo G. , Pasumarthi Ravi K. , Reagan Lawrence P. , Fadel Jim
Published: June 2007

Depressive illness is associated with changes in amygdalar volume, and stressful life events are known to precipitate depressive episodes in this patient population. Stress affects amygdalar synaptic plasticity and several neurotransmitter systems have been implicated in stress‐mediated changes in the brain, including the glutamatergic system. However, the role of the glutamatergic system in stress‐mediated plasticity in the amygdala remains to be determined. Accordingly the current study examined the stress modulation of extracellular glutamate levels in the basolateral nucleus (BLA) and the central nucleus (CeA) of the amygdala byin vivomicrodialysis. Acute stress increased extracellular glutamate levels in the BLA and CeA, although the dynamics of these stress‐mediated changes were dramatically different in these amygdalar nuclei. Tetrodotoxin administration reduced basal, and completely eliminated stress‐mediated increases in glutamate efflux in the amygdala, demonstrating that stress effects are dependent on local axonal depolarization. Moreover, stress‐mediated increases in glutamate efflux in the BLA were inhibited by the antidepressant tianeptine but not by the selective serotonin‐reuptake inhibitor fluoxetine. Collectively, these data demonstrate that stress‐induced modulation of glutamate neurochemistry reflects a fundamental pathological change that may contribute to the aetiology and progression of depressive illness, and suggest that some antidepressants such as tianeptine may elicit their clinical effects by modulation of glutamatergic neurotransmission.
Testosterone decreases reactive astroglia and reactive microglia after brain injury in male rats: role of its metabolites, oestradiol and dihydrotestosterone
Authors: Barreto George , Veiga Sergio , Azcoitia Iñigo , Garcia‐Segura Luis M. , Garcia‐Ovejero Daniel
Published: June 2007

Previous studies have shown that the neuroprotective hormone, testosterone, administered immediately after neural injury, reduces reactive astrogliosis. In this study we have assessed the effect of early and late therapy with testosterone or its metabolites, oestradiol and dihydrotestosterone, on reactive astroglia and reactive microglia after a stab wound brain injury in orchidectomized Wistar rats. Animals received daily s.c. injections of testosterone, oestradiol or dihydrotestosterone on days 0–2 or on days 5–7 after injury. The number of vimentin immunoreactive astrocytes and the volume fraction of major histocompatibility complex‐II (MHC‐II) immunoreactive microglia were estimated in the hippocampus in the lateral border of the wound. Both early and delayed administration of testosterone or oestradiol, but not dihydrotestosterone, resulted in a significant decrease in the number of vimentin‐immunoreactive astrocytes. The volume fraction of MHC‐II immunoreactive microglia was significantly decreased in the animals that received testosterone or oestradiol in both early and delayed treatments and in animals that received early dihydrotestosterone administration. Thus, both early and delayed administration of testosterone reduces reactive astroglia and reactive microglia and these effects may be at least in part mediated by oestradiol, while dihydrotestosterone may mediate part of the early effects of testosterone on reactive microglia. In conclusion, testosterone controls reactive gliosis and its metabolites, oestradiol and dihydrotestosterone, may be involved in this hormonal effect. The regulation of gliosis may be part of the neuroprotective mechanism of testosterone.
Long‐term reduction of brain‐derived neurotrophic factor levels and signaling impairment following prenatal treatment with the cannabinoid receptor 1 receptor agonist (R)‐(+)‐[2,3‐dihydro‐5‐methyl‐3‐(4‐morpholinyl‐methyl) pyrrolo[1,2,3‐de]‐1,4‐benzoxazin‐6‐yl]‐1‐ naphthalenylmethanone
Authors: Maj Paola Francesca , Collu Maria , Fadda Paola , Cattaneo Annamaria , Racagni Giorgio , Riva Marco Andrea
Published: June 2007

It is well accepted that adverse life events occurring early in development may alter the correct program of brain maturation leading to enhanced vulnerability to neuropsychiatric disorders. It has recently been demonstrated that prenatal exposure to the cannabinoid receptor 1 agonist (R)‐(+)‐[2,3‐dihydro‐5‐methyl‐3‐(4‐morpholinyl‐methyl)pyrrolo[1,2,3‐de]‐1,4‐benzoxazin‐6‐yl]‐1‐naphthalenylmethanone (WIN 55,212‐2) produces memory deficit in adulthood, an effect associated with a reduced functionality of the glutamatergic system. The aim of our study was to identify molecular changes produced by prenatal exposure to WIN 55,212‐2 that might contribute to late disruption in synaptic plasticity and cognition. For this purpose, WIN 55,212‐2 was injected in pregnant wistar rats from gestation day 5 to 20 and a detailed analysis of the levels of the neurotrophin brain‐derived neurotrophic factor (BDNF) as well as of the signaling molecules extracellular signal‐regulated kinase (ERK)1/2 and α‐calcium/calmodulin‐dependent protein kinase II (α‐CaMKII) was carried out in adult offspring. We found that exposure to WIN 55,212‐2 significantly reduced BDNF levels in hippocampus and frontal cortex. This effect was associated with decreased activation of pathways linked to neurotrophin and glutamate receptor signaling. In particular, prenatal cannabinoid treatment reduced the phosphorylated levels of ERK1/2 in selected subcellular compartments of hippocampus, frontal and prefrontal cortex, whereas no changes were observed in the total levels of these proteins. Furthermore, a robust reduction of total and phospho‐α‐CaMKII was found in the hippocampus of rats prenatally exposed to WIN 55,212‐2. In summary, the present data suggest that deficits of BDNF levels and signaling through ERK1/2 and α‐CaMKII might contribute to cognitive and neuroplastic defects associated with prenatal exposure to cannabinoids.
Cloning and early expression pattern of two melatonin biosynthesis enzymes in the turbot (Scophthalmus maximus)
Authors: Vuilleumier Robin , Boeuf Gilles , Fuentes Michael , Gehring Walter J. , Falcón Jack
Published: June 2007

Melatonin biosynthesis from serotonin involves the sequential activation of the arylalkylamine N‐acetyltransferase (AANAT) and hydroxyindole‐O‐methyltransferase (HIOMT). Photoperiod synchronizes a daily rhythm in pineal and retinal melatonin secretion through controlling AANAT activity. Teleost fish possess two Aanat, one expressed in the retina (AANAT1) and the other expressed in the pineal gland (AANAT2). We report here the full‐length cloning of Aanat1, Aanat2, SmHiomt and Otx5 (orthodenticle homeobox homolog 5) in the turbot (Scophthalmus maximus, Sm), a flatfish belonging to an evolutionary recent group of Teleost. The temporal expression pattern of the genes investigated is consistent with the idea that OTX5 is needed for photoreceptor specification, and that the pineal gland differentiates before the retina. SmAanat2 expression remained pineal specific during the period of time investigated, whereas SmOtx5 and SmHiomt expressions were seen in both the retina and pineal gland. Our results do not support the existence of a second SmHiomt, as is the case for SmAanat. Neither SmAanat2 nor SmHiomt mRNAs displayed cyclic accumulation in the pineal organ of embryos and larvae maintained under a light–dark cycle from fertilization onward. This is in marked contrast with the situation observed with zebrafish Aanat2, indicating that the molecular mechanisms controlling the development of the pineal melatonin system have been modified during the evolution of Teleost.
Incorporating dispersal distance into the disperser effectiveness framework: frugivorous birds provide complementary dispersal to plants in a patchy environment
Authors: Spiegel Orr , Nathan Ran
Published: June 2007

Fleshy‐fruited plants are usually dispersed by an array of frugivores, differing in the effectiveness of the dispersal service they provide to the plant. Body size differences among frugivores are hypothesized to affect seed dispersal distances and consequently their effectiveness as dispersers. We tested this hypothesis by comparing the effectiveness of two passerine birds, grackles (Onychognathus tristramii) and bulbuls (Pycnonotus xanthopygos), dispersing the desert shrub Ochradenus baccatus. Laboratory experiments, quantifying gut retention time and the effect on germination, were combined with field observations quantifying bird movements and fruit consumption rates. An empirically parameterized mechanistic model showed that the two dispersers switch roles as a function of spatial‐scale: while most seeds within the local habitat were dispersed by bulbuls, the larger grackles were exclusively responsible for between‐patches, long‐distance dispersal. We suggest that distance‐related differences are common and important to plant fitness, and thus should explicitly be considered in studies of disperser effectiveness.
The multicopper oxidase (CueO) and cell aggregation in Escherichia coli
Authors: Tree Jai J. , Ulett Glenn C. , Hobman Jon L. , Constantinidou Chrystala , Brown Nigel L. , Kershaw Christopher , Schembri Mark A. , Jennings Michael P. , McEwan Alastair G.
Published: June 2007

cueO encodes a periplasmic multicopper oxidase, which is known to be involved in copper homeostasis and protection against oxidative stress in Escherichia coli K12. Transcriptional profiling showed that expression of genes associated with motility was lowered in a cueO mutant while expression of genes associated with autoaggregation was elevated. Increased aggregation was correlated with increased expression of cell surface proteins antigen 43 and curli. Changes in gene expression caused by the deletion of cueO were essentially independent of SoxR and OxyR, the global regulators of oxidative stress response.
Local scale DNA barcoding of bivalves (Mollusca): a case study
Authors: Mikkelsen Nina T. , Schander Christoffer , Willassen Endre
Published: June 2007

Divergence in cytochrome c oxidase 1 (COI), the genetic marker proposed for DNA barcoding, was investigated in marine bivalves from the genera Ennucula, Nucula, Yoldiella and Thyasira. No overlap in levels of intra‐ and interspecific variation was found. The levels of divergence found suggest that barcodes from COI will be useful in distinguishing between the species investigated in this study. The insufficiency of blast searches in GenBank to assign many of the obtained sequences to correct phylum was noted and clearly demonstrates the need for better search strategies specifically targeted at identification using DNA barcodes.
Bilateral synchronous sporadic renal cell carcinoma: surgical management, oncological and functional outcomes
Authors: Pahernik Sascha , Cudovic Dragan , Roos Frederik , Melchior Sebastian W. , Thüroff Joachim W.
Published: June 2007

OBJECTIVE

To analyse the functional and oncological outcomes of surgical treatment of bilateral synchronous sporadic renal cell carcinoma (RCC).

PATIENTS AND METHODS

Between 1969 and 2006, 57 patients with bilateral synchronous sporadic RCC were identified from our kidney database. The mean (range) follow‐up was 4.8 (0.1–23.8) years; 28 patients (49%) had radical nephrectomy (RN) and contralateral nephron‐sparing surgery (NSS), and 22 (39%) had bilateral NSS. The oncological outcome and long‐term renal function were analysed.

RESULTS

After excluding four patients (7%) with bilateral benign renal tumours, six (11%) with metastatic bilateral RCC and three (5%) who had bilateral RN, the cancer‐specific outcome was analysed. For 44 patients with bilateral RCC who had surgery with intent to cure and avoid dialysis, 13 (30%) had stage pT1a, 10 (23%) pT1b, nine (17%) pT2 and 12 (27%) pT3 disease. At 5 and 10 years, the cancer‐specific survival rates were 86% and 75%, and the local recurrence‐free survival rates were 87% and 80%. The median serum creatinine level at the latest follow‐up was 1.18 mg/dL in patients after bilateral NSS and 1.40 mg/dL after unilateral NSS and contralateral RN (P < 0.05).

CONCLUSIONS

These long‐term data support the concept that NSS, whenever possible bilateral, is the treatment of choice for bilateral synchronous sporadic RCC. NSS provides adequate local tumour control and cancer‐specific survival. Preservation of renal function is more efficient with bilateral NSS than with unilateral NSS and contralateral RN.
The Dual State: The Unruly “Subordinate”, Caste, Community And Civil Service Recruitment In North India, 1930–1955
Authors: GOULD WILLIAM
Published: June 2007

Abstract  This paper explores the nature of the everyday state in historical perspective in colonial and postcolonial Uttar Pradesh, north India, through the lens of civil service recruitment. It argues that social relationships between different cadres of the revenue and police services effectively created a bureaucratic space in which citizens' approaches to the state recreated forms of ambiguity in the reach and authority of state power. In this sense, it provides a deeper historical basis for anthropological and sociological work on the nature of the “fuzzy” everyday state in postcolonial India. But it develops this literature further, arguing that important structural changes over independence in 1947, also transformed the ways in which caste and community lobby groups represented their corporate interests through bureaucratic recruitment. These lobby groups, as a result of disjunctions in state power and discourses, between centre, province and locality, were often able to subvert systems of caste and community reservation. In the process, their actions emphasized the inability of the state at central and provincial levels to adjust to local political identities that depended on hybridity.
The Politics of Commensuration: The Violence of Partition and the Making of the Pakistani State
Authors: NAQVI TAHIR HASNAIN
Published: June 2007

Abstract  This article examines how official representations of the violence and displacement of Partition organized the sovereign power of the post‐independence Pakistani state. It addresses how Partition's chain of violence and displacement engendered the state as an entity capable of wielding the sovereign power to decide on life and death. Crucial to this process were practices of knowledge and power in which the refugee was produced ambivalently, as a figure of right and a biopolitical problem in need of resolution. Focusing on Pakistan's official response to the “refugee problem”, I analyze how the management of the potential and actual movement of populations relied upon, and informed implicit logics of official commensuration with the communal violence of the mass.
“There is a village somewhere out there”: Representations of Anatolia as Terra Incognita”
Authors: YAKIN ASLI YAZICI
Published: June 2007

Abstract  Travel notes on Anatolia written in Turkey until the 1950's represent Anatolia as terra incognita. Anatolia becomes invisible through the values attributed to community relationships and the statements about the sameness of the rural area. Invisibility here is a syndrome of modernity, which based on positivist epistemology
Situation‐Based Contingencies Underlying Trait‐Content Manifestation in Behavior
Authors: Fleeson William
Published: June 2007

ABSTRACTTwo studies investigated whether situations are associated with the manifestation of Big Five trait contents in behavior. Several times per day for 2 or 5 weeks, participants reported their current Extraversion, Agreeableness, Conscientiousness, and Emotional Stability states and rated the concurrent situation on several characteristics. Multilevel models tested for the average individual's contingency of each Big Five state on each situation characteristic and for whether individuals differed from each other reliably in those contingencies. Results showed that (1) there are psychologically active characteristics of situations on which trait‐manifesting behavior is contingent; (2) contingencies on psychologically active characteristics of varying situations are part of the explanation for the sizeable within‐person variability in behavior; (3) individuals differ reliably in their contingencies, and such individual differences may partially explain individual differences in amount of variability; and (4) the situation characteristics that are psychologically active differ by trait. These findings suggest that within‐person variability in personality states is meaningful and is related to situations, that personality psychology should characterize situations in terms of their relevance to personality states, and that process and individual‐difference structure approaches can be integrated in personality psychology.
A Nested Clustering Technique for Freeway Operating Condition Classification
Authors: Xia Jingxin , Chen Mei
Published: June 2007

Abstract:  This article introduces a nested clustering technique and its application to the analysis of freeway operating condition. A clustering model is developed using the traffic data (flow, speed, occupancy) collected by the detectors and aggregated to 5‐minute increments. An optimum fit of the statistical characteristics of the data set is provided by the model based on the Bayesian Information Criterion and the ratio of changes in dispersion measurement. This technique is flexible in determining the number of clusters based on the statistical characteristics of the data. Tests on multiple sites with varying operating conditions have attested to its effectiveness as a data mining tool for the analysis of freeway operating condition.
Research and development (R&D) beyond manufacturing: the strange case of services R&D
Authors: Miles Ian
Published: June 2007

The share of business research and development (R&D) expenditure stemming from the services sector of the economy has been growing rapidly in many (though not all) OECD countries, according to official statistics. The same data sources also indicate, however, that services contribute less to R&D than would be expected given their large shares of employment and output in national economies. In part, incomplete sampling of services in R&D surveys may lead to some underestimation of their R&D activity, but this is unlikely to account for their apparently poor performance. This paper draws on an analysis of existing statistical sources, and on interviews and workshops with service firms' managers. It finds difficulties associated with the ways in which R&D has been operationalised in survey questions. Examination of survey questionnaires suggests that the formulation of these questions, focusing on technological R&D and ruling out much social scientific R&D, disproportionately reduces the reporting of R&D by service firms. But beyond this, the R&D concept itself has some problematic features where it comes to documenting innovation in service firms. This was investigated through a programme of interviews and workshops with service firms, where a lack of familiarity with the R&D concept and R&D management practices was found to be commonplace. R&D performance and innovation activities vary across services of different sorts, even though most service subsectors appear to be low R&D investors. It is thus important to examine services' innovation patterns and processes, to establish what types of R&D‐like activity are underway in these subsectors. While some modification in R&D measurement would be desirable to capture services' activities, effort to understand the non‐R&D elements of services innovation is also important – for management and for policy (given that governments are seeking to create R&D incentives and targets for services and other sectors).

There are grounds for expecting (a) services' share of business R&D to continue to grow; (b) this share to continue to be well below what would be expected from the prevalence of services in economic activity, and (c) for many services' innovation to continue to rely heavily on sources that are not directly associated with R&D.