bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression profile of mucins (MUC2, MUC5AC and MUC6) in Helicobacter pylori infected pre-neoplastic and neoplastic human gastric epithelium
Authors: Babu Subramani Durai , Jayanthi Venkataraman , Devaraj Niranjali , Reis Celso A , Devaraj Halagowder
Published: April 2006

Background

Helicobacter pylori (H. pylori) causes gastritis and intestinal metaplasia (IM) that may evolve to gastric carcinoma. The objective of this study was to compare the profile of mucins in the progressive stages of H. pylori infected pre-neoplastic and neoplastic human gastric epithelium. We used a panel of monoclonal antibodies with well-defined specificities of MUC2, MUC5AC and MUC6 to characterize the expression pattern of mucins by immunohistochemistry.

Methods

RUT and ELISA were down for H. pylori confirmation. Human gastric biopsy sections were stained using immunohistochemistry with MUC2, MUC5AC and MUC6 antibodies.

Results

MUC5AC was expressed in the superficial epithelium and the upper part of the gastric pits. MUC6 expression was detected in the lower part of the gastric glands. MUC2 was expressed in intestinal metaplasia, mostly in goblet cells. The mucin expression profile in the progressive stages of H. pylori infected human gastric epithelium allows the identification of intestinal metaplasia, which is characterized by a decreased expression of the gastric mucins (MUC5AC and MUC6) and de novo expression of MUC2.

Conclusion

In conclusion, our results suggest that there is altered expression of MUC5AC and MUC6 together with the aberrant expression of MUC2 in intestinal metaplasia, during the process of gastric carcinogenesis. The present study indicates that the MUC2 mucin expression pattern is a reliable marker of intestinal metaplasia, which appears in the context of H. pylori infected individuals.
Application of cytology and molecular biology in diagnosing premalignant or malignant oral lesions
Authors: Mehrotra Ravi , Gupta Anurag , Singh Mamta , Ibrahim Rahela
Published: April 2006

Early detection of a premalignant or cancerous oral lesion promises to improve the survival and the morbidity of patients suffering from these conditions. Cytological study of oral cells is a non-aggressive technique that is well accepted by the patient, and is therefore an attractive option for the early diagnosis of oral cancer, including epithelial atypia and squamous cell carcinoma. However its usage has been limited so far due to poor sensitivity and specificity in diagnosing oral malignancies. Lately it has re-emerged due to improved methods and it's application in oral precancer and cancer as a diagnostic and predictive method as well as for monitoring patients. Newer diagnostic techniques such as "brush biopsy" and molecular studies have been developed. Recent advances in cytological techniques and novel aspects of applications of scraped or exfoliative cytology for detecting these lesions and predicting their progression or recurrence are reviewed here.
A cross-sectional study of health-related quality of life deficits in individuals with comorbid diabetes and cancer
Authors: Bowker Samantha L , Pohar Sheri L , Johnson Jeffrey A
Published: April 2006

Background

Numerous studies have identified a reduced health related quality of life (HRQL) in patients that have either diabetes or cancer. We assessed the HRQL burden in patients with these comorbid conditions, postulating that they would have even greater HRQL deficits.

Methods

Data from the Public Use File of the Canadian Community Health Survey (PUF CCHS) Cycle 1.1 (September 2000–November 2001) were used for this analysis. The total sample size of the CCHS PUF is 130,880 individuals. We used the Health Utilities Index Mark 3 (HUI3) to assess HRQL in patients with: 1) comorbid diabetes and cancer, 2) diabetes alone, 3) cancer alone, and 4) no diabetes or cancer. Analysis of covariance was used to compare the mean overall HUI3 score, controlling for age, sex, marital status, body mass index (BMI), physical activity level, smoking status, education level, depression status, and other chronic conditions.

Results

We identified 113,587 individuals (87%) with complete data for the analysis. The comorbid diabetes and cancer group were older and a larger proportion reported being obese, inactive, having less than a secondary education and more chronic conditions when compared to the other three cohorts (p < 0.0001). However, the diabetes and cancer cohort was less likely to be depressed (p < 0.0001). Overall HUI3 scores were significantly lower for the diabetes and cancer group (unadjusted mean (SD): 0.67 (0.30)), compared to diabetes (0.78 (0.27)), cancer (0.78 (0.25)), and the reference group (0.89 (0.18)) (p < 0.0001). After adjusting for covariates, the comorbid diabetes and cancer group continued to have significantly lower overall HUI3 scores than the reference group (unstandardized mean difference: -0.11, 95% CI: -0.13 to -.0.09) (p < 0.0001).

Conclusion

Individuals with diabetes and cancer had a clinically important and significantly lower HRQL than those with either condition alone. A better understanding of the relationship between diabetes and cancer, and their associated comorbidities, complications, and HRQL deficits may have important implications for prevention and management strategies.
Assessing normative cut points through differential item functioning analysis: An example from the adaptation of the Middlesex Elderly Assessment of Mental State (MEAMS) for use as a cognitive screening test in Turkey
Authors: Tennant Alan , Küçükdeveci Ayse A , Kutlay Sehim , Elhan Atilla H
Published: April 2006

Background

The Middlesex Elderly Assessment of Mental State (MEAMS) was developed as a screening test to detect cognitive impairment in the elderly. It includes 12 subtests, each having a 'pass score'. A series of tasks were undertaken to adapt the measure for use in the adult population in Turkey and to determine the validity of existing cut points for passing subtests, given the wide range of educational level in the Turkish population. This study focuses on identifying and validating the scoring system of the MEAMS for Turkish adult population.

Methods

After the translation procedure, 350 normal subjects and 158 acquired brain injury patients were assessed by the Turkish version of MEAMS. Initially, appropriate pass scores for the normal population were determined through ANOVA post-hoc tests according to age, gender and education. Rasch analysis was then used to test the internal construct validity of the scale and the validity of the cut points for pass scores on the pooled data by using Differential Item Functioning (DIF) analysis within the framework of the Rasch model.

Results

Data with the initially modified pass scores were analyzed. DIF was found for certain subtests by age and education, but not for gender. Following this, pass scores were further adjusted and data re-fitted to the model. All subtests were found to fit the Rasch model (mean item fit 0.184, SD 0.319; person fit -0.224, SD 0.557) and DIF was then found to be absent. Thus the final pass scores for all subtests were determined.

Conclusion

The MEAMS offers a valid assessment of cognitive state for the adult Turkish population, and the revised cut points accommodate for age and education. Further studies are required to ascertain the validity in different diagnostic groups.
Desmoid tumor in Gardner's Syndrome presented as acute abdomen
Authors: Hatzimarkou Andreas , Filippou Dimitrios , Papadopoulos Vasilios , Filippou Georgios , Rizos Spiros , Skandalakis Panagiotis
Published: April 2006

Background

Gardner's syndrome can occasionally be complicated with intra-abdominal desmoid tumor. These tumors usually remain asymptomatic but can exhibit symptoms due to intestinal, vascular and ureteral compression and obstruction.

Case presentation

A rare case of a 41-year-old male patient with Gardner's syndrome complicated with intra-abdominal desmoid tumor, which first presented as acute abdomen, is presented.

Conclusion

Extra-abdominal manifestations of Gardner's syndrome along with a palpable abdominal mass would raise suspicion for the presence of a desmoid tumor in the majority of cases. In life-threatening cases, surgical treatment should be considered as a palliative approach, though the extent of excision remains debatable
Zygote arrest 1 gene in pig, cattle and human: evidence of different transcript variants in male and female germ cells
Authors: Uzbekova Svetlana , Roy-Sabau Monica , Dalbiès-Tran Rozenn , Perreau Christine , Papillier Pascal , Mompart Florence , Thelie Aurore , Pennetier Sophie , Cognie Juliette , Cadoret Veronique , Royere Dominique , Monget Philippe , Mermillod Pascal
Published: April 2006

Background

Zygote arrest 1 (ZAR1) is one of the few known oocyte-specific maternal-effect genes essential for the beginning of embryo development discovered in mice. This gene is evolutionary conserved in vertebrates and ZAR1 protein is characterized by the presence of atypical plant homeobox zing finger domain, suggesting its role in transcription regulation. This work was aimed at the study of this gene, which could be one of the key regulators of successful preimplantation development of domestic animals, in pig and cattle, as compared with human.

Methods

Screenings of somatic cell hybrid panels and in silico research were performed to characterize ZAR1 chromosome localization and sequences. Rapid amplification of cDNA ends was used to obtain full-length cDNAs. Spatio-temporal mRNA expression patterns were studied using Northern blot, reverse transcription coupled to polymerase chain reaction and in situ hybridization.

Results

We demonstrated that ZAR1 is a single copy gene, positioned on chromosome 8 in pig and 6 in cattle, and several variants of correspondent cDNA were cloned from oocytes. Sequence analysis of ZAR1 cDNAs evidenced numerous short inverted repeats within the coding sequences and putative Pumilio-binding and embryo-deadenylation elements within the 3'-untranslated regions, indicating the potential regulation ways. We showed that ZAR1 expressed exclusively in oocytes in pig ovary, persisted during first cleavages in embryos developed in vivo and declined sharply in morulae and blastocysts. ZAR1 mRNA was also detected in testis, and, at lower level, in hypothalamus and pituitary in both species. For the first time, ZAR1 was localized in testicular germ cells, notably in round spermatids. In addition, in pig, cattle and human only shorter ZAR1 transcript variants resulting from alternative splicing were found in testis as compared to oocyte.

Conclusion

Our data suggest that in addition to its role in early embryo development highlighted by expression pattern of full-length transcript in oocytes and early embryos, ZAR1 could also be implicated in the regulation of meiosis and post meiotic differentiation of male and female germ cells through expression of shorter splicing variants. Species conservation of ZAR1 expression and regulation underlines the central role of this gene in early reproductive processes.
Interleukin-1 mediates Alzheimer and Lewy body pathologies
Authors: Griffin W Sue T , Liu Ling , Li Yuekui , Mrak Robert E , Barger Steven W
Published: April 2006

Background

Clinical and neuropathological overlap between Alzheimer's (AD) and Parkinson's disease (PD) is now well recognized. Such cases of concurrent AD and Lewy body disease (AD/LBD) show neuropathological changes that include Lewy bodies (α-synuclein aggregates), neuritic amyloid plaques, and neurofibrillary tangles (hyperphosphorylated tau aggregates). The co-occurrence of these clinical and neuropathological changes suggests shared pathogenic mechanisms in these diseases, previously assumed to be distinct. Glial activation, with overexpression of interleukin-1 (IL-1) and other proinflammatory cytokines, has been increasingly implicated in the pathogenesis of both AD and PD.

Methods

Rat primary cultures of microglia and cortical neurons were cultured either separately or as mixed cultures. Microglia or cocultures were treated with a secreted fragment (sAPPα) of the β-amyloid precursor protein (βAPP). Neurons were treated with IL-1β or conditioned medium from sAPPα-activated microglia, with or without IL-1 receptor antagonist. Slow-release pellets containing either IL-1β or bovine serum albumin (control) were implanted in cortex of rats, and mRNA for various neuropathological markers was analyzed by RT-PCR. Many of the same markers were assessed in tissue sections from human cases of AD/LBD.

Results

Activation of microglia with sAPPα resulted in a dose-dependent increase in secreted IL-1β. Cortical neurons treated with IL-1β showed a dose-dependent increase in sAPPα release, an effect that was enhanced in the presence of microglia. IL-1β also elevated the levels of α-synuclein, activated MAPK-p38, and phosphorylated tau; a concomitant decrease in levels of synaptophysin occurred. Delivery of IL-1β by slow-release pellets elevated mRNAs encoding α-synuclein, βAPP, tau, and MAPK-p38 compared to controls. Finally, human cases of AD/LBD showed colocalization of IL-1-expressing microglia with neurons that simultaneously overexpressed βAPP and contained both Lewy bodies and neurofibrillary tangles.

Conclusion

Our findings suggest that IL-1 drives production of substrates necessary for formation of the major neuropathological changes characteristic of AD/LBD.
Cyclooxygenase-2 mediates microglial activation and secondary dopaminergic cell death in the mouse MPTP model of Parkinson's disease
Authors: Vijitruth Rattanavijit , Liu Mei , Choi Dong-Young , Nguyen Xuan V , Hunter Randy L , Bing Guoying
Published: April 2006

Background

Accumulating evidence suggests that inflammation plays an important role in the progression of Parkinson's disease (PD). Among many inflammatory factors found in the PD brain, cyclooxygenase (COX), specifically the inducible isoform, COX-2, is believed to be a critical enzyme in the inflammatory response. Induction of COX-2 is also found in an experimental model of PD produced by administration of 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Method

COX-2-deficient mice or C57BL/6 mice were treated with MPTP to investigate the effects of COX-2 deficiency or by using various doses of valdecoxib, a specific COX-2 inhibitor, which induces inhibition of COX-2 on dopaminergic neuronal toxicity and locomotor activity impairment. Immunohistochemistry, stereological cell counts, immunoblotting, an automated spontaneous locomotor activity recorder and rotarod behavioral testing apparatus were used to assess microglial activation, cell loss, and behavioral impariments.

Results

MPTP reduced tyrosine hydroxylase (TH)-positive cell counts in the substantia nigrapars compacta(SNpc); total distance traveled, vertical activity, and coordination on a rotarod; and increased microglia activation. Valdecoxib alleviated the microglial activation, the loss of TH-positive cells and the decrease in open field and vertical activity. COX-2 deficiency attenuated MPTP-induced microglial activation, degeneration of TH-positive cells, and loss of coordination.

Conclusion

These results indicate that reducing COX-2 activity can mitigate the secondary and progressive loss of dopaminergic neurons as well as the motor deficits induced by MPTP, possibly by suppression of microglial activation in the SNpc.
The retrovirus RNA trafficking granule: from birth to maturity
Authors: Cochrane Alan W , McNally Mark T , Mouland Andrew J
Published: April 2006

Post-transcriptional events in the life of an RNA including RNA processing, transport, translation and metabolism are characterized by the regulated assembly of multiple ribonucleoprotein (RNP) complexes. At each of these steps, there is the engagement and disengagement of RNA-binding proteins until the RNA reaches its final destination. For retroviral genomic RNA, the final destination is the capsid. Numerous studies have provided crucial information about these processes and serve as the basis for studies on the intracellular fate of retroviral RNA. Retroviral RNAs are like cellular mRNAs but their processing is more tightly regulated by multiple cis-acting sequences and the activities of many trans-acting proteins. This review describes the viral and cellular partners that retroviral RNA encounters during its maturation that begins in the nucleus, focusing on important events including splicing, 3' end-processing, RNA trafficking from the nucleus to the cytoplasm and finally, mechanisms that lead to its compartmentalization into progeny virions.
Reconstruction of skeletal movement using skin markers: comparative assessment of bone pose estimators
Authors: Cereatti Andrea , Della Croce Ugo , Cappozzo Aurelio
Published: April 2006

Background

The assessment of the accuracy of the pose estimation of human bones and consequent joint kinematics is of primary relevance in human movement analysis. This study evaluated the performance of selected pose estimators in reducing the effects of instrumental errors, soft tissue artifacts and anatomical landmark mislocations occurring at the thigh on the determination of the knee kinematics.

Methods

The pattern of a typical knee flexion-extension during a gait cycle was fed into a knee model which generated a six-components knee kinematics and relevant marker trajectories. The marker trajectories were corrupted with both instrumental noise and soft tissue artifacts. Two different cluster configurations (4 and 12-marker cluster) were investigated. Four selected pose estimators, a Geometrical method, a SVD-based method, and the Pointer Cluster Technique in the optimized and non optimized version, were analyzed. The estimated knee kinematics were compared to the nominal kinematics in order to evaluate the accuracy of the selected pose estimators.

Results

Results have shown that optimal pose estimators perform better than traditional geometric pose estimators when soft tissue artifacts are present. The use of redundant markers improved in some cases the estimation of the dynamics of the kinematics patterns, while it does not reduce the offsets from the nominal kinematics curves. Overall, the best performance was obtained by the SVD-based pose estimator, while the performance of the PCT pose estimator in its optimal version was not satisfactory. However, the knee kinematics errors reached 5 deg for rotations and 10 mm for translations).

Conclusion

Given the favorable experimental conditions of this study (soft tissue artifacts determined from a young, healthy and non overweight subject), the errors found in estimating the knee kinematics have to be considered unsatisfactory even if the best performing pose estimator is used. Therefore, it is the authors' opinion that the movement analysis research community should make additional efforts in the search of more subject specific error models to increase the accuracy of joint kinematics estimations.
Genome comparison of two Coccolithoviruses
Authors: Allen Michael J , Schroeder Declan C , Donkin Andrew , Crawfurd Katharine J , Wilson William H
Published: April 2006

Background

The Coccolithoviridae is a recently discovered family of viruses that infect the marine coccolithophorid Emiliania huxleyi. Following on from the sequencing of the type strain EhV-86, we have sequenced a second strain, EhV-163.

Results

We have sequenced approximately 80% of the EhV-163 genome, equating to more than 200 full length CDSs. Conserved and variable CDSs and a gene replacement have been identified in the EhV-86 and EhV-163 genomes.

Conclusion

The sequencing of EhV-163 has provided a wealth of information which will aid the re-annotating of the EhV-86 genome and identified a gene insertion in EhV-163.
Testosterone correlates with Venezuelan equine encephalitis virus infection in macaques
Authors: Muehlenbein Michael P , Cogswell Frank B , James Mark A , Koterski James , Ludwig George V
Published: April 2006

Here we briefly report testosterone and cytokine responses to Venezuelan equine encephalitis virus (VEEV) in macaques which were used as part of a larger study conducted by the Department of Defense to better characterize pathological responses to aerosolized VEEV in non-human primates. Serial samples were collected and analyzed for testosterone and cytokines prior to and during infection in 8 captive male macaques. Infected animals exhibited a febrile response with few significant changes in cytokine levels. Baseline testosterone levels were positively associated with viremia following exposure and were significantly higher than levels obtained during infection. Such findings suggest that disease-induced androgen suppression is a reasonable area for future study. Decreased androgen levels during physiological perturbations may function, in part, to prevent immunosuppression by high testosterone levels and to prevent the use of energetic resources for metabolically-expensive anabolic functions.
Cerebrospinal fluid adenosine deaminase activity: A complimentary tool in the early diagnosis of tuberculous meningitis
Authors: Kashyap Rajpal S , Kainthla Rani P , Mudaliar Anju V , Purohit Hemant J , Taori Girdhar M , Daginawala Hatim F
Published: April 2006

Background

Tuberculous meningitis (TBM) is the commonest form of neurotuberculosis caused by Mycobacterium tuberculosis bacilli (MTB). The diagnosis of TBM is often difficult. A reliable, cost-effective and rapid diagnostic test, which can be performed in any standard pathology laboratory, could be of help in the diagnosis of TBM. In the present study we measured the adenosine deaminase (ADA) activity in cerebrospinal fluid (CSF) of TBM and non-TBM patients.

Method

ADA activity in CSF was determined according to a method based on the Berthlot reaction, which is the formation of a colored indophenol complex from ammonia liberated from adenosine, and quantified spectrophotometrically.

Results

The CSF ADA activity from TBM patients was compared with CSF ADA from non-TBM infectious meningitis patients, and from patients with non-infectious neurological disorders. The mean CSF ADA activity was found to be significantly higher in CSF of TBM patients, 14.31 ± 3.87 (2.99–26.94), mean ± SD with range, than in the CSF from non-TBM infectious meningitis, 9.25 ± 2.14 (4.99–13.96) and from the non-infectious neurological disorders group, 2.71 ± 1.96 (0.00–7.68), P < 0.0001 for both comparisons. A cut-off value of 11.39 U/L/min for the TBM patients was calculated from the mean + SD of the non-TBM patients. The ADA test gave a sensitivity of 82% and a specificity of 83% for infectious TBM when this cut-off value was used.

Conclusion

This study demonstrated that ADA activity in the CSF of TBM patients, using a cut-off value 11.39 U/L/min, can be useful for the early differential diagnosis of TBM. This test can be performed in any pathology laboratory where more sophisticated methods are not available.
Protein Phosphatase 2A Regulates Central Sensitization in the Spinal Cord of Rats following Intradermal Injection of Capsaicin
Authors: Zhang Xuan , Wu Jing , Lei Yongzhong , Fan Li , Willis William D
Published: April 2006

Background

Intradermal injection of capsaicin into the hind paw of rats induces spinal cord central sensititzation, a process in which the responsiveness of central nociceptive neurons is amplified. In central sensitization, many signal transduction pathways composed of several cascades of intracellular enzymes are involved. As the phosphorylation state of neuronal proteins is strictly controlled and balanced by the opposing activities of protein kinases and phosphatases, the involvement of phosphatases in these events needs to be investigated. This study is designed to determine the influence of serine/threonine protein phosphatase type 2A (PP2A) on the central nociceptive amplification process, which is induced by intradermal injection of capsaicin in rats.

Results

In experiment 1, the expression of PP2A protein in rat spinal cord at different time points following capsaicin or vehicle injection was examined using the Western blot method. In experiment 2, an inhibitor of PP2A (okadaic acid, 20 nM or fostriecin, 30 nM) was injected into the subarachnoid space of the spinal cord, and the spontaneous exploratory activity of the rats before and after capsaicin injection was recorded with an automated photobeam activity system. The results showed that PP2A protein expression in the spinal cord was significantly upregulated following intradermal injection of capsaicin in rats. Capsaicin injection caused a significant decrease in exploratory activity of the rats. Thirty minutes after the injection, this decrease in activity had partly recovered. Infusion of a phosphatase inhibitor into the spinal cord intrathecal space enhanced the central sensitization induced by capsaicin by making the decrease in movement last longer.

Conclusion

These findings indicate that PP2A plays an important role in the cellular mechanisms of spinal cord central sensitization induced by intradermal injection of capsaicin in rats, which may have implications in clinical pain therapy.
Administering the MADRS by telephone or face-to-face: a validity study
Authors: Hermens Marleen LM , Adèr Herman J , van Hout Hein PJ , Terluin Berend , van Dyck Richard , de Haan Marten
Published: April 2006

Background

The Montgomery Åsberg Depression Rating Scale (MADRS) is a frequently used observer-rated depression scale. In the present study, a telephonic rating was compared with a face-to-face rating in 66 primary care patients with minor or mild-major depression. The aim of the present study was to assess the validity of the administration by telephone. Additional objective was to study the validity of the first item, 'apparent sadness', the only item purely based on observation.

Methods

The present study was a validity study. During an in-person interview at the patient's home a trained interviewer administered the MADRS. A few days later the MADRS was administered again, but now by telephone and by a different interviewer. The validity of the telephone rating was calculated through the appropriate intraclass correlation coefficient (ICC).

Results

Mean total score on the in-person administration was 24.0 (SD = 11.1), and on the telephone administration 23.5 (SD = 10.4). The ICC for the full scale was 0.65. Homogeneity analysis showed that the observation item 'apparent sadness' fitted well into the scale.

Conclusion

The full MADRS, including the observation item 'apparent sadness', can be administered reliably by telephone.
Optimal search strategies for identifying mental health content in MEDLINE: an analytic survey
Authors: Wilczynski Nancy L , Haynes R Brian ,   Team Hedges
Published: April 2006

Objective

General practitioners, mental health practitioners, and researchers wishing to retrieve the best current research evidence in the content area of mental health may have a difficult time when searching large electronic databases such as MEDLINE. When MEDLINE is searched unaided, key articles are often missed while retrieving many articles that are irrelevant to the search. The objectives of this study were to develop optimal search strategies to detect articles with mental health content and to determine the effect of combining mental health content search strategies with methodologic search strategies calibrated to detect the best studies of treatment.

Method

An analytic survey was conducted, comparing hand searches of 29 journals with retrievals from MEDLINE for 3,395 candidate search terms and 11,317 combinations. The sensitivity, specificity, precision, and accuracy of the search strategies were calculated.

Results

3,277 (26.8%) of the 12,233 articles classified in the 29 journals were considered to be of interest to the discipline area of mental health. Search term combinations reached peak sensitivities of 98.4% with specificity at 50.0%, whereas combinations of search terms to optimize specificity reached peak specificities of 97.1% with sensitivity at 51.7%. Combining content search strategies with methodologic search strategies for treatment led to improved precision: substantive decreases in the number of articles that needed to be sorted through in order to find target articles.

Conclusion

Empirically derived search strategies can achieve high sensitivity and specificity for retrieving mental health content from MEDLINE. Combining content search strategies with methodologic search strategies led to more precise searches.
Relationship between impulsivity, hyperactivity and working memory: a differential analysis in the rat
Authors: Dellu-Hagedorn Françoise
Published: April 2006

Background

Impulsivity is a behavioural trait that comprises several distinct processes. It is a key feature of many psychopathologies such as mania, addictive disorders or attention deficit-hyperactivity disorders. To date, the aspects of impulsiveness involved in these pathologies have not yet been explicitly defined. In these disorders, sensation or drug seeking and cognitive deficits are closely related, but the nature of these relationships remains largely unknown. A new animal model of impulsiveness based on spontaneous inter-individual differences is proposed here to help clarify the relationship between characteristic aspects of impulsive-related pathologies.

Methods

Rats were divided into sub-groups according to their scores in three operant tasks with varying degrees of behavioural inhibition, timing and motor vs. cognitive impulsivity demands. These tasks included a fixed consecutive number schedule (ability to complete an action to receive a reinforcer), a multiple fixed-interval/extinction schedule of reinforcement (high level of responding), and a delayed reward task (delay discounting). In addition, measurements of locomotor responses to novelty and to amphetamine in a circular corridor, and working memory in an 8-arm radial maze were obtained.

Results

Substantial behavioural inter-individual differences were observed in each task, whereas few inter-task relationships were found. Impulsive rats, as defined in a task requiring inhibition of premature responses, presented a higher increase in amphetamine-induced locomotion. Reduced working memory performance was only observed in hyperactive rats in an extinction schedule.

Conclusion

This novel approach shows that distinct aspects of impulsiveness and hyperactivity can be expressed based on large inter-individual differences that vary from poorly to highly adapted behaviours ones in a normal population of rats. Inhibitory deficit was related to a higher response to psychostimulants a characteristic of rats predisposed to amphetamine self-administration and related to higher limbic dopaminergic activity, whereas working memory capacity was only related to hyperactivity. This approach allows for the identification of particular individuals presenting distinct behavioural characteristics of impulsive-related psychopathologies. These individuals may be of great interest in the modelling of these disorders and the exploration of their neurobiological bases.
Long-term effects of a single adult methamphetamine challenge: Minor impact on dopamine fibre density in limbic brain areas of gerbils
Authors: Brummelte Susanne , Grund Thorsten , Czok Andrea , Teuchert-Noodt Gertraud , Neddens Jörg
Published: April 2006

Background

The aim of the study was to test long-term effects of (+)-methamphetamine (MA) on the dopamine (DA) innervation in limbo-cortical regions of adult gerbils, in order to understand better the repair and neuroplasticity in disturbed limbic networks.

Methods

Male gerbils received a single high dose of either MA (25 mg/kg i.p.) or saline on postnatal day 180. On postnatal day 340 the density of immunoreactive DA fibres and calbindin and parvalbumin cells was quantified in the right hemisphere.

Results

No effects were found in the prefrontal cortex, olfactory tubercle and amygdala, whereas the pharmacological impact induced a slight but significant DA hyperinnervation in the nucleus accumbens. The cell densities of calbindin (CB) and parvalbumin (PV) positive neurons were additionally tested in the nucleus accumbens, but no significant effects were found. The present results contrast with the previously published long-term effects of early postnatal MA treatment that lead to a restraint of the maturation of DA fibres in the nucleus accumbens and prefrontal cortex and a concomitant overshoot innervation in the amygdala.

Conclusion

We conclude that the morphogenetic properties of MA change during maturation and aging of gerbils, which may be due to physiological alterations of maturing vs. mature DA neurons innervating subcortical and cortical limbic areas. Our findings, together with results from other long-term studies, suggest that immature limbic structures are more vulnerable to persistent effects of a single MA intoxication; this might be relevant for the assessment of drug experience in adults vs. adolescents, and drug prevention programs.
Declarative and procedural learning in children and adolescents with posterior fossa tumours
Authors: Quintero-Gallego Eliana A , Gómez Carlos M , Casares Encarnación Vaquero , Márquez Javier , Pérez-Santamaría Fco Javier
Published: April 2006

Background

This quasi-experimental study was designed to assess two important learning types – procedural and declarative – in children and adolescents affected by posterior fossa tumours (astrocytoma vs. medulloblastoma), given that memory has an important impact on the child's academic achievement and personal development.

Methods

We had three groups: two clinical (eighteen subjects) and one control (twelve subjects). The learning types in these groups were assessed by two experimental tasks evaluating procedural-implicit and declarative memory. A Serial Reaction-Time Task was used to measure procedural sequence learning, and the Spanish version [1] of the California Verbal Learning Test-Children's Version- CVLT- [2] to measure declarative-explicit learning. The learning capacity was assessed considering only the blocks that represent learning, and were compared with MANOVA in clinical and normal subjects. The Raven, simple reaction-time, finger-tapping test, and grooved pegboard tests were used to assess the overall functioning of subjects. The results were compared with those from a control group of the same age, and with Spanish norm-referenced tools where available

Results

The results indicate the absence of procedural-implicit learning in both clinical groups, whereas declarative-explicit learning is maintained in both groups.

Conclusion

The clinical groups showed a conservation of declarative learning and a clear impairment of procedural learning. The results support the role of the cerebellum in the early phase of procedural learning.
Origin and evolution of the peroxisomal proteome
Authors: Gabaldón Toni , Snel Berend , Zimmeren Frank van , Hemrika Wieger , Tabak Henk , Huynen Martijn A
Published: April 2006

Background

Peroxisomes are ubiquitous eukaryotic organelles involved in various oxidative reactions. Their enzymatic content varies between species, but the presence of common protein import and organelle biogenesis systems support a single evolutionary origin. The precise scenario for this origin remains however to be established. The ability of peroxisomes to divide and import proteins post-translationally, just like mitochondria and chloroplasts, supports an endosymbiotic origin. However, this view has been challenged by recent discoveries that mutant, peroxisome-less cells restore peroxisomes upon introduction of the wild-type gene, and that peroxisomes are formed from the Endoplasmic Reticulum. The lack of a peroxisomal genome precludes the use of classical analyses, as those performed with mitochondria or chloroplasts, to settle the debate. We therefore conducted large-scale phylogenetic analyses of the yeast and rat peroxisomal proteomes.

Results

Our results show that most peroxisomal proteins (39–58%) are of eukaryotic origin, comprising all proteins involved in organelle biogenesis or maintenance. A significant fraction (13–18%), consisting mainly of enzymes, has an alpha-proteobacterial origin and appears to be the result of the recruitment of proteins originally targeted to mitochondria. Consistent with the findings that peroxisomes are formed in the Endoplasmic Reticulum, we find that the most universally conserved Peroxisome biogenesis and maintenance proteins are homologous to proteins from the Endoplasmic Reticulum Assisted Decay pathway.

Conclusion

Altogether our results indicate that the peroxisome does not have an endosymbiotic origin and that its proteins were recruited from pools existing within the primitive eukaryote. Moreover the reconstruction of primitive peroxisomal proteomes suggests that ontogenetically as well as phylogenetically, peroxisomes stem from the Endoplasmic Reticulum.

Reviewers

This article was reviewed by Arcady Mushegian, Gáspár Jékely and John Logsdon

Open peer review

Reviewed by Arcady Mushegian, Gáspar Jékely and John Logsdon. For the full reviews, please go to the Reviewers' comments section.
Serotypes, virulence genes, and PFGE profiles of Escherichia coliisolated from pigs with postweaning diarrhoea in Slovakia
Authors: Vu Khac Hung , Holoda Emil , Pilipcinec Emil , Blanco Miguel , Blanco Jesús E , Mora Azucena , Dahbi Ghizlane , López Cecilia , González Enrique A , Blanco Jorge
Published: April 2006

Background

Postweaning diarrhoea (PWD) in pigs is usually the main infectious problem of large-scale farms and is responsible for significant losses worldwide. The disease is caused mainly by enterotoxigenic E. coli (ETEC) and Shiga-toxin producing E. coli (STEC). In this study a total of 101 E. coli isolated from pigs with PWD in Slovakia were characterized using phenotypic and genotypic methods.

Results

These 101 isolates belonged to 40 O:H serotypes. However, 57% of the isolates belonged to only six serotypes (O9:H51, O147:H-, O149:H10, O163:H-, ONT:H-, and ONT:H4), including two new serotypes (O163:H- and ONT:H4) not previously found among porcine ETEC and STEC isolated in other countries. Genes for EAST1, STb, STa, LT and Stx2e toxins were identified in 64%, 46%, 26%, 20%, and 5% of isolates, respectively. PCR showed that 35% of isolates carried genes for F18 colonization factor, and further analyzed by restriction endonuclease revealed that all of them were F18ac. Genes for F4 (K88), F6 (P987), F17, F5 (K99), F41, and intimin (eae gene) adhesins were detected in 19 %, 5%, 3%, 0.9%, 0.9%, and 0.9% of the isolates, respectively. The study of genetic diversity, carried out by PFGE of 46 representative ETEC and STEC isolates, revealed 36 distinct restriction profiles clustered in eight groups. Isolates of the same serotype were placed together in the dendrogram, but high degree of polymorphism among certain serotypes was detected.

Conclusion

Seropathotype O149:H10 LT/STb/EAST1/F4 (14 isolates) was the most commonly detected followed by O163:H- EAST1/F18 (six isolates), and ONT:H4 STa/STb/Stx2e/F18 (five isolates). Interestingly, this study shows that two new serotypes (O163:H- and ONT:H4) have emerged as pig pathogens in Slovakia. Furthermore, our results show that there is a high genetic variation mainly among ETEC of O149:H10 serotype.
Neoadjuvant radiochemotherapy in the treatment of fixed and semi-fixed rectal tumors. Analysis of results and prognostic factors
Authors: Ferrigno Robson , dos Santos Novaes Paulo Eduardo Ribeiro , Silva Maria Letícia Gobo , Nishimoto Ines Nobuko , Nakagawa Wilson Toshihiko , Rossi Benedito Mauro , de Oliveira Ferreira Fábio , Lopes Ademar
Published: April 2006

Purpose

To report the retrospective analysis of patients with locally advanced rectal cancer treated with neodjuvant radiochemotherapy.

Methods and Materials

From January 1994 to December 2003, 101 patients with fixed (25%) or semi-fixed (75%) rectal adenocarcinoma were treated by preoperative radiotherapy with a dose of 45Gy at the whole pelvis and 50.4Gy at primary tumor, concomitant to four weekly chemotherapies with 5-Fluorouracil (425 mg/m2) and Leucovorin (20 mg/m2). In 71 patients (70.3%) the primary tumor was located up to 6 cm from the anal verge and in 30 (29.7%) from 6.5 cm to 10 cm. Age, gender, tumor fixation, tumor distance from the anal verge, clinical response, surgical technique, and postoperative TNM stage were the prognostic factors analyzed for overall survival (OS), disease-free survival (DFS), and local control (LC) at five years.

Results

Median follow-up time was 38 months (range, 2–141). Complete response was observed in eight patients (7.9%), partial in 54 (53.4%) and absence in 39 (38.7%). OS, DFS and LC were 52.6%, 53.8%, and 75.9%, respectively. Distant metastasis occurred in 40 (39.6%) patients, local recurrence in 20 (19.8%) and both in 16 (15.8%). Patients with fixed tumors had lower OS (17% Vs 65.6%; p < 0.001), DFS (31.2% Vs 60.9%;p= 0.005), and LC (58% Vs 82%;p= 0.004). Patients with tumors more than 6 cm above the anal verge had better LC (93% Vs 69%;p= 0.04). The postoperative TNM stage was a significant factor for DFS (I:64.1%, II:69.6%, III:35.2%, IV:11.1%;p< 0.001) and for LC (I:75.7%, II: 92.9%, III:54.1%, IV:100%;p= 0.005). Patients with positive lymph nodes had worse OS (37.9% Vs 70.4%,p= 0.006), DFS (32% Vs 72.7%,p< 0.001) and LC (56.2% Vs 93.4%;p< 0.001).

Conclusion

This study suggests that the neoadjuvant treatment employed was effective for local control. Fixation of the lesion and lymph nodes metastasis were the main adverse prognostic factors. Distant failures were frequent, supporting the need of new drugs for adjuvant chemotherapy.
An unusual and difficult diagnosis of intestinal obstruction: The abdominal cocoon. Case report and review of the literature
Authors: Devay Ali O , Gomceli Ismail , Korukluoglu Birol , Kusdemir Ahmet
Published: April 2006

Abdominal cocoon is a rare cause of intestinal obstruction. The abdominal cocoon is probably a developmental abnormality, largely asymptomatic, and is found incidentally at laparotomy or autopsy. Pre-operative diagnosis cannot be often made correctly. This rare entity of intestinal obstruction has been described in the whole literature as a thick fibrotic sac covering the small bowel partially or completely. The etiology of abdominal cocoon is unknown and most often it is found in adolescent girls from tropical or subtropical countries. Complete recovery is generally expected after the removal of the membrane surgically. This paper reports a male patient who has had intestinal obstruction symptoms and has per-operatively been diagnosed as abdominal cocoon.
The validity of a rheumatoid arthritis medical records-based index of severity compared with the DAS28
Authors: Sato Masayo , Schneeweiss Sebastian , Scranton Richard , Katz Jeffrey N , Weinblatt Michael E , Avorn Jerry , Ting Gladys , Shadick Nancy A , Solomon Daniel H
Published: April 2006

The objective of this work was to assess the convergent validity of a previously developed rheumatoid arthritis medical records-based index of severity (RARBIS) by comparing it with the 28-joint Disease Activity Score (DAS28). This study was conducted in subjects within the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS). We selected 100 patients with rheumatoid arthritis (RA) from the BRASS with DAS28 scores equally distributed in four quartiles. The medical records were reviewed to calculate the RARBIS, which includes indicators from the following categories: prior surgical history, radiologic and laboratory findings, clinical and functional status, and extra-articular manifestations. The Spearman correlation between the RARBIS and the DAS28 was assessed in the total study population and in relevant subgroups. We re-weighted on subscales and recalculated the RARBIS score. This was performed based on findings of correlations between the DAS28 and subscales; and also the result from a multiple linear regression with the DAS28 (as a dependent variable) and five subscales (as independent variables). The mean RARBIS was 4.36 (range 0–11). Among the total study cohort, the RARBIS was moderately correlated with the DAS28 (r = 0.41, 95% confidence interval [CI] 0.23–0.56). In subgroup analyses, including age, gender, rheumatoid factor status, and disease duration, we found no statistically significant differences in the correlations. After re-weighting, the correlation between the RARBIS and the DAS28 was somewhat improved (r = 0.48, 95% CI 0.31–0.62). In conclusion, the RARBIS correlated moderately well with the DAS28 in this population. The RARBIS has both face and convergent validity for patients with RA and relevant subgroups and may have application for medical records studies in patients with RA.
Cartilage oligomeric matrix protein is involved in human limb development and in the pathogenesis of osteoarthritis
Authors: Koelling Sebastian , Clauditz Till Sebastian , Kaste Matthias , Miosge Nicolai
Published: April 2006

As a member of the thrombospondin gene family, cartilage oligomeric protein (COMP) is found mainly in the extracellular matrix often associated with cartilage tissue. COMP exhibits a wide binding repertoire and has been shown to be involved in the regulation of chondrogenesis in vitro. Not much is known about the role of COMP in human cartilage tissue in vivo. With the help of immunohistochemistry, Western blot, in situ hybridization, and real-time reverse transcription-polymerase chain reaction, we aimed to elucidate the role of COMP in human embryonic, adult healthy, and osteoarthritis (OA) cartilage tissue. COMP is present during the earliest stages of human limb maturation and is later found in regions where the joints develop. In healthy and diseased cartilage tissue, COMP is secreted by the chondrocytes and is often associated with the collagen fibers. In late stages of OA, five times the COMP mRNA is produced by chondrocytes found in an area adjacent to the main defect than in an area with macroscopically normal appearance. The results indicate that COMP might be involved in human limb development, is upregulated in OA, and due to its wide binding repertoire, could play a role in the pathogenesis of OA as a factor secreted by chondrocytes to ameliorate the matrix breakdown.