bluuebunny/crossref_metadata_2025 huggingface dataset:
Fibrosis progression in initially mild chronic hepatitis C
Authors: Boccato S. , Pistis R. , Noventa F. , Guido M. , Benvegnù L. , Alberti A.
Published: December 2005

Summary.  The natural history of chronic hepatitis C presenting with no/minimal liver fibrosis is uncertain with controversies on risk of progression and need for antiviral treatment. We studied rates and determinants of fibrosis progression in initially mild chronic hepatitis C. One hundred and six patients (mean age 41.65 ± 12.83 years) with chronic hepatitis C virus infection and no/minimal fibrosis in the initial liver biopsy (F0/F1 by METAVIR score) were followed prospectively while untreated with repeated biopsy after 5 or more years (mean interval 7.8 ± 1.51 years). Patients showing fibrosis progression were compared with nonprogressors for baseline and follow‐up parameters. Sixty‐four patients (60.4%) showed fibrosis progression including 13 of 27 (49%) with F0 and 51 of 79 (65%) with F1. Progression to F3 or cirrhosis was seen in 36% of those with F1 initially. Fibrosis progression (ΔF/year) was associated with age (P < 0.0001), baseline and follow‐up alanine aminotransferase (ALT) (P = 0.005), histological activity (P = 0.004) and steatosis (P = 0.002) in the initial biopsy and use of alcohol (P = 0.008). Thus liver fibrosis progression occurs in two‐thirds of patients with initially mild chronic hepatitis C within 5–10 years and advanced fibrosis/cirrhosis develops in one‐third of those with F1 initially. Fibrosis is facilitated by older age and alcohol and associated with inflammatory activity and ALT levels. Antiviral therapy should be considered in mild chronic hepatitis C.
Ca2+ transient induced by extracellular changes in osmotic pressure in Arabidopsis leaves: differential involvement of cell wall–plasma membrane adhesion
Authors: HAYASHI TERUYUKI , HARADA AKIKO , SAKAI TATSUYA , TAKAGI SHINGO
Published: December 2005

We investigated the mechanism underlying the perception of extracellular changes in osmotic pressure in Vallisneria gigantea Graebner and transgenic Arabidopsis thaliana (L.) Heynh. expressing cytoplasmic aequorin. Hypertonic and hypotonic treatments of A. thaliana leaves each rapidly induced a Ca2+ transient. Both responses were essentially dependent on the presence of extracellular Ca2+ and were sensitive to Gd3+, a potential blocker of stretch‐activated Ca2+ channels. Immediately after plasmolysis caused by hypertonic treatment and subsequent deplasmolysis caused by hypotonic treatment, the cells did not respond to a second hypertonic treatment and exhibited an impaired adhesion of the plasma membrane (PM) to the cell wall (CW). Recovery of the responsiveness required about 6 h. By contrast, no refractory phenomenon was observed in response to hypotonic treatment. Pretreatment with cellulase completely inhibited the Ca2+ transient induced by hypertonic treatment, but it did not affect the response to hypotonic treatment. V. gigantea mesophyll cells pretreated with cellulase exhibited an impaired adhesion of the PM to the CW. The leaf cells of multicellular plants can respond to both hypertonic and hypotonic treatments through the stretch‐activated Ca2+ channels, whereas cellulase‐sensitive adhesion of the PM to the CW is involved only in the response to hypertonic treatment.
Evidence for altered polar and lateral auxin transport in the gravity persistent signal (gps) mutants of Arabidopsis
Authors: NADELLA VIJAYANAND , SHIPP MATTHEW J. , MUDAY GLORIA K. , WYATT SARAH E.
Published: December 2005

Plant shoots do not respond when they are reoriented relative to gravity at 4 °C. However, when returned to vertical at room temperature, these organs bend in response to the previous cold gravistimulation. The inflorescence stem of the Arabidopsis thaliana gravity persistent signal (gps) mutants respond abnormally after the cold gravistimulation: gps1 does not bend when returned to room temperature, gps2 bends the wrong way and gps3 over‐responds, curving past the predicted angle. In wild type and the mutants, basipetal auxin transport in the inflorescence stem was abolished at 4 °C but restored when plants were returned to room temperature. In gps1, auxin transport was increased; in both gps2 and gps3, no significant difference was found when compared to wild type. Expression of the auxin‐inducible PIAA2::GUS reporter gene, indicated that auxin‐induced gene expression was redistributed to the lower side of the inflorescence stem in wild type after gravistimulation at 4 °C. In gps1, no asymmetries in PIAA2::GUS expression were seen. In gps2, PIAA2::GUS expression was localized to the upper side of the stem and in gps3, asymmetric PIAA2::GUS expression was extended throughout the elongation zone of the inflorescence stem. These results are consistent with altered lateral Indole‐3‐acetic‐acid (IAA) gradients being responsible for the phenotype of each mutant.
Low growth temperatures modify the efficiency of light use by photosystem II for CO2 assimilation in leaves of two chilling‐tolerant C4 species, Cyperus longus L. and Miscanthus × giganteus
Authors: FARAGE PETER K. , BLOWERS DAVID , LONG STEPHEN P. , BAKER NEIL R.
Published: December 2005

Two C4 plants, Miscanthus × giganteus and Cyperus longus L., were grown at suboptimal growth temperatures and the relationships between the quantum efficiencies of photosynthetic electron transport through photosystem II (PSII) (PSII operating efficiency; Fq′/Fm′) and CO2 assimilation (φCO2) in leaves were examined. When M. × giganteus was grown at 10 °C, the ratio of the PSII operating efficiency to φCO2 increased relative to that found in leaves grown at 14 and 25 °C. Similar increases in the Fq′/Fm′ : φCO2 occurred in the leaves of two C. longus ecotypes when the plants were grown at 17 °C, compared to 25 °C. These elevations of Fq′/Fm′ : φCO2 at low growth temperatures were not attributable to the development of anthocyanins, as has been suggested for maize, and were indicative of the operation of an alternative sink to CO2 assimilation for photosynthetic reducing equivalents, possibly oxygen reduction via a Mehler reaction, which would act as a mechanism for protection of PSII from photoinactivation and damage. Furthermore, in M. × giganteus grown at 10 °C, further protection of PSII was effected by a 20‐fold increase in zeaxanthin content in dark‐adapted leaves, which was associated with much higher levels of non‐photochemical quenching of excitation energy, compared to that observed in leaves grown at 14 and 25 °C. These differences may explain the long growing season and remarkable productivity of this C4 plant in cool climates, even in comparison to other C4 species such as C. longus, which occur naturally in such climates.
Equine cutaneous non‐neoplastic nodular and proliferative lesions in the Pacific Northwest
Authors: VALENTINE BETH A.
Published: November 2005

Abstract  A retrospective study examined data on cutaneous nodular and proliferative lesions in horses, donkeys and mules submitted to the Veterinary Diagnostic Laboratory at Oregon State University in a 3.5‐year period. One hundred and sixteen non‐neoplastic nodular and proliferative lesions were identified, comprising 18% of all lesions studied and 6.4% of total equine pathology accessions. Exuberant granulation tissue, eosinophilic granuloma, fungal granuloma, cysts and habronaemiasis were most common, and constituted 91% of non‐neoplastic lesions, 16% of all lesions studied, and 5.85% of total equine pathology accessions. Calcinosis circumscripta and cutaneous granulomas, including eosinophilic granuloma, fungal granuloma, and other granulomas, were most common in horses up to 10 years of age. Eosinophilic granuloma was more common in males than in females, and was diagnosed most often in autumn and winter. Fungal granuloma was common in this population and was most often diagnosed in the spring. Habronaemiasis was diagnosed in late summer and early autumn, and was most common in males. Results of this study indicate that equine non‐neoplastic nodular and proliferative skin lesions are commonly submitted for histopathologic examination. Results also suggest that regional differences exist regarding incidence of cutaneous fungal granuloma and season of occurrence of eosinophilic granuloma in horses.
The metabolite products of chlorocholine chloride (CCC) in eggs and meat of laying hens fed 15N‐CCC containing diets
Authors: Nurhayati  , Chakeredza S. , Chaidir  , Edrada R. A. , Ebel R. , Ter Meulen U.
Published: December 2005

An experiment was conducted to evaluate the metabolic products of chlorocholine chloride (CCC) in eggs and meat of laying hens fed a diet containing 15N‐CCC. Ten brown laying hens were randomly divided into two groups of five each. One group was offered 15N‐CCC free diet while the other group received a diet with 100 ppm 15N‐CCC for 11 days. Samples of eggs and meat from the laying hens were collected. Egg yolks and albumen were separated. Meat was collected from the breast and femur. The metabolic products of CCC were measured using ion trap electrospray ionisation mass spectrometry (ion trap‐ESI‐MS/MS). Determination of CCC or its metabolites in eggs and meat showed that CCC was metabolised to choline. Corresponding MS/MS spectra were obtained for m/z 104 (choline) or 105 (15N‐choline), whereas nothing was detected at m/z 122 (CCC) or 123 (15N‐CCC). The results from this study indicate that CCC will be metabolised in tissues of laying hens.
Effects of amount of intake and stage of forage maturity on urinary allantoin excretion and estimated microbial crude protein synthesis in the rumen of steers
Authors: Südekum K.‐H. , Brüsemeister F. , Schröder A. , Stangassinger M.
Published: December 2005

Using ruminally cannulated steers, we investigated how urinary allantoin excretion was related to variations in feed intake and stage of forage maturity. Further, different approaches were compared for predicting ruminal microbial crude protein (MCP) synthesis and its efficiency. Experimental diets were arranged in a replicated 3 × 3 Latin square design (experiment 1) and a 4 × 4 Latin square design (experiment 2). In experiment 1, a mixed diet [forage to concentrate, 68:32 on a dry matter (DM) basis] was fed at three intake levels corresponding to 1, 1.5 and 2 times maintenance energy requirements. In experiment 2, four silage‐based diets were fed based on perennial ryegrass (Lolium perenneL.), which was harvested at four maturity stages. Both experiments demonstrated the influence of diet on microbial growth rate and by this on efficiency of MCP synthesis, although the magnitude of the effects differed between approaches used for estimating MCP. Linear functions satisfactorily characterised the relationship between urinary allantoin excretion (y) and digestible organic matter (OM) intake (x, kg/day; experiment 1: y = 7.94 + 17.34 x; R2 = 0.785) or intake of OM effectively degraded in the rumen (x, kg/day; experiment 2; y = 22.32 + 5.93 x; R2 = 0.695). Urinary excretion of allantoin permitted a semi‐quantitative prediction of MCP synthesis: ranking of diets and magnitude of changes in MCP synthesis were reflected.
Primary hair growth in dogs depends on dietary selenium concentrations*
Authors: Yu S. , Wedekind K. J. , Kirk C. A. , Nachreiner R. F.
Published: December 2005

Selenium (Se) plays an important role in hair growth. The objective of this study was to investigate the effect of dietary selenium concentration on hair growth in dogs. Thirty‐six beagles were stratified into six groups based on age, gender and body condition score. The dogs were fed a torula yeast‐based canned food for 3 weeks. Then the dogs were fed varying amounts of selenium supplied as selenomethionine for an additional 24 weeks. Analysed selenium concentrations in the experimental foods for the six groups were 0.04, 0.09, 0.12, 0.54, 1.03 and 5.04 mg/kg dry matter respectively. Body weight and food intake were not affected by the selenium treatments. Serum selenium concentration was similar initially but was significantly different at the end of the study among groups. Dietary selenium concentration below 0.12 mg/kg diet may be marginal for an adult dog. Dietary treatment had no effect on serum total thyroxine (TT4), free thyroxine (FT4), and free 3,3′,5‐triiodothyronine (FT3). There was a significant diet and time interaction (p = 0.038) for total 3,3′,5 triiodothyronine (TT3). Hair growth was similar among groups initially but significantly reduced in dogs fed diets containing 0.04, 0.09 or 5.04 mg Se/kg when compared with 0.12, 0.54 and 1.03 mg Se/kg at week 11 (p < 0.05) and week 22 (p = 0.061). These results demonstrated that both low and high selenium diets reduce hair growth in adult dogs.
Possible involvement of selenium inStaphylococcus aureusinhibition in cow's whey
Authors: Malbe M. , Attila M. , Atroshi F.
Published: December 2005

Previous investigations have shown that selenium supplementation inhibits growth of mastitis pathogens in cow's milk. The present study was performed to clarify the role of selenium in defence mechanisms of mammary gland. We have examined the effects of selenium supplementation onStaphylococcus aureusgrowth inhibiting activity in whey. Six selenium‐supplemented and six non‐supplemented Estonian dairy cows were used for this study. Selenium‐supplemented cows received 4 mg organic selenium in the form of selenium yeast in their daily diet for 8‐week period. Cows from non‐supplemented group received the same amount of yeast free of selenium in their diet. All cows had initially low blood glutathione peroxidase (GPx) activity (≤1.02 μkat/g Hb). During the 8‐week experiment these cows had low somatic cell count (<300 000 cells/ml) and negative bacteriological findings in their quarter milk samples. Bacterial growth inhibitory activity in specific whey fractions was clearly evident in 3 out of 6 cows supplemented with selenium. The inhibitory effect was more profound if the cow's blood GPx activity exceeded 4 μkat/g Hb, whereas in non‐supplemented cows the inhibition ofS. aureusgrowth was not observed. This study confirms the presence of selenium‐dependent antibacterial activity in cow's milk.
The influence of an increased cobalt supply to dairy cows on the vitamin B12 status of their calves
Authors: Stemme K. , Meyer U. , Flachowsky G. , Scholz H.
Published: December 2005

In the experiment the influence of an elevated oral cobalt supply (Co content in the ration 0.27 mg Co/kg DM; supplement of 0.14 mg Co/kg DM as CoSO4) to pregnant dairy cows on the vitamin B12 concentration in milk, colostrum and vitamin B12 status of their calves was tested in comparison with unsupplemented controls (0.13 mg Co/kg DM). While there was no significant difference in vitamin B12 concentration in the at 70th day of lactation (start of the experiment; 3.77 ± 1.41 vs. 3.66 ± 1.03 ng/ml) and 290th day of lactation (almost drying off; 4.75 ± 3.05 vs. 4.44 ± 0.96 ng/ml), cobalamin concentration in the milk colostrum showed a tendency towards a higher cobalt content in the ration of the supplemented cows in comparison with the controls (21.0 ± 8.4 vs. 16.7 ± 11.9 ng/ml). Differences in the vitamin B12 concentration in the serum of the newborn calves before and after ingestion of colostrum were not detected. From these results it can be concluded that cobalt content of 0.13 mg Co/kg DM in the ration based on wilted grass silage seems to be sufficient for pregnant dairy cows.
An in vitro evaluation of the adhesion of Candida species to oral and lung tissue cells
Authors: Nikawa H. , Egusa H. , Makihira S. , Okamoto T. , Kurihara H. , Shiba H. , Amano H. , Murayama T. , Yatani H. , Hamada T.
Published: November 2005

The analysis of the adherence capacity of fungi to surfaces of both oral tissue and different tissues would be of interest in the fungal dissemination as an oral and systemic pathogen. We developed an in vitro adenosine triphosphate (ATP)‐based assay technique to extract the cellular and fungal ATP separately, which allowed the quantitative evaluation of the adhesion of the yeast to monolayers of human gingival epithelial cells (GEC), gingival fibroblasts (GF) and pulmonary fibroblasts (PF). Seven oral isolates of Candida species (three of Candida albicans, three of Candida tropicalis and one of Candida glabrata) were used in the study. The adherent level of the Candida species varied depending on both the isolates and the cell origins, although all the Candida isolates had a significantly higher level of adherence to GEC than to GF except the single isolate of C. tropicalis. Whereas the adherent level of the five isolates to GEC was significantly higher than that to PF, the adherent level of the remaining two isolates of C. tropicalis to GEC was significantly lower than that to PF. These results suggest that candidal adherence to host tissue cells should be regulated in an isolate‐dependent and cell‐origin‐dependent manner, and that the phenomena may be involved in the colonisation and/or dissemination of the fungi.
Cockroaches as carriers of fungi of medical importance
Authors: Lemos A. A. , Lemos J. A. , Prado M. A. , Pimenta F. C. , Gir E. , Silva H. M. , Silva M. R. R.
Published: November 2005

The fungal pathogenic flora of the external surface of 103 cockroaches (Periplaneta americana) collected from the intensive care unit of a hospital were investigated. In this study, a high percentage of test cockroaches (93.2%) were found to carry fungi of medical importance. The main fungi isolated were species of Candida, Aspergillus and Penicillium. Information about the carriage of pathogenic fungi by cockroaches in hospital environment is scanty. The results suggest that cockroaches can play a role in dissemination of fungi, which they can carry on their external surface.
Panic disorder with and without agoraphobia: comorbidity within a half‐year of the onset of panic disorder
Authors: KIKUCHI MITSURU , KOMURO RYUTAROU , OKA HIROSHI , KIDANI TOMOKAZU , HANAOKA AKIRA , KOSHINO YOSHIFUMI
Published: December 2005

Abstract  The present study was performed to compare the clinical features of patients with panic disorder with and without agoraphobia. The subjects were 233 outpatients with panic disorder (99 males and 134 females) diagnosed according to DSM‐IV criteria. Sixty‐three patients met the criteria for panic disorder without agoraphobia, and 170 met the criteria for panic disorder with agoraphobia. Patients with agoraphobia showed a significantly longer duration of panic disorder and higher prevalence of generalized anxiety disorder. However, there were no significant differences in prevalence of major depressive episodes, in current severity of panic attacks, or in gender ratio between the two groups. The second aim of the present study was to investigate the effects of onset age and sex differences on the development of agoraphobia within a half‐year. The subjects were divided into two groups according to their self‐report: patients who did or did not develop agoraphobia within 24 weeks of onset of panic disorder. A total of 40.6% of the patients developed agoraphobia within 24 weeks of the onset of panic disorder, and onset age and sex differences had no robust effect on the development of agoraphobia within 24 weeks.
High prevalence of self‐reported winter depression in a Swedish county
Authors: RASTAD CECILIA , SJÖDÉN PER‐OLOW , ULFBERG JAN
Published: December 2005

Abstract  The prevalence of winter depression was unknown in Sweden, therefore prevalence figures of seasonal affective disorder (SAD) and subsyndromal SAD (S‐SAD) were estimated. Age and gender differences, prevalence in the group of non‐responders and some psychometric qualities of the Seasonal Pattern Assessment Questionnaire (SPAQ) were calculated. A modified version of the SPAQ was sent to a random sample of 2500 persons (response rate 66.3%, n = 1657) between 18 and 64 years residing in Dalarna, a county in central Sweden. The sample was proportionally stratified according to age, gender and home municipality. The prevalence of winter SAD was estimated at 8% and S‐SAD at 10.8%. It was approximately twice as common among women and younger persons. A total of 3.1% reported seasonal problems to be severe or disabling and 19.3% that everyday life was negatively affected. Experiencing seasonally changing depressive symptoms was common in the population. Factor analysis of the Global Seasonal Score resulted in one factor and the internal consistency was 0.88 (Cronbach's alpha). The results indicate that self‐reported recurrent depression during winter is common in Sweden and should therefore receive more attention from healthcare authorities.
Evaluation of cerebral blood flow volume using color duplex sonography in patients with untreated panic disorder
Authors: GECICI OMER , ACAR MURAT , HAKTANIR ALPAY , EMUL MURAT , DEMIREL REHA , YÜCEL AYLIN , ALBAYRAK RAMAZAN
Published: December 2005

Abstract  The aim of this study was to compare cerebral blood flow (CBF) using color duplex sonography in panic disorder and normal controls. We report 24 untreated patients and 20 healthy subjects. State–Trait Anxiety Inventory, Beck Depression Inventory, Beck Anxiety Inventory, and Symptom Check List‐90 were completed on each subject. The internal carotid artery (ICA) and vertebral artery (VA) of both sides were explored with a 7.5‐Mhz linear array transducer. CBF volume and mean ICA flow velocity were significantly higher in patients than normal subjects adjusted for age. However, we could not find a statistically significant difference in flow volume and velocity of VA and the sum of bilateral ICA volume between patients and controls adjusted for age. There was also no correlation between CBF volume and the other radiological data with STAI scores. In conclusion, we found that independent of anxiety levels, CBF volume has increased in panic disorder patients. In addition, color duplex sonography is a non‐invasive and easily applicable technique and it is a preferable alternative to quantify CBF volume.
High serum leptin levels in depressive disorders with atypical features
Authors: GECICI OMER , KULOGLU MURAT , ATMACA MURAD , TEZCAN A. ERTAN , TUNCKOL HIKMET , EMÜL H. MURAT , USTUNDAG BILAL
Published: December 2005

Abstract  Leptin is thought to be related to vegetative symptoms of depression such as alterations in food intake and weight. Fifty‐seven drug‐free patients and 26 healthy controls were enrolled in this study. We have found that the serum leptin levels were higher in patients with atypical depressive disorder than in controls, but not in patients with nonatypical depressive disorder, however, body mass index, age, and gender were not significantly different between these groups. Probably, these findings seem to be associated with some features of the atypical depressive disorders such as weight gain, a result of hyperphagia.
The effectiveness of mirtazapine in the treatment of post‐traumatic stress disorder: A 24‐week continuation therapy
Authors: KIM WON , PAE CHI‐UN , CHAE JEONG‐HO , JUN TAE‐YOUN , BAHK WON‐MYONG
Published: December 2005

Abstract  Few studies for the long‐term effects of antidepressants on post‐traumatic stress disorder (PTSD) have been conducted. The aim of the present study was to investigate the effectiveness of mirtazapine during the 24‐week continuation treatment in patients with PTSD. Out of 15 patients who participated in the previous 8‐week short‐term study, 12 patients completed 24‐week continuation treatment with mirtazapine. The effectiveness was evaluated at week 12 and week 24 using Impact of Event Scale‐Revised (IES‐R), Short PTSD Rating Interview (SPRINT), Interviewer‐Administered Structured Interview for PTSD (SIP) and Montgomery‐Åsberg Depression Rating Scale (MADRS). The tolerability of continuation treatment was also reported. The scores on the IES‐R, SPRINT, SIP and MADRS were significantly reduced over time from baseline to week 24, the end‐point (F = 36.1, d.f. = 4, P < 0.001; F = 106.3, d.f. = 4, P < 0.001; F = 121.1, d.f. = 4, P < 0.001; F = 198.9, d.f. = 4, P < 0.001). On post‐hoc analysis, the scores of all four measures were significantly reduced at the end point since week 8. However, after Bonferroni's correction, that was statistically significant in SPRINT only. The number of patients whose scores were reduced over 50% in all four scales had a tendency of incremental increase from three at week 8 to eight at the end point (P = 0.063). No serious drug‐related side‐effects occurred. These results suggest that the mirtazapine may be effective in the continuation treatment of PTSD as well as short‐term treatment. Further and better‐designed studies are necessary.
A preliminary validation of Attention, Relevance, Confidence and Satisfaction model‐based Instructional Material Motivational Survey in a computer‐based tutorial setting
Authors: Huang Wenhao , Huang Wenyeh , Diefes‐Dux Heidi , Imbrie Peter K.
Published: December 2005

This paper describes a preliminary validation study of the Instructional Material Motivational Survey (IMMS) derived from the Attention, Relevance, Confidence and Satisfaction motivational design model. Previous studies related to the IMMS, however, suggest its practical application for motivational evaluation in various instructional settings without the support of empirical data. Moreover, there is a lack of discussion regarding the validity of the instrument. Therefore, this study empirically examined the IMMS as a motivational evaluation instrument. A computer‐based tutorial setting was selected owing to its wide application in teaching large entry‐level college courses. Data collected from 875 subjects were subjected to exploratory and confirmatory factor analyses, and measurement modelling LISREL. Findings suggested that 16 original items should be excluded from the IMMS; the retained 20 items were found to fall into different constructs, indicating that instructional features of the tutorial may influence the validity of the survey items. The implication of the study supports the situational  feature  of  the  IMMS.  Therefore,  a  preevaluation  adjustment  on the IMMS items is recommended to identify suitable items before the full motivational evaluation. Future research should focus on the further validation of the IMMS based on this preliminary evidence.
The use of botulinum toxin type‐B in the treatment of patients who have become unresponsive to botulinum toxin type‐A – initial experiences
Authors: Barnes M. P. , Best D. , Kidd L. , Roberts B. , Stark S. , Weeks P. , Whitaker J.
Published: November 2005

The increasing use of botulinum toxin type‐A, especially for focal dystonia and spasticity has highlighted the issue of secondary non‐responsiveness. Within the last few years botulinum toxin type‐B (Myobloc®/Neurobloc®) has become commercially available as an alternative to type‐A. This paper discusses our initial experience of botulinum toxin type‐B in a total of 63 individuals who attended our botulinum clinic. Thirty‐six patients had cervical dystonia and a secondary non‐response to type‐A toxin. Thirteen of these patients (36%) had a reasonable clinical response to Neurobloc® and continue to have injections. The other 23 patients either had no response, or a poor response, or had unacceptable side effects and ceased treatment. A small number of people with blepharospasm, hemifacial spasm and foot dystonia also had a disappointing response to injection. Twenty patients with spasticity were also type‐A resistant. Seven of these show some continuing response to type‐B, without unacceptable side effects. These findings demonstrate that botulinum toxin type‐B has a place in the management of patients who have become non‐responsive to type‐A, but overall the responses to type‐B toxin were disappointing.
EFNS guideline on treatment of multiple sclerosis relapses: report of an EFNS task force on treatment of multiple sclerosis relapses
Authors: Sellebjerg F. , Barnes D. , Filippini G. , Midgard R. , Montalban X. , Rieckmann P. , Selmaj K. , Visser L. H. , Sørensen P. S.
Published: November 2005

Relapses, exacerbations or attacks of multiple sclerosis are the dominating feature of relapsing‐remitting multiple sclerosis (MS), but are also observed in patients with secondary progressive MS. High‐dose methylprednisolone is the routine therapy for relapses at present, but other treatments are also in current use. The objective of the task force was to review the literature on treatment of MS relapses to provide evidence‐based treatment recommendations. Review was carried out on the literature with classification of evidence according to the EFNS guidelines for scientific task forces. Short‐term, high‐dose methylprednisolone treatment should be considered for the treatment of relapses of MS (level A recommendation). The optimal glucocorticoid treatment regimen, in terms of clinical efficacy and adverse events, remains to be established. A more intense, interdisciplinary rehabilitation programme should be considered as this probably further improves recovery after treatment with methylprednisolone (level B recommendation). Plasma exchange is probably efficacious in a subgroup of patients with severe relapses not responding to methylprednisolone therapy, and should be considered in this patient subgroup (level B recommendation). There is a need for further randomized, controlled trials in order to establish the optimal treatment regimen for relapses of MS.
An event‐related potential study on the “check operation” in the Eriksen task1
Authors: IWAKI NOBUYOSHI , MIYATANI MAKOTO , TOSHIMA TAMOTSU
Published: December 2005

Abstract:  We examined two issues for the Eriksen task with two types of stimuli, the central target letter of which was flanked with noise (e.g., HHHHH for compatible stimuli and SSHSS for incompatible stimuli). First, we examined whether or not a response‐stop function is carried out until the check operation to detect and correct erroneous response readiness has finished (Eriksen & Eriksen, 1974). Second, reaction times for incompatible stimuli are not prolonged if only identical noise stimuli are used throughout the block. This phenomenon is called the blocking effect. We then explored whether or not the blocking effect can be caused by the selective inhibition of erroneous response readiness (Eriksen & Schultz, 1979). Sixteen participants (18–29 years old) selectively pressed one of two buttons for the target letter. The results showed that the negative potential related to the response‐stop function was enlarged for incompatible stimuli. Moreover, the blocking effect was observed, while erroneous response readiness was still observable for incompatible stimuli. These results suggest that the blocking effect is caused by something other than reciprocal inhibition.
Effect of the A118G polymorphism on binding affinity, potency and agonist‐mediated endocytosis, desensitization, and resensitization of the human mu‐opioid receptor
Authors: Beyer Andrea , Koch Thomas , Schröder Helmut , Schulz Stefan , Höllt Volker
Published: December 2005

The most prevalent single‐nucleotide polymorphism (SNP) A118G in the human µ‐opioid receptor gene predicts an amino acid change from an asparagine residue to an aspartatic residue in amino acid position 40. This N40D mutation, which has been implicated in the development of opioid addiction, was previously reported to result in an increased β‐endorphin binding affinity and a decreased potency of morphine‐6‐glucuronide. Therefore, in the present study we have investigated whether this mutation might affect the binding affinity, potency, and/or the agonist‐induced desensitization, internalization and resensitization of the human µ‐opioid receptor stably expressed in human embryonic kidney 293 cells. With the exception of a reduced expression level of N40D compared to human µ‐opioid receptor (hMOR) in HEK293 cells, our analyses revealed no marked functional differences between N40D and wild‐type receptor. Morphine, morphine‐6‐glucuronide and β‐endorphin revealed similar binding affinities and potencies for both receptors. Both the N40D‐variant receptor and hMOR exhibited robust receptor internalization in the presence of the opioid peptide [d‐Ala2,N‐MePhe4,Glyol5]enkephalin (DAMGO) and β‐endorphin but not in response to morphine or morphine‐6‐glucuronide. After prolonged treatment with morphine, morphine‐6‐glucuronide or β‐endorphin both receptors showed similiar desensitization time courses. In addition, the receptor resensitization rates were nearly identical for both receptor types.
The cloning and characterization of a second brain enzyme with NAAG peptidase activity
Authors: Bzdega Tomasz , Crowe Samantha L. , Ramadan Epolia R. , Sciarretta Kathryn H. , Olszewski Rafal T. , Ojeifo Olumide A. , Rafalski Victoria A. , Wroblewska Barbara , Neale Joseph H.
Published: December 2005

The peptide neurotransmitterN‐acetylaspartylglutamate is inactivated by extracellular peptidase activity following synaptic release. It is speculated that the enzyme, glutamate carboxypeptidase II (GCPII, EC 3.14.17.21), participates in this inactivation. However, CGCPII knockout mice appear normal in standard neurological tests. We report here the cloning and characterization of a mouse enzyme (tentatively identified as glutamate carboxypeptidase III or GCPIII) that is homologous to an enzyme identified in a human lung carcinoma. The mouse peptidase was cloned from two non‐overlapping EST clones and mouse brain cDNA using PCR. The sequence (GenBank,AY243507) is 85% identical to the human carcinoma enzyme and 70% homologous to mouse GCPII. GCPIII sequence analysis suggests that it too is a zinc metallopeptidase. Northern blots revealed message in mouse ovary, testes and lung, but not brain. Mouse cortical and cerebellar neurons in culture expressed GCPIII message in contrast to the glial specific expression of GCPII. Message levels of GCPIII were similar in brains obtained from wild‐type mice and mice that are null mutants for GCPII. Chinese hamster ovary (CHO) cells transfected with rat GCPII or mouse GCPIII expressed membrane bound peptidase activity with similarVmaxandKmvalues (1.4 µmand 54 pmol/min/mg; 3.5 µmand 71 pmol/min/mg, respectively). Both enzymes are activated by a similar profile of metal ions and their activities are blocked by EDTA. GCPIII message was detected in brain and spinal cord by RT‐PCR with highest levels in the cerebellum and hippocampus. These data are consistent with the hypothesis that nervous system cells express at least two differentially distributed homologous enzymes with similar pharmacological properties and affinity for NAAG.
Serotoninergic neurotransmission is affected by n‐3 polyunsaturated fatty acids in the rat
Authors: Kodas Ercem , Galineau Laurent , Bodard Sylvie , Vancassel Sylvie , Guilloteau Denis , Besnard Jean‐Claude , Chalon Sylvie
Published: December 2005

We explored the effects of chronic α‐linolenic acid dietary deficiency on serotoninergic neurotransmission. In vivo synaptic serotonin (5‐HT) levels were studied in basal and pharmacologically stimulated conditions using intracerebral microdialysis in the hippocampus of awake 2‐month‐old rats. We also studied the effects of reversion of the deficient diet on fatty acid composition and serotoninergic neurotransmission. A balanced (control) diet was supplied to deficient rats at different stages of development, i.e. from birth, 7, 14 or 21 days of age. We demonstrated that chronic n‐3 polyunsaturated fatty acid dietary deficiency induced changes in the synaptic levels of 5‐HT both in basal conditions and after pharmacological stimulation with fenfluramine. Higher levels of basal 5‐HT release and lower levels of 5‐HT‐stimulated release were found in deficient than in control rats. These neurochemical modifications were reversed by supply of the balanced diet provided at birth or during the first 2 weeks of life through the maternal milk, whereas they persisted if the balanced diet was given from weaning (at 3 weeks of age). This suggests that provision of essential fatty acids is durably able to affect brain function and that this is related to the developmental stage during which the deficiency occurs.
Brevetoxin activation of voltage‐gated sodium channels regulates Ca2+dynamics and ERK1/2 phosphorylation in murine neocortical neurons
Authors: Dravid Shashank M. , Baden Daniel G. , Murray Thomas F.
Published: December 2005

Voltage‐gated sodium channels (VGSC) are involved in the generation of action potentials in neurons. Brevetoxins (PbTx) are potent allosteric enhancers of VGSC function and are associated with the periodic ‘red tide’ blooms. Using PbTx‐2 as a probe, we have characterized the effects of activation of VGSC on Ca2+dynamics and extracellular signal‐regulated kinases 1/2 (ERK1/2) signaling in neocortical neurons. Neocortical neurons exhibit synchronized spontaneous Ca2+oscillations, which are mediated by glutamatergic signaling. PbTx‐2 (100 nm) increased the amplitude and reduced the frequency of basal Ca2+oscillations. This modulatory effect on Ca2+oscillations produced a sustained rise in ERK1/2 activation. At 300 nm, PbTx‐2 disrupted oscillatory activity leading to a sustained increase in intracellular Ca2+([Ca2+]i) and induced a biphasic, activation followed by dephosphorylation, regulation of ERK1/2. PbTx‐2‐induced ERK1/2 activation was Ca2+dependent and was mediated by Ca2+entry through manifold routes. PbTx‐2 treatment also increased cAMP responsive element binding protein (CREB) phosphorylation and increased gene expression of brain‐derived neurotrophic factor (BDNF). These findings indicate that brevetoxins, by influencing the activation of key signaling proteins, can alter physiologic events involved in survival in neocortical neurons, as well as forms of synaptic plasticity associated with development and learning.
Synapse associated protein 102 is a novel binding partner to the cytoplasmic terminus of neurone‐glial related cell adhesion molecule
Authors: Davey Fleur , Hill Maria , Falk Julien , Sans Nathalie , Gunn‐Moore Frank J.
Published: December 2005

Neurone glial‐related cell adhesion molecule (NrCAM) is a member of the L1 family of transmembrane cell adhesion receptors which are involved in the development and function of the mammalian nervous system. How these receptors interact with intracellular signalling pathways is not understood. To date the only identified binding partner to the cytoplasmic terminus of NrCAM is ankyrin G. We screened a developing rat brain cDNA yeast two‐hybrid library with the cytoplasmic domain of NrCAM to identify further intracellular binding partners. We identified synapse associated protein 102 (SAP102) as a new binding partner for NrCAM. The interaction was confirmed biochemically using glutathione S‐transferase (GST)‐pull‐down and tandem affinity purification, and also immunocytochemically as NrCAM and SAP102 co‐localized in COS‐7 and cerebellar granule cells. Binding was specific to NrCAM as neither neurofascin nor L1 bound SAP102, and this interaction was reliant on the last three amino acids of NrCAM. Additionally, NrCAM constructs whose last three amino acids had been deleted appeared to have a dominant negative effect on neurite extension of cerebellar granule cells. This is the first interaction reported for NrCAM, and its association with SAP102 suggests that it is part of a larger complex which can interact with many different signalling pathways.
Two domains within the first putative transmembrane domain of presenilin 1 differentially influence presenilinase and γ‐secretase activity
Authors: Brunkan A. L. , Martinez M. , Wang J. , Walker E. S. , Beher D. , Shearman M. S. , Goate A. M.
Published: December 2005

Presenilins (PS) are thought to contain the active site for presenilinase endoproteolysis of PS and γ‐secretase cleavage of substrates. The structural requirements for PS incorporation into the γ‐secretase enzyme complex, complex stability and maturation, and appropriate presenilinase and γ‐secretase activity are poorly understood. We used rescue assays to identify sequences in transmembrane domain one (TM1) of PS1 required to support presenilinase and γ‐secretase activities. Swap mutations identified an N‐terminal TM1 domain that is important for γ‐secretase activity only and a C‐terminal TM1 domain that is essential for both presenilinase and γ‐secretase activities. Exchange of residues 95–98 of PS1 (sw95–98) completely abolishes both activities while the familial Alzheimer's disease mutation V96F significantly inhibits both activities. Reversion of residue 96 back to valine in the sw95–98 mutant rescues PS function, identifying V96 as the critical residue in this region. The TM1 mutants do not bind to an aspartyl protease transition state analog γ‐secretase inhibitor, indicating a conformational change induced by the mutations that abrogates catalytic activity. TM1 mutant PS1 molecules retain the ability to interact with γ‐secretase substrates and γ‐secretase complex members, although Nicastrin stability is decreased by the presence of these mutants. γ‐Secretase complexes that contain V96F mutant PS1 molecules display a partial loss of function for γ‐secretase that alters the ratio of amyloid‐β peptide species produced, leading to the amyloid‐β peptide aggregation that causes familial Alzheimer's disease.
Somatostatin and the somatostatin receptor 2 are reciprocally controlled by calcineurin during cerebellar granule cell maturation
Authors: Kramer Dana , Caruso Alessandra , Nicoletti Ferdinando , Genazzani Armando A.
Published: December 2005

Activity‐dependent Ca2+ influx into neurones and the subsequent changes in gene expression are thought to be important in shaping neuronal development. In this study, we investigated whether an important mediator of neuronal migration, somatostatin (Srif), alongside its receptors, is controlled in this manner in cerebellar granule cells. We show that Ca2+ influx increases the expression of somatostatin mRNA (srif), while somatostatin receptor 2 (sst2) mRNA expression is decreased. Both genes appear to be regulated independently of each other and in a calcineurin‐dependent manner that does not depend on either the ERK1/2 MAP kinase or the cAMP/CREB pathway. Nonetheless, a second pathway is required to induce changes in srif and sst2 expression, since constitutively active calcineurin alone is not sufficient to induce these changes. Furthermore, calcineurin activation reciprocally regulates the expression of brain‐derived neurotrophic factor, bdnf, and its receptor trkb, which have also been shown to play a role in neuronal migration. Finally, calcineurin appears to control the expression of the neuronal marker transient axonal glycoprotein 1, tag‐1, thereby strongly suggesting that calcineurin activation in vivo occurs during the late stages of neuronal migration, possibly during synaptogenesis with mossy fibres. We therefore propose that calcineurin might play an important role as a switch between transcriptional programs during neuronal development.
Sleep and wakefulness modulate gene expression in Drosophila
Authors: Cirelli Chiara , LaVaute Timothy M. , Tononi Giulio
Published: December 2005

In the mammalian brain, sleep and wakefulness are associated with widespread changes in gene expression. Sleep in fruit flies shares many features with mammalian sleep, but it is currently unknown to what extent behavioral states affect gene expression in Drosophila. To find out, we performed a comprehensive microarray analysis of gene expression in spontaneously awake, sleep‐deprived and sleeping flies. Fly heads were collected at 4 am, after 8 h of spontaneous sleep or sleep deprivation, and at 4 pm, after 8 h of spontaneous wakefulness. As in rats, we found that behavioral state and time of day affect Drosophila gene expression to a comparable extent. As in rats, transcripts with higher expression in wakefulness and in sleep belong to different functional categories, and in several cases these groups overlap with those previously identified in rats. Wakefulness‐related genes code for transcription factors and for proteins involved in the stress response, immune response, glutamatergic transmission, and carbohydrate metabolism. Sleep‐related transcripts include the glial gene anachronism and several genes involved in lipid metabolism. Finally, the expression of many wakefulness‐related and sleep‐related Drosophila transcripts is also modulated by the time of day, suggesting an interaction at the molecular level between circadian and homeostatic mechanism of sleep regulation.
Hypoxia‐activated metabolic pathway stimulates phosphorylation of p300 and CBP in oxygen‐sensitive cells
Authors: Zakrzewska Adriana , Schnell Phillip O. , Striet Justin B. , Hui Anna , Robbins Jennifer R. , Petrovic Milan , Conforti Laura , Gozal David , Wathelet Marc G. , Czyzyk‐Krzeska Maria F.
Published: December 2005

Transcription co‐activators and histone acetyltransferases, p300 and cyclic AMP responsive element‐binding protein‐binding protein (CBP), participate in hypoxic activation of hypoxia‐inducible genes. Here, we show that exposure of PC12 and cells to 1–10% oxygen results in hyperphosphorylation of p300/CBP. This response is fast, long lasting and specific for hypoxia, but not for hypoxia‐mimicking agents such as desferioxamine or Co2+ ions. It is also cell‐type specific and occurs in pheochromocytoma PC12 cells and the carotid body of rats but not in hepatoblastoma cells. The p300 hyperphosphorylation specifically depends on the release of intracellular calcium from inositol 1,4,5‐triphosphate (IP3)‐sensitive stores. However, it is not inhibited by pharmacological inhibitors of any of the kinases traditionally known to be directly or indirectly calcium regulated. On the other hand, p300 hyperphosphorylation is inhibited by several different inhibitors of the glucose metabolic pathway from generation of NADH by glyceraldehyde 3‐phosphate dehydrogenase, through the transfer of NADH through the glycerol phosphate shuttle to ubiquinone and complex III of the mitochondrial respiratory chain. Inhibition of IP3‐sensitive calcium stores decreases generation of ATP, and this inhibition is significantly stronger in hypoxia than in normoxia. We propose that the NADH glycerol phosphate shuttle participates in generating a pool of ATP that serves either as a co‐factor or a modulator of the kinases involved in the phosphorylation of p300/CBP during hypoxia.
Involvement of spinal metabotropic glutamate receptor 5 in the development of tolerance to morphine‐induced antinociception
Authors: Narita Minoru , Suzuki Masami , Narita Michiko , Niikura Keiichi , Nakamura Atsushi , Miyatake Mayumi , Aoki Takeshi , Yajima Yoshinori , Suzuki Tsutomu
Published: December 2005

It is well known that prolonged exposure to morphine results in tolerance to morphine‐induced antinociception. In the present study, we found that either intrathecal (i.t.) or subcutaneous (s.c.) injection of the selective metabotropic glutamate receptor 5 (mGluR5) antagonist, methyl‐6‐(phenylethynyl)‐pyridine hydrochloride (MPEP), attenuated the development of tolerance to morphine‐induced antinociception. Using the receptor binding assay, we found here that the number of mGluR5 in the mouse spinal cord was significantly increased by repeated treatment with morphine. Furthermore, repeated treatment with morphine produced a significant increase in the level of mGluR5 immunoreactivity in the dorsal horn of the mouse spinal cord. Double‐labeling experiments showed that the increased mGluR5 was predominantly expressed in the neurons and sparsely expressed in the processes of astrocytes following repeated treatment with morphine. Consistent with these results, the response of Ca2+to the selective group I mGluR agonist, 3,5‐dihydroxyphenylglycine (DHPG), in cultured spinal cord neurons was potently enhanced by 3 days ofin vitrotreatment with morphine. These findings support the idea that the increased mGluR5 following repeated treatment with morphine leads to enhanced neuronal excitability and synaptic transmission in the dorsal horn of the spinal cord and, in turn, suppresses the morphine‐induced antinociception in mice.