bluuebunny/crossref_metadata_2025 huggingface dataset:
Backcross breeding for improved resistance to common bacterial blight in pinto bean (Phaseolus vulgaris L.)
Authors: Mutlu N. , Miklas P. , Reiser J. , Coyne D.
Published: July 2005

Common bacterial blight (CBB) caused by Xanthomonas campestris pv. phaseoli reduces common bean (Phaseolus vulgaris L.) yield and quality worldwide. Genetic resistance provides effective disease control; however. a high level of resistance is difficult to attain and does not exist in pinto bean, the most important dry bean market class in North America. Our objective was to determine if a backcross breeding approach with the aid of molecular markers linked to quantitative trait loci (QTL) for resistance to CBB in a donor parent could be used to attain higher levels of resistance to CBB in pinto bean. QTL conditioning CBB resistance from the donor parent XAN 159 were introgressed into the recurrent parent‘Chase’using classical backcross breeding and intermittent marker‐assisted selection.‘Chase’pinto bean is moderately resistant and the breeding line XAN 159 is highly resistant to Xanthomonas campestris. Marker assays confirmed the presence of independent QTL from GN no. 1 Sel 27 and XAN 159 in advanced backcross‐derived pinto bean lines with improved CBB resistance. Agronomic characteristics of‘Chase’were fully recovered in the backcross‐derived lines. An important QTL for CBB resistance from XAN 159 on linkage group B6 was not introgressed because tight linkage between this QTL and the dominant V allele that causes an unacceptable black‐mottled seed coat colour pattern in pinto bean could not be broken.
Mapping antixenosis genes on chromosome 6A of wheat to greenbug and to a new biotype of Russian wheat aphid
Authors: Castro A. M. , Vasicek A. , Manifiesto M. , Giménez D. O. , Tacaliti M. S. , Dobrovolskaya O. , Röder M. S. , Snape J. W. , Börner A.
Published: July 2005

Greenbug and Russian wheat aphid (RWA) are two devastating pests of wheat. The first has a long history of new biotype emergence and recently. RWA resistance has just started to break down. Thus, it is necessary to find new sources of resistance that will broaden the genetic base against these pests in wheat. Seventy‐five doubled haploid recombinant (DHR) lines for chromosome 6A from the F1 of the cross between “Chinese Spring’ and the “Chinese Spring (Synthetic 6A) (Triticum dicoccoides × Aegilops tauschii)” substitution line were used as a mapping population for testing resistance to greenbug biotype C and to a new strain of RWA that appeared in Argentina in 2003. A quantitative trait locus (QTL) (br antixenosis to greenbug was significantly associated with the marker loci Xgwm1009 and Xgwm1185 located in the centromere region of chromosome 6A. Another QTL which accounted for most of the antixenosis against RWA was associated with the marker loci Xgwm1291 and Xiinni1150. both located on the long arm of chromosome 6A. This is the first report of greenbug and RWA resistance genes located on chromosome 6A. It is also the first report of antixenosis against the new strain of RWA. As most of the RWA resistance genes present in released cultivars have been located in [he D‐genome, it is highly desirable to find new sources in other genomes to combine the existing resistance genes with new sources.
Effects of increased atmospheric CO2 on varieties of oat
Authors: Johannessen M. M. , Mikkelsen T. N. , Nersting L. G. , Gullord M. , von Bothmer R. , Jörgensen R. B.
Published: July 2005

The effects of elevated CO2 were investigated on seven Scandinavian varieties of oat. Three landraces (before 1920), two varieties of intermediate‐age (1920‐1940), and two recent varieties (after 1940) were exposed to two atmospheric CO2 concentrations (approx. 380 and 700 ppm). Elevated CO2 increased the yield 7% on average but with large variation between varieties. The yield‐response was variety specific and not related to the age of the variety. The mean seed number increased about 11%, with an increase in the landraces and diverging responses within the other age groups. The mean seed weight was reduced about 5.5%, with small changes within the landraces and diverging results within the two other age‐groups. The mean dry biomass was increased about 20%; the landraees had a marked increase in dry biomass, while the response in the other varieties ranged from a large increase to a small decrease. These different responses among varieties provide a spectrum of trait‐combinations desirable in breeding oats for different purposes. The quality of the seeds was not affected by the elevated CO2.
Genetic diversity assessment in cultivated cardoon by AFLP (amplified fragment length polymorphism) and microsatellite markers
Authors: Portis E. , Barchi L. , Acquadro A. , Macua J. I. , Lanteri S.
Published: July 2005

Cultivated cardoon (Cynara cardunculus L. var. altilis DC) belongs, together with globe artichoke (C. (cardunculus L. var. sylvestris L.) and wild cardoon (C. cardunculus L. var., sylvestris (Lamk) Fiori). to the family Asteraceae (Compositae). Cultivated cardoon is of regional importance in Italy. Spain and southern France, where it is used for the preparation of traditional dishes. It has been shown to have potential as a source of oil from its seeds, inulin from its roots and various biopharmaceuticals from its leaves. Levels of genetic diversity and relatedness between eleven Italian and 10 Spanish accessions were assessed by DNA profiling with eight AFLP primer combinations and at five microsatellite loci. The AFLP analysis of genetic similarities showed that the Spanish and Italian accessions represent two distinct gene pools; substantial variation was present within each accession. On the other hand a limited variation was detectable by applying SSR markers.
The protective role of melatonin in experimental hypoxic brain damage
Authors: Tütüncüler Filiz , Eskiocak Sevgi , BaŞaran Ümit Nusret , Ekuklu Galip , Ayvaz Süleyman , Vatansever Ülfet
Published: July 2005

Background
: It is known that oxygen‐derived free radicals play an important role in the pathogenesis of brain injury. Melatonin is a powerful scavenger of the oxygen free radicals. In this study, the protective effect of melatonin against the damage inflicted by reactive oxygen species during brain hypoxia was investigated in newborn rats using biochemical parameters.

Methods
: For biochemical analyses, the levels of lipid peroxidation product (malondialdehyde ([MDA]), levels of reduced glutathione (GSH) and the activities of superoxide dismutase (SOD) and catalase (CAT) were estimated.

Results
: After the third day of brain hypoxia, the brain levels of MDA increased. Pretreatment of animals with melatonin abolished the rise in MDA induced by hypoxia. GSH concentration did not increase by pretreatment with melatonin. Additonally, the activities of two antioxidative enzymes (SOD and CAT) decreased after the experimental period with melatonin only preventing the change of CAT. The activity of SOD was not influenced by melatonin administration as expected.

Conclusion
: In this experimental study, exogenously administered melatonin effectively protected against brain injury by oxidative stress. This protective effect of melatonin may be due to its direct scavenger activity and activation of CAT. Thus, melatonin may potentially be useful in the treatment of neurodegenerative conditions that may involve free radical production, such as perinatal hypoxia.
Assessment of the short‐term effect of antispastic positioning on spasticity
Authors: Akbayrak Turkan , Armutlu Kadriye , Gunel Mintaze Kerem , Nurlu Gulay
Published: July 2005

Background: This study was performed in order to investigate the effect of antispastic positioning on spasticity by using different assessment methods.

Methods: A total of 16 patients (11 males [68.75%] and five females [31.25%]), diagnosed as spastic diplegic and referred to the School of Physical Therapy and Rehabilitation, Paediatric Rehabilitation Unit for treatment, were included in this study. The mean age of patients was 6.43 ± 1.99 years (range, 4–13 years). Passive dorsi‐flexion movement was measured by using goniometer and intensity of spasticity was determined by using Modified Ashworth Scale (MAS) and electromyography. For the objective measurement of severity of spasticity, Hoffman reflex (H) and Hoffman reflex/motor response (H/M) ratios were used. Children were placed in an antispastic position for 20 min. The patient was placed in a sitting position, by a physiotherapist, with hips abducted at a 45° angle and externally rotated, knees extended, and ankles placed in a neutral position.

Results: The decrease in H responses, H/M ratios, MAS values and the increase in goniometric measurement values were found statistically significant after antispastic positioning (P < 0.05).

Conclusion: Our study supports that antispastic positioning can be used with neurodevelopmental treatment approaches when it is required. Antispastic positioning may help exercises to be performed more easily, and also has importance in a home exercise program to prevent muscle contractures and joint limitation in children with long‐term spastic diplegia.
Safety and efficacy of palivizumab prophylaxis in children with congenital heart disease*
Authors: Saji Tsutomu , Nakazawa Makoto , Harada Kensuke
Published: July 2005

Background
: Infants with congenital heart diseases (CHD) are at high risk for Respiratory syncytial virus (RSV) infection, which causes severe respiratory distress. Palivizumab, an anti‐RSV monoclonal antibody, was licensed in the USA, Europe and Canada, and a large‐scale placebo‐controlled double‐blind test in these countries confirmed its efficacy and safety. A survey using questionnaires to assess usage, prophylactic efficacy, and safety of palivizumab in Japanese infants and young children with CHD was conducted.

Methods
: The survey was conducted between October 2002 and March 2003. The questionnaire asked for patients’ characteristics, presence of CHD, underlying diseases, starting date and number of injection, adverse events, correlation between adverse events and treatment with palivizumab, and evaluation of efficacy.

Results
: In total, 108 infants were reported from 61 institutions. A total of 60 of the 108 infants evaluated without major non‐cardiac complications received intramuscular injection of 15 mg/kg per month of palivizumab in a manner not consistent with approved indications for this drug. A total of 43 cases (39.8%) had complexed CHD, while 64 cases (59.3%) had the first injection in October or November. The average number of injections was 3.0 ± 1.4. Seven children (6.5%) had notable respiratory infections confirmed by positive test for RSV antigen, and five (4.6%) were hospitalized. No children died nor received mechanical ventilation. The number of adverse events was nine in five cases. There was no significant relationship between adverse events and treatment with palivizumab.

Conclusion
: Palivizumab is well‐tolerated, fairly effective and safe in preventing severe RSV infection in infants and young children with CHD.
Lamivudine treatment in maternally transmitted chronic hepatitis B virus infection patients
Authors: Ni Yen‐Hsuan , Huang Fu‐Chen , Wu Tzee‐Chung , Kong Man‐Shan , Jeng Yung‐Ming , Chen Pei‐Jer , Tsuei Daw‐Jen , Chen Huey‐Ling , Hsu Hong‐Yuan , Chang Mei‐Hwei
Published: July 2005

Background
: Lamivudine treatment in chronic carriers who acquired hepatitis B virus through maternal transmission were investigated.

Methods
: A total of 29 subjects (Male : Female, 24:5; mean age, 14.7 ± 5.6 years) who were hepatitis B e antigen (HBeAg) seropositive for >6 months, alanine aminotransferase (ALT) was >1.3 times of upper limit of normal value, and receiving a 52 week‐long treatment, received open‐label lamivudine (3 mg/kg per day, maximum 100 mg/day). Another 29 subjects matched for gender, age, liver function, and HBeAg status followed up before the introduction of lamivudine served as the control group. The control group did not receive any treatment and were evaluated at week 52 after the onset of abnormal ALT. Mothers of all study subjects were hepatitis B surface antigen (HBsAg) carriers. A successful treatment response at week 52 was defined as: (i) undetectable hepatitis B virus DNA by real time polymerase chain reaction; (ii) normal ALT; and (iii) HBeAg/anti‐HBe seroconversion. Lamivudine‐resistant YMDD mutants were checked at week 52.

Results
: The lamivudine group did not reach a better successful treatment response rate than the control group (17 vs 10%, P = 0.44), except in patients with a baseline ALT >5 times of the upper limit of normal value. YMDD mutants developed in 34% of patients in the lamivudine group.

Conclusion
: Lamivudine treatment is effective for maternally transmitted subjects with high ALT.
Assessing the effectiveness of a mammography screening service
Authors: Clayforth Cassandra , Fritschi Lin , McEvoy Suzanne , Byrne Michael J. , Wylie Elizabeth , Threlfall Tim , Sterrett Greg , Harvey Jennet M. , Jamrozik Konrad
Published: August 2005

Background:  Trials have shown that mammography screening reduces mortality and probably decreases morbidity related to breast cancer.

Methods:  We assessed whether the major mammography service in Western Australia (BreastScreen WA) is likely to reduce mortality by comparing prognostic variables between screen‐detected and other cases of breast cancer diagnosed in 1999. We assessed likely reductions in morbidity by comparing treatments received by these two groups. To confirm mortality and morbidity reduction, we also compared prognostic variables and treatments with targets. Information on demographic variables, tumour characteristics at presentation and treatments were collected from medical records for all incident cases of breast cancer in Western Australia in 1999. We matched cases with the Western Australian Cancer Registry records to determine which cases had been detected by BreastScreen WA.

Results:  BreastScreen WA achieved the targets for mortality reduction. Tumours detected by BreastScreen WA were smaller in size, less likely to have vascular invasion, of lower histological grade and were more likely to be ductal carcinoma in situ alone without invasive carcinoma. Oestrogen receptor status was more likely to be positive, the difference in progesterone status was not significant, and lymph node involvement tended to be lower. BreastScreen WA patients were treated more often with local therapy and less often with systemic therapy, and the proportion of patients treated with breast‐conserving surgery was close to the target for minimizing morbidity in breast cancer.

Conclusion:  Mammographic detection of breast cancer by BreastScreen WA is associated with reduced breast cancer morbidity and a more favourable prognosis.
Impact of skip metastasis in gastric cancer
Authors: Park Sung‐Soo , Ryu Je‐Seock , Min Byung‐Wook , Kim Wan‐Bae , Kim Seung‐Joo , Kim Chong‐Suk , Mok Young‐Jae
Published: August 2005

Background:  Several studies have shown the features of skip metastasis in other cancers besides gastric cancer. Since minimally invasive surgery has been applied to gastric cancer, the concerns and awareness of skip metastasis have grown in the medical community. We conducted the present retrospective study to reveal the clinicopathological characteristics of patients with skip metastasis. We also wished to clarify the clinical impact of skip metastasis for gastric cancer.

Methods:  Five hundred and eighty‐nine patients having lymphatic metastases were enrolled in the present study. Among them, 266 patients had positive nodes extending into the N2 group. We divided these patients into the skip positive (+) and the skip negative (−) group, and we comparatively analysed clinicopathological factors and calculated the survival probabilities for the two groups.

Results:  The skip (+) and skip (−) groups involved 14 (5.3%) and 252 (94.7%) patients, respectively. Of all the investigated factors, a significant difference between two groups was observed only in the total number of retrieved nodes. Stations of skip nodes were along left gastric (7), anterior common hepatic (8a), celiac (9), splenic (11) artery and right paracardial nodes (1). The survival curves calculated in the present study did not show any statistical differences between the groups.

Conclusions:  Due to problems of skip metastasis in gastric cancer, D2 lymph node dissection should be performed until sentinel node detection is feasible and reliable. The potential risk from skip metastasis is not great and skip metastasis itself should not be a major consideration in therapeutic decisions.
Negotiating the Dichotomy of Boffin and Triad: British-Chinese Pupils' Constructions of ‘Laddism’
Authors: Francis Becky , Archer Louise
Published: July 2005

Little research has examined constructions of gender among young British-Chinese. This paper seeks to further understanding in this area, particularly in relation to notions of ‘laddism’ currently deployed in educational policy discourse around gender and achievement. As a group British-Chinese boys tend to very high achievement in the British Education system. The notion of ‘laddish behaviour’ as an explanation for boys’ apparent underachievement in comparison to girls at GCSE level was discussed with British-Chinese pupils. An overwhelming majority of British-Chinese pupils supported this explanation, and a majority of these pupils applied notions of ‘laddish behaviour’ to British-Chinese boys, to some extent contesting stereotypes of the Chinese as uniformly ‘good pupils’. However, the discourses of ‘the good Chinese pupil’ and ‘Chinese value of education’ were frequently drawn on by pupil respondents, with the result that the pupils often presented British-Chinese manifestations of ‘laddism’ as mild versions in comparison with pernicious ‘others’. The paper discusses different presentations of laddism among some of the male respondents. It concludes by analysing the impact of ‘raced’ and gendered discourses on British-Chinese constructions of masculinity. British-Chinese boys may be able to adopt versions of masculinity which do not impede their learning, but this tended to result in their masculinity being problematised in teacher discourse.
‘Listen to my madness’: understanding the experiences of people with serious mental illness
Authors: Lester Helen , Tritter Jonathan Q.
Published: August 2005

This article explores the salience of disability theory for understanding the experiences of people with serious mental illness. Drawing on data from a focus group study, we suggest that users experience both impairment (as embodied irrationality) which can, in itself, be oppressive, and also have to manage their lives within a largely disabling society. We outline some of the strategies adopted by users to manage their situation and ensure they access and receive health services, and illustrate how these are a result of the complex relationship between disability and impairment. We suggest that using a framework of the social model of disability provides a useful way of understanding and making sense of the experience of users with serious mental illness.
Improving Communication Between Children with Autism and Their Peers Through the ‘Circle of Friends’: A Small‐scale Intervention Study
Authors: Kalyva Efrosini , Avramidis Elias
Published: August 2005

Background  The ‘circle of friends’ is an educational approach that facilitates the inclusion of children with disabilities into the school community by engaging their peer group in supporting the individual proactively. The present small‐scale study examines the efficacy of this intervention in improving the communication (and ultimately social) skills of pre‐school aged children with autism.

Methods  Five children identified with autism aged between 3.10 and 4.7 years participated in the study – three in the intervention and two in the control group. The ‘circle of friends’ was applied for 30 min on a weekly basis at a nursery setting for a period of 3 months with the active involvement of one teacher and five peers of each child with autism. The effects of the intervention were systematically examined by means of an observation schedule which recorded the number of responses and initiation attempts – both unsuccessful and successful – of all participating children with autism during baseline, post‐intervention and at 2 months follow‐up.

Results  The statistical analysis of the data revealed that children in the intervention group had significantly lower unsuccessful response and initiation rates at post‐intervention and follow‐up than children in the control group. Moreover, children in the intervention group had significantly higher successful response and initiation rates at post‐intervention and follow‐up than those in the control group.

Conclusions  The recorded changes in the interaction patterns indicate that the ‘circle of friends’ is a powerful intervention that, if carefully applied, can improve the social skills of children with autism and their ability to communicate, and ultimately facilitate their ‘inclusion’ in mainstream settings. Further larger‐scale longitudinal research is needed to examine the long‐term benefits of the approach for children with autism and the broader changes in the nexus of relations within the mainstream environment.
Staff Stress and Morale in Community‐Based Settings for People with Intellectual Disabilities and Challenging Behaviour: A Brief Report
Authors: Robertson Janet , Hatton Chris , Felce David , Meek Andrea , Carr Deborah , Knapp Martin , Hallam Angela , Emerson Eric , Pinkney Lisa , Caesar Emma , Lowe Kathy
Published: August 2005

Background  There are no studies that have compared outcomes for staff in different types of supported accommodation for people with intellectual disabilities and challenging behaviour. This study looked at stress, morale and intended job turnover in staff in two types of community‐based residential supports: non‐congregate settings where the minority of residents have challenging behaviour; and congregate settings where the majority of residents have challenging behaviour.

Materials and methods  A self‐completion survey questionnaire was used to collect information on the basic characteristics of staff, levels of staff stress, job satisfaction and propensity to leave their employment.

Results  One hundred and fifty‐seven questionnaires were returned from staff, the majority of whom were on fixed‐term contracts. Congregate settings were not associated with higher levels of stress as might be assumed. Overall, over a quarter of staff reached criterion on the General Health Questionnaire‐12 for experiencing emotional distress, and over a third were likely to actively seek new employment in the next year. The greatest perceived sources of stress were lack of resources and lack of staff support. The lowest level of satisfaction was with the rate of pay. Those in non‐congregate settings reported greater perceived stress because of lack of procedures to deal with challenging behaviour.

Conclusions  High levels of intended staff turnover may be more due to job insecurity and lack of support than service user challenging behaviour. Employers seeking to reduce turnover should pay attention to basic pay and conditions, as well as staff training in appropriate methods for dealing with challenging behaviour.
Dicer and eIF2c are enriched at postsynaptic densities in adult mouse brain and are modified by neuronal activity in a calpain‐dependent manner
Authors: Lugli Giovanni , Larson John , Martone Maryann E. , Jones Ying , Smalheiser Neil R.
Published: July 2005

We have hypothesized that small RNAs may participate in learning and memory mechanisms. Because dendritic spines are important in synaptic plasticity and learning, we asked whether dicer, the rate‐limiting enzyme in the formation of small RNAs, is enriched within dendritic spines. In adult mouse brain, dicer and the RNA‐induced silencing complex (RISC) component eIF2c were expressed in the somatodendritic compartment of principal neurons and some interneurons in many regions, and dicer was enriched in dendritic spines and postsynaptic densities (PSDs). A portion of dicer and eIF2c were associated with each other and with fragile X mental retardation protein (FMRP), as assessed by co‐immunoprecipitation. Calpain I treatment of recombinant dicer or immunopurified brain dicer caused a marked increase in RNAse III activity. Purified PSDs did not exhibit RNAse III activity, but calpain caused release of dicer from PSDs in an enzymatically active form, together with eIF2c. NMDA stimulation of hippocampal slices, or calcium treatment of synaptoneurosomes, caused a 75 kDa dicer fragment to appear in a calpain‐dependent manner. The findings support a model whereby acute neuronal stimulation at excitatory synapses increases intracellular calcium, which activates calpain, which liberates dicer and eIF2c bound to PSDs. This supports the hypothesis that dicer could be involved in synaptic plasticity.
Subcellular localization suggests novel functions for prolyl endopeptidase in protein secretion
Authors: Schulz Ingo , Zeitschel Ulrike , Rudolph Thomas , Ruiz‐Carrillo David , Rahfeld Jens‐Ulrich , Gerhartz Bernd , Bigl Volker , Demuth Hans‐Ulrich , Roßner Steffen
Published: July 2005

For a long time, prolyl endopeptidase (PEP) was believed to inactivate neuropeptides in the extracellular space. However, reports on the intracellular activity of PEP suggest additional, as yet unidentified, physiological functions for this enzyme. Here, we demonstrate using biochemical methods of subcellular fractionation, immunocytochemical double‐labelling procedures and localization of PEP–enhanced green fluorescent protein fusion proteins that PEP is mainly localized to the perinuclear space, and is associated with the microtubulin cytoskeleton in human neuroblastoma and glioma cell lines. Disassembly of the microtubules by nocodazole treatment disrupts both the fibrillar tubulin and PEP labelling. Furthermore, in a two‐hybrid screen, PEP was identified as binding partner of tubulin. These findings indicate novel functions for PEP in axonal transport and/or protein secretion. Indeed, a metabolic labelling approach revealed that both PEP inhibition and PEP antisense mRNA expression result in enhanced peptide/protein secretion from human U‐343 glioma cells. Because disturbances in intracellular transport and protein secretion mechanisms are associated with a number of ageing‐associated neurodegenerative diseases, cell‐permeable PEP inhibitors may be useful for the application in a variety of related clinical conditions.
Structural requirements for steady‐state localization of the vesicular acetylcholine transporter
Authors: Ferreira Lucimar T. , Santos Magda S. , Kolmakova Natalia G. , Koenen Janaina , Barbosa Jose , Gomez Marcus V. , Guatimosim Cristina , Zhang Xiaodong , Parsons Stanley M. , Prado Vania F. , Prado Marco A. M.
Published: July 2005

The vesicular acetylcholine transporter (VAChT) regulates the amount of acetylcholine stored in synaptic vesicles. However, the mechanisms that control the targeting of VAChT and other synaptic vesicle proteins are still poorly comprehended. These processes are likely to depend, at least partially, on structural determinants present in the primary sequence of the protein. Here, we use site‐directed mutagenesis to evaluate the contribution of the C‐terminal tail of VAChT to the targeting of this transporter to synaptic‐like microvesicles in cholinergic SN56 cells. We found that residues 481–490 contain the trafficking information necessary for VAChT localization and that within this region L485 and L486 are strictly necessary. Deletion and alanine‐scanning mutants lacking most of the carboxyl tail of VAChT, but containing residues 481–490, were still targeted to microvesicles. Moreover, we found that clathrin‐mediated endocytosis of VAChT is required for targeting to microvesicles in SN56 and PC12 cells. The data provide novel information on the mechanisms and structural determinants necessary for VAChT localization to synaptic vesicles.
Topiramate reduces AMPA‐induced Ca2+ transients and inhibits GluR1 subunit phosphorylation in astrocytes from primary cultures
Authors: Ängehagen Mikael , Rönnbäck Lars , Hansson Elisabeth , Ben‐Menachem Elinor
Published: July 2005

Topiramate (TPM) is a structurally novel broad spectrum anticonvulsant known to have a negative modulatory effect on the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA)/kainate subtypes of glutamate receptors and some types of voltage‐gated Na+ and Ca2+ channels, and a positive modulatory effect on some types of γ‐aminobutyric acidA (GABAA) receptors and at least one type of K+ channels in neurons. In an earlier work, we showed that the negative modulatory effect of TPM (100 μm) on AMPA/kainate receptors in neurons is dependent on TPM modulation of the phosphorylation state of these receptors. In this work, we investigated the effect of TPM on AMPA‐induced intracellular calcium ([Ca2+]i) responses in cultured rat cortical astrocytes, with special interest in intracellular mechanisms. Here, we report that the ability of TPM (1–100 μm) to inhibit AMPA‐induced accumulation of Ca2+ in astrocytes is inversely related to the level of protein kinase A (PKA) ‐mediated phosphorylation of channels activated by AMPA. The level of receptor phosphorylation was further determined with western blot using phosphorylation specific antibodies that recognize the glutamate receptor 1 (GluR1) subunit phosphorylated on Ser845. These results demonstrated that, even in cultured cortical astrocytes, TPM significantly reduced the phophorylation level of GluR1 subunits. Furthermore, it was shown that TPM binds to AMPA receptors in the dephosphorylated state and thereby exerts an allosteric modulatory effect on the ion channel.
Insulin modulates hippocampal activity‐dependent synaptic plasticity in a N‐methyl‐d‐aspartate receptor and phosphatidyl‐inositol‐3‐kinase‐dependent manner
Authors: Van Der Heide Lars P. , Kamal Amer , Artola Alain , Gispen Willem Hendrik , Ramakers Geert M. J.
Published: July 2005

Insulin and its receptor are both present in the central nervous system and are implicated in neuronal survival and hippocampal synaptic plasticity. Here we show that insulin activates phosphatidylinositol 3‐kinase (PI3K) and protein kinase B (PKB), and results in an induction of long‐term depression (LTD) in hippocampal CA1 neurones. Evaluation of the frequency–response curve of synaptic plasticity revealed that insulin induced LTD at 0.033 Hz and LTP at 10 Hz, whereas in the absence of insulin, 1 Hz induced LTD and 100 Hz induced LTP. LTD induction in the presence of insulin required low frequency synaptic stimulation (0.033 Hz) and blockade of GABAergic transmission. The LTD or LTP induced in the presence of insulin was N‐methyl‐d‐aspartate (NMDA) receptor specific as it could be inhibited by α‐amino‐5‐phosphonopentanoic acid (APV), a specific NMDA receptor antagonist. LTD induction was also facilitated by lowering the extracellular Mg2+ concentration, indicating an involvement of NMDA receptors. Inhibition of PI3K signalling or discontinuing synaptic stimulation also prevented this LTD. These results show that insulin modulates activity‐dependent synaptic plasticity, which requires activation of NMDA receptors and the PI3K pathway. The results obtained provide a mechanistic link between insulin and synaptic plasticity, and explain how insulin functions as a neuromodulator.
Aging of hair
Authors: Trüeb Ralph M
Published: August 2005

The appearance of hair plays an important role in people's overall physical appearance and self‐perception. With today's increasing life expectation, the desire to look youthful plays a bigger role than ever. The hair care industry has become aware of this and also more capable to deliver active products that are directed toward meeting this consumer demand. The discovery of pharmacological targets and the development of safe and effective drugs also indicate strategies of the drug industry for maintenance of healthy and beautiful hair. Hair aging comprises weathering of the hair shaft and aging of the hair follicle. The latter manifests as decrease of melanocyte function or graying, and decrease in hair production in androgenetic and senescent alopecia. The scalp is also subject to intrinsic or physiologic aging and extrinsic aging caused by external factors. Intrinsic factors are related to individual genetic and epigenetic mechanisms with interindividual variation. Prototypes are familial premature graying and androgenetic alopecia. Extrinsic factors include ultraviolet radiation and smoking. Experimental evidence supports the hypothesis that oxidative stress plays a role in skin and hair aging. Topical anti‐aging compounds for hair include humefactants, hair conditioners, photoprotectors, and antioxidants. Current available treatment modalities with proven efficacy for treatment of androgenetic alopecia are topical minoxidil, oral finasteride, and autologous hair transplantation. In the absence of another way to reverse hair graying, hair colorants are the mainstays of recovering lost hair color. Topical liposome targeting for melanins, genes, and proteins selectively to hair follicles are under current investigation.
Comparative Tolerability of Oral 5‐HT1B/1D Agonists
Authors: Fox Anthony W. , Ffpm
Published: July 2005

Objectives.—To compare the relative tolerability of 5‐HT1B/1D agonists and to investigate the relationships (if any) among systemic exposure, lipophilicity, and clinical tolerability for 5‐HT1B/1D agonists.

Methods.—Post hoc correlations were sought among the following variables: absolute dose (=administered dose × oralbioavailability), Cmax, LogDpH7.4 (LogD), frequencies of all, neurological and dizziness/somnolence/drowsiness adverse events, adjusted for corresponding placebo‐associated frequencies.

Results.—For effective doses of all drugs with available data, absolute dose‐response relationships exist for adverse event frequencies. The overall rank order of the frequency of adverse events was as follows: naratriptan < sumatriptan = rizatriptan < zolmitriptan.

With the exception of eletriptan, 5‐HT1B/1D agonists exhibit correlations between absolute dose, Cmax (R = 0.97), and LogD (R = 0.71). For neurological and dizziness/somnolence/drowsiness adverse event frequencies, the overall rank order was sumatriptan < naratriptan < rizatriptan < zolmitriptan. Neither LogD nor absolute dose size predicted adverse event frequencies.

Conclusions.—Triptans may be distinguished in terms of their tolerability. Effectiveness, absolute dose size, and lipophilicity are related for the 5‐HT1B/1Dagonists considered here, except eletriptan. Adverse event frequencies cannot be predicted from in vitro measures of lipophilicity, in vivo estimates of absolute bioavailability, dose size, or any combination of these variables. Since these drugs are all agonists at 5‐HT1B/1D receptors in the low nanomolar range, but differ in their tolerability profiles, adverse effects are not likely to be mediated through 5‐HT1B/1D receptors. Drugs of this class must be studied individually and on a reasonably large scale in clinical development programs.
Infantile Spasms in One Member of a Family with Benign Familial Neonatal Convulsions
Authors: Mori Kenji , Yano Ichiro , Hashimoto Toshiaki
Published: August 2005

Summary: Seven members of two generations experienced benign familial neonatal convulsions (BFNC) in the neonatal period and/or early infancy. All but 1 family member had a good prognosis. One family member with infantile spasms (IS) was delivered by cesarean section at 37 weeks gestation. Birth weight (2,562 g) was slightly lower than that of other family members. At age 20 days, adversive seizures started. At age 1 month, 10 days, she developed complex partial seizures (CPS) and IS. Interictal EEG showed hypsarrhythmia. Biochemical investigations and head magnetic resonance imaging (MRI) scan showed no abnormalities. Treatment with valproate (VPA) and carbamazepine (CBZ) stopped the seizures, and she had no seizures after age 3 months. Psychomotor development was moderately delayed at 8 months. This is the first reported case of a severe epilepsy, IS, in association with BFNC.
Reappraisal of Interictal Electroencephalograms in Infantile Spasms
Authors: Watanabe Kazuyoshi , Negoro Tamiko , Aso Kosaburo , Matsumoto Akiko
Published: August 2005

Summary: To delineate interictal electroencephalographic (EEC) features before treatment of patients with clinically defined infantile spasms, EEGs of 82 infants having tonic spasms in clusters were analyzed by type of paroxysmal abnormalities, continuity, interhemispheric synchrony, topography, and wave component of hypsarrhythmia during wakefulness and sleep. Hypsarrhythmia occurred less frequently in wakefulness than in non‐rapid eye movement (NREM) sleep at any age, least frequently in wakefulness after 1 year of age, and disappeared in rapid eye movement (REM) sleep at any age. The continuity of hypsarrhythmia changed with states, but did not change with age, and was greatest in wakefulness and stage 1 and decreased in stage 2–3. Interhemispheric synchrony increased with increasing age but decreased with advancing sleep stage. The term modified hypsarrhythmia should be discarded, and unusual features, if present, should be specified.
Value of Magnetic Resonance Imaging in West Syndrome of Unknown Etiology
Authors: van Bogaert P. , Chiron C. , Adamsbaum C. , Robain O. , Diebler C. , Dulac O.
Published: August 2005

Summary: Magnetic resonance imaging (MRI) studies of 46 patients with West syndrome (WS) of unknown etiology were reviewed retrospectively. The criteria for cryptogenic WS were met by 25 and 21 were considered symptomatic because other types of seizure or psychomotor retardation were apparent before spasm onset. Computed tomographic (CT) scans were normal in 38 patients and showed diffuse atrophy in eight symptomatic patients. In five patients, MRI was more informative than CT, demonstrating one case of delayed myelination and four cases of focal lesion. The focal lesion in 2 of these patients was similar on MRI consisting of poor gray‐white matter demarcation in the parieto‐occipitotemporal region. Surgical resection was performed in one because of intractable seizures, and neuropathological examination revealed cortical dysplasia. The remaining two cases with focal lesion had increased signal intensity on T2‐weighted images in the posterior frontal cortex and in the temporal lobe, respectively. Our data indicate that MRI is useful in some cases of WS, especially in demonstrating focal corticosubcortical lesions not visible on CT scan.
Epilepsy and the Electroencephalogram in Progressive Encephalopathy with Edema, Hypsarrhythmia, and Optic Atrophy (the PEHO Syndrome)
Authors: Somer Mirja , Sainio Kimmo
Published: August 2005

Summary: Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO syndrome) is an apparently autosomal recessive disorder manifested by infantile spasms, severe hypotonia, and early arrest of psychomotor development. Subcutaneous edema in the limbs, typical facial features, and blindness with optic atrophy are also present. Neuropathologic and radiographic studies show progressive brain atrophy, which is accentuated infratentorially. We recorded 85 EEGs from 10 patients between the ages of 3 weeks and 12.7 years; follow‐up ranged from 7 months to 12.1 years. The infantile spasms were preceded by other neurological symp‐ toms in all patients. Seven of nine patients showed focal or generalized epileptiform activity or abnormal EEG background. All patients developed hypsarrhythmia, first recorded between 3 and 11 months of age, that was resistant to therapy with ACTH and antiepileptic drugs. After the hypsarrhythmia disappeared, five patients showed slow spike‐wave activity generally seen in the Lennox‐Gastaut syndrome, and three patients showed background EEG abnormality with generalized or diffuse paroxysmal activity. There were no specific EEG features that could help in the diagnosis of PEHO. The PEHO syndrome should be borne in mind in the diagnostic work‐up of patients with infantile spasms, so that potentially harmful treatment can be avoided, and the parents can be counseled about the inheritability of the disorder.
Predicting Favorable Outcome in Idiopathic West Syndrome
Authors: Dulac Olivier , Plouin Perrine , Jambaqué Isabelle
Published: August 2005

Summary: Among 45 patients with cryptogenic West Syndrome (WS) we report 30 with a favorable outcome consisting of normal psychomotor development and cessation of epilepsy with at least 2 years follow‐up (mean 4 years 7 months). These favorable patients could be recognized from onset by (a) absence of significant mental regression with a preserved visual function; (b) absence of focal interictal EEG abnormalities after intravenous diazepam; and (c) reappearance of hypsarrhythmia between consecutive spasms of a cluster. The latter criterion requires EEG recording of a series of spasms. The favorable outcome in these patients suggests that they had no cortical brain lesions. This new type of idiopathic epilepsy referred to as idiopathic West syndrome has important prognostic, therapeutic, and etiologic implications.
Burst Suppression and Impairment of Neocortical Ontogenesis: Electroclinical and Neuropathologic Findings in Two Infants with Early Myoclonic Encephalopathy
Authors: Spreafico R. , Angelini L. , Binelli S. , Granata T. , Rumi V. , Rosti D. , Runza L. , Bugiani O.
Published: August 2005

We report the electroclinical and neuropathologic correlations in 2 children aged 2.5 months affected by early myoclonic encephalopathy characterized by epileptic seizures, erratic myoclonus, and an EEG pattern of burst suppression. Despite different etiologies, the neuropathologic findings showed similar abnormalities in both cases, with no substantial impairment of the myelination processes. Islands of matrix tissue scattered in the periventricular region and neurons aligned marginally in the bulbar olives were detected. The presence of numerous large spiny neurons dispersed in the white matter along the axons of the cortical gyri was the most striking finding. These neurons have been interpreted as abnormally persisting interstitial cells in 2.5‐month‐old children. These early generated neurons, normally present during neocortical histogenesis, are programmed to die near the end of gestation or soon after birth. The interstitial cells are regarded as a waiting compartment of afferent fibers during cortical development. Their persistence in our patients represents an anatomic condition for cortical disconnection providing a pathophysiologic basis to burst‐suppression phenomena.
Usefulness of Unilateral Interictal Sharp Waves of Temporal Lobe Origin in Prolonged Video‐EEG Monitoring Studies
Authors: Kanner Andres M. , Morris Harold H. , Lüders Hans , Dinner Dudley S. , Van Ness Paul , Wyllie Elaine
Published: August 2005

The value of EEG interictal epileptiform activity in predicting location of the seizure focus remains controversial. In 64 patients, scalp video‐EEG monitoring studies showed one or two ipsilateral interictal foci in the temporal lobe. The site of these interictal foci correlated with location of the seizure focus recorded during prolonged video‐electrocorticography (ECoG) with use of subdural grids placed under the mesiobasal temporal region and over the lateral temporal convexity. Our findings suggest that unilateral anterotemporal interictal foci can accurately predict location of seizure onset. This is also true in patients with two ipsilateral temporal interictal foci, provided that the dominant focus is localized in anterotemporal regions. We believe that in such patients invasive recordings are not warranted, but we caution against sole use of interictal epileptiform criteria for localization of the seizure focus. Correlation with clinical information, ictal EEG, neuropsychometric, and neu‐roimaging studies is required before performance of epilepsy surgery.
Adjuvant Vigabatrin in Refractory Epilepsy: A Ceiling to Effective Dosage in Individual Patients?
Authors: McKee P. J. W. , Blacklaw J. , Friel E. , Thompson G. G. , Gillham R. A. , Brodie M. J.
Published: August 2005

A double‐blind, randomized, cross‐over study of additional vigabatrin (γ‐vinyl‐GABA, VGB, 1.0 g twice daily for 6 weeks, followed by 1.5 g twice daily for 6 weeks) and matched placebo was undertaken in 24 patients with refractory epilepsy. Nineteen completed the trial satisfactorily. Fewer seizure days were reported during VGB treatment [placebo 41, VGB 23, p < 0.05, 95% confidence interval (CI) −1.5 to −14]. An overall reduction in median seizure numbers failed to reach statistical significance (n = 19; placebo 52, VGB 32, NS, 95% CI −18 to + 24). Subgroup analysis, however, showed a significant reduction in partial seizures (n = 17) with 2 g VGB daily (placebo 22, VGB 13, p < 0.05, 95% CI −0.5 to −16.5), but not with higher dosage (placebo 28, VGB 22, NS, 95% CI − 18 to + 11). A deterioration in control of partial seizures as compared with the equivalent placebo phase was observed when patients were changed from 2 to 3 g/day VGB (2 g VGB 13, 3 g VGB 22, p = 0.05, 95% CI 0 to +20). Loss of efficacy was noted in 3 patients, and seizure control worsened slightly in 5 others. One previously resistant patient developed a therapeutic response, and 2 other patients reported an additional useful reduction in seizures. In the remaining 8 patients, seizure frequency did not change. VGB did not appear to benefit tonic‐clonic seizures. Serum VGB concentrations were higher during treatment with 3 g (15.5 ± 8.9 mg/L) daily than with 2 g (13.5 ± 11.2 mg/L). No important alterations were noted in the concentrations of concomitantly administered antiepileptic drugs (AEDs) throughout the trial. VGB is useful adjuvant therapy for treatment of partial seizures. There may be a ceiling to effective dosage. This demands individual dose titration for each patient.
Discordant Occurrence of Cerebral Unilateral Heterotopia and Epilepsy in Monozygotic Twins
Authors: Kuzniecky Ruben , Gilliam Frank , Faught Edward
Published: August 2005

Summary: Cerebral developmental malformations are increasingly recognized as a cause of epilepsy. Magnetic resonance imaging (MRI) has advanced our understanding of these disorders and their relation to epilepsy. We report the occurrence of discordant unilateral heterotopia and epilepsy in monozygotic twins. The affected individual developed intractable focal seizures at age 16 years. Mild cognitive difficulties had been present in early life. Evaluation showed right hemisphere EEG epileptogenic abnormalities, and the MRI scan showed massive right hemisphere heterotopia. EEG and MRI examinations in the patient's twin brother were normal. These findings suggest that the development of some developmental brain malformations and epilepsy is strongly influenced by nongenetic factors such as anenvironmental insult.
Oculogyric Crisis Induced by Carbamazepine
Authors: Gorman Mark , Barkley Gregory L.
Published: August 2005

Summary: A 32‐year‐old man with mental retardation and uncontrolled complex partial epilepsy receiving carbamazepine (CBZ) and divalproex sodium (VPA), developed frequent episodes of forced upward gaze after increase in the daily VPA dosage. CBZ dosage was decreased, with prompt resolution of symptoms. The upward gaze problem recurred several months later. CBZ dosage was decreased further with subsequent resolution of symptoms. Therefore, the oculogyric crisis (OGC) appeared to be induced by CBZ.