bluuebunny/crossref_metadata_2025 huggingface dataset:
Nefiracetam Attenuates Methamphetamine‐Induced Discriminative Stimulus Effects in Rats
Authors: YAN YIJIN , MIZUNO TOMOKO , NITTA ATSUMI , YAMADA KIYOFUMI , NABESHIMA TOSHITAKA
Published: November 2004

Abstract: Nefiracetam has been reported to increase intracellular cyclic AMP levels and enhance calcium channel current. Since the cAMP cascade is involved in the development of drug dependence, we investigated whether nefiracetam attenuates the methamphetamine (MAP)‐induced discriminative responses in rats. Nefiracetam (50 mg/kg) inhibited MAP‐induced discriminative responses. Furthermore, rolipram, raclopride, and L‐745870, all of which can enhance cAMP activity, disrupted MAP‐paired lever press of rats. Nifedipine and neomycin, which are blockers of voltage‐sensitive calcium channels (VSCCs), decreased MAP‐induced discriminative responses. However, pretreatment of these VSCC blockers failed to affect the inhibitory effects of nefiracetam on MAP‐induced discriminative responses. Our findings suggested that nefiracetam inhibits MAP‐induced discriminative responses, which may be at least partly associated with the changes in intracellular cAMP levels.
Study of Association between α‐Synuclein Gene Polymorphism and Methamphetamine Psychosis/Dependence
Authors: KOBAYASHI HIDEAKI , IDE SOICHIRO , HASEGAWA JUNKO , UJIKE HIROSHI , SEKINE YOSHIMOTO , OZAKI NORIO , INADA TOSHIYA , HARANO MUTSUO , KOMIYAMA TOKUTARO , YAMADA MITSUHIKO , IYO MASAOMI , SHEN HAO‐WEI , IKEDA KAZUTAKA , SORAA ICHIRO
Published: November 2004

Abstract: Methamphetamine (MAP) dissipates proton gradients across the membranes of synaptic vesicles, enhances cytoplasmic dopamine (DA) concentrations, and causes calcium‐independent, nonvesicular DA release into synapses. MAP is taken into the cytosol by the dopamine transporter (DAT) on the synaptic terminals of DA neurons, and endogenous DA is concurrently released through the transporter by carrier exchange mechanisms, resulting in a robust increase in DA concentration in the synaptic clefts. The enhanced DA release through DAT by MAP is the main mechanism for the reinforcing effects of MAP. The complexes of α‐synuclein and DAT facilitate membrane clustering of the DAT, thereby accelerating DA uptake in vitro. α‐Synuclein has been shown to be overexpressed in the midbrain DA neurons of chronic cocaine abusers. The present study was performed to study the association between the α‐synuclein gene polymorphisms and MAP psychosis/dependence in Japanese population. Since the T10A7 polymorphic site at the 5′ end of the noncoding exon 1′ in the α‐synuclein gene is highly polymorphic, we analyzed the noncoding exon 1′ and intron 1, including this polymorphic site by sequencing. We confirmed four single nucleotide polymorphisms (SNPs) within 1.38 kbp of the T10A7 polymorphic site. No significant difference was found in genotype or allele frequencies in the T10A7 polymorphic site between MAP psychotic/dependent and control subjects. We found significant association between three SNPs in the vicinity of this polymorphic site in intron 1 and MAP psychosis/dependence in female subjects, but not in males. These results suggest an association of the α‐synuclein gene polymorphisms with MAP psychosis/dependence in our female subjects. Further analyses are necessary to clarify the gender difference, by using a larger sample size and/or different ethnic groups, as well as functional variations in the α‐synuclein gene.
Cocaine Downregulates the Expression of the Mitochondrial Genome in Rat Brain
Authors: DIETRICH JEAN‐BERNARD , POIRIER RAPHAËL , AUNIS DOMINIQUE , ZWILLER JEAN
Published: November 2004

Abstract: Analysis by differential display of genes induced in response to acute cocaine administration to rats revealed the significant downregulation of several mitochondrial genes in the cingulate cortex, including the subunits 1, 2, 4, 5, and 6 of NADH dehydrogenase and the subunit 2 of cytochrome c oxidase. Although the mechanism of the downregulation of expression of these mitochondrial genes by cocaine is presently not well understood, one can envisage that it involves an increased production of reactive oxygen species in cells of the cerebral cortex.
CART Peptides: Modulators of Mesolimbic Dopamine, Feeding, and Stress
Authors: DOMINGUEZ GERALDINA , VICENTIC ALEXANDRA , DEL GIUDICE EMANUELE MIRAGLIA , JAWORSKI JASON , HUNTER RICHARD G. , KUHAR MICHAEL J.
Published: November 2004

Abstract: CART peptides have been shown to be peptide neurotransmitters and endocrine factors in a series of cumulative studies over the past eight years or so. This brief review touches on three aspects of CART: CART as a mediator or modulator of mesolimbic dopamine, CART's regulation by glucocorticoids, and CART as a regulator of feeding, satiety, and body weight. There have been several recent reviews and publications on various aspects of CART peptides. These aspects include the sequence and numbering of the peptides, and their structure, processing, and roles in various physiologic processes.
Possible Pharmacotherapy of the Opioid κ Receptor Agonist for Drug Dependence
Authors: HASEBE KO , KAWAI KOJI , SUZUKI TOMOHIKO , KAWAMURA KUNIAKI , TANAKA TOSHIAKI , NARITA MINORU , NAGASE HIROSHI , SUZUKI TSUTOMU
Published: November 2004

Abstract: Because there are few efficacious medications for drug dependence, many clinical trials are being conducted in earnest to find such medications. Considerable evidence has shown that opioid κ receptor agonists attenuate several behavioral responses induced by drugs of abuse. Although this raises the possibility that opioid κ receptor agonists may be useful for the treatment of drug dependence on drugs of abuse, it has been previously reported that treatment with selective opioid κ receptor agonists causes a psychotomimetic effect and dysphoria both in clinical studies and experimental animal models. As a result, we found the novel opioid κ receptor agonist TRK‐820, another chemical class of opioid κ receptor agonist that has a morphinan scaffold unlike prototypical opioid κ receptor agonists, by application of a modified message‐address concept. TRK‐820 showed high selectivity for an opioid κ receptor, and strong agonistic activity in both in vitro and in vivo experiments. Like other opioid κ receptor agonists, TRK‐820 could markedly suppress the rewarding effects induced by morphine and cocaine and the discriminative stimulus effect of cocaine. Furthermore, TRK‐820 attenuated the mecamylamine‐precipitated nicotine‐withdrawal aversion in a conditioned place preference paradigm. It is worthwhile to note that unlike prototypical opioid κ receptor agonists, TRK‐820 failed to produce a significant place aversion in rodents at doses that were sufficient to produce significant antinociception. Taken together, these findings indicate that TRK‐820 may be useful for the treatment of drug dependence without any aversive effects.
Recent Trends of Drug Abuse in Japan
Authors: YAMAMOTO J
Published: November 2004

Abstract: Methamphetamine has been a continuous cause for concern for many years in Japan. Japan experienced the pandemics of methamphetamine abuse twice after World War II and is now facing the third pandemic. New data indicate that the abuse of drugs such as MDMA (ecstasy) and cannabis is rising at an alarming pace. An epidemiologic survey conducted by the National Research Institute reveals that drug abuse in Japan is still very low compared to that in other countries and regions; however, the current situation seems to be changing for the worse. Two major factors accelerate access to illicit drugs among young people. One is the presence of illicit drug‐dealing groups, which indiscriminately offer drugs. The other is new technology such as the Internet and mobile phones. Strict law enforcement and intensive public awareness and prevention activities are indispensable in protecting young people from drug abuse.
Influence of Genetic Variations of Ethanol‐Metabolizing Enzymes on Phenotypes of Alcohol‐Related Disorders
Authors: HIGUCHI SUSUMU , MATSUSHITA SACHIO , MASAKI TOSHIHIRO , YOKOYAMA AKIRA , KIMURA MITSURU , SUZUKI GO , MOCHIZUKI HITOSHI
Published: November 2004

Abstract: Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase‐2 (ALDH2) play central roles in the metabolism of ethanol and its metabolite, acetaldehyde, in the liver. In ADH2, one nucleotide replacement causes either a super‐active beta 2 subunit encoded by the ADH2*2 allele or a less active beta 1 subunit (ADH2*1 allele). In the same way, a G/A replacement at codon 487 of the ALDH2 gene produces an inactive form of the enzyme. Because the geno‐types of these genes may explain individual differences in concentration and elimination of ethanol and acetaldehyde in the blood after drinking, they could be used as models to elucidate the contribution of these substances to the development of addiction and various types of organ damage. We have examined the influence of genetic variations of these enzymes on alcohol‐related disorders in the Japanese. The results revealed that (1) the less active allele of the ADH2 gene (ADH2*1) is associated with an increased risk for alcohol dependence, alcohol‐induced persistent amnestic disorder, alcohol withdrawal syndrome, and cancer of the upper GI tract; (2) the inactive allele of the ALDH2 gene (ALDH2*2) is associated with a decreased risk for alcohol dependence, and an increased risk for alcoholic polyneuropathy and cancer in the same region; and (3) these genetic variations modify clinical features of alcohol dependence. Possible mechanisms of altered risk for these disorders are discussed.
α7‐Type Nicotinic Acetylcholine Receptor and Prodynorphin mRNA Expression after Administration of (−)‐Nicotine and U‐50,488H in β‐Amyloid Peptide (25‐35)‐Treated Mice
Authors: HIRAMATSU M , WATANABE M , BABA S , KOJIMA R , NABESHIMA T
Published: November 2004

Abstract: We previously reported that (−)‐nicotine and κ‐opioid receptor agonists lessened impairment of learning and/or memory in several animal models. Furthermore, these drugs prevented neurodegenerative damage induced by ischemia or β‐amyloid peptide (25‐35). In the present study, we tested whether (−)‐nicotine and U‐50,488H prevent delayed‐memory impairment induced by β‐amyloid peptide (25‐35), and changes of expression of α7‐type nicotinic acetylcholine receptor mRNA and prodynorphin mRNA. Seven days after treatment with β‐amyloid peptide (25‐35) (9 nmol/mouse, i.c.v.), memory impairment was observed in the Y‐maze test. Memory impairment was prevented when (−)‐nicotine (6.16 μmol/kg, s.c.) or U‐50,488H (21 μmol/kg, s.c.) was administered 1 h before, but not 1 h after, β‐amyloid peptide (25‐35) treatment. There was no change in prodynorphin mRNA or α7‐type nicotinic acetylcholine receptor mRNA expression in the hippocampus 10 days after β‐amyloid peptide (25‐35) treatment alone. Of interest, mRNA expression of not only prodynorphin, but also the α7‐type nicotinic acetylcholine receptor, was significantly decreased when U‐50,488H was administered 1 h before, but not 1 h after, treatment with β‐amyloid peptide (25‐35). However, these changes were not observed after the administration of (−)‐nicotine. These results suggest that activation of the κ‐opioid system, but not β7‐type nicotinic receptors has a neuroprotective effect on β‐amyloid peptide (25‐35)‐induced memory impairment, and may be involved in the long‐lasting changes in the expression of these mRNAs.
Effects of Neonatal Exposure to Methamphetamine: Catecholamine Levels in Brain Areas of the Developing Rat
Authors: GOMES‐DA‐SILVA JOANA , de MIGUEL ROSARIO , FERNÁNDEZ‐RUIZ JAVIER , SUMMAVIELLE TERESA , TAVARES M AMÉLIA
Published: November 2004

Abstract: Neonatal exposure to moderate doses of methamphetamine during the first month of life in the rat affects tyrosine hydroxylase gene expression in the substantia nigra and nigrostriatal tyrosine hydroxylase activity. The main goal of this work was to evaluate the ontogeny of the neurochemical effects of repeated exposure to moderate doses of methamphetamine during the first month of life in the rat. Norepinephrine, dopamine, and dihydroxyphenylacetic acid levels were measured in target areas of methamphetamine: the substantia nigra, ventral tegmental area, caudate‐putamen, nucleus accumbens, and medial prefrontal cortex. On postnatal day 1 (PND1), Wistar rat litters, culled to eight pups, sex balanced, were randomly attributed to either methamphetamine or control groups. Methamphetamine groups were administered 10 mg of (±)‐methamphetamine/kg body weight/day, subcutaneously, from PND1 until the day prior to sacrifice; control groups received isovolumetric saline. Groups were sacrificed on PND7, PND14, and PND30. Neonatal methamphetamine exposure increased norepinephrine levels in the substantia nigra of PND30 rats; on PND14, this variation was evident only in male pups. In the substantia nigra, the dihydroxyphenylacetic/dopamine ratio was also affected in PND30 males. In the ventral tegmental area, catecholamine levels were not affected by methamphetamine. Norepinephrine levels were also increased in the caudate‐putamen of PND7 male and PND14 female methamphetamine‐exposed pups and in the nucleus accumbens of PND14 female and PND30 male and female pups. Catecholamine levels in the medial prefrontal cortex were not affected by neonatal methamphetamine administration.
Risk-Adapted, Combined-Modality Therapy With VAMP/COP and Response-Based, Involved-Field Radiation for Unfavorable Pediatric Hodgkin's Disease
Authors: Hudson Melissa M. , Krasin Matthew , Link Michael P. , Donaldson Sarah S. , Billups Catherine , Merchant Thomas E. , Kun Larry , Billet Amy L. , Kaste Sue , Tarbell Nancy J. , Howard Scott , Friedmann Alison M. , Hurwitz Craig A. , Young Jeffrey A. , Marcus Karen C. , Rai Shesh , Cowan Traci , Weinstein Howard J.
Published: November 2004

Purpose

To evaluate the efficacy of vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) and cyclophosphamide, vincristine, and procarbazine (COP) chemotherapy and response-based, involved-field radiation, a combined-modality regimen that limits doses of alkylating agents, anthracyclines, and radiation, in children with advanced and unfavorable Hodgkin's disease.

Patients and Methods

From 1993 to 2000, 159 children and adolescents with unfavorable Hodgkin's disease received three alternating cycles (total of six cycles) of VAMP/COP chemotherapy followed by response-based, involved-field radiation therapy: 15 Gy was administered to patients achieving a complete response, and 25.5 Gy was administered to those achieving a partial response after the first two cycles of chemotherapy and to all sites of bulky lymphadenopathy. Unfavorable disease was defined as clinical stage I and II with bulky peripheral nodal disease greater than 6 cm, initial bulky mediastinal mass 33% or more of the intrathoracic diameter, and/or “B” symptoms and all stage III and IV.

Results

Study enrollment was closed after an interim analysis estimated a 5-year event-free survival (EFS) rate below a predefined level. Disease presentation was localized (stage I/II) in 77 patients (48.4%) and advanced (stage III/IV) in 82 patients (51.6%). At a median follow-up of 5.8 years (range, 1.3 to 10.0 years), 38 patients had events, including relapse/progression (n = 35), second malignancy (n = 2), and accidental death (n = 1); nine relapses (25.7%) occurred greater than 4 years from diagnosis. Five-year survival and EFS estimates are 92.7% ± 2.5% and 75.6% ± 4.1%, respectively.

Conclusion

Risk-adapted combined-modality therapy with VAMP/COP and response-based, involved-field radiation therapy results in an unsatisfactory outcome for pediatric patients with unfavorable presentations of Hodgkin's disease.
DNA Methylation and Cancer
Authors: Das Partha M. , Singal Rakesh
Published: November 2004

DNA methylation is an important regulator of gene transcription, and its role in carcinogenesis has been a topic of considerable interest in the last few years. Alterations in DNA methylation are common in a variety of tumors as well as in development. Of all epigenetic modifications, hypermethylation, which represses transcription of the promoter regions of tumor suppressor genes leading to gene silencing, has been most extensively studied. However, global hypomethylation has also been recognized as a cause of oncogenesis. New information concerning the mechanism of methylation and its control has led to the discovery of many regulatory proteins and enzymes. The contribution of dietary folate and methylene terahydrofolate reductase polymorphisms to methylation patterns in normal and cancer tissues is under intense investigation. As methylation occurs early and can be detected in body fluids, it may be of potential use in early detection of tumors and for determining the prognosis. Because DNA methylation is reversible, drugs like 5′-azacytidine, decitabine, and histone deacetylase inhibitors are being used to treat a variety of tumors. Novel demethylating agents such as antisense DNA methyl transferase and small interference RNA are being developed, making the field of DNA methylation wider and more exciting.
The Zinc Finger-Containing Transcription Factor Gata-4 Is Expressed in the Developing Endocrine Pancreas and Activates Glucagon Gene Expression
Authors: Ritz-Laser Beate , Mamin Aline , Brun Thierry , Avril Isabelle , Schwitzgebel Valérie M. , Philippe Jacques
Published: November 2004

Gene inactivation studies have shown that members of the Gata family of transcription factors are critical for endoderm development throughout evolution. We show here that Gata-4 and/or Gata-6 are not only expressed in the adult exocrine pancreas but also in glucagonoma and insulinoma cell lines, whereas Gata-5 is restricted to the exocrine pancreas. During pancreas development, Gata-4 is expressed already at embryonic d 10.5 and colocalizes with early glucagon+ cells at embryonic d 12.5. Gata-4 was able to transactivate the glucagon gene both in heterologous BHK-21 (nonislet Syrian baby hamster kidney) and in glucagon-producing InR1G9 cells. Using gel-mobility shift assays, we identified a complex formed with nuclear extracts from InR1G9 cells on the G5 control element (−140 to −169) of the glucagon gene promoter as Gata-4. Mutation of the GATA binding site on G5 abrogated the transcriptional activation mediated by Gata-4 and reduced basal glucagon gene promoter activity in glucagon-producing cells by 55%. Furthermore, Gata-4 acted more than additively with Forkhead box A (hepatic nuclear factor-3) to trans-activate the glucagon gene promoter. We conclude that, besides its role in endoderm differentiation, Gata-4 might be implicated in the regulation of glucagon gene expression in the fetal pancreas and that Gata activity itself may be modulated by interactions with different cofactors.
Quantitative Analysis of Circulating Plasma DNA as a Tumor Marker in Thoracic Malignancies
Authors: Herrera Luis J , Raja Siva , Gooding William E , El-Hefnawy Talal , Kelly Lori , Luketich James D , Godfrey Tony E
Published: November 2004

Background: Increased plasma DNA has been found in cancer patients and may have potential as a tumor marker. The objectives of this study were to develop a controlled, quantitative PCR (QPCR) assay to measure plasma DNA and then evaluate plasma DNA concentrations as a tumor marker in patients with thoracic malignancies.

Methods: We developed a QPCR assay for DNA, using the human β-actin gene. Plasma samples were analyzed from 58 patients with esophageal cancer (EC; 20 banked samples and 38 prospectively collected samples) and 25 patients with lung cancer (LC; all prospectively collected). Control groups consisting of 51 patients with gastroesophageal reflux disease (GERD; 23 banked samples and 28 prospectively collected) and 11 healthy volunteers were also analyzed.

Results: The assay had an experimental variability <4%. In our banked samples, the mean concentration of plasma DNA in EC was 819.0 μg/L (range, 46.2–4738.0 μg/L) vs 432.0 μg/L (6.0–2888.0 μg/L) in GERD (P = 0.02). However, the prospectively collected samples had lower DNA concentrations, and there was no difference between cancer patients and controls. The mean DNA concentration was 10.6 μg/L (range, 7.0–14.0 μg/L) in healthy volunteers and 10.5 μg/L (range, 4.0–23.5 μg/L) in GERD controls vs 13.0 μg/L (range, 4.5–46.5 μg/L) in EC and 14.6 μg/L (range, 3.0–30.0 μg/L) in LC.

Conclusions: Our data indicate that plasma DNA concentrations are of limited diagnostic value when samples are prospectively collected and uniformly handled. This is in contrast to previously published results. Qualitative analysis of DNA may be needed if plasma nucleic acids are to be used as a diagnostic tool in cancer screening.
Behavioural coherence in violent group activity: An interpersonal model of sexually violent gang behaviour
Authors: Porter Louise E. , Alison Laurence J.
Published: November 2004

This study provides an analysis of offender‐victim interactions in 223 cases of sexual violence committed in gangs. Cases were derived from archival sources such as law reports. A multivariate analysis revealed four interpersonal themes (dominance, submission, co‐operation, and hostility) previously identified in studies of lone sexual assault [Alison and Stein, Vicious Circles: Accounts of stranger sexual assault reflect abusive variants of conventional interactions. J Forensic Psychiatry 12:515–538, 2001]. These themes have also been identified in many other forms of human relating [Wiggins, An informal history of the interpersonal circumplex tradition. J Pers Assess 66:217–233, 1996] and conform to a structure known as the interpersonal circumplex. The circumplex has previously been used to conceptualise the relationships between individuals in terms of dynamic interactions that are mutually influencing. Thus, dominance elicits submission and submission elicits dominance. Each interpersonal style could be further subdivided according to the use of either verbally or physically abusive strategies. Point‐Biserial correlations with other aspects of the offence (e.g., mobility of the group, post‐offence treatment of the victim) provided additional support for these conceptually different themes and demonstrated that gang rape represents a distorted and violent form of interpersonal relating. Further, this dynamic interaction emerges not just at an individual level, but at a group level, suggesting that the thematic concepts underpinning the interpersonal circumplex can be extended to group activity and sexually aggressive behaviour. Aggr. Behav. 30:449–468, 2004. © 2004 Wiley‐Liss, Inc.
Going Deep Learning from Campuses that are Responsibility for Student Success
Authors: Kinzie Jillian , Kuh George D.
Published: November 2004

Nearly two years of intensive research into the daily work of twenty institutions may finally put to rest any doubt that building cross-campus collaborations to facilitate student success is essential.
What the Building Boom Says about Campus Values
Authors: Bonfiglio Robert A.
Published: November 2004

Critics claim that well-appointed residence halls and fully loaded recreation centers are sending the wrong message to students about what college is for. The author argues that welcoming communal spaces are an important educational tradition.
Adaptive output feedback actuator failure compensation for a class of non‐linear systems
Authors: Tang Xidong , Tao Gang , Joshi Suresh M.
Published: November 2004

An adaptive compensation control scheme using output feedback is designed and analysed for a class of non‐linear systems with state‐dependent non‐linearities in the presence of unknown actuator failures. For a linearly parameterized model of actuator failures with unknown failure values, time instants and pattern, a robust backstepping‐based adaptive non‐linear controller is employed to handle the system failure, parameter and dynamics uncertainties. Robust adaptive parameter update laws are derived to ensure closed‐loop signal boundedness and small tracking errors, in general, and asymptotic regulation, in particular. An application to controlling the angle of attack of a non‐linear hypersonic aircraft dynamic model in the presence of elevator segment failures is studied and simulation results show that the developed adaptive control scheme has desired actuator failure compensation performance. Copyright © 2004 John Wiley & Sons, Ltd.
Rejection of periodic disturbances of unknown and time‐varying frequency
Authors: Bodson Marc
Published: November 2004

The paper reviews available methods for the rejection of periodic disturbances. Such disturbances are often encountered in active noise and vibration control, due to rotating machinery. The emphasis of the paper is on feedback control problems where reference sensors are not available. The case where the frequency of the disturbance is known is considered first. Two sets of algorithms are discussed: one based on the internal model principle of feedback control theory, and the second based on adaptive feedforward cancellation. An interesting observation is that algorithms originating from both approaches can be shown to be equivalent under certain conditions. When the frequency of the disturbance is unknown, an intuitive approach consists in combining a method for the rejection of disturbances of known frequency with a frequency estimator. Alternatively, one may seek to develop a stable adaptation mechanism so that the disturbance is cancelled asymptotically. While algorithms can be designed to adapt to plant and disturbance parameters, the most successful approaches use some limited plant information to adapt the magnitude, frequency, and phase parameters of the control signal. Applications are discussed throughout the paper. Copyright © 2004 John Wiley & Sons, Ltd.
Ultra Fine Microstructure in WC‐Co Cermet
Authors: Lay S. , Loubradou M. , Donnadieu P.
Published: November 2004

Grain growth inhibitors like VC are added to WC‐Co cermets to avoid abnormal grain growth during sintering. Though the effect of vanadium is known for a long time, the controlling mechanism remains to understand. Microstructural investigations carried out on industrial samples have permitted to locate precisely the inhibitor after sintering. These results are discussed in connection with WC grain growth mechanism.
Phenotypic and molecular characterization of Bruck syndrome (osteogenesis imperfecta with contractures of the large joints) caused by a recessive mutation in PLOD2
Authors: Ha‐Vinh Russia , Alanay Yasemin , Bank Ruud A. , Campos‐Xavier Ana Belinda , Zankl Andreas , Superti‐Furga Andrea , Bonafé Luisa
Published: November 2004

Bruck syndrome (BS) is a recessively‐inherited phenotypic disorder featuring the unusual combination of skeletal changes resembling osteogenesis imperfecta (OI) with congenital contractures of the large joints. Clinical heterogeneity is apparent in cases reported thus far. While the genes coding for collagen 1 chains are unaffected in BS, there is biochemical evidence for a defect in the hydroxylation of lysine residues in collagen 1 telopeptides. One BS locus has been mapped at 17p12, but more recently, two mutations in the lysyl hydroxylase 2 gene (PLOD2, 3q23‐q24) have been identified in BS, showing genetic heterogeneity. The proportion of BS cases linked to 17p22 (BS type 1) or caused by mutations in PLOD2 (BS type 2) is still uncertain, and phenotypic correlations are lacking. We report on a boy who had congenital contractures with pterygia at birth and severe OI‐like osteopenia and multiple fractures. His urine contained high amounts of hydroxyproline but low amounts of collagen crosslinks degradation products; and he was shown to be homozygous for a novel mutation leading to an Arg598His substitution in PLOD2. The mutation is adjacent to the two mutations previously reported (Gly601Val and Thr608Ile), suggesting a functionally important hotspot in PLOD2. The combination of pterygia with bone fragility, as illustrated by this case, is difficult to explain; it suggests that telopeptide lysyl hydroxylation must be involved in prenatal joint formation and morphogenesis. Collagen degradation products in urine and mutation analysis of PLOD2 may be used to diagnose BS and differentiate it from OI. © 2004 Wiley‐Liss, Inc.
Reevaluating confined placental mosaicism
Authors: Stetten Gail , Escallon Cathleen S. , South Sarah T. , McMichael Joseph L. , Saul Daniel O. , Blakemore Karin J.
Published: November 2004

Chromosomal mosaicism was found in 38 of 4,000 chorionic villus samples examined from 1998 to 2003. A small fraction of these (5/38) were confirmed as true mosaics by analysis of amniotic fluid. Twenty‐nine cases that fit the definition of confined placental mosaicism were followed with clinical and cytogenetic analysis throughout the pregnancy, at birth and in a few cases into infancy. This was done to determine the prognostic interpretation of prenatal cytogenetic results from multiple specimens in a single pregnancy and thus allow for reevaluation of the genetic counseling. In 2 of these 29 cases, low‐level mosaicism was found in the neonate, and in 1 of these the chromosome abnormality is probably the cause of the resulting minor phenotypic abnormalities. Families face unique difficulties when confined placental mosaicism is the prenatal diagnosis, and it is extremely important that the counseling they receive takes into consideration the unlikely possibility of the placental abnormality appearing in fetal tissues. © 2004 Wiley‐Liss, Inc.
Pronounced short stature in a girl with tricho‐rhino‐phalangeal syndrome II (TRPS II, Langer–Giedion syndrome) and growth hormone deficiency
Authors: Riedl S. , Giedion A. , Schweitzer K. , Müllner‐Eidenböck A. , Grill F. , Frisch H. , Lüdecke H.‐J.
Published: November 2004

We report on a 10‐year‐old girl with tricho‐rhino‐phalangeal syndrome type II (TRPS II) and pronounced short stature (−4.8 SD). The patient has an interstitial chromosome 8q24.1 deletion of 12–15 Mb. The deletion spans all genes from CSMD3 to at least ANXA13 including the TRPS1 and EXT1 genes, which are responsible for the TRPS II phenotype. In addition to the features of TRPS II, the patient had growth hormone (GH) deficiency with diminished response in three stimulation tests. Therapy with 0.2 mg GH/kg/week led to an increase of growth velocity from 2.5 to 6.6 cm/year. To our knowledge, such a combination of TRPS II and GH deficiency has not yet been described. © 2004 Wiley‐Liss, Inc.
Symptomatic Chiari I malformation in Kabuki syndrome
Authors: Ciprero Karen L. , Clayton‐Smith Jill , Donnai Dian , Zimmerman Robert A. , Zackai Elaine H. , Ming Jeffrey E.
Published: November 2004

Kabuki (Niikawa–Kuroki) syndrome is associated with a characteristic facial appearance, cleft palate, congenital heart defects, and developmental delay. Structural brain anomalies have only occasionally been described in Kabuki syndrome. Chiari type I malformation, characterized by caudal herniation of the cerebellar tonsils through the foramen magnum, has been described only infrequently in association with defined syndromes and has been reported once in association with Kabuki syndrome. We report three additional children with Kabuki syndrome who have Chiari I malformation. Two children presented with chronic headaches and the third patient presented with gait abnormalities in adolescence. The incidence of Chiari I malformation may be higher than previously reported in Kabuki syndrome since it may not be diagnosed until later in childhood, whereas most reports of Kabuki syndrome are of young children. Further, symptoms of Chiari I anomaly can be somewhat nonspecific. Thus, we suggest that Chiari type I be considered in patients with Kabuki syndrome who present with persistent headache, neck pain, or other symptoms suggestive of Chiari I anomaly. © 2004 Wiley‐Liss, Inc.
A novel frameshift mutation of FOXC2 gene in a family with hereditary lymphedema‐distichiasis syndrome associated with renal disease and diabetes mellitus
Authors: Yildirim‐Toruner Cagri , Subramanian Kavitha , El Manjra Lamya , Chen Emily , Goldstein Stanley , Vitale Emilia
Published: November 2004

Lymphedema‐distichiasis (LD) syndrome is a clinically variable autosomal dominant disorder. The disorder is caused by mutations in the forkhead transcription factor FOXC2 gene on chromosome band 16q24.3. Here, we report the sequence of the FOXC2 gene in a German–Irish family with LD in six affected relatives over three generations and identify a single adenine base pair insertion at nt 1006⁁1007. This insertion creates a frameshift mutation that predicts a premature stop at codon 462. In addition to LD, four of the affected family members have renal disease and three have diabetes mellitus (DM), not usually seen in the LD syndrome. Polymorphisms of FOXC2 in diabetics have been studied in different populations. Our sequence analysis of the 5′ untranslated region (UTR) C‐512T shows the homozygous T allele in all family members tested. The sequencing data in this family suggests the possibility of a novel phenotype–haplotype. This novel phenotype, LD/renal disease/type 2 diabetes, might be the result of a combination of the nt 1006⁁1007 insA and the upstream UTR homozygous T polymorphism. © 2004 Wiley‐Liss, Inc.
Deficit of in vivo mitochondrial ATP production in OPA1‐related dominant optic atrophy
Authors: Lodi Raffaele , Tonon Caterina , Valentino Maria Lucia , Iotti Stefano , Clementi Valeria , Malucelli Emil , Barboni Piero , Longanesi Lora , Schimpf Simone , Wissinger Bernd , Baruzzi Agostino , Barbiroli Bruno , Carelli Valerio
Published: November 2004

Dominant optic atrophy has been associated with mutations in the OPA1 gene, which encodes for a dynamin‐related GTPase, a mitochondrial protein implicated in the formation and maintenance of mitochondrial network and morphology. We used phosphorus magnetic resonance spectroscopy to assess calf muscle oxidative metabolism in six patients from two unrelated families carrying the c.2708‐2711delTTAG deletion in exon 27 of the OPA1 gene. The rate of postexercise phosphocreatine resynthesis, a measure of mitochondrial adenosine triphosphate production rate, was significantly delayed in the patients. Our in vivo results show for the first time to our knowledge a deficit of oxidative phosphorylation in OPA1‐related DOA. Ann Neurol 2004;56:719–723
Defective mitochondrial translation caused by a ribosomal protein (MRPS16) mutation
Authors: Miller Chaya , Saada Ann , Shaul Nava , Shabtai Naama , Ben‐Shalom Efrat , Shaag Avraham , Hershkovitz Eli , Elpeleg Orly
Published: November 2004

The mitochondrial respiratory chain comprises 85 subunits, 13 of which are mitochondrial encoded. The synthesis of these 13 proteins requires many nuclear‐encoded proteins that participate in mitochondrial DNA replication, transcript production, and a distinctive mitochondrial translation apparatus. We report a patient with agenesis of corpus callosum, dysmorphism, and fatal neonatal lactic acidosis with markedly decreased complex I and IV activity in muscle and liver and a generalized mitochondrial translation defect identified in pulse‐label experiments. The defect was associated with marked reduction of the 12S rRNA transcript level likely attributed to a nonsense mutation in the MRPS16 gene. A new group of mitochondrial respiratory chain disorders is proposed, resulting from mutations in nuclear encoded components of the mitochondrial translation apparatus. Ann Neurol 2004;56:734–738
Childhood‐onset restless legs syndrome
Authors: Kotagal Suresh , Silber Michael H.
Published: November 2004

The clinical characteristics of childhood‐onset restless legs syndrome are described. Thirty‐two of 538 subjects (5.9%) examined in our sleep disorders center received diagnoses of restless legs syndrome. They were classified based on published criteria into probable (n = 9/32 or 28%) and definite (n = 23/32 or 78%) categories. Apart from an earlier age of diagnosis of the probable group, no differences were found between the two categories. Sleep onset or sleep maintenance insomnia was the most common symptoms, being present in 28 of 32 subjects (87.5%). Inattentiveness was seen in 8 of 32 subjects (25%). Serum ferritin levels were measured in 24 of 32 subjects and were below 50μg/L in 20 of 24 subjects (83%). A family history of restless legs syndrome was present in 23 of 32 (72%) subjects, with mothers almost three times more likely to be affected than fathers (p = 0.02). We conclude that iron deficiency and a strong family history are characteristic of childhood‐onset restless legs syndrome. Ann Neurol 2004.
Vitamin E intake and risk of amyotrophic lateral sclerosis
Authors: Ascherio Alberto , Weisskopf Marc G. , O'Reilly Eilis J. , Jacobs Eric J. , McCullough Marjorie L. , Calle Eugenia E. , Cudkowicz Merit , Thun Michael J.
Published: November 2004

Oxidative stress may contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS). We therefore examined prospectively whether individuals who regularly use supplements of the antioxidant vitamins E and C have a lower risk of ALS than nonusers. The study population comprised 957,740 individuals 30 years of age or older participating in the American Cancer Society's Cancer Prevention Study II. Information on vitamin use was collected at time of recruitment in 1982; participants then were followed up for ALS deaths from 1989 through 1998 via linkage with the National Death Index. During the follow‐up, we documented 525 deaths from ALS. Regular use of vitamin E supplements was associated with a lower risk of dying of ALS. The age‐ and smoking‐adjusted relative risk was 0.99 (95% confidence interval [CI], 0.69–1.41) among occasional users, 0.59 (95% CI, 0.36–0.96) in regular users for less than 10 years, and 0.38 (95% CI, 0.16–0.92) in regular users for 10 years or more as compared with nonusers of vitamin E (p for trend = 0.004). In contrast, no significant associations were found for use of vitamin C or multivitamins. These results suggest that vitamin E supplementation could have a role in ALS prevention. Ann Neurol 2004
Performance characteristics of subdenier monofilament polypropylene fiber reinforced mortars
Authors: Pei Meishan , Wang Dujin , Hu Xianbo , Zhao Ying , Xu Yizhuang , Wu Jingguang , Xu Duanfu
Published: November 2004

An experimental investigation on the properties of fresh and hardened mortars reinforced with subdenier monofilament polypropylene fiber (MMPPF) is reported. Fiber effects on properties of mortars were assessed. Properties studied were flow, unit weight, setting time, bleeding ratio, compressive strength, impact resistance, water infiltration, and flexural load‐deflection. The results revealed that the addition of MMPPF had a positive effect on workability of fresh mortars, impact resistance, water impermeability, and flexural toughness, but had no positive effect on compressive strength. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2251–2256, 2004
Morphological and grafting modification of natural cellulose fibers
Authors: Ouajai S. , Hodzic A. , Shanks R. A.
Published: November 2004

Crystal structure and mechanical properties of cellulose fibers were studied to investigate the effect of chemical treatment on the fiber. Pretreatment by acetone extraction, mercerization with 3–20% wt/v sodium hydroxide (NaOH), and acrylonitrile (AN) grafting initiated by azo‐bis‐isobutylonitrile were performed. From Fourier transform infrared spectroscopy and wide‐angle X‐ray diffraction quantitative measurements, the pretreated fibers showed an induced slight decrease of crystallinity index. The structural transformation of the fibers from cellulose I to cellulose II was observed at high NaOH concentration of 10–20% wt/v. The amount of grafting, 1.56, 2.94, 6.04, 8.34, or 10.46%, was dependent upon the initiator concentration and the volume of monomer in the reactor. The AN grafted fibers had no transformation of crystalline structure as observed after mercerization. Only a variation of X‐ray crystallinity index with grafting amount was observed. Moisture regain of pretreated and modified fibers depended on the structure of the fiber and the amount of grafting. The mechanical properties performed by a single fiber test method were strongly influenced by the cellulose structure, lateral index of crystallinity, and fraction of grafting. Scanning electron microscopy was used for analysis of surface morphologies of treated fibers. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2456–2465, 2004
Particle size distribution, mixing behavior, and mechanical properties of carbon black (high‐abrasion furnace)–filled powdered styrene butadiene rubber
Authors: Lin Yaling , Wang Lianshi , Zhang Anqiang , Hu Hongjun , Zhou Yiyu
Published: November 2004

High‐abrasion furnace black (HAF, grade N330)–filled powdered styrene butadiene rubber [P(SBR/HAF)] was prepared and the particle size distribution, mixing behavior in a laboratory mixer, and mechanical properties of P(SBR/HAF) were studied. A carbon black–rubber latex coagulation method was developed for preparing carbon black–filled free‐flowing, noncontact staining SBR powders, with particle diameter less than 0.9 mm, under the following conditions: carbon black content > 40 phr, emulsifier/carbon black ratio > 0.02, and coating resin content > 2.5 phr. Over the experimental range, the mixing torque ταof P(SBR/HAF) was not as sensitive to carbon black content and mixing temperature as that of HAF‐filled bale SBR (SBR/HAF), whereas the temperature build‐up ΔTshowed little dependency on carbon black content. Compared with SBR/HAF, P(SBR/HAF) showed a 20–30% mixing energy reduction with high carbon black content (>30 phr), which confers to powdered SBR good prospects for internal mixing. Carbon black and the rubber matrix formed a macroscopic homogenization in P(SBR/HAF), and the incorporation step is not obvious in the internal mixing processing results in these special mixing behaviors of P(SBR/HAF). A novel mixing model of carbon black–filled powdered rubber, during the mixing process in an internal mixer, was proposed based on the special mixing behaviors. P(SBR/HAF) vulcanizate showed better mechanical properties than those of SBR/HAF, dependent primarily on the absence of free carbon black and a fine dispersion of filler on the rubber matrix attributed to the proper preparation conditions of noncontact staining carbon black–filled powdered SBR. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2494–2508, 2004
Histological structure of antlers in castrated male fallow deer (Dama dama)
Authors: Kierdorf Uwe , Kierdorf Horst , Schultz Michael , Rolf Hans J.
Published: November 2004

Antlers are periodically replaced cranial appendages that, except for the reindeer, are grown only by male deer. The annual antler cycle is controlled by seasonal fluctuations of sex steroid concentrations in the blood, and accordingly castration of male deer causes deviations from normal antler growth. The present study investigated antler histology of castrated fallow bucks (Dama dama). Castration in early spring was followed by casting of the hard antlers carried by the bucks and the growth of a new set of antlers, which remained in velvet permanently. In the following year, numerous bony protuberances developed from the original antler surface. Further growth of these protuberances, which were formed by subperiosteal intramembranous ossification, led to a marked increase in antler diameter in the affected areas. Compared to antlers of intact bucks, the antlers of the castrates showed histological signs of immaturity, suggestive of a reduced bone remodeling and an impairment of the mineralization process. These changes point to the dependence of the above processes on a stimulation by higher levels of sex steroids. Two years after castration, the antlers also developed integumental thickening and showed an initial formation of skin outgrowths. Cystic structures were present in the skin, which were often filled with a presumably sebaceous and/or keratinous material. Formation of intradermal bone or cartilage was not observed in the antlers of the castrated fallow bucks. The histological structure of the skin outgrowths suggested that they were caused by a hypertrophy of the dermal component of the velvet. Due to the localized bone overgrowth, resulting from the periosteal bone apposition onto the original antler surface, skin‐lined infoldings originated, which reached deep into the newly formed bone. Our study revealed no indication of invasive/destructive bone growth in the antlers, i.e., of a penetration of the newly formed bone tissue into the pre‐existing bone. The hypertrophic bone growth in the antlers of the castrates is compared with other forms of periosteally derived hypertrophic bone formation, including osteomas, in the mammalian skeleton. It is discussed whether the skin and bone outgrowths of the antlers of castrated fallow bucks may be classified as benign tumors. © 2004 Wiley‐Liss, Inc.
Skeletal muscle development in normal and double‐muscled cattle
Authors: Martyn Julie K. , Bass John J. , Oldham Jenny M.
Published: November 2004

This study examined the effect of genotype on prenatal muscle development in both normal‐muscled (NM) animals and in double‐muscled (DM) animals harboring a mutation in the gene for myostatin that results in the production of a functionally inactive protein. The following muscle development parameters were analyzed at four gestational ages: muscle weight, fiber type, by both enzyme histochemistry and myosin heavy‐chain (MHC) immunocytochemistry, and average fiber area. The weights of both M. vastus lateralis and M. vastus medialis were greater throughout prenatal development in the DM animals compared to NM. The percentage of type 1 muscle fibers initially declined with gestational age and subsequently increased in both NM and DM. The percentage of type 1 fibers was consistently lower in DM than in NM. A pattern of MHC isoform localization was shown in DM muscle that is indicative of a delay in muscle development relative to NM. Muscle fiber size was differentially regulated in NM and DM, depending on fiber type. Type 1 fibers were smaller in DM than NM in late gestation, while type 2 fibers were smaller throughout gestation. This study suggests that the inactivating myostatin mutation in DM animals may be associated with changes in both skeletal muscle fiber type and fiber size during bovine muscle development. © 2004 Wiley‐Liss, Inc.
Enhanced interpretation of magnetic survey data using artificial neural networks: a case study from Butrint, southern Albania
Authors: Bescoby David J. , Cawley Gavin C. , Chroston P. Neil
Published: November 2004

The classical city of Butrint in southern Albania embodies over three millennia of settlement history. A Roman colony was established sometime after 31 BC, which led to the expansion of the city southwards onto a low‐lying floodplain where settlement continued well into the late antique period.

In this paper we describe the results of a detailed magnetometry survey undertaken to investigate Roman settlement upon the floodplain. The study included the use of multilayer perceptron neural networks to further process the magnetic data and derive estimates of feature burial depths, allowing a three‐dimensional reconstruction of buried subsurface remains to be made. The neural network approach potentially offers several advantages in terms of efficiency and flexibility over more conventional data inversion techniques. The paper demonstrates how this can lead to an enhanced interpretation of magnetic survey data, which when combined with other geoarchaeological data can provide a clearer picture of settlement evolution within the context of landscape change. The value of this processing technique is also evident within the context of cultural resource management strategies, which potentially restrict more intrusive methods of investigation. Copyright © 2004 John Wiley & Sons, Ltd.