bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental and Genetic Influences upon Gender Differences in Methamphetamine‐Induced Nigrostriatal Dopaminergic Neurotoxicity
Authors: DLUZEN DEAN E. , MCDERMOTT JANET L.
Published: November 2004

Abstract: The gonadal steroid hormone estrogen (E) may play an important role in sex differences in methamphetamine (MA)‐induced neurotoxicity of the nigrostriatal dopaminergic (NSDA) system because E can serve as a neuroprotectant in female, but not male, mice. Gonadal steroid hormones also exert important organizational/developmental effects upon the brain at critical developmental periods. In Part 1 we assessed whether organizational (neonatal) or developmental (prepubertal) effects of gonadal steroids would alter gender/E‐dependent neuroprotection of MA‐induced NSDA neurotoxicity. Attempts to feminize male mice by gonadectomy at either the neonatal or prepubertal period failed to enable E to function as a neuroprotectant within the adult male mouse. Attempts to masculinize the female by testosterone administration at the neonatal period did not abolish the capacity for E to function as a neuroprotectant. However, prepubertal gonadectomy of female mice did disrupt E's capacity to serve as a neuroprotectant. These results suggest that genetic sex may prove the primary determinant for the sex differences observed in response to MA‐induced NSDA neurotoxicity. In Part 2 we examined whether gender differences in response to MA‐induced NSDA neurotoxicity would interact with a specific genetic alteration in a neurotrophic factor, brain‐derived neurotrophic factor (BDNF). Female and male mice that were either deficient (+/− BDNF) or overexpressing (DBH:BDNF+) BDNF were treated with MA. Sex differences in MA‐induced NSDA neurotoxicity remained present in +/− BDNF mice and were less severe as compared with their wild‐type controls. A similar result was obtained in mice that overexpress BDNF, with female and mutant mice showing less NSDA neurotoxicity. In both BDNF‐deficient mice and mice that overexpress BDNF, the relative degree of MA‐induced NSDA neurotoxicity was lower in males. Taken together, these results suggest that a selective alteration in BDNF expression offers some neuroprotective potential against MA‐induced NSDA neurotoxicity, and the relative degree of this neuroprotection may interact with the gender of the subject.
Social Isolation Stress Significantly Enhanced the Disruption of Prepulse Inhibition in Mice Repeatedly Treated with Methamphetamine
Authors: DAI HONGMEI , OKUDA HIROTOMO , IWABUCHI KENTARO , SAKURAI EIKO , CHEN ZHONG , KATO MOTOHISA , IINUMA KAZUIE , YANAI KAZUHIKO
Published: November 2004

Abstract: Repeated administration of methamphetamine (METH) causes reverse tolerance or behavioral sensitization in mice. However, the effects of social isolation stress on the METH‐caused reverse tolerance have not been studied until now. The aim of this study was to investigate the effects of social isolation stress on METH‐caused reverse tolerance by examining the prepulse inhibition of startle response (PPI). PPI was tested in socially isolated and grouped mice after repeated METH injections. Locomotor activity and PPI were also examined just after a four‐week isolation rearing period as a control experiment. After completing behavioral experiments, the mice were sacrificed, and the contents of monoamines, including histamine in the brain, were measured. Social isolation stress significantly lowered the locomotion and disrupted PPI. Repeated injections of METH enhanced the effects of social isolation on PPI. The content of dopamine and histamine significantly increased in the cortex, and the turnover rate of dopamine decreased significantly. These findings demonstrate that social isolation stress significantly enhances METH‐induced behavioral sensitization and that the altered histaminergic neuron system might play an important role in METH‐induced behavioral sensitization in addition to dopaminergic and serotoninergic neurotransmission. Our data suggest that social isolation is involved in the development of METH‐induced psychosis, schizophrenia, and other related psychiatric disorders.
Pharmacological Characterization of Nociceptin/Orphanin FQ Receptors, a Novel Opioid Receptor Family, in the Midbrain Periaqueductal Gray
Authors: CHIOU LIH‐CHU , FAN SHU‐HUAI , CHUANG KUANG‐CHIEH , LIAO YEN‐YU , LEE SUN‐ZHI
Published: November 2004

Abstract: A fourth opioid receptor family was cloned and named after its endogenous ligand as nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor. We have characterized several NOP receptor ligands pharmacologically at native NOP receptors of ventrolateral periaqueductal gray (vlPAG) neurons by investigating their interactions with N/OFQ in activating G protein‐coupled inwardly rectifying K+ (GIRK) channels. They are listed here: (1) [Phe1Ψ(CH2‐NH)Gly2]N/OFQ(1‐13)NH2, which was claimed to be the first selective antagonist of NOP receptors, is a partial agonist of NOP receptors in vlPAG neurons. (2) [Nphe1]N/OFQ(1‐13)NH2 is a pure, selective, and competitive peptide antagonist of NOP receptors (pA2 value = 6.6). (3) CompB (J‐113397) is a potent and selective nonpeptide antagonist of NOP receptors (pA2 = 8.4). (4) Naloxone benzoylhydrazone is a competitive NOP receptor antagonist but also a noncompetitive μ‐opioid receptor antagonist. (5) Ro 64‐6198, though being developed as a potent nonpeptide NOP receptor agonist, affected only part of vlPAG neurons and acted as a weak NOP receptor agonist. In Ro 64‐6198‐unresponsive neurons, N/OFQ activated GIRK channels through NOP receptors. (6) Nocistatin, a functional antagonist of N/OFQ in the spinal cord, did not affect the effect of N/OFQ in most of the recorded neurons. Our functional studies of NOP receptor ligands at native brain NOP receptors reveal that some of them act differently from those at expressed receptors of cell cultures.
A Single Exposure to Morphine Induces Long‐Lasting Hyporeactivity of Rat Caudate Putamen Dopaminergic Nerve Terminals
Authors: PEREIRA FREDERICO C. , SANTOS SANDRA D. , RIBEIRO CARLOS F. , ALI SYED F. , MACEDO TICE R.
Published: November 2004

Abstract: The long‐lasting effects of exposure to drugs of abuse on the brain is a central theme in drug addiction research. This study was designed to evaluate whether enduring neurochemical adaptations within caudate putamen can be evoked by a single injection of a high dose of morphine. Rats were pretreated once with 10 mg/kg morphine. Seven days later the effect of another injection of 10 mg/kg morphine on total levels of dopamine (DA), 3,4‐dihydroxyphenylacetic acid (DOPAC), and homovanilic acid (HVA) in caudate putamen was assessed in half the pretreated animals. An irreversible μ‐opioid receptor antagonist, cloccinamox (C‐CAM; 0.1 mg/kg), significantly antagonized the elevation of the HVA/DA ratio, but not the elevation of the DOPAC/DA ratio induced by morphine in the caudate putamen from drug‐naive animals. Pretreatment with morphine blunted changes in the HVA/DA ratio induced by another morphine challenge, but it had no effect on the DOPAC/DA ratio within the caudate putamen. Therefore, a single dose of 10 mg/kg morphine hampered nigrostriatal DA release and extraneuronal metabolism, μ‐opioid receptor mediated, on another 10 mg/kg morphine challenge. This confirms that the first exposure to morphine does not go without long‐lasting neurochemical adaptations.
Clinical Features of Nicotine Dependence Compared with Those of Alcohol, Methamphetamine, and Inhalant Dependence
Authors: MIYATA HISATSUGU , KONO JUNKO , USHIJIMA SADANOBU , YANAGITA TOMOJI , MIYASATO KATSUMASA , FUKUI KENJI
Published: November 2004

Abstract: A new clinical evaluation form was developed to compare the clinical features of nicotine dependence with those associated with other abused drugs. A new scoring system for clinical evaluation was developed. The form consisted of five scoring items: subjective effects, liking (of drug), withdrawal syndrome, acute psychic and physical disorders, and social disturbance. A preliminary clinical investigation was performed to test the validity of the evaluation form. Study subjects were those showing dependence on nicotine (cigarette smoking, n= 40), alcohol (n= 39), methamphetamine (n= 31), and inhalants (n= 30), who fulfilled the DSM‐IV‐TR criteria for drug dependence disregarding the state of “a maladaptive pattern of substance use, leading to clinically significant impairment or distress,” and gave written informed consent for participation in the study. Nicotine caused a mild or the least degree of subjective effects, liking, and psychic and physical withdrawal symptoms, without any significant social disturbance or acute disorders. With alcohol, liking, withdrawal syndrome, and acute physical disorders were prominent. Methamphetamine produced the most serious acute psychic disorders, with intensive acute physical disorders and psychic withdrawal symptoms. Inhalants were characterized by an intensive degree of acute psychic disorders. As for social disturbance, alcohol, methamphetamine, and inhalants showed more significant influence than nicotine. Our study findings revealed that the clinical features of drug dependence could be evaluated by using the new clinical evaluation form. Further study is required to clarify the clinical features of nicotine dependence compared with those of other drugs of dependence.
Influence of Nicotine on Brain Reward Systems: Study of Intracranial Self‐Stimulation
Authors: NAKAHARA DAIICHIRO
Published: November 2004

Abstract: We used the rate‐frequency curve‐shift procedure to evaluate the effects of nicotinic blockers, locally infused into the mesopontine tegmentum or ventral tegmentum, on the threshold of brain stimulation reward. Meca‐mylamine, the nicotinic acetylcholine receptor blocker, was infused one hour before the self‐stimulation of the medial forebrain bundle. When injected into the mesopontine tegmentum, mecamylamine shifted rate‐frequency curves to the right. Similar effects were also observed when the drug was injected into the ventral tegmentum. Thus, in both the mesopontine tegmentum and the ventral tegmentum, nicotinic receptors appear to facilitate the rewarding effect of the self‐stimulation.
Nicotine Attenuates Relapse to Methamphetamine‐Seeking Behavior (Craving) in Rats
Authors: HIRANITA TAKATO , ANGGADIREDJA KUSNANDAR , FUJISAKI CHIE , WATANABE SHIGENORI , YAMAMOTO TSUNEYUKI
Published: November 2004

Abstract: This study clarifies the modulating action of the nicotinic cholinergic system on reinstatement of methamphetamine (MAP)‐seeking behavior (craving) using an intravenous, self‐administration paradigm in rats. After self‐administration of MAP for 10 days, replacing MAP with saline solution (MAP withdrawal) gradually decreased lever‐pressing responses. On the sixth day of MAP withdrawal, MAP (1.0 mg/kg, i.p.)‐priming injection significantly increased lever‐pressing responses (reinstatement of MAP‐seeking behavior). This MAP‐seeking behavior was attenuated by repeated nicotine administration for 5 days during MAP withdrawal, and this attenuating effect was antagonized by the nicotinic antagonist mecamylamine. These results suggest that the appearance of MAP‐seeking behavior may be due to inactivation of the nicotinic cholinergic neuron. Furthermore, it is suggested that nicotinic activating agents may be useful in preventing relapse to drug abuse.
The Role of N‐Methyl‐d‐aspartate Receptors in Neurobehavioral Changes Induced by Toluene Exposure during Synaptogenesis
Authors: CHEN HWEI‐HSIEN , LEE YEH‐FU , CHAN MING‐HUAN , LO PI‐SHIH
Published: November 2004

Abstract: Toluene abuse during pregnancy results in newborns with fetal solvent syndrome. N‐Methyl‐d‐aspartate (NMDA) receptor has been identified as a target site for toluene. Since the normal function of NMDA receptor is critical for synaptogenesis, the long‐term effects of toluene exposure during synaptogenesis on the neurobehavioral function and the expression of NMDA receptor subunits (NR1, NR2A, and NR2B) were examined. Rats exposed to l g/kg of toluene (i.p.) over postnatal days 4 to 9 were found to exhibit reduction in body weight, NMDA‐induced seizure thresholds, and MK‐801‐induced hyperlocomotor activity. Furthermore, immunoblotting and immunohistochemical analysis revealed a significant increase in NR2A subunit expression in the hippocampus and cerebellum of toluene‐exposed rats on PN30. These results suggest that the region‐specific changes in the expression of NMDA receptor subunits may play a role in the neurobehavioral dysfunction following toluene exposure during synaptogenesis.
Pharmacological Basis for Management of Drug Dependence
Authors: KATSURA MASASHI , OHKUMA SEITARO
Published: November 2004

Abstract: Neurochemical mechanisms underlying development of drug dependence and withdrawal syndrome remain unclear. Several clinical features of withdrawal syndrome, such as anxiety, are considered to be common among patients with drug dependence induced by different drugs of abuse. In the present study, we investigated whether diazepam‐binding inhibitor (DBI), an endogenous anxiogenic neuropeptide, participates in the anxiety associated with drug dependence and its withdrawal symptoms. When we examined brain from mice dependent on alcohol, nicotine, and morphine, we observed that the levels of DBI protein and its mRNA significantly increased. Abrupt cessation of these drugs facilitated further increases in DBI expression. In the cases of nicotine‐ and morphine‐dependent mice, concomitant administration of specific antagonists for nicotinic acetylcholine and m‐opioid receptors, respectively, abolished the increased expression. Similar patterns of DBI expression were observed in the neurons after sustained exposure to these drugs and its removal from culture medium. Sustained exposure of the neurons to abused drugs significantly increased the KCl (30 mM)‐induced 45Ca2+ influx and enhanced expression of α1 subunits for L‐type high voltage‐gated Ca2+ channels (HVCCs). In addition, the increase in DBI expression was completely blocked by L‐type HVCC inhibitors. Therefore, these alterations in DBI expression, mediated via increased influx of Ca2+ through upregulated L‐type HVCCs, are closely related to drug dependence and/or its withdrawal syndrome and are considered to be part of a common biochemical process in drug dependence induced by different drugs of abuse.
Repeated Exposure to the Abused Inhalant Toluene Alters Levels of Neurotransmitters and Generates Peroxynitrite in Nigrostriatal and Mesolimbic Nuclei in Rat
Authors: RIEGEL A C , ALI S F , TORINESE S , FRENCH E D
Published: November 2004

Abstract: Toluene, a volatile hydrocarbon found in a variety of chemical compounds, is misused and abused by inhalation for its euphorigenic effects. Toluene's reinforcing properties may share a common characteristic with other drugs of abuse, namely, activation of the mesolimbic dopamine system. Prior studies in our laboratory found that acutely inhaled toluene activated midbrain dopamine neurons in the rat. Moreover, single systemic injections of toluene in rats produced a dose‐dependent increase in locomotor activity which was blocked by depletion of nucleus accumbens dopamine or by pretreatment with a D2 dopamine receptor antagonist. Here we examined the effects of seven daily intraperitoneal injections of 600 mg/kg toluene on the content of serotonin and dopamine in the caudate nucleus (CN) and nucleus accumbens (NAC), substantia nigra, and ventral tegmental area at 2, 4, and 24 h after the last injection. Also, the roles of nitric oxide, peroxynitrite, and the production of 3‐nitrosotyrosine (3‐NT), in the CN and NAC were assessed at the same time points. Toluene treatments increased dopamine levels in the CN and NAC, and serotonin levels in CN, NAC, and ventral tegmental area. Measurements of the dopamine metabolite dihydroxyphenylacetic acid (DOPAC) further suggested a change in transmitter utilization in CN and NAC. Lastly, 3‐NT levels also showed a differential change between CN and NAC, but at different time points post‐toluene injection. These results point out the complexity of action of toluene on neurotransmitter function following a course of chronic exposure. Changes in the production of 3‐NT also suggest that toluene‐induced neurotoxicity may mediate via generation of peroxynitrite.
Adjuvant Chemotherapy for Resected Adenocarcinoma of the Esophagus, Gastro-Esophageal Junction, and Cardia: Phase II Trial (E8296) of the Eastern Cooperative Oncology Group
Authors: Armanios Mary , Xu Ronghui , Forastiere Arlene A. , Haller Daniel G. , Kugler John W. , Benson Al B.
Published: November 2004

Purpose

To evaluate the effect of postoperative paclitaxel and cisplatin on 2-year survival in patients with completely resected adenocarcinoma of the distal esophagus, gastro-esophageal (GE) junction, and cardia.

Patients and Methods

We conducted a multicenter phase II trial. Patients had pathologically staged T2 node-positive to T3-4, any node status adenocarcinoma of the distal esophagus, GE junction, or gastric cardia with negative margins (R0). Treatment consisted of four cycles of paclitaxel 175 mg/m2 intravenously (IV) over 3 hours followed by cisplatin 75 mg/m2 IV every 21 days. A positive outcome was considered to be an improvement in 2-year survival rate by ≥ 20% compared to historic controls.

Results

Fifty-nine patients were recruited from 20 centers. Of 55 eligible patients, 49 (89%) had lymph node involvement. Forty-six patients (84%) completed all four cycles. Of the total 59 patients, 31 (56%) developed grade 3 or 4 toxicity with leukopenia/neutropenia, nausea/vomiting, and metabolic toxicities were most common. The median follow-up for surviving patients was 4 years. At 2 years, 33 patients were alive and 22 were dead, with a survival rate of 60% (95% CI, 46% to 73%; one-sided P = .0008 compared with the historic controls).

Conclusion

Our data suggest that adjuvant paclitaxel and cisplatin may improve survival in R0 resected patients with locally advanced adenocarcinoma of the distal esophagus, GE junction, and cardia. These results warrant further testing in randomized trials.
Prevalence of KIT Expression in Human Tumors
Authors: Went Philip Th. , Dirnhofer Stephan , Bundi Marcel , Mirlacher Martina , Schraml Peter , Mangialaio Sara , Dimitrijevic Sasa , Kononen Juha , Lugli Alessandro , Simon Ronald , Sauter Guido
Published: November 2004

Purpose

KIT is a target for imatinib mesylate (Gleevec; Novartis Pharma, Basel, Switzerland). Gastrointestinal stromal tumors (GISTs) express KIT and respond favorably to imatinib therapy. To determine other tumors in which such a molecular targeted therapy might be indicated, we investigated KIT expression in different human tumor types. Because recent studies in GISTs suggest that KIT-activating mutations predict response to imatinib therapy, we also sequenced a subset of positive tumors.

Materials and Methods

More than 3,000 tumors from more than 120 different tumor categories were analyzed by immunohistochemistry in a tissue microarray format. Seven commercially available anti-KIT antibodies were initially evaluated. The antibody A4502 (DAKO) was selected for analysis because of a high frequency of positivity in GIST and low staining background in other tissues. To determine the frequency of KIT mutations in various tumor types, the exons 2, 8, 9, 11, 13, and 17 (where mutations previously were reported) were sequenced in 36 tumors with strong KIT expression.

Results

KIT positivity was detected in 28 of 28 GISTs (100%), 42 of 50 seminomas (84%), 34 of 52 adenoid-cystic carcinomas (65%), 14 of 39 malignant melanomas (35%), and eight of 47 large-cell carcinomas of the lung (17%), as well as in 47 additional tumor types. KIT mutations were found in six of 12 analyzed GISTs, but only in one of 24 other tumors.

Conclusion

The results suggest that KIT expression occurs infrequently in most tumor types and that, with the exception of GISTs, KIT gene mutations are rare in immunohistochemically KIT-positive tumors.
Immunologic and Clinical Outcomes of Vaccination With a Multiepitope Melanoma Peptide Vaccine Plus Low-Dose Interleukin-2 Administered Either Concurrently or on a Delayed Schedule
Authors: Slingluff Craig L. , Petroni Gina R. , Yamshchikov Galina V. , Hibbitts Sarah , Grosh William W. , Chianese-Bullock Kimberly A. , Bissonette Eric A. , Barnd Donna L. , Deacon Donna H. , Patterson James W. , Parekh Jayashree , Neese Patrice Y. , Woodson Elizabeth M.H. , Wiernasz Catherine J. , Merrill Priscilla
Published: November 2004

Purpose

A phase II trial was performed to test whether systemic low-dose interleukin-2 (IL-2) augments T-cell immune responses to a multipeptide melanoma vaccine. Forty patients with resected stage IIB-IV melanoma were randomly assigned to vaccination with four gp100- and tyrosinase-derived peptides restricted by human leukocyte antigen (HLA) -A1, HLA-A2, and HLA-A3, and a tetanus helper peptide plus IL-2 administered daily either beginning day 7 (group 1), or beginning day 28 (group 2).

Patients and Methods

T-cell responses were assessed by an interferon gamma ELIspot assay in peripheral blood lymphocytes (PBL) and in a lymph node draining a vaccination site (sentinel immunized node [SIN]). Patients were followed for disease-free and overall survival.

Results

T-cell responses to the melanoma peptides were observed in 37% of PBL and 38% of SINs in group 1, and in 53% of PBL and 83% of SINs in group 2. The magnitude of T-cell response was higher in group 2. The tyrosinase peptides DAEKSDICTDEY and YMDGTMSQV were more immunogenic than the gp100 peptides YLEPGPVTA and ALLAVGATK. T-cell responses were detected in the SINs more frequently, and with higher magnitude, than responses in the PBL. Disease-free survival estimates at 2 years were 39% (95% CI, 18% to 61%) for group 1, and 50% (95% CI, 28% to 72%) for group 2 (P = .32).

Conclusion

The results of this study support the safety and immunogenicity of a vaccine composed of four peptides derived from gp100 and tyrosinase. The low-dose IL-2 regimen used for group 1 paradoxically diminishes the magnitude and frequency of cytotoxic T lymphocyte responses to these peptides.
Aggressive behavior in children's dolls' house play
Authors: Tallandini Maria A.
Published: November 2004

The present study addressed the question of whether there are gender and age differences in aggressive behavior when it is studied as the spontaneous expression of mental contents and not as the result of immediate social interaction. This study also investigated whether aggression, in terms of mental content, is related to temperamental aspects. Aggressive behaviors were examined in make‐believe play, in relation to age, gender, and temperament in a near‐ecological context, i.e., the Dolls' House Play. The participants, 55 boys and 47 girls, subdivided into three age levels (4 years–4 years and 6 months; 5–6 years; and 7 years and 6 months–8 years and 6 months) were requested to represent what happens in their family 1) during Mealtimes; 2) at Bedtime; 3) on the Saddest day; and 4) the Happiest day; their Dolls' House Play was then recorded. Children's temperaments were measured with the TABC‐Teachers' form [Martin, The Temperament Assessment Battery for Children, Brandon, VT: Clinical Psychology Publishing, 1998]. Data analysis was conducted considering aggressive behaviors in their distinct expressions—physical, verbal, direct, and indirect. Results revealed no statistical differences between boys and girls when all aggressive behaviors were compounded. However, when the distinct types of aggressiveness were considered, boys presented statistically higher levels of physical aggression than girls did. Moreover, boys and girls reacted with different types of aggression in the different emotional contexts created by the four episodes. Few age differences were observed. Surprisingly, there was a significantly greater presence of indirect verbal aggressiveness in younger children. With respect to temperament, a higher level of negative emotivity was significantly linked to a greater degree of aggressive behaviors in some of the episodes. In conclusion, this paper confirms gender differences in the type of aggressive behavior children display even in the absence of any immediate social interaction, which might itself trigger aggression. Aggr. Behav. 30:504–519, 2004. © 2004 Wiley‐Liss, Inc.
Stoichiometry Defect at Grain Boundary Observed by Nano‐Scale TEM Microanalysis in Spinel MgAl2O4
Authors: Nuns N. , Béclin F. , Crampon J.
Published: November 2004

Spinel presents a grain boundary sliding deformation accommodated by diffusion during creep at high temperature. A space charge layer at grain boundary in ionic ceramics can explain the observed interface reaction controlling diffusion at low stress. The purpose of this work is to study the grain boundary region stoichiometry to confirm this theory.
On the Core Localization of Grain Boundary Extrinsic Dislocations in Nickel
Authors: Décamps B. , Priester L. , Thibault J.
Published: November 2004

Grain boundaries (GBs) have a significant influence on mechanical properties of single‐phase materials. During deformation, matrix dislocations interact with GBs that constitute very strong barriers to dislocation glide processes. Some dislocations may enter the GB, giving rise to extrinsic grain‐boundary dislocations (EGBDs) which disturb the ntrinsic GB structure. Stress relaxation associated to EGBDs must occur for the plastic deformation to go on and for the GB to return to equilibrium.
Multifunctional Carbon Nanotube Composite Fibers
Authors: Muñoz E. , Dalton A.B. , Collins S. , Kozlov M. , Razal J. , Coleman J.N. , Kim B.G. , Ebron V.H. , Selvidge M. , Ferraris J.P. , Baughman R.H.
Published: November 2004

Continuous carbon nanotube composite fibers having record energy‐to‐break (toughness) are reported. These fibers have been employed in the fabrication of lightweight fiber supercapacitors, which can be woven or sewn into fabrics and, therefore, be potentially considered as components for electronic textiles. Moreover, these fibers provided remarkable electromechanical actuator capabilities.
Molecular Self‐Assembly and Nanomanipulation – Two Key Technologies in Nanoscience and Templating
Authors: Heckl W.M.
Published: November 2004

If at some time in the future we will want to build objects out of single atoms and molecules so that we can manufacture them with molecule assembly machines then we must think about which techniques need to be mastered in order to move things on the scale of atoms or molecules.
Pair diffusion and kick‐out: Contributions to diffusion of boron in silicon
Authors: Jung M. Y. L. , Gunawan R. , Braatz R. D. , Seebauer E. G.
Published: November 2004

Diffusion of boron in silicon has great technological relevance to microelectronic processing. Despite considerable effort spanning over many years, the dominant mechanism for this diffusion remains strongly debated, together with the values of key activation energies. Some evidence indicates that the principal mobile species is a B‐Si complex (so‐called “pair diffusion”), whereas other evidence points to a lone boron interstitial (“kick‐out”). An attempt to resolve the question is made by formulating a comprehensive kinetic model that incorporates both mechanisms. Rate parameters for the elementary steps are estimated systematically, based on literature reports or physical arguments. In the frequent cases where reports conflict, maximum likelihood estimation is employed to determine the best value, and multivariate statistics to quantify its accuracy. A Monte Carlo technique is used to show that kick‐out very likely dominates pair diffusion in both implanted Si and unimplanted silicon. © 2004 American Institute of Chemical Engineers AIChE J, 50: 3248–3256, 2004
Fatal lymphoproliferative disorder in a child with Schimke immuno‐osseous dysplasia
Authors: Taha Doris , Boerkoel Cornelius F. , Balfe John Williamson , Khalifah Mohammed , Sloan Emily A. , Barbar Maha , Haider Abdulrazzaq , Kanaan Hassan
Published: November 2004

Schimke immuno‐osseous dysplasia (SIOD) is a rare autosomal recessive disorder characterized by spondyloepiphyseal dysplasia, nephrotic syndrome, and cell‐mediated immunodeficiency. Mutations in the SMARCAL1 gene (SW1/SNF2‐related, matrix‐associated, actin‐dependent regulator of chromatin, subfamily a‐like1) cause SIOD. We report a patient with SIOD and SMARCAL1 mutations, who presented with fever of unknown origin secondary to B‐cell lymphoma. To our knowledge, this is the first report of an SIOD patient with a primary lymphoproliferative disorder (LPD). © 2004 Wiley‐Liss, Inc.
Intron 7 retention and exon 9 skipping EAAT2 mRNA variants are not associated with amyotrophic lateral sclerosis
Authors: Flowers Joanna M. , Powell John F. , Leigh P. Nigel , Andersen Peter , Shaw Christopher E.
Published: November 2004

Glutamate‐mediated excitotoxicity is implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). The astroglial glutamate transporter EAAT2 plays a major role in maintaining low levels of extracellular glutamate in the central nervous system. Multiple EAAT2 mRNA transcripts have been described, but those retaining intron 7 or skipping exon 9 are reported to be specific to the motor cortex, spinal cord, and cerebrospinal fluid of ALS patients. We sought to verify these findings using a TaqMan (Elmer Biosystems, Warrington, UK) real‐time reverse transcriptase polymerase chain reaction assay, which provides a sensitive and reliable quantitative measure of EAAT2 transcript copy ratios. We analyzed RNA extracted from frozen postmortem tissue from affected and unaffected central nervous system regions dissected from 17 sporadic ALS patients, 7 Alzheimer's disease patients, and 19 control subjects. We have demonstrated unequivocally that intron 7 retaining and exon 9 skipping variants can be detected in all individuals and in all central nervous system regions studied. The mean ratio of “variant” to “normal” transcripts did not differ significantly between patient and control groups. Although our assay could detect transcript concentrations in cerebrospinal fluid as low as 10 pg/ml, none were detected in 17 ALS and 8 control samples. We conclude that ALS is not associated with elevated levels of EAAT2 transcripts retaining intron 7 and skipping exon 9. An alternative explanation must be sought for the disturbance of glutamate homeostasis reported in ALS.
Cardiac and respiratory failure in limb‐girdle muscular dystrophy 2I
Authors: Poppe Maja , Bourke John , Eagle Michelle , Frosk Patrick , Wrogemann Klaus , Greenberg Cheryl , Muntoni Francesco , Voit Thomas , Straub Volker , Hilton‐Jones David , Shirodaria Cheerag , Bushby Kate
Published: November 2004

Mutations in the gene encoding fukutin‐related protein cause limb‐girdle muscular dystrophy 2I. In this multicenter retrospective analysis of 38 patients, 55.3% had cardiac abnormalities, of which 24% had developed cardiac failure. Heterozygotes for the common C826A mutation developed cardiac involvement earlier than homozygotes. All patients initially improved while receiving standard therapy. Independent of cardiac status, forced vital capacity was below 75% in 44.4% of the patients. There was no absolute correlation between skeletal muscle weakness and cardiomyopathy or respiratory insufficiency. These complications are a primary part of this specific type of limb‐girdle muscular dystrophy, with important implications for management. Ann Neurol 2004;56:738–741
Titelbild: High‐Resolution Soft Lithography: Enabling Materials for Nanotechnologies (Angew. Chem. 43/2004)
Authors: Rolland Jason P. , Hagberg Erik C. , Denison Ginger M. , Carter Kenneth R. , De Simone Joseph M.
Published: November 2004

Ideal geeignet für lithographisches Hochleistungsprägen sind auf Perfluorpolyethern basierende Elastomere. Das Titelbild zeigt Muster im Subnanometerbereich, die mit diesen Materialien repliziert wurden. Gründe des erfolgreichen Einsatzes sind die bemerkenswert niedrige Oberflächenenergie und die große Flexibilität. Es besteht die Hoffnung, dass mit diesen Materialien sogar noch kleinere Muster repliziert werden können. Mehr darüber erfahren Sie in der Zuschrift von J. M. De Simone, K. R. Carter et al. auf S. 5920 ff.
Titelbild: Crystal Structure of Tricolorin A: Molecular Rationale for the Biological Properties of Resin Glycosides Found in Some Mexican Herbal Remedies (Angew. Chem. 44/2004)
Authors: Rencurosi Anna , Mitchell Edward P. , Cioci Gianluca , Pérez Serge , Pereda‐Miranda Rogelio , Imberty Anne
Published: November 2004

In traditionellen mexikanischen Rezepten kommt die himmelblaue Trichterwinde (Ipomea tricolor Cav.) als Deckfrucht vor. Tricolorin A ist eines von mehreren in ihr vorhandenen phytotoxischen Harzglycosiden. R. Pereda‐Miranda, A. Imberty et al. berichten in ihrer Zuschrift auf S. 6044 ff. über seine kristallographisch ermittelte Struktur, die erste eines natürlichen Harzglycosids. Das einen Makrolactonring enthaltende Lipopolysaccharid bildet Kanalstrukturen, die mit seiner biologischen Aktivität in Beziehung gesetzt werden könnten.
Cure characterization of unsaturated polyester resin by fluorescence spectroscopy
Authors: Grunden Bradley L. , Sung Chong Sook Paik
Published: November 2004

A strong fluorescence emission was observed during cure of an unsaturated polyester resin containing about 30% styrene by weight. As the cure proceeded, the emission intensity at 306 nm increased. Model compound studies confirmed that the unsaturated polyester component exhibited negligible fluorescence when excited at 250 nm where styrene has strong absorption. Based on the studies of styrene/polystyrene mixtures, the fluorescence emission at 306 nm was attributed to a reduced inner‐filter effect of styrene monomer. Fluorescence intensity changes following cure at 75°C were correlated to the extent of styrene conversion determined by FT‐IR spectroscopy, demonstrating that the fluorescence measurement is more sensitive to styrene conversion in the later stages of cure than conventional IR measurements. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2446–2450, 2004
Application of hindered piperidine amine and/or tertiary amine in the modification of polyamide 6
Authors: Guo Xitao , Zhao Yaoming , Ning Ping , Ai Xiying
Published: November 2004

PA 6 resin was produced in a hydrolytic‐polymeric process in which ε‐caprolactam was polymerized in the presence of water as initiator, isophthalic acid and benzoic acid as chain regulators, by polymerizing caprolactam in the presence of 7.5% by weight of water, 0.2% by weight of isophthalic acid, 0.1% by weight of benzoic acid, each percentage being based on caprolactam. By adding hindered piperidine amine and/or tertiary amine to the polymeric system, the effects of additives on the polymer were studied. The results showed that: the addition of 0.1 ∼ 0.2% additives can improve the melt stability of polyamide 6; the addition of 0.2% additives can protect mechanical properties of polyamide 6 fibers after exposure to high temperature; and the addition of 0.05 ∼ 0.25% additives can increase the amino end group content of polyamide 6 and thereby increase the dyeability of polyamide fibers. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2489–2493, 2004
Role of alendronate in therapy for posttraumatic complex regional pain syndrome type I of the lower extremity
Authors: Manicourt Daniel‐Henri , Brasseur Jean‐Pierre , Boutsen Yves , Depreseux Geneviève , Devogelaer Jean‐Pierre
Published: November 2004

Objective

To evaluate the effects of the antiresorptive agent alendronate at a daily oral dose of 40 mg in patients with posttraumatic complex regional pain syndrome type I (CRPS I) of the lower extremity.

Methods

Forty patients were enrolled in this 8‐week randomized, double‐blind, placebo‐controlled study of alendronate therapy for CRPS I, a condition associated with regional osteoclastic overactivity. An optional 8‐week open extension of alendronate therapy (weeks 12–20) was available after a 4‐week period without therapy. Clinical assessments included joint mobility, edema of the lower extremity, tolerance to pressure in the lower extremity, and levels of spontaneous pain. Urinary levels of type I collagen N‐telopeptide (NTX) were assessed by enzyme‐linked immunosorbent assay. Patients were examined at weeks 4, 8, 12, 16, 20, and 24. Statistical analysis included two‐way factorial analysis of variance.

Results

In contrast to placebo‐treated patients (n = 20), all of the alendronate‐treated patients (n = 19) exhibited a marked and sustained improvement in levels of spontaneous pain, pressure tolerance, and joint mobility, as well as a significant reduction in urinary levels of NTX at weeks 4 and 8. The improvement was maintained at week 12. Twelve patients from each treatment group volunteered for the 8‐week open trial, and all of them had a positive response to alendronate.

Conclusion

Our findings support the use of oral alendronate in posttraumatic CRPS I. By reducing local acceleration of bone remodeling, alendronate might relieve pain by effects on nociceptive primary afferents in bone, pain‐associated changes in the spinal cord, and possibly also through a central mechanism.
Association between nuclear antigens and endogenous retrovirus in the generation of autoantibody responses in murine lupus
Authors: Tucker Rebecca M. , Roark Christina L. , Santiago‐Raber Marie‐Laure , Izui Shozo , Kotzin Brian L.
Published: November 2004

Objective

(NZB × NZW)F1(NZB/NZW) mice and other strains of mice with experimental lupus frequently produce autoantibodies to both chromatin constituents and murine leukemia virus envelope gp70. These autoantibody responses are involved in the glomerulonephritis that develops in these mice. This study was undertaken to explore possible connections between these 2 antigen systems.

Methods

We used monoclonal antibodies (mAb) derived from unmanipulated NZB/NZW mice to investigate the specificity of anti‐gp70 and antichromatin autoantibodies for chromatin constituents, recombinant gp70, NZB retroviruses, and retrovirally infected cells. NZB mice were also immunized with retroviral particles and followed up for study of autoantibody responses.

Results

Spontaneous autoantibody production in NZB/NZW mice reflects high‐level autoimmune responses to nuclear antigens and gp70 that do not cross‐react with the other antigen. However, both types of autoantibodies have the capability to bind to the endogenous xenotropic virions NZB‐X1 or NZB‐X2. The mAbs to recombinant gp70 cross‐reacted only with the NZB‐X2 virus, whereas the antichromatin mAb frequently bound to both retroviruses. The binding of antichromatin autoantibodies was mediated by nuclear material complexed to the retrovirus, and studies showed that this material can be acquired through the budding process. Immunization with NZB‐X1 or NZB‐X2 virions induced strong responses to gp70 and was much more effective than chromatin at inducing autoantibody responses to chromatin and double‐stranded DNA in NZB mice.

Conclusion

These studies suggest that retroviral virions may harbor nuclear antigens and may link together the autoimmune responses to the disparate antigens, chromatin and gp70.
Identification of new quantitative trait loci in mice with collagen‐induced arthritis
Authors: Bauer Kristin , Yu Xinhua , Wernhoff Patrik , Koczan Dirk , Thiesen Hans‐Juergen , Ibrahim Saleh M.
Published: November 2004

Objective

Collagen‐induced arthritis (CIA) in the mouse is one of the most widely used autoimmune experimental models, with many features similar to rheumatoid arthritis. This study sought to identify potential genetic regulatory mechanisms of CIA in major histocompatibility complex–matched (H2‐q) F2 hybrid mice.

Methods

We used 126 polymorphic markers to perform simple sequence‐length polymorphism analysis on 290 F2 hybrids of arthritis‐susceptible (DBA/1J) and arthritis‐resistant (FVB/N) inbred mouse strains. The major clinical traits (disease severity and onset) were assessed, and serum antibodies specific to type II collagen (CII) were determined by enzyme‐linked immunosorbent assay in 270 F2 mice. Lymph nodes from 94 F2 mice were used to test the ratio of CD4 to CD8 by fluorescence‐activated cell sorter analysis, and cell proliferation was determined by XTT test.

Results

Two quantitative trait loci (QTLs) identified in previous studies were confirmed; these were severity‐controlling Cia2 and onset‐controlling Cia4 on chromosome 2. Moreover, we identified 5 new QTLs, 1 for CII‐specific IgG2a antibodies on chromosome 5, 2 controlling the CII‐specific IgG1 antibody response on chromosomes 10 and 13, 1 for the CD4:CD8 ratio on chromosome 2, and 1 for cell proliferation (measured by XTT test) on chromosome 16. Complement component C5 was identified as the probable main candidate gene for the QTLs Cia2 and Cia4. F2 mice carrying a 2‐basepair deletion of C5, the FVB/N allele, had low incidence and less severe disease as compared with those carrying the DBA/1J allele.

Conclusion

This genome scan provides additional evidence confirming the role of C5 as a probable candidate gene for Cia2 and Cia4 loci, and identifies new QTLs controlling new traits in autoimmune arthritis.
Passive transfer of Sjögren's syndrome IgG produces the pathophysiology of overactive bladder
Authors: Wang Fang , Jackson Michael W. , Maughan Vicki , Cavill Dana , Smith Anthony J. , Waterman Sally A. , Gordon Tom P.
Published: November 2004

Objective

The presence, in patients with primary and secondary Sjögren's syndrome (SS), of autoantibodies that acutely inhibit M3 muscarinic receptor (M3R)–mediated bladder contractions is difficult to reconcile with the fact that symptoms of detrusor overactivity and other features of cholinergic hyperresponsiveness occur in this disease. This study was undertaken to examine the in vivo effects of these autoantibodies on bladder function by examining bladder responsiveness and compliance following passive transfer of patient IgG to mice.

Methods

Contractile responses of isolated bladder strips both to the muscarinic agonist carbachol and to electrically evoked acetylcholine release were measured 48 hours after injection of mice with patient or control IgG. A whole bladder assay with intact neuronal pathways was developed to assess bladder wall compliance on filling cystometry. Expression of M3R in bladders from IgG‐injected mice was assessed by immunohistochemistry.

Results

Passive transfer of SS IgG with inhibitory anti‐M3R activity produced a paradoxical increase in contractile responses of detrusor strips to cholinergic stimulation. Cystometry of whole bladders revealed a corresponding decrease in bladder wall compliance and phasic detrusor contractions upon filling, replicating the urodynamic features of an overactive bladder. The features of cholinergic hyperresponsiveness were associated with increased postsynaptic M3R expression and were reproduced by injecting mice with a rabbit antibody against the second extracellular loop of M3R.

Conclusion

These findings are consistent with the notion that there is initial inhibition of parasympathetic neurotransmission by antagonistic autoantibodies to M3R, which produces a compensatory increase in M3R expression in vivo. The enhanced cholinergic responses during bladder distention result in detrusor overactivity. We conclude that the overactive bladder associated with SS is an autoantibody‐mediated disorder of the autonomic nervous system, which may be part of a wider spectrum of cholinergic hyperresponsiveness.
Bone morphogenetic protein and transforming growth factor β inhibitory Smads 6 and 7 are expressed in human adult normal and osteoarthritic cartilage in vivo and are differentially regulated in vitro by interleukin‐1β
Authors: Kaiser Martina , Haag Jochen , Söder Stephan , Bau Brigitte , Aigner Thomas
Published: November 2004

Objective

Bone morphogenetic protein (BMP) and transforming growth factor β (TGFβ) are potent anabolic factors in adult articular chondrocytes. In this study, we investigated whether intracellular inhibitors of BMP and TGFβ signaling, inhibitory Smad6 (I‐Smad6) and I‐Smad7, are expressed in articular chondrocytes in normal and osteoarthritic (OA) cartilage, and whether their expression shows a correlation with the anabolic activity of OA chondrocytes in vivo and after interleukin‐1β (IL‐1β) stimulation in vitro.

Methods

RNA isolated directly from normal and OA human knee cartilage as well as from cultured articular chondrocytes was analyzed by (quantitative) polymerase chain reaction technology. Immunolocalization of the I‐Smads was performed on tissue sections and compared with the anabolic cellular activity as documented by in situ hybridization experiments for aggrecan and type II collagen.

Results

Both Smad6 and Smad7 were expressed in all samples of normal and OA cartilage. Immunostaining (including confocal microscopy) confirmed the presence of Smad6 and Smad7 in the majority of normal and degenerated articular chondrocytes; localization was mostly cytoplasmic. No correlation between expression of the main anabolic genes and expression of the I‐Smads was found. In cultured articular chondrocytes, stimulation with IL‐1β showed up‐regulation of Smad7, whereas Smad6 was down‐regulated.

Conclusion

Both Smad6 and Smad7 are expressed in adult human articular chondrocytes. The primarily cytoplasmic localization suggests permanent activation of the I‐Smads in articular cartilage in vivo. No evidence was found that up‐regulation or down‐regulation of I‐Smads in OA cartilage correlates directly with the anabolic (or catabolic) activity of articular chondrocytes. The regulation in chondrocytes of Smad6 and Smad7 expression by IL‐1β suggests a potentially important role of IL‐1β signaling in chondrocytes, via indirect influencing of the BMP/TGFβ signaling cascade.
Kinetics of baculovirus replication and release using real‐time quantitative polymerase chain reaction
Authors: Rosinski Matthew , Reid Steven , Nielsen Lars Keld
Published: November 2004

The study of viral‐based processes is hampered by (a) their complex, transient nature, (b) the instability of products, and (c) the lack of accurate diagnostic assays. Here, we describe the use of real‐time quantitative polymerase chain reaction to characterize baculoviral infection. Baculovirus DNA content doubles every 1.7 h from 6 h post‐infection until replication is halted at the onset of budding. No dynamic equilibrium exists between replication and release, and the kinetics are independent of the cell density at the time of infection. No more than 16% of the intracellular virus copies bud from the cell. © 2002 John Wiley & Sons, Inc. Biotechnol Bioeng 77: 476–480, 2002; DOI 10.1002/bit.10126