bluuebunny/crossref_metadata_2025 huggingface dataset:
Lake-Effect Snowstorms over Southern Ontario, Canada, and Their Associated Synoptic-Scale Environment
Authors: Liu A. Q. , Moore G. W. K.
Published: November 2004

Lake-effect snowstorms are an important source of severe winter weather over the Great Lakes region and are often triggered by the passage of synoptic-scale low pressure systems. In this paper, a climatology of lake-effect snowstorms over southern Ontario, Canada, for the period 1992–99 is developed. The distinguishing characteristics of the synoptic-scale environment associated with intense lake-effect snowstorms in the region are identified through the study of individual events and through composite analysis. In particular, it is found that a low pressure and a cold-temperature anomaly situated over Hudson Bay, north of the Great Lakes, is a favorable environment for the development of intense lake-effect snowstorms over southern Ontario. It is also found that the track of the low pressure system can have a significant impact on the development or lack thereof of lake-effect snowstorms over southern Ontario. It is found that the low pressure systems that trigger intense lake-effect snowstorms tend to have an anomalous northeastward track as compared to the eastward track of most low pressure systems that transit the region.
Optimization of a Direct Elliptic Boundary Value Problem Solver by the Combined Use of Symmetry and Strassen's Algorithm
Authors: Qaddouri Abdessamad , Côté Jean
Published: November 2004

A direct elliptic boundary value problem solver used for meteorological applications has been optimized. The problem to be solved is symmetric under a parity operation, and this is preserved by discretization. Therefore if the mesh possesses this symmetry, then the discretized problem will share this symmetry as well. The direct method can make use of this symmetry on a variable mesh to reduce the cost associated with the slow transform, a matrix product, by half. It is also shown that this can be combined with the Strassen–Winograd algorithm for even better results.
Constructing Mentors: Latina Educational Leaders’ Role Models and Mentors
Authors: Méndez-Morse Sylvia
Published: November 2004

This article reports on the mentoring aspects of a qualitative study of 6 Mexican American female school leaders in west Texas. One goal of the study was the identification of any individuals who had been role models or mentors important to the careers of these women. A role model was defined as someone whose characteristics or traits another person would want to emulate; a mentor was defined as someone who actively helps, supports, or teaches someone else how to do a job so that she will succeed. The findings indicate that for the Latina educational leaders in the study, significant role models and mentors, primarily from nonprofessional areas of the women’s lives, mitigated the absence of a formal, traditional mentoring relationship. Moreover, the experiences of these school leaders demonstrate that these Latinas assembled or constructed a mentor from varied sources that collectively met their specific needs and priorities.
Diffusion of Naturopathic State Licensing in the United States and Canada
Authors: Albert Donald Patrick , Butar Ferry Butar
Published: November 2004

State licensing of naturopathic medicine is currently in the middle of the early majority stage of diffusion. This research found that licensing is occurring in a contagious manner; therefore, spatial proximity is an important determinant in predicting new adopters. Using the proportion of licensed neighbors to al neighbors as a measure for spatial proximity and the S-shaped curve, the remaining early majority and the first half of the late majority states and provinces were predicted. Lobbyists and recruiters might use this information to allocate resources to early majority states first.
Trafficking
Authors: Scanlan John
Published: November 2004

In cities the world over, we are able to determine stability in daily existence, to identify with our social spaces, because modes of transport have become essential components of subjective autonomy. But would it not be just as accurate to say that in transit, modern life puts the self in abeyance? The author argues that the ways we allow ourselves to be moved around in “traffic space” create a passivity that renders almost invisible the complex mechanics of movement, which we become alert to only at the moment of breakdown, precisely when they become a threat to autonomy. Our trafficking has an almost narcotic effect, rendering us immobile against the continual movements that constitute urban life, one that also magnifies out of all proportion the accidents or aberrations that sometimes disturb our traffic space, making it seem as if we may easily descend into an uncontrollable chaos.
Architecture, Al-Qaeda, and the World Trade Center
Authors: Reid Julian
Published: November 2004

The 9/11 attack on the World Trade Center has been widely interpreted as representing a new form of terrorism born of anti-Western political sentiment. This article challenges such interpretations by contextualizing the attack not as an original act in creating a new form of terrorism born outside the West but as the culminating act in the perpetration of a relatively long-standing tradition of waging war on modern architectural forms that originates in the West itself. The argument is that we can understand Al-Qaeda not as a force born outside Western control and civilization but, in opposition to that reading, as very much a product of the development of Western modernity. The weight of symbolic value that Al-Qaeda derived from its attack on the World Trade Center was, this article argues, a product of the extent to which the vertical and orthogonal form of that particular building had become incongruous with the newfound fluidity and dynamism of more contemporary Western forms.
Variants in estrogen-biosynthesis genes CYP17 and CYP19 and breast cancer risk: a family-based genetic association study
Authors: Ahsan Habibul , Whittemore Alice S , Chen Yu , Senie Ruby T , Hamilton Steven P , Wang Qiao , Gurvich Irina , Santella Regina M
Published: November 2004

Background

Case-control studies have reported inconsistent results concerning breast cancer risk and polymorphisms in genes that control endogenous estrogen biosynthesis. We report findings from the first family-based association study examining associations between female breast cancer risk and polymorphisms in two key estrogen-biosynthesis genes CYP17 (T→C promoter polymorphism) and CYP19 (TTTA repeat polymorphism).

Methods

We conducted the study among 278 nuclear families containing one or more daughters with breast cancer, with a total of 1123 family members (702 with available constitutional DNA and questionnaire data and 421 without them). These nuclear families were selected from breast cancer families participating in the Metropolitan New York Registry, one of the six centers of the National Cancer Institute's Breast Cancer Family Registry. We used likelihood-based statistical methods to examine allelic associations.

Results

We found the CYP19 allele with 11 TTTA repeats to be associated with breast cancer risk in these families. We also found that maternal (but not paternal) carrier status of CYP19 alleles with 11 repeats tended to be associated with breast cancer risk in daughters (independently of the daughters' own genotype), suggesting a possible in utero effect of CYP19. We found no association of a woman's breast cancer risk either with her own or with her mother's CYP17 genotype.

Conclusion

This family-based study indicates that a woman's personal and maternal carrier status of CYP19 11 TTTA repeat allele might be related to increased breast cancer risk. However, because this is the first study to report an association between CYP19 11 TTTA repeat allele and breast cancer, and because multiple comparisons have been made, the associations should be interpreted with caution and need confirmation in future family-based studies.
Transgenic expression of CCL2 in the central nervous system prevents experimental autoimmune encephalomyelitis
Authors: Elhofy Adam , Wang Jintang , Tani Mari , Fife Brian T , Kennedy Kevin J , Bennett Jami , Huang DeRen , Ransohoff Richard M , Karpus William J
Published: November 2004

CC chemokine ligand 2 (CCL2)/monocyte chemotactic protein-1, a member of the CC chemokine family, is a chemoattractant for monocytes and T cells through interaction with its receptor CCR2. In the present study, we examined a T helper cell type 1 (Th1)-dependent disease, proteolipid protein-induced experimental autoimmune encephalomyelitis, in a transgenic mouse line that constitutively expressed low levels of CCL2 in the central nervous system (CNS) under control of the astrocyte-specific glial fibrillary acidic protein promoter. CCL2 transgenic mice developed significantly milder clinical disease than littermate controls. As determined by flow cytometry, mononuclear cell infiltrates in the CNS tissues of CCL2 transgenic and littermate-control mice contained equal numbers of CD4+ and CD8+ T cells, and the CCL2 transgenic mice showed an enhanced number of CNS-infiltrating monocytes. CNS antigen-specific T cells from CCL2 transgenic mice produced markedly less interferon-γ. Overexpression of CCL2 in the CNS resulted in decreased interleukin-12 receptor expression by antigen-specific T cells. Collectively, these results indicate that sustained, tissue-specific expression of CCL2 in vivo down-regulates the Th1 autoimmune response, culminating in milder clinical disease.
No Association Is Found between the Candidate Genes of t‐PA/Plasminogen System and Japanese Methamphetamine‐Related Disorder: A Collaborative Study by the Japanese Genetics Initiative for Drug Abuse
Authors: IWATA N , INADA T , HARANO M , KOMIYAMA T , YAMADA M , SEKINE Y , IYO M , SORA I , UJIKE H , OZAKI N
Published: November 2004

Abstract: In the central nervous system, tissue‐plasminogen activator (t‐PA)/plasmin system is involved in long‐term synaptic plasticity and remodeling, and participates in rewarding effects of methamphetamine (MAP), by acutely regulating MAP‐induced dopamine release in the nucleus accumbens. The aim of this study was to examine the relationships between the patients with MAP abusers/psychosis and the t‐PA/plasminogen system genes. Subjects comprised 185 MAP abusers and 288 healthy controls. Four polymorphisms in the t‐PA, plasminogen activator inhibitor, and plasminogen genes were examined in the present study. No significant differences were observed in each polymorphism between healthy controls and MAP abusers/psychosis. This study suggests that t‐PA/plasminogen system is unlikely to be a major contributor to the substance abuse liability and/or the development of MAP psychosis.
Specific Gene Expression and Possible Involvement of Inflammation in Methamphetamine‐Induced Neurotoxicity
Authors: ASANUMA MASATO , MIYAZAKI IKUKO , HIGASHI YOUICHIROU , TSUJI TAKESHI , OGAWA NORIO
Published: November 2004

Abstract: To reveal specific gene expression in methamphetamine (METH) ‐induced dopamine neurotoxicity, temporal characteristics of METH‐induced changes in gene expression in dopaminergic neuronal cells were examined using the cDNA array and the differential display method. A number of genes in the class of “trafficking & protein turnover,”“metabolic pathways,”“transmitters & receptors,” and “growth factors, cytokines” were upregulated after the METH treatment in the cDNA array assay. Whereas, some genes related to trafficking & protein turnover and “modulators, effectors & intracellular transducers” were decreased by METH. Some proteins associated with synaptic vesicle transportation indeed up‐ or downregulated after the METH treatment. These data suggest that the protein trafficking and degradation system is involved in the dopaminergic cell death induced by METH. Furthermore, focusing on inflammatory reactions after METH injection, possible neuroprotective property of nonsteroidal anti‐inflammatory drugs were examined against METH‐induced neurotoxicity. Coadministration of NSAID with METH significantly attenuated striatal dopamine terminal degeneration and microgliosis induced by METH, suggesting that the protective effects are based on their inhibitory activity on production of cytokines and nitric oxides or their suppressive action against microglia activation.
Food‐Reinforced Operant Behavior in Dopamine Transporter Knockout Mice: Enhanced Resistance to Extinction
Authors: HIRONAKA NAOYUKI , IKEDA KAZUTAKA , SORA ICHIRO , UHL GEORGE R. , NIKI HIROAKI
Published: November 2004

Abstract: Dopamine (DA) plays roles in circuits that are important for brain reward and in striatal brain regions that are important for certain types of habit learning. These processes in wildtype, heterozygous, and homozygous dopamine transporter knockout (DAT‐KO) mice, which were mildly food deprived and allowed to make nose‐poke responses for food reinforcement, were studied. The mice were given 20‐min sessions of daily (a) baseline exposure to the operant chambers, (b) acquisition of nose‐poke responses in which responses were reinforced under a fixed ratio (FR5) schedule, (c) a progressive ratio schedule in which the number of responses required to obtain food was gradually increased, and (d) extinction of responses in which nose pokes were not followed by food. Neither heterozygous nor homozygous DAT‐KO mice differed from their wildtype litter mates in the number of nose pokes displayed during baseline exposures to the chambers, the number of sessions required for acquisition, the number of responses under the FR5 schedule, or the number of responses under the progressive ratio schedule. Interestingly, however, in the five extinction sessions in which food was no longer delivered by nose poking, homozygous DAT‐KO mice exerted significantly more responses than mice of either of the other two genotypes. These lines of evidence suggest a greater resistance of DAT‐KO mice to the elimination of the response and support roles of dopaminergic systems in habit memory.
Substituted Amphetamines That Produce Long‐Term Serotonin Depletion in Rat Brain (“Neurotoxicity”) Do Not Decrease Serotonin Transporter Protein Expression
Authors: ROTHMAN RICHARD B. , JAYANTHI SUBRAMANIAM , CADET JEAN L. , WANG XIAOYING , DERSCH CHRISTINA M. , BAUMANN MICHAEL H.
Published: November 2004

Abstract: Administration of high‐dose d‐fenfluramine (d‐FEN) or parachloroamphetamine (PCA) produces long‐lasting decreases in serotonin transporter (SERT) binding and tissue levels of serotonin (5‐HT) in rat forebrain. These changes have been viewed as evidence for 5‐HT neurotoxicity, but few studies have measured SERT protein levels. Thus, in the present study we determined the effect of high‐dose d‐FEN or PCA, administered according to a “neurotoxic” dosing regimen, on the density of SERT sites using ligand binding methods and on SERT protein levels using Western blots. Rats were sacrificed 2 days and 2 weeks after administration of drug or saline. The density of SERT was determined in homogenates of caudate and whole brain minus caudate. d‐FEN and PCA decreased SERT binding by 30 to 60% in both tissues and at both time points. Similarly, d‐FEN and PCA administration profoundly decreased tissue 5‐HT and 5‐HIAA in frontal cortex. Despite the large decreases in SERT binding and depletion of tissue 5‐HT that occurred with d‐FEN administration, SERT protein expression, as determined by Western blot analysis, did not change in either tissue or time point. PCA administration decreased SERT protein by about 20% only at the 2‐day point in the caudate. Drug treatments did not change expression of glial fibrillary acidic protein (GFAP), a hallmark indicator of neuronal damage, in whole brain minus caudate in the 2‐week group. These results support the hypothesis that d‐FEN‐ and PCA‐induced decreases in tissue 5‐HT and SERT binding sites reflect neuroadaptive changes rather than neurotoxic effects.
Comparative Effects of NO‐Synthase Inhibitor and NMDA Antagonist on Generation of Nitric Oxide and Release of Amino Acids and Acetylcholine in the Rat Brain Elicited by Amphetamine Neurotoxicity
Authors: BASHKATOVA V , KRAUS M M , VANIN A , HORNICK A , PRAST H
Published: November 2004

Abstract: The aim of this study was to clarify the role of nitric oxide (NO) and lipid peroxidation (LPO) processes as well as the contribution of various neurotransmitters in pathophysiological mechanisms of neurotoxicity induced by amphetamine (AMPH). NO level was determined directly in brain tissues using electron paramagnetic resonance spectroscopy technique. The content of the products of lipid peroxidation (LPO) was measured spectrophotometrically as thiobarbituric acid reactive species (TBARS). The output of neurotransmitter amino acids (glutamate, aspartate, and GABA) and acetylcholine (ACH) was monitored in nucleus accumbens (NAc) by push‐pull technique with HPLC detection. Repeated, systemic application of AMPH elevated striatal and cortical NO generation and LPO production. Moreover, administration of AMPH led to a marked and long‐lasting increase of ACH release. Surprisingly, while glutamate output was not affected, aspartate release was enhanced 30 to 50 min after each AMPH injection. The release rate of GABA was also elevated. The selective NO‐synthase inhibitor 7‐nitroindazole (7‐NI) was highly effective in abating the rise in the neurotransmitter release induced by the AMPH. The NOS inhibitor also abolished the increase of NO generation produced by AMPH, but did not influence the intensity of LPO elicited by the AMPH administration. Pretreatment with the noncompetitive NMDA receptor antagonist dizocilpine (MK‐801) completely prevented increase of NO generation and TBARS formation induced by multiple doses of AMPH. Dizocilpine also abolished the effect of the psychostimulant drug on the release of neurotransmitters ACH, glutamate, aspartate, and GABA in the NAc. Our findings suggest a key role of NO in AMPH‐induced transmitter release, but not in the formation of LPO products. It appears that AMPH enhances release of ACH and neurotransmitter amino acids through increased NO synthesis and induces neurotoxicity via NO and also by NO‐independent LPO.
Clinical Features of Sensitization to Methamphetamine Observed in Patients with Methamphetamine Dependence and Psychosis
Authors: UJIKE HIROSHI , SATO MITSUMOTO
Published: November 2004

Abstract: Metamphetamine (METH) has been the most popular drug of abuse in Japan for more than 50 years, resulting in serious health and social issues. Most adult abusers in Japan consume only METH; multiple‐substance abusers are rare. This unusual aspect of drug abuse makes it possible to observe clearly the sequential alteration of psychiatric symptoms induced by METH without modification by other illegal drugs. Clinical investigation reveals three core characteristics of METH abuse: (1) progressive qualitative alteration in mental symptoms from a nonpsychotic to a prepsychotic to a severely psychotic state; (2) enhanced vulnerability to relapse of psychosis; and (3) very long duration of the vulnerability to relapse. These findings indicate that the phenomenon of sensitization to METH develops during abuse and plays a key role in the susceptibility to and onset of psychosis and in the refractory process. Molecular findings using animal sensitization models may facilitate a better understanding of, and open the way for innovative therapies for, METH psychosis and also chronic schizophrenia.
The Role of Noradrenergic and Dopaminergic Hyperactivity in the Development of Spontaneous Recurrence of Methamphetamine Psychosis and Susceptibility to Episode Recurrence
Authors: YUI KUNIO , GOTO KIMIHIKO , IKEMOTO SHIGENORI
Published: November 2004

Abstract: The role of dopaminergic activity in susceptibility of methamphetamine (MAP) psychosis (flashbacks) to subsequent spontaneous recurrences was studied. Plasma monoamine metabolite levels were assayed in 23 flashbackers, of whom 10 experienced a single flashback, 8 exhibited subsequent flashbacks and 5 with the last episode; 18 nonflashbackers with a history of MAP psychosis; 9 subjects with persistent MAP psychosis; and 19 MAP user and 10 nonuser controls. All flashbackers had undergone frightening stressful experiences during previous MAP use. Their flashbacks were triggered by mild psychosocial stressors. Plasma norepinephrine (NE) levels increased with the increase in plasma levels of 3‐methoxytyramine (3‐MT), an index of dopamine release, during flashbacks in the 23 flashbackers. Of these, the 8 with subsequent episodes had markedly increased NE levels and increased 3‐methoxytyramine levels during flashbacks. However, the 5 flashbackers with the last episode had moderately increased NE levels, and the 10 with a single episode displayed small increases in NE levels during flashbacks. Their 3‐MT levels did not significantly differ from the levels in the control groups. Thus, increased DA release in addition to robust noradrenergic hyperactivity in response to mild psychosocial stressors may be important in susceptibility to subsequent flashbacks.
Drug Abuse in China
Authors: CHENGZHENG ZHAO , ZHIMIN LIU , DONG ZHAO , YANHONG LIU , JIANHUI LIANG , YILANG TANG , ZEYUAN LIU , JIWANG ZHENG
Published: November 2004

Abstract: The drug problem in China reappeared in the late 1980s. At that time, most drug abusers used opium only, with heroin accounting for a very small proportion and its use being limited to border areas in the southwest and rural areas in the northwest. Beginning in the early 1990s, drug abuse spread quickly. The number of registered drug addicts increased from 70,000 in 1990 to one million by the end of 2002. Besides opioids, some “new” kinds of drugs including amphetamines and ketamine have penetrated the country through various channels since 1997. Drug abuse has caused severe problems for both the abusers and society. Three types of treatment settings for detoxification and rehabilitation are available: compulsory detoxification institutions, rehabilitation units through labor, and voluntary detoxification institutions run by sections of public security, justice, and health, respectively. Medical treatment is often combined with psychological counseling and physical training. Pharmaceutical therapy, traditional Chinese medicine, and nonpharmaceutical therapy are utilized for opioid addiction. Drug prevention, especially for young people, is emphasized. NGOs at different levels have all joined in this work. Intervention work was also started in regions where drug abuse and HIV/AIDS problems are serious. Drug abusers are helped to keep drug free after being released from detoxification settings by their communities. Different levels of institutions engaged in research on drug abuse are found in all parts of China.
Drug Problem in Southeast and Southwest Asia
Authors: KULSUDJARIT KONGPETCH
Published: November 2004

Abstract: In 2002, the drug problem in Southeast and Southwest Asia was serious, particularly in the production of opium and heroin in Afghanistan, Myanmar, and Laos, the three largest producers of illicit opium in the world. The increasing illicit manufacture of ATS, particularly methamphetamine, in Southeast Asia, mainly in China and Myanmar, was also a major concern. Some reports indicated that ephedrine, used for illicitly producing methamphetamine in Southeast Asia, is diverted and smuggled out of China and India, whereas caffeine, the adulterant used for producing methamphetamine tablets, is mainly smuggled into Myanmar through its border with Thailand. Seizure data showed a dramatic increase in trafficking in MDMA through Southeast Asia. In terms of the drug epidemic, in 2002, cannabis remained overall the main drug of abuse in all of the countries of Southeast and Southwest Asia. Opiates, mainly opium and heroin, were also the drugs of choice except in Thailand, where opiate abuse declined, but ATS was the main drug of abuse due to its low cost and availability. A significant increase in ATS abuse, amphetamine, methamphetamine, and MDMA among the youth who smoked, sniffed, and inhaled them was reported in Cambodia, China, Indonesia, Laos, Myanmar, the Philippines, and Thailand. Injecting drug use among opiate abusers has been identified as the prime cause of the rapid spread of HIV/AIDS in Southeast and Southwest Asia.
Drug Abuse Trends among Youth in the United States
Authors: BANKEN JOSEPH A.
Published: November 2004

Abstract: Several years of survey data indicate that illicit drug use among U.S. youth was at its highest level in 1979. Generally, the use of some illicit drugs declined progressively throughout the 1980s, stabilized, and then decreased slightly. Reducing illicit drug use among U.S. youth continues to be a priority of federal, state, and local law enforcement agencies. The U.S. government tracks youth illicit drug use through three nationally representative surveys: National Household Survey on Drug Abuse, Monitoring the Future Study, and Youth Risk Behavior Survey. Other surveys include the Partnership Attitudes Tracking Study, conducted annually to assess youth and parental attitudes about drugs, and Drug Abuse Awareness Network (DAWN), a national surveillance system that monitors trends in drug‐related emergency department visits and deaths. Although survey methods differ, similar trends in drug use are well documented by these surveys. Among American youth, illicit use of drugs such as tobacco, alcohol, inhalants, marijuana, LSD, cocaine, heroin, and methamphetamine has remained relatively stable. However, a noteworthy exception is the increased use of MDMA (methylenedioxymethamphetamine). The physical consequences of “club and recreational drug use” are evidenced in the increased numbers of emergency department visits, specifically those related to MDMA and gamma‐hydroxy‐butyrate use, which may represent a new and emerging trend in illicit drug use.
Role of Endocannabinoids and Cannabinoid CB1 Receptors in Alcohol‐Related Behaviors
Authors: HUNGUND BASALINGAPPA L. , BASAVARAJAPPA BALAPAL S.
Published: November 2004

Abstract: This review presents the remarkable research during the past several years indicating that some of the pharmacological and behavioral effects of alcohol, including alcohol drinking and alcohol‐preferring behavior, are mediated through one of the most abundant neurochemical systems in the central nervous system, the endocannabinoid signaling system. The advances, with the discovery of specific receptors and the existence of naturally occurring cannabis‐like substances in the mammalian system and brain, have helped in understanding the neurobiological basis for drugs of abuse, including alcoholism. The cDNA and genomic sequences encoding G‐protein‐coupled cannabinoid receptors (CB1 and CB2) from several species have now been cloned. This has facilitated discoveries of endogenous ligands (endocannabinoids). To date, two fatty acid derivatives characterized to be arachidonylethanolamide and 2‐arachidonylglycerol have been isolated from both nervous and peripheral tissues. Both these compounds have been shown to mimic the pharmacological and behavioral effects of Δ9‐tetrahydrocannabinol, the psychoactive component of marijuana. The involvement of the endocannabinoid signaling system in tolerance development to drugs of abuse, including alcohol, were unknown until recently. Studies from our laboratory demonstrated for the first time the downregulation of CB1 receptor function and its signal transduction by chronic alcohol. The observed downregulation of CB1 receptor binding and its signal transduction results from the persistent stimulation of receptors by the endogenous CB1 receptor agonists arachidonylethanolamide and 2‐arachidonylglycerol, the synthesis of which is increased by chronic alcohol treatment. The deletion of CB1 receptor has recently been shown to block voluntary alcohol intake in mice, which is consistent with our previous findings where the DBA/2 mice known to avoid alcohol intake had significantly reduced brain CB1 receptor function. These findings suggest a role for the CB1 receptor gene in excessive alcohol drinking behavior and development of alcoholism. Ongoing investigations may lead to the development of potential therapeutic agents to modulate the endocannabinoid signaling system, which will be helpful for the treatment of alcoholism.
Using a DNA Microarray Method to Examine Gene Expression in Brain from Clozapine‐Injected Mice
Authors: TAKAHASHI Y , KUMANISHI T , HAYASHI S
Published: November 2004

Abstract: After our 2002 report on the changes of gene expression in the brain from phencyclidine‐treated mouse by using DNA microarray (Toyooka et al., Ann. N.Y. Acad. Sci. 965: 10‐20), we decided to apply this DNA microarray method for the brain of the mouse treated with other drugs. We are now examining the effects of clozapine on the brain function. Clozapine is an atypical antipsychotic drug. Clozapine has affinity for neurotransmitter receptors, including D4 dopamine, serotonin, histamine, and adrenergic receptors. MacGibbon et al. (Mol. Brain Res. 23: 21‐32) reported that clozapine and haloperidol produced a differential pattern of immediate early gene expression in rat caudate‐putamen. Kobayashi et al. (Br. J. Pharmacol. 123: 421‐426) have observed the effects of clozapine on the opioid receptors and G‐protein‐activated inwardly rectifying potassium channel of Xenopus oocytes. Thomas et al. (J. Neurochem. 76: 789‐796) found that clozapine increases apolipoprotein D expression in the mouse brain. Therefore, we are going to apply this DNA microarray method to examine the effects of clozapine on mouse brain function. After we injected clozapine into mice for 20 days, we decapitated the mice. We then used the DNA microarray method to examine the gene expression of mouse brain. We found some changes in the mouse brain treated with clozapine. For example, the intensity of a potassium channel spot decreased, and that of a serotonin receptor spot increased.
Convergent Effects on Cell Signaling Mechanisms Mediate the Actions of Different Neurobehavioral Teratogens: Alterations in Cholinergic Regulation of Protein Kinase C in Chick and Avian Models
Authors: YANAI JOSEPH , BEER AVITAL , HULEIHEL RABAB , IZRAEL MICHAL , KATZ SOFIA , LEVI YAARIT , ROZENBOIM ISRAEL , YANIV SHIRI P. , SLOTKIN THEODORE A.
Published: November 2004

Abstract: Although the actions of heroin on central nervous system (CNS) development are mediated through opioid receptors, the net effects converge on dysfunction of cholinergic systems. We explored the mechanisms underlying neurobehavioral deficits in mouse and avian (chick, Cayuga duck) models. In mice, prenatal heroin exposure (10 mg/kg on gestation days 9‐18) elicited deficits in behaviors related to hippocampal cholinergic innervation, characterized by concomitant pre‐ and postsynaptic hyperactivity, but ending in a reduction of basal levels of protein kinase C (PKC) isoforms βII and γ and their desensitization to cholinergic receptor‐induced activation. PKCα, which is not involved in the behaviors studied, was unaffected. Because mammalian models possess inherent confounding factors from maternal effects, we conducted parallel studies using avian embryos, evaluating hyperstriatal nucleus (intermedial part of the hyperstriatum ventrale, IMHV)‐related, filial imprinting behavior. Heroin injection to the eggs (20 mg/kg) on incubation days 0 and 5 diminished the post‐hatch imprinting ability and reduced PKCg and bII content in the IMHV membrane fraction. Two otherwise unrelated agents that converge on cholinergic systems, chlorpyrifos and nicotine, elicited the same spectrum of effects on PKC isoforms and imprinting but had more robust actions. Pharmacological characterization also excluded direct effects of opioid receptors on the expression of imprinting; instead, it indicated participation of serotonergic innervation. The avian models can provide rapid screening of neuroteratogens, exploration of common mechanisms of behavioral disruption, and the potential design of therapies to reverse neurobehavioral deficits.
Cohort Analysis of Patients With Localized, High-Risk, Extremity Soft Tissue Sarcoma Treated at Two Cancer Centers: Chemotherapy-Associated Outcomes
Authors: Cormier Janice N. , Huang Xuelin , Xing Yan , Thall Peter F. , Wang Xuemei , Benjamin Robert S. , Pollock Raphael E. , Antonescu Cristina R. , Maki Robert G. , Brennan Murray F. , Pisters Peter W.T.
Published: November 2004

Purpose

Patients with American Joint Committee on Cancer stage III soft tissue sarcoma (STS) have high risks of distant recurrence and death. The role of chemotherapy for these patients remains controversial despite several randomized trials and a meta-analysis.

Methods

We reviewed the treatments and outcomes of 674 consecutive adult patients presenting with primary stage III extremity STS between 1984 and 1999. Pre- or postoperative doxorubicin-based chemotherapy was used in a nonrandomized fashion in approximately half of this high-risk population. The objective of this review was to evaluate the impact of chemotherapy while accounting for known prognostic variables.

Results

Among 674 patients, 338 (50%) were treated with local therapy only, and 336 (50%) were treated with local therapy plus chemotherapy. The median follow-up for survivors was 6.1 years. Five-year local and distant recurrence-free interval probabilities were 83% and 56%, respectively, for the two groups combined. The 5-year disease-specific survival (DSS) rate was 61%. Cox regression analyses showed a time-varying effect associated with chemotherapy. During the first year, the hazard ratio associated with DSS for patients treated with chemotherapy versus no chemotherapy was 0.37 (95% CI, 0.20 to 0.69; P = .002). Thereafter, this hazard ratio was 1.36 (95% CI, 1.02 to 1.81; P = .04).

Conclusion

It seems that the clinical benefits associated with doxorubicin-based chemotherapy in patients with high-risk extremity STS are not sustained beyond 1 year. These results suggest that caution should be used in the interpretation of randomized clinical trials of adjuvant chemotherapy that seem to demonstrate clinical benefits with relatively short-term follow-up.
High-Dose Therapy and Autologous Hematopoietic Stem-Cell Transplantation for Recurrent or Refractory Pediatric Hodgkin's Disease: Results and Prognostic Indices
Authors: Lieskovsky YeeYie E. , Donaldson Sarah S. , Torres Mylin A. , Wong Ruby M. , Amylon Michael D. , Link Michael P. , Agarwal Rajni
Published: November 2004

Purpose

To evaluate the outcome of pediatric patients with refractory or relapsed Hodgkin's disease (HD) who undergo high-dose therapy and autologous hematopoietic stem-cell transplantation (AHSCT).

Patients and Methods

From 1989 to 2001, 41 pediatric patients with relapsed or primary refractory HD underwent high-dose therapy followed by AHSCT according to one of four autologous transplantation protocols at Stanford University Medical Center (Stanford, CA). Pretreatment factors were analyzed by univariate and multivariate analysis for prognostic significance for 5-year overall survival (OS), event-free survival (EFS), and progression-free survival (PFS).

Results

At a median follow-up of 4.2 years (range, 0.7 to 11.9 years), the 5-year OS, EFS, and PFS rates were 68%, 53%, and 63%, respectively. Multivariate analysis determined the following three factors to be significant predictors of poor OS and EFS: extranodal disease at first relapse, presence of mediastinal mass at time of AHSCT, and primary induction failure. Two of these factors also predicted for poor PFS (extranodal disease at time of first relapse and presence of mediastinal mass at time of transplantation).

Conclusion

More than half of children with relapsed or refractory HD can be successfully treated with the combination of high-dose therapy and AHSCT, confirming the efficacy of this approach. Further investigation is now required to determine the optimal timing of AHSCT, as well as to develop alternative regimens for those patients with factors prognostic for poor outcome after AHSCT.
White Matter Lesions Detected by Magnetic Resonance Imaging After Radiotherapy and High-Dose Chemotherapy in Children With Medulloblastoma or Primitive Neuroectodermal Tumor
Authors: Fouladi Maryam , Chintagumpala Murali , Laningham Fred H. , Ashley David , Kellie Stewart J. , Langston James W. , McCluggage Charles W. , Woo Shaio , Kocak Mehmet , Krull Kevin , Kun Larry E. , Mulhern Raymond K. , Gajjar Amar
Published: November 2004

Purpose

White matter lesions (WMLs) have been described as a delayed effect of cranial irradiation in children with brain tumors, or a transient subacute effect characterized by an intralesional or perilesional reaction. We report the occurrence of subacute WMLs detected by magnetic resonance imaging (MRI) in children treated for medulloblastoma or primitive neuroectodermal tumor (PNET) and document the associated clinical, radiologic, and neurocognitive findings.

Patients and Methods

Among 134 patients with medulloblastoma or supratentorial PNET treated prospectively with risk-adjusted craniospinal irradiation and conformal boost to the tumor bed, followed by four high-dose chemotherapy (HDC) cycles with stem-cell rescue, 22 developed WMLs on T1-weighted imaging with and without contrast and/or T2-weighted imaging on MRI. Patients had ≥ 12 months of follow-up. Neurocognitive assessments included intelligence quotient (IQ) tests and tests of academic achievement.

Results

Twenty-two patients developed WMLs at a median of 7.8 months after starting therapy (range, 1.9 to 13.0 months). Lesions were predominantly in the pons (n = 8) and cerebellum (n = 6). Sixteen patients (73%) had WML resolution at a median of 6.2 months (range, 1.68 to 23.5 months) after onset; two patients developed necrosis and atrophy. Three developed persistent neurologic deficits. Cumulative incidence of WMLs at 1 year was 15% ± 3%. Patients with WMLs had a significant decline in estimated IQ (−2.5 per year; P = .03) and math (−4.5 per year; P = .003) scores.

Conclusion

WMLs in medulloblastoma or PNET patients treated with conformal radiotherapy and HDC are typically transient and asymptomatic, and may mimic early tumor recurrence. A minority of patients with WMLs develop permanent neurologic deficits and imaging changes. Overall, the presence of WMLs is associated with greater neurocognitive decline.
Insulin, Physical Activity, and Caloric Intake in Postmenopausal Women: Breast Cancer Implications
Authors: Chlebowski Rowan T. , Pettinger Mary , Stefanick Marcia L. , Howard Barbara V. , Mossavar-Rahmani Yasmin , McTiernan Anne
Published: November 2004

Purpose

Increased physical activity and programs to reduce body mass index (BMI) with both increased physical activity and decreased caloric intake have been proposed to reduce insulin as a potential mediator of breast cancer and other chronic diseases. However, there are few data on the relative contribution of physical activity, caloric intake, and BMI to fasting insulin levels.

Materials and Methods

An ethnically diverse subsample of 2,996 mostly healthy postmenopausal women with no prior cancer history was randomly identified from the 161,809 participants in the Women's Health Initiative clinical trials and observational study. Information was collected on diet, recreational physical activity, and anthropometrics including BMI. Fasting insulin levels were determined. Using a cross-sectional design, insulin levels were then compared across quintiles of caloric intake and physical activity in linear regression model analyses controlled for BMI and other factors.

Results

Lower BMI (P < .0001), higher levels of physical activity (P < .0001), and lower caloric intake (P < .02) were all independently associated with significantly lower mean fasting insulin levels throughout the range of observed values. Insulin levels of 8.74 μU/mL ± 4.16 SD were seen in the highest physical activity and lowest caloric intake quintile compared with insulin levels of 15.08 μU/mL ± 16.32 SD in the lowest physical activity and highest caloric intake quintile (P < .0001).

Conclusion

These findings suggest that reduction in BMI achieved by increasing physical activity, reducing caloric intake, or both, should lower insulin levels, providing support for clinical trials evaluating insulin level change and breast cancer risk.
Angiotensin II Stimulates Protein Synthesis and Inhibits Proliferation in Primary Cultures of Rat Adrenal Glomerulosa Cells
Authors: Otis Mélissa , Campbell Shirley , Payet Marcel D. , Gallo-Payet Nicole
Published: November 2004

Angiotensin II (Ang II) is one of the most important stimuli of rat adrenal glomerulosa cells. The aim of the present study was to investigate whether Ang II can stimulate cell proliferation and/or hypertrophy and investigate pathways and intracellular targets. A 3-d treatment with Ang II (5–100 nm), through the Ang II type 1 receptor subtype, abolished cell proliferation observed in control cells but increased protein synthesis. Preincubation with PD98059 (a MAPK kinase inhibitor) abolished basal proliferation and had no effect on basal protein synthesis but did reverse the effect of Ang II on protein synthesis. The p38 MAPK inhibitor SB203580 reversed the inhibitory effect on cell proliferation and abolished the increase in protein synthesis, whereas the c-Jun N-terminal kinase inhibitor SP600125 had no effect. Time-course studies revealed that Ang II stimulated phosphorylation of both p42/p44mapk and p38 MAPK but did not activate c-Jun N-terminal kinase. Ang II had no effect on the level of cyclin E expression but increased the expression of the cyclin-dependent kinase, p27Kip1, an effect abolished in cells preincubated with SB203580 and PD98059. In conclusion, in cultured rat glomerulosa cells, a 3-d treatment with Ang II increases protein synthesis, with a concomitant decrease in proliferation. These effects are mediated by both the p42/p44mapk and p38 MAPK pathways, which increase expression of the steroidogenic enzymes, steroidogenic acute regulatory protein and 3β-hydroxysteroid dehydrogenase and p27Kip1, a protein known to block the cell cycle in G1 phase. Together these results support the key role of Ang II as a stimulus of steroid synthesis rather than a proliferating factor.
Economics of Antibiotic Use Policies
Authors: Paladino Joseph A.
Published: November 2004

Today more than ever, hospitals must effectively manage the use of antibiotics to control costs and preserve their usefulness. To achieve this goal, antibiotic management must evolve from overly simplistic antibiotic cost containment to more complex, multidisciplinary, appropriate use programs that are founded on clinical outcomes‐based pharmacoeconomic analyses. This article addresses common cost‐containment activities as they relate to antibiotics and examines their consequences. Examples of successful antimicrobial stewardship and the role of pharmacoeconomic analyses also are provided. Cost‐effectiveness studies of cefepime are presented to illustrate the utility of these analyses and provide information that can form the basis for decisions regarding placement of cefepime on hospital formularies.
The HCR–20 and post‐discharge outcome in male patients discharged from medium security in the UK
Authors: Dolan Mairead , Khawaja Afshan
Published: November 2004

The Historical Clinical Risk–20 (HCR–20) [Webster et al., 1997a,b] is a structured clinical judgement 20–item risk assessment scale, which was developed for use in Canadian forensic facilities. Data on the HCR–20 in UK samples is limited. We examined the predictive validity of the HCR–20 in relation to post‐discharge outcomes in male medium secure patients who had a history of violent offending. HCR–20 scores (omitting the psychopathy item) at the point of discharge were rated in 70 violent patients released into the community using case file data. Relationships between post‐discharge outcomes (reconviction, readmission, self/collateral reports of violence) over a minimum two‐year follow‐up period were rated blind to the HCR–20 score and examined using a variety of risk prediction statistics. HCR–20 score did not predict reconviction, but was a significant predictor of readmission and self/collateral reports of violence. Subscale analyses indicated that all subscales had predictive validity. High scores on the Historical items were better at predicting who would have poor outcome. High scores on the Clinical and Risk scales were better at predicting how long an individual remained at liberty in the community following discharge. The findings suggest that the HCR–20, without the psychopathy rating, is a reasonably robust predictor of self‐reported violence and readmission in medium secure services. Our finding that it did not predict violent recidivism reflects the utility of this measure in the management of risk in violent patients discharged to the community. Aggr. Behav. 30:469–483, 2004. © 2004 Wiley‐Liss, Inc.
Aggressive encounters between patients and general hospital staff: Staff perceptions of the context and assailants' levels of cognitive processing
Authors: Winstanley Sue , Whittington Richard
Published: November 2004

A considerable body of research has accumulated regarding aggression toward health care staff, yet little is known about the contextual factors involved. The present study examined the context within which aggressive incidents occurred and the dynamics of the interaction between staff and patients. Two aspects in particular were investigated; firstly, whether incidents were preceded by some anxiety provoking stimulus and secondly, the assailants' levels of cognitive processing apparent at the time of the incident. A prospective study collected data concerning incidents of physical assault and threatening behaviour in a general hospital. Staff were interviewed soon after the incident occurred. A content analysis determined that 82.8% of incidents involved experiences delivered by the staff victims likely to have provoked anxiety in the assailant. Most commonly, incidents involved staff intervening in the patient's intended behaviour. In addition, in 64% of cases, assailants were actually displaying some impairment in cognitive processing at the time of the incident Data suggest that many patients may not have been fully aware of their situation and might have experienced some difficulty in comprehending the staff member's actions. Patients who do not appear to understand what is happening may require additional time and effort to ensure they comprehend fully and accept what the staff member is intending to do, particularly if patients are experiencing an event likely to increase anxiety levels. Aggr. Behav. 30:534–543, 2004. © 2004 Wiley‐Liss, Inc.
Student as Teacher: the Insiders’ View of Peer Instruction
Authors: Boice-Pardee Heath P. , Shirvanian Daniel S.
Published: November 2004

Rutgers College, the oldest college of Rutgers, The State University of New Jersey, relies solely on peer instructors to teach its first-year seminar course. The authors offer a look inside the selection and training of these peer instructors and share the students’ thoughts on their experiences.
High‐Temperature Speciation Studies of Al‐Ion Hydrolysis
Authors: Shafran K. , Deschaume O. , Perry C.C.
Published: November 2004

Preliminary results of a multi‐technique study for Al‐ion speciation are presented for the formation of large aluminium polycations. Information on the reaction pathway may aid the development of routes to solutions containing single species that can be used in model studies to investigate the effects of aluminium in the environment as well as for the generation of Al‐containing materials from molecular scale precursors.
Microstructural and Mechanical Properties of Zinc Die Casting Alloys
Authors: Gelfi M. , Bontempi E. , Pola A. , Roberti R. , Rollez D. , Depero L.E.
Published: November 2004

Microstructure and tensile properties of thin walled zinc diecasting alloys have been studied by means of X‐Ray microdiffraction, metallographic analysis and tensile tests in order to evaluate the correlation between the elastic modulus and the component thickness. Results revealed a strong influence of skin layer microstructure on samples stiffness.