bluuebunny/crossref_metadata_2025 huggingface dataset:
Chloroquine poisoning in Zimbabwe: a toxicoepidemiological study
Authors: Ball D. E. , Tagwireyi D. , Nhachi C. F. B.
Published: October 2002

Chloroquine is commonly implicated in pharmaceutical poisonings in Zimbabwe. A retrospective hospital record review was performed to describe the epidemiology of chloroquine poisoning compared with that of other medicines. All records of admissions to eight referral hospitals in Zimbabwe due to poisoning with single pharmaceutical agents were collated and separated into those involving either chloroquine or other medicines. Case characteristics were compared and a retrospective cohort study performed to investigate the association of pregnancy with chloroquine overdose. Of 544 cases, antimalarials accounted for the largest proportion of admissions (53.1%), with chloroquine accounting for 96.2% (279 cases) of these. The latter were compared with the remaining 265 cases. The median length of hospital stay for the chloroquine group was significantly lower (1 vs 2 days; P = 0.001) and a greater proportion of patients took chloroquine deliberately (80.3% vs 68.7%; P < 0.05). The mortality rate due to chloroquine poisoning was significantly higher than that of poisoning due to other drugs (5.7% vs 0.7%; P < 0.0001). There was no significant gender bias in mortality. Women of childbearing age admitted with chloroquine poisoning (188 cases) were twice as likely to be found pregnant (relative risk = 2.3, 95% CI = 1.2–4.5) than similar women admitted due to other medicines (157 cases).

In conclusion, chloroquine is the most common cause of pharmaceutical poisoning admission at referral hospitals in Zimbabwe. It is normally taken deliberately with significant mortality. In women of childbearing age admitted with chloroquine poisoning, pregnancy should be suspected. Copyright © 2002 John Wiley & Sons, Ltd.
The roles of types XII and XIV collagen in fibrillogenesis and matrix assembly in the developing cornea
Authors: Young Blanche B. , Zhang Guiyun , Koch Manuel , Birk David E.
Published: October 2002

Corneal transparency depends on the architecture of the stromal extracellular matrix, including fibril diameter, packing, and lamellar organization. The roles of collagen types XII and XIV in regulation of corneal fibrillogenesis and development were examined. The temporal and spatial expression patterns were analyzed using semi‐quantitative RT‐PCR, in situ hybridization, Western analysis, and immunohistochemistry. Expression of types XII and XIV collagens in cornea development demonstrated that type XII collagen mRNA levels are constant throughout development (10D‐adult) while type XIV mRNA is highest in early embryonic stages (10D–14D), decreasing significantly by hatching. The spatial expression patterns of types XII and XIV collagens demonstrated a homogeneous signal in the stroma for type XIV collagen, while type XII collagen shows segregation to the sub‐epithelial and sub‐endothelial stroma during embryonic stages. The type XII collagen in the anterior stroma was an epithelial product during development while fibroblasts contributed in the adult. Type XIV collagen expression was highest early in development and was absent by hatching. Both types XII and type XIV collagen have different isoforms generated by alternative splicing that may alter specific interactions important in fibrillogenesis, fibril–fibril interactions, and higher order matrix assembly. Analysis of these splice variants demonstrated that the long XII mRNA levels were constant throughout development, while the short XII NC3 mRNA levels peaked early (12D) followed by a decrease. Both type XIV collagen NC1 splice variants are highest during early stages (12D–14D) decreasing by 17D of development. These data suggest type XII collagen may have a role in development of stromal architecture and maintenance of fibril organization, while type XIV collagen may have a role in regulation of fibrillogenesis. J. Cell. Biochem. 87: 208–220, 2002. © 2002 Wiley‐Liss, Inc.
Analysis of the intermolecular interaction between CH3OCH3, CF3OCH3, CF3OCF3, and CH4: High levelab initiocalculations
Authors: Urata Shingo , Tsuzuki Seiji , Mikami Masuhiro , Takada Akira , Uchimaru Tadafumi , Sekiya Akira
Published: October 2002

The intermolecular interaction energies of the CH3OCH3CH4, CF3OCH3CH4, and CF3OCF3CH4systems were calculated byab initiomolecular orbital method with the electron correlation correction at the second order Møller–Plesset perturbation (MP2) method. The interaction energies of 10 orientations of complexes were calculated for each system. The largest interaction energies calculated for the three systems are −1.06, −0.70, and −0.80 kcal/mol, respectively. The inclusion of electron correlation increases the attraction significantly. It gains the attraction −1.47, −1.19, and −1.27 kcal/mol, respectively. The dispersion interaction is found to be the major source of the attraction in these systems. In the CH3OCH3CH4system, the electrostatic interaction (−0.34 kcal/mol) increases the attraction substantially, while the electrostatic energies in the other systems are not large. Fluorine substitution of the ether decreases the electrostatic interaction, and therefore, decreases the attraction. In addition the orientation dependence of the interaction energy is decreased by the substitution. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 1472–1479, 2002
Effects of three types of potentially biasing information on symptom severity judgments for major depressive episode
Authors: Mumma Gregory H.
Published: October 2002

Two experiments examined the effects of potentially biasing information on judgments of symptom severity pertaining to the diagnosis of major depressive episode (MDE). In both experiments, clinicians viewed videotapes of two actor‐simulated patients responding to questions from a standardized diagnostic interview. In Study 1, an expectancy effect was found for both patients such that prior information about a clear‐cut history of depression resulted in lower rated severity of current symptoms. In addition, a halo effect was observed for one patient in Study 1 and both patients in Study 2: Clear‐cut depressive nonverbal behavior (DNVB) resulted in greater rated severity for symptoms that should not have been affected (e.g., appetite/weight change, suicidal ideation). Clear‐cut versus near‐threshold information for the two essential criteria for MDE did not affect subsequent judgments in either study. Implications for diagnostic interviewing are discussed. © 2002 Wiley Periodicals, Inc. J Clin Psychol 58: 1327–1345, 2002.
Community sector and gender differences in the perception of community‐based prevention
Authors: Riggs Nathaniel R. , Feinberg Mark E. , Greenberg Mark T.
Published: October 2002

Community‐based collaborative prevention often relies on the cooperation of individuals from different community sectors. The attitudes of those associates regarding certain domains of collaborative prevention may influence the degree to which this collaboration is successful. The current study is an analysis of the attitudes of 196 designated leaders (key leaders) in 21 communities of the Pennsylvania Communities That Care (CTC) Project. Questions examined include whether key leaders differ by community sector and/or gender in their perceptions of prevention‐related issues. ANOVAs were carried out to determine whether there were such group differences, and results demonstrate that collaborators do in fact vary by both community sector and gender with respect to their attitudes toward domains related to prevention. One implication is that differences in these attitudes should be recognized when establishing and constructing collaborative boards. © 2002 Wiley Periodicals, Inc.
Defining the nature of participation in rural Australian communities: A qualitative approach
Authors: Coakes Sheridan J. , Bishop Brian J.
Published: October 2002

Within the literature, theories and analyses of social involvement or participation have focussed primarily on the political and formal role of participation within the community or neighborhood. This study illustrates, through qualitative inquiry, that within small rural communities, individuals find it difficult to separate formal and informal participation, when both have an equally important role to play in community life. Fifty‐five structured interviews were conducted with women across six rural shires in the southwest region of Western Australia. Qualitative analysis revealed that approximately 50% of women, when asked about their involvement in their community, referred initially to their informal participation within the community, rather than their participation in formal community groups or associations. These results are discussed in relation to life in small rural towns. © 2002 Wiley Periodicals, Inc.
Migration of an intrauterine contraceptive device to the urinary bladder: Sonographic findings
Authors: Mahmutyazıcıoğlu Kamran , Özdemir Hüseyin , Özkan Perihan
Published: October 2002

Migration of an intrauterine contraceptive device (IUD) to the urinary bladder is very rare. We describe a case in which transabdominal sonography demonstrated such migration of an IUD in a 30‐year‐old woman who sought treatment for pelvic pain and dysuria. The IUD had originally been inserted 10 years earlier, and the patient had given birth without complications 2 years before the onset of her symptoms. Cytoscopic examination confirmed the diagnosis and allowed removal of the IUD. © 2002 Wiley Periodicals, Inc. J Clin Ultrasound 30:496–498, 2002; Published online in Wiley InterScience (www.interscience.wiley. com). DOI: 10.1002/jcu.10098
Melanoma development and pigment cell transformation in xiphophorus
Authors: Wellbrock Claudia , Gómez Ana , Schartl Manfred
Published: October 2002

As early as 1927, it was recognised that hybridisation of platyfish (Xiphophorus maculatus) and swordtails (Xiphophorus helleri) results in offspring that develop tumours according to Mendelian laws. Most obviously, the primary event, namely the cell lineage‐specific overexpression of a structurally altered receptor tyrosine kinase, finds its parallel in many tumours of birds and mammals. Once expressed at high levels, this receptor, the Xiphophorus melanoma inducing receptor kinase Xmrk, shows constitutive activation. By using different pathways, Xmrk induces both proliferative as well as anti‐apoptotic signalling in pigment cells finally leading to cell transformation, tumour induction, and progression. Analyses of the different signalling cascades induced by the Xmrk‐receptor led to the identification of the src‐kinase Fyn, the MAP kinases ERK1 and ERK2, the “Signal Transducer and Activator of Transcription” STAT5, and the PI3‐kinase as its major downstream substrates. This review describes some of the genetic findings, as well as the results from the recent molecular analyses of the factors involved in the initiation and manifestation of pigment cell transformation and melanoma development in Xiphophorus. Microsc. Res. Tech. 58:456–463, 2002. © 2002 Wiley‐Liss, Inc.
Morphological color changes in fish: Regulation of pigment cell density and morphology
Authors: Sugimoto Masazumi
Published: October 2002

Pigment cells enable fish to change their coloration. It has been recognized that fish color changes can be divided into two categories; one is a physiological color change, which is attributed to rapid motile responses of chromatophores, and the other is a morphological color change, which results from changes in the morphology and density of chromatophores. Long‐term adaptation of fish to a certain background can be a general cue to morphological color changes, and has been studied from the beginning of the 19th century. Although the motile mechanism and its control in fish chromatophores are now being elucidated, it is not yet clear how chromatophores change their density and what controls morphological color changes. In recent years, chromatophores, especially melanophores, have been shown to differentiate and to die by apoptosis under the influence of factors that regulate motile responses. Those factors are likely to utilize common intracellular signaling pathways used in part to regulate both types of color changes. In this article, after briefly reviewing the history of early studies, recent findings are discussed relevant to increases or decreases in chromatophores, and changes in their morphology. Finally, morphological color changes are discussed as physiological phenomena involved in the balance between differentiation and apoptosis of chromatophores. Microsc. Res. Tech. 58:496–503, 2002. © 2002 Wiley‐Liss, Inc.
Protein kinases in mammary gland development and cancer
Authors: Kumar Rakesh , Wang Rui‐An
Published: October 2002

Protein kinases, the enzymes responsible for phosphorylation of a wide variety of proteins, are the largest class of genes known to regulate growth, development, and neoplastic transformation of mammary gland. Mammary gland growth and maturation consist of a series of highly ordered events involving interactions among several distinct cell types that are regulated by complex interactions among many steroid hormones and growth factors. The mammary gland is one of the few organ systems in mammals that complete their morphologic development postnatally during two discrete physiologic states, puberty and pregnancy. Thus, the mammary gland is an excellent model for studying normal development and the early steps of tumor formation. The susceptibility of the mammary gland to tumorigenesis is influenced by its normal development, particularly during stages of puberty and pregnancy. Numerous experimental and epidemiological studies have suggested that specific details in the development of the mammary gland play a critical role in breast cancer risk. Mammary gland development is characterized by dynamic changes in the expression and functions of protein kinases. Perturbations in the regulated expression or function of protein kinases or their associated signaling pathways can lead to malignant transformation of the breast. For example, overexpression of several receptor‐tyrosine kinases, including human epidermal growth factor receptor and HER2/Neu, has been shown to contribute to the development of breast cancer. Since receptor‐tyrosine kinases regulate several essential processes such as mitogenesis, motility, invasion, cell survival, and angiogenesis, targeting receptor‐tyrosine kinases may have important implications in designing strategies against breast cancer. Microsc. Res. Tech. 59:49–57, 2002. © 2002 Wiley‐Liss, Inc.
It's not just about anatomy: In vivo bioluminescence imaging as an eyepiece into biology
Authors: Contag Christopher H. , Ross Brian D.
Published: October 2002

Among the newly described tools that enable analyses of cellular and molecular events in living animals, in vivo bioluminescence imaging (BLI) offers important opportunities for investigating a wide variety of disease processes. BLI utilizes luciferase as an internal biological light source that can be genetically programmed to noninvasively “report” the presence or activation of specific biological events. Applications of BLI have included the use of luciferase to demonstrate expression of cell‐ and tissue‐specific promoters, label cell populations, guide detection by other imaging modalities, and detect protein‐protein interaction. These applications of BLI technology have allowed quantitative measurements of tumor burden and treatment response, immune cell trafficking, and detection of gene transfer. Spatiotemporal information can be rapidly obtained in the context of whole biological systems in vivo, which can accelerate the development of experimental therapeutic strategies. This paper provides a review of the biological applications in which in vivo BLI has been utilized to nondestructively monitor biological processes in intact small animal models, and highlights some of the advancements that will increase the versatility of BLI as a molecular imaging tool. J. Magn. Reson. Imaging 2002;16:378–387. © 2002 Wiley‐Liss, Inc.
Insights into the use of paramagnetic Gd(III) complexes in MR‐molecular imaging investigations
Authors: Aime Silvio , Cabella Claudia , Colombatto Sebastiano , Geninatti Crich Simonetta , Gianolio Eliana , Maggioni Fabio
Published: October 2002

Can gadolinium III [Gd(III)] complexes be considered good candidates for magnetic resonance (MR)‐molecular imaging studies? In this review article, we examine the principal issues that are the basis of successful use of Gd‐based protocols in molecular imaging applications. High relaxivity is the primary requisite. Therefore, the design of such paramagnetic probes has to be pursued keeping in mind the relationships between structure, dynamics, and the relevant parameters involved in paramagnetic relaxation processes. Moreover, the limited number of target molecules on cellular membranes makes it necessary to define strategies aimed at delivering many Gd‐containing moieties to the sites of interest. Examples are reported for the attainment of very high relaxivities for the design of new routes for pursuing the accumulation of small sized Gd(III) complexes at the targeting sites. An efficient cellular uptake of Gd‐containing probes is the key step for attaining the visualization of targeted cells by MR imaging, and selected examples are reported. In this context, the problem of the assessment of the minimum amount of Gd(III) complexes necessary for the MR imaging‐visualization of cells has been addressed by reporting the authors' observations on the cell‐internalization of Gd(III) complexes. A particularly efficient delivery system is represented by Gd‐loaded apoferritin, which allows the MR visualization of hepatocytes when the number of Gd‐complexes per cell is 4 ± 1 × 107. Finally, the potential of responsive systems is considered by outlining the exploitation of the amplification effect brought about by the action of a specific enzymatic activity on the relaxivity of a suitably functionalized Gd(III) complex. J. Magn. Reson. Imaging 2002;16:394–406. © 2002 Wiley‐Liss, Inc.
A stable subcell model for arbitrarily oriented thin wires for the FDTD method
Authors: Ledfelt G.
Published: October 2002

Thin‐wire subcell models are widely used to allow the FDTD method to take wires thinner than the cell size into account. In this paper, a subcell model is generalized to handle arbitrarily oriented thin wires in an accurate way. The coupling of the Maxwell equations and the wire equations is discussed in detail. Stability of the subcell model is also shown and results for dipole antennas and loop antennas illustrates the performance of the new subcell model. Copyright © 2002 John Wiley & Sons, Ltd.
Time‐domain prediction of the radiated susceptibility in a shielded cable inside a penetrable shielded box
Authors: Feliziani Mauro , Maradei Francescaromana
Published: October 2002

The radiated susceptibility of a shielded cable inside a penetrable shielded enclosure is analysed by a numerical procedure based on the finite‐difference time‐domain (FDTD) method. Impedance network boundary conditions (INBCs) are used to model the field penetration through the shield. The induced effects of the field‐excited shielded cable are analysed by using a hybrid technique based on the FDTD method and on the multiconductor transmission line (MTL) model. Application examples are given. Copyright © 2002 John Wiley & Sons, Ltd.
Gene expression profiling in developing human hippocampus
Authors: Zhang Yan , Mei Pinchao , Lou Rong , Zhang Michael Q. , Wu Guanyun , Qiang Boqin , Zhang Zhengguo , Shen Yan
Published: October 2002

The gene expression profile of developing human hippocampus is of particular interest and importance to neurobiologists devoted to development of the human brain and related diseases. To gain further molecular insight into the developmental and functional characteristics, we analyzed the expression profile of active genes in developing human hippocampus. Expressed sequence tags (ESTs) were selected by sequencing randomly selected clones from an original 3′‐directed cDNA library of 150‐day human fetal hippocampus, and a digital expression profile of 946 known genes that could be divided into 16 categories was generated. We also used for comparison 14 other expression profiles of related human neural cells/tissues, including human adult hippocampus. To yield more confidence regarding differential expression, a method was applied to attach normalized expression data to genes with a low false‐positive rate (<0.05). Finally, hierarchical cluster analysis was used to exhibit related gene expression patterns. Our results are in accordance with anatomical and physiological observations made during the developmental process of the human hippocampus. Furthermore, some novel findings appeared to be unique to our results. The abundant expression of genes for cell surface components and disease‐related genes drew our attention. Twenty‐four genes are significantly different from adult, and 13 genes might be developing hippocampus‐specific candidate genes, including wnt2b and some Alzheimer's disease‐related genes. Our results could provide useful information on the ontogeny, development, and function of cells in the human hippocampus at the molecular level and underscore the utility of large‐scale, parallel gene expression analyses in the study of complex biological phenomena. © 2002 Wiley‐Liss, Inc.
Functional expression of CCR2 by human fetal astrocytes
Authors: Andjelkovic Anuska V. , Song Li , Dzenko Kirk A. , Cong Hui , Pachter Joel S.
Published: October 2002

Astrocytes from different sources bind the chemokine monocyte chemoattractant factor (MCP‐1), yet functional expression in these cells of CCR2, the major receptor for this ligand, has been a matter of controversy. Here we show that cultured human fetal astrocytes express CCR2 at the mRNA and protein levels, and display chemotaxis and calcium flux in response to MCP‐1. Surface CCR2 protein expression and MCP‐1 binding activity were observed to undergo near parallel downmodulation and recovery following MCP‐1 exposure, supporting the argument that CCR2, and not another receptor, mediates MCP‐1 ligation in these cells. Downmodulation was further determined to occur via receptor internalization, and to apparently proceed via both clathrin‐coated vesicles and caveolae, the latter being a novel mode for the endocytosis of chemokine receptors. Insofar as MCP‐1 is thought to mediate inflammatory and developmental processes within the central nervous system (CNS), such astrocyte responses to this chemokine are likely to significantly impact physiological and pathophysiological events at the blood‐brain barrier and within the CNS parenchyma. © 2002 Wiley‐Liss, Inc.
Glutamate‐dependent transcriptional regulation of the chkbp gene: Signaling mechanims
Authors: Aguirre Adán , López‐Bayghen Esther , Ortega Arturo
Published: October 2002

Glutamate, the major excitatory neurotransmitter, induces a signal from the membrane to the nucleus that regulates gene expression. The gene encoding the chick kainate binding protein undergoes a glutamate‐dependent transcriptional regulation via an activator protein‐1 site within its promoter region. To characterize this event, cultured chick Bergmann glia cells were exposed to glutamate, and a dose‐dependent increase in promoter activity was established. The glutamate effect is mediated through Ca2+‐permeable α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid/kainate receptors. The signaling cascade includes phosphatidyl inositol 3‐kinase, Ca2+/calmodulin‐dependent protein kinase II, mitogen‐activated protein kinase, and p90 ribosomal S6 kinase activation. The cAMP response‐element binding protein becomes phosphorylated and activates fos transcription. Finally, the activator protein‐1 complex binds to the glutamate response element in the chick kainate binding protein promoter region inducing its activity. We propose that the mitogen‐activated protein kinase/p90 ribosomal S6 kinase pathway plays a critical role in glutamate‐induced gene transcription. © 2002 Wiley‐Liss, Inc.
Micromechanical analysis of silicon nitride: a comparative study by fracture mechanics and Raman microprobe spectroscopy
Authors: Tochino Shigemi , Pezzotti Giuseppe
Published: October 2002

Raman microprobe spectroscopy was used to characterize in situ microstress fields which develop during fracture of a toughened silicon nitride (Si3N4) polycrystal. Maps of microscopic stress were collected in the neighborhood of a propagating crack both at zero and at critical loading conditions. Micromechanics results by Raman spectroscopy were analyzed and compared with conventional fracture mechanics assessments, such as the evaluation of rising R‐curve behavior and crack opening displacement. Outcomes of these assessments illustrate that, despite the approximations involved in the piezo‐spectroscopic equations used for calculating the microstress field from a local Raman shift, Raman microprobe spectroscopy is a viable method for semi‐quantitative investigations of microfracture mechanisms in advanced ceramic materials. Copyright © 2002 John Wiley & Sons, Ltd.
Anthocyanins in fruits of Prunus padus (bird cherry)
Authors: Kucharska Alicja Z , Oszmiański Jan
Published: October 2002

Bird cherry (Prunus padus) anthocyanins were extracted with acidified methanol, fractionated by column chromatography on Toyopearl HW40(S) and purified in a C‐18 Sep‐Pak cartridge. The pigment composition was very simple, as there were only two compounds. The anthocyanins cyanidin‐3‐rutinoside (60%) and cyanidin‐3‐glucoside (40%) were determined using chromatographic and spectroscopic methods.

© 2002 Society of Chemical Industry
An experimental paradigm for studying the cellular and molecular mechanisms of cancer inhibition by energy restriction
Authors: Zhu Zongjian , Jiang Weiqin , Thompson Henry J.
Published: October 2002

With a rapid‐emergence, chemically induced animal model for breast cancer, an experiment designed to test the hypothesis that energy restriction (ER) induces the loss of carcinogen‐initiated cells from the mammary gland, thereby conferring a permanent protective effect against the development of cancer, failed to support this hypothesis. Nonetheless, this experiment served to define an experimental approach and a time frame on which to focus mechanistic inquiry. With an ER and energy repletion (ER‐REP) protocol as a tool for identifying potential mediators of the cancer‐inhibitory activity of ER, concomitant changes in plasma corticosterone and insulin‐like growth factor 1 during energy restriction and repletion were observed. The relationship of the timing of these hormonal changes to the time frame of change in the carcinogenic response during ER‐REP was consistent with the role of both hormones in mediating the protective effects of ER. However, a similar pattern of change in the energy‐regulated hormone leptin indicated that its role in cancer inhibition also merits consideration. © 2002 Wiley‐Liss, Inc.
Anticardiolipin antibody in vascular parkinsonism
Authors: Huang Zhigao , Jacewicz Michael , Pfeiffer Ronald F.
Published: October 2002

Vascular parkinsonism (VP) is characterized by predominantly lower body involvement with gait impairment and postural instability, often without tremor, and by relative levodopa unresponsiveness. Neuroimaging studies demonstrate multiple infarcts or ischemic changes in periventricular white matter. Anticardiolipin antibodies (ACLA) are associated with hypercoagulable states and increased stroke risk. Review of our Movement Disorders Clinic records identified 44 individuals with a diagnosis of VP. ACLA have been obtained in 22 of these patients (mean age, 78.3 years; mean Mini‐Mental Status Exam score, 25.8). Gait disturbance was the initial clinical feature in 82% of the patients, and levodopa responsiveness was present in 18% of those treated. In 9 of the 22 (40.9%), ACLA immunoglobulin G was positive. No significant differences in clinical features or risk factors (hypertension, diabetes, coronary artery disease, and clinical stroke) were evident between ACLA+ and ACLA− groups. Since the presence of ACLA in individuals with stroke is usually treated by full‐scale anticoagulation with warfarin, our findings raise the question whether such treatment should also be used in persons with VP who are ACLA positive. © 2002 Movement Disorder Society
Quantitative description of loss of clinical benefit following withdrawal of levodopa–carbidopa and bromocriptine in early Parkinson's disease
Authors: Hauser Robert A. , Holford Nicholas H.G.
Published: October 2002

In Parkinson's disease, effects of medications on the progression of the underlying disease can be assessed clinically by evaluating patients at baseline prior to treatment and at endpoint following medication washout. With this design, it is critical to employ a washout of sufficient duration to ensure elimination of all symptomatic effects. To assess the time course of resolution of symptomatic effects, we evaluated 31 patients with early Parkinson's disease for 2 weeks following discontinuation of levodopa–carbidopa and bromocriptine after 14 months of treatment. Patients had previously been randomly assigned to treatment with selegiline or placebo, and these had been discontinued 2 months earlier. Data from 20 patients with a clear washout of clinical benefit were used to investigate quantitative models describing the time course of total (Activities of Daily Living + motor) Unified Parkinson's Disease Rating Scale score change. The mean half‐life of loss of clinical benefit was 7.9 days (95% confidence interval, 2.2–30.4 days). This indicates that a washout period of 32 days (4 half‐lives) may be required to eliminate approximately 90% of the long‐term symptomatic effects of levodopa–carbidopa and bromocriptine following their withdrawal from patients with early Parkinson's disease. © 2002 Movement Disorder Society
New anti‐HIV agents and targets
Authors: Clercq Erik De
Published: October 2002

Virtually all the compounds that are currently used or are subject of advanced clinical trials for the treatment of HIV infections, belong to one of the following classes: (i) nucleoside reverse transcriptase inhibitors (NRTIs): i.e., zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir, emtricitabine and nucleotide reverse transcriptase inhibitors (NtRTIs) (i.e., tenofovir disoproxil fumarate); (ii) non‐nucleoside reverse transcriptase inhibitors (NNRTIs): i.e., nevirapine, delavirdine, efavirenz, emivirine; and (iii) protease inhibitors (PIs): i.e., saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, and lopinavir. In addition to the reverse transcriptase and protease reaction, various other events in the HIV replicative cycle can be considered as potential targets for chemotherapeutic intervention: (i) viral adsorption, through binding to the viral envelope glycoprotein gp120 (polysulfates, polysulfonates, polycarboxylates, polyoxometalates, polynucleotides, and negatively charged albumins); (ii) viral entry, through blockade of the viral coreceptors CXCR4 (i.e., bicyclam (AMD3100) derivatives) and CCR5 (i.e., TAK‐779 derivatives); (iii) virus–cell fusion, through binding to the viral envelope glycoprotein gp41 (T‐20, T‐1249); (iv) viral assembly and disassembly, through NCp7 zinc finger‐targeted agents [2,2′‐dithiobisbenzamides (DIBAs), azadicarbonamide (ADA)]; (v) proviral DNA integration, through integrase inhibitors such as 4‐aryl‐2,4‐dioxobutanoic acid derivatives; (vi) viral mRNA transcription, through inhibitors of the transcription (transactivation) process (flavopiridol, fluoroquinolones). Also, various new NRTIs, NNRTIs, and PIs have been developed that possess, respectively: (i) improved metabolic characteristics (i.e., phosphoramidate and cyclosaligenyl pronucleotides by‐passing the first phosphorylation step of the NRTIs), (ii) increased activity [“second” or “third” generation NNRTIs ( i.e., TMC‐125, DPC‐083)] against those HIV strains that are resistant to the “first” generation NNRTIs, or (iii), as in the case of PIs, a different, modified peptidic (i.e., azapeptidic (atazanavir)) or non‐peptidic scaffold (i.e., cyclic urea (mozenavir), 4‐hydroxy‐2‐pyrone (tipranavir)). Non‐peptidic PIs may be expected to inhibit HIV mutant strains that have become resistant to peptidomimetic PIs. © 2002 Wiley Periodicals, Inc. Med Res Rev, 22, No. 6, 531–565, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/med.10021
High angular resolution diffusion imaging reveals intravoxel white matter fiber heterogeneity
Authors: Tuch David S. , Reese Timothy G. , Wiegell Mette R. , Makris Nikos , Belliveau John W. , Wedeen Van J.
Published: October 2002

Magnetic resonance (MR) diffusion tensor imaging (DTI) can resolve the white matter fiber orientation within a voxel provided that the fibers are strongly aligned. However, a given voxel may contain a distribution of fiber orientations due to, for example, intravoxel fiber crossing. The present study sought to test whether a geodesic, highb‐value diffusion gradient sampling scheme could resolve multiple fiber orientations within a single voxel. In regions of fiber crossing the diffusion signal exhibited multiple local maxima/minima as a function of diffusion gradient orientation, indicating the presence of multiple intravoxel fiber orientations. The multimodality of the observed diffusion signal precluded the standard tensor reconstruction, so instead the diffusion signal was modeled as arising from a discrete mixture of Gaussian diffusion processes in slow exchange, and the underlying mixture of tensors was solved for using a gradient descent scheme. The multitensor reconstruction resolved multiple intravoxel fiber populations corresponding to known fiber anatomy. Magn Reson Med 48:577–582, 2002. © 2002 Wiley‐Liss, Inc.
Update on the glutamatergic neurotransmitter system and the role of excitotoxicity in amyotrophic lateral sclerosis
Authors: Heath Paul R. , Shaw Pamela J.
Published: October 2002

Excitotoxicity may play a role in certain disorders of the motor system thought to be caused by environmentally acquired toxins, including lathyrism and domoic acid poisoning. Motor neurons appear to be particularly susceptible to toxicity mediated via α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA)–kainate receptors. There is a body of evidence implicating glutamatergic toxicity as a contributory factor in the selective neuronal injury occurring in amyotrophic lateral sclerosis (ALS). Interference with glutamate‐mediated toxicity is so far the only neuroprotective therapeutic strategy that has shown benefit in terms of slowing disease progression in ALS patients. Biochemical studies have shown decreased glutamate levels in central nervous system (CNS) tissue and increased levels in the cerebrospinal fluid (CSF) of ALS patients. CSF from ALS patients is toxic to neurons in culture, apparently via a mechanism involving AMPA receptor activation. There is evidence for altered expression and function of glial glutamate transporters in ALS, particularly excitatory amino acid transporter 2 (EAAT2). Abnormal splice variants of EAAT2 have been detected in human CNS. Mitochondrial dysfunction may contribute to excitotoxicity in ALS. Induction of neuronal nitric oxide synthase and cyclooxygenase 2 in ALS may also lead to significant interactions with regulation of the glutamate transmitter system. Certain features of motor neurons may predispose them to the neurodegenerative process in ALS, such as the cell size, mitochondrial activity, neurofilament content, and relative lack of certain calcium‐binding proteins and molecular chaperones. Motor neurons appear vulnerable to toxicity mediated by calcium‐permeable AMPA receptors. The relatively low expression of the glutamate receptor 2 (GluR2) AMPA receptor subunit and the high current density caused by the large number and density of cell surface AMPA receptors are potentially important factors that may predispose to such toxicity. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 438–458, 2002
Biopsy sampling requirements for the estimation of muscle capillarization
Authors: Porter Michelle M. , Koolage Chris W. , Lexell Jan
Published: October 2002

The aim of this study was to determine the number of tibialis anterior biopsy samples and muscle fibers required to estimate the capillary supply of individual muscle fibers (C:Fi). C:Fi was calculated for 25 type 1 fibers in each of 8 images from 3 biopsies of 5 young healthy individuals. Sequential estimation analysis indicated that 50 fibers from one biopsy are sufficient to characterize the C:Fi of the tibialis anterior for a group of subjects. Thus, when analyzing the capillarization of the tibialis anterior, the requirements of only one biopsy sample and 50 fibers means a great reduction in time for analysis and in the invasiveness of the procedure. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 546–548, 2002
Electrocardiographic findings in mdx mice: A cardiac phenotype of Duchenne muscular dystrophy
Authors: Chu Victor , Otero Jose M. , Lopez Orlando , Sullivan Matthew F. , Morgan James P. , Amende Ivo , Hampton Thomas G.
Published: October 2002

The mdx mouse is a model of Duchenne muscular dystrophy (DMD). As many DMD patients die of cardiac failure, we investigated whether mdx mice exhibited clinically relevant cardiac phenotypes. We applied a recently developed method for noninvasively recording electrocardiograms (ECGs) to study male mdx mice (n = 15) and control mice (n = 15). The mdx mice had significant tachycardia and decreased heart rate variability, consistent with observations in DMD patients. Heart rate was nearly 15% faster in mdx mice than control mice (P < 0.05). The rate‐corrected QT interval duration and PR interval were shorter in mdx compared to control mice (P < 0.05). The muscarinic antagonist atropine significantly increased heart rate and decreased PR interval in C57 mice. In contrast, atropine significantly decreased heart rate and increased PR interval in all mdx mice. Pharmacological autonomic blockade and baroreflex sensitivity testing demonstrated an imbalance in autonomic nervous system modulation of heart rate, with decreased parasympathetic activity and increased sympathetic activity in mdx mice. Baseline ECGs and contrary responses to muscarinic blockade by atropine in mice deficient in neuronal nitric oxide synthase (nNOS) suggest that the autonomic dysfunction in mdx mice may be independent of decreased myocardial nNOS. These electrocardiographic findings in dystrophin‐deficient mice may provide new bases for diagnosing, understanding, and treating DMD patients. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 513–519, 2002
Randomized, controlled trial of intravenous immunoglobulin in myasthenia gravis
Authors: Wolfe Gil I. , Barohn Richard J. , Foster Barbara M. , Jackson Carlayne E. , Kissel John T. , Day John W. , Thornton Charles A. , Nations Sharon P. , Bryan Wilson W. , Amato Anthony A. , Freimer Miriam L. , Parry Gareth J.
Published: October 2002

We initiated a randomized, double‐blinded, placebo‐controlled trial of intravenous immunoglobulin (IVIG) treatment in myasthenia gravis (MG). Patients received IVIG 2 gm/kg at induction and 1 gm/kg after 3 weeks vs. 5% albumin placebo. The primary efficacy measurement was the change in the quantitative MG Score (QMG) at day 42. Fifteen patients were enrolled (6 to IVIG; 9 to placebo) before the study was terminated because of insufficient IVIG inventories. At day 42, there was no significant difference in primary or secondary outcome measurements between the two groups. In a subsequent 6‐week open‐label study of IVIG, positive trends were observed. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 549–552, 2002
Axonal neuropathy in chronic peripheral arterial occlusive disease
Authors: Weber Frank , Ziegler Andrea
Published: October 2002

Chronic peripheral arterial occlusive disease of the lower limbs may cause tissue damage. Type and extent of peripheral nerve involvement is controversial. We examined 25 patients with peripheral arterial occlusive disease in various grades of severity and 37 age‐matched healthy controls using conventional angiography and motor and sensory nerve conduction tests. Subjects with confounding factors for peripheral neuropathies were excluded. We found prolongation of distal motor latencies, decrease of motor and sensory nerve conduction velocities, and reduction in amplitude of the compound muscle action potential. Amplitudes of the compound muscle action potentials were lower in patients with pain at rest than in patients with intermittent claudication and decreased with increasing neurological disability score. Sural nerve conduction velocity, peroneal nerve F‐wave chronodispersion, and tibial nerve F‐wave persistence were the most frequent abnormal findings. Therefore we concluded that chronic peripheral arterial occlusive disease causes axonal degeneration, resulting in axonal polyneuropathy. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 471–476, 2002
Altered regional brain glucose metabolism in Duchenne muscular dystrophy: A pet study
Authors: Lee Joon Soo , Pfund Zoltán , Juhász Csaba , Behen Michael E. , Muzik Otto , Chugani Diane C. , Nigro Michael A. , Chugani Harry T.
Published: October 2002

The basis for cognitive impairment in Duchenne muscular dystrophy (DMD) is not well understood but may be related to abnormal expression of dystrophin in brain. The aim of this study was to determine whether regional brain glucose metabolism is altered in children with DMD and whether such metabolic disturbances are localized to regions shown to be normally rich in dystrophin expression. Ten boys (mean age, 11.8 years) with DMD and 17 normal adults as a control group (mean age, 27.6 years) underwent 2‐deoxy‐2[18F]fluoro‐D‐glucose positron emission tomography (PET) and neuropsychological evaluation. The PET data were analyzed by statistical parametric mapping (SPM). The SPM analysis showed five clusters of decreased glucose metabolism in children with DMD, including the

medial temporal structures and cerebellum bilaterally and the sensorimotor and lateral temporal cortex on the right side. At the voxel level, significant glucose hypometabolism was found in the right postcentral and middle temporal gyri, uncus, and VIIIB cerebellar lobule, as well as in the left hippocampal gyrus and cerebellar lobule. The neuropsychological profile of the DMD group revealed borderline nonverbal intellectual functioning, impaired manual dexterity bilaterally, borderline cognitive functioning, and internalizing behavioral difficulties. Our findings demonstrate region‐specific hypometabolism, as well as cognitive and behavioral deficits in DMD children. As the regions showing hypometabolism on PET include those normally rich in dystrophin expression, it will be important to determine whether the hypometabolic regions also show cytoarchitectural abnormalities related to the lack of dystrophin. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26:506‐512, 2002
Timing of neurodegeneration and beta‐amyloid (Aβ) peptide deposition in the brain of aging kokanee salmon
Authors: Maldonado Tammy A. , Jones Richard E. , Norris David O.
Published: October 2002

Brains of kokanee salmon (Oncorhynchus nerka kennerlyi) in one of four reproductive stages (sexually immature, maturing, sexually mature, and spawning) were stained with cresyl violet and silver stain to visualize neurodegeneration. These reproductive stages correlate with increasing somatic aging of kokanee salmon, which die after spawning. Twenty‐four regions of each brain were examined. Brains of sexually immature fish exhibited low levels of neurodegeneration, whereas neurodegeneration was more marked in maturing fish and greatest in spawning fish. Neurodegeneration was present in specific regions of the telencephalon, diencephalon, mesencephalon, and rhombencephalon. Pyknotic neurons were observed in all regions previously reported to be immunopositive for Aβ. Regions that did not exhibit neurodegeneration during aging included the magnocellular vestibular nucleus, the nucleus lateralis tuberis of the hypothalamus, and Purkinje cells of the cerebellum, all of which also lack Aβ; perhaps these regions are neuroprotected. In 14 of 16 brain areas for which data were available on both the increase in Aβ deposition and pyknosis, neurodegeneration preceded or appeared more or less simultaneously with Aβ production, whereas in only two regions did Aβ deposition precede neurodegeneration. This information supports the hypothesis that Aβ deposition is a downstream product of neurodegeneration in most brain regions. Other conclusions are that the degree of neurodegeneration varies among brain regions, neurodegeneration begins in maturing fish and peaks in spawning fish, the timing of neurodegeneration varies among brain regions, and some regions do not exhibit accelerated neurodegeneration during aging. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 21–35, 2002
Aging fetal and juvenile skeletons from Roman Period Egypt using basiocciput osteometrics
Authors: Tocheri Matthew W. , Molto J. Eldon
Published: October 2002

This paper tests the use of basiocciput osteometrics against those of femoral diaphyseal length and dental development for aging fetal and juvenile skeletal remains. The study sample consists of 39 fetal and juvenile skeletons recovered from Kellis 2, a Roman Period cemetery in Dakhleh, Egypt. The results add to the corpus of data supporting the reliability of this method for use in both bioarchaeological and forensic contexts. Copyright © 2002 John Wiley & Sons, Ltd.
For richer or for poorer: Marriage as an antipoverty strategy
Authors: Thomas Adam , Sawhill Isabel
Published: October 2002

This study examines the effects of changes in family structure on children's economic well‐being.
An initial shift‐share analysis indicates that, had the proportion of children living in
female‐headed families remained constant since 1970, the 1998 child poverty rate would have been 4.4
percentage points lower than its actual 1998 level of 18.3 percent. The March 1999 Current Population Survey is
then used to conduct a second analysis in which marriages are simulated between single mothers and demographically
similar, unrelated males. The microsimulation analysis addresses some of the shortcomings of the
shift‐share approach by making it possible to account for the possibility of a shortage of marriageable
men, to control for unobservable differences between married men and women and their unmarried counterparts, and
to measure directly the effects of increases in marriage on the economic well‐being of children. Results
from the microsimulation analysis suggest that, had the proportion of children living in female‐headed
families remained constant since 1970, the child poverty rate would have been 3.4 percentage points lower than its
actual 1998 level. Among children whose mother participated in a simulated marriage, the poverty rate would have
fallen by almost two‐thirds. © 2002 by the Association for Public Policy Analysis and Management.