bluuebunny/crossref_metadata_2025 huggingface dataset:
CTNNB1 mutations and β‐catenin protein accumulation in human hepatocellular carcinomas associated with high exposure to aflatoxin B1†
Authors: Devereux Theodora R. , Stern Mariana C. , Flake Gordon P. , Yu Mimi C. , Zhang Zhen‐Quan , London Stephanie J. , Taylor Jack A.
Published: August 2002

β‐Catenin plays a key role in the Wnt signaling pathway, and mutations of CTNNB1, the gene that encodes β‐catenin, have been identified in about one‐fourth of human hepatocellular carcinomas from regions of low aflatoxin B1 exposure. In this study 62 hepatocellular carcinomas (HCCs) from people highly exposed to aflatoxin B1 in Guangxi, People's Republic of China, were laser‐capture microdissected and examined for CTNNB1 mutations. In addition, 41 of the HCCs were evaluated for the presence of the β‐catenin protein by immunohistochemical methods. Twenty of the HCCs showed positive results for β‐catenin, with strong membrane staining, while adjacent non‐neoplastic liver tissue lacked or showed only weak membrane staining. One HCC, in which a CTNNB1 mutation was not detected, showed nuclear staining for the β‐catenin protein. Mutations of CTNNB1 were identified in five HCCs. These consisted of four point mutations in the glycogen serine kinase‐3β phosphorylation region of codons 32–45 and one deletion of codons 32–38. These mutations were similar to those previously reported for human HCC, although at a lower frequency. A signature mutation profile associated with aflatoxin B1 exposure could not be identified. The immunohistochemical findings indicate a role for accumulation of β‐catenin and possibly increased Wnt signaling in aflatoxin B1–associated HCC. The low frequency of CTNNB1 mutations, however, suggests that mutation of another Wnt signaling component, such as the Wnt scaffolding protein axin or the adenomatous polyposis coli protein, both of which modulate β‐catenin stability, also may be involved in aflatoxin‐associated HCC. Published 2001 Wiley‐Liss, Inc.
Liver carcinogen aflatoxin B1 as an inducer of mitotic recombination in a human cell line
Authors: Stettler Peter Markus , Sengstag Christian
Published: August 2002

The mycotoxin aflatoxin B1 (AFB1) is one of the most potent rodent and human liver carcinogens. Upon cytochrome P450–specific metabolism, it induces mutations as well as mitotic recombination events in in vitro systems. We have found that in the lower eukaryote yeast, the recombinagenic activity of AFB1 surpasses its mutagenic activity, and we speculated on possible consequences in terms of the mechanism of liver carcinogenesis. In this study we investigated whether the recombinagenic activity of AFB1 also would be identified in human cells. To address this question, we followed the fate of a heterozygous thymidine kinase (tk) allele in the human lymphoblastoid cell line TK6 upon exposure to AFB1. Individual mutants that had lost tk activity were subjected to loss of heterozygosity analysis of the tk locus and its flanking markers. Fluorescence in situ hybridization analysis on chromosome 17 also was performed. In parallel, a similar analysis was performed on TK6 cells exposed to the alkylating agent N‐nitrosomethylurea, a well‐known classic point mutagen. Our analysis showed a difference in the molecular mechanism leading to inactivation of the tk allele upon exposure to these two mutagens. In AFB1‐exposed cells the fraction of recombination‐derived mutants predominated, whereas in N‐nitrosomethylurea–exposed cells the fraction of point mutants was higher. Thus, the recombinagenic activity of AFB1 previously identified in a lower eukaryote also was found in the human cell line TK6. Our data support the hypothesis that mitotic recombination represents a central mechanism of action in AFB1‐induced liver carcinogenesis. © 2001 Wiley‐Liss, Inc.
Inhibition of osteoclast differentiation and bone resorption by cathepsin K antisense oligonucleotides
Authors: Ishikawa Takashi , Kamiyama Masako , Tani‐Ishii Nobuyuki , Suzuki Hiroaki , Ichikawa Yasushi , Hamaguchi Yohei , Momiyama Nobuyoshi , Shimada Hiroshi
Published: August 2002

We confirmed the expression of cathepsin K, the most abundant and specific cysteine protease found in osteoclasts, at the mRNA level in most of our cases of breast cancer, and even at the protein level in bone metastatic lesions. Therefore, we investigated the functions of cathepsin K in osteoclasts with special attention to bone metastasis from breast cancer. Mouse osteoclast‐like cells (OCLs) were established by coculture of mouse bone marrow cells and osteoblastic cells. Rodent cathepsin K antisense (AS) or random control (CL) oligonucleotides were added on day 0, 3, or 6 of culture. Tartrate‐resistant acid phosphatase staining confirmed the formation of OCLs after 9 d of incubation. AS treatment significantly reduced both the number of TRAP‐positive cells and the percentage of multinuclear cells. For the pit‐forming assay, after 9 d of incubation, mature OCLs were collected and incubated on ivory slices with AS or CL for 48 h. The antisense oligonucleotides also inhibited the bone‐resorbing activity of OCLs. CL treatment did not affect either the number of TRAP‐positive cells or pit formation. Cathepsin K may play important roles in bone resorption as well as in differentiation of osteoclasts. These findings indicate that the inhibition of this enzyme may prevent the development of bone metastasis from breast cancer. © 2001 Wiley‐Liss, Inc.
Material handling device selection in cellular manufacturing
Authors: Braglia Marcello , Gabbrielli Roberto , Miconi Dante
Published: August 2002

This paper presents a new multi‐criteria decision model for the material handling device (MHD) selection problem in cellular manufacturing systems. Given a set of manufacturing cells based on several automatic work‐centres, the technique makes it possible to select a particular MHD for each cell in an integrated way, with different constraints being taken into consideration. The approach is based on two different multi‐attribute analyses executed with analytic hierarchy process (AHP) methodology, and a final integer linear programming including important limitations faced by the designer when making MHD investment decisions. An example using real data is provided to illustrate this methodology. Copyright © 2002 John Wiley & Sons, Ltd.
In utero bacterial endotoxin exposure causes loss of tyrosine hydroxylase neurons in the postnatal rat midbrain
Authors: Ling ZaoDung , Gayle Dave A. , Ma Shang Yong , Lipton Jack W. , Tong Chong Wai , Hong Jau‐Shyong , Carvey Paul M.
Published: August 2002

We investigated whether in utero exposure to the Gram(−) bacteriotoxin lipopolysaccharide (LPS) induces dopamine (DA) neuron loss in rats. The proinflammatory cytokine tumor necrosis factor α (TNF‐α) kills DA neurons and is elevated in the brains of patients with Parkinson's disease (PD). LPS is a potent inducer of TNF‐α, and both are increased in the chorioamniotic environment of women who have bacterial vaginosis (BV) during pregnancy, suggesting that BV might interfere with the normal development of fetal DA neurons. Gravid female rats were injected intraperitoneally with either LPS or normal saline at embryonic day 10.5 and their pups were killed at postnatal day 21. The brains of the pups were assessed for DA and TNF‐α levels and DA cell counts in the mesencephalon using tyrosine hydroxylase immunoreactive (THir) cells as a DA neuron marker. Prenatal LPS exposure significantly reduced striatal DA (29%) and increased DA activity (72%) as well as TNF‐α (101%). Stereological cell counts in the mesencephalon were also significantly reduced (27%) by prenatal LPS exposure. Prenatal exposure to LPS, as might occur in humans with BV, produces a significant loss of THir cells in rats that is still present 33 days following a single injection of LPS. Since this cell loss is well past the normal phase of DA neuron apoptosis that occurs in early postnatal life, rats so exposed may have a permanent loss of DA neurons, suggesting that prenatal infections may represent risk factors for PD. © 2001 Movement Disorder Society.
Emergence of complex, involuntary movements after gamma knife radiosurgery for essential tremor
Authors: Siderowf Andrew , Gollump Stephen M. , Stern Matthew B. , Baltuch Gordon H. , Riina Howard A.
Published: August 2002

Gamma knife radiosurgery is generally considered a safer alternative to traditional pallidotomy or thalamotomy. We report the case of a 59‐year‐old patient with essential tremor who developed a complex, disabling movement disorder following gamma knife thalamotomy. This case illustrates the need for long‐term follow‐up to fully evaluate the potential for complications following radiosurgery. © 2001 Movement Disorder Society.
Effects of bilateral pallidal or subthalamic stimulation on gait in advanced Parkinson's disease
Authors: Allert N. , Volkmann J. , Dotse S. , Hefter H. , Sturm V. , Freund H.‐J.
Published: August 2002

Bilateral high‐frequency stimulation of the internal globus pallidus (GPi) and the subthalamic nucleus (STN) both alleviate akinesia, rigidity, and tremor in idiopathic Parkinson's disease. To test the specific effect of these procedures on gait, we used quantitative gait analysis in addition to relevant subscores of the Unified Parkinson's Disease Rating Scale in a group of 10 patients with advanced Parkinson's disease treated by GPi stimulation and eight patients treated by STN stimulation. Patients were assessed before and 3 months after surgery. Thirty age‐matched healthy subjects served as controls. The non‐random selection allowed a descriptive but no direct statistical comparison of the respective procedure. Gait analysis showed significant stimulation‐induced improvements of spatiotemporal gait and step parameters in both patient groups. Moreover, the effects on step length and cadence suggested a differential effect of both basal ganglia targets. Hence, the increase in gait velocity in the STN group was almost exclusively due to a significant increase in step length, while in the GPi group statistically non‐significant increases in both step length and cadence contributed. © 2001 Movement Disorder Society.
Postural asymmetries following unilateral subthalomotomy for advanced Parkinson's disease
Authors: Su Philip C. , Tseng Ham‐Min , Liou Horng‐Huei
Published: August 2002

Two cases of postural asymmetries following unilateral stereotaxic subthalamotomy were observed with head and body tilting to the side contralateral to the STN lesion, which corrected itself completely or partially with levodopa treatment. After subsequent contralateral STN surgery, the postural asymmetry disappeared in both patients. Possible mechanism is discussed. © 2002 Movement Disorder Society.
Nonsteroidal aromatase inhibitors: Recent advances
Authors: Recanatini Maurizio , Cavalli Andrea , Valenti Piero
Published: August 2002

Aromatase is the cytochrome P450 enzyme responsible for the last step of estrogen biosynthesis, and aromatase inhibitors constitute an important class of drugs in clinical use for the treatment of breast cancer. Nonsteroidal aromatase inhibitors (NSAIs) are competitive inhibitors of aromatase, which bind to the enzyme active site by coordinating the iron atom present in the heme group of the P450 protein. Presently, third generation NSAIs are in use, and research efforts are being carried out both to identify new molecules of therapeutic interest and to clarify the mechanism of action. In this article, we present a survey of the compounds that have been recently reported as NSAIs, to provide a broad view on the general structure–activity relationships of the class. Moreover, starting from the current knowledge of the mechanistic aspects of aromatase action and from recent theoretical work on the molecular modeling of both enzyme and inhibitors, we try to indicate a way to integrate these different studies in view of a more general understanding of the aromeatase‐inhibitor system. Finally, some aspects regarding the possible future development of the field are considered briefly. © 2002 Wiley Periodicals, Inc. Med Res Rev, 22, No. 3, 282–304, 2002; Published online in wiley InterScience (www.interscience.wiley.com). DOI 10.1002/med.10010
Orbofiban: An orally active GPIIb/IIIa platelet receptor antagonist
Authors: Nicholson Nancy S. , Abood Norman A. , Panzer‐Knodle Susan G. , Frederick Leo G. , Page Jimmy D. , Salyers Anita K. , Suleymanov Osman D. , Szalony James A. , Taite Beatrice B. , Anders Robert J.
Published: August 2002

A key role has been established for platelet activation and thrombus formation in the pathogenesis of acute coronary syndromes, and restenosis after percutaneous interventions. Antiplatelet agents that have a wider spectrum of activity than aspirin, and clopidogrel would be expected to provide improved antithrombotic protection. Preclinical studies were used to predict clinical efficacy of orally active GPIIb/IIIa antagonists such as xemilofiban, sibrafiban, lefradafiban, and orbofiban. While clinical trials have shown potent and sustained platelet inhibition, outcomes of trials with these first generation GPIIb/IIIa compounds have been disappointing. The active moiety of orbofiban is a potent and specific inhibitor of fibrinogen binding to GPIIb/IIIa, leading to inhibition of platelet aggregation to a wide variety of agonists. Studies comparing inhibition of aggregation and bleeding suggest that chronic inhibition of platelet aggregation can be achieved without major bleeding side effects. Thrombus formation is prevented in canine models of thrombosis. Orbofiban is approximately 28% bioavailable with a t1/2 of 18 hr. The high bioavailability, long half‐life, and potential safety suggest orbofiban would be suitable for chronic oral administration. Clinical data demonstrate that orally administered orbofiban has the desired pharmacodynamic effect of inhibiting platelet aggregation but does not demonstrate clinical benefit when examined in large‐scale trials. © 2001 John Wiley & Sons, Inc. Med Res Rev, 21, No. 3, 211–226, 2001
Vancomycin, teicoplanin, and ramoplanin: Synthetic and mechanistic studies†
Authors: Boger Dale L.
Published: August 2002

Vancomycin, teicoplanin, and ramoplanin are potent glycopeptide antibiotics that act by inhibiting bacterial cell wall biosynthesis. The former are used clinically as the antibiotics of last resort for the treatment of methicillin‐resistant Staphylococcus aureus and the latter is a promising new antibiotic that is not susceptible to the emerging bacterial resistance to vancomycin and teicoplanin. A summary of our recent total synthesis of the vancomycin aglycon, our first and second generation total syntheses of the teicoplanin aglycon, and our progress on the total synthesis of the ramoplanins is presented. This work lays the foundation for ongoing structure–function studies on the antibiotics that may clarify or define their site and mechanism of action leading to the development of improved or reengineered antibiotics. © 2001 John Wiley & Sons, Inc. Med Res Rev, 21, No. 5, 356–381, 2001
Pharmacokinetics and its role in small molecule drug discovery research
Authors: Jang Graham R. , Harris Robert Z. , Lau David T.
Published: August 2002

Pharmacokinetics (PK), which describes the disposition of a drug in the body, should be a primary consideration in the selection of a drug candidate, ultimately contributing to its eventual clinical success or failure. Accordingly, a sound understanding of PK concepts and an appreciation of the judicious use of PK and related (e.g., metabolism, transporter) data in drug discovery can be beneficial to those involved in the process. This review defines important PK parameters (e.g., clearance, volume of distribution, half‐life), describes methods of PK data analysis (noncompartmental vs. compartmental) and provides an overview of additional concepts such as allometric scaling, PK/pharmacodynamic modeling, and nonlinear PK. Furthermore, the role and strategic use of PK screens in drug discovery are discussed. © 2001 John Wiley & Sons, Inc. Med Res Rev, 21, No. 5, 382–396, 2001
Optimization of metabolic stability as a goal of modern drug design
Authors: Thompson Thomas N.
Published: August 2002

Metabolism and other pharmacokinetic (PK) studies have always played a critical role in helping to optimize the bioavailability and duration of action of new drugs thereby increasing their success rate. With the advent of automated combinatorial synthesis, high‐throughput pharmacological testing, and the ability to create extensive databases in the past decade, drug discovery has undergone an amazing evolution. With the increased throughput of drug discovery, metabolism and other PK studies have evolved to keep pace. Often called “early ADME” studies, these studies are characterized by parallel processing and higher throughput than before. This article focuses on a particular class of early ADME (absorption, distribution mechanism, and excretion) studies known as “metabolic stability” studies. The theoretical basis for metabolic stability and its relationship to the concept of metabolic intrinsic clearance is briefly presented. Some key relationships between structure and metabolism are summarized. Several case studies from recent medicinal chemistry literature are reviewed to exemplify how metabolic stability studies influenced drug design and led to improvements in bioavailability and half‐life. Finally, future trends in drug metabolism and analytical chemistry and how they may influence metabolic stability studies are reviewed. © 2001 John Wiley & Sons, Inc. Med Res Rev, 21, No. 5, 412–449, 2001
Muscle preservation using an implantable electrical system after nerve injury and repair
Authors: Nicolaidis Stephen C. , Williams H. Bruce
Published: August 2002

The value of continuous electrical stimulation of denervated muscles after nerve injury and repair has been clearly shown in a series of laboratory experiments in three animal models. This experimental background, which showed improved muscle preservation and better functional results, evolved into a clinical study that included 15 patients with peripheral nerve injuries in the upper extremities, 3 patients with brachial plexus injuries, and three patients with facial nerve paralysis. Improved functional results were obtained using this implantable system, which were similar to those achieved with the animal experiments. All patients had muscle stimulation for extended periods ranging from 127 to 346 days. Analysis of the results showed satisfactory nerve regeneration on clinical examination and with electromyographic studies. Functional muscle analysis varied somewhat from patient to patient, but every patient had a satisfactory to excellent recovery. The results from this study have clearly shown the benefits of continuous muscle stimulation using an implantable electrical system after nerve injury and repair expansion of the project to a larger patient cohort is indicated. © 2001 Wiley‐Liss, Inc. MICROSURGERY 21:241–247 2001
Perturbation of microstrip ring structure by grain moisture and its angle dependence
Authors: Abegaonkar Mahesh P. , Karekar R. N. , Aiyer R. C.
Published: August 2002

A microstrip ring resonator (MRR) is perturbed by overlaying mug grains (Phaseolus Radiatus Linn.), having different moisture contents (7–42%), at eight different angles. Out of the two orthogonal degenerate modes (even and odd) of MRR, only the even mode is sensitive to the strength of perturbation (grain moisture). The overlay angle and moisture‐dependent perturbation factor is reported. The results are compared with the reported perturbation results of Yogi et al. [16]. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 33: 128–132, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10252
Cytogenetics in pediatric low‐grade astrocytomas
Authors: Orr Lesley C. , Fleitz Julie , McGavran Loris , Wyatt‐Ashmead Josephine , Handler Michael , Foreman Nicholas K.
Published: August 2002

Background

Cytogenetic analysis in certain tumors is a vital part of classification and assignment of prognosis. Few studies have examined the value of cytogenetic analysis in pediatric brain tumors. This is especially true of low‐grade astrocytomas (LGA) of childhood. This study examines the correlation between cytogenetic abnormalities and survival in children with low‐grade astrocytomas. The literature on adults with LGA suggest better survival for those whose tumors have normal cytogenetics compared to those with abnormal. We hypothesized this would also be true of children with low‐grade astrocytomas.

Procedure

A retrospective study was performed of children presenting between 1980 and 1998 to The Children's Hospital, Denver, who had LGA and on whose tumors informative cytogenetics had obtained.

Results

One hundred and forty‐nine children were diagnosed with histologically proven LGA. Twenty‐nine had successful cytogenetic analysis. One or more chromosomal abnormalities were observed in eight tumors while normal karyotypes were observed in 21 tumors. Actuarial progression‐free survival at 5 years was 87.5% for the eight children with abnormal cytogenetics and 43% for those with normal (P = 0.56). Overall survival at 5 years was 83% for those with abnormal cytogenetics and 78% for those with normal (P = 0.8). The differences in progression‐free survival and overall survival between these two groups were not significant. Those children with WHO Grade I tumors had significantly superior progression‐free and overall survival than those with Grade II tumors.

Conclusions

It appears unlikely that, for children with LGA, those with normal cytogenetics have a better prognosis than those with abnormal. Histologic grade is a better predictor of outcome than cytogenetics. Med Pediatr Oncol 2002;38:173–177. © 2002 Wiley‐Liss, Inc.
Receptor mediated yolk protein uptake in the crab Scylla serrata: crustacean vitellogenin receptor recognizes related mammalian serum lipoproteins
Authors: Warrier Sudha , Subramoniam T.
Published: August 2002

The receptor‐mediated uptake of major yolk protein precursor, vitellogenin (Vg) is crucial for oocyte growth in egg laying animals. In the present study plasma membrane receptor for Vg was isolated from the oocyte of the red mud crab, Scylla serrata. Vitellogenin receptor (VgR) protein was visualized by ligand blotting using labeled crab Vg (125I‐Vg) as well as labeled low density lipoprotein (125I ‐LDL) and very low density lipoprotein (125I‐VLDL) isolated from rat. The endocytosis of Vg was visualized in the crab oocyte by ultrastructural immunolocalization of Vg. The Vg receptor was purified by gel filtration high performance liquid chromatography (HPLC) and its molecular weight was estimated to be 230 kDa. In direct binding studies, the receptor exhibited high affinity (dissociation constant Kd 0.8 × 10−6 M) for crab Vg. Vitellogenin receptor was observed to have an increased affinity to crab Vg in the presence of Ca2+ and the binding was inhibited by suramin, suggesting similarities between crab VgR and low density lipoprotein receptor (LDLR) superfamily of receptor protein. Furthermore, the crab VgR showed significant binding ability to mammalian atherogenic lipoproteins such as LDL and VLDL. This suggests that there is a tight conservation of receptor binding sites between invertebrate (crab) Vg and vertebrate (rat) LDL and VLDL. Mol. Reprod. Dev. 61:536–548, 2002. © 2002 Wiley‐Liss, Inc.
Cigarette smoking and aneuploidy in human sperm
Authors: Shi Qinghua , Ko Evelyn , Barclay Leona , Hoang Tina , Rademaker Alfred , Martin RenÉe
Published: August 2002

Cigarette smoke contains chemicals which are capable of inducing aneuploidy in experimental systems. These chemicals have been shown to reach the male reproductive system, increasing oxidative DNA damage in human sperm and lowering semen quality. We have examined the association between smoking and aneuploid sperm by studying 31 Chinese men with similar demographic characteristics and lifestyle factors except for cigarette smoking. None of the men drank alcohol. These men were divided into three groups: nonsmokers (10 men), light smokers (< 20 cigarettes/day, 11 men), and heavy smokers (≥ 20 cigarettes/day, 10 men). There were no significant differences in semen parameters or in age across groups. Two multi‐color fluorescence in situ hybridizations (FISH) were performed: two‐color FISH for chromosomes 13 and 21, and three‐color FISH for the sex chromosomes using chromosome 1 as an internal autosomal control for diploidy and lack of hybridization. The mean hybridization efficiency was 99.78%. The frequency of disomy 13 was significantly higher in light and heavy smokers than in non‐smokers, while no significant differences in the frequency of disomy 21, X or Y were observed across groups. Significant inter‐donor heterogeneity in every category of disomic sperm examined was found in both light and heavy smokers, while in nonsmokers only XY disomy showed significant inter‐donor differences. Thus, we conclude that cigarette smoking may increase the risk of aneuploidy only for certain chromosomes and that men may have different susceptibilities to aneuploidy in germ cells induced by cigarette smoking. Mol. Reprod. Dev. 59: 417–421, 2001. © 2001 Wiley‐Liss, Inc.
17β‐estradiol induces spermatogonial proliferation through mitogen‐activated protein kinase (extracellular signal‐regulated kinase 1/2) activity in the lizard (Podarcis s. sicula)
Authors: Chieffi Paolo , D'Amato Luca Colucci , Guarino Fabio , Salvatore Gaetano , Angelini Francesco
Published: August 2002

There are always more evidences indicating that 17β‐estradiol (E2) is necessary for normal male fertility. We have used a nonmammalian vertebrate model (the lizard Podarcis s. sicula) to investigate the regulation of extracellular signal‐regulated kinase 1 and 2 (ERK1/2) activity in the testis during the annual sexual cycle and to study whether E2 exerts a role in the spermatogenesis through ERK1/2 activity. Immunocytochemistry analysis shows that ERK1/2 proteins are present in the nucleus of the spermatogonia (SPG), and in primary (I) spermatocytes (SPC). The annual E2 profile shows a progressive increase during the active spermatogenesis (from April to June) and a peak in the month of August (spermatogonial mitosis). In parallel, ERK1/2 (molecular weight 44 and 42 kDa, respectively) are highly phosphorylated during the period of active spermatogenesis and in post‐refractory period (August) compared with the winter stasis (from November to March). Present results demonstrate that E2 treatment induces spermatogonial proliferation, possibly via the activation of ERK1/2, and this effect is counteracted by the antiestrogen ICI 182‐780. Mol. Reprod. Dev. 61: 218–225, 2002. © 2002 Wiley‐Liss, Inc.
Different excitation and reception distributions with a single‐loop transmit‐receive surface coil near a head‐sized spherical phantom at 300 MHz
Authors: Collins C.M. , Yang Q.X. , Wang J.H. , Zhang X. , Liu H. , Michaeli S. , Zhu X.‐H. , Adriany G. , Vaughan J.T. , Anderson P. , Merkle H. , Ugurbil K. , Smith M.B. , Chen W.
Published: August 2002

Calculations and experiments were used to examine the B1 field behavior and signal intensity distribution in a 16‐cm diameter spherical phantom excited by a 10‐cm diameter surface coil at 300 MHz. In this simple system at this high frequency very complex RF field behavior exists, resulting in different excitation and reception distributions. Included in this work is a straightforward demonstration that coil receptivity is proportional to the magnitude of the circularly polarized component of the B1 field that rotates in the direction opposite to that of nuclear precession. It is clearly apparent that even in very simple systems in head‐sized samples at this frequency it is important to consider the separate excitation and reception distributions in order to understand the signal intensity distribution. Magn Reson Med 47:1026–1028, 2002. © 2002 Wiley‐Liss, Inc.
Improved selectivity of double quantum coherence filtering for the detection of glutathione in the human brain in vivo
Authors: Trabesinger Andreas H. , Boesiger Peter
Published: August 2002

An improved double quantum coherence (DQC) filter for the selective in vivo detection of glutathione (GSH) in the human brain at 1.5 Tesla is presented. The goal was to minimize contamination of the DQC‐filtered GSH signal at 2.9 ppm with contributions arising from GABA. The modification consists of tailoring the frequency response of the read pulse, which converts DQC into anti‐phase single quantum coherence in such a way that the GABA β and γ resonances at 3.0 and 1.9 ppm, respectively, remain unaffected. An implementation incorporating a Dante pulse train is used for in vitro tests as well as for in vivo applications. Magn Reson Med 45:708–710, 2001. © 2001 Wiley‐Liss, Inc.
Rapid measurement of aortic wave velocity: In vivo evaluation
Authors: Kraft Kenneth A. , Itskovich Vitalii V. , Fei Ding‐Yu
Published: August 2002

A 1D MR sequence has been developed for determining aortic flow wave velocity (WV), a metric of arterial compliance, within a single cardiac cycle. Studies were carried out on the thoracic aortas of 10 normal volunteers. Correlative WV data were also acquired from each subject using a conventional phase‐velocity 2D mapping technique. Aortic WV in this cohort was found to range from 411 to 714 cm/s and was highly correlated (R = 0.95) between the two methods. Peak blood velocity was also measured using both methods and found to agree closely. The reproducibility of WV measurements using the rapid 1D method averaged 7.6%, which is comparable or better than that achieved using existing noninvasive techniques. Magn Reson Med 46:95–102, 2001. © 2001 Wiley‐Liss, Inc.
Coil‐by‐coil image reconstruction with SMASH
Authors: McKenzie Charles A. , Ohliger Michael A. , Yeh Ernest N. , Price Mark D. , Sodickson Daniel K.
Published: August 2002

The SiMultaneous Acquisition of Spatial Harmonics (SMASH) technique uses linear combinations of undersampled datasets from the component coils of an RF coil array to reconstruct fully sampled composite datasets in reduced imaging times. In previously reported implementations, SMASH reconstructions were designed to reproduce the images that would otherwise be obtained by simple sums of fully gradient encoded component coil images. This strategy has left SMASH images vulnerable to phase cancellation artifacts when the sensitivities of RF coil array elements are not suitably phase‐aligned. In fully gradient encoded imaging schemes these artifacts can be eliminated using a variety of methods for combining the individual coil images, including matched filter combinations as well as sum of squares combinations. Until now, these reconstruction schemes have been unavailable to SMASH reconstructions as SMASH produced a final composite image directly from the raw component coil k‐space datasets. This article demonstrates a modification to SMASH that allows reconstruction of a full set of accelerated individual component coil images by fitting component coil sensitivity functions to a complete set of spatial harmonics tailored for each coil in the array. Standard component coil combinations applied to the individual reconstructed images produce final composite images free of phase cancellation artifacts. Magn Reson Med 46:619–623, 2001. © 2001 Wiley‐Liss, Inc.
Improved spatial harmonic selection for SMASH image reconstructions
Authors: McKenzie Charles A. , Yeh Ernest N. , Sodickson Daniel K.
Published: August 2002

The fitting of coil sensitivity functions to spatial harmonics is central to image reconstructions using the simultaneous acquisition of spatial harmonics (SMASH) technique. It has previously been shown that the selection of the set of spatial harmonics used in a SMASH reconstruction can have a noticeable effect on the quality of the reconstructed image. However, a mechanism for automatic selection of the best set of harmonics in any particular situation has not been provided. In this work, a modification to the SMASH reconstruction procedure is introduced that allows the use of a weighted average of all possible harmonics in a reconstruction. The new reconstruction procedure is shown to allow automatic selection of the spatial harmonics and substantially improve SNR for both phantom and in vivo images. Magn Reson Med 46:831–836, 2001. © 2001 Wiley‐Liss, Inc.
Quality of life and well‐being of patients with myasthenia gravis
Authors: Paul Robert H. , Nash Justin M. , Cohen Ronald A. , Gilchrist James M. , Goldstein Jonathan M.
Published: August 2002

The cardinal symptom of myasthenia gravis (MG) is weakness of voluntary muscles, a feature that may restrict full participation in life activities. In turn, such limitations may negatively affect quality of life (QOL) and well‐being among individuals with the disease. In the present study, we administered a measure of QOL to 27 patients with generalized MG. Results revealed that functional status was negatively impacted in the domains of physical functioning, energy, and general health. However, a clinically meaningful difference was evident only on perceived ability to accomplish physical tasks. The results suggest that although MG requires accommodations in physical activities, general QOL and well‐being does not differ markedly from the general population. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 512–516, 2001
Leukemia inhibitory factor enhances regeneration in skeletal muscles after myoblast transplantation
Authors: White Jason D. , Bower John J. , Kurek John B. , Austin Lawrie
Published: August 2002

Cell‐based therapies, such as myoblast transfer therapy, are likely to become an integral part of any approach to treat myopathies such as Duchenne muscular dystrophy. Previous studies have shown that an increased level of regeneration in the host muscle enhances incorporation of donor myoblasts. Leukemia inhibitory factor (LIF) increases the number of dystrophic fibers expressing dystrophin after myoblast transplantation and enhances regeneration in injured and diseased muscle. Morphometric analysis was used to investigate whether an increased level of regeneration is induced by LIF after myoblast transplantation. We found that, in muscles treated with LIF, the number of fibers undergoing regeneration was increased. The increased incorporation of donor myoblasts and thus dystrophin expression induced by LIF may be due, at least in part, to an increased level of regeneration of dystrophic muscle. © 2001 John Wiley & Sons, Inc. Muscle and Nerve 24:695–697, 2001
The pathophysiology of tremor
Authors: Deuschl Günther , Raethjen Jan , Lindemann Michael , Krack Paul
Published: August 2002

Tremor is defined as rhythmic oscillatory activity of body parts. Four physiological basic mechanisms for such oscillatory activity have been described: mechanical oscillations; oscillations based on reflexes; oscillations due to central neuronal pacemakers; and oscillations because of disturbed feedforward or feedback loops. New methodological approaches with animal models, positron emission tomography, and mathematical analysis of electromyographic and electroencephalographic signals have provided new insights into the mechanisms underlying specific forms of tremor. Physiological tremor is due to mechanical and central components. Psychogenic tremor is considered to depend on a clonus mechanism and is thus believed to be mediated by reflex mechanisms. Symptomatic palatal tremor is most likely due to rhythmic activity of the inferior olive, and there is much evidence that essential tremor is also generated within the olivocerebellar circuits. Orthostatic tremor is likely to originate in hitherto unidentified brainstem nuclei. Rest tremor of Parkinson's disease is probably generated in the basal ganglia loop, and dystonic tremor may also originate within the basal ganglia. Cerebellar tremor is at least in part caused by a disturbance of the cerebellar feedforward control of voluntary movements, and Holmes' tremor is due to the combination of the mechanisms producing parkinsonian and cerebellar tremor. Neuropathic tremor is believed to be caused by abnormally functioning reflex pathways and a wide variety of causes underlies toxic and drug‐induced tremors. The understanding of the pathophysiology of tremor has made significant progress but many hypotheses are not yet based on sufficient data. Modern neurology needs to develop and test such hypotheses, because this is the only way to develop rational medical and surgical therapies. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 716–735, 2001
Pathology‐related differential expression regulation of NGF, GDNF, CNTF, and IL‐6 mRNAs in human vasculitic neuropathy
Authors: Yamamoto Masahiko , Ito Yasuhiro , Mitsuma Norimasa , Li Mei , Hattori Naoki , Sobue Gen
Published: August 2002

The mRNA levels of nerve growth factor (NGF), glial cell line–derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF), and interleukin‐6 (IL‐6) were examined in sural nerves of 22 patients with acute necrotizing vasculitic neuropathies. NGF, GDNF, and IL‐6 mRNAs were upregulated and CNTF mRNA was downregulated in the lesioned nerves, but their up‐ and down‐regulation levels were not correlated with each other, showing that these mRNAs were independently expressed. The expression of NGF and CNTF mRNAs was clearly correlated with the degree of infiltrated macrophages and T cells, and myelinated fiber density, respectively. These findings indicate that these neurotrophic factors are differentially expressed temporally and spatially in the vasculitic nerve lesion by an underlying pathology‐related process. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 830–833, 2001
Contractile speed and fatigue of adductor pollicis muscle in multiple sclerosis
Authors: de Ruiter Cornelis J. , Jongen Peter J.H. , van der Woude Luc H.V. , de Haan Arnold
Published: August 2002

The purpose of the study was to investigate differences in contractile speed, force, and fatigability of the adductor pollicis muscle between 12 patients with multiple sclerosis (MS) and 8 sedentary control subjects matched for age and gender. There were no differences between the patients with MS and control subjects with respect to the percentage of maximal muscle force that could be recruited during voluntary effort (95.5 ± 3.9% and 98.2 ± 2.0%, respectively, P = 0.10), the stimulation frequency/force and force/velocity relationships, the rates of force development and relaxation, fatigue resistance, and the recovery rate of adductor pollicis muscle. However, previous results from the same group of MS patients showed that quadriceps femoris muscle force and resistance to fatigue were reduced. Therefore, our data support the clinical experience that, in patients with MS, lower limb muscle function is more or earlier affected than upper limb muscle function. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 1173–1180, 2001
Learned voiding dysfunction (non‐neurogenic, neurogenic bladder) among adults
Authors: Groutz Asnat , Blaivas Jerry G. , Pies Christoph , Sassone A. Margherita
Published: August 2002

Data concerning learned voiding dysfunction (Hinman syndrome; non‐neurogenic, neurogenic bladder) in adults are scarce. The present study was conducted to assess the pre‐valence and clinical characteristics of this dysfunction among adults referred for evaluation of lower urinary tract symptoms. Learned voiding dysfunction was suggested by a characteristic clinical history and intermittent “free” uroflow pattern and by the absence of any detectable neurological abnormality or anatomic urethral obstruction. A definitive diagnosis was made by the demonstration of typical external urethral sphincter contractions during micturition by EMG or fluoroscopy. A urodynamic database of 1,015 consecutive adults was reviewed. Twenty‐one (2%) patients (age, 24–76 years) met our strict criteria of learned voiding dysfunction. Obstructive symptoms were the most common presenting symptoms, followed by frequency, nocturia, and urgency. Eight (35%) patients had recurrent urinary tract infections, seven of these being women. None of the patients had any clinically significant upper urinary tract damage. First sensation volume was significantly lower in women than in men. Both detrusor pressure at maximum flow and maximum detrusor pressure during voiding were found to be significantly higher in men than in women. Further differentiation between adult women and men failed to reveal any other clinically significant differences. In conclusion, by strict video‐urodynamic criteria, 2% of our patients had learned voiding dysfunction. Other patients, with presumed learned voiding dysfunction, who did not undergo video‐urodynamics were not included in the present series. Thus, the prevalence of learned voiding dysfunction among adults referred for evaluation of lower urinary tract symptoms is likely to be even higher. Neurourol. Urodynam. 20:259–268, 2001. © 2001 Wiley‐Liss, Inc.
The collection depots location problem on networks
Authors: Berman Oded , Drezner Zvi , Wesolowsky George O.
Published: August 2002

In this paper we investigate the collection depots location problem on a network. A facility needs to be located to serve a set of customers. Each service consists of a trip to the customer, collecting materials, dropping the materials at one of the available collection depots and returning to the facility to wait for the next call. Two objectives are considered: minimizing the weighted sum of distances and minimizing the maximum distance. The properties of the solutions to these problems are described. © 2002 John Wiley & Sons, Inc. Naval Research Logistics, 49: 15–24, 2002; DOI 10.1002/nav.10000
A branch and bound algorithm for computing optimal replacement policies in consecutive k‐out‐of‐n‐systems
Authors: Flynn James , Chung Chia‐Shin
Published: August 2002

This paper presents a branch and bound algorithm for computing optimal replacement policies in a discrete‐time, infinite‐horizon, dynamic programming model of a binary coherent system with n statistically independent components, and then specializes the algorithm to consecutive k‐out‐of‐n systems. The objective is to minimize the long‐run expected average undiscounted cost per period. (Costs arise when the system fails and when failed components are replaced.) An earlier paper established the optimality of following a critical component policy (CCP), i.e., a policy specified by a critical component set and the rule: Replace a component if and only if it is failed and in the critical component set. Computing an optimal CCP is a optimization problem with n binary variables and a nonlinear objective function. Our branch and bound algorithm for solving this problem has memory storage requirement O(n) for consecutive k‐out‐of‐n systems. Extensive computational experiments on such systems involving over 350,000 test problems with n ranging from 10 to 150 find this algorithm to be effective when n ≤ 40 or k is near n. © 2002 Wiley Periodicals, Inc. Naval Research Logistics 49: 288–302, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/nav.10017
Asymptotically optimal component assembly plans in repairable systems and server allocation in parallel multiserver queues
Authors: Dinopoulou V.D. , Melolidakis C.
Published: August 2002

T identical exponential lifetime components out of which G are initially functioning (and B are not) are to be allocated to N subsystems, which are connected either in parallel or in series. Subsystem i, i = 1,…, N, functions when at least Ki of its components function and the whole system is maintained by a single repairman. Component repair times are identical independent exponentials and repaired components are as good as new. The problem of the determination of the assembly plan that will maximize the system reliability at any (arbitrary) time instant t is solved when the component failure rate is sufficiently small. For the parallel configuration, the optimal assembly plan allocates as many components as possible to the subsystem with the smallest Ki and allocates functioning components to subsystems in increasing order of the Ki's. For the series configuration, the optimal assembly plan allocates both the surplus and the functioning components equally to all subsystems whenever possible, and when not possible it favors subsystems in decreasing order of the Ki's. The solution is interpreted in the context of the optimal allocation of processors and an initial number of jobs in a problem of routing time consuming jobs to parallel multiprocessor queues. © John Wiley & Sons, Inc. Naval Research Logistics 48: 732–746, 2001
Multiple common due dates
Authors: Dickman Bernard , Wilamowsky Yonah , Epstein Sheldon
Published: August 2002

Common due date problems have been extensively discussed in the scheduling literature. Initially, these problems discussed finding a common due date for a set of jobs on a single machine. These single machine problems were later extended to finding the common due date on a set of parallel machines. This paper further extends the single machine problem to finding multiple common due dates on a single machine. For a basic and important class of penalty functions, we show that this problem is comparable to the parallel machine problem. © 2001 John Wiley & Sons, Inc. Naval Research Logistics 48: 293–298, 2001
1H‐ and 31P‐MR spectroscopy of primary and recurrent human brain tumors in vitro: malignancy‐characteristic profiles of water soluble and lipophilic spectral components
Authors: Lehnhardt Fritz‐Georg , Röhn Gabriele , Ernestus Ralf‐Ingo , Grüne Matthias , Hoehn Mathias
Published: August 2002

In vitro NMR spectrocopy was performed on specimen of human brain tumors. From all patients, tissue samples of primary tumors and their first recurrences were examined. 31P‐ and 1H‐spectra were recorded from samples of meningioma, astrocytoma and glioblastoma. A double extraction procedure of the tissue samples permitted acquisition of information from the membrane fraction and from the cytosolic fraction. 31P‐spectra were used to analyze the lipophilic fraction (phospholipids of the membrane) of the tissue extracts, while the 1H‐spectra reflected information on the metabolic alterations of the hydrophilic, cytosolic fraction of the tissue. The tumor types showed distinctive spectral patterns in both the 31P‐ and the 1H‐spectra. Based on the total detectable 31P signal, the level of phosphatidylcholine was about 34% lower in primary astrocytomas than in primary glioblastomas (p = 0.0003), whereas the level of sphingomyelin was about 45% lower in primary gioblastomas than in primary astrocytomas (p = 0.0061). A similar tendency of these phospholipids was observed when comparing primary and recurrent astrocytoma samples from the same individuals [+15% (p = 0.0103) and −23% (p = 0.0314) change, respectively]. 1H‐spectra of gliomas were characterized by an increase of the ratios of alanine, glycine and choline over creatine as a function of the degree of malignancy. In agreement with findings in the 31P‐spectra, the 1H‐spectra of recurrent astrocytomas showed metabolic profiles of increased malignancy in comparison to their primary occurrence. Since gliomas tend to increase in malignancy upon recurrence, this may reflect evolving tumor metabolism. 1H‐spectra of meningiomas showed the highest ratio of alanine over creatine accompanied by a near absence of myo‐inositol. Phospholipid profiles of meningiomas showed higher fractional contents of phosphatidylcholine along with lower phosphatidylserine compared to astrocytomas, while higher phosphatidylethanolamine and sphingomyelin fractional contents distinguished meningiomas from glioblastomas. The extraction method being used in this study combined with high‐resolution 1H‐ and 31P‐MRS provides a wide range of biochemical information, which enables differentiation not only between tumor types but also between primary and recurrent gliomas, reflecting an evolving tumor metabolism. Copyright © 2001 John Wiley & Sons, Ltd.