bluuebunny/crossref_metadata_2025 huggingface dataset:
REPLY TO THE COMMENT ON "NONCOMMUTATIVITY AS A POSSIBLE ORIGIN OF THE ULTRAHIGH-ENERGY COSMIC RAY AND THE TEV PHOTON PARADOXES"
Authors: CHEN SHAO-XIA , YANG ZHAO-YU
Published: June 2004

A cogitative comment on Ref. 1 was given by the author of Ref. 2 arguing that the Lorentz-noninvariant modification of the kinematic dispersion law does not follow from deformed oscillator systems, and it cannot evade ultrahigh energy threshold anomalies by raising the respective thresholds. It is pointed out that the dispersion relations of a q-deformed boson and fermion are derived heedlessly and further study on noncommutative theories is necessary. However if such dispersion relations are assumed tenable, the tachyonic propagation and photon instability do not exist at all because the deviation from 1 in q must be imaginary.
WORD-LEVEL OPTICAL FONT RECOGNITION USING TYPOGRAPHICAL FEATURES
Authors: KIM SOO H. , KWAG HEE K. , SUEN CHING Y.
Published: June 2004

Previous research efforts on optical font recognition have mostly limited applications since they deal with only a few types of font attributes and estimate them from a line or block of text. This paper proposes a word-level optical font recognition system for printed Korean and English documents. At the word-level, it has the advantages of obtaining more detailed font attributes including the following: script (Korean and English), font style (regular, bold, italic, and underlined), typeface (Myung-jo and Gothic), point size (10, 12, 14 pts), and word length (2, 3, 4, 5 for Korean, and 4 to 10 for English). A hierarchical classifier and several typographical features have been devised for the system, and their effectiveness are proven by an experiment with a database of 100 sets of 264 font categories.
SEGMENTATION OF OVARIAN ULTRASOUND IMAGES USING CELLULAR NEURAL NETWORKS
Authors: CIGALE BORIS , ZAZULA DAMJAN
Published: June 2004

Segmentation of ovarian ultrasound images using cellular neural networks (CNNs) is studied in this paper. The segmentation method consists of five successive steps where the first four uses CNNs. In the first step, only rough position of follicles is determined. In the second step, the results are improved by expansion of detected follicles. In the third step, previously undetected inexpressive follicles are determined, while the fourth step detects the position of ovary. All results are joined in the fifth step. The templates for CNNs were obtained by applying genetic algorithm. The segmentation method has been tested on 50 ovarian ultrasound images. The recognition rate of follicles was around 60% and misidentification rate was around 30%.
KNOWLEDGE-BASED SCENE EXPLORATION USING COMPUTER VISION AND LEARNED ANALYSIS STRATEGIES
Authors: AHLRICHS U. , PAULUS D. , NIEMANN H.
Published: June 2004

In this contribution we demonstrate how the task of visual scene exploration can be solved by a knowledge-based vision system. During scene exploration, the system searches for a fixed number of a priori known objects in a static scene. If not all objects are visible using the initial camera set-up, the camera parameters have to be adjusted and the camera has to be moved by the system. This problem is reduced to the choice of optimal camera actions. The information about the objects and the camera actions is uniformly represented in a semantic network. In addition, a control algorithm is provided that finds the optimal assignment from objects to parts of a scene based on a suitable analysis strategy. This strategy is acquired by the system itself using reinforcement learning methods. The paper focuses on aspects of knowledge representation concerning the integration of camera actions and on the integration of reinforcement learning methods in a semantic network formalism and applies them in a realistic setup. Experiments are shown for images of two office rooms.
ON THE USE OF A VISUAL CORTICAL SUB-BAND MODEL FOR INTERACTIVE HEURISTIC EDGE DETECTION
Authors: LYON DOUGLAS A.
Published: June 2004

We present a novel interactive edge detection algorithm that combines A* search with low-level adaptive image processing. The algorithm models the semantically driven interpretation that we hypothesize to occur between the mind and visual cortex in the human brain. The basic idea is that oriented Gabor sub-bands are used to model grating cells in the mammalian visual system. These sub-bands are used during the search for a path to a marker in an image. A domain expert uses image markers to select edges of interest.

We demonstrate the system in several image domains. Examples are shown in the areas of photo-interpretation, medical imaging, path planning and general edge finding. The A* search finds a suboptimal result, but executes in a time that is typically 10 to 1,000 times faster than the dynamic programming approach currently used for this type of edge detection.
UNIVERSAL VASSILIEV INVARIANTS OF LINKS IN COVERINGS OF 3-MANIFOLDS
Authors: LIEBERUM JENS
Published: June 2004

We study Vassiliev invariants of links in a 3-manifold M by using chord diagrams labeled by elements of the fundamental group of M. We construct universal Vassiliev invariants of links in M, where M=P2×[0,1] is a cylinder over the real projective plane P2, M=Σ×[0,1] is a cylinder over a surface Σ with boundary, and M=S1×S2. A finite covering p:N→M induces a map π1(p)* between labeled chord diagrams that corresponds to taking the preimage p-1(L)⊂N of a link L⊂M. The maps p-1 and π1(p)* intertwine the constructed universal Vassiliev invariants.
HOW DOES THE DIFFUSION EQUATION ON FRACTALS LOOK?
Authors: ROMAN H. EDUARDO
Published: June 2004

Different forms of diffusion equations on fractals proposed in the literature are reviewed and critically discussed. Variants of the known fractional diffusion equations are suggested here and worked out analytically. On the basis of these results we conclude that the quest: "what is the form of the diffusion equation on fractals," is still open, but we are possibly close to obtaining a satisfactory answer.
SCALE INVARIANCE IN SELECTIN-MEDIATED LEUKOCYTE ROLLING
Authors: KING MICHAEL R.
Published: June 2004

White blood cells slowly roll along the walls of blood vessels, due to the coordinated formation and breakage of chemical selectin-carbohydrate bonds. Using detailed computer simulations of cells rolling on a selectin surface under flow, we show the time series of the cell translational velocity to be fractal in nature over time scales ranging from 22–211 ms. A rescaled range analysis was performed to determine the Hurst exponent of the velocity time series, for simulations of cells rolling on either a uniform or punctate distribution of P-selectin molecules. The rolling behavior was found to exhibit two very distinct regimes, with a negative Hurst exponent ranging from -(1.2-0.6) over time scales of 23-27 ms, and a positive Hurst exponent of +0.47±0.03 over time scales of 27-211 ms. The short-time Hurst exponent was found to be a strong function of the molecular distribution and also a function of average molecular density, while the long-time Hurst exponent was unchanged over all conditions studied. The implication is that the short-time adhesive behavior of cells interacting with a reactive surface is sensitive to the spatial arrangement of molecules, and the total number of molecules on the surface.
Analyzing Cellular Biochemistry in Terms of Molecular Networks
Authors: Xia Yu , Yu Haiyuan , Jansen Ronald , Seringhaus Michael , Baxter Sarah , Greenbaum Dov , Zhao Hongyu , Gerstein Mark
Published: June 2004

▪ Abstract  One way to understand cells and circumscribe the function of proteins is through molecular networks. These networks take a variety of forms including webs of protein-protein interactions, regulatory circuits linking transcription factors and targets, and complex pathways of metabolic reactions. We first survey experimental techniques for mapping networks (e.g., the yeast two-hybrid screens). We then turn our attention to computational approaches for predicting networks from individual protein features, such as correlating gene expression levels or analyzing sequence coevolution. All the experimental techniques and individual predictions suffer from noise and systematic biases. These problems can be overcome to some degree through statistical integration of different experimental datasets and predictive features (e.g., within a Bayesian formalism). Next, we discuss approaches for characterizing the topology of networks, such as finding hubs and analyzing subnetworks in terms of common motifs. Finally, we close with perspectives on how network analysis represents a preliminary step toward a systems approach for modeling cells.
Role of Glycosylation in Development
Authors: Haltiwanger Robert S. , Lowe John B.
Published: June 2004

▪ Abstract  Researchers have long predicted that complex carbohydrates on cell surfaces would play important roles in developmental processes because of the observation that specific carbohydrate structures appear in specific spatial and temporal patterns throughout development. The astounding number and complexity of carbohydrate structures on cell surfaces added support to the concept that glycoconjugates would function in cellular communication during development. Although the structural complexity inherent in glycoconjugates has slowed advances in our understanding of their functions, the complete sequencing of the genomes of organisms classically used in developmental studies (e.g., mice, Drosophila melanogaster, and Caenorhabditis elegans) has led to demonstration of essential functions for a number of glycoconjugates in developmental processes. Here we present a review of recent studies analyzing function of a variety of glycoconjugates (O-fucose, O-mannose, N-glycans, mucin-type O-glycans, proteoglycans, glycosphingolipids), focusing on lessons learned from human disease and genetic studies in mice, D. melanogaster, and C. elegans.
IDENTIFICATION OF TRACE ELEMENT–CONTAINING PROTEINS IN GENOMIC DATABASES
Authors: Gladyshev Vadim N. , Kryukov Gregory V. , Fomenko Dmitri E. , Hatfield Dolph L.
Published: June 2004

▪ Abstract  Development of bioinformatics tools provided researchers with the ability to identify full sets of trace element–containing proteins in organisms for which complete genomic sequences are available. Recently, independent bioinformatics methods were used to identify all, or almost all, genes encoding selenocysteine-containing proteins in human, mouse, and Drosophila genomes, characterizing entire selenoproteomes in these organisms. It also should be possible to search for entire sets of other trace element–associated proteins, such as metal-containing proteins, although methods for their identification are still in development.
MOLECULAR ASPECTS OF ALCOHOL METABOLISM: Transcription Factors Involved in Early Ethanol-Induced Liver Injury
Authors: Nagy Laura E.
Published: June 2004

▪ Abstract  Alcohol metabolism takes place primarily in the liver. Initial exposures to ethanol have a major impact on the hepatic redox state and intermediary metabolism as a consequence of ethanol metabolism via alcohol dehydrogenase. However, upon continued exposure to ethanol, the progression of liver injury involves ethanol metabolism via CYP2E1 and consequent oxidant stress, as well as potential direct effects of ethanol on membrane proteins that are independent of ethanol metabolism. Multiple organ systems contribute to liver injury, including the innate immune system and adipose tissue. In response to ethanol exposure, specific signal transduction pathways, including NFκB and the mitogen-activated protein kinase family members ERK1/2, JNK, and p38, are activated. These complex responses to ethanol exposure translate into activation of nuclear transcription factors and altered gene expression within the liver, leading to the development of steatosis and inflammation in the early stages of alcohol-induced liver injury.
NUTRITION AND CANCER PREVENTION: A Multidisciplinary Perspective on Human Trials
Authors: Forman M.R. , Hursting S.D. , Umar A. , Barrett J.C.
Published: June 2004

▪ Abstract  More than one million Americans were expected to be diagnosed with cancer in 2003 ( 7a ). Compelling experimental, epidemiological, and clinical evidence indicates that many cancers are preventable, especially because diet and nutrition are key factors in the modulation of cancer risk. The road to nutritional intervention in cancer prevention has led to successful trials as well as trials that did not reach their intended endpoints. This chapter reviews four case studies of trials, with two ending in success and two ending in null findings or adverse effects. The goal is to identify lessons learned from all four case studies and from the investigations of the complexities inherent to nutritional intervention trials. Additional insights are presented by the research addressing potential mechanisms underlying the endpoints of human trials. Future progress in nutrition and cancer prevention will require expertise from multidisciplinary teams to develop new knowledge about specific nutrients and dietary modifications within a framework of interaction between animal and human research.
SULFUR AMINO ACID METABOLISM: Pathways for Production and Removal of Homocysteine and Cysteine
Authors: Stipanuk Martha H.
Published: June 2004

▪ Abstract  Tissue concentrations of both homocysteine (Hcy) and cysteine (Cys) are maintained at low levels by regulated production and efficient removal of these thiols. The regulation of the metabolism of methionine and Cys is discussed from the standpoint of maintaining low levels of Hcy and Cys while, at the same time, ensuring an adequate supply of these thiols for their essential functions. S-Adenosylmethionine coordinately regulates the flux through remethylation and transsulfuration, and glycine N-methyltransferase regulates flux through transmethylation and hence the S-adenosylmethionine/S-adenosylhomocysteine ratio. Cystathionine β-synthase activity is also regulated in response to the redox environment, and transcription of the gene is hormonally regulated in response to fuel supply (insulin, glucagon, and glucocorticoids). The H2S-producing capacity of cystathionine γ-lyase may be regulated in response to nitric oxide. Cys is substrate for a variety of anabolic and catabolic enzymes. Its concentration is regulated primarily by hepatic Cys dioxygenase; the level of Cys dioxygenase is upregulated in a Cys-responsive manner via a decrease in the rate of polyubiquitination and, hence, degradation by the 26S proteasome.
Leukocyte elastase induces epithelial apoptosis: role of mitochondial permeability changes and Akt
Authors: Ginzberg Hedy H. , Shannon Patrick T. , Suzuki Tomoko , Hong Ouyang , Vachon Eric , Moraes Theo , Abreu Maria Teresa Herrera , Cherepanov Vera , Wang Xiaomin , Chow Chung-Wai , Downey Gregory P.
Published: June 2004

During acute inflammation, neutrophil-mediated injury to epithelium may lead to disruption of epithelial function, including the induction of epithelial apoptosis. Herein, we report the effects of neutrophil transmigration and of purified leukocyte elastase on epithelial cell survival. Neutrophil transmigration induced apoptosis of epithelial cells [control monolayers: 5 ± 1 cells/25 high-power fields (HPF) vs. neutrophil-treated monolayers: 29 ± 10 cells/HPF, P < 0.05, n = 3 as determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay] as did low concentrations (0.1 U/ml) of purified leukocyte elastase (control monolayers: 6.4 ± 2.5% apoptotic vs. elastase: 26.2 ± 2.9% apoptotic, P < 0.05, as determined by cytokeratin 18 cleavage). Treatment with elastase resulted in decreased mitochondrial membrane potential, release of cytochrome c to the cytosol, and cleavage of caspases-9 and -3 as determined by Western blot analysis, implicating altered mitochondrial membrane permeability as a primary mechanism for elastase-induced apoptosis. Additionally, incubation of epithelial cells with leukocyte elastase resulted in an early increase followed by a decrease in the phosphorylation of epithelial Akt, a serine/threonine kinase important in cell survival. Inhibition of epithelial Akt before elastase treatment potentiated epithelial cell apoptosis, suggesting that the initial activation of Akt represents a protective response by the epithelial cells to the proapoptotic effects of leukocyte elastase. Taken together, these observations suggest that epithelial cells exhibit a dual response to cellular stress imposed by leukocyte elastase with a proapoptotic response mediated via early alterations in mitochondrial membrane permeability countered by activation of the survival pathway involving Akt.
Patterns of Referring of Patients with Frontotemporal Lobar Degeneration to Psychiatric In- and Out-Patient Services
Authors: Ibach B. , Poljansky S. , Barta W. , Koller M. , Wittmann M. , Hajak G.
Published: June 2004

Dementia with frontotemporal lobar degeneration (FTLD) is clinically characterized by the occurrence of various psychiatric symptoms. In a recent study, the hospital-based prevalence of FTLD and the circumstances of the patients’ admission to German psychiatric state hospitals were estimated. On the basis of further continuous assessment, this original FTLD group (n = 33) has been enlarged to 58 patients. The authors here present demographic and clinical data, and reasons for admission to geriatric psychiatry hospitals in comparison with 17 patients, who primarily attended the Memory Disorders Clinic of the University of Regensburg. The results implicate that both institutions see patients with different clinical syndromes: (1) patients were primarily referred to the Memory Disorders Clinic presenting memory and/or speech difficulties as the leading symptoms; (2) major reasons for hospitalisation of patients with FTLD in geriatric psychiatry hospitals were behavioural disturbances; (3) late-onset FTLD (>65 years) was more common than previously assumed in both institutions, and (4) increasing age at admission increased the likelihood to obtain a limited diagnostic approach of brain imaging (only cranial computer tomography) to evaluate the cause of dementia.
Pick’s Disease Pathology of a Missense Mutation of S305N of Frontotemporal Dementia and Parkinsonism Linked to Chromosome 17: Another Phenotype of S305N
Authors: Kobayashi Katsuji , Hayashi Masahiro , Kidani Tomokazu , Ujike Hiroshi , Iijima Masaaki , Ishihara Takeshi , Nakano Hiroyuki , Sugimori Kaoru , Shimazaki Masao , Kuroda Shigetoshi , Koshino Yoshifumi
Published: June 2004

We report the second phenotype of frontotemporal dementia and parkinsonism linked to chromosome 17 with S305N similar to Pick’s disease pathology in two brothers. The brain of the older brother showed macroscopic atrophy compatible with Pick’s disease, and subsequent tau gene analysis revealed heterozygous S305N mutation in exon 10 of the tau gene. Round-shaped neuronal inclusions similar to Pick’s bodies were positive for phosphorylated serine 262 as well as other anti-tau antisera, which is different from immunoexpression of Pick’s bodies. Ultrastructurally, these neuronal inclusions consisted of straight, randomly orientated fibrils measuring approximately 10–20 nm in width and 60–600 nm in length. This ultrastructural profile is similar to that of the first case of S305N. S305N reported here can cause another phenotype closely resembling Pick’s disease.
Lateralization on Neuroimaging Does Not Differentiate Frontotemporal Lobar Degeneration from Alzheimer’s Disease
Authors: Lipton Anne M. , Benavides Raul , Hynan Linda S. , Bonte Frederick J. , Harris Thomas S. , White III Charles L. , Bigio Eileen H.
Published: June 2004

Lateralization on neuroimaging was compared in cases of frontotemporal lobar degeneration (FTLD; n = 10) and cases of definite Alzheimer’s disease (AD; n = 17). All of the cases were pathologically confirmed and semi-quantitative and statistical parametric mapping methods were employed. Seven of the 10 FTLD cases had lateralization on at least one neuroimaging modality: single photon emission computerized tomography (SPECT), MRI, or CT. All 6/6 FTLD cases with SPECT showed lateralization. MRI results generally agreed with SPECT findings. Three of 4 FTLD cases had lateralized atrophy on CT. For the AD cases, 10/17 SPECTs, 2/7 MRIs, and 1/9 CTs showed lateralized findings. Of the neuroimaging modalities utilized, SPECT was the most sensitive in detecting lateralization.
Characterization of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
Authors: Lomen-Hoerth Catherine
Published: June 2004

Amyotrophic lateral sclerosis (ALS) produces progressive weakness, muscular wasting, and spasticity leading to death from respiratory failure at a median of 3 years after onset. ALS and frontotemporal dementia (FTD) overlap in both familial and sporadic cases of ALS. When both occur in families, the affected members may have only ALS, only FTD, or both. This suggests a relationship in the cause of these disorders. We investigated the frequency of ALS in FTD patients and of FTD in ALS patients and found the overlap to be more common than had previously been reported. We report the features of cognitive impairment and pattern of motor involvement in these ALS-FTD patients, and the degree of overlap in both populations.
Frontotemporal Dementia: A Randomised, Controlled Trial with Trazodone
Authors: Lebert Florence , Stekke Willy , Hasenbroekx Christine , Pasquier Florence
Published: June 2004

Behavioural troubles due to frontotemporal dementia (FTD) are difficult to treat. The serotonergic system is associated with frontal lobes, the degeneration of which contributes to FTD. Trazodone increases the extracellular 5-HT levels in the frontal cortex. In a randomised, double-blind, placebo-controlled cross-over study, we investigated the effect of trazodone. There was a significant decrease in the Neuropsychiatry Inventory (NPI) total score with trazodone (p = 0.028) in the 26 evaluable patients. A decrease of more than 50% in the NPI score was observed in 10 patients with trazodone. This improvement was mainly based on the improvement of 4 items of the scale (irritability, agitation, depressive symptoms and eating disorders). The Mini-Mental State Examination was not modified and trazodone was well tolerated. Results of this first placebo-controlled trial suggest that trazodone is an effective treatment for the behavioural symptoms of FTD.
The Multiparametric Scanning System for Evaluation of Minimal Residual Disease in Hematological Malignancies
Authors: Trakhtenbrot Luba , Rechavi Gideon , Amariglio Ninette
Published: June 2004

Combined simultaneous analysis of morphology, immunophenotyping and fluorescence in situ hybridization on the same cell offers advantages that may help to disclose the relevance of minimal residual disease (MRD) detection. Morphological analysis of small populations of cells related either to malignancy or recipient-associated markers may improve the accuracy of chimerism and MRD testing and delineate their clinical significance.
Standardization of Preanalytical Factors for Minimal Residual Disease Analysis in Chronic Myelogenous Leukemia
Authors: Müller Martin C. , Hördt Tanja , Paschka Peter , Merx Kirsten , La Rosée Paul , Hehlmann Rüdiger , Hochhaus Andreas
Published: June 2004

Optimal sample quality is a prerequisite to generate valid data in the detection of minimal residual disease (MRD) in leukemias. Thus, the risk of obtaining ‘false’-negative results is increased when both quality and quantity of RNA are suboptimal. Factors which affect the sensitivity and consequently the validity of MRD results are reviewed. RNA degradation in unstabilized peripheral blood (PB) samples does not play a major role in samples being processed on the day of blood collection. However, the simulation of sample shipping at room temperature with a delay of sample processing of up to 3 days causes a dramatic loss of intact RNA. RNA degradation can be prevented by the use of a bedside RNA stabilization system. Additionally, the stabilizing procedure is capable of keeping real-time quantitative polymerase chain reaction (RQ-PCR) results comparable whether the sample is processed immediately or with a delay of up to 3 days. Consistent quantitative data cannot be obtained with unstabilized blood samples. Furthermore, the optimum volume of PB required for MRD diagnostics in patients with BCR-ABL-positive chronic myelogenous leukemia in complete cytogenetic remission is revisited. Ten milliliters of PB is sufficient for processing on the day of blood collection whereas the use of only 5 ml PB may result in false-negative results. Standardization of preanalytical and analytical factors is necessary to provide a comparability of RQ-PCR results from different laboratories within multicenter studies. The definition of ‘undetectable BCR-ABL’ in an individual patient should take these preanalytical parameters into consideration.
Reintroduction of Antidepressant Therapy across Pregnancy in Women Who Previously Discontinued Treatment
Authors: Cohen Lee S. , Altshuler Lori L. , Stowe Zachary N. , Faraone Stephen V.
Published: June 2004

Background: Pregnancy has frequently been described as a time of emotional well-being conferring ‘protection’ against psychiatric disorders. However, data to support this impression are sparse. Methods: A retrospective review was undertaken in order to examine rates of reintroduction of antidepressants across pregnancy among a cohort of 54 euthymic pregnant women who had discontinued these medications around the time of conception. Reintroduction of antidepressants was used as a marker suggesting relapse of depression. Results: Forty-two percent (n = 23) of these women reintroduced antidepressant therapy during pregnancy, with nearly half of these (n = 11) doing so in the first trimester. A greater time spent in episodes since depressive onset and a prior history of suicide attempts was associated with antidepressant reintroduction. Conclusions: Nearly half of the women who discontinued antidepressants during pregnancy to avoid fetal exposure appeared to experience symptoms severe enough to prompt reintroduction of treatment with these medications. The implications of these findings are discussed with respect to treatment planning for women who are maintained on antidepressants and who plan to conceive.
Influence of Age on the Lips and Perioral Skin
Authors: Lévêque J.-L. , Goubanova E.
Published: June 2004

Background: There are few objective descriptions of the age-related changes taking place on the lips and perioral skin. This zone, however, has great importance in relational functions. Objectives: To describe quantitatively the age-related changes in dimension of the lips and the appearance of the perioral wrinkles, to revisit, thanks to a new method, the pattern of the lip furrows, to compare the hydration states of the upper and lower lips. Methods: On 100 women, we clinically scored wrinkles, dryness of the lips and the general photoageing of the facial skin. We used a Corneometer® for measuring dryness of the lips and SkinChip® for recording lip surface patterns. Results: The upper lip is more hydrated than the lower one, and there is no correlation between lip capacitance and the clinical score of lip dryness. The surface pattern can be classified into 3 main groups with no relation to age. Wrinkle number and visibility are linearly related to age, becoming visible during the fifth decade. The intercommissural distance increases with age, whereas lip height decreases. Conclusions: Both lips are different in terms of dryness. Inversely to their surface pattern, their dimensions are markedly changed with age. The time of apparition of vertical wrinkles suggests a possible influence of hormones.
Secondary Lymphoedema of the Lower Leg as an Unusual Side-Effect of a Liquid Silicone Injection in the Hips and Buttocks
Authors: Gaber Yvonne
Published: June 2004

We report an unusual case of secondary lymphoedema of the lower extremities as a result of injections of liquid silicone. A 30-year-old transsexual had received large-volume injections of silicone in the hips and buttocks for cosmetic purposes in order to obtain a female body form. Painful silicone granulomas developed in both the treated areas and areas outside the original injection location, and a progressive lymphoedema of feet and legs developed during a period of 5 years.
Blue Rubber Bleb Nevus Syndrome Associated with Consumption Coagulopathy: Treatment with Interferon
Authors: Apak H. , Celkan T. , Özkan A. , Yildiz I. , Aydemir E.H. , Ozdil S. , Kuruoglu S.
Published: June 2004

The blue rubber bleb nevus syndrome (BRBNS) is a rare vascular malformation syndrome with cutaneous and visceral lesions frequently associated with serious, even fatal bleeding. No systemic therapy is currently available. We report here a case with disseminated skin and gastrointestinal venous malformations and findings of disseminated intravascular coagulation that was treated with interferon β. The disseminated intravascular coagulation manifestations were cleared with the treatment. The regression of the coagulopathy in our patient led us to think that the use of interferon β in BRBNS might be beneficial.
Hemodynamic Effects of Negative Emotional Pictures – A Test-Retest Analysis
Authors: Stark Rudolf , Schienle Anne , Walter Bertram , Kirsch Peter , Blecker Carlo , Ott Ulrich , Schäfer Axel , Sammer Gebhard , Zimmermann Mark , Vaitl Dieter
Published: June 2004

We investigated subjective and hemodynamic responses towards disgust-inducing, fear-inducing, and neutral pictures in a functional magnetic resonance imaging study. Within an interval of 1 week, 24 male subjects underwent the same block design twice in order to analyze possible response changes to the repeated picture presentation. The results showed that disgust-inducing and fear-inducing scenes provoked a similar activation pattern in comparison to neutral scenes. This included the thalamus, primary and secondary visual fields, the amygdala, the hippocampus, and various regions of the prefrontal cortex. During the retest, the affective ratings hardly changed. In contrast, most of the previously observed brain activations disappeared, with the exception of the temporo-occipital activation. An additional analysis, which compared the emotion-related activation patterns during the two presentations, showed that the responses to the fear-inducing pictures were more stable than the responses to the disgust-inducing ones.
Use of whole genome amplification and comparative genomic hybridisation to detect chromosomal copy number alterations in cell line material and tumour tissue
Authors: Hughes S. , Lim G. , Beheshti B. , Bayani J. , Marrano P. , Huang A. , Squire J.A.
Published: June 2004

We have established that whole genome amplification (WGA), in conjunction with genomic DNA array comparative genomic hybridisation (gaCGH) allows for the identification of genome-wide copy number abnormalities (CNAs) in DNA extracted from both cell line and patient material. To determine the fidelity and reproducibility of WGA to detect copy number imbalances using gaCGH, well characterized cell line genomic DNA was analysed. The gaCGH data obtained from non-amplified DNA and amplified DNA for the neuroblastoma cell line NUB7 and a paediatric medulloblastoma patient was almost identical. In addition, laser capture microdissection (LCM) of prostate tumour cells and subsequent WGA allowed for the detection of a number of CNAs that may not have been identified if DNA had been extracted in bulk from heterogeneous tissue. The results presented here demonstrate the use of WGA for generating sufficient DNA for gaCGH analysis without the introduction of significant sequence representation bias. The combination of amplification and gaCGH using DNA extracted from archival patient material has the potential for permitting the studying of DNA from small cancerous or pre-cancerous foci, which may help to identify potential genomic markers for early diagnosis.
Interspecies comparison of neuroglobin, cytoglobin and myoglobin: Sequence evolution and candidate regulatory elements
Authors: Wystub S. , Ebner B. , Fuchs C. , Weich B. , Burmester T. , Hankeln T.
Published: June 2004

Neuroglobin and cytoglobin are two novel members of the vertebrate globin family. Their physiological role is poorly understood, although both proteins bind oxygen reversibly and may be involved in cellular oxygen homeostasis. Here we investigate the selective constraints on coding and non-coding sequences of the neuroglobin and cytoglobin genes in human, mouse, rat and fish. Neuroglobin and cytoglobin are highly conserved, displaying very low levels of non-synonymous nucleotide substitutions. An oxygen supply function predicts distinct modes of gene regulation, involving hypoxia-responsive transcription factors. To detect conserved candidate regulatory elements, we compared the neuroglobin and cytoglobin genes in mammals and fish. The myoglobin gene was included to test if it also contains hypoxia-responsive regulatory elements. Long conserved non-coding sequences, indicative of gene-regulatory elements, were found in the cytoglobin and myoglobin, but not in the neuroglobin gene. Sequence comparison and experimental data allowed us to delimit upstream regions of the neuroglobin and cytoglobin genes that contain the putative promoters, defining candidate regulatory regions for functional tests. The neuroglobin and the myoglobin genes both lack conserved hypoxia-responsive elements (HREs) for transcriptional activation, but contain conserved hypoxia-inducible mRNA stabilization signals in their 3′ untranslated regions. The cytoglobin gene, in contrast, harbors both conserved HREs and mRNA stabilization sites, strongly suggestive of an oxygen-dependent regulation.
Role of Iodine-131 MIBG Scanning in the Management of Paediatric Patients with Neuroblastoma
Authors: Shah Syed G.M. , Naseer H. , Usmani G.N. , Cheema M.A.
Published: June 2004

Objectives: To evaluate the role of iodine-131 metoiodobenzylguanidine (iodine-131 MIBG) scanning in the management of paediatric patients with neuroblastoma. Subjects and Methods: Forty-three iodine-131 MIBG scans were performed on 26 children, 18 male and 8 female, ranging in age from 8 months to 11 years. Bone scan, computed tomography (CT) images and findings of bone marrow biopsy were compared with the iodine-131 MIBG scan findings. Results: Of the 26 patients, 18 (69%) showed abnormal iodine-131 MIBG avidity and were proven to have a neural crest tumour on histology. The remaining 8 (31%) patients had normal iodine-131 MIBG scans, and histology showed a malignancy other than a neural crest tumour. Iodine-131 MIBG scans showed the primary site in 16 of 17 patients while CT showed 14 primary sites. In follow-up studies, the results were as follows: iodine-131 MIBG showed no evidence of disease in 4 compared with 3 on CT, persistent disease in 2 on iodine-131 MIBG and 4 on CT; recurrence in 1 on iodine-131 MIBG and 0 on CT; MIBG scans detected double the number of bony lesions compared with bone scans. The findings on iodine-131 MIBG scans and bone marrow biopsy were in agreement in 16/18 cases. Patients in whom iodine-131 MIBG scans showed disease resolution had better clinical outcomes. Conclusion: The findings indicate that iodine-131 MIBG scanning is useful for the diagnosis, staging, evaluation of response to therapy and detection of recurrences in patients with neuroblastoma. It exhibited a clear advantage over CT in detecting the primary site and soft issue metastases and was also superior to bone scanning in detecting skeletal metastases. It also reliably demonstrated bone marrow involvement.
Estrogen Receptor Profiles: Changes in Mouse and Rat Mammary Tumors by Treatment with Selective Estrogen Receptor Modifiers
Authors: Actis A.M. , Cocca C.M. , Gutierrez A. , Croci M. , Rivera E.S. , Bergoc R.M.
Published: June 2004

Objective: The aim of this work was to analyze the effect of estradiol (E2), medroxyprogesterone and the two selective estrogen receptor modulators (SERMs) (tamoxifen (Tam) and raloxifene (Ral)) on the estrogen receptor (ER) conformers profile performed by size exclusion HPLC in relation to hormone dependence of mammary tumors. Materials and Methods: Two types of mammary tumors were studied: tumors transplanted in BALB/c mice that are medroxyprogesterone acetate (MPA)-dependent for growth, and tumors induced in Sprague-Dawley rats by intraperitoneal injection of N-nitroso-N-methylurea (NMU). Tumors from mice treated with MPA, E2, Tam or Ral and NMU-treated rats were analyzed and compared to that of control. Results: The tumor conformer profiles were as follows: control and MPA-treated mice showed only one peak (oligomeric form); E2-treated mice also showed only one peak (dimer); Tam-treated mice showed one peak corresponding to a possible proteolytic fragment, and Ral-treated mice showed two peaks (oligomeric and a possible proteolytic fragment). On the other hand, NMU-induced mammary tumors from rats showed three peaks (oligomeric, monomeric and proteolytic). Conclusion: Our findings may indicate that SERMs affect the aggregation state of ER and thereby its ability to modulate genomic transcription mechanisms related to growth rate.
Long-Term Efficacy and Safety of Pimecrolimus Cream 1% in Adults with Moderate Atopic Dermatitis
Authors: Meurer Michael , Fartasch Manige , Albrecht Gisela , Vogt Thomas , Worm Margitta , Ruzicka Thomas , Altmeyer Peter Josef , Schneider Dirk , Weidinger Gottfried , Braeutigam Matthias
Published: June 2004

Background: Pimecrolimus cream 1% is a non-steroid, selective inflammatory cytokine inhibitor indicated for atopic dermatitis (AD). Objective: To compare the safety and efficacy of pimecrolimus cream 1%-based treatment versus conventional therapy in adults with moderate AD. Methods: Patients were randomized to receive pimecrolimus cream 1% (n = 62) or vehicle (n = 68) at the first signs/symptoms of AD, for 24 weeks as required. A moderately potent topical corticosteroid (prednicarbate 0.25% cream) was allowed in both groups to treat flares. Results: Corticosteroids were required on fewer days in the pimecrolimus group, compared with the vehicle group (9.7 vs. 37.8%, p < 0.001). Furthermore, 59.7% of pimecrolimus-treated patients experienced no flares during the study period, compared with 22.1% of vehicle-treated patients (p < 0.001). Pimecrolimus cream 1% was well tolerated throughout the study. Conclusion: For adults with moderate AD, pimecrolimus cream 1% is well tolerated, reduces the incidence of flares, reduces/eliminates corticosteroid use, improves long-term disease control and enhances the patients’ quality of life.
Analysis of 16,922 Patients with Acute Ischemic Stroke and Transient Ischemic Attack in Japan
Authors: Kimura Kazumi , Kazui Seiji , Minematsu Kazuo , Yamaguchi Takenori
Published: June 2004

Objective: The purpose of the present study was to clarify the present status of stroke medicine in Japan using a hospital-based, prospective registration study of 156 hospitals from all over Japan. Methods: Consecutive patients with acute ischemic stroke and transient ischemic attack (TIA) who presented to hospital within 7 days of onset from May 1999 to April 2000 were enrolled in this study. A common protocol was applied in every participating hospital. Results: A total of 16,922 patients (TIA, 6.4%) with a mean age of 70.6 ± 11.5 years (median 71 years, range 18–107 years) were enrolled in the study. Lacunar stroke was the most frequent stroke subtype (38.8%), followed by atherothrombotic (33.3%), cardioembolic (21.8%) and other stroke (6.1%). NIHstroke scale score on admission was 8.0 ± 7.9 (median 5; 25th to 75th percentile, 2–11). 36.8% arrived at hospital within 3 h of symptom onset, and 49.5% within 6 h. The ambulance was used for 70.2% of patients arriving within 3 h after onset, but in only 29.9% of patients visiting the hospital later than 3 h after onset (p < 0.0001). 60.8% displayed good outcome (modified Rankin Scale score of 0–2 at discharge), while 32.3% displayed poor outcome (score 3–5), and mortality rate was 6.9%. Conclusions: More than half of the acute stroke patients arrived at hospital later than 6 h after onset. Establishment of ideal emergency systems is needed for better management of stroke and for improvement of patient outcome, in particular, in the future after approval of intravenous recombinant tissue plasminogen activator for acute ischemic stroke by the Japanese government.
Carotid Artery Stenting:The Need for Randomised Trials
Authors: Brown Martin M. , Hacke Werner
Published: June 2004

Endovascular treatment for carotid artery stenosis avoids some of the complications of carotid endarterectomy, but has not been widely accepted. Concerns about the risks and benefits of endovascular treatment led to the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS). There was no difference in major outcome events between endovascular treatment and carotid endarterectomy, but the rate of procedural stroke or death was higher than desirable. There was no difference either in the rate of stroke during follow-up, but the confidence intervals were very wide and severe ipsilateral carotid stenosis was more frequent 1 year after endovascular treatment than after carotid surgery. Two other randomised trials of carotid stenting were stopped early after poor outcomes in stented patients. These early trials used techniques which have now been superseded, but the results emphasise the need to improve the safety of endovascular treatment. Recent advances designed to improve safety include new designs of stents and delivery systems, and devices designed to protect the brain from embolisation during stenting. However, there is little convincing evidence that these new devices reduce the rate of stroke. Moreover, a systematic review of the existing randomised trial data concluded that there the current evidence does not support a shift away from recommending carotid endarterectomy as the standard treatment for carotid stenosis. There is therefore a clear need for further randomised trials of carotid stenting. Three of the ongoing trials, EVA-3S, SPACE and ICSS (CAVATAS-2), have prospectively agreed to combine individual patient data after completion of follow-up. This meta-analysis will provide results similar to a mega-trial and should also allow informative subgroup analyses. The co-operation between the trials in agreeing to perform this meta-analysis is a major advance in trial design. The result should determine whether carotid stenting truly rivals carotid endarterectomy as the treatment of choice for carotid stenosis.
T Lymphocyte-Mediated Immune Responses to Chemical Haptens and Metal Ions: Implications for Allergic and Autoimmune Disease
Authors: Martin Stefan F.
Published: June 2004

Chemical haptens and metal ions interact with proteins and thereby become recognizable by T and B lymphocytes. They induce the production of proinflammatory cytokines and chemokines by various cell types due to triggering of innate immune responses. This is an important prerequisite for the activation of the adaptive immune system and the development of diseases like allergic contact dermatitis and adverse drug and autoimmune reactions. Our increasing knowledge about the molecular basis of hapten and metal ion recognition by T cells and about the pathomechanisms of contact hypersensitivity and chemical-induced autoimmune reactions allows concomitant progress in the development of modern strategies for immunotherapy and will hopefully enable more specific intervention in hapten- and metal ion-induced human diseases in the future.
Quantitative Analysis of Mast Cells in Benign and Malignant Breast Lesions
Authors: Kashiwase Yayoi , Morioka Junichiro , Inamura Hiroaki , Yoshizawa Yoshitomo , Usui Ryu , Kurosawa Motohiro
Published: June 2004

Background: It has been reported that the number of mast cells was significantly greater in malignant breast carcinomas than in benign breast lesions. This was due to tryptase-containing mast cells while tryptase, chymase-containing mast cells had no effect. However, analysis of mast cells in breast carcinomas and benign breast lesions based on their histological findings remains to be elucidated. Methods: Using immunohistochemical methods morphological examinations of mast cells were undertaken in benign and malignant breast tissues from 51 patients (30 benign, 21 malignant), which were formalin-fixed and paraffin-embedded. In the study with malignant breast tissues, samples of malignant tissues and adjacent healthy tissues were obtained from a single patient, and the number of mast cells was compared. Results: Among benign breast tissues, the number of mast cells in intracanalicular fibroadenoma was significantly lower than that in pericanalicular fibroadenoma as well as that in mastopathy. The number of mast cells was significantly greater in malignant lesions than that in benign lesions. The number of mast cells in scirrhous carcinoma and that in solid-tubular carcinoma were significantly increased compared with that in adjacent healthy tissues. In addition, the number of mast cells in scirrhous carcinoma was highest among breast carcinomas, and significantly greater than that in papillotubular carcinoma. Conclusion: We were the first to find the significant lower number of mast cells in intracanalicular breast fibroadenoma when compared with that in pericanalicular fibroadenoma as well as that in mastopathy. Moreover, the number of mast cells in scirrhous carcinoma was significantly greater than that in papillotubular carcinoma.
Association of IL4 Gene Polymorphisms with Asthma in North Indians
Authors: Nagarkatti Rana , Kumar Raj , Sharma Surendra K. , Ghosh Balaram
Published: June 2004

Background: Asthma is a complex airway disorder, and a number of genetic loci have been found to be associated with asthma. The 5q31–33 region is one of the most important loci linked to asthma and atopic disorders. However, association studies with candidate genes in this region, such as IL4, were inconclusive, as both positive and negative results were obtained in several populations studied. The aim of our case-control study was to determine the association between IL4 and asthma in North Indians. Patients and Methods: Polymorphisms in the promoter and a dinucleotide repeat in the 2nd intron in IL4 were genotyped by sequencing and GeneScan analysis, respectively, in ethnically matched, unrelated patients (n = 171) and controls (n = 128), following the guidelines of the American Thoracic Society. Results: The proximal promoter region of the IL4 gene was found to be invariant. Previously reported polymorphisms, –590 C/T and +33 C/T, were found to be absent in our population. The χ2 test using only large expected cell counts (more than 5% of the sample size) showed a significant association between allele size and disease status (χ2 = 38.08, d.f. = 6, p < 0.05). In addition, a significant difference was observed for the allele and genotype frequencies (p < 0.0005 and p = 0.0009, respectively) in the patient and the control groups using the Fisher-Freeman-Halton test. Conclusion: Our studies indicate that the promoter of the IL4 gene is invariant in our population. The case-control studies on the CA repeat polymorphism in the 2nd intron of the IL4 gene have shown interesting results and indicate the need for further family-based studies.