bluuebunny/crossref_metadata_2025 huggingface dataset:
ERROR DETECTION IN GENETIC LINKAGE DATA FOR HUMAN PEDIGREES USING LIKELIHOOD RATIO METHODS
Authors: EHM MARGARET GELDER , KIMMEL MAREK , COTTINGHAM ROBERT W.
Published: November 2004

The occurrence of laboratory typing error in pedigree data collected for use in linkage analysis cannot be ignored. In maps where recombinations between nearby markers rarely occur, each erroneous recombinations (result of typing error) is given substantial weight thereby increasing the estimate of θ, the recombination fraction. As the maps being developed become more dense, θ approaches the error rate and most of all observed crossovers will be erroneous. We present a method for detecting errors in pedigree data. The index is a variant of the likelihood ratio test statistic and is used to test the null hypothesis of no error for an individual at a locus versus the alternative hypothesis of error. High values of the index correspond to unlikely genotypes. The method has been shown to detect errors introduced into CEPH pedigrees and an error in a larger experimental pedigree (retinitis pigmentosa). While the method was designed to detect typing error, it is sufficiently general to detect any relatively unlikely genotype and therefore can also be used to detect pedigree error.
TOPOGRAPHIC MODELING OF #1 G-BANDED CHROMOSOME
Authors: RINALDI G. RUBBIA , BIANCHI N. , MARVEGGIO G. , MORABITO A. , MUSSIO P. , DI LERNIA R.
Published: November 2004

An approach to a quantitative description of bands and interbands, representing alternating visible zones of chromatin packaging is presented. The study is performed on selected human chromosome (#1) obtained from G-banded metaphases observed by the optical microscope.

In order to segment the image into structures of interest a topographic approach is proposed: greytone images are seen as landsurfaces (i.e., the grey tone of a pixel is the elevation in that point) and structures to be detected are considered as topographic relieves.

In the segmentation process a rewriting process translates the greytone digital image into an image where each pixel is labelled by a symbol denoting the type of structure to which the pixel belongs. Rewriting is performed by repeatedly applying the rules of Bidimensional Lindenmayer Systems (BLS) to the input image.

In each step BLS rules are applied to evaluate a local property. The repeated application of the rules combine the local properties of pixels up to an arbitrary distance, simulating an information diffusion process that determines the emergence of global properties of sets of pixels of arbitrary shape.

Detected Troughs and Lowlands are interpreted as tracks of bands and interbands and from their description there derives a set of geometrical attributes. These attributes are useful to measure the distances between bands and interbands and hence to follow the dynamic packaging of chromosomes before cell division.

Finally, topographic labelling seems to enhance the resolution level of chromosome features, especially for faint bands, thus it is reasonable to expect that even microvariations important in cytogenetic pathology can be detected.
PARALLEL ANALOG COMPUTATION OF COUPLED BIOLOGICAL OSCILLATORS
Authors: BODE M. , RUWISCH D. , SCHÜTZ P. , ALONSO M. , PÉREZ-MUÑUZURI V. , PÉREZ-VILLAR V. , MARKUS M.
Published: November 2004

In this work the dynamics of coupled nonlinear oscillators, which are ubiquitous in biology, is experimentally studied by using electrical relaxation oscillators. The results of this analog computation obtained with two and three coupled oscillators are in agreement with the results known from numerical approaches. Phase death, which is a mutual annihilation of oscillations, is a generic phenomenon. All modes known from approaches using identical oscillators have been found. Additionally we observed new generic modes that are caused by inhomogeneities of the oscillators, such differences being typical for biological cells. Simulations of excitable electrical oscillators yield similar results.
PRINCIPLES OF METABOLIC CONTROL THEORY
Authors: HEINRICH REINHART
Published: November 2004

Starting from parameter independent definitions of scaled and unscaled control coefficients for fluxes and metabolite concentrations the basic assumption and equations of metabolic control theory are explained. The theory is extended for the control of relaxation processes as well as by consideration of finite perturbations of reaction rates.
HIERARCHIES IN CONTROL
Authors: JENSEN P.R. , VAN DER GUGTEN A.A. , BIER M. , VAN HEESWIJK W.C. , ROHWER J. , MOLENAAR D. , VAN WORKUM M. , RICHARD P. , TEUSINK B. , BAKKER B.M. , KHOLODENKO B.N. , WESTERHOFF H.V.
Published: November 2004

The living cell functions by virtue of an enormous number of different processes. It is one of the most difficult challenges of modern biology to elucidate how all those processes are coordinated quantitatively so as to lead to a viable system with optimal responses to various changes in the environment. The biochemical and biophysical processes of the living cell do not constitute a network with random connections. In this paper we shall discuss that cell function is organized in hierarchical substructures. We will briefly touch on the topics of (i) metabolic control and regulated gene expression, (ii) time dependent metabolism in intact yeast cells, and (iii) metabolite channelling.
EVOLUTION OF METABOLISM: OPTIMIZATION OF GLYCOGEN STRUCTURE
Authors: MELÉNDEZ-HEVIA ENRIQUE , WADDELL THOMAS G. , RAPOSO RAQUEL R. , LUPIÁÑEZ JOSÉ A.
Published: November 2004

The animal glycogen molecule has to be designed in accordance with its metabolic function as a very effective fuel store which allows the quick release of large amounts of glucose, and also should account for a high capacity of glucose storage occupying the least possible space. We have studied the optimization of these variables by means of a mathematical model of the glycogen molecule. Our results demonstrate that the structure of the glycogen molecule has an optimized design for (a) maximizing the total stored glucose in the smallest possible volume of the molecule, (b) maximizing the proportion of it which can be directly released by phosphorylase before any debranching occurs, and (c) maximizing the number of non reducing ends (points of attack for phosphorylase), which maximizes the quickness of fuel release. This has been achieved with appropriate values of two key parameters in glycogen design: the branching degree and the length of the chains.
A CHEMICAL SYSTEM WITH HOPF BIFURCATION CONSISTING OF THREE INTERMEDIATES AND MONO- AND BIMOLECULAR REACTIONS
Authors: WILHELM THOMAS , HEINRICH REINHART
Published: November 2004

The smallest system with only mono- and bimolecular reactions, defined from the mathematical point of view, with Hopf bifurcation is presented. Since two-component systems with only mono- and bimolecular reactions cannot have a Hopf bifurcation, the smallest system must have at least three mtermediates. On the basis of a necessary and sufficient condition for a Hopf bifurcation in three-dimensional systems, it is possible to find one reaction system which is the smallest -one. In the first part of this paper it is shortly pictured and in the second part a proof that this system is really the searched smallest one is given.
AZT EFFECT ON THE BONE MARROW — A NEW PERSPECTIVE ON THE CONCORDE TRIAL
Authors: AGUR Z. , COJOCARU L. , SCHECHTER B. , TAGLIABUE G. , UBEZIO P.
Published: November 2004

The Concorde trial shows an increase in CD4 + lymphocytes, but not a higher survival, in AZT treated asymptomatic patients. Our murine bone-marrow experiments show that in chronic AZT treatments a large increase in the lymphoids/erythroids compartment is due to host cytotoxicity. We put forward a mathematical formula for predicting cytotoxicity of given drug protocols, which can be used for modulating the schedule so as to increase its efficacy while maintaining its toxicity low. Our study suggests that in chronic treatments a large, single, daily dose will be less toxic than the same dose divided into several daily dosings.
STABILITY DUE TO VARIABILITY IN DAISYWORLD MODELS
Authors: STÖCKER SABINE
Published: November 2004

The Daisyworld is a mathematical model to describe a coupling between biosphere and climate. It was developed by J.E. Lovelock in context with the so-called Gaia-Hypothesis, which postulates that conditions on earth are suitable for life because of the existence of life itself. Some variations of the classical model will be discussed and so it can be shown, that the occurrence of mutations of the existing species will not harm the capability of regulating the system. Furthermore models provoking structures either in time or in space by self-organization will be presented. Such structures in time and space will enlarge the biological diversity and stabilize the system because of a more effective use of resources.
PATTERN FORMATION IN A MODEL FOR PREBIOTIC EVOLUTION
Authors: CHACÓN P. , NUÑO J.C.
Published: November 2004

The dynamics of a catalytic network formed by four kinds of self-replicative species (replicators) with nonspecific catalytic capabilities is analysed. The evolution takes place in an extended closed reactor, so that the total population is kept constant. In the limit of no diffusion, the system exhibits tristability between chaos and two fixed points for a particular set of parameters. We show that under this setup, the system undergoes pattern formation when diffusive forces are considered. The biological implications of these results within a hypothetic prebiotic scenario (RNA-world) are also discussed.
CLINICAL DATA ANALYSIS AND MATHEMATICAL MODELING OF MIXED INFECTIONS
Authors: YU MATVEEV A. , ROMANYUKHA A. A.
Published: November 2004

Quantitative analysis data describing course of viral hepatitis show that concominal viral respiratory infection did not influence hepatitis severity and the rate of recovery after it. In the groups of hepatitis patients with different severity we also found the upper respiratory infections increasing proportional to the hepatitis severity. The rhinoviral infection initiation model in healthy and in hepatitis patients was obtained. Using this model allowed us to describe the phenomenon of upper respiratory infection incidence increasing in viral hepatitis dynamics.
THE ROLE OF ANTIGEN PRESENTATION IN THE REGULATION OF CLASS-SPECIFIC (TH1/TH2) IMMUNE RESPONSES
Authors: MURAILLE E. , LEO O. , KAUFMAN M.
Published: November 2004

To prevent progressive and fatal expansion of an infectious agent, it is critical for the host to develop the appropriate immune response. The induction of a given set of effector cells is determined by the activation of T helper lymphocytes. These CD4 T cells can be classified into TH1 and TH2 lines according to their cytokine release pattern and their regulatory functions. Each subclass regulates a different set of immune effectors and they are, most of the time, mutually exclusive. Since not all immune effectors are effective against a given pathogen, the choice of a class response is thus a crucial event. We propose a qualitative model for understanding the dynamics of the TH1-TH2 network. In our model, the induction of a TH1 or a TH2 response is a function of the physical features of the pathogen, of the site of infection and of the efficiency of the ongoing response. One of our predictions is that anergy, in addition to its role in the mechanisms of peripheral tolerance, could have an important influence on the regulation of the TH1-TH2 balance. In summary, our model accounts for several important experimental observations in terms of transitions between multiple steady states. It emphazises the role of antigen presentation in directing the choice of a class-specific response.
THRESHOLD CROSSING PROBABILITIES FOR POPULATION GROWTH MODELS IN RANDOM ENVIRONMENTS
Authors: BRAUMANN CARLOS A.
Published: November 2004

Consider the general population growth model in a random environment dN/dt= (r+σε(t))Nf(N), N(0)=N0>0, where N=N(t) is the (animal, cell, etc.) population size or biomass at time t≥0, r>0 is an intrinsic growth parameter subjected to environmental random fluctuations approximately described by σε(t) (σ>0 noise intensity parameter, ε(t) standard white noise), and f(N) is a well-behaved density-dependence function. Due to demographic stochasticity and Allee effects, a slightly modified model that corrects for inadequacies at small population sizes is also considered. In many applications (wildlife management, environmental impact assessment, pest control, growth of bacterial cultures, tumor or body growth, etc.), one needs the probability of N(t) ever crossing a given threshold during a given time horizon. We consider the cases of a low threshold N1N0 (for instance, a pest’s damaging level). We also obtain other related threshold crossing probabilities of interest. A reference is made to statistical estimation and hypothesis testing.
THE FORCE OF INFECTION IN POPULATIONS OF VARYING SIZE: A MODELLING PROBLEM
Authors: DIEKMANN O. , DE JONG M.C. M. , DE KOEIJER A.A. , REIJNDERS P.
Published: November 2004

It is argued that the (quasi-) mechanistic modelling of the incidence of an infectious disease in a population of varying size is a nontrivial problem, deserving careful thinking. The spread of a virus among seals is used to illustrate how a submodel for the contact process may be helpful. In that same context the impact of the disease on the population growth of the host is investigated.
A MODEL FOR ANNUAL PLANT DYNAMICS WITH SEED BANK AND DENSITY-DEPENDENT EFFECTS
Authors: KHALADI MOHAMED , JARRY MARC , HOSSAERT-MCKEY MARTINE
Published: November 2004

A model is proposed for the population dynamics of an annual plant with a seed bank (i.e. in which a proportion of seeds remain dormant for at least one year). In this model, demographic parameters (dormancy and germination rate) of the seeds of the year are different from those of the seeds of the seed bank. First, a simple linear matrix model is deduced from the life cycle graph and a more complicated model is built by introducing density dependence effect. The obtained system, nonlinear with delay, can be simplified by a change of variables. A non-trivial fixed point of this system is obtained and the conditions of stability are studied. Under certain conditions (choice of exponential law for functional response of density dependence and absence of seed mortality before germination) we show that conditions of stability depend only on 3 parameters, the dormancy rate of the seeds of the year, dormancy rate of the seeds of the seed bank and the maximum potential fecundity of adults. Study of the behaviour of this model in the parameter space shows that the domain of demographic stability can be reduced if the dormancy rate of seeds of the year is low, even if the dormancy rate of seeds of the seed bank is high.
SIMULATION OF THE DYNAMICS OF MYXOBACTERIA SWARMS BASED ON A ONE-DIMENSIONAL INTERACTION MODEL
Authors: PFISTNER BEATE
Published: November 2004

Myxobacteria have a high level of intercellular coordination. Their swarms show “streets” and “whirls” of parallel gliding cells as well as wave-like moving cell density fields, so called “rippling”. The dependence from two phenomenological parameters, gliding velocity and turning frequency, has turned out to be characteristic for cell behavior at the swarm edge. As cells at the swarm edge are mostly gliding parallel in one dimension, the behavior of single cells can be comprised in a one-dimensional model describing interactions between cells of the same species in a homogenous environment, where turning frequency determines the cell density distribution via a hyperbolic differential integral equation. After specifying the parameter functions appearing in the integral, it is examined how these parameters influence the turning behavior and therefore the edge development of swarms over time.

Numerical simulations of this model are performed both for the stationary and the time dependent case. For the time dependent model a front tracking method is applied using a Lagrange interpolation at the swarm edge. The simulations show that perception of different gliding directions is significant for the dynamics of swarm expansion and retraction.
NUMERICAL SIMULATION OF ELECTRIC FIELDS GENERATED BY OBLIQUE DIPOLE LAYERS IN ELECTROCARDIOLOGY
Authors: GROPPI M. , PENNACCHIO M.
Published: November 2004

In this paper we present two approximate models for the excitation wavefront which gives rise to the electric field measurable in electrocardiology. The first model is based on the singular perturbation technique and the second on the oblique dipole layer theory. By means of the finite element method we compute extracellular potentials generated during the depolarization phase of the excitation process in a simplified model of cardiac muscle, consisting of an insulated infinite tridimensional wall of anisotropic myocardium. Numerical results for the two approximations are compared and discussed.
ON THE CAPABILITY OF THE FOURIER APPROXIMATION TO DESCRIBE BREATHING PATTERNS
Authors: HÄMÄLÄINEN RAIMO P. , KETTUNEN ANU
Published: November 2004

The characterization of respiratory air flow patterns is a subject of continous interest. The graphical analysis of the air flow curves started with visual indices and subsequently lead to harmonic analysis. The research group of Dr. Benchetrit suggests that respiratory patterns can be accurately described by the Fourier approximation. It is suggested that the first four Fourier sine components satisfactorily reproduce the shape of the cycle. This paper evaluates the accuracy of the Fourier approximation approach in describing the breathing pattern. Our analysis shows that for smooth, nearly symmetric air flow curves even the first three components give a reasonable approximation. However, as the shape of the air flow curve differs from smooth, quite symmetric patterns and flattens, the accuracy of fit of the Fourier approximation deteriorates and becomes unsatisfactory.
TRAIL FOLLOWING AND AGGREGATION OF MYXOBACTERIA
Authors: STEVENS ANGELA
Published: November 2004

This paper deals with the question whether myxobacteria can aggregate due to slime trail following. The starting point is a stochastic cellular automaton model where the bacteria are particles moving due to the rules of a jump process. A simplified case of this automaton shows that the slime has to be produced in an extremely high amount to account for aggregation. This simplified cellular automaton is connected to a stochastic many particle system from which a system of partial differential equations can be derived, a so-called chemotaxis-system. Here a moderate interaction between the particles has to be taken into account. In the last part this system is analyzed numerically to see whether it reflects the results of the simplified cellular automaton.
SINGLE CELL-AGGREGATE DYNAMICS
Authors: TIMM UWE , OKUBO AKIRA
Published: November 2004

We present a dynamical model for the particle-cluster aggregation process of marine snow. The model consists of only two parts, i.e. single cells and one type of aggregates. The parameters are settling and decomposition of aggregates; growth and aggregation of single cells. There are developed numerical results of the system.
A PROBABILISTIC MODEL OF NEURONAL INTEGRATION
Authors: BERTHOMMIER FRÉDÉRIC
Published: November 2004

A probabilistic estimation of an integrate and fire model commonly used for performing biologically plausible neurocomputing is proposed. It processes the temporal information of the input stimuli as a group of cells — the stellate or Chopper cells of the cochlear nucleus. The main properties are the same as the ones of the common Hodgkin–Huxley system. This model has a limited set of parameters: time constant of the membrane potential, threshold level, refractory durations. It is defined by a delay differential system having a low cost of computation. Original properties such as blocking and reset are introduced, providing a control of the oscillatory behaviour useful for building functional neural nets. In order to recover the parameters of neurons, we also analyze the first interspike interval histogram.
"DYNAMICAL CONFINEMENT" IN NEURAL NETWORKS
Authors: JÉZÉQUEL C. , NÉROT O. , DEMONGEOT J.
Published: November 2004

Randomisation of a well known mathematical model is proposed (i.e. the Hopfield model for neural networks) in order to facilitate the study of its asymptotic behavior: in fact, we replace the determination of the stability basins for attractors and for stability boundaries by the study of a unique invariant measure, whose distribution function maxima (or respectively, percentile contour lines) correspond to the location of the attractors (or respectively, boundaries of their stability basins). We give the name of "confinement" to this localization of the mass of the invariant measure. We intend to show here that the study of the confinement is in certain cases easier than the study of underlying attractors, in particular if these last are numerous and possess small stability basins (for example, for the first time we calculate the invariant measure in the random Hopfield model in a case for which the deterministic version exhibits many attractors, and after in a case of phase transition).
ECOLOGICAL ECONOMICS AND ECOLOGICAL DARWINISM
Authors: KHALIL ELIAS L.
Published: November 2004

The paper assesses the ecological approach which challenges the standard concept of scarcity in both neoclassical economics and neo-Darwinian orthodoxy. The focus is on comparative theory analysis with regards to the relevance of matter/energy influx. It should not be surprising, in light of the mathematical structure, that the ideas of optimization of utility in orthodox economics and optimization of fitness in mainstream biology are based on common assumptions. One of the assumptions is that environmental resources are given or exist passively in relation to the actor. Otherwise, the mathematical maximization functions would not be feasible. The orthodox assumption of resources as given for a specific population of firms or organisms need not deny that the environment continuously changes, but the assumption entails that such changes are by-products of the interaction of the population with the environment, the interference of other populations, and other exogenous factors. Thus, the orthodox assumption of resources as given, according to the ecological school, excludes, at first approximation, endogenous factors in the explanation of environmental dynamics or the economy-environment nexus. Inspired by Alfred Lotka's work, the ecological agenda in economics (as led by Daly and Costanza) and in biology (as advocated by Odum, Wicken, Depew, Weber, and Ulanowicz) advance the same alternative to the orthodox axiom concerning resources; viz., resources are a function of the active agent. While such an alternative is very fruitful, it does not go far enough. It has limitations: In economics, the ecological approach generally cannot solve the long-term problem of the asymmetric exchange between human economy and the environment. In the life sciences, the ecological approach, as far as it adheres to reformed Darwinism, faces difficulties with regards to the concepts of organization and the process of development/evolution. These problems call for similar conceptual innovations in both disciplines.
A PHYSICAL MODEL OF THE WRIST DYNAMICS
Authors: PEREZ ALAIN
Published: November 2004

The wrist articulation represents one of the most complex mechanical system of the human body. It is composed of eight bones rolling and sliding along their surface and along the faces of the five metacarpals of the hand and the two bones of the arm. The wrist dynamics is however fundamental for the hand movement, but it is so complex that it still remains incompletely explored. This work is part of a new concept of Computer Assisted Surgery, which consists in developing computer models to perfect surgery acts by predicting their consequences.

The physical wrist dynamics model is based first on the static model of its bones in three dimensions. Their 3D model is chosen to optimize the collision detection procedure, which is the necessary step to estimate the physical contact constraints. As many other possible computer vision models do not fit with enough precision to this problem, a new 3D model has been developed using the Median Axis of the digital distance map of the bones reconstructed volume. The collision detection procedure is then simplified for contacts were detected between spheres.

With a good 3D model of the solids, the dynamics of the wrist can then be approached by integrating its fundamental differential equations, and thanks to a geometric model of the contact constraints. The experiments of this original 3D dynamic model has already produced computer animations. The wrist dynamic model must be however completed with ligament models to reach realistic animations, which would be then compared to radio-camera data.
Topiramate is an insulin-sensitizing compound in vivo with direct effects on adipocytes in female ZDF rats
Authors: Wilkes Jason J. , Nelson Elizabeth , Osborne Melville , Demarest Keith T. , Olefsky Jerrold M.
Published: November 2004

We have studied the in vivo and in vitro effects of Topiramate (TPM) in female Zucker diabetic fatty (ZDF) rats. After weight matching, drug treatment had a marked effect to lower fasting glucose levels of relatively normoglycemic animals as well as during an oral glucose tolerance test. The glucose clamp studies revealed a ∼30% increased glucose disposal, increased hepatic glucose output (HGO) suppression from ∼30 to 60%, and an increased free fatty acid suppression from 40 to 75%. Therefore, TPM treatment led to enhanced insulin sensitivity at the level of tissue glucose disposal (increased ISGDR), liver (increased inhibition of HGO), and adipose tissue (enhanced suppression of lipolysis). When soleus muscle strips of control or TPM-treated ZDF rats were studied ex vivo, insulin-stimulated glucose transport was not enhanced in the drug-treated animals. In contrast, when isolated adipocytes were studied ex vivo, a marked increase (+55%) in insulin-stimulated glucose transport was observed. In vitro treatment of muscle strips and rat adipocytes showed no effect on glucose transport in muscle with a 40% increase in insulin-stimulated adipocyte glucose transport. In conclusion, 1) TPM treatment leads to a decrease in plasma glucose and increased in vivo insulin sensitivity; 2) insulin sensitization was observed in adipocytes, but not muscle, when tissues were studied ex vivo or in vitro; and 3) TPM directly enhances insulin action in insulin-resistant adipose cells in vitro. Thus the in vivo effects of TPM treatment appear to be exerted through adipose tissue.
Comparative effects of DHEA vs. testosterone, dihydrotestosterone, and estradiol on proliferation and gene expression in human LNCaP prostate cancer cells
Authors: Arnold Julia T. , Le Hanh , McFann Kimberly K. , Blackman Marc R.
Published: November 2004

Serum levels of the adrenal androgen dehydroepiandrosterone (DHEA) peak in men and women in the third decade of life and decrease progressively with age. Increasing numbers of middle-aged and older individuals consume over-the-counter preparations of DHEA, hoping it will retard aging by increasing muscle and bone mass and strength, decreasing fat, and improving immunologic and neurobehavioral functions. Because DHEA can serve as a precursor to more potent androgens and estrogens, like testosterone (T), dihydrotestosterone (DHT), and 17β-estradiol (E2), supplemental DHEA use may pose a cancer risk in patients with nascent or occult prostate cancer. The steroid-responsive human LNCaP prostate cancer cells, containing a functional but mutated androgen receptor (AR), were used to compare effects of DHEA with those of T, DHT, and E2 on cell proliferation and protein and/or gene expression of AR, prostate-specific antigen (PSA), IGF-I, IGF-I receptor (IGF-IR), IGF-II, IGF-binding proteins-2, -3, and -5, (IGFBPs-2, -3, and -5), and estrogen receptor-β (ERβ). Cell proliferation assays revealed significant stimulation by all four steroids. DHEA- and E2-induced responses were similar but delayed and reduced compared with that of T and DHT. All four hormones increased gene and/or protein expression of PSA, IGF-IR, IGF-I, and IGFBP-2 and decreased that of AR, ERβ, IGF-II, and IGFBP-3. There were no significant effects of hormone treatment on IGFBP-5 mRNA. DHEA and E2 responses were similar, and distinct from those of DHT and T, in time- and dose-dependent studies. Further studies of the mechanisms of DHEA effects on prostate cancer epithelial cells of varying AR status, as well as on prostate stromal cells, will be required to discern the implications of DHEA supplementation on prostatic health.
Prenatally Detected Cystic Adrenal Mass Associated with Beckwith-Wiedemann Syndrome
Authors: Merrot Thierry , Walz Jochen , Anastasescu Robert , Chaumoître Kathia , D’Ercole Claude
Published: November 2004

We report a case of a right-sided cystic adrenal mass, detected after the 21st week of gestation, associated with fetal macrosomia. The diagnosis of Beckwith-Wiedemann syndrome was evoked. Prenatal sonography and magnetic resonance imaging did not allow establishing the origin of the suprarenal mass. The differential diagnosis of cystic neuroblastoma, pseudocystic adrenal haemorrhage, and adrenocortical macrocysts was discussed. A laparotomy was performed 2 weeks after birth due to the increasing size of the tumour and due to its possible malignant origin. Histological findings were haemorrhagic lesions without evidence of malignancy and adrenal cortical cytomegaly. The diagnosis of an adrenocortical macrocyst component of Beckwith-Wiedemann syndrome was established.
Effective Counselling of Pre-Natal Diagnosis of Serious Heart Disease – An Aid to Maternal Bonding?
Authors: Menahem Samuel , Grimwade James
Published: November 2004

The pre-natal diagnosis of a serious anomaly in the fetus precipitates a crisis for the parents. Effective counselling may help during this difficult phase. We postulated that if parents opted to continue with the pregnancy, then they are better prepared to care for the newborn infant having already experienced the grieving process. Objectives: This paper reviews our early experience, focusing on the parental perception of the counselling. Methods and Subjects: Questionnaires were developed and forwarded to patients previously seen in a private obstetric ultrasound practice, diagnosed with or specifically referred because of the diagnosis of a complex cardiac abnormality in the fetus. The diagnosis was subsequently confirmed by a further scan in the presence of a paediatric cardiologist, who initiated explanation of the anomaly with the obstetrician ultrasonologist asking and seeking explanations in lay terms on behalf of the parents, concerning the nature of the anomaly, its possible consequences, the need for intervention, the short- and long-term risks, concentrating on quality of life issues. Results: Over a 3-year period a cohort of 40 such patients were reviewed of whom a third opted for termination. The anomalies were complex and many life-threatening, most requiring surgical intervention in the newborn period or subsequently. Of the 27 that proceeded to term, responses were obtained from 21. Most described the shock at learning the diagnosis and of being very distressed at the time. Most commented that the information provided was ‘just right’. The majority felt that the previous contact with the obstetrician and cardiologist was very helpful in their subsequent care of their newborn infant. Three parents noted that they continued to experience anxiety about their baby, while 3 others indicated that the previous counselling had ‘no effect’ on the handling of their baby. Anecdotal observations made of the parents especially of the mother’s handling of the newborn infant seemed to support the parents’ perception that they were helped by their prior knowledge of the diagnosis. Conclusion: With increasing pre-natal diagnosis of major anomalies, it is important that parents so affected have the opportunity to understand the nature of the abnormality, its significance and effects on the infant’s and child’s functioning and survival, and the need for intervention. Such information together with working through the grieving process during the latter part of the pregnancy may help with the handling of the infant once born and further improve their bonding with their baby, despite the need for, at times, life-threatening intervention. Further objective studies are required to confirm these preliminary observations.
Second- and Third-Trimester Therapeutic Terminations of Pregnancy in Cases with Complete Placenta previa – Does Feticide Decrease Postdelivery Maternal Hemorrhage?
Authors: Ruano R. , Dumez Y. , Cabrol D. , Dommergues M.
Published: November 2004

Objective: To study the feasibility of second- and third-trimester termination of pregnancy (TOP) with complete placenta previa, and the impact of performing feticide before labor induction on maternal hemorrhagic morbidity. Patients and Methods: From 1987 to 2002, the databases of two referral hospitals were reviewed. We identified 15 cases of second- or third-trimester TOP in women with complete placenta previa. Feticide was performed 2–14 days before induction in 6/15 cases. Cervical ripening was achieved in 8 cases by mifepristone alone (n = 2) or by mifepristone and dilapan (n = 6). Labor was induced by vaginal gemeprost (n = 2), intramuscular (n = 5) or intravenous (n = 4) sulprostone, vaginal misoprostol (n = 1) or a combination of misoprostol and sulprostone (n = 3). Hemorrhage was defined by the need for transfusion. The difference between the preoperative and the lowest per- or postoperative maternal hemoglobin level was also analyzed. Results: Of the 9 women who underwent labor induction without previous feticide, 4 required blood transfusions, 1 of whom had a hemostat hysterectomy. The mean hemoglobin difference was 2.5 g/dl (range: 0.5–5.3). None of the 6 patients with preinduction feticide required transfusion. The hemoglobin difference was significantly smaller in this group than in terminations without previous feticide (mean: 1.0 g/dl ; range: 0.1–2.2; p = 0.03). Conclusion: In cases with complete placenta previa, second- or third-trimester TOP is feasible. It carries a substantial risk of hemorrhage that might be decreased by preinduction feticide.
Sonographic, Pathologic andKaryotypic Findings in a Rare Case of Placenta fenestrata
Authors: Linhart Jessica M. , Grafe Marjorie R. , Saade George R. , Velagaleti Gopalrao V.N.
Published: November 2004

Abnormalities of placental shape are occasionally seen on ultrasound. They have not been reported to be associated with abnormalities in fetal anatomy and karyotype. Here, we report on a rare case of placenta fenestrata with triploid karyotype. A 15-year-old patient presented at 21 weeks and 3 days gestation for ultrasound evaluation following an abnormal triple screen and abnormal ultrasound. Multiple fetal abnormalities were noted as well as several cystic areas with pulsatile flow on Doppler ultrasound in the placenta. After termination of the pregnancy, a rare abnormality in the placental shape, placenta fenestrata, was noted. The fetal karyotyping showed a triploid karyotype. This is the first reported case of placenta fenestrata diagnosed on ultrasound. In addition, this is also the first reported case of karyotype abnormality associated with abnormality of placental shape.
Association of Deletions of the Chromosomal Region 15q24-ter and Diaphragmatic Hernia: A New Case and Discussion of the Literature
Authors: Hengstschläger Markus , Mittermayer Christoph , Repa Christa , Drahonsky Regina , Deutinger Josef , Bernaschek Gerhard
Published: November 2004

Objective: To provide new insights into how chromosomal aberrations affect fetal development, as well as for the counseling of parents in comparable situations, it is important to characterize and report the genotypes of fetuses with clinical anomalies. Methods: Molecular cytogenetic analyses in a fetus with congenital diaphragmatic hernia (CDH). Results: This report describes the first case of a deletion of the region q26.1-ter on chromosome 15 occurring as a de novo event associated with CDH. A detailed review of the literature provides further evidence of a functional association between deletions within the chromosomal region 15q24-ter and the development of CDH. Conclusions: The obtained data argue that detection of such a deletion in the region 15q24-ter associated with CDH likely predicts a poor prognosis. This report highlights the importance of giving special diagnostic attention to the chromosomal region 15q24-ter when prenatal ultrasound examination provides evidence of a CDH and warrants further research to identify genetic elements within the chromosomal region 15q24-ter related to the development of diaphragmatic hernia.
Influences of Gender and Region on Responses to 5-HT in the Rat Small Intestine
Authors: Liu H. , Irving H.R. , Tan Y.Y. , Meng L. , Chetty N. , Coupar I.M.
Published: November 2004

The aim of this study was to obtain more information regarding the ‘atypical’ 5-HT7 receptor of the rat jejunum. 5-HT7-induced contractions of the jejunum were elicited by 5-HT in the presence of ondansetron. Maximal responses were slightly larger in tissues from male compared to female rats of comparable age, with Emax values of 97.2 ± 3.3 and 84.25 ± 4.3% respectively compared to acetylcholine as an internal standard. However, the pEC50 valuesfor 5-HT were not significantly different. The mRNA expression levels of the 5-HT7 receptor were similar in whole jejunum and longitudinal muscle tissues taken from males and females. It was also shown that the maximal response of the jejunum from male rats was larger than the responses from mid intestine and ileum. However, in female tissues, the Emax of the mid intestine was significantly larger than the ileum, but not different from the jejunum. The results provide further insights into the ‘atypical’ 5-HT7 receptor of the rat jejunum and are also useful in optimising the preparation for further studies.
Relaxation Induced by Acetylcholine Involves Endothelium-Derived Hyperpolarizing Factor in 2-Kidney 1-Clip Hypertensive Rat Carotid Arteries
Authors: Sendão Oliveira Ana Paula , Bendhack Lusiane M.
Published: November 2004

Acetylcholine induced relaxation in a concentration-dependent way in isolated phenylephrine-contracted carotid artery rings from normotensive two-kidney (2K) and hypertensive two-kidney one-clip (2K-1C) rats. In the presence of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NOARG, 100 µmol/l), the relaxation stimulated with acetylcholine was blocked in 2K arteries. However, in 2K-1C arteries, the relaxation was only partially inhibited. Indomethacin (3 µmol/l) had no effect in both groups. In 2K arteries, the combination of L-NOARG and indomethacin had similar effects to L-NOARG alone. On the other hand, in 2K-1C arteries, indomethacin further inhibited the maximum effect induced by acetylcholine. Endothelium-dependent relaxation induced by acetylcholine was markedly reduced in 2K arteries contracted with 90 mmol/l KCl, and it was abolished in 2K-1C arteries. The remaining response to acetylcholine in 2K arteries was blocked by L-NOARG. Thus, in addition to NO, a relaxing factor sensitive to extracellular K+ changes in the membrane potential contributes to endothelium-dependent relaxation in 2K-1C rat carotid artery. On the other hand, in arteries from 2K rats, only NO is involved in the relaxation induced by acetylcholine. The combination of 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 3 µmol/l), indomethacin (3 µmol/l) and L-NOARG (100 µmol/l) reduced the relaxation induced by acetylcholine in arteries from 2K-1C rats contracted with phenylephrine. On the other hand, in 2K arteries, the relaxation induced by acetylcholine was abolished. The combination of ODQ and K+ channel blockers charybdotoxin (100 nmol/l), apamin (500 nmol/l) and 4-aminopyridine (1 µmol/l) abolished the relaxation induced by acetylcholine in 2K and 2K-1C carotid arteries. These data indicate that the endothelium-derived relaxing factors that contribute to relaxation induced by acetylcholine are different in 2K and 2K-1C arteries. In 2K arteries, the only factor is NO, which involves the activation of K+ channels and the cGMP pathway. However, in 2K-1C arteries, the relaxation induced by acetylcholine is dependent on NO in addition to another factor, which is insensitive to indomethacin, but also activates the K+ channels and the cGMP pathway, presumably by membrane hyperpolarization through endothelium-derived hyperpolarizing factor.
Effects of a Novel Anti-Hyperlipidemic Agent, S-2E, on Blood Lipid Levels in Rats with Fructose-Induced Hypertriglyceridemia
Authors: Ohmori Koichi , Yamada Haruo , Yasuda Akio , Yamamoto Akira , Matsuura Naosuke , Kiniwa Mamoru
Published: November 2004

Using rats with fructose-induced hypertriglyceridemia, an animal model of human hypertriglyceridemia, we investigated whether (+)-(S)-p-[1-(p-tert-butylphenyl)-2-oxo-4-pyrrolidinyl]-methoxybenzoic acid (S-2E), a novel anti-hyperlipidemic agent, reduced the elevated levels of triglyceride (TG) and non-high-density lipoprotein cholesterol (non-HDL-C), and then whether it elevated HDL-C levels. At doses of 3–30 mg/kg, S-2E reduced elevated TG levels and non-HDL-C levels simultaneously in a dose-dependent manner after a week. Furthermore, S-2E treatment at 10 mg/kg for 4 weeks showed similar effects, while the elongation of intervals between feeding periods led to further increases in these levels. Interestingly, S-2E increased blood HDL-C levels after 4 weeks of treatment. It is therefore reasonable to assume that S-2E may be useful to improve dyslipidemia such as hypertriglyceridemia and low levels of HDL-C.
Activation of the Smad Pathway in Glomeruli from a Spontaneously Diabetic Rat Model, OLETF Rats
Authors: Furuse Yoko , Hashimoto Naotake , Maekawa Mamiko , Toyama Yoshiro , Nakao Atsuhito , Iwamoto Itsuo , Sakurai Kenichi , Suzuki Yoshifumi , Yagui Kazuo , Yuasa Shigeki , Toshimori Kiyotaka , Saito Yasushi
Published: November 2004

Background/Aims: Transforming growth factor-β (TGF-β) mediates the excess accumulation of extracellular matrix in the diabetic kidney. Smad family proteins have been identified as signal transducers for the TGF-β superfamily. We sought to characterize the role of Smad proteins in mediating TGF-β responses in the development of diabetic nephropathy. Methods: We evaluated the time course of TGF-β1 fibronectin, Smad2 and Smad3 protein expression and Smad3 activation in glomeruli from spontaneously diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats, using immunohistochemistry and Western blot analysis. Results: The glomeruli of diabetic OLETF rats showed not only accelerated activation of Smad3, but also enhanced protein expression of Smad2 and Smad3, which occurred in parallel to the increased expression of TGF-β and fibronectin compared with glomeruli of control, Long-Evans Tokushima Otsuka (LETO) rats at 30 weeks of age. No differences were found in TGF-β1 fibronectin, Smad2 and Smad3 protein expression and Smad3 activation in glomeruli between the two strains at 12 weeks of age when OLETF rats were not diabetic. Conclusions: The enhancement of Smad protein expression and activation may be involved in the TGF-β signaling cascade that plays an important role in the development of diabetic nephropathy through progressive expansion of the mesangial matrix.
Is the Atopy Patch Test with House Dust Mites Specific for Atopic Dermatitis?
Authors: Ingordo Vito , Dalle Nogare Roberto , Colecchia Bruno , D’Andria Corrado
Published: November 2004

Background: The atopy patch test (APT), namely the patch test with aeroallergens, is regarded as specific for patients with atopic dermatitis (AD), but small numbers of positive APT were reported in the past also in atopic subjects without dermatitis and in healthy persons. Objective: The aim of this study was to evaluate the response to the APT with house dust mites (HDM) in subjects nonaffected by AD and to compare the outcomes observed in these cases with those pointed out in AD patients, evaluating also the differences between two allergen extracts manufactured at different purifications and concentrations. Methods: Forty-seven atopic subjects without eczema (AWE), 33 nonatopic (NA) subjects and 77 adult AD patients were patch tested with an extract of purified bodies of HDM at 20% and with another extract of whole bodies of HDM at 30%, the latter corresponding to 300 µg/g of Der p 1. The reproducibility of APT was also tested in 8 AD patients, in 37 AWE subjects and in 19 NA subjects. Results: Positive responses with extract at 20% were observed in 29 (37.7%) AD, in 5 (10.6%) AWE and in 4 (12.1%) NA subjects. The APT with HDM at 30% was positive in 32 (41.6%) AD, 9 (19.1%) AWE and 4 (12.1%) NA persons. The rates of positivity and the intensity scores of responses were significantly different between AD and non-AD subjects (p < 0.01). The reproducibility of the APT in the three groups was satisfactory. Conclusion: These observations lead to conclude that the APT with HDM is positive also in non-AD subjects but it is probably more specific for AD.
Plexiform Neurofibromas Express the Transcription Factor Gli1
Authors: Endo Hideharu , Oikawa Ayako , Utani Atsushi , Shinkai Hiroshi
Published: November 2004

Background: Plexiform neurofibromas occur commonly in individuals with neurofibromatosis type 1 (NF1) and consist of neurofibromatous change in multiple nerve fascicles. Previously, we had observed that both plexiform neurofibromas and normal cutaneous nerves expressed Hedgehogs (Hhs), which are intercellular signaling molecules and regulate growth and patterning during embryonic development, and their receptors. In the present study, we examined the expression of Gli1, a transcription factor which mediates Hh signaling to investigate the activation of Hh signaling in plexiform neurofibromas and normal cutaneous nerves. Methods: An antihuman Gli1 antibody was used with a standard immunoperoxidase technique to determine Gli1 expression in 5 specimens of plexiform neurofibromas and 5 specimens of normal cutaneous nerves. Results: Our results showed Gli1 expression in S-100-positive tumor cells within the involved nerve fascicles in plexiform neurofibromas but not in control normal skins. Conclusions: Our findings indicate that the Hh signaling pathway is activated in plexiform neurofibromas.
Serological Immunomarkers in Cutaneous T Cell Lymphoma
Authors: Hassel Jessica C. , Meier Ramon , Joller-Jemelka Helen , Burg Günter , Dummer Reinhard
Published: November 2004

Introduction: As serological immunomarkers like neopterin, β2-microglobulin, soluble IL-2 receptor (sIL-2R) and IL-6 have been described to be elevated in various malignancies, the aim of this study was to investigate whether they would be of diagnostic and prognostic value for leukemic and non-leukemic cutaneous T cell lymphoma (CTCL). Patients and Methods: Forty-one CTCL patients from the lymphoma clinics of the Department of Dermatology, University of Zürich, were tested for the serum levels of the above-mentioned immunomarkers at several time points, and clinical status and clinical outcome were recorded. Thirty-nine patients with CBCL and T cell inflammatory diseases served as controls. Results: The study revealed that neopterin, β2-MG and sIL-2R are significantly elevated in Sézary syndrome, whereby sIL-2R seemed to be the most sensitive marker and is typically increased in Sézary syndrome. Moreover, there is a correlation between tumor burden index values and serum parameters. Concerning the outcome of the disease (progression versus non-progression), only neopterin showed a significant prognostic value in non-leukemic CTCL patients. Conclusion: Serological immunomarkers are helpful tools in determining the tumor burden in CTCL and thus might be useful for disease monitoring during treatment. They may have prognostic value for predicting the clinical course.