bluuebunny/crossref_metadata_2025 huggingface dataset:
FINITE SIZE EFFECTS IN ENTANGLED RINGS OF QUBITS
Authors: MEYER T. , POULSEN U. V. , ECKERT K. , LEWENSTEIN M. , BRUß D.
Published: June 2004

We study translationally invariant rings of qubits with a finite number of sites N, and determine the maximal nearest-neighbor entanglement for a fixed z-component of the total spin. For small numbers of sites we present analytical results. We establish a relation between the maximal nearest-neighbor concurrence and the ground state energy of an XXZ spin model. This connection allows us to calculate the concurrence numerically for N≤24. We point out some interesting finite-size effects. Finally, we generalize our results beyond nearest neighbors.
SCHEME FOR PREPARATION OF W STATE VIA CAVITY QED
Authors: YANG MING , YI YOU-MING , CAO ZHUO-LIANG
Published: June 2004

In this paper, we presented a physical scheme to generate the multi-cavity maximally entangled W state via cavity QED. All the operations needed in this scheme are to modulate the interaction time only once.
DETERMINISTIC REMOTE IMPLEMENTATION OF A PAULI CHANNEL
Authors: ZOU XUBO , PAHLKE K. , MATHIS W.
Published: June 2004

We propose a scheme that allow the deterministic remote implementation of a Pauli channel on the state of a distant qubit. The scheme requires two e-bits of entanglements and two classical bits. We also demonstrate that scheme can be extended to higher dimensional quantum system.
ENTANGLEMENT BOUNDS FOR A FAMILY OF TWO-MODE GAUSSIAN STATES
Authors: JIANG LI-ZHEN
Published: June 2004

I study a family of bipartite quantum Gaussian states with three parameters, calculate Gaussian entanglement of formation analytically and the upper bound of relative entropy of entanglement, compare them with the coherent information of the states. Based on the numerical observation, I determine the relative entropy of entanglement and distillable entanglement of the states with infinitive squeezing.
SCHEMES FOR REMOTELY PREPARING MULTIPARTITE EQUATORIAL ENTANGLED STATES IN HIGH DIMENSIONS
Authors: LIU JIN-MING , WANG YU-ZHU
Published: June 2004

In this paper, we present two kinds of schemes for remotely preparing multiparticle d-dimensional equatorial entangled states with unit probability. It is found that the first remote state preparation scheme is realized by a multiparticle projective measurement, while the second scheme is achieved by a single particle orthogonal measurement. Each scheme can be perfectly implemented whatsoever the particle number N and the dimension d are.
ANALYTIC SOLUTIONS FOR QUANTUM LOGIC GATES AND MODELING PULSE ERRORS IN A QUANTUM COMPUTER WITH A HEISENBERG INTERACTION
Authors: BERMAN G. P. , KAMENEV D. I. , TSIFRINOVICH V. I.
Published: June 2004

We analyze analytically and numerically quantum logic gates in a one-dimensional spin chain with Heisenberg interaction. Analytic solutions for basic one-qubit gates and swap gate are obtained for a quantum computer based on logical qubits. We calculated the errors caused by imperfect pulses which implement the quantum logic gates. It is numerically demonstrated that the probability error is proportional to ε4, while the phase error is proportional to ε, where ε is the characteristic deviation from the perfect pulse duration.
Palmitoylation of Intracellular Signaling Proteins: Regulation and Function
Authors: Smotrys Jessica E. , Linder Maurine E.
Published: June 2004

▪ Abstract  Protein S-palmitoylation is the thioester linkage of long-chain fatty acids to cysteine residues in proteins. Addition of palmitate to proteins facilitates their membrane interactions and trafficking, and it modulates protein-protein interactions and enzyme activity. The reversibility of palmitoylation makes it an attractive mechanism for regulating protein activity, and this feature has generated intensive investigation of this modification. The regulation of palmitoylation occurs through the actions of protein acyltransferases and protein acylthioesterases. Identification of the protein acyltransferases Erf2/Erf4 and Akr1 in yeast has provided new insight into the palmitoylation reaction. These molecules work in concert with thioesterases, such as acyl-protein thioesterase 1, to regulate the palmitoylation status of numerous signaling molecules, ultimately influencing their function. This review discusses the function and regulation of protein palmitoylation, focusing on intracellular proteins that participate in cell signaling or protein trafficking.
Pyridoxal Phosphate Enzymes: Mechanistic, Structural, and Evolutionary Considerations
Authors: Eliot Andrew C. , Kirsch Jack F.
Published: June 2004

▪ Abstract  Pyridoxal phosphate (PLP)-dependent enzymes are unrivaled in the diversity of reactions that they catalyze. New structural data have paved the way for targeted mutagenesis and mechanistic studies and have provided a framework for interpretation of those results. Together, these complementary approaches yield new insight into function, particularly in understanding the origins of substrate and reaction type specificity. The combination of new sequences and structures enables better reconstruction of their evolutionary heritage and illuminates unrecognized similarities within this diverse group of enzymes. The important metabolic roles of many PLP-dependent enzymes drive efforts to design specific inhibitors, which are now guided by the availability of comprehensive structural and functional databases. Better understanding of the function of this important group of enzymes is crucial not only for inhibitor design, but also for the design of improved protein-based catalysts.
The Molecular Mechanics of Eukaryotic Translation
Authors: Kapp Lee D. , Lorsch Jon R.
Published: June 2004

▪ Abstract  Great advances have been made in the past three decades in understanding the molecular mechanics underlying protein synthesis in bacteria, but our understanding of the corresponding events in eukaryotic organisms is only beginning to catch up. In this review we describe the current state of our knowledge and ignorance of the molecular mechanics underlying eukaryotic translation. We discuss the mechanisms conserved across the three kingdoms of life as well as the important divergences that have taken place in the pathway.
SECULAR TRENDS IN DIETARY INTAKE IN THE UNITED STATES
Authors: Briefel Ronette R. , Johnson Clifford L.
Published: June 2004

▪ Abstract  This review focuses on dietary intake and dietary supplement use among the U.S. population age 1–74 based on four National Health and Nutrition Examination Surveys conducted in 1971–74, 1976–80, 1988–94, and 1999–2000. Secular trends in intake of energy, macronutrients, cholesterol, sodium, calcium, iron, folate, zinc, vitamins A and C, fruits, vegetables, and grain products are summarized. During the 30-year period, mean energy intake increased among adults, and changed little among children age 1–19, except for an increase among adolescent females. Factors contributing to increases in energy intake include increases in the percentage of the population eating away from home (particularly at fast-food restaurants), larger portion sizes of foods and beverages, increased consumption of sweetened beverages, changes in snacking habits, and improved dietary methodology. Dietary supplement use increased among adult men and women, decreased among children age 1–5, and was stable for children age 6–11 and adolescents.
CALCIUM AND BONE MINERAL METABOLISM IN CHILDREN WITH CHRONIC ILLNESSES
Authors: Abrams S.A. , O'Brien K.O.
Published: June 2004

▪ Abstract  Increased longevity and improved medical management of children with chronic illnesses has led to a focus on the short- and long-term consequences of these conditions on bone health. Bone loss is influenced by diet, malabsorption, and disease-related imbalances in bone turnover. It may be exacerbated by common medications, especially corticosteroids. Assessment of bone mass and quality, calcium absorption, kinetically derived rates of bone turnover, and biochemical markers of bone turnover have increased our knowledge of the pathophysiology of bone loss in these children as well as provided insights into possible therapeutic interventions. Increased intake of calcium and vitamin D, while useful, is unlikely to prevent or resolve bone loss in many chronically ill children. Emphasis on combination of nutritional interventions with exercise and newer bone-sparing therapies may be necessary.
NUTRITIONAL PROTECTION AGAINST SKIN DAMAGE FROM SUNLIGHT
Authors: Sies Helmut , Stahl Wilhelm
Published: June 2004

▪ Abstract  The concept of systemic photoprotection by dietary means is gaining momentum. Skin is continuously exposed to ultraviolet (UV) radiation, the major cause of skin disorders such as sunburn, photodamage, and nonmelanoma skin cancer. Most of the erythemal annual UV dose is encountered under nonvacation conditions, when no sunscreen is applied. In the absence of topically added compounds, skin protection depends solely on endogenous defense. Micronutrients can act as UV absorbers, as antioxidants, or can modulate signaling pathways elicited upon UV exposure. UV-induced erythema is a suitable parameter to assess photoprotection. Dietary protection is provided by carotenoids, tocopherols, ascorbate, flavonoids, or n-3 fatty acids, contributing to maintenance resistance as part of lifelong protection.
THE CRITICAL ROLE OF THE MELANOCORTIN SYSTEM IN THE CONTROL OF ENERGY BALANCE
Authors: Seeley Randy J. , Drazen Deborah L. , Clegg Deborah J.
Published: June 2004

▪ Abstract  Animals have developed highly adaptive and redundant mechanisms to maintain energy balance by matching caloric intake to caloric expenditure. Recent evidence has pointed to a variety of peripheral signals that inform specific central nervous system (CNS) circuits about the status of peripheral energy stores as critical to the maintenance of energy balance. A critical component of these CNS circuits is the melanocortin system. Regulation of signaling by melanocortin 3 and melanocortin 4 receptors in the CNS is controlled via neuronal cell bodies in the arcuate nucleus of the hypothalamus that synthesize melanocortin receptor agonists such as alpha-melanocyte-stimulating hormone (α-MSH) or antagonists such as agouti-related protein (AgRP). The activity of these two populations of neurons is reciprocally regulated by a number of peripheral and central systems that influence energy balance. Further, increased melanocortin signaling via pharmacological or genetic means in the CNS causes potent reductions in food intake and weight loss. Decreased melanocortin signaling via pharmacological or genetic means results in increased food intake and weight gain. Reviewed here is the wide range of evidence that points to the melanocortin system as a critical node in the diverse neurocircuitry that regulates food intake and body weight.
Critical role of p63 in the development of a normal esophageal and tracheobronchial epithelium
Authors: Daniely Yaron , Liao Grace , Dixon Darlene , Linnoila R. Ilona , Lori Adriana , Randell Scott H. , Oren Moshe , Jetten Anton M.
Published: June 2004

The trachea and esophagus originate from the foregut endoderm during early embryonic development. Their epithelia undergo a series of changes involving the differentiation of stem cells into unique cell types and ultimately forming the mature epithelia. In this study, we monitored the expression of p63 in the esophagus and the trachea during development and examined in detail morphogenesis in p63−/− mice. At embryonic day 15.5 (E15.5), the esophageal and tracheobronchial epithelia contain two to three layers of cells; however, only the progenitor cells express p63. These progenitor cells differentiate first into ciliated cells (p63−/β-tubulin IV+) and after birth into mature basal cells (p63+/K14+/K5+/BS-I-B4+). In the adult pseudostratified, columnar tracheal epithelium, K14+/K5+/BS-I-B4+ basal cells stain most intensely for p63, whereas ciliated and mucosecretory cells are negative. In stratified squamous esophageal epithelium and during squamous metaplasia in the trachea, cells in the basal layer stain strongest for p63, whereas p63 staining declines progressively in transient amplifying and squamous differentiated cells. Generally, p63 expression is restricted to human squamous cell carcinomas, and adenocarcinomas and Barrett's metaplasia do not stain for p63. Examination of morphogenesis in newborn p63−/− mice showed an abnormal persistence of ciliated cells in the esophagus. Significantly, in both tissues, lack of p63 expression results in the development of a highly ordered, columnar ciliated epithelium deficient in basal cells. These observations indicate that p63 plays a critical role in the development of normal esophageal and tracheobronchial epithelia and appears to control the commitment of early stem cells into basal cell progeny and the maintenance of basal cells.
The dopamine precursorl-dihydroxyphenylalanine is transported by the amino acid transporters rBAT and LAT2 in renal cortex
Authors: Quiñones Henry , Collazo Roberto , Moe Orson W.
Published: June 2004

The intrarenal autocrine-paracrine dopamine (DA) system is critical for Na+homeostasis. l-Dihydroxyphenylalanine (l-DOPA) uptake from the glomerular filtrate and plasma provides the substrate for DA generation by the renal proximal tubule. The transporter(s) responsible for proximal tubule l-DOPA uptake has not been characterized. Renal cortical poly-A+RNA injected into Xenopus laevis oocytes induced l-DOPA uptake in a time- and dose-dependent fashion with biphasic Kms in the millimolar and micromolar range and independent of inward Na+, K+, or H+gradients, suggesting the presence of low- and high-affinity l-DOPA carriers. Complementary RNA from two amino acid transporters yielded l-DOPA uptake significantly above water-injected controls the rBAT/b0,+AT dimer (rBAT) and the LAT2/4F2 dimer (LAT2). In contradistinction to renal cortical poly-A+, l-DOPA kinetics of rBAT and LAT2 showed classic Michaelis-Menton kinetics with Kms in the micromolar and millimolar range, respectively. Sequence-specific antisense oligonucleotides to rBAT or LAT2 (AS) caused inhibition of rBAT and LAT2 cRNA-induced l-DOPA transport and cortical poly-A+-induced arginine and phenylalanine transport. However, the same ASs only partially blocked poly-A+-induced l-DOPA transport. In cultured kidney cells, silencing inhibitory RNA (siRNA) to rBAT significantly inhibited l-DOPA uptake. We conclude that rBAT and LAT2 can mediate apical and basolateral l-DOPA uptake into the proximal tubule, respectively. Additional l-DOPA transport mechanisms exist in the renal cortex that remain to be identified.
Upregulation of macula densa cyclooxygenase-2 expression is not dependent on glomerular filtration
Authors: Schweda Frank , Kammerl Martin , Wagner Charlotte , Krämer Bernhard K. , Kurtz Armin
Published: June 2004

Although the regulation of cyclooxygenase-2 (COX-2) expression in the kidney cortex has been extensively characterized, the physiological control mechanisms of COX-2 expression at the level of the kidney and at the level of the tubular cells are not well understood. Based on the current hypothesis that tubular salt transport might be a crucial regulator of COX-2 expression, this study aimed to determine the impact of salt delivery to the tubules (glomerular filtration) for the regulation of COX-2 in the kidney cortex in vivo. To this end, glomerular filtration of the right kidney was abrogated by the ligation of the right ureter of male Sprague-Dawley rats. After 1 wk of ligation, the animals were treated with subcutaneous infusions of furosemide (12 mg·kg−1·day−1) or with a low-salt or a high-salt diet (0.02% wt/wt; 8% wt/wt), and COX-2 as well as renin mRNA expression were determined in the ligated and the nonligated contralateral kidney. During ureteral ligation, hydronephrosis developed with a reduction of medullary mass, while the cortex was preserved. Expressions of the Na-K-2Cl cotransporter isoforms A and B were both reduced in the hydronephrotic cortex to 70 and 35% of the corresponding contralateral intact kidney. Despite the abrogation of glomerular filtration, detected by inulin clearance measurements, renocortical COX-2 mRNA abundance was stimulated by furosemide treatment (3.2-fold) or low-salt diet (2.9-fold) to similar degrees compared with the intact contralateral kidney (2.7-fold for both treatments), whereas a high-salt diet did not significantly suppress COX-2 mRNA in the macula densa region of either kidney. Renin mRNA expression was regulated strictly in parallel in both kidneys, a low-salt diet or furosemide treatment stimulating and a high-salt diet suppressing it. We conclude from these findings that salt delivery to the tubules is not an essential requirement for the upregulation of COX-2 by salt deficiency or by loop diuretics in the rat kidney cortex nor is it for chronic stimulation of renin mRNA expression.
The role of von Hippel-Lindau tumor suppressor protein and hypoxia in renal clear cell carcinoma
Authors: Sufan Roxana I. , Jewett Michael A. S. , Ohh Michael
Published: June 2004

The majority of kidney cancers are caused by the mutation of the von Hippel-Lindau ( VHL) tumor suppressor gene. VHL protein (pVHL) is part of an E3 ubiquitin ligase complex called VEC that is composed of elongin B, elongin C, cullin 2, NEDD8, and Rbx1. VEC targets a hypoxia-inducible factor (HIF) transcription factor for ubiquitin-mediated destruction selectively in the presence of oxygen. In the absence of wild-type pVHL, as in VHL patients or in the majority of sporadic clear cell renal cell carcinomas, HIF-responsive genes are inappropriately activated even under normoxia. Recent insights into the molecular mechanisms regulating the function of pVHL, and thereby HIF, in the context of kidney cancer are the focus of this review.
Hepatocyte growth factor in kidney fibrosis: therapeutic potential and mechanisms of action
Authors: Liu Youhua
Published: June 2004

Hepatocyte growth factor (HGF) is a pleiotropic factor that plays an imperative role in tubular repair and regeneration after acute renal injury. Growing evidence indicates that HGF is also an endogenous renoprotective factor that possesses a potent antifibrotic ability. HGF prevents the initiation and progression of chronic renal fibrosis and inhibits transforming growth factor (TGF)-β1expression in a wide variety of animal models. In vitro, HGF counteracts the action of TGF-β1in different types of kidney cells, resulting in blockade of the myofibroblastic activation from interstitial fibroblasts and glomerular mesangial cells, as well as inhibition of the mesenchymal transition from tubular epithelial cells. Recent studies reveal that HGF antagonizes the profibrotic actions of TGF-β1by intercepting Smad signal transduction through diverse mechanisms. In interstitial fibroblasts, HGF blocks activated Smad-2/3 nuclear translocation, whereas it specifically upregulates the expression of the Smad transcriptional corepressor SnoN in tubular epithelial cells. In glomerular mesangial cells, HGF stabilizes another Smad corepressor, TGIF, by preventing it from degradation. Smad corepressors bind to activated Smad-2/3 and sequester their ability to transcriptionally activate TGF-β target genes. This article reviews recent advances in our understanding of the cellular and molecular mechanisms underlying HGF inhibition of renal fibrosis.
Relationship between Frontotemporal Dementia and Corticobasal Degeneration/Progressive Supranuclear Palsy
Authors: Kertesz Andrew , Munoz David
Published: June 2004

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) were described as separate entities, but prior to that an extrapyramidal variety of Pick’s disease was recognized. Subsequently a pathological overlap between these conditions and clinical overlap between frontotemporal dementia, primary progressive aphasia, corticobasal degeneration syndrome and more recently PSP was recognized. Initially only the movement disorder had been emphasized, but now the behavioral and language symptoms are considered common. The syndromes of frontotemporal dementia/Pick’s disease can be produced by underlying CBD, PSP or Pick pathology as well as with neural inclusions of the motor neuron disease type. The concept of this overlap has been confirmed genetically finding a similar spectrum of pathology with different tau mutations and even with tau negative pathology, which could be a deficiency of normal tau. The overlap of CBD with PSP and both with PPA and FTD allows to consider these relatively rare conditions as part of a more commonly occurring degenerative disease than previously recognized.
Familial Presenile Dementia with Bitemporal Atrophy
Authors: Passant Ulla , Ostojic Jovanka , Froelich Fabre Susanne , Gustafson Lars , Lannfelt Lars , Larsson Elna-Marie , Nilsson Karin , Rosén Ingmar , Elfgren Christina
Published: June 2004

This study describes the clinical, neuropsychological, neuroimaging and genetic characteristics in two generations of a Swedish family affected by presenile dementia. The pedigree includes 5 cases (mother and 4 of 5 children) of progressive dementia with onset between 54 and 62 years. The clinical picture is characterized by insidious onset and progressive decline in episodic memory without spatial impairment or dyspraxia, followed by changes in personality and behaviour, with signs of disinhibition, irritability, impulsivity and loss of social awareness. Three siblings, examined after 10 years of duration, showed moderate language deficits but preserved spatial function and praxis. CT and MRI showed progressive bilateral temporal atrophy and moderate frontal white matter changes. Regional cerebral blood flow measurements showed hypoperfusion in temporal areas bilaterally. Quantitative EEG was normal within 5 years after symptom onset and thereafter showed a moderate increase in relative theta power. Sequencing of the tau gene (chromosome 17) revealed the previously described R406W mutation in exon 13 as a likely cause of the disease. This mutation was identified in all affected cases. The clinical picture of this family shows striking similarities not only to frontotemporal dementia but also to Alzheimer’s disease.
Initial Complaints in Frontotemporal Lobar Degeneration
Authors: Pijnenburg Yolande A.L. , Gillissen Freek , Jonker Cees , Scheltens Philip
Published: June 2004

Aims: Frontotemporal lobar degeneration (FTLD) is probably underrecognized. The goal of this study was to investigate initial complaints of both patients and their caregivers at first specialist referral. Also, we tried to assess whether misrecognition of symptoms contributed to diagnostic delay. Methods: The case notes of all patients diagnosed with FTLD at the VU University Medical Center, Alzheimer Center of Amsterdam, The Netherlands, since 1998 were retrospectively reviewed. Only patients of whom detailed information of first specialist referral was available were included. The diagnosis of FTLD was based on the clinical diagnostic criteria of Neary and Snowden, supported by ancillary investigations. Results: Forty-six patients with FTLD were included. Twenty-one patients had frontotemporal dementia (FTD), 17 semantic dementia (SD) and 8 progressive nonfluent aphasia (PA). The majority of the FTD patients presented without complaints or with somatic complaints and nearly a quarter of them expressed memory complaints. The presenting complaints of most of their caregivers differed from the patients’ complaints and often consisted of cognitive complaints. In SD and PA, language problems but also forgetfulness were presented. Misrecognition of the initial symptoms in some cases seemed to have contributed to diagnostic delay. Conclusion: Presenting complaints in FTLD can be misleading. In our cohort, memory complaints occurred relatively often. A multidisciplinary approach, including a structured behavioral interview, is important to recognize symptoms of FTLD.
Minimal Residual Disease Studies by Flow Cytometry in Acute Leukemia
Authors: Campana Dario , Coustan-Smith Elaine
Published: June 2004

Minimal residual disease (MRD) assays are increasingly important in the clinical management of patients with acute leukemia. Among the methods available for monitoring MRD, flow cytometry holds great promise for clinical application because of its simplicity and wide availability. Several studies have demonstrated strong correlations between MRD levels by flow cytometry during clinical remission and treatment outcome, lending support to the reliability of this approach. Flow-cytometric detection of MRD is based on the identification of immunophenotypic combinations expressed on leukemic cells but not on normal hematopoietic cells. Its sensitivity depends on the specificity of the immunophenotypes used to track leukemic cells and on the number of cells available for study. Immunophenotypes that allow detection of 1 leukemic cell in 10,000 normal cells can be identified in at least 90% of patients with acute lymphoblastic leukemia; immunophenotypes that allow detection of 1 leukemic cell in 1,000–10,000 normal cells can be identified in at least 85% of patients with acute myeloid leukemia. Identification of new markers of leukemia by gene array technology should lead to the design of simple and reliable antibody panels for universal monitoring of MRD. Here we review the relative advantages and disadvantages of flow cytometry for MRD studies, as well as results obtained in correlative studies with treatment outcome.
Pathogenesis, Diagnosis and Monitoring of Residual Disease in Acute Promyelocytic Leukaemia
Authors: Reiter Andreas , Lengfelder Eva , Grimwade David
Published: June 2004

The clinical course of acute promyelocytic leukaemia (APL) has changed over the last 25 years from one that was fatal for the majority of patients to representing one of the most curable subtypes of acute myeloid leukaemia. Besides improved supportive care this has mainly been achieved through the introduction of novel targeted therapies in the form of all-trans retinoic acid (ATRA) and arsenic trioxide that specifically address the underlying molecular lesion. APL is characterized by chromosomal rearrangements of 17q21 leading to the formation of fusion proteins involving retinoic acid receptor alpha (RARA). To date five different fusion partners of RARA have been identified, but the vast majority of cases are characterized by the presence of the t(15;17)(q22;q12–21), which involves the promyelocytic leukaemia (PML) gene. The identification of different breakpoint microclusters within RARA intron 2 suggests that sequence-associated or structural factors play a role in the formation of the t(15;17). In addition, the comparison of forward and reverse genomic junctions has revealed microhomologies, deletions and/or duplications of either gene consistent with the hypothesis that the t(15;17) occurs by non-homologous recombination of DNA after processing of the double strand breaks by a dysfunctional DNA damage repair mechanism. The detection of the PML-RARA fusion gene by reverse-transcription polymerase chain reaction (RT-PCR) is routinely used for diagnosis and monitoring of minimal residual disease (MRD). In PML-RARA-positive APL about 70% of patients are expected to be cured with a combination of ATRA and anthracycline-based chemotherapy. However, relapse remains a major problem. The identification of patients at high risk of relapse and the development of risk-adapted treatment schedules are therefore clearly the most challenging tasks in the treatment of APL. Recent studies have shown that pre-emptive chemotherapy at the time of molecular relapse improves survival compared to treatment at the point of haematological relapse. Quantitative RT-PCR technology is expected to further improve the predictive value of MRD monitoring and therefore to guide therapy in order to reduce the rate of relapses and to increase rates of cure in high-risk patients.
Significance of Minimal Residual Disease in Lymphoid Malignancies
Authors: Brüggemann Monika , Pott Christiane , Ritgen Matthias , Kneba Michael
Published: June 2004

Modern treatment protocols lead to complete remission (CR) in a considerable proportion of patients with lymphoproliferative disorders. However, many of these patients ultimately relapse, implying that achievement of a clinical CR is compatible with significant amounts of residual malignant cells. Cytogenetic, molecular and immunological techniques that are more sensitive than morphology are increasingly used to assess and quantify minimal residual disease (MRD). Immunological marker analysis allows the detection of aberrant or unusual immunophenotypes, PCR techniques target fusion regions of chromosome aberrations and clone-specific immunoglobulin and T-cell receptor gene rearrangements. The rationale underlying MRD studies is to improve measurement of treatment response, to provide independent prognostic information and to optimise therapeutic strategies. In acute lymphoblastic leukemia (ALL), the MRD based evaluation of initial response to front-line therapy emerged as a highly relevant diagnostic tool, particularly in childhood ALL, where MRD has been shown to be an independent prognostic factor allowing a precise risk group classification. In patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma (NHL) the prognostic significance of MRD is still a matter of debate, as the majority of patients remain MRD positive after conventional treatment. This phenomenon has changed with the implementation of new treatment modalities, such as application of monoclonal antibodies, where a significant proportion of patients with NHL converts to MRD negativity and experiences prolonged remission. Whether this molecular remission will translate into a superior overall survival is currently the goal of ongoing prospective studies.
Association Study of –1727 A/T, –50 C/T and (CAA)n Repeat GSK-3β Gene Polymorphisms with Schizophrenia
Authors: Scassellati Catia , Bonvicini Cristian , Perez Jorge , Bocchio-Chiavetto Luisella , Tura Gian Battista , Rossi Giuseppe , Racagni Giorgio , Gennarelli Massimo
Published: June 2004

Glycogen synthase kinase-3 (GSK-3) is a downstream component of the Wnt pathway and recent studies have reported abnormal levels of GSK-3β in schizophrenia. In a sample of 147 schizophrenic patients and 212 healthy individuals, we analyzed two common SNPs at position –1727 A/T and –50 C/T and a (CAA)n repeat polymorphism localized in intron 1 of the gene. The results showed that the allele, genotype and haplotype distributions for the three polymorphisms investigated do not differ between schizophrenic patients in general and control subjects. However, in the subtype of paranoid schizophrenic patients, we found that the (CAA)3/(CAA)5 heterozygotes were more often represented. Although taken from a small sample, our results support the reports that GSK-3β appears to be involved in a subtype of schizophrenic patients, but not in schizophrenia in general. In conclusion, we would speculate that this gene may be linked to some features of psychotic disorders rather than to schizophrenia itself.
Effects of the South American Psychoactive Beverage Ayahuasca on Regional Brain Electrical Activity in Humans: A Functional Neuroimaging Study Using Low-Resolution Electromagnetic Tomography
Authors: Riba Jordi , Anderer Peter , Jané Francesc , Saletu Bernd , Barbanoj Manel J.
Published: June 2004

Ayahuasca, a South American psychotropic plant tea obtained from Banisteriopsis caapi and Psychotria viridis, combines monoamine oxidase-inhibiting β-carboline alkaloids with N,N-dimethyltryptamine (DMT), a psychedelic agent showing 5-HT2A agonist activity. In a clinical research setting, ayahuasca has demonstrated a combined stimulatory and psychedelic effect profile, as measured by subjective effect self-assessment instruments and dose-dependent changes in spontaneous brain electrical activity, which parallel the time course of subjective effects. In the present study, the spatial distribution of ayahuasca-induced changes in brain electrical activity was investigated by means of low-resolution electromagnetic tomography (LORETA). Electroencephalography recordings were obtained from 18 volunteers after the administration of a dose of encapsulated freeze-dried ayahuasca containing 0.85 mg DMT/kg body weight and placebo. The intracerebral power density distribution was computed with LORETA from spectrally analyzed data, and subjective effects were measured by means of the Hallucinogen Rating Scale (HRS). Statistically significant differences compared to placebo were observed for LORETA power 60 and 90 min after dosing, together with increases in all six scales of the HRS. Ayahuasca decreased power density in the alpha-2, delta, theta and beta-1 frequency bands. Power decreases in the delta, alpha-2 and beta-1 bands were found predominantly over the temporo-parieto-occipital junction, whereas theta power was reduced in the temporomedial cortex and in frontomedial regions. The present results suggest the involvement of unimodal and heteromodal association cortex and limbic structures in the psychological effects elicited by ayahuasca.
The use of a cell-cycle phase-marker may decrease the percentage of errors when using FISH in PGD
Authors: Pujol A. , Benet J. , Campillo M. , Codina-Pascual M. , Egozcue J. , Navarro J.
Published: June 2004

Fluorescent DNA probes are used to characterise the chromosome constitution of preimplantation embryos. FISH is used to select normal or balanced embryos in carriers of balanced chromosomal rearrangements, for embryo sexing or for aneuploidy screening in women of advanced age, who have had recurrent abortions or IVF failures. In most cases, FISH is performed on interphase blastomeres which are asynchronously dividing cells, that can be in G1, S or G2. However, a correct interpretation of a double FISH signal, which may correspond to a split signal, to a replicated chromosome region or to the presence of an extra chromosome is essential to establish an accurate diagnosis. To determine if the cell stage could influence the interpretation of FISH results, we compared the signal characteristics of one locus-specific probe, two different subtelomere region probes, and a centromere region probe in non-dividing Sertoli cells and in proliferating lymphocytes. Most cells had two signals per chromosome pair (i.e., a situation corresponding to G0 in Sertoli cells and to G1 or to a prereplication stage in lymphocytes). Nevertheless, in proliferating cells the percentage of nuclei with a number of signals different from the expected (two unreplicated chromosomes per pair) was different from that found in non-dividing cells (P < 0.05). It was estimated that 10.8% of double dots in dividing cells resulted from DNA replication. The sequence of replication was first the locus-specific region, second a telomere region, and third the centromere. In conclusion, the DNA replication process could result in errors of interpretation (misdiagnosis) in 7% of proliferating cells. Thus, the use of a cell cycle phase-specific marker could avoid errors by indicating the cell stage in which the nucleus analysed is found.
The evolutionary conservation of the human chitotriosidase gene in rodents and primates
Authors: Gianfrancesco F. , Musumeci S.
Published: June 2004

Chitinases have been identified in a variety of organisms ranging from prokaryotes to eukaryotes, known to specifically degrade chitin, an abundant polymer of N-acetylglucosamine. Recently a human chitinolytic enzyme called CHIT1 was discovered. CHIT1 is expressed by activated macrophages and hydrolyzes artificial chitotrioside substrates, but its specific function in humans is unknown, since it is generally believed that man completely lacks endogenous chitin and endogenous substrates for chitinases. An intriguing question is whether the chitotriosidase activity is just an evolutionary remnant or it has a physiological function in man. To test these hypotheses we utilized a “phylogenomic” approach performing accurate sequence analyses of this gene, coding for CHIT1, in rodents and primates. Inspecting the sequences available in public databases, we determined that this gene is conserved in rodents (mouse and rat) and primates (chimpanzee, gorilla, orangutan, gibbon, baboon, a common marmoset and black macaque). Moreover we found that a 24-base pair duplication that determines an enzymatically inactive human protein is not present in primates, suggesting that this polymorphism was created during human evolution. These results indicate that chitotriosidase is conserved across the evolutionary scale. Such conservation of the CHIT1 gene argues in favour of an important biological role.
Isolation and characterization of two families of satellite DNA with repetitive units of 135 bp and 2.5 kb in the ant Monomorium subopacum (Hymenoptera, Formicidae)
Authors: Lorite P. , Carrillo J.A. , Aguilar J.A. , Palomeque T.
Published: June 2004

Analyzing the satellite DNA in the ant species Monomorium subopacum we found two unrelated families of satellite DNA. Because these satellite DNA families were isolated using the two enzymes HaeIII and EcoRI we called the two families HaeIII and EcoRI family, respectively. The HaeIII family proved to be organized in a 135-bp basic unit repeat, the EcoRI family in a 2.5-kb basic unit repeat. The latter represents perhaps the longest satellite DNA isolated up to now in insects. The HaeIII family apparently comprises about 10% of the total genomic DNA whereas the EcoRI family represents only about 1–2%. A comparative analysis of the two satellite DNA sequences showed no homology between the two families although both sequences possessed long A and T stretches. Eight of the 34 chromosomes showed hybridization with the HaeIII family and hybridization signals are visible in six chromosomes with the EcoRI family. Analysis of the electrophoretic mobility of satellite DNA on non-denaturing polyacrylamide showed that the HaeIII family is only slightly curved. However, the unit of the EcoRI satellite DNA family has curvature, especially the first 1000 bp of the monomeric repeat, in which this DNA is AT rich and has numerous A and T stretches. There are also internal inverted subrepeats in each family. The sequences of satellite DNA families found in Monomorium subopacum are different from the sequences of other satellite DNAs cloned in insects, including other species of ants.
Cloning and characterization of the murine Vmd2 RFP-TM gene family
Authors: Krämer F. , Stöhr H. , Weber B.H.F.
Published: June 2004

Mutations in the human vitelliform macular dystrophy type 2 (VMD2) gene are known to cause autosomal dominant Best macular dystrophy (BMD), a degenerative disorder of the central retina. VMD2, together with VMD2L1, VMD2L2 and VMD2L3, belong to a closely related gene family characterized by several transmembrane (TM) spanning helical domains and an invariant arginine, phenylalanine and proline (RFP) tripeptide motif, thus termed VMD2 RFP-TM. The four genes are thought to encode a novel family of anion channels. We now report the cloning and characterization of the murine orthologs by combining biocomputational analyses and molecular genetic approaches. While the murine Vmd2, Vmd2l1 and Vmd2l3 genes are functional, murine Vmd2l2p was found to be a non-transcribed pseudogene. Expression profiling of the murine Vmd2 RFP-TM family members revealed tissue-restricted expression with predominant transcription of Vmd2 in testis, of Vmd2l1 in colon and of Vmd2l3 in heart. Differential splicing was observed for Vmd2l3 in a number of tissues (e.g. in brain, retina/RPE, kidney) although the functional importance of the splice variants remains to be determined.
Comparative chromosome painting between the domestic pig (Sus scrofa) and two species of peccary, the collared peccary (Tayassu tajacu) and the white-lipped peccary (T. pecari): a phylogenetic perspective
Authors: Bosma A.A. , de Haan N.A. , Arkesteijn G.J.A. , Yang F. , Yerle M. , Zijlstra C.
Published: June 2004

The Suidae and the Dicotylidae (or Tayassuidae) are related mammalian families, both belonging to the artiodactyl suborder Suiformes, which diverged more than 37 million years ago. Cross-species chromosome painting was performed between the domestic pig (Sus scrofa; 2n = 38), a representative of the Suidae, and two species of the Dicotylidae: the collared peccary (Tayassu tajacu; 2n = 30) and the white-lipped peccary (T. pecari; 2n = 26). G-banded metaphase chromosomes of the two peccaries were hybridized with whole chromosome painting probes derived from domestic pig chromosomes 1–18 and X. For both peccary species, a total of 31 autosomal segments that are conserved between pig and peccary could be identified. The painting results confirm conclusions inferred from G-band analyses that the karyotypes of the collared peccary and the white-lipped peccary are largely different. The karyotypic heterogeneity of the Dicotylidae contrasts with the relative homogeneity among the karyotypes of the Suidae. For this difference between the Dicotylidae and the Suidae, a number of explanations are being postulated: 1) the extant peccaries are phylogenetically less closely related than is usually assumed; 2) the peccary genome is less stable than the genome of the pigs; and 3) special (e.g. biogeographical or biosocial) circumstances have facilitated the fixation of chromosome rearrangements in ancestral dicotylid populations.
Chromosomal anchoring of linkage groups and identification of wing size QTL using markers and FISH probes derived from microdissected chromosomes in Nasonia (Pteromalidae: Hymenoptera)
Authors: Rütten K.B. , Pietsch C. , Olek K. , Neusser M. , Beukeboom L.W. , Gadau J.
Published: June 2004

Nasonia vitripennis is a small parasitic hymenopteran with a 50-year history of genetic work including linkage mapping with mutant and molecular markers. For the first time we are now able to anchor linkage groups to specific chromosomes. Two linkage maps based on a hybrid cross (N. vitripennis × N. longicornis) were constructed using STS, RAPD and microsatellite markers, where 17 of the linked STS markers were developed from single microdissected banded chromosomes. Based on these microdissections we anchored all linkage groups to the five chromosomes of N. vitripennis. We also verified the chromosomal specificity of the microdissection through in situ hybridization and linkage analyses. This information and technique will allow us in the future to locate genes or QTL detected in different mapping populations efficiently and fast on homologous chromosomes or even chromosomal regions. To test this approach we asked whether QTL responsible for the wing size in two different hybrid crosses (N. vitripennis × N. longicornis and N. vitripennis × N.giraulti) map to the same location. One QTL with a major effect was found to map to the centromere region of chromosome 3 in both crosses. This could indicate that indeed the same gene/s is involved in the reduction of wing in N. vitripennis and N. longicornis.
Intra-Oral Acid Production Associated with Eating Whole or Pulped Raw Fruits
Authors: Beighton D. , Brailsford S.R. , Gilbert S.C. , Clark D.T. , Rao S. , Wilkins J.C. , Tarelli E. , Homer K.A.
Published: June 2004

The hypotheses that raw fruits, whether whole or pulped, were cleared rapidly from the mouth and that the sugars in the whole and pulped fruits are fermented with equal efficiency to acids by the oral microflora were tested in this study. Groups of 7–9 adult subjects chewed 10 g of raw, whole or pulped fruit (apple, banana, orange, pear and pineapple) for 1 min and whole, unstimulated saliva samples were collected during the following 60-min interval. Each saliva sample was assayed for the concentrations of fruit-derived sugars (glucose, fructose and sucrose), fruit-derived acids (malic and citric) and acids which may be produced as a result of bacterial fermentation (acetic, lactic, formic and succinic). We found the fruit-derived sugars were rapidly cleared from the mouth (within 5 min). The major bacterially produced acids were lactic and succinic, which reached maximum concentrations in the 5-min sample. There was no significant difference, within a fruit, in the salivary levels of any of the sugars or acids between the raw whole or raw pulped forms. In light of these findings it seems unwise to assume that fruits may be consumed without consideration of their acidogenic potential.
Evaluation of Several Techniques for the Detection of Secondary Caries Adjacent to Amalgam Restorations
Authors: Ando M. , González-Cabezas C. , Isaacs R.L. , Eckert G.J. , Stookey G.K.
Published: June 2004

The objective of this study was to determine the ability of several techniques to detect natural secondary caries adjacent to proximal class II amalgam restorations. Two sites were selected and marked on each of 50 human extracted posterior teeth. Three examiners visually characterized each site independently for signs of demineralization (VI), ditching presence (VD), and color change, and utilized light-induced fluorescence (QLF), and infrared laser fluorescence (LF) techniques. The teeth were sectioned through the selected sites, and the severity of each lesion was determined by confocal laser scanning microscopy (CLSM) as the ‘gold standard’. Agreement among examiners was assessed using weighted kappa statistics and showed fair to moderate correlation with all techniques. Sensitivity, specificity, positive predictive value (PPV), negative predictive value and accuracy were determined by utilizing three arbitrary CLSM thresholds. Higher sensitivity was indicated by the QLF and LF than by VI. For PPV and accuracy, QLF and LF showed values higher or similar to VI. Low sensitivity was found for VD. The results obtained in this study suggest that LF and QLF may improve the ability to detect early secondary caries around amalgam restorations.
A Randomised Study Comparing Escitalopram with Venlafaxine XR in Primary Care Patients with Major Depressive Disorder
Authors: Montgomery S.A. , Huusom A.K.T. , Bothmer J.
Published: June 2004

This 8-week, randomised, double-blind study compared the efficacy and tolerability of escitalopram to that of venlafaxine XR in primary care patients with major depressive disorder. The efficacy of escitalopram (10– 20 mg; n = 148) was similar to venlafaxine XR (75– 150 mg; n = 145), based on mean change from baseline to week 8 in Montgomery and Åsberg Depression Rating Scale total score. In ad hoc analyses, escitalopram-treated patients achieved sustained remission significantly faster than did venlafaxine-treated patients. More venlafaxine-treated patients had nausea, constipation, and increased sweating (p < 0.05). When treatment was completed after 8 weeks, significantly more venlafaxine-treated patients had discontinuation symptoms (p < 0.01). Thus escitalopram treatment was similar to venlafaxine treatment with respect to efficacy and was better tolerated by patients in primary care.
Benign Acute Childhood Myositis
Authors: Müjgan Sonmez Fatma , Çakir Murat , Yayla Şeker , Boz Cavit
Published: June 2004

Objective: To evaluate the clinical and laboratory findings of benign acute childhood myositis. Subjects andMethods: Six children, 1 girl and 5 boys, aged 3–9 years, were admitted to Karadeniz Technical University Paediatric Neurology Department in Trabzon, Turkey, with the diagnosis of benign acute childhood myositis in January and February 2002. The clinical and laboratory findings on the patients were analysed. Results: Serum creatine kinase and aspartate aminotransferase levels were increased in all cases. Two patients had leucopenia. Viral studies were negative. All the patients had a good outcome, and full recovery was achieved within 12 h to 3 days. Conclusion: Benign acute childhood myositis is a self-limiting disease with a good prognosis. Pediatricians and pediatric neurologists must be aware of this condition to avoid unnecessary investigations and to differentiate this condition from other causes of acute onset of inability to walk. It may occur in epidemics mainly in the wintertime, suggesting a viral aetiology.