bluuebunny/crossref_metadata_2025 huggingface dataset:
Unusual duodenal presentation of leishmaniasis: Figure 1
Authors: Álvarez-Nebreda M L , Álvarez-Fernández E , Rada S , Brañas F , Marañón E , Vidán M T , Serra-Rexach J A
Published: November 2005

This case report describes an atypical case of duodenal leishmaniasis in an elderly patient not infected with human immunodeficiency virus. Investigation of this 84 year old woman with a constitutional syndrome and dysphagia revealed anaemia of chronic disorder, a high erythrocyte sedimentation rate, and polyclonal hypergammaglobulinaemia. Abdominal ultrasonography revealed thickening of the stomach wall, which was seen to be inflamed during gastroscopy. Duodenal histology revealed numerous leishmania amastigotes within macrophages. This was confirmed by bone marrow biopsy and leishmania serology. This case report stresses the importance of atypical symptoms and the unusual location of visceral leishmaniasis, not only in immunodepressed patients, but also in elderly immunocompetent patients.
Blood film examination for vacuolated lymphocytes in the diagnosis of metabolic disorders; retrospective experience of more than 2500 cases from a single centre
Authors: Anderson G , Smith V V , Malone M , Sebire N J
Published: November 2005

Background:A range of metabolic diseases can result in abnormal accumulation of metabolic byproducts, resulting in abnormal lymphocyte cytoplasmic vacuolation, identifiable on routine blood film examination.

Aims:This study retrospectively examines the usefulness of blood film examination for vacuolated lymphocytes in a specialist paediatric pathology department in relation to patient’s age and presentation. It also describes specific diagnostic features in relation to specific classes of metabolic disease.

Methods:Retrospective review of a histopathology database to identify all blood films examined for the detection of vacuolated lymphocytes during a 15 year period (1989–2004).

Results:In total, 2550 blood films were investigated. The median age at submission was 2 years (range, birth to 88), and > 90% of samples were from children < 18 years. The most common indications were developmental delay/regression, ataxia, seizures, and cardiomyopathy. Vacuolated lymphocytes were identified in 156 films (6.1%). The frequency of vacuolated lymphocytes varied with clinical presentation, with ophthalmic indications having the highest positive rate (40%). In cases with vacuolated lymphocytes, a wide range of underlying metabolic diagnoses was apparent, the most common being juvenile neuronal ceroid lipofuscinosis and acid maltase deficiency, which accounted for more than half of the diagnoses.

Conclusions:The examination of blood films for lymphocyte vacuolation is clinically useful in patients with a history suggestive of metabolic disease. The test is cheap, rapid, minimally invasive, and provides first line screening, with some findings indicating clues to a specific underlying diagnosis.
My approach to superficial inflammatory dermatoses
Authors: Alsaad K O , Ghazarian D
Published: November 2005

Superficial inflammatory dermatoses are very common and comprise a wide, complex variety of clinical conditions. Accurate histological diagnosis, although it can sometimes be difficult to establish, is essential for clinical management. Knowledge of the microanatomy of the skin is important to recognise the variable histological patterns of inflammatory skin diseases. This article reviews the non-vesiculobullous/pustular inflammatory superficial dermatoses based on the compartmental microanatomy of the skin.
Sclerochoroidal calcification associated with Gitelman syndrome and calcium pyrophosphate dihydrate deposition
Authors: Gupta R , Hu V , Reynolds T , Harrison R
Published: November 2005

Sclerochoroidal calcification is an uncommon condition. Metabolic evaluation and clinical examination are important to exclude associated systemic conditions such as the Bartter and Gitelman syndromes. It has been suggested that the lesions seen in sclerochoroidal calcification are calcium pyrophosphate dihydrate crystals. This report describes the first documented case in the UK of sclerochoroidal calcification associated with Gitelman syndrome and calcium pyrophosphate dihydrate deposition.
Expression of CD1d in human scalp skin and hair follicles: hair cycle related alterations
Authors: Adley M A , Assaf H A , Hussein M
Published: November 2005

Background:CD1d belongs to a family of antigen presenting molecules that are structurally and distantly related to the classic major histocompatibility complex class I (MHC I) proteins. However, unlike MHC I molecules, which bind protein antigens, CD1d binds to lipid and glycolipid antigens. CD1d is expressed by cells of lymphoid and myeloid origin, and by cells outside of the lymphoid and myeloid lineages, such as human keratinocytes of psoriatic skin.

Aims:To investigate whether CD1d is also expressed in sun exposed skin and in the immunoprivileged anagen hair follicle.

Materials/Methods:CD1d immunoreactivity was studied in human scalp skin and hair follicles of healthy women in situ by immunofluorescent and light microscopic immunohistology. Skin biopsies were obtained from normal human scalp containing mainly anagen VI hair follicles from women (age, 53–57 years) undergoing elective plastic surgery.

Results:CD1d showed strong immunostaining in human scalp skin epidermis, pilosebaceous units, and eccrine glands. In the epidermis, CD1d was strongly expressed by basal and granular keratinocytes. In hair follicles, CD1d was expressed in the epithelial compartment and showed hair cycle related alterations, with an increase in the anagen and a reduction in the catagen and telogen phases.

Conclusions:These results suggest that CD1d plays a role in human scalp skin immunology and protection against lipid antigen rich infectious microbes. They also raise the question of whether keratinocytes of the immunoprivileged anagen hair follicle can present lipid antigens to natural killer T cells. These data could help provide new strategies for the manipulation of hair related disorders.
Light microscopic examination of scalp hair samples as an aid in the diagnosis of paediatric disorders: retrospective review of more than 300 cases from a single centre
Authors: Smith V V , Anderson G , Malone M , Sebire N J
Published: November 2005

Background:Microscopic examination of scalp hair can provide important diagnostic information in a range of paediatric conditions. It is a non-invasive and cost effective investigation, which is not widely performed.

Aims:To examine retrospectively the value of hair examination by light microscopy, including polarising microscopy, in a specialist paediatric pathology department during a 15 year period (1989–2004) and to describe the morphological abnormalities indicative of specific paediatric conditions.

Methods:Three hundred and twenty two hair samples were submitted. Microscopic changes were analysed in the light of clinical information categorised as: (1) erythroderma, (2) neurological impairment, (3) immunological/haematological defect, (4) ectodermal dysplasia, (5) abnormal hair only, and (6) non-specific/absent clinical details.

Results:Abnormalities were evident in 49% of the samples. In 25%, the changes were compatible with specific diagnoses including Menkes disease, Netherton’s syndrome, trichothiodystrophy, Griscelli and Chediak-Higashi syndromes, monilethrix, uncombable hair, and loose anagen syndromes. In respect of the clinical presentation groups noted above, diagnostic changes were seen in 41%, 32%, 33%, 0%, 29%, and 0%, respectively.

Conclusions:Morphological light microscopic examination of scalp hair is an inexpensive, rapid, and non-invasive investigation, which can provide valuable diagnostic information in a range of paediatric conditions.
Survey of clinical allergy services provided by clinical immunologists in the UK
Authors: El-Shanawany T M , Arnold H , Carne E , Misbah S A , Egner W , Wallington T B , Herriot R , Williams P E
Published: November 2005

Background:The UK National Health Service is failing to meet the need for diagnosis and treatment of allergic disorders, which are common and increasing in prevalence. The House of Commons select committee report on allergy services highlighted the inequalities and urgent need for investment.

Aim:To survey the allergy workload provided by clinical immunologists to inform service planning and resource allocation.

Methods:The allergy services performed by clinical immunologists during a 12 month period from 1 April 2003 to 31 March 2004 were surveyed by means of a questionnaire via supraregional audit groups.

Results:The immunology centres surveyed serve 32 million people and offer almost the complete repertoire of a specialised allergy service. There were large variations in clinic capacity, new referrals, appointment duration, and service configuration. Services were largely consultant delivered, but availability of joint clinics with paediatricians and anaesthetists was locally variable. Novel service delivery models utilising nurses and clinical assistants have been developed and merit further investigation.

Conclusion:Consultant immunologists and trainees currently make a major contribution to the development and provision of specialised allergy services. Consultant immunologists will probably remain key providers of tertiary level allergy care in the UK in the long term (in line with other countries) and will be pivotal in supporting and developing the provision of equitable national access to specialist allergy services in a timely manner. Rapid progress in developing the new specialty of allergy and securing better access to services for patients in the short term will be best served by strengthening the collaborative relationship between allergists and clinical immunologists.
Histological examination has a major impact on macroscopic necropsy diagnoses
Authors: Bernardi F D C , Saldiva P H N , Mauad T
Published: November 2005

Background:Necropsy is the gold standard for clinicopathological discrepancy studies and epidemiological surveys. Inadequate sampling or lack of tissue may hamper the final interpretation and quality of the necropsy.

Aim:To compare the histological and gross necropsy diagnoses of different organs.

Methods:A retrospective comparison of the provisional reports (gross findings only) and the final reports (after histological examination) of the necropsies performed at the department of pathology of the Hospital das Clínicas, Sao Paulo University, Brazil, a large tertiary care complex, in 2001. The total number of diagnoses listed for the lungs, heart, liver, pancreas, kidneys, and spleen were calculated. Findings were categorised into concordant/refined diagnosis, discordant/additional diagnosis, histology needed, and inconclusive.

Results:Three hundred and seventy one postmortem reports were analysed. There were 214 men and 157 women, with a mean age of 50.3 years, ranging from 1 to 92. The lung received the highest number (954) and the pancreas the lowest number (390) of diagnoses. The highest frequencies of discrepancies between the gross and microscopic findings were found in the lung and the liver: 38.7% and 35.1%, respectively. The brain had the lowest frequency of discrepancies. In a small number of cases, the final diagnosis could only be achieved through microscopic analysis, with the highest frequency being found in the kidneys (8.5%).

Conclusions:Histological analysis has a major impact on previously performed gross diagnosis at necropsy, especially in the lungs, liver, and kidneys. Adequate sampling and histological analysis are important for necropsy quality.
Extensive intestinal metaplasia in gastric carcinoma and in other lesions requiring surgery. A study of 3421 gastrectomy specimens from dwellers of the Atlantic and Pacific basins
Authors: Rubio C A , Jónasson J , Nesi G , Mandai K , Pisano R , King A , Owen D
Published: November 2005

Background:Extensive intestinal metaplasia (EIM) has been reported in gastrectomies from patients dwelling in the Pacific and Atlantic basins.

Aims:To compare all the results in an attempt to explain the findings.

Method:All sections from 3421 gastrectomies were reviewed at various hospitals: 1946 in the Atlantic and 1475 in the Pacific basin. Sections with EIM showed IM encompassing one or more entire low power field (⩾5 mm in length/section) in one or more section.

Results:In the Atlantic basin, EIM was present in 18.8% (153 of 814) of specimens with intestinal carcinoma (IC) and in 10.3% (65 of 630) of those with diffuse carcinoma (DC). In the Pacific basin, EIM was found in 62.9% (412 of 655) of gastrectomies with IC and in 33.3% (160 of 481) of those with DC. The numbers of specimens with EIM were significantly higher in the Pacific than in the Atlantic basin for both carcinoma phenotypes, particularly among elderly patients (⩾60 years).

Conclusions:The proportion of gastrectomies with EIM was higher among populations at a higher gastric cancer risk than in those with a lower cancer risk. EIM was mostly associated with IC rather than DC or with miscellaneous gastric diseases (841 control gastrectomies) in both basins. The proportion of gastrectomies with EIM was significantly higher in Vancouver than in New York and in Santiago de Chile than in Buenos Aires, even though these populations reside at approximately the same geographical latitude, but in different basins. Environmental factors seem to accelerate the evolution of EIM.
Effects of Acupuncture on Potential Along Meridians of Healthy Subjects and Patients with Gastric Disease
Authors: Lee Yong-Heum , Lee Myeong Soo , Shin Byung-Cheul , Jeong Jin-Sang , Jeong Dong-Myong , Hwang In Chul , Kim Jong Il
Published: November 2005

The purpose of this study was to investigate the differences in bio-potential in the stomach meridians of 20 normal healthy control subjects (NHC) and 20 patients with gastric disease (PGD). We measured changes in potential between ST-39 and ST-37 on the stomach meridian in response to invasive insertion of a needle at ST-36. The response patterns of NHC were regular in both the left and right meridians, whereas the response patterns of PGD were irregular. The potential of the NHC was significantly higher than that of the PGD group. The potential values in the left and right meridians of NHC were the same. However, the potential in the right meridian was significantly higher than that in the left meridian of PGD ( p < 0.001). This study indicates that there may be changes in Qi or in the electrical properties of meridians according to health status, reflected in the regularity of the response to acupuncture or in the level of potential along meridians. Therefore, it may be possible to make a diagnosis from the state of a meridian by comparing levels of potential difference and its regularity.
MAGNETIC ORDERING IN QUASICRYSTALS
Authors: VEDMEDENKO E. Y.
Published: November 2005

An overview of the theoretical advances in description of the magnetic ordering and its stability in two-dimensional quasiperiodic tilings with strongly localized magnetic moments is presented. It is demonstrated that combination of the magnetic frustration and the quasiperiodic order of atoms leads to noncollinear ground states. An experimental and theoretical evidence for the possibility of coexistence of stable, magnetically ordered subtilings with highly frustrated, glass-like phases in a single sample is given.
Heart rate variability and cardiac reflexes in small for gestational age infants
Authors: Galland Barbara C. , Taylor Barry J. , Bolton David P. G. , Sayers Rachel M.
Published: November 2005

To assess the influence of intrauterine growth retardation and postnatal development on heart rate variability (HRV) and cardiac reflexes, we studied 27 healthy small for gestational age (SGA) and 23 appropriate for gestational age (AGA) infants during a nap study. Resting HRV was assessed by point dispersion of Poincaré plots for overall (SDRR) and instantaneous beat-to-beat variability (SDΔRR) and the ratio (SDRR/SDΔRR). Heart rate reflex and arousal responses to a 60° head-up tilt were determined. All tests/measures were repeated twice in quiet and active sleep and in prone and supine sleep positions at 1 and 3 mo of age. SGA infants exhibited higher resting sympathetic tone [SDRR/SDΔRR: 1.9 (95% confidence interval: 1.7, 2.0) and 1.7 (95% confidence interval: 1.5, 1.8) in SGA and AGA, respectively; P = 0.046] and a tendency for a smaller tachycardic reflex response to the tilt [Δheart rate: 24 beats/min (95% confidence interval: 20, 28) and 30 (95% confidence interval: 25, 34)] in SGA and AGA, respectively; P = 0.06]. HRV indexes were reduced in the prone compared with supine position ( P < 0.0001), but reflex tilt responses were unchanged with position. SGA/AGA differences were independent of sleep position. Gestational age weight status did not influence the likelihood of arousal, but prone sleeping per se reduced the odds 2.5-fold. The findings suggest reduced autonomic activity and cardiac reflexes in SGA infants. The finding that the sympathetic component of the control of HRV was higher in SGA infants could link with findings in adulthood of an association between being born SGA and a higher risk of cardiovascular disease.
The RsbRST Stress Module in Bacteria: A Signalling System That May Interact with Different Output Modules
Authors: Pané-Farré Jan , Lewis Richard J. , Stülke Jörg
Published: November 2005

In the Gram-positive bacterium Bacillus subtilis, the activity of the alternative sigma factor σB is triggered upon exposure of the bacteria to environmental stress conditions or to nutrient limitation. σB activity is controlled by protein-phosphorylation-dependent interactions of anti-sigma with anti-anti-sigma factors. Under stress conditions, the phosphatase RsbU triggers release of σB and thus induces the expression of stress genes. RsbU activity is controlled by three proteins, RsbR, RsbS and RsbT which form a supramolecular complex called the stressosome. Here we review the occurrence of the genes encoding the stressosome proteins (called the RsbRST module) in a wide variety of bacteria. While this module is linked to the gene encoding σB and its direct regulators in B. subtilis and its close relatives, genes encoding two-component regulatory systems and more complex phosphorelays are clustered with the RsbRST module in bacteria as diverse as cyanobacteria, bacteroidetes, proteobacteria, and deinococci. The conservation of the RsbRST module and its clustering with different types of regulatory systems suggest that the stressosome proteins form a signal sensing and transduction unit that relays information to very different output modules.
Biosynthesis Pathways for Deoxysugars in Antibiotic-Producing Actinomycetes: Isolation, Characterization and Generation of Novel Glycosylated Derivatives
Authors: Salas José A. , Méndez Carmen
Published: November 2005

Many bioactive natural products synthesized by actinomycetes are glycosylated compounds in which the appended sugars contribute to specific interactions with their biological target. Most of these sugars are 6-deoxyhexoses, of which more than 70 different forms have been identified, and an increasing number of gene clusters involved in 6-deoxyhexoses biosynthesis are being characterized from antibiotic-producing actinomycetes. Novel glycosylated compounds have been generated by modifying natural deoxysugar biosynthesis pathways in the producer organisms, and/or the simultaneous expression in these strains of selected deoxysugar biosynthesis genes from other strains. Non-producing strains endowed with the capacity to synthesize novel deoxysugars through the expression of engineered deoxysugar biosynthesis clusters can also be used as alternative hosts. Transfer of these deoxysugars to a multiplicity of aglycones relies upon the existence of glycosyltransferases with an inherent degree of ‘relaxed substrate specificity’. In this review, we analyze how the knowledge coming out from isolation and characterization of deoxysugar biosynthesis pathways from actinomycetes is being used to produce novel glycosylated derivatives of natural products.
Prediction of Functional Class of Novel Bacterial Proteins without the Use of Sequence Similarity by a Statistical Learning Method
Authors: Cui J. , Han L.Y. , Cai C.Z. , Zheng C.J. , Ji Z.L. , Chen Y.Z.
Published: November 2005

A substantial percentage of the putative protein-encoding open reading frames (ORFs) in bacterial genomes have no homolog of known function, and their function cannot be confidently assigned on the basis of sequence similarity. Methods not based on sequence similarity are needed and being developed. One method, SVMProt (http://jing.cz3.nus.edu.sg/cgi-bin/svmprot.cgi), predicts protein functional family irrespective of sequence similarity (Nucleic Acids Res. 2003;31:3692–3697). While it has been tested on a large number of proteins, its capability for non-homologous proteins has so far been evaluated for a relatively small number of proteins, and additional tests are needed to more fully assess SVMProt. In this work, 90 novel bacterial proteins (non-homologous to known proteins) are used to evaluate the capability of SVMProt. These proteins are such that none of their homologs are in the Swiss-Prot database, their functions not clearly described in the literature, and they themselves and their homologs are not included in the training sets of SVMProt. They represent proteins whose function cannot be confidently predicted by sequence similarity methods at present. The predicted functional class of 76.7% of each of these proteins shows various levels of consistency with the literature-described function, compared to the overall accuracy of 87% for the SVMProt functional class assignment of 34,582 proteins that have at least one homolog of known function. Our study suggests that SVMProt is capable of assigning functional class for novel bacterial proteins at a level not too much lower than that of sequence alignment methods for homologous proteins.
Inhibition of Mycobacterium smegmatis Gene Expression and Growth Using Antisense Peptide Nucleic Acids
Authors: Kulyté Agné , Nekhotiaeva Natalia , Awasthi Satish Kumar , Good Liam
Published: November 2005

Antisense agents that inhibit genes at the mRNA level are attractive tools for genome-wide studies and drug target validation. The approach may be particularly well suited to studies of bacteria that are difficult to manipulate with standard genetic tools. Antisense peptide nucleic acids (PNA) with attached carrier peptides can inhibit gene expression in Escherichia coli and Staphylococcus aureus. Here we asked whether peptide-PNAs could mediate antisense effects in Mycobacterium smegmatis. We first targeted the gfp reporter gene and observed dose- and sequence-dependent inhibition at low micromolar concentrations. Sequence alterations within both the PNA and target mRNA sequences eliminated inhibition, strongly supporting an antisense mechanism of inhibition. Also, antisense PNAs with various attached peptides showed improved anti-gfp effects. Two peptide-PNAs targeted to the essential gene inhA were growth inhibitory and caused cell morphology changes that resemble that of InhA-depleted cells. Therefore, antisense peptide-PNAs can efficiently and specifically inhibit both reporter and endogenous essential genes in mycobacteria.
Pathways in the Degradation of Hydrolyzed Alcohols of Butyl Benzyl Phthalate in Metabolically Diverse Gordonia sp.Strain MTCC 4818
Authors: Chatterjee Subhankar , Mallick Somnath , Dutta Tapan K.
Published: November 2005

In the present study, the metabolic pathways involved in the degradation of benzyl alcohol and 1-butanol, the hydrolyzed products of butyl benzyl phthalate, were investigated by the Gordonia sp. strain MTCC 4818. The strain can utilize both benzyl alcohol and 1-butanol individually as sole carbon sources, where benzyl alcohol was found to be metabolized via benzaldehyde, benzoic acid and catechol, which was further degraded by ortho-cleavage dioxygenase to cis,cis-muconic acid and subsequently to muconolactone leading to tricarboxylic acid cycle. On the other hand, 1-butanol was metabolized via butyraldehyde and butyric acid, which was channeled into the tricarboxylic acid cycle via the β-oxidation pathway. Numbers of dehydrogenases, both NAD+-dependent and NAD+-independent, were found to be involved in the degradation of benzyl alcohol and 1-butanol, where several dehydrogenases exhibited relaxed substrate specificity. Both 2,3- and 3,4-dihydroxybenzoic acids were utilized by the test organism for growth and metabolized by the ortho-cleavage pathway by the cell-free extract of benzoate-grown cells, similar to catechol, suggesting possible broad substrate specificity of the ring cleavage dioxygenase. Moreover, the test organism can utilize various primary and secondary alcohols, aliphatic aldehydes and acids in the C2–C5 range besides n-hexadecane, 1,4-butanediol and cyclohexanol individually as the sole carbon sources indicating metabolic diversity in the Gordonia sp. strain MTCC 4818.
The Bias Introduced by Population Stratification in IBD Based Linkage Analysis
Authors: Wang Tao , Elston Robert C.
Published: November 2005

The lack of replication of model-free linkage analyses performed on complex diseases raises questions about the robustness of these methods to various biases. The confounding effect of population stratification on a genetic association study has long been recognized in the genetic epidemiology community. Because the estimation of the number of alleles shared identical by descent (IBD) does not depend on the marker allele frequency when founders of families are observed, model-free linkage analysis is usually thought to be robust to population stratification. However, for common complex diseases, the genotypes of founders are often unobserved and therefore population stratification has the potential to impair model-free linkage analysis. Here, we demonstrate that, when some or all of the founder genotypes are missing, population stratification can introduce deleterious effects on various model-free linkage methods or designs. For an affected sib pair design, it can cause excess false-positive discoveries even when the trait distribution is homogeneous among subpopulations. After incorporating a control group of discordant sib pairs or for a quantitative trait, two circumstances must be met for population stratification to be a confounder: the distributions for both the marker and the trait must be heterogeneous among subpopulations. When this occurs, the bias can result in either a liberal, and hence invalid, test or a conservative test. Bias can be eliminated or alleviated by inclusion of founders’ or other family members’ genotype data. When this is not possible, new methods need to be developed to be robust to population stratification.
Multi-Locus Penetrance Variance Analysis Method for Association Study in Complex Diseases
Authors: Sun Xiangqing , Zhang Zhongqi , Zhang Yulong , Zhang Xuegong , Li Yanda
Published: November 2005

Common heritable diseases often result from the action of several different genes, each of which contributes to the total observed variability in the disease trait. Traditional single-locus association approaches rely heavily on the marginal effects of single-locus and tend to ignore the multigenic nature of complex diseases. The increasing request for localizing genes underlying traits in multi-gene diseases has led to the development of some statistical methods. In this study, we develop a multi-locus analysis method – multi-locus penetrance variance analysis (MPVA), and conduct systematical simulation studies to evaluate its performance. Our results show that compared with other multi-locus methods, MPVA has some advantage in detecting complicated interactions under different epistatic models, and its performance is stable and robust.
Neuroticism Mediates the Association of the Serotonin Transporter Gene with Lifetime Major Depression
Authors: Munafò Marcus R. , Clark Taane G. , Roberts Kate H. , Johnstone Elaine C.
Published: November 2005

Background and Objectives: An association between a polymorphism in the serotonin transporter gene (5HTT-LPR) and the personality trait of neuroticism has been reported. We sought to address the question of whether trait neuroticism mediates the putative association between this polymorphism and lifetime major depression in adults drawn from the general population. Methods: Two hundred and fifty-one participants completed the Eysenck Personality Questionnaire and an adapted version of the depression section of the Structured Clinical Interview for DSM-III-R diagnosis, modified for implementation by a self-report questionnaire. A path method was applied to assess the mediator effect of neuroticism on the association between 5HTT-LPR genotype and lifetime major depression. Results: 5HTT-LPR genotype was significantly associated with both neuroticism (p = 0.02) and lifetime major depression (p = 0.04), and neuroticism with lifetime major depression (p < 0.001). Neuroticism accounted for 42.3% of the effect of 5HTT-LPR genotype on lifetime major depression, indicating possible mediation (p < 0.001). Conclusions: These results suggest that neuroticism mediates the association between 5HTT-LPR genotype and lifetime major depression, consistent with models of the aetiology of depression which suggest that anxiety-related personality traits represent a substantial risk factor for affective disorder.
Temperament and Character in Mood Disorders: Influence of DRD4, SERTPR, TPH and MAO-A Polymorphisms
Authors: Serretti Alessandro , Mandelli Laura , Lorenzi Cristina , Landoni Samuela , Calati Raffaella , Insacco Chiara , Cloninger C. Robert
Published: November 2005

Gene variants exert a complex range of effects on human normal and abnormal behavior. We previously reported the effect of gene variants in serotoninergic and dopaminergic pathways, in a range of clinical features in mood disorders, such as symptomathology, periodicity, social adjustment and treatment response. In this paper we hypothesized that the same gene variants could influence temperamental traits in mood disorders patients. We focused on genes of the serotoninergic and dopaminergic systems (dopamine receptor D4 gene, DRD4; serotonin transporter gene, promoter region SERTPR; tryptophan hydroxylase gene, TPH; monoamine oxidase A gene, MAO-A). Two hundred and seven euthymic subjects, affected by major depressive disorder (n = 73) and bipolar disorder (n = 134) were assessed by the Cloninger’s Temperament and Character Inventory (TCI) and typed using PCR-based analyses. Possible stratification factors such as demographic, clinical and other temperamental factors were also taken into account. We observed that homozygosity for the short SERTPR allele was associated with low novelty-seeking scores (p = 0.006) and genotypes containing the DRD4 long allele were marginally associated with low harm avoidance (p = 0.05). Finally, the long MAO-A allele was associated with decreased persistence scores among females (p = 0.006). Our observation of a pattern of influence on temperamental dimension exerted by serotonergic and dopaminergic genes suggests that the contribution of these polymorphisms to the clinical presentation of mood disorders could be mediated by an influence on personality differences.
ASPD Blunts the Effects of HIV and Antiretroviral Treatment on Event-Related Brain Potentials
Authors: Bauer Lance O. , Shanley John D.
Published: November 2005

Several studies have demonstrated that antiretroviral therapy diminishes the adverse effects of HIV/AIDS on brain function. Yet, few studies have examined the role of comorbid psychiatric disorders in limiting the magnitude of recovery. The present study examined the effects of the presence versus absence of one such disorder – antisocial personality disorder (ASPD) – on brain function in an HIV-1 seronegative control group (n = 68) and in HIV-1 seropositive patients receiving (n = 26), versus not receiving (n = 71), antiretroviral treatment. The primary dependent measures of brain function were the amplitude, latency, and topography of the P300 event-related potential. ANCOVA revealed a significant main effect of ASPD as well as an interaction between ASPD and HIV-1/treatment status. Participants with ASPD exhibited a significant decrement in frontal P300 amplitude in comparison to the ASPD-negative groups. More importantly, further analyses showed that ASPD blunted the decrement in P300 accompanying untreated HIV/AIDS as well as the improvement in P300 accompanying antiretroviral treatment. The results suggest that P300 is minimally improved by antiretroviral therapy among HIV-1 seropositive patients with comorbid ASPD. The lack of antiretroviral efficacy is not easily explained by poor medication compliance. The diminished response to treatment is more likely related to a pre-existing neurophysiological decrement localized to the same brain regions where HIV/AIDS and antiretroviral treatment exert their maximal effect.
Mental, Physical and Social Components in Leisure Activities Equally Contribute to Decrease Dementia Risk
Authors: Karp Anita , Paillard-Borg Stephanie , Wang Hui-Xin , Silverstein Merril , Winblad Bengt , Fratiglioni Laura
Published: November 2005

Background: There is accumulating evidence in the literature that leisure engagement has a beneficial effect on dementia. Most studies have grouped activities according to whether they were predominantly mental, physical or social. Since many activities contain more than one component, we aimed to verify the effect of all three major components on the dementia risk, as well as their combined effect. Methods: A mental, social and physical component score was estimated for each activity by the researchers and a sample of elderly persons. The correlation between the ratings of the authors and the means of the elderly subjects’ ratings was 0.86. The study population consisted of 776 nondemented subjects, aged 75 years and above, living in Stockholm, Sweden, who were still nondemented after 3 years and were followed for 3 more years to detect incident dementia cases. Results: Multi-adjusted relative risks (RRs) of dementia for subjects with higher mental, physical and social component score sums were 0.71 (95% CI: 0.49–1.03), 0.61 (95% CI: 0.42–0.87) and 0.68 (95% CI: 0.47–0.99), respectively. The most beneficial effect was present for subjects with high scores in all or in two of the components (RR of dementia = 0.53; 95% CI: 0.36–0.78). Conclusions: These findings suggest that a broad spectrum of activities containing more than one of the components seems to be more beneficial than to be engaged in only one type of activity.
Trends in Incidence of Colorectal Cancer in Jewish and Arab Populations in Central Israel
Authors: Fireman Zvi , Neiman Elena , Abu Mouch Saif , Kopelman Yael
Published: November 2005

Background/Aims: To compare the current differences with our earlier findings on the incidence and locations of colorectal cancer (CRC) among Israeli-born Jews and Arabs living within the same central coastal region in Israel. Methods: Data on demographics and the incidence and locations of malignancies were retrieved from hospital files of pathology-diagnosed patients with CRC throughout 1997–2003 and compared with equivalent data from 1988 to 1996. Results: Of the 624 patients recently diagnosed as having CRC, 562 (90.1%) were Jews and 62 (9.9%) were Arabs (p < 0.001). The average age of the entire cohort was significantly lower since our earlier study (72.9 ± 12.5 compared to 67.9 ± 12.7 years, p < 0.0001). The Jewish patients were significantly younger (p < 0.0001) but the Arab patients were not. The percentage of the adenocarcinoma being located in the right colon was significantly lower (p < 0.0006) and significantly higher in the rectum (p < 0.008). The reverse was true among the Jewish patients, but not significantly. Conclusions: Both study groups were younger than those in our earlier study. The lower incidence of CRC among the Arab patients persisted over time, but the location of their adenocarcinoma changed significantly. The increased incidence of CRC in ‘westernized’ countries is reflected in the Jewish but not the Arab community.
In vivo Dilatation of the Fetal and Postnatal Ductus Arteriosus by Inhibition of Phosphodiesterase 3 in Rats
Authors: Toyoshima Katsuaki , Momma Kazuo , Imamura Shinichiro , Nakanishi Toshio
Published: November 2005

Background: Clinically, it appears that phosphodiesterase 3 (PDE 3) inhibitors, which are used for acute cardiac failure in premature infants, dilate the ductus arteriosus (DA). Objectives: To clarify the ductus-dilating effects of PDE 3 inhibitors in near-term rat pups and their differential effects in near-term and preterm fetal rats, in in vivo studies. Methods: The in vivo ductal diameter of rat pups and fetuses was measured using a rapid whole-body freezing method, by cutting on a freezing microtome and measuring with a microscope and micrometer. Eight to twenty pups and fetuses were studied in each group. Milrinone and amrinone (specific inhibitors of PDE 3) were injected into 1-hour-old pups and the DA was studied 0.5 and 1 h later. The differential effects of these PDE 3 inhibitors on the near-term and preterm ductus were studied by injecting indomethacin (10 mg/kg) and PDE 3 inhibitors into 21D (21st day of pregnancy: term-21.5 days) and 19D dams and studying the fetal ductus 4 and 8 h later. Results: Milrinone and amrinone dilated the postnatal ductus dose-dependently. Large doses of these drugs dilated it completely, and clinically equivalent doses dilated it minimally. Milrinone and amrinone prevented constriction of the fetal ductus by indomethacin. Their ductus-dilating effects were more potent in the preterm than in the near-term fetuses, and clinically equivalent doses of these PDE 3 inhibitors dilated preterm ductus completely. Conclusion: In rats, PDE 3 inhibitors reopen the constricted postnatal DA slightly. PDE 3 inhibitors dilate the fetal DA constricted with indomethacin effectively and more sensitively in preterm than in near-term fetuses.
Pharmacokinetic and Clinical Phase II Trial of Imatinib in Patients with Impaired Liver Function and Advanced Hepatocellular Carcinoma
Authors: Eckel F. , von Delius S. , Mayr M. , Dobritz M. , Fend F. , Hosius C. , Schleyer E. , Schulte-Frohlinde E. , Schmid R.M. , Lersch C.
Published: November 2005

Objectives: No effective chemotherapy for advanced hepatocellular carcinoma (HCC) exists. Expression of the platelet-derived growth factor receptor (PDGFR) has been demonstrated in HCC, which may derive from hepatic stem cells that express c-kit. The aim of this trial was to evaluate imatinib, a tyrosine kinase inhibitor of PDGFR and c-kit, in patients with advanced HCC and impaired liver function. Patients and Methods: Patients were treated with 400–600 mg imatinib daily. Immunohistochemical staining was performed for PDGFR and c-kit. Response was assessed by CT scans every 8 weeks. For pharmacokinetics studies, 74 plasma samples were assessed. Results: Of the 17 patients enrolled in the study, 15 were evaluable for response. Only 1 tumor was positive for PDGFR and none was positive for c-kit. Grade 3/4 neutropenia occurred in 2 patients (1 had neutropenic fever). There was no objective response, and 5 (33%) patients had stable disease. Median time to treatment failure was 1.8 months in the whole study cohort and 3.7 months in the patients with stable disease. Patients treated with 400 mg imatinib did not significantly differ in pharmacokinetics from patients with chronic myelogenous leukemia (CML). Conclusion: In this small group of patients with advanced, mostly PDGFR- and c-kit-negative HCC, imatinib showed no therapeutic effect. In contrast to CML patients, the pharmacokinetics of imatinib were not significantly affected by impaired liver function.
Phase II Study of Gemcitabine and Cisplatin in Patients with Advanced or Metastatic Bladder Cancer: Long-Term Follow-Up of a 3-Week Regimen
Authors: Adamo V. , Magno C. , Spitaleri G. , Garipoli C. , Maisano C. , Alafaci E. , Adamo B. , Rossello R. , Scandurra G. , Scimone A.
Published: November 2005

Background: Bladder cancer is the fifth most common cancer among men and the seventh among women. At diagnosis, at least 25% of bladder cancer tumors are locally or systemically advanced. Systemic chemotherapy is the only current modality for advanced or metastatic transitional cell carcinoma of the bladder. Recently, a phase III randomized study has demonstrated that the regimen with gemcitabine (GMC) and cisplatin (CDDP) had a survival advantage similar to the standard M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin), with a better safety profile. Aim: It was the aim of this study to evaluate the tumor response rate, the median time to progression, the median survival and toxicity in a 21-day schedule with GMC and CDDP in patients with advanced/metastatic bladder cancer. Patients and Methods: From September 1998 to December 2000, 27 patients with advanced/metastatic transitional cell carcinoma were enrolled. All patients received 1,200 mg/m2 GMC administered as a 30-min intravenous infusion on days 1 and 8, and 75 mg/m2 CDDP as a 1-hour infusion on day 2. Cycles were repeated every 21 days. The patients had a median age of 59.8 years (range 39–75) and an Eastern Cooperative Oncology Group performance status of 0–2. Results: Twenty-five patients were valuable for toxic effects, length of survival and tumor response. The statistical analysis was performed in May 2004. Mean and median follow-up were 20.23 and 13.2 months (range 2–68), respectively. The overall remission rate (complete response + partial response) was 48% (95% CI 28.4–67.6%). The median time to progression was 9 months (range 2–56). The median duration of survival for all patients was 13.2 months (range 2–68+), with 1-year and 23-month survival rates of 60 and 20%, respectively. There was no grade 4 toxicity or treatment-related death. Grade 3 anemia was observed in 4 patients (16%) and grade 3 thrombocytopenia occurred in 6 patients (24%). No grade 3–4 nausea/vomiting or neutropenia was observed. Conclusion: GMC and CDDP is an active schedule with a good safety profile in a 21-day regimen. It may be a valid alternative to the standard 28-day regimen due to its high tumor response and survival with a low incidence of toxicity, especially in pretreated and metastatic patients.
Generation of Antigen-Presenting Cells Using Cultured Dendritic Cells and Amplified Autologous Tumor mRNA
Authors: Minami Kazuhito , Yamaguchi Yoshiyuki , Ohshita Akiko , Kawabuchi Yoshiharu , Ohta Koji , Hihara Jun , Toge Tetsuya
Published: November 2005

Novel antigen-presenting cells (APCs) were generated using cultured dendritic cells (DCs) and amplified tumor mRNA, and the potential of tumor antigen-reactive T cell induction by the tumor RNA-introduced DCs (DC/tumor RNA) was analyzed in a patient with melanoma antigen-encoding gene (MAGE3)-positive malignant melanoma of the esophagus. DCs were generated from an adherent fraction of peripheral blood mononuclear cells in the presence of granulocyte macrophage colony-stimulating factor and interleukin-4. Tumor mRNA was purified from tumor tissue, amplified in vitro using a T7 RNA polymerase system, and then introduced into DCs by electroporation (150 V/150 µF or 100 V/200 µF). The gene introduction efficiency was 44–55% as measured by enhanced green fluorescent protein reporter gene expression, and the viability of RNA-introduced DCs was approximately 80%. DC/tumor RNA could induce tumor antigen-reactive cytotoxic T lymphocytes (CTLs) in an mRNA-specific manner, but had no effect on the self-antigen-reactive T cells. DC/tumor RNA could induce the polyspecific antigen-reactive CTL responses mediated by both human leukocyte antigen class I and class II molecules, whereas MAGE3 peptide-pulsed DCs induced only the monospecific MAGE3-reactive CTL responses mediated by human leukocyte antigen class I molecules, showing the superiority of the DC/tumor RNA over the DC/peptide. It is suggested that the use of DC/tumor RNA as antigen-presenting cells may be more effective, convenient and practical for the DC-based anti-cancer immunotherapy.
Weekly Cisplatin plus Capecitabine in Metastatic Breast Cancer Patients Heavily Pretreated with both Anthracycline and Taxanes
Authors: Donadio M. , Ardine M. , Berruti A. , Beano A. , Bottini A. , Mistrangelo M. , Bonardi S. , Castiglione F. , Generali D. , Polimeni M.A. , Bretti S. , Alabiso O. , Bertetto O.
Published: November 2005

Background: Treating patients with anthracycline- and taxane-pretreated metastatic breast cancer is challenging. This study evaluated the activity and safety of a combination of cisplatin and capecitabine in this setting. Patients and Methods: Thirty-nine consecutive patients entered the study. All had experienced failures or relapse after previous treatment with anthracyclines and taxanes plus/minus other chemotherapeutic regimens. The present treatment consisted of intravenous cisplatin 20 mg/m2 every week for 6 weeks, followed by 1 week of rest, and oral capecitabine 1,000 mg/m2 twice daily for 14 days, followed by a 7-day rest period. Results: Objective response was obtained in 14 patients (35.9%), with complete remission in 3 (7.7%). Median time to progression was 5.2 months and survival was 10.9 months in the entire population and 8.7 and 16.5 months in the responding patients, respectively. The dose-limiting toxicity for the regimen was leucopenia, while gastrointestinal discomfort was the most frequent cause of capecitabine reduction or delay. Conclusions: The cisplatin and capecitabine combination regimen is active and manageable. It seems to be non-cross resistant to anthracyclines and taxanes.
The Politics of Handel's Early London Operas, 1711–1718
Authors: Monod Paul
Published: November 2005

Athough aristocratic Whigs were the primary supporters of opera during the last years of Queen Anne's reign, Whig publicists launched a series of attacks against Italian opera that revealed social and ideological tensions within the party. The Earl of Shaftesbury, an ardent Whig, gave intellectual weight to the Whig aristocratic taste for opera, but proponents of the popular theater remained unconvinced that this foreign art form could be reconciled with Whig principles. Handel's operas reflected, as well as responded to, these debates.
Redefining the Status of Opera: London and Leipzig, 1800–1848
Authors: Weber William
Published: November 2005

Between about 1750 and 1800, concerts of any significance usually included several numbers from opera, within strictly patterned “miscellaneous” programs. Around 1800, when the political condition of European society was particularly unstable, idealists began to challenge this old order of musical life, calling for a new, “higher” order of programming and musical taste. Distinct musical worlds evolved from this movement. Some concerts focused almost entirely on opera, or on excerpts from old operas, and others abandoned opera altogether. Chamber music and orchestral concerts tended to draw exclusively from repertories comprised of works from the classical era.
Poppea's Legacy: The Julio-Claudians on the Venetian Stage
Authors: Heller Wendy
Published: November 2005

In a context already established by Claudio Monteverdi's L'incoronazione di Poppea and other Venetian treatments of the Julio-Claudians, Giovanni A. Boretti and Aurelio Aureli's opera Claudio Cesare bears the heavy influence of the Roman historian Cornelius Tacitus. Aureli took extraordinary care to incorporate specific details from Book 12 of Tacitus' Annals into his libretto, deftly blending fact with fanciful supposition in a manner that echoes many of the concerns about women and monarchy explored in Monteverdi's opera. An aria sung by the young Nero to his mother Agrippina demonstrates the complex ways in which music could teach the lessons of history—both seducing the listener and providing a chilling lesson about the political and moral liabilities of empire.