bluuebunny/crossref_metadata_2025 huggingface dataset:
Time to Cardioversion of Recurrent Atrial Arrhythmias After Catheter Ablation of Atrial Fibrillation and Long‐Term Clinical Outcome
Authors: BAMAN TIMIR S. , GUPTA SANJAYA K. , BILLAKANTY SREEDHAR R. , ILG KARL J. , GOOD ERIC , CRAWFORD THOMAS , JONGNARANGSIN KRIT , EBINGER MATT , PELOSI FRANK , BOGUN FRANK , CHUGH AMAN , MORADY FRED , ORAL HAKAN
Published: July 2009

Introduction: It is unclear whether early restoration of sinus rhythm in patients with persistent atrial arrhythmias after catheter ablation of atrial fibrillation (AF) facilitates reverse atrial remodeling and promotes long‐term maintenance of sinus rhythm. The purpose of this study was to determine the relationship between the time to restoration of sinus rhythm after a recurrence of an atrial arrhythmia and long‐term maintenance of sinus rhythm after radiofrequency catheter ablation of AF.

Methods and Results: Radiofrequency catheter ablation was performed in 384 consecutive patients (age 60 ± 9 years) for paroxysmal (215 patients) or persistent AF (169 patients). Transthoracic cardioversion was performed in all 93 patients (24%) who presented with a persistent atrial arrhythmia: AF (n = 74) or atrial flutter (n = 19) at a mean of 51 ± 53 days from the recurrence of atrial arrhythmia and 88 ± 72 days from the ablation procedure. At a mean of 16 ± 10 months after the ablation procedure, 25 of 93 patients (27%) who underwent cardioversion were in sinus rhythm without antiarrhythmic therapy. Among the 46 patients who underwent cardioversion at ≤30 days after the recurrence, 23 (50%) were in sinus rhythm without antiarrhythmic therapy. On multivariate analysis of clinical variables, time to cardioversion within 30 days after the onset of atrial arrhythmia was the only independent predictor of maintenance of sinus rhythm in the absence of antiarrhythmic drug therapy after a single ablation procedure (OR 22.5; 95% CI 4.87–103.88, P < 0.001).

Conclusion: Freedom from AF/flutter is achieved in approximately 50% of patients who undergo cardioversion within 30 days of a persistent atrial arrhythmia after catheter ablation of AF.
Awake anon the tales of valour: the career of a war memorial in St. Catharines, Ontario
Authors: JOHNSTON RUSSELL , RIPMEESTER MICHAEL
Published: July 2009

Memorials cultivate a common understanding of the past that is communicated through the celebration of select people, places or events. Because memorials are located in public space and crafted from time‐defeating materials, the process of commemoration is inherently political. Scholars have studied this process to discover the agendas that inform the ideological content of memorials, but rarely how this content is received by its audience. This question is especially pertinent when memorials outlast the generation and the ideology that created them. This study attempts an answer by exploring the career of one memorial: the monument in St. Catharines, Ontario, dedicated to Private Alexander Watson, a casualty of the Battle of Batoche (1885). It finds that the monument's significance was transformed by political, cultural and historiographical shifts. While its local audience has forgotten its specific message, its generic intent to honour fallen soldiers is still recognized.
Does oral health say anything about survival in later life? Findings in a Swedish cohort of 80+ years at baseline
Authors: Thorstensson Helene , Johansson Boo
Published: July 2009

Abstract –  Background:  Oral health is an integral part of general health; oral health contributes to and is influenced by a nexus of inputs from biological, psychological, and social functioning. Little is known about the relationship between markers of oral health and subsequent survival in late life.

Objectives:  The aim of this study was to examine the relative importance of oral health indicators in the context of demographic and psychosocial variables on subsequent survival during an 8‐year period in a population‐based sample of the oldest‐old.

Methods:  The study sample comprised 357 individuals with a median age of 86 years who were selected from participants in the comprehensive longitudinal Origins of Variance in the Old‐Old: Octogenarian Twins (OCTO‐Twin) study, which examined monozygotic and dizygotic twins aged 80 years and older on five occasions at 2‐year intervals. The OCTO‐Twin study includes a broad spectrum of biobehavioural measures of health and functional capacity, personality, well‐being, and interpersonal functioning. Oral health variables were number of teeth, per cent decayed and filled surfaces (DFS%), and periodontal disease experience. A longevity quotient (LQ), the ratio between years actually lived and those statistically expected, was determined. The survival categories were shorter than expected, as expected, or longer‐than‐expected. Multivariate analyses and the Kaplan–Meier method were used in the survival analyses.

Results:  No associations between LQ and number of teeth, edentulousness, and periodontal disease experience were found. But survival of men with severe periodontal disease experience was shorter than expected. DFS% was significantly associated with survival. Individuals with a low number of decayed and filled surfaces (DFS) had a shorter‐than‐expected survival time compared with those with high DFS scores. The overall predictor of survival was cognitive status, independent of age and gender when dental variables were analysed in the context of psychosocial factors. In addition, number of teeth, smoking, and better financial status in childhood and during working life were also significant predictors.

Conclusions:  Oral health was significantly associated with subsequent survival in a sample of oldest‐old individuals, although psychosocial factors were stronger predictors.
The influence of sense of coherence on the relationship between childhood socioeconomic status and adult oral health‐related behaviours
Authors: Bernabé Eduardo , Watt Richard G. , Sheiham Aubrey , Suominen‐Taipale Anna L. , Nordblad Anne , Savolainen Jarno , Kivimäki Mika , Tsakos Georgios
Published: July 2009

Abstract –  Objectives:  To assess the role of adulthood socioeconomic status (SES) and sense of coherence (SOC) in the relationship between childhood SES and adult oral health‐related behaviours.

Methods:  This study analysed responses of 5318 dentate subjects aged 30 years and over who participated in the Finnish Health 2000 Survey. Participants provided information on their demographic characteristics (sex, age, marital status and urbanization), childhood SES (parental education), adulthood SES (years of education and household income), the SOC scale and four oral health‐related behaviours (dental attendance, toothbrushing frequency, sugar intake frequency and daily smoking). Structural equation modelling was used to test a model including adult SES and SOC as mediating factors of the relationship between childhood SES and adult oral health‐related behaviours. Multi‐group comparison was conducted to test the model within each sex and age group.

Results:  Childhood SES was related to adult oral health‐related behaviours (P < 0.001) but only indirectly, via adulthood SES (P < 0.001) and adult SOC (P = 0.001). However, the relationship via adulthood SES was much stronger than that via SOC (standardized path coefficients were 0.24 and 0.01 respectively). In the multi‐group comparison, the model was invariant across sex and age groups.

Conclusions:  The relationship between childhood SES and adult oral health‐related behaviours was mainly mediated by adulthood SES, and to a much less extent by SOC. A stronger SOC was significantly associated with better adult oral health‐related behaviours, after controlling for the effect of adulthood SES and demographic characteristics of the participants.
Keratinocytes efficiently process endogenous antigens for cytotoxic T‐cell mediated lysis
Authors: Zhou Fang , Frazer Ian H. , Leggatt Graham R.
Published: July 2009

Abstract:  The generation of a robust CD8+ cytotoxic T lymphocyte (CTL) response is a key feature of many immunotherapeutic strategies against epithelial tumors and virally infected epithelial tissue. However, surprisingly few studies have addressed whether primary epithelial cells, expressing defined endogenous antigens, are good targets for CTL‐mediated lysis. Here, we show that primary keratinocytes (KCs), expressing endogenous ovalbumin (OVA) as a transgene, present measurable H‐2Kb/SIINFEKL complexes at the cell surface and are killed by OVA‐specific CTL. Target cell lysis was comparable with a more traditional CTL target cell, EL4, and was enhanced by KC pretreatment with interferon‐γ. These results suggest that primary KCs will be susceptible to CTL‐mediated apoptosis when endogenous KC antigens are targeted during immunotherapy.
Protein oligomerization induced by oleic acid at the solid–liquid interface – equine lysozyme cytotoxic complexes
Authors: Wilhelm Kristina , Darinskas Adas , Noppe Wim , Duchardt Elke , Mok K. Hun , Vukojević Vladana , Schleucher Jürgen , Morozova‐Roche Ludmilla A.
Published: July 2009

Protein oligomeric complexes have emerged as a major target of current research because of their key role in aggregation processes in living systems and in vitro. Hydrophobic and charged surfaces may favour the self‐assembly process by recruiting proteins and modifying their interactions. We found that equine lysozyme assembles into multimeric complexes with oleic acid (ELOA) at the solid–liquid interface within an ion‐exchange chromatography column preconditioned with oleic acid. The properties of ELOA were characterized using NMR, spectroscopic methods and atomic force microscopy, and showed similarity with both amyloid oligomers and the complexes with oleic acid and its structural homologous protein α‐lactalbumin, known as humanα‐lactalbumin made lethal for tumour cells (HAMLET). As determined by NMR diffusion measurements, ELOA may consist of 4–30 lysozyme molecules. Each lysozyme molecule is able to bind 11–48 oleic acids in various preparations. Equine lysozyme acquired a partially unfolded conformation in ELOA, as evident from its ability to bind hydrophobic dye 8‐anilinonaphthalene‐1‐sulfonate. CD and NMR spectra. Similar to amyloid oligomers, ELOA also interacts with thioflavin‐T dye, shows a spherical morphology, assembles into ring‐shaped structures, as monitored by atomic force microscopy, and exerts a toxic effect in cells. Studies of well‐populated ELOA shed light on the nature of the amyloid oligomers and HAMLET complexes, suggesting that they constitute one large family of cytotoxic proteinaceous species. The hydrophobic surfaces can be used profitably to produce complexes with very distinct properties compared to their precursor proteins.
Autism and Vaccination—The Current Evidence
Authors: Miller Lisa , Reynolds Joni
Published: July 2009

PURPOSE.  The purpose of this article is to review relevant background literature regarding the evidence linking thimerosal‐containing vaccine and the measles, mumps, and rubella vaccine to autism.

CONCLUSIONS.  Rigorous scientific studies have not identified links between autism and either thimerosal‐containing vaccine or the measles, mumps, and rubella vaccine.

PRACTICE IMPLICATIONS.  Nurses are often in the position of providing advice regarding vaccines in their formal practice areas as well as in their daily lives. Families need current and credible evidence to make decisions for their children. Excellent vaccine information resources are available online.
Collaborative Approach to Autism: A Parent's Perspective
Authors: Quirantes Deborah
Published: July 2009

Deborah Quirantes
 
Column Editor: Joseph P. De Santis

Collaborative Practice provides a forum for healthcare professionals to share expertise and enhance communication.
Helping the Student with Asperger's Disorder with Social and Behavioral Issues in the School: Nursing, Psychology, and Educators Working in Unison
Authors: Bellando Jayne , Pulliam Elizabeth
Published: July 2009

Jayne Bellando and Elizabeth Pulliam Column Editor: Cordelia Robinson

School Health provides a forum to discuss policy, practice, research, issues and trends, and pearls of wisdom to enhance the day‐to‐day care of children in the school setting, from day care to high school.
Autism and the Courts
Authors: Rhodes Ann M.
Published: July 2009

Ann M. Rhodes
 
Column Editor: Ann M. Rhodes

Ask the Expert provides research‐based answers to practice questions submitted by JSPN readers.
Forest Fragment and Breeding Habitat Characteristics Explain Frog Diversity and Abundance in Singapore
Authors: Bickford David , Ng Tze How , Qie Lan , Kudavidanage Enoka P. , Bradshaw Corey J. A.
Published: July 2009

Habitat loss and fragmentation can have severe negative and irreversible effects on biodiversity. We investigated the effects of forest fragmentation on frog diversity in Singapore because of its high rates of deforestation and the demonstration that frogs are some of the most sensitive species to habitat degradation. We surveyed frog species in 12 forest fragments varying from 11 to 935 ha. We compared differences in species richness, abundance, and Shannon's index in relation to forest fragment size, connectivity (distance between fragments), and breeding habitat heterogeneity. A total of 20 species from 12 genera and five families were encountered in 12 fragments. Larger fragments and those closer to larger fragments had higher species richness. Abundance, however, was not correlated with forest area or connectivity, but we found fewer individual frogs in the larger fragments. We also found that breeding habitat heterogeneity best explained frog species diversity and abundance in forest fragments. Fragments with a high diversity of breeding habitats had more species. We found no evidence to suggest that abundance and diversity are strongly correlated, particularly in disturbed areas, but that breeding habitat heterogeneity is an under‐appreciated factor that should be considered when prioritizing areas for anuran conservation. Enriching breeding habitat heterogeneity, creating corridors between fragments, and reforesting degraded areas are some of the most beneficial strategies for preserving urban frog biodiversity.
Disturbance effects on community structure of Ficus tinctoria fig wasps in Xishuangbanna, China: Implications for the fig/fig wasp mutualism
Authors: Ma Wen‐Juan , Yang Da‐Rong , Peng Yan‐Qiong
Published: July 2009

Abstract  Fig trees are important components of tropical forests, because their fruits are eaten by so many vertebrates, but they depend on pollinating fig wasps to produce mature fruits. Disturbance to habitat structure can have a major impact on insect diversity and composition, potentially reducing fruit yields. We investigated the impact of habitat disturbance on the fig wasp community associated with male figs of Ficus tinctoria in Xishuangbanna, China. The community comprised one pollinator species Liporrhopalum gibbosae and six non‐pollinating wasp species: Sycoscapter sp.1, Philotrypesis ravii, Philotrypesis sp.1, Neosycophila omeomorpha, Sycophila sp.1, and Walkerella sp.1. More disturbed areas were characterized by higher temperatures, less shade, and more vehicle noise. The response of the fig wasp community was complex, with no simple relationship between intensity of disturbance and pollinator abundance. However, the sex ratios (proportion of male progeny) of pollinators increased significantly in more disturbed areas. We conclude that potential changes in fig wasp community composition brought about by disturbance, are unpredictable, with unclear consequences for tropical rainforest biodiversity.
The Epidemiology of Endometriosis
Authors: CRAMER DANIEL W. , MISSMER STACEY A.
Published: July 2009

Abstract: Advances in understanding the epidemiology of endometriosis have lagged behind other diseases because of methodologic problems related to disease definition and control selection. Nevertheless, a better picture of the epidemiology of endometriosis has emerged over the past few decades. Prevalence estimates of the disease in clinic populations vary from about a 4% occurrence of largely asymptomatic endometriosis found in women undergoing tubal ligation to 50% of teenagers with intractable dysmenorrhea. General population incidence during the 1970s in this country has been suggested to be 1.6 per 1000 white females aged 15‐49, while a more current study based upon hospital discharges finds endometriosis as a first listed diagnosis in 1.3 per 1000 discharges in women aged 15‐44. There is a clinical impression that blacks have lower rates of endometriosis and Orientals have higher rates than whites. A variety of personal risk factors for endometriosis have also been described. Women with endometriosis may be taller and thinner. Menstrual factors reported to increase risk include dysmenorrhea, early menarche, and shorter cycle lengths. There is support for the idea that lifestyle exposures that might raise or lower estrogen levels could affect risk, including a decreased risk associated with smoking and exercise and an increased risk associated with caffeine or alcohol use. These risk factors appear to be compatible with the central importance of retrograde menstruation influenced by outflow obstruction that might affect its amount, immune factors that might affect its ability to be cleared, or hormonal stimuli that might affect its growth. In this model, dysmenorrhea could be either a disease symptom or a manifestation of outflow obstruction. Nulliparity could be either a consequence of disease or a cause since nulliparous women would not have the benefit of cervical dilation associated with labor and delivery. Since there is evidence that family history is a risk factor for disease, a challenge is how to integrate genetic factors into the model. The genetics of endometriosis might be advanced if we could identify an “endometriosis phenotype”. We propose that this may consist of early menarche, short cycles, painful periods, subfertility, and possibly tall stature that could be explained by genetic factors that predispose to poor endowment of germ cells and canalization defects of the cervix. The value of establishing an “endometriosis phenotype” is that, as candidates for genetic markers are identified, particular genotypes can be correlated with these factors even if a formal diagnosis of endometriosis has not been made. Additional well‐designed case‐control and cohort studies will be necessary to test theories related to pathogenesis, establish the precise relationship between reproductive morbidity and endometriosis, identify specific genetic factors, and establish long‐term risks.
Progesterone‐Mediated Endometrial Maturation Limits Matrix Metalloproteinase (MMP) Expression in an Inflammatory‐like Environment
Authors: OSTEEN KEVIN G. , BRUNER‐TRAN KAYLON L. , KELLER NANCY R. , EISENBERG ESTHER
Published: July 2009

Abstract:The human endometrium exhibits regular cycles of growth, differentiation, and breakdown in response to changing levels of ovarian steroids. Following the tissue loss and repair processes of menstruation, rising levels of estradiol initiate a development‐like process leading to a complete restructuring of the endometrial surface. In contrast, while under the predominate influence of progesterone, proliferation declines as cell‐specific differentiation prepares the endometrium for pregnancy over a 5‐ to 6‐day period. In the absence of nidation, steroid support is lost; the endometrial surface begins a complex process of tissue breakdown and bleeding, producing a viscous mixture of cellular debris within a bloody menstrual effluent. Although most of the menstrual fluid exits the body, reflux of some material occurs in most women, providing a poorly understood opportunity for ectopic endometrial growth and establishment of the disease endometriosis. The cyclic restructuring of the endometrium requires numerous matrix metalloproteinases (MMPs) that mediate normal and pathological tissue turnover throughout the reproductive tract. The expression of multiple MMPs facilitates degradation of extracellular matrix during growth‐related remodeling as well as tissue breakdown at the time of menstruation. However, these enzymes are absent during the early and midsecretory phase and the suppression of endometrial MMPs remains important to maintaining the integrity of the endometrium during the highly invasive events required to establish a normal hemochorial placenta. Several research groups have suggested that steroid‐mediated expression and action of MMPs during the menstrual cycle may provide a key mechanistic link between endometrial turnover and the invasive processes necessary for establishment of endometriosis.
Mechanisms of Action of Estrogen and Progesterone
Authors: DeMAYO FRANCESCO J. , ZHAO BIHONG , TAKAMOTO NORIO , TSAI SOPHIA Y.
Published: July 2009

Abstract: Estrogen and progesterone are steroid hormones that play a pivotal role in the regulation of mammalian reproduction. One primary action of these hormones is to regulate the development and function of the uterus. These hormones act by regulating the transcription of specific genes in the uterus. The actions of these hormones are mediated by their specific hormone receptors. These receptors are nuclear transcription factors, whose transcriptional regulatory activity is mediated by the binding of the specific steroid to these molecules. Once these receptors bind hormone, they can bind to specific cis‐acting sequences in the promoter region of responsive genes and regulate transcription of these genes. In the regulation of transcription, these receptors interact with specific cofactors to activate the transcriptional machinery. A second gene family, the Steroid Receptor Coactivator (SRC) family, has been identified that serves to modulate the transcriptional activity of the hormone receptors. To date, three members of the SRC family have been identified. During the last decade, gene targeting technology has been used to identify the role of these receptors in the regulation of reproduction and uterine biology.
Estrogen Production and Metabolism in Endometriosis
Authors: BULUN SERDAR E. , YANG SIJUN , FANG ZHOJUAN , GURATES BILGIN , TAMURA MITSUTOSHI , SEBASTIAN SIBY
Published: July 2009

Abstract: Aromatase activity is absent in normal endometrium. In contrast, aromatase is expressed aberrantly in endometriosis, which gives rise to strikingly high levels of aromatase activity in this tissue. Both aromatase expression and activity are stimulated by PGE2. This results in local production of estrogen, which induces PGE2 formation and establishes a positive feedback cycle. Another abnormality in endometriosis, that is, deficient 17β‐HSD type 2 expression, impairs the inactivation of estradiol to estrone. These molecular aberrations collectively favor accumulation of increasing quantities of estradiol and PGE2 in endometriosis. The clinical relevance of these findings was exemplified by the successful treatment of an unusually aggressive case of postmenopausal endometriosis using an aromatase inhibitor.
Local Cytokines in Endometrial Tissue: The Role of Interleukin‐8 in the Pathogenesis of Endometriosis
Authors: ARICI AYDIN
Published: July 2009

Abstract: Endometriosis, defined by the presence of viable endometrial tissue outside the uterine cavity, is among the most common gynecologic disorders affecting women of reproductive age. Endometriosis is associated with an inflammatory peritoneal environment, where multiple cytokines and growth factors are found at elevated levels. Interleukin‐8 (IL‐8) is a cytokine that induces chemotaxis of neutrophils and is a potent angiogenic agent. In addition, IL‐8 was recently found to stimulate proliferation of various cells. We have observed that IL‐8 is elevated in the peritoneal fluid of women with endometriosis and the levels correlate with the severity of the disease. We hypothesized that IL‐8 may play a role in the growth and maintenance of ectopic endometrial tissue not only by chemoattracting and stimulating leukocytes to secrete growth factors and cytokines, but also by directly affecting endometrial cell proliferation. We found that IL‐8 mRNA and protein levels in the endometrium were significantly higher during early proliferative and late secretory phases than during the mid‐cycle. IL‐8 receptors A and B are also expressed in the endometrium mostly localized in the stroma. Interestingly, IL‐8 receptor expression is higher in the eutopic endometrium of women with endometriosis compared to the endometrium of women without endometriosis. Endometrial cells in culture proliferate significantly when treated with IL‐8, which is inhibited by anti‐IL‐8 neutralizing antibody. More convincingly, IL‐8 antisense oligonucleotide treatment decreases IL‐8 production by endometrial cells as well as cell proliferation when compared to non‐sense oligonucleotide treatment. The addition of IL‐8 reverses the inhibitory effect of IL‐8 antisense oligonucleotides on cell proliferation. These findings suggest that IL‐8 may act as an autocrine growth factor in the endometrium. We have also studied the effect of endometrial cell adhesion on IL‐8 expression and observed that IL‐8 stimulates the adhesion of endometrial cells to fibronectin. Treatment of the cells with anti‐IL‐8 neutralizing antibody inhibited partially the cell adhesion. Thus, IL‐8 may also be relevant for stimulating the attachment of endometrial implants in the pathogenesis of endometriosis. In addition, adherence of endometrial cells induced further IL‐8 expression by an integrin‐dependent mechanism. In summary, IL‐8 may act as an autocrine growth factor in the endometrium and may also play a role in the pathogenesis of endometriosis by promoting the vicious circle of endometrial cell attachment, cell growth, and further secretion of this cytokine.
Paracrine Mediators of Endometrial Matrix Metalloproteinase Expression
Authors: OSTEEN KEVIN G. , BRUNER‐TRAN KAYLON L. , ONG DAVID , EISENBERG ESTHER
Published: July 2009

Abstract: The endometrial lining of the human uterus is a highly specialized, steroid‐sensitive tissue. Throughout the reproductive years, the endometrium undergoes dramatic cycles of growth, differentiation, and breakdown under the influence of ovarian steroids. In response to changes in steroid exposure throughout the menstrual cycle, the endometrium produces an array of bioactive growth factors and other cytokines that are critical components of paracrine communication. For example, cell‐cell communication via paracrine factors directs the expression of matrix metalloproteinases (MMPs), enzymes that mediate tissue remodeling during the menstrual cycle. The disease endometriosis is thought to occur as a consequence of retrograde menstruation, and MMPs appear to contribute to the establishment and progression of ectopic endometrial growth in the peritoneal cavity. Although the risk for developing endometriosis is linked to a woman's steroid exposure, locally produced paracrine factors can modify steroid action on multiple gene targets, including the MMPs. Estrogen‐associated growth factors as well as inflammatory cytokines are potent stimulators of MMP expression and may contribute to the ability of endometrial fragments to invade the peritoneal surface and establish ectopic sites of growth. In contrast, paracrine factors associated with progesterone action during early pregnancy inhibit MMP expression and prevent ectopic endometrial growth in an experimental model. For example, locally produced retinoic acid and transforming growth factor‐β (TGF‐β) act in concert with progesterone to suppress MMPs, while enhancing expression of MMP inhibitors (TIMPs) during endometrial differentiation. Targeting pregnancy‐associated factors that inhibit endometrial‐specific MMP expression and action may enhance the effectiveness of progestin‐related treatments for endometriosis.
Autoantibody Responses to Carbohydrate Epitopes in Endometriosis
Authors: YEAMAN GRANT R. , COLLINS JANE E. , LANG GILLIAN A.
Published: July 2009

Abstract: Autoantibody responses to endometrial and serum antigens are a common feature of endometriosis. We have shown that the serum autoantibody response in endometriosis to a number of previously identified antigens, including α2‐Heremans Schmidt glycoprotein and carbonic anhydrase, is specific for a carbohydrate epitope common to these proteins. Removal of carbohydrate moieties from these antigens resulted in a loss of antibody binding. Antibody reactivity was abolished following adsorption with the lectin jacalin, which specifically binds the Thomsen‐Friedenreich (T) antigen (Galβ1‐3GalNAc). Demonstration that the autoantibodies also reacted with other Thomsen‐Friedenreich antigen‐bearing proteins, such as serum IgA1, hemopexin, and MMP‐9, confirmed that this glycotope is involved in the autoantibody response. However, the autoantibody binding requires the presence of at least one sialic acid residue. Thus, the glycotope involved may be a sialylated T antigen. These findings allow us to hypothesize a number of mechanisms whereby the autoimmune response plays a direct role in several aspects of the disease process. The proposed mechanisms take into account the salient endocrine dependency of endometriotic lesions and other aspects of the disease process such as aberrant matrix metalloproteinase function and the ability of endometrial cells to implant at ectopic sites. The anti‐T‐like response may also be indicative of an underlying genetic defect in glycosylation or in the control of glycosylation by steroid sex hormones. Further characterization of this autoimmune response may prove useful in the development of serum‐based diagnostic tests for endometriosis and may lead to the development of therapeutic strategies.
The Genetic Epidemiology of Spontaneous Endometriosis in the Rhesus Monkey
Authors: ZONDERVAN KRINA , CARDON LON , DESROSIERS RONALD , HYDE DALLAS , KEMNITZ JOSEPH , MANSFIELD KEITH , ROBERTS JEFF , SCHEFFLER JOAN , WEEKS DANIEL E. , KENNEDY STEPHEN
Published: July 2009

Abstract: The etiology of endometriosis is uncertain, but there is increasing evidence that it is inherited as a complex genetic trait like diabetes or asthma. In such complex traits, multiple gene loci conferring susceptibility to the disease interact with each other and the environment to produce the phenotype. The study of such interactions in humans can be problematic. Thus, the availability of an animal model, which shares many aspects of anatomy and physiology with humans, is potentially a valuable tool for investigating the genetic epidemiology of the disease. Since endometriosis develops spontaneously in the rhesus monkey (Macaca mulatta) and the tissue is morphologically identical to its human counterpart, this population provides a unique opportunity to conduct such studies in this condition.
Heritability and Molecular Genetic Studies of Endometriosis
Authors: SIMPSON JOE LEIGH , BISCHOFF FARIDEH Z.
Published: July 2009

Abstract: Endometriosis is well established as a condition showing heritable tendencies. Polygenic/multifactorial etiology appears far more likely to be the etiology than Mendelian inheritance. The current task is to determine the number and location of genes responsible for endometriosis. This paper shall review the basis for concluding that endometriosis is a genetic disorder of polygenic/multifactorial inheritance and outline selected strategies for identifying the number and location of causative genes. It shall also illustrate our approach to testing the hypothesis that endometriosis bears similarity to neoplasia and, hence, is a multistep phenomenon of clonal origin.
Role of Endometriosis in Cancer and Tumor Development
Authors: SWIERSZ LILLIAN MARIE
Published: July 2009

Abstract: Endometriosis, like cancer, is characterized by cell invasion and unrestrained growth. Furthermore, endometriosis and cancer are similar in other aspects, such as the development of new blood vessels and a decrease in the number of cells undergoing apoptosis. In spite of these similarities, endometriosis is not considered a malignant disorder. The possibility that endometriosis could, however, transform and become cancer has been debated in the literature since 1925. Mutations in the genes that encode for metabolic and detoxification enzymes, such as GALT and GSTM, have been implicated in the pathogenesis of endometriosis and in the progression to carcinoma of the ovary. PTEN, a tumor suppressor commonly mutated (50%) in endometrial carcinoma, is found mutated in endometrioid carcinoma of the ovary, but not in other forms of ovarian cancer. A recent study has shown that somatic mutations in the PTEN gene were identified in 20% of endometrioid carcinomas and 20.6% of solitary endometrial cysts, suggesting that inactivation of the PTEN tumor suppressor gene is an early event in the development of ovarian endometrioid carcinoma. In addition to cancerous transformation at the site of endometriosis, there is recent evidence to indicate that having endometriosis itself may increase a woman's risk of developing non‐Hodgkin's lymphoma, malignant melanoma, and breast cancer.
An In Vitro Model to Study the Pathogenesis of the Early Endometriosis Lesion
Authors: WITZ CRAIG A. , DECHAUD HERVE , MONTOYA‐RODRIGUEZ IRIS A. , THOMAS MIKA R. , NAIR ANITHA S. , CENTONZE VICTORIA E. , SCHENKEN ROBERT S.
Published: July 2009

Abstract: Objective—To determine if whole fragments of endometrium can adhere to peritoneum with intact mesothelium. Design—Tissue culture and immunohistochemical study. Setting—University Medical Center. Patients—Reproductive‐age women undergoing surgery for benign conditions. Interventions—Whole explants of human peritoneum from the anterior abdominal wall and the posterior surface of the uterus were cultured with whole fragments of mechanically dispersed endometrium. Main Outcome Measures—Adhesion of endometrial fragments to the surface of the peritoneum was evaluated. Adherent fragments of endometrium were identified using the dissecting microscope and by performing serial sections of the peritoneum explants for light and confocal laser‐scanning microscopy. Immunohistochemical staining of the mesothelium with antibodies to cytokeratin and vimentin was used to ensure an intact layer of mesothelium beneath the endometrial implants. Transmission electron microscopy was also used to evaluate the adhesion of endometrium to the mesothelium. Results—Endometrium was identified attached to the surface of the peritoneum. After 18‐24 hours of culture, the majority of implants did not have identifiable mesothelium beneath them, but most had intact mesothelium running up to the point of attachment. Approximately 10% of the endometrial implants had intact mesothelium at the site of attachment. After 1 hour of culture, both endometrial stromal and epithelial cells were attached to intact mesothelium in nearly all cases. Early transmesothelial invasion involves endometrial stromal cells. Conclusions—Endometrial stromal and epithelial cells can attach to the intact mesothelial surface of the peritoneum. Endometrial stromal cell invasion through the mesothelium occurs in less than 18‐24 hours.
A Modified Baboon Model for Endometriosis
Authors: FAZLEABAS ASGERALLY T. , BRUDNEY ALLISON , GURATES BILGIN , CHAI DANIEL , BULUN SERDAR
Published: July 2009

Abstract: Endometriosis is one of the most common causes of infertility and chronic pelvic pain and affects 1 in 10 women in the reproductive‐age group. Although existence of this disease has been known for over 100 years, our current knowledge of its pathogenesis, the pathophysiology of related infertility, and its spontaneous evolution is limited. Several reasons contribute to our lack of knowledge, the most critical being the difficulty in carrying out objective long‐term studies in women. Thus, we and others have developed the baboon as an appropriate nonhuman primate to study the etiology of this disease. We suggested that endometriosis develops in two distinct phases. Phase I is invasive and dependent on ovarian steroids. Phase II, which is the active phase of the disease, is characterized by endogenous estrogen biosynthesis. Following inoculation with menstrual endometrial tissues in two consecutive menstrual cycles, baboons develop lesions that are similar to those seen in humans. Laparoscopy at 1, 4, and 10 months revealed a preponderance of red raised nodules at the first month, while both red lesions and reddish‐blue proliferative endometriotic lesions were evident at 4 and 10 months. The presence of glandular tissue and stromal fibroblasts in these lesions was confirmed by histology. Lesions obtained at 1 and 4 months expressed estrogen receptor β (ERβ), matrix metalloproteinase‐7 (MMP‐7), and vascular endothelial growth factor (VEGF) predominantly. However, aromatase expression was only readily evident at 10 months, although some lesions obtained at 4 months expressed low levels of aromatase. Therefore, our preliminary data suggest that endometriosis can be artificially induced in baboons, and the role of exogenous and endogenous estradiol in proliferation, angiogenesis, and immune modulations can now be evaluated in a potentially systemic manner.
Midbrain Disorders of Vertical Gaze
Authors: SHARPE JAMES A. , KIM JI SOO
Published: July 2009

Abstract: The mesodiencephalic junction is the site of the prenuclear control of vertical eye motion. We measured vertical saccades, smooth pursuit (SP), the vertical vestibulo‐ocular reflex (VOR), and its interactions with vision during active head motion in 21 patients with midbrain lesions causing palsy of vertical saccades, upward, downward, or in both directions. Most patients with limited slow or slowed saccades in one direction on clinical examination had slowed saccades in the opposed direction. SP gain was decreased in both directions in most patients, and decreased upward or downward in few. VOR gain was subnormal in both directions in many patients, and upward only in one; phase lead of the VOR was recorded in 33% of them. Subnormal SP and VOR gains were often dissociated. Visually enhanced VOR gains were subnormal in both directions in many patients. Cancellation of the VOR was impaired in many patients, both upward and downward in most and upward in few patients. Gaze (eye plus head) tracking gain was subnormal in 29% of patients. Defective SP and defective cancellation of the VOR during head free tracking were often dissociated. We conclude that VOR and SP gains are usually subnormal in patients with paresis of vertical saccades. Impairment of pursuit and the VOR are often dissociated. Phase lead of the VOR implicates damage to velocity‐to‐position neural integrator for vertical eye motion. These associations and dissociations of impaired vertical eye motion signify discrete structural and functional effects of supranuclear midbrain damage that are undetected by examination of saccades.
Antisaccades and Task Switching
Authors: BARTON JASON J. S. , CHERKASOVA MARIYA V. , LINDGREN KRISTEN , GOFF DONALD C. , INTRILIGATOR JAMES M. , MANOACH DARA S.
Published: July 2009

Abstract: Executive functions allow us to respond flexibly rather than stereotypically to the environment. We examined two such functions, task switching and inhibition in the antisaccade paradigm, in two studies. One study involved 18 normal subjects; the other, 21 schizophrenic patients and 16 age‐matched controls. Subjects performed blocks of randomly mixed prosaccades and antisaccades. Repeated trials were preceded by the same type of trial (i.e., an antisaccade following an antisaccade), and switched trials were preceded by a trial of the opposite type. We measured accuracy rate and latency as indices of processing costs. Whereas schizophrenic patients had a threefold increase in error rate for antisaccades compared to normals, the effect of task switching on their accuracy did not differ from that in normal subjects. Moreover, the accuracy rate of trials combining antisaccade and task switching was equivalent to a multiplication of the accuracy rates from trials in which each was done alone. Schizophrenic latencies were disproportionately increased for antisaccades, but again they were no different from normal subjects in the effect of task switching. In both groups the effect of task switching on antisaccades was a paradoxical latency reduction. We conclude that the executive dysfunction in schizophrenia is not generalized but selective, sparing task switching from exogenous cues, in which the switch is limited to a stimulus‐response remapping. The accuracy data in both groups support independence of antisaccade and task‐switching functions. The paradoxical task‐switching benefit in antisaccadic latency effects challenges current models of task switching. It suggests either carryover inhibition by antisaccadic performance in the prior trial or facilitation of antisaccades by simultaneous performance of other cognitive operations.
Inferior Vestibular Neuritis
Authors: HALMAGYI G. M. , AW S. T. , KARLBERG M. , CURTHOYS I. S. , TODD M. J.
Published: July 2009

Abstract: Sudden, spontaneous, unilateral loss of vestibular function without simultaneous hearing loss or brain stem signs is generally attributed to a viral infection involving the vestibular nerve and is called acute vestibular neuritis. The clinical hallmarks of acute vestibular neuritis are vertigo, spontaneous nystagmus, and unilateral loss of lateral semicircular function as shown by impulsive and caloric testing. In some patients with vestibular neuritis the process appears to involve only anterior and lateral semicircular function, and these patients are considered to have selective superior vestibular neuritis. Here we report on two patients with acute vertigo, normal lateral semicircular canal function as shown by both impulsive and caloric testing, but selective loss of posterior semicircular canal function as shown by impulsive testing and of saccular function as shown by vestibular evoked myogenic potential testing. We suggest that these patients had selective inferior vestibular neuritis and that contrary to conventional teaching, in a patient with acute spontaneous vertigo, unilateral loss of lateral semicircular canal function is not essential for a diagnosis of acute vestibular neuritis.
A Neurobiological Approach to Acquired Nystagmus
Authors: LEIGH R. JOHN , DAS VALLABH E. , SEIDMAN SCOTT H.
Published: July 2009

Abstract: The development of animal and mathematical models for several forms of acquired nystagmus has led to more comprehensive knowledge of these disorders. In the best understood forms, such as periodic alternating nystagmus, our range of knowledge includes an animal model, the neurotransmitters involved, and effective treatment. For some other forms, such as downbeat nystagmus, we have an animal model, but reliable treatment is lacking. In other cases, exemplified by acquired pendular nystagmus, we have only a provisional hypothesis for pathogenesis to account for the oscillations, without an animal model, but effective treatment is possible in some patients. The present trend of studying all aspects of the neurobiology of nystagmus, from molecules to behavior, seems to be the best approach to extend our knowledge and to identify new treatments, but much remains to be done.
Bioflavonoid‐Rich Botanical Extracts Show Antioxidant and Gene Regulatory Activity
Authors: GOHIL KISHORCHANDRA , PACKER LESTER
Published: July 2009

Abstract: Reactive oxygen and nitrogen metabolites are obligatory and essential products of metabolism. Unregulated increase in their production is associated with a number of chronic illnesses. Diets rich in fruits, vegetables, and wines are implicated in the prevention of chronic diseases. Molecular mechanisms by which fruits and vegetables confer their disease‐preventive actions are poorly defined. However, recent developments in the fields of genomics and bioinformatics provide powerful tools to investigate the mechanisms by which botanicals affect cellular functions. This monograph illustrates the potential of large‐scale messenger RNA analysis to unravel the role of transcription in mediating the effects of botanical extracts with antioxidant properties. The application of microarrays and oligonucleotide arrays shows multiple effects of antioxidant extracts on the expression of a broad spectrum of genes.
Inhibition by Wine Polyphenols of Peroxynitrite‐Initiated Chemiluminescence and NADH Oxidation
Authors: BOVERIS ALBERTO , VALDEZ LAURA , ALVAREZ SILVIA
Published: July 2009

Abstract: Peroxynitrite (ONOO−) is a powerful oxidant produced by neutrophils, macrophages, and lymphocytes as a signaling and cytotoxic molecule from their primary production of nitric oxide (NO) and superoxide anion (O2−). In the vascular space, ONOO− will likely oxidize lipoproteins and promote atherogenesis. Pure wine flavonoids (catechin, epicatechin, myricetin), hydroxycinnamates (caffeic acid, ferulic acid, chlorogenic acid), and plain Argentine red wines were assayed as ONOO− scavengers in two assays: (a) ONOO−‐initiated chemiluminescence and (b) ONOO−‐dependent oxidation. The assayed polyphenols as well as the red wines were effective inhibitors of the ONOO−‐driven oxidation reactions. Fifty percent of the pure substances were observed in the range of 30‐300 μM and in the case of red wines with the equivalent of 80‐120 μM of flavonoids. The amphipatic nature of wine polyphenols will lead to their accumulation at the lipoprotein surface, according to the Gibbs adsorption equation, where they are likely to prevent ONOO−‐induced tyrosine nitration and LDL modification.
Antithrombotic Effect of Polyphenols in Experimental Models
Authors: DE GAETANO GIOVANNI , DE CURTIS AMALIA , DI CASTELNUOVO AUGUSTO , DONATI MARIA BENEDETTA , IACOVIELLO LICIA , ROTONDO SERENELLA
Published: July 2009

Abstract: Epidemiological studies have suggested that cardiovascular disease can be decreased by moderate wine consumption, but an overall quantitative estimation of the relationship between wine intake and vascular risk is lacking. A meta‐analysis was therefore performed on 19 studies selected on the basis of the availability of specific information on the cardiovascular relative risk (RR) associated with wine consumption. A significant risk reduction (RR: 0.66, 95% CI 0.57‐0.75) was associated with moderate (1‐2 drinks or 150‐300 mL/d) versus no wine consumption. In five studies which excluded ex‐drinkers as reference group, the overall RR associated with wine consumption was 0.61 (95% CI 0.57‐0.75). A dose‐response relation between wine intake and vascular risk resulted in a J‐shaped curve, with a significant risk reduction at about 300 mL/d (trend analysis p= 0.032). Two studies were also performed to investigate the effects of wine polyphenols on experimental thrombosis in rats. Supplementation for 10 days with alcohol‐free red wine—but not white wine or alcohol—induced a significant reduction of stasis‐induced venous thrombosis, an effect blunted by NO synthase inhibitor L‐NAME. In rats with diet‐induced hyperlipidemia, alcohol‐free red wine supplementation significantly delayed the thrombotic occlusion of an artificial prosthesis inserted into the abdominal aorta, but did not affect the increased cholesterol and triglyceride levels. TRAP values were significantly higher in animals receiving alcohol‐free wine. Altogether these experimental data support an antithrombotic role of polyphenols in the reduced vascular risk associated with moderate wine consumption in man, as shown by our epidemiological studies.