bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor Necrosis Factor Alpha Stimulation of Human Clara Cell Secretory Protein Production by Human Airway Epithelial Cells
Authors: COWAN M. J. , HUANG X. , YAO X. L. , SHELHAMER J. H.
Published: July 2010

Abstract: Clara cell secretory protein (CCSP) or uteroglobin/CC10 is a product of epithelial cells in a variety of organs including the lung. CCSP has anti‐inflammatory properties and may act as an inhibitor of secretory phospholipase A2's. Tumor necrosis factor alpha (TNF‐α) is capable of inducing the expression of gene products including a variety of cytokines and chemokines in the airway epithelium that may upregulate the airway inflammatory response. Therefore, it was of interest to determine whether this proinflammatory cytokine might also induce the production of a counterregulatory protein such as CCSP, which might modulate the inflammatory response in the airway. Normal human tracheobronchial epithelial cells in primary culture and a human bronchial epithelial cell line (BEAS‐2B) were studied. CCSP mRNA levels in BEAS‐2B cells were detected by ribonuclease protection assay. CCSP mRNA levels increased in response to TNF‐α (20 ng/mL) stimulation after 8–36 h, with the peak increase at 18 h. Immunoblotting of CCSP released from BEAS‐2B cells into the culture media demonstrated that TNF‐α induced the synthesis and secretion of CCSP over 8 to 18 h. Similarly, TNF stimulated the release of CCSP from human tracheobronchial epithelial cells in primary culture at 8 and 18 h. The CCSP reporter gene including 801 bases 5′ of the transcription start site did not increase transcriptional activity in response to TNF‐α stimulation. A CCSP mRNA half‐life assay indicated that TNF‐α induced increases in CCSP mRNA at least in part at a posttranscriptional level. Therefore, TNF‐α induces airway epithelial cell expression of human CCSP and may modulate airway inflammatory responses in this manner.
The Role of CC10 in Pulmonary Carcinogenesis: From a Marker to Tumor Suppression
Authors: LINNOILA R. ILONA , SZABO EVA , DEMAYO FRANCESCO , WITSCHI HANSPETER , SABOURIN CAROL , MALKINSON AL
Published: July 2010

Abstract: CC10 is infrequently expressed in human non‐small cell lung cancers (NSCLCs), despite being abundantly produced by progenitor cells for normal and neoplastic epithelium. Many abnormalities in the surrounding lung associated with field carcinogenesis, which reflect prolonged exposure to such carcinogens as tobacco smoke, also revealed altered expression of CC10. Exposure of hamsters and mice to the tobacco‐specific carcinogen NNK led to reduced CC10 expression, which was partially reversible. Overexpression of CC10 in immortalized bronchial epithelial cells delayed the induction of anchorage‐independent growth in response to NNK. The data suggest that downregulation of CC10 contributes to carcinogenesis because CC10 antagonizes the neoplastic phenotype.
The Long Reach of Evolution and Development: Effects on the Alzheimer Brain
Authors: KOSIK KENNETH S.
Published: July 2010

Abstract: Genes that cause late‐onset neurodegenerative disease may have the property of evolvability. Their tendency to collect mutations may have contributed to the rapid evolution of the brain.
Apolipoprotein E and Alzheimer's Disease
Authors: STRITTMATTER WARREN J.
Published: July 2010

Abstract: The specific molecular pathway by which apolipoprotein E modifies the expression of Alzheimer's disease remains elusive. Isoform‐ specific interactions of apolipoprotein E with other molecules determine the outcome from other neurologic disorders and may provide more tractable model systems.
“Who Knows the Power of His Bones”: Reburial Redux
Authors: CANTWELL ANNE‐MARIE
Published: July 2010

Abstract: This paper discusses the repatriation of human remains to indigenous peoples in Australia and the United States and the role anthropologists play in the construction of past, present, and future identities for contemporary indigenous peoples. Using examples from both countries, I suggest that many of the participants at the reburials, and in the events leading up to them, were not only reburying their dead ancestors and addressing religious concerns, but were also redeeming past social injustices, renegotiating the status quo, and affirming their modern social and religious identity‐all important issues for Fourth World peoples living in First World nation‐states today. Reburials are powerful social dramas, testimony to the complex historical relationships between and among all concerned, living and dead, indigenous and non‐indigenous. I also argue that as Fourth World peoples attempt to renegotiate the status quo by turning to the past and reburying their ancestors, the important role of anthropologists in this effort should be considered in terms of both practice and theory. Because of the combination of heritage/cultural resource management legislation, government regulations, a changing professional ethic in regards to issues of repatriation, anthropologists in all subdisciplines are increasingly involved in the witting and unwitting reproduction of indigenous social orders. The implications of this and its ethical dilemmas for anthropologists working in all the subdisciplines and in varied workplaces are explored. The necessity of working with indigenous communities is underscored and suggestions for working toward a common universal heritage are presented.
Ethical Issues in the Ethnography of Cyberspace
Authors: HAKKEN DAVID
Published: July 2010

Abstract: The project of developing an anticipatory anthropology of the future reveals unique ethical opportunities. For example, the increased importance of performance means there is a substantial potential for a substantive “resocialing”. of work in organizations, just as the decline of Modernism opens space for collective, situated ethics as opposed to individualized categorical imperatives. An anthropology of the future should address the question of the future of ethics in general. The very possibility of human agency, of informed individual moral action, is brought into question in new ways. The profound flexibility of the computer as a medium carries with it the dangers of hyper‐abstraction, while the consolidation of capital reproduction on a global level increases the scope for apparently permanent mystification. Also important are the new ethical challenges raised for those engaged in knowledge “production” or science broadly conceived. These include the necessary effort to acknowledge fully the role of non‐human agency, and the potentially profound possibilities in a transformation in the character of knowledge, a correlate, at least in part, of the commodification of knowledge associated with distance learning. These challenges accompany the more overt threats of transgenic entities and ecological degradation. How can one be an ethical intellectual or academic under these circumstances, let alone teach others to be? There are also some specific challenges facing anthropology in particular. Some derive from the increasing “privatization” of ethnography, both in its growing popularity in modes of social reproduction more directly implicated in the reproduction of capital and in the declining academic support for anthropology. In a very specific sense, anthropology has grounded its ethics on an appreciation of and support for the reproduction of “really existing” culture. This ethical compass is not available to the ethnographer who studies the future. How do we participate ethically in the construction of a future in whose character we are inevitably implicated?
Tissue Biology of Apoptosis: Ref‐1 and Cell Differentiation in the Developing Retina
Authors: CHIARINI LUCIANA B. , LINDEN RAFAEL
Published: July 2010

Abstract: Programmed cell death by apoptosis plays a major role in neurogenesis. The sensitivity to apoptosis in developing nervous tissue is strongly dependent on cell interactions taking place within a highly structured environment, composed of various cell types at distinct stages of differentiation. In this article, we review evidence gathered both in vivo and in a histotypical retinal explant preparation in vitro that the bifunctional AP endonuclease/redox factor Ref‐1 (HAP1, APE, APEX) may be an anti‐apoptotic protein associated with cell differentiation in the developing retina.
First and Second Messenger Role of Calcium: Survival versus Apoptosis in Serum‐Free Cultured Granulosa Explants
Authors: MUSSCHE SYLVIE , LEYBAERT LUC , D'HERDE KATHARINA
Published: July 2010

Abstract: In order to elucidate the causal relationship between increased intracellular free calcium ([Ca2+]i) and induction of apoptosis, serum‐free cultured granulosa cell (GC) explants were subjected to various experimental protocols interfering with normal Ca2+ homeostasis. Modulation of apoptotic indices was calculated on DAPI‐stained GC explants. In some experiments [Ca2+]i was measured with the Ca2+ probe fura‐2 in combination with epifluorescence microscopy. Buffering of [Ca2+]i with BAPTA‐AM resulted in inhibition of apoptosis, while increasing extracellular Ca2+ (otherwise called [Ca2+]e load) resulted in a biphasic response characterized by an initial inhibitory effect on apoptosis followed by a delayed phase of increased apoptosis that became apparent at 4 h after withdrawal of the [Ca2+]e load. The initial inhibitory effect of the [Ca2+]e load on apoptosis was dependent on the concentration of the load (range 2–50 mM), was augmented when the [Ca2+]e load was applied in the presence of the Ca2+ channel blocker methoxyverapamil, and was mimicked by applying Mg2+ and Gd3+, two Ca2+‐receptor agonists. These observations point towards the involvement of an extracellular Ca2+‐sensing receptor (CaR). Measurements of [Ca2+]i showed that the ion was increased just after [Ca2+]e load, followed by recovery that was complete at 2 h after the load. Collectively these data suggest that a [Ca2+]e load initiates apoptosis, becoming manifest 4 h later, by the provoked [Ca2+]i increase, and this effect is preceded by an apoptosis‐inhibiting phase presumably involving CaR activation. We conclude that Ca2+ may act as a first (extracellular) messenger promoting cell survival and as a second (intracellular) messenger activating the cell death pathway.
Molecular Mapping of the Physiological Cell Death Process: Mitochondrial Events May Be Disordered
Authors: FLORYK DANIEL , UCKER DAVID S.
Published: July 2010

Abstract: The mitochondrion plays a central role in BCL‐2‐Inhibitable physiological cell deaths. the detailed order of mitochondrial and other events during cell death in vivo remains ambiguous, however. as part of an effort to explore this issue, we have asked whether mitochondrial dissolution during physiological cell death occurs in an orderly and concerted process. here, we describe the characterization of two elements of mitochondrial disintegration on the level of individual cells. using a novel cytofluorimetric approach, we have assessed simultaneously the release of cytochrome c (specifically a fluorescently tagged transfected construct) from mitochondria and the dissipation of mitochondrial membrane potential. our results indicate that mitochondrial disintegration does not follow a strictly ordered process and is not concerted. we are extending these studies to further characterize mitochondrial events in the context of bcl‐2 family members and place them definitively within the context of the caspase cascade.
A Caspase‐Independent Cell Clearance Program: The LEI/L‐DNase II Pathway
Authors: TORRIGLIA ALICIA , PERANI PAOLO , BROSSAS JEAN YVES , ALTAIRAC SÉVERINE , ZEGGAI SAMIA , MARTIN ELISABETH , TRÉTON JACQUES , COURTOIS YVES , COUNIS MARIE‐FRANCE
Published: July 2010

Abstract: The discovery of caspase‐mitochondrial pathway counts as one of the most important discovery in apoptosis biochemistry. Today, however, we begin to recognize its limits. Inhibition of caspase does not prevent cell death in many mammalian models. Targeted disruption of caspases does not impair every type of apoptosis. Other pathways, caspase independent, are now described. Here we present one of these pathways. It is a serine‐protease dependent pathway and its key event is the transformation of LEI (a serine protease inhibitor) into L‐DNase II (an endonuclease). When using this apoptotic pathway the cell activates, at the same time, its endonuclease activity (L‐DNase II appears) and its protease activity (there is a release of inhibition of proteases).
Role of Apoptosis in the Response of Lung Carcinomas to Anti‐Cancer Treatment
Authors: JOSEPH BERTRAND , LEWENSOHN ROLF , ZHIVOTOVSKY BORIS
Published: July 2010

Abstract: Resistance of tumor cells to treatment often accounts for the failure of traditional forms of anti‐cancer therapy. It is well known that tumors from the same histological group and stage of development are highly heterogeneous in their sensitivity to therapy. Among the factors that can influence tumor sensitivity are DNA repair capacity, distribution of cells throughout the cell cycle, proliferation potential, etc. In many cases, anti‐cancer therapy eliminates tumor cells via apoptosis, an active form of cell death characterized by cell shrinkage and the removal of cells in a neat, orderly fashion. However, this process is not always efficient. In the present review, the precise role that apoptosis plays in the response of lung carcinomas to chemotherapy and radiation treatment is discussed.
Realistic Solar Surface Convection Simulations
Authors: STEIN ROBERT F. , NORDLUND ÅKE
Published: July 2010

Abstract: We perform essentially parameter free simulations with realistic physics of convection near the solar surface. We summarize the physics that is included and compare the simulation results with observations. Excellent agreement is obtained for the depth of the convection zone, the p‐mode frequencies, the p‐mode excitation rate, the distribution of the emergent continuum intensity, and the profiles of weak photospheric lines. We describe how solar convection is nonlocal. It is driven from a thin surface thermal boundary layer where radiative cooling produces low entropy gas which forms the cores of the downdrafts in which most of the buoyancy work occurs. We show that turbulence and vorticity are mostly confined to the intergranular lanes and underlying downdrafts. Finally, we illustrate our current work on magneto‐convection.
Time‐Dependent Turbulent Convection in 1D Radiation Hydrodynamics of Pulsating Stars
Authors: FEUCHTINGER MICHAEL
Published: July 2010

Abstract: Due to the lack of a self‐consistent convection theory, each model of turbulent convection has to pass through several tests based on detailed comparisons with observations of real astrophysical objects. In this context nonlinear investigations of radially pulsating stars play an important role. They provide a unique opportunity to confront results of model calculations with a huge, detailed and accurate material of observational data.

Using a state‐of‐the‐art numerical technique we investigate the nonlinear behavior of radially pulsating stars by solving the full time‐dependent system of radiation hydrodynamics including a time‐dependent turbulent convection model.

As a first example we discuss nonlinear models of RR Lyrae stars. We present fundamental as well as first overtone lightcurves for two sets of stellar parameters. A standard Fourier decomposition is used to confront the resulting light and radial velocity variations with recent observations and we show that well‐known problems like the phase discrepancy problem or the problem of stable nonlinear double mode models can be treated.
Low Frequency Oscillation in Turbulent Convection
Authors: KRISHNAMURTI RUBY
Published: July 2010

Abstract: Large fluid systems such as the atmosphere of the Earth or the convection zone of the Sun are no doubt turbulent, but contain considerable organization on many scales. Not all of these scales are directly forced; some arise as a result of internal arrangements of energy and momentum, giving rise, in the Earth's atmosphere, to such phenomena as the atmospheric jet streams.

This paper is about an investigation of large‐scale organization that arises in turbulent Rayleigh‐Benard convection. We report on observations of low‐frequency oscillations in the Rayleigh number (R) range 107‐108, with Prandtl number (Pr) equal to seven. It has been known that for convecting layers with large aspect ratio A (where A is the ratio of fluid layer width to depth), a steady large‐scale flow sets in at R= 2× 106. Tilted transient plumes embedded in this flow, and maintaining it through Reynolds stresses, drift in one direction along the bottom of the layer, and in the opposite direction along the top. At a fixed point near the bottom or top boundary, there is a variability associated with the passage of these plumes. We call this the high‐frequency variability. A new kind of organization is observed for 107 < R < 108; clusters of transient tilted plumes travel in a horizontal direction as coherent units. These clusters are separated from each other by quiescent zones with almost no plumes. Now at a fixed point near the bottom boundary, there is a low‐frequency variability associated with the passage of clusters, as well as the high frequency variabilty from the passage of plumes within the cluster. Quantitative information on this low‐frequency oscillation derived from space‐time portraits and from temperature‐time series is described. A mathematical model of the low‐frequency oscillation is presented.
Two‐phase Shear Instability: Waves, Fingers, and Drops
Authors: YECKO PHILIP , ZALESKI STEPHANE
Published: July 2010

Abstract: We examine the development of instability for a shear flow made up of two distinct immiscible fluids, taking into account their disparate densities, viscosities, and the possibility of tension acting on the interface that separates them. Linear theory leads to a pair of coupled Orr‐Sommerfeld equations supplemented by the required matching conditions at the interface. The most unstable mode found here is believed to explain the nature of the instability essential to breakup at its onset. In addition, we find a second mode, which can be most unstable in certain situations of interest. Direct numerical simulations are performed for a range of parameter values. At early times, the simulations reveal the linear and nonlinear amplitude growth, verifying the applicability and accuracy of the numerical method over a range of density and viscosity ratios. At later times, the simulations show the development of elongated structures and the subsequent breakup of the heavier fluid into drops.
Mapping Oxidative DNA Damage and Mechanisms of Repair
Authors: AKMAN STEVEN A. , O'CONNOR TIMOTHY R. , RODRIGUEZ HENRY
Published: July 2010

Abstract: We developed a method to map oxidative‐induced DNA damage at the nucleotide level using ligation‐mediated polymerase chain reaction (LMPCR) technology. In vivo and in vitro DNA base modification patterns inflicted by reactive oxygen species (ROS) in the human P53 and PGK1 gene were nearly identical in vitro and in vivo. In human male fibroblasts, these patterns are independent of the transition metal used (Cu (II), Fe(II), or Cr(VI)). Therefore, local probability of H2O2‐mediated DNA base damage is determined primarily by DNA sequence. Moreover, in cells undergoing severe oxidative stress, extranuclear sites contribute metals that enhance nuclear DNA damage. The role of the base excision repair pathway in human cells responsible for the repair of the majority of ROS base damage is also discussed.
Differential Regulation of MAP Kinase Signaling by Pro‐ and Antioxidant Biothiols
Authors: SUZUKI YUICHIRO J. , SHI SUSAN S. , DAY REGINA M. , BLUMBERG JEFFREY B.
Published: July 2010

Abstract: Some biologically derived thiol‐containing compounds have potential for health benefits whereas others elicit biochemical events leading to pathogenesis. Effects of two biothiols, a‐lipoic acid (aLA), a therapeutic antioxidant, and homocysteine (Hcy), a risk factor for age‐associated cardiovascular disease, on cell signaling events involving p44 and p42 MAP kinases (p44/42 MAPK) were evaluated in cell culture. Treatment of serum‐deprived NIH/3T3 cells with Hcy (20 μM) resulted in the activation of p44/42 MAPK as determined by Western blot analysis using the phospho‐specific p44/42 MAPK antibody. p44/42 MAPK phosphorylation was rapid and transient with maximal activation occurring at 10–30 min. Transient activation of p44/42 MAPK was also observed in response to treatment of serum‐deprived cells with αLA. In cells grown in serum, serum‐dependent p44/42 MAPK phosphorylation was transiently enhanced by Hcy or Hcy thiolactone, but inhibited by αLA. Thus, αLA and Hcy differentially influence signal transduction events depending on the state of cells. These observations may be important in understanding how some biothiols are associated with pathogenic events while others have potential as therapeutic agents.
A Positive‐Feedback Model for the Loss of Acetylcholine in Alzheimer's Disease
Authors: EHRENSTEIN GERALD , GALDZICKI ZYGMUNT , LANGE G. DAVID
Published: July 2010

Abstract: We describe a two‐component positive‐feedback system that could account for the large reduction of acetylcholine that is characteristic of patients with Alzheimer's disease (AD). One component is β‐amyloid‐induced apoptosis of cholinergic cells, leading to a decrease in acetylcholine. The other component is an increase in the concentration of β‐amyloid in response to a decrease in acetylcholine. We describe each mechanism with a differential equation, and then solve the two equations numerically. The solution provides a description of the time course of the reduction of acetylcholine in AD patients that is consistent with epidemiological data. This model may also provide an explanation for the significant, but lesser, decrease of other neurotransmitters that is characteristic of AD.
Ovarian Regulators of Gonadotropin Secretion
Authors: MESSINIS IOANNIS E.
Published: July 2010

Abstract: Great progress in the ovarian mechanisms that control gonadotrophin secretion in women has recently been achieved. Estradiol (E2) is the main component of the ovarian negative effect on basal gonadotropin secretion during the normal menstrual cycle. However, nonsteroidal substances such as inhibins and activins that can affect follicle‐stimulating hormone (FSH) secretion in vitro may also participate in the control of FSH secretion in vivo. Recent evidence has shown that the ovaries also produce another nonsteroidal substance, named gonadotropin surge‐attenuating factor (GnSAF), that specifically attenuates GnRH‐induced LH secretion and the endogenous LH surge in superovulated women. It is possible that during the normal menstrual cycle GnSAF controls the amplitude of the midcycle LH surge by antagonizing the stimulating effect of E2 on the pituitary.
Recent Advances in Respiratory Care of the Term Neonate
Authors: GROSS IAN
Published: July 2010

Abstract: Persistent pulmonary hypertension is a major cause of morbidity and mortality in the term and near‐term infant. Management of this condition, which is characterized by respiratory distress and cyanosis, has been greatly enhanced by inhaled nitric oxide (NO) therapy. The following treatment regime is suggested: Conventional ventilation should be used initially, and hyper‐ventilation should be avoided. Surfactant should be administered early, preferably within 6 hours of diagnosis. If conventional ventilation fails, the next step is high‐frequency ventilation or inhaled NO. Some infants who do not respond to inhaled NO when administered by conventional ventilation will respond to NO delivery via a high‐frequency ventilator. If all of these therapies fail, extracorporeal membrane oxygenation (ECMO) should be considered. By the use of this approach, the mortality from PPH has been considerably reduced, and concerns today relate primarily to morbidity, particularly long‐term neurologic outcome and chronic lung disease resulting from ventilation and barotrauma.
The Genetics of Obesity Lessons for Polycystic Ovary Syndrome
Authors: LEGRO RICHARD S.
Published: July 2010

Abstract: Both polycystic ovary syndrome (PCOS) and obesity are common disorders with a complex phenotype. Both are presumably heterogeneous in etiology. Understanding the genetics of obesity, which has a longer and richer history, may therefore illuminate the genetics of PCOS, where major projects are now underway. Obesity may be the penultimate condition in which the effects of heredity and environment will forever mingle. Most obesity mutations identified to date (with the exception of the Agouti mutation) are inherited in an autosomal recessive manner. Therefore, it is unlikely that such mutations, even when identified in a human population, could explain only a fraction of the cases that make up the high prevalence of both of these disorders. Although the mouse models of single gene defects causing obesity contain many similar aspects of the PCOS phenotype such as obesity and subfecundity, there is no mouse model that mimics all aspects of the syndrome, especially the circulating androgen excess. This elevation in circulating androgens may be the sine qua non of the syndrome as indicated by our findings in sisters of PCOS probands that hyperandrogenemia may be the distintinctive reproductive phenotype. Isolation of PCOS and obesity genes may allow the development of targeted interventions that will lead to effective and safe treatment of both obesity and PCOS.
Insulin Sensitizers and Antiandrogens in the Treatment of Polycystic Ovary Syndrome
Authors: DIAMANTI‐KANDARAKIS E. , ZAPANTI E.
Published: July 2010

Abstract:The heterogeneous origin of polycystic ovary syndrome (PCOS) has been demonstrated by several studies. Abnormalities in steroidogenesis and metabolism are present, but the exact link between these two pathologic features remains to be clarified. In clinical practice, more than one therapeutic approach for the treatment of this syndrome has been proposed over the last few decades. Because hyperandrogenism and hyperinsulinemia contribute to a different degree to the phenotype of PCOS, therapeutic efforts have focused on agents that could treat or modify the clinical manifestations of these disorders. Antiandrogens as a sole treatment or combined with oral contraceptives are considered the treatment of choice for the manifestations of hyperandrogenemia, but there is no agreement about their efficacy on the metabolic sequelae of PCOS (insulin resistance, hyperinsulinemia, dislipidemia). Furthermore, the improvement of insulin sensitivity by insulin sensitizers may be of therapeutic value directly and/or indirectly in the management of clinical manifestations of hyperinsulinemia and hyperandrogenemia.
Management of Hydrosalpinx: Reconstructive Surgery or IVF?
Authors: BONTIS JOHN N. , DINAS KONSTANTINOS D.
Published: July 2010

Abstract: Tubal disease remains the most important factor in female infertility. Many investigators reported that patients with hydrosalpinx had a decreased clinical pregnancy rate and an increased miscarriage rate, resulting in a decreased ongoing pregnancy rate when compared to that of patients with other types of tubal disease. Different studies showed a deleterious effect of the presence of hydrosalpinx on the outcome of in vitro fertilization‐embryo transfer, because toxic agents flowing from the hydrosalpinx to the uterus impair the implantation rate. Operative laparoscopy is effective in the treatment of hyrosalpinges (Stage I or II). Fertility outcome is related to tubal damage. Patients with Stage III and IV disease should be managed from the beginning with in vitro fertilization. Excision of hydrosalpinx(‐ges) improves the pregnancy potential after in vitro fertilization. We believe that assisted reproductive technology and reproductive surgery can be complementary. The development of laparoscopic surgery and in vitro fertilization improved the pregnancy rate in patients with tubal factor infertility.
Chlamydia Screening‐Yes, but of Whom, When, by Whom, and with What?
Authors: MÅRDH PER‐ANDERS
Published: July 2010

Abstract: The importance of screening programs in reducing the prevalence of genital chlamydial infections is stressed by the fact that the majority of infected persons are more or less asymptomatic. The use of oral contraceptives may mask infections affecting the upper genital tract. This imposes selective screening and rescreening of women with a history of pelvic inflammatory disease. The recent knowledge that vaginal introital samples will provide a detection rate equal to or even higher than that of cervical samples collected in the same women opens up the possibility of screening women in health units lacking a gynecological examination chair. It also opens up the possibility of outpatient screening programs, for example, home sampling and mailing samples to laboratories that will perform analyses. The use of nucleic acid‐based assays means increased sensitivity and specificity compared with earlier used techniques such as ELISA. These former methods can also be used in low‐prevalence populations with acceptable positive predictable value, but may be misleading if used in post‐therapy check‐ups because the antigen may persist in microbiologically cured cases.
PID: Clinical and Laparoscopic Aspects
Authors: HENRY‐SUCHET JEANINE
Published: July 2010

Abstract: Clinical signs of pelvic inflammatory disease (PID) are not constant and are often limited to slight pelvic pain. Laparoscopy can lead to a rapid and correct diagnosis of PID. Intrapelvic bacteriologic samples can be obtained so as to administer the proper antibiotic. The exact nature of the lesions can be evaluated, and in severe cases, recent abscesses can be treated with good results for fecundity. Because the results in cases of long‐standing abscess are not so good, laparoscopy should be performed at the onset of infection and not be reserved until after some weeks of inefficient medical treatment, especially in young women who have not completed their family. In primary chronic salpingitis, the lack of any clinical signs usually leads to a delay in diagnosis until women consult for fertility problems. The ideal point would be to detect some biologic or clinical change that may lead to diagnosis such as a positive anti‐Chlamydia trachomatis (CT) serology or, in the future, positive anti‐CT Hsp 60 antibody could be the key to detecting and treating silent salpingitis in young women, CT being the main microorganism involved in chronic salpingitis. Screening for C. trachomatis low genital tract infection is mandatory in young people in order to control the epidemic.
Conservative Management of PID
Authors: GEORGILIS KOSTIS
Published: July 2010

Abstract: The goals in the management of pelvic inflammatory disease (PID) are not only treatment of the infection and prevention of immediate complications, but also prevention of its long‐term consequences. There are criteria for hospitalization, but patients who do not meet them can be safely treated as outpatients. A variety of sexually transmitted and other microorganisms can cause this infection, but the most important are Chlamydia trachomatis and Neisseria gonorrhoeae. Regimens with activity against gonococci, chlamydiae, streptococci, gram‐negative bacteria, and anaerobes should be administered. Several such antimicrobial regimens have shown very good clinical and microbiologic efficacy. However, their efficacy in preventing long‐term complications, such as infertility, has not been established. Close follow‐up is an important part of management. Evaluation of male sexual partners is imperative to prevent reinfection. Better diagnostic techniques and treatment modalities for PID must be developed to prevent its long‐term consequences.
Biological Factors in Culture Media Affecting in Vitro Fertilization, Preimplantation Embryo Development, and Implantation
Authors: LOUTRADIS D. , DRAKAKIS P. , KALLIANIDIS K. , SOFIKITIS N. , KALLIPOLITIS G. , MILINGOS S. , MAKRIS N. , MICHALAS S.
Published: July 2010

Abstract: Optimal culture conditions are of paramount importance for in vitro fertilization of gametes, preimplantation embryo development, and implantation for all species. Water is the basis of all culture media, and ultrapure water should be employed. The main energy sources of a medium are lactate, pyruvate, and glucose. The concentrations of the first two vary in different media, whereas the latter is necessary mainly for the later stages (morula to blastocyst) of development. A fixed nitrogen source is essential for implantation embryo development whether this is provided by amino acids, albumin, or serum. Suboptimal culture conditions can block development. Pronuclear zygotes of most species (but not human) arrest at some point between the two‐cell and the 16‐cell stage. Modifying culture conditions can lead the embryos to develop through this block. Hypoxanthine also causes a two‐cell block to mouse pronuclear zygotes, and this again depends largely on culture conditions. Simple culture media are bicarbonate‐buffered systems with pyruvate, lactate, and glucose. Complex media, such as Ham's F‐10, contain in addition amino acids and other elements found in serum. Human tubal fluid simulates the fallopian tube microenvironment. EDTA, gonadotropins, growth factors, and other substances can be included in the media to stimulate development. Coculture of embryos with oviductal cells has shown promising results.
Intracytoplasmic Sperm Injection Survey of World Results
Authors: TARLATZIS BASIL C. , BILI HELEN
Published: July 2010

Abstract: The widespread application of intracytoplasmic sperm injection (ICSI) has raised concern about the efficacy and safety of this novel technique. The European Society of Human Reproduction and Embryology (ESHRE) has established an ICSI Task Force to collect annually the clinical results, the outcome of pregnancy, and the follow‐up of children after ICSI using ejaculated, epididymal, and testicular sperm in order to address these important issues in a relatively short time. Over a 3‐year span (1993–1995), the number of centers for ICSI increased from 35 to 101, and the total number of ICSI cycles per year rose from 3,157 to 23,932. The incidence of oocytes damaged by the procedure remained low (<10%), whereas the fertilization rates obtained with ejaculated, epididymal, and testicular spermatozoa for 1995 were 64%, 62%, and 52%, respectively. Thus, 86–90% of the couples had embryo transfer, and the viable pregnancy rate was 21% for ejaculated, 22% for epididymal, and 19% for testicular sperm, while the incidence of multiple gestations was 29%, 30%, and 38%, respectively. It is noteworthy that no difference was found in ICSI results concerning the etiology of azoospermia, for example, obstructive (congenital or acquired) or nonobstructive. Furthermore, 3,149 transfers of frozen‐thawed embryos after ICSI with ejaculated, epididymal, or testicular sperm were performed, and in 11%, 9%, and 7% of them, respectively, a viable pregnancy was achieved. The ICSI results were similar during this 3‐year period, irrespective of the origin of the sperm. The perinatal outcome of children born after ICSI was not different from that after in vitro fertilization or natural conception and was only affected by multiplicity. Moreover, the incidence of major or minor malformations was not increased, but the chromosomal, especially the sex chromosomal, aberration rate was slightly elevated (∼2%). Therefore, ICSI has opened new horizons in the treatment of male infertility. The achievement of pregnancy after ICSI using ejaculated, epididymal, or testicular sperm is very satisfactory. The procedure seems to be safe, but further follow‐up of the children is necessary to more accurately assess its safety.
Estrogen Replacement Therapy in the Management of Osteopenia Related to Eating Disorders
Authors: BRUNI VINCENZINA , DEI METELLA , VICINI ILARIA , BENINATO LAURA , MAGNANI LEONARDO
Published: July 2010

Abstract: The effect of hormone replacement therapy on the bone mineral content of hypoestrogenic subjects depends on the pathogenesis of the disease as well as on the dosage and route of administration. This is particularly true in hypoestrogenism related to eating disorders. We present a longitudinal study of 26 young women with diet‐induced amenorrhea compared with a group of subjects with POF. The study protocol included the quantification of weight loss, the endocrine profile (follicle‐stimulating hormone, luteinizing hormone, prolactin, E2, FT3, FT4, thyroid‐stimulating hormone, and cortisol), the evaluation of markers of bone turnover (GLA, OSTK‐PR, ALP, OHP, and DPYR), and spinal bone density by DEXA at observation and after weight recovery. No hormone replacement therapy was administered. Mean BMD and Z scores before and after recovery do not differ significantly; OHP and DPYR appear significantly higher during basal evaluation, whereas GLA and ALP do not. Data on the impact of oral contraceptive use on bone mineral density are controversial. We particularly discuss the question of long‐term treatment with 20 μg ethinyl estradiol pills on peak bone mass acquisition during adolescence.
Hormone Replacement Therapy and Breast Cancer Risk
Authors: KOUKOULIS GEORGE N.
Published: July 2010

Abstract: The female breast is subject to a lifetime of hormonal control. After menopause, breast tissue becomes quiescent when estrogens drop to low levels. Menopause‐associated hormonal decreases produce short‐ and long‐term consequences that can be treated successfully by hormone replacement therapy (HRT). Despite the beneficial effects of HRT, the potential risk of breast cancer is a concern of both women and physicians. The available data indicate that HRT administered for longer than 5 years moderately increases the risk of breast cancer, but overall the benefits outweigh the potential risk.
Closure, Open Systems, and the Modeling Imperative
Authors: ALVAREZ DE LORENZANA JUAN M.
Published: July 2010

Abstract: Natural systems cannot be closed to the environment. At the same time there is a necessity for closure in order to build the system. It is this quintessential tension between openness and closure that drives systems to unfold into further stages or levels of growth and development. In other words, the emergence of organization in natural systems is a result of cycles of openness and closure. There are two distinct and complementary ways by which a system will carry over closure while involved in a process of expansion across the environment. These two ways need to be expressed in any formal representation: (1) within a level this will be by means of transitive closure, which is additive; and (2) between levels (i.e., from one level to the next higher level) this requires algebraic closure, which is multiplicative. The former expresses space closure, whereas the latter expresses topological or time closure. The conjunction of these two closures generates a hierarchy of levels. Prior to, and outside of, the system lies semantic closure.
The Scientific Origin of Life: Considerations on the Evolution of Information, Leading to an Alternative Proposal for Explaining the Origin of the Cell, a Semantically Closed System
Authors: VANEECHOUTTE MARIO
Published: July 2010

Abstract: We hypothesize that the origin of life, that is, the origin of the first cell, cannot be explained by natural selection among self‐replicating molecules, as is done by the RNA‐world hypothesis. To circumvent the chicken and egg problem associated with semantic closure of the cell‐no replication of information molecules (nucleotide strands) without functional enzymes, no functional enzymes without encoding in information molecules‐a prebiotic evolutionary process is proposed that, from the informational point of view, must somehow have resembled the current scientific process. The cell was the outcome of interactions of a complex premetabolic community, with information molecules that were devoid of self‐replicative properties. In a comparable manner, scientific progress is possible, essentially because of interaction between a complex cultural society and permanent information carriers like printed matter. This may eventually lead to self‐replicating technology in which semantic closure occurs anew. Explaining the origin of life as a scientific process might provide a unifying theory for the evolution of information, wherebye at two moments symbolization/encoding of interactions into permanent information occurred: at one moment that of chemical interaction and at another moment that of animal behavior interaction. In one event this encoding led to autonomously duplicating chemistry (the cell), an event that possibly may be one of the outcomes of current scientific progress.
From Autopoiesis to Semantic Closure
Authors: STEWART JOHN
Published: July 2010

Abstract: This article addresses the question of providing an adequate mathematical formulation for the concepts of autopoiesis and closure under efficient cause. What is required is metaphorically equivalent to reducing the act of writing to a set of mathematical equations, habitually effected by a human mathematician, within the ongoing function of the system itself. This, in turn, raises the question of the relationship between autopoiesis and semantics. The hypothesis suggested is that whereas semantics clearly requires autopoiesis, it may be also be the case that autopoiesis itself can only be materially realized in a system that is characterized by a semantic dimension.
Ontic Closure and the Hierarchy of Scale
Authors: ULANOWICZ ROBERT E.
Published: July 2010

Abstract: The Newtonian, universalist world view is incompatible with the notion of ontological indeterminacy. A hierarchical, or granular perspective, however, reveals how the consequences of pure chance, at scales far removed from those at which the event occurs, can be mitigated.
Active Motion, Communicative Aggregations, and the Spatial Closure of Umwelt
Authors: KULL KALEVI
Published: July 2010

Abstract: On the basis of a simple model of movable organisms that are supplied by semiotic force of attraction or repulsion, several general features of spatial behavior are demonstrated: (1) the stochastic spatial distribution of actively moving organisms is unstable; (2) simple or complex aggregations of organisms appear as a result of active motion; and (3) the ability for active motion ties the organisms with place. These results show that models that apply an internalist approach can considerably simplify the theory of spatial behavior of organic systems. Explanations based on the effects of Darwinian fitness may not be necessary for understanding the origin of biological aggregations.
Autonomy and Process Closure as the Basis for Functionality
Authors: COLLIER JOHN
Published: July 2010

Abstract: Most accounts of functionality are based in etiology, either design or selection. In this paper I give an account of function as serving autonomy, which is the closure of self‐maintaining processes, including those interacting with the environment. Autonomy is inherently dynamic, being based entirely on interacting processes, whose organization constitutes the integrity of the autonomous system. The etiological account focuses on external factors, either intentions in design or outcomes in selection. It ignores any but idiosyncratic organizational requirements within the biological entity and in its interactions with its environment, even though these may play a central role in the functionality of the trait in question. In particular, there is no simple relation between adaptation on the etiological account and adaptability, a higher order emergent trait that plays a central role in behavior and the evolutionary and developmental genesis of intelligence. I propose redefining adaptiveness in terms of autonomy. The definition naturally extends to adaptability and focuses on the organizational character of adaptiveness, forcing attention on this central biological characteristic, which is easily ignored in the etiological account. The result is a much richer account of both adaptation and selection.
The Role of Adaptive Immunity in Atherosclerosis
Authors: HANSSON GÖRAN K. , ZHOU XINGHUA , TÖRNQUIST ELISABETH , PAULSSON GABRIELLE
Published: July 2010

Abstract: Atherosclerosis is an inflammatory disease induced by a lipid metabolic disturbance at sites of hemodynamic strain in the vasculature. Studies in both man and experimental animal models show an involvement of innate and adaptive immune mechanisms in the disease process. Our recent studies in apoE‐knockout mice show that the level of hypercholesterolemia affects the functional properties of the immune response. Modulating immune activity by injections of polyclonal immunoglobulins inhibits disease progression, suggesting that immunomodulation may be useful to treat atherosclerosis. Analysis of T cell receptor (TCR) mRNA in atherosclerotic lesions shows expansions of T cells expressing TCR‐Vβ6, a receptor type that is also expressed by T cells recognizing oxidized low density lipoprotein (oxLDL). This suggests that oxLDL is an autoantigen that induces strong, local T cell responses in the plaque. Further characterization of this and other candidate antigens, such as heat shock proteins and macromolecular components of Chlamydia pneumoniae, may provide important information on which specific interference with the disease process could be based.
Regulation of Angiogenesis by Controlling VEGF Receptor
Authors: MUROTA SEI‐ITSU , ONODERA MITSUE , MORITA IKUO
Published: July 2010

Abstract: The endothelial cells cultured in collagen gel caused upregulation of KDR expression, which resulted in an increase in tube formation. Endothelial cells exposed to high glucose (33 mmol/l) for 30 days increased the tube formation induced by VEGF, but not by serum and bFGF. Immunohistochemical study showed that KDR expression was upregulated by the high‐glucose treatment. The endothelial cells treated with 0.5 ∼ 5 μg/ml eicosapentaenoic acid (EPA, 20:5, n‐3) for 48 h displayed a dose‐dependent suppression of tube formation, VEGF‐induced proliferation, and activation of p42/p44 MAP kinase but not bFGF‐induced ones. Pretreatment with arachidonic acid (20:4, n‐6) and docosahexaenoic acid (22:6, n‐3) did not show such effects. The expression of KDR was downregulated by the EPA pretreatment. The bone is the richest tissue in microvessel networks except for the liver. Osteoblasts produced VEGF and some factor(s) that could induce KDR upregulation in endothelial cells and could enhance tube formation. These results lead to the speculation that the regulation of KDR expression as well as VEGF production is deeply involved in angiogenesis under various conditions.
Composition of Skeletal Muscle Evaluated with Computed Tomography
Authors: GOODPASTER BRET H. , THAETE F. LELAND , KELLEY DAVID E.
Published: July 2010

Abstract: Computed tomography (CT) can yield quantitative imaging data from detailed maps of linear attenuation coefficients within tissue. The attenuation characteristics of skeletal muscle and adipose tissue can be quantified in vivo to provide information about the composition of skeletal muscle and the distribution of adipose tissue within muscle. Several studies have taken advantage of this utility to quantify skeletal muscle composition and fatty infiltration of muscle, in particular to quantify the attenuation characteristics of muscle as a marker of its lipid content. In this manner we found that the mean muscle attenuation of skeletal muscle reflects an increase in its fat content in obesity, and that this regional body composition parameter is strongly related to insulin‐resistant glucose metabolism. In addition, muscle composition and adipose tissue distribution within muscle may be altered with clinical weight‐loss interventions. CT may also provide important information about the changes in muscle mass and composition with aging and disease, which may, in turn, affect the muscle's function. In summary, CT can provide important quantitative data on the composition of muscle, and the distribution of adipose tissue within it, and this may be important in examining the relationships among skeletal muscle metabolism, lipid accumulation within muscle, and muscle function.