bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathogenesis of HSV and CMV Infections in Pregnancy
Authors: Askienazy-Elbhar Myriam , Sifer Christophe
Published: March 2007

Human herpesvirus (HHSV) and human cytomegalovirus (HCMV) infections during pregnancy are a major concern of public health because of the risk for severe sequelae for the fetuses and the neonates and because primary infections, reinfections and reactivations can be asymptomatic. The risk for neonatal herpes is mostly congenital, while the risk for HCMV infection is either prenatal or congenital. Screening exposed women has not brought definite solutions but is currently being evaluated. Among pregnant women with active infection, evaluation of the fetus for contamination and thus for the risk for severe immediate or long-term sequelae for neonates is the major goal. Diagnostic tools are available, cell culture still being the gold standard, and polymerase chain reaction (PCR) being currently evaluated for its contribution to diagnosis of active infection. Consensus for screening pregnant women as well as achievement of antiviral vaccines are the most urgent intervention strategies to develop in the near future.
Endocrine‐Immune Interactions in Pregnant Non‐Human Primates With Intrauterine Infection
Authors: Gravett Michael G. , Novy Miles J.
Published: March 2007

Preterm birth remains the most common cause of perinatal mortality. Although the causes of preterm labor are multifactorial and vary according to gestational age, preterm labor and term labor share common cellular and molecular mechanisms, including stimulation of the fetal hypothalamic‐pituitary‐adrenal (HPA) axis and endocrine/immune system interactions. We have developed a non‐human primate experimental model for intrauterine infection and preterm labor using chronically instrumented rhesus monkeys (Macaca mulatta) with timed gestations. We have documented the temporal and quantitative relationships among intrauterine infection, the synthesis and release of proinflammatory cytokines, prostaglandins, and fetal‐placental steroid biosynthesis in this model. Infection‐induced preterm parturition is characterized by significant elevations in amniotic fluid proinflammatory cytokines and by increases in fetal adrenal steroid biosynthesis, but not by corresponding increases in placental estrogen biosynthesis characteristic of spontaneous parturition. This suggests that activation of the fetal HPA axis by the stress of infection is accompanied by placental dysfunction and also that infection‐induced preterm parturition is not dependent upon the increased estrogen biosynthesis observed in spontaneous parturition. These different endocrine and immune responses have important diagnostic and therapeutic implications in the management of preterm labor.
Prevention of Infection in Pregnancy
Authors: Ledger William J. , Skupski Daniel
Published: March 2007

We believe the prevention of infection-related adverse pregnancy outcome is the most important focus for obstetricians today. An emphasis upon immunization of susceptible women, prevention of transmissible disease by modification of patient behavior, and identification and treatment of silent infections should become standards of practice. This will require educational initiatives for physicians and their patients as well as continued clinical trials to determine costs and effectiveness.
Analysis of Lactobacillus Products for Phages and Bacteriocins That Inhibit Vaginal Lactobacilli
Authors: Tao Lin , Pavlova Sylvia I. , Mou Susan M. , Ma Wen-ge , Kiliç Ali O.
Published: March 2007

Objective: Bacterial vaginosis is associated with an unexplained loss of vaginal lactobacilli. Previously, we have identified certain vaginal lactobacilli‐released phages that can inhibit in vitro other vaginal lactobacilli. However, there is no apparent route for phages to be transmitted among women. The purpose of this study was to identify whether certain Lactobacillus products commonly used by women release phages or bacteriocins that can inhibit vaginal lactobacilli.

Methods: From 26 Lactobacillus products (2 acidophilus milks, 20 yogurts, 3 Lactobacillus pills, and 1 vaginal douche mix), lactobacilli were isolated with Rogosa SL agar (Difco, Detroit, MI). From these lactobacilli, phages and bacteriocins were induced with mitomycin C and tested against a collection of vaginal Lactobacillus strains.

Results: From the 26 products, 43 Lactobacillus strains were isolated. Strains from 11 yogurts released phages, among which 7 inhibited vaginal lactobacilli. Eleven strains released bacteriocins that inhibited vaginal lactobacilli. While about one‐half of the vaginal strains were lysed by bacteriocins, less than 20% were lysed by phages.

Conclusions: Some vaginal lactobacilli were inhibited in vitro by phages or bacteriocins released from Lactobacillus products used by women, implying that vaginal lactobacilli may be reduced naturally due to phages or bacteriocins from the environment.
Metronidazole Appears Not to Be a Human Teratogen: Review of Literature
Authors: Struthers Barbara J.
Published: March 2007

Metronidazole is used to treat trichomoniasis, bacterial vaginosis, and other diseases. As is the case with many drugs, physicians often hesitate to use it during pregnancy, particularly in the first trimester. A review of the nearly four decades' worth of published literature on metronidazole use in pregnant women indicates that it is not teratogenic, regardless of the trimester in which it is used. On the other hand, a number of published studies indicate that bacterial vaginosis and trichomoniasis are associated with preterm birth and low birth weight. Treatment of these conditions with metronidazole during pregnancy may decrease the incidence of preterm birth and low birth weight, thus potentially decreasing the complications that can result from prematurity.
Chlamydial Lower Genital Tract Infection and Spontaneous Abortion
Authors: Sozio J. , Ness R. B.
Published: March 2007

Objective:Few previous studies have examined the role that acuteChlamydia trachomatislower genital tract infection plays in the development of spontaneous abortion. This study evaluated cervicalC. trachomatisinfections among 52 women experiencing spontaneous abortion and 59 controls.

Methods:Pregnant women at less than 22 weeks of gestation who sought medical care in an emergency department in West Philadelphia were eligible for enrollment. Urine samples from enrolled women were tested for chlamydia using ligase chain reaction DNA amplification. All women were followed up to 22 weeks of pregnancy to ascertain the outcome of spontaneous abortion.

Results:The proportion of women with chlamydial infection was 3.8% among spontaneous abortion cases and 8.5% among controls. After adjustment for potentially confounding factors, there was no substantial difference in the rate of chlamydial infection between women with and without spontaneous abortion (odds ratio 1.8, 95% confidence interval 0.3–10.7).

Conclusion:These data do not support a relationship between acuteC. trachomatisinfection and the development of spontaneous abortion.
Cutaneous Anergy in Pregnant and NonpregnantWomen With Human Immunodeficiency Virus
Authors: Eriksen N. L. , Helfgott A. W.
Published: March 2007

Objective: To determine the prevalence of cutaneous anergy in pregnant and nonpregnant women
who are seropositive for human immunodeficiency virus.

Methods and materials: The medical records of 159 women seropositive for human immunodeficiency
virus were reviewed. Demographic characteristics and tuberculin skin test results were
abstracted from the chart. Tuberculin skin testing was performed by the Mantoux method (5
tuberculin units of purified protein derivative injected intradermally). Anergy testing was performed
using any two of the three following antigens; tetanus toxoid, mumps, or Candida skin test
antigen. A positive tuberculin test was defined as induration of 5 mm or more, and a positive test for
the other antigens was defined as any amount of induration over the skin test area. Anergy was
defined as any amount of induration to the other antigens. A CD4+T lymphocyte count was
obtained at the time of skin testing. Continuous variables were analyzed using the Mann Whitney—U
test. Categorical data were analyzed with the chi‐square or Fisher′s exact test as appropriate.
A two‐tailed P value <0.05 was considered significant.

Results: There were 102 nonpregnant and 57 pregnant women who returned to have their skin
test results read. There was no significant difference in the prevalence of positive, negative or
anergic skin test results between groups. The CD4+T lymphocyte count (mean ± standard deviation)
in patients with anergic results was similar between pregnant (375 ± 256/mm3) and nonpregnant
(358 ± 305/mm3) women (P = 0.64).

Conclusion: The prevalence of cutaneous anergy is similar among pregnant and nonpregnant
women seropositive for human immunodeficiency virus.
Congenital Syphilis After Treatment of MaternalSyphilis With a Penicillin Regimen ExceedingCDC Guidelines
Authors: Conover Craig S. , Rend Charles A. , Miller Grayson B. , Schmid George P.
Published: March 2007

Background: Although congenital syphilis usually occurs as a result of a failure to detect and treat
syphilis in pregnant women, failures of the currently recommended regimen to prevent congenital
syphilis have been reported.

Case: This report describes an infant with congenital syphilis despite maternal treatment with a
regimen exceeding current CDC guidelines .

Conclusion: Regardless of the regimen used to treat syphilis during pregnancy, clinicians should
recognize the possibility of occasional treatment failures and the importance of adequate follow‐up
of infants at risk for congenital syphilis.
The Use of Once‐Daily Dosing of Gentamicin inObstetrics and Gynecology
Authors: Wiesenfeld H. C. , Heine R. P.
Published: March 2007

Gentamicin is a widely‐used antimicrobial agent for obstetric and gynecologic infections. Renewed
excitement in this antibiotic has arisen from recent information supporting less frequent dosing. In
this symposium, we will describe the pharmacokinetics of gentamicin and review new information
advocating the use of once‐daily administration of gentamicin.
Effect of Gliotoxin on HumanPolymorphonuclear Neutrophils
Authors: Shah D. T. , Jackman S. , Engle J. , Larsen B.
Published: March 2007

Objectives:Candida albicans is known to produce gliotoxin, which has several prominent biological
effects, including immunosuppression. interference with host defenses may arise from the effects of
this toxin on leukocyte structure and function.

Methods: Flow cytometric analysis revealed that polymorphonuclear leukocytes (PMN) were
more sensitive to gliotoxin than were mononuclear cells. Structural and various functional aspects
of PMN exposed to gliotoxin were studied.

Results: Gliotoxin at (1 μg/mL) did not affect the viability but did diminish PMN chemotaxis and
reduced their ability to ingest particles. Other functional aberrations included decreased nitroblue
tetrazolium dye reduction, decreased superoxide production, and release of lactoferrin suggesting
by degranulation. Gliotoxin also affected the ability of PMN to kill Escherichia coli.

Conclusions: This study suggests a previously unrecognized potential virulence factor of C. albicans
that could contribute to persistence of yeast colonization or recurrence of symptomatic infection
through diminished host resistance.
Chronic Plasma Cell Endometritis in Hysterectomy Specimens of HIV-Infected Women: A Retrospective Analysis
Authors: Kerr-Layton J. A. , Stamm C. A. , Peterson L. S. , Mcgregor J. A.
Published: March 2007

Objective:Abnormal uterine bleeding is a common and troublesome problem in human immunodeficiency virus (HIV)-infected women. We sought to evaluate endometrial pathology among HIVinfected women requiring hysterectomy to explore if endometritis may be common among these patients.

Methods:We performed a retrospective analysis of uterine pathology specimens obtained from HIV-infected and control patients requiring hysterectomy in two urban hospitals between 1988 and 1997 matched for age, surgical indication, and history of gonadotropin-releasing hormone (GnRH) use. Cases were evaluated for the presence of plasma cells and assigned a grade between 0 and 3.

Results:Indications included cervical dysplasia (4), carcinoma in situ (2), abnormal uterine bleeding (3), and adnexal mass (3). Some degree of abnormal uterine bleeding occurred in all cases. Plasma cell endometritis was twice as common in HIVoinfected women compared to HIV-negative specimens (11/11 versus 11/22) (P< 0.05). Plasma cell endometritis was also of a higher grade in specimens from HIV-infected women than in controls (P< 0.001).

Conclusion:Chronic endometritis was common and of a higher grade among HIV-infected women requiring hysterectomy in our series. Diagnosis and treatment of endometritis should be considered in HIV-infected women with uterine bleeding and/or tenderness. We speculate that antiretroviral and/or antimicrobial treatment for endometritis may effectively treat endometritis and eliminate the need for surgery in some HIV-infected women. We suggest that consideration and treatment of endometritis in HIV-1 infected women being evaluated for possible hysterectomy has the potential to reduce costs and morbidity for patients and providers who may be exposed during surgical procedures.
Performance of a Commercial Polymerase ChainReaction Test for Endocervical Chlamydia trachomatisInfection in a University Hospital Population
Authors: Livengood C. H. , Boggess K. A. , Wrenn J. W. , Murtha A. P.
Published: March 2007

Objectives: To examine the accuracy of a commercial polymerase chain reaction (PCR) test (Amplicor
CTR,
Roche Diagnostic Systems, Branchburg NJ) for identification of endocervical chlamydial
infections through both laboratory evaluation and among a diverse teaching hospital patient
population.

Methods: Testing of reliable threshold inocula and reproducibility were carried out using laboratory
stock organisms. Paired endocervical samples from patients with a wide range of indications
were tested by PCR and an established culture procedure, and discrepant pairs were further
analyzed to determine true results.

Results: Laboratory evaluation suggested that one copy of target DNA from a viable organism
consistently yielded a positive result, and test reproducibility was very good, with an overall coefficient
of variation of 15%. Compared to true results in 1,588 paired clinical samples from 1,489
women with a 10% prevalence of infection, the PCR test and culture yielded respective sensitivities
of 87.4% and 78.0%, and negative predictive values of 98.6% and 97.6%. Specificity and positive
predictive value for both tests were 100%. Cost per specimen was nearly identical at $18.84 and
$18.88 respectively. Polymerase inhibitors and organisms lacking target DNA were not found in
false‐negative PCR samples.

Conclusion: This commercial PCR test is accurate, cost‐competitive, and much faster than culture
for diagnosis of endocervical chlamydia infections in our population of intermediate prevalence
of chlamydial infection.
Initial Multicenter Experience With DoubleNucleoside Therapy for Human ImmunodeficiencyVirus Infection During Pregnancy
Authors: Silverman N. S. , Watts D. H. , Hitti J. , Money D. M. , Livingston E. , Axelrod J. , Ernest J. M. , Robbins D. , DiVito M. M.
Published: March 2007

Objective: To study maternal and neonatal effects of combination nucleoside analog therapy administered
to human immunodeficiency virus (HIV)‐infected pregnant women for maternal indications.

Methods: A multicenter, prospective observational study was undertaken at six perinatal centers
in the United States and Canada that supported regional referral programs for the treatment of
HIV‐infected pregnant women. Demographic, laboratory, and pregnancy outcome data were collected
for 39 women whose antiretroviral treatment regimens were expanded to include more than
one nucleoside analog for maternal indications. The 40 newborns were monitored at pediatric
referral centers through at least three months of age to ascertain their HIV infection status.

Results: For all 39 women, zidovudine (ZDV) therapy was instituted at 13.4 ± 8.2 weeks, with
a second agent (lamivudine [3TC] in 85% of cases) being added at a mean gestational age of 17.6
weeks. Duration of therapy with two agents was 20.6±10.4 weeks overall, with no women stopping
medications because of side effects or toxicity. No significant changes in maternal laboratory values
were seen, except for an increase in mean corpuscular volume, over the course of pregnancy. No
clinically significant adverse neonatal outcomes were noted, with all but the three preterm newborns
leaving hospital with their mothers. Neonatal anemia (hematocrit < 50%) was seen in 62% of
newborns, with no children needing transfusion; mild elevations of liver function tests, primarily
aspartate aminotransferase, were noted in 58% of newborns tested, though none were clinically
jaundiced. Overall rate of neonatal HIV infection was 2.5% (95% confidence interval: 0.1–13.2%).

Conclusion: Combination antiretroviral therapy during pregnancy with two nucleoside analogs
was well‐tolerated by mothers and newborns, with no significant short‐term toxicities or side effects
noted. Surveillance of exposed newborns’ hematologic and liver function appears warranted.
Heat Shock Proteins in Human Endometrium Throughout the Menstrual Cycle
Authors: Tabibzadeh S. , Broome J.
Published: March 2007

Human endometrium, in response to steroid hormones, undergoes characteristic cycles of proliferation, secretory changes, and tissue shedding. Human endometrium expresses a molecular repertoire which includes the heat shock proteins (Hsps) Hsp27, Hsp60, Hsp70, Hsp90, and alpha crystallin B chain. The expression of Hsp27, Hsp60, and the constitutive form of Hsp70 (Hsc70) shows a sharp increase in human endometrium after ovulation. The maximal expression of the molecular chaperone, alpha crystallin B chain, occurs during the secretory phase. In view of known functions of the Hsps, it is likely that these proteins are involved in protection of the endometrial proteins against factors with the potential to lead to protein denaturation. Tumor necrosis factor-α (TNF-α) is a cytotoxic cytokine that is produced in progressive amounts during the secretory phase. The function of the Hsps may be to protect cells against the cytotoxic damage of TNF-α, particularly during the critical period of “implantation window.” Infect. Dis. Obstet. Gynecol. 7:5–9, 1999. (C) 1999 Wiley-Liss, Inc.
Immunity to Heat Shock Proteins and Arthritic Disorders
Authors: van Eden W.
Published: March 2007

Adjuvant arthritis (AA) is a frequently used model of experimental arthritis. Because of its histopathology, which is reminiscent of rheumatoid arthritis in humans, AA is used as a model for the development of novel anti-inflammatory drugs. Recently, it has become evident that AA is a typical T-cell-mediated autoimmune condition. Therefore, novel immunotherapies targeted to T cells can be developed in this model. Analysis of responding T cells in AA have now led to the definition of various antigens with potential relevance to arthritis, including human arthritic conditions. One such antigen defined in AA is the 60kD heat shock protein. Both T-cell vaccination approaches and active antigen immunizations and antigen toleration approaches have turned out to be effective in suppressing AA. Infect. Dis. Obstet. Gynecol. 7:49–54, 1999.
Surface‐Associated Heat Shock Proteins of Legionella pneumophila and Helicobacter pylori: Roles in Pathogenesis and Immunity
Authors: Hoffman P. S. , Garduno R. A.
Published: March 2007

Bacterial heat shock proteins (Hsps) are abundantly produced during the course of most microbial infections and are often targeted by the mammalian immune response. While Hsps have been well characterized for their roles in protein folding and secretion activities, little attention has been given to their participation in pathogenesis. In the case of Legionella pneumophila, an aquatic intracellular
parasite of protozoa and cause of Legionnaires′ disease, Hsp60 is uniquely located in the periplasm and on the bacterial surface. Surface‐associated Hsp60 promotes attachment and invasion in a HeLa cell model and may alter an early step associated with the fusion of phagosomes with lysosomes. Avirulent strains of L. pneumophila containing defined mutations in several dot/icm genes
are defective in localizing Hsp60 onto their surface and are reduced approximately 1000‐fold in their invasiveness towards HeLa cells. For the ulcer‐causing bacterium Helicobacter pylori, surfaceassociated Hsp60 and Hsp70 mediate attachment to gastric epithelial cells. The increased expression of these Hsps following acid shock correlates with both increased association with and inflammation of the gastric mucosa. A role for Hsps in colonization, mucosal infection and in promoting inflammation is discussed. Infect. Dis. Obstet. Gynecol. 7:58–63, 1999.
A Randomized, Double-Blind, Placebo-Controlled Trial of 5-Fluorouracil for the Treatment of Cervicovaginal Human Papillomavirus
Authors: Holmes M. M. , Weaver II S. H. , Vermillion S. T.
Published: March 2007

Objective:To compare intravaginal 5-fluorouracil (5-FU) and placebo for the treatment of cervical and/or vaginal human papillomavirus (HPV).

Methods:A randomized, placebo-controlled trial was performed. Women with HPV detected visually or by Papanicolaou (Pap)test and confirmed by colposcopic biopsy were randomized to receive either intravaginal 5-FU cream or an intravaginal placebo cream. Women with cervical or vaginal intraepithelial neoplasia were excluded. The primary outcome measure was cytologic regression ofHPV as determined by Pap test screening 4 to 6 months after treatment. The secondary outcome was cytologic evidence of disease progression at both the 4–6-month and 12-month followup evaluations. Data were analyzed using the Chi square test with significance established atP< 0.05.

Results:A total of forty patients were randomized, and thirty patients had a follow-up Pap test 4 to 6 months after treatment. Of those patients treated with 5-FU, 28% demonstrated regression of HPV on cytologic evaluation, compared with 69% of those treated with placebo (P< 0.05). Twelve-month follow-up cytology was available from 18 of the study participants. There were no significant differences in the frequency of cytologic progression or regression between groups at 12 months.

Conclusion:Four to six months post treatment, the use of intravaginal 5-FU for the treatment of cervical or vaginal HPV is associated with a lower rate of regression than the use of placebo. Infect. Dis. Obstet. Gynecol. 7:186–189, 1999.
Evaluation of the Strep B OIA Test Compared to Standard Culture Methods for Detection of Group B Streptococci
Authors: Song J. Y. , Lin L. L. , Shott S. , Kimber N. , Tangora J. , Cohen A. , Wells A. , Maezes M. , Aroutcheva A. , Faro S.
Published: March 2007

Objective:This study evaluated the accuracy of the commercial product Strep B OIA (optical immunoassay) compared to the standard agar and broth culture methods for detecting vaginal colonization with group B streptococcus (GBS).

Methods:Preoperative vaginal cultures were obtained from 141 nonpregnant gynecological patients undergoing major gynecologic surgery. Major gynecologic surgery was defined as benign gynecologic, gyne-oncology, and urogynecologic procedures. The results of the Strep B OIA test were compared to the results obtained from SXT agar (selective for GBS), colistin-nalidixic acid (CNA) agar, and Todd-Hewitt broth cultures.

Results:The prevalence of vaginal GBS colonization in this population was 20.6%. The sample sensitivity and specificity of the OIA method were 58.6% and 85.7%, respectively. These values are lower than the sensitivity and specificity of 85.4% and 91.5%, respectively, given in the OIA package insert. Although the sample negative predictive value was fairly high (88.9%), the positive predictive value was low (51.5%).

Conclusion:Although a previous study stated that the product Strep B OIA reduces the time required to obtain results (30 minutes versus days) and can, therefore, function as a useful diagnostic tool in the management of early-onset GBS disease, the present study's finding of low sensitivity and low positive predictive value indicates that this test may have very limited clinical value. Infect. Dis. Obstet. Gynecol. 7:202–205, 1999.
Pattern of Parvovirus B19 Infection During Different Trimesters of Pregnancy in Kuwait
Authors: Makhseed Ma'asoumah , Pacsa Alexander , Ahmed Mohammad Abrar , Essa Sahar Sultan
Published: March 2007

Objective:Aims of this study were to determine the IgG and IgM seropositivity to parvovirus B19 during the three trimesters of pregnancy.

Methods:Initially, a total of 1,047 pregnant women were included in a prospective study. Blood samples were obtained from 343, 406 and 298 cases in the first, second and third trimesters, respectively. To study the incidence of seroconversion, a second sample of blood was obtained 2–4 weeks later from the first 100 cases, who were IgG and IgM negative in the first trimester.

Results:The seroprevalence of parvovirus B19 IgG and IgM was 53.3% and 2.2%, respectively. The incidence of seroconversion was 16.5%. The rate of fetal loss was 15.4% in patients with acute infection, all of which occurred in the first two trimesters.

Conclusions:The percentage of IgG positive cases is significantly higher in first and second trimesters compared to the third trimester. The seroconversion rate was 16.5%. Infect. Dis. Obstet. Gynecol. 7:287–292, 1999.
Organic/inorganic nanocomposite gels employed as electrolyte supports in Dye‐sensitized Photoelectrochemical cells
Authors: Stathatos Elias , Lianos Panagiotis
Published: March 2007

Dye‐sensitized photoelectrochemical cells based on TiO2 mesoporous films, a ruthenium bipyridyl derivative as photosensitizer and a SiO2/poly(ethylene glycol)‐200 nanocomposite thin film as electrolyte
support, have been constructed. TiO2 films have been deposited on conductive transparent Indium‐Tin Oxide glass slides by means of a sol‐gel procedure carried out in reverse‐micellar solutions. The photosensitizer
has been adsorbed on titania films from ethanolic solutions while the electrolyte layer has been
synthesized by a sol‐gel procedure. The presence of silica in the nanocomposite electrolyte gel provides the
gelifying agent, the compound that holds the cell together in a sandwich form and the sealing agent that
protects the cell and secures its long‐term function. PEG‐200 makes the organic subphase which provides
the ionic conductivity. The present work describes the construction of the cell and the study of its efficiency.
A variant of the cell has also been made by incorporating Ag+ and Ru3+ ions into titania particles, but these
dopants did not improve cell efficiency, either in their oxidized or in their reduced form.
The recurrent event process of a success preceded by a failure and its application
Authors: Lai C. D.
Published: March 2007

We describe a simple discrete time renewal process of an event where a success is preceded by a failure. Its properties, especially the distributions of the counting and the interval processes, are investigated. We also propose an application to statistical process control based on the waiting time between two adjacent events. It is shown that the average number inspected under the new control scheme is larger than with the so called CCC control chart.
Composing Questions through Conceptual Authoring
Authors: Hallett Catalina , Scott Donia , Power Richard
Published: March 2007

This article describes a method for composing fluent and complex natural language questions, while avoiding the standard pitfalls of free text queries. The method, based on Conceptual Authoring, is targeted at question-answering systems where reliability and transparency are critical, and where users cannot be expected to undergo extensive training in question composition. This scenario is found in most corporate domains, especially in applications that are risk-averse. We present a proof-of-concept system we have developed: a question-answering interface to a large repository of medical histories in the area of cancer. We show that the method allows users to successfully and reliably compose complex queries with minimal training.
Identifying Sources of Disagreement: Generalizability Theory in Manual Annotation Studies
Authors: Bayerl Petra Saskia , Paul Karsten Ingmar
Published: March 2007

Many annotation projects have shown that the quality of manual annotations often is not as good as would be desirable for reliable data analysis. Identifying the main sources responsible for poor annotation quality must thus be a major concern. Generalizability theory is a valuable tool for this purpose, because it allows for the differentiation and detailed analysis of factors that influence annotation quality. In this article we will present basic concepts of Generalizability Theory and give an example for its application based on published data.
Beliefs and Community Responses to Mental Illness in Ghana: The Experiences of Family Carers
Authors: Quinn Neil
Published: March 2007

Background: There is often a lack of agreement on how to understand mental illness in low-income countries and support those experiencing it. This article explores the debate on beliefs and the implications for how society responds.

Material: Semi-structured interviews were undertaken with 80 family carers across four sites in Ghana to explore the themes of beliefs, attitudes, carer burden and support.

Discussion and conclusions: There appears to be greater reliance on culturally specific explanations of mental illness in rural areas, combined with more acceptance and support, particularly in one rural area with strong traditional belief systems. This suggests the need to develop integrated mental health services, which reflect these differing beliefs.
Quality Of Life In Schizophrenia On Conventional Versus Atypical Antipsychotic Medication: A Comparative Cross-Sectional Study
Authors: Mortimer Ann M. , Ahmed Al-Agib Ahemed Omar
Published: March 2007

Introduction: Atypical antipsychotic drugs, with superior tolerability and possibly superior efficacy, were expected to give schizophrenia patients better quality of life (QOL) than conventional treatment. Research findings are equivocal.

Method: We evaluated QOL using three subjective measures – Drug Attitude Inventory (DAI); Sickness Impact Profile (SIP); Schizophrenia Quality of Life Scale (SQLS) – in 126 routinely seen patients whose treatment was stable for six months, regardless of co-morbidity, current clinical status and concomitant medications. Severity of disorder was assessed with the Global Assessment Schedule (GAS).

Results: Fifty patients were on conventional treatment and 76 on atypical treatment. Atypical patients were more likely to be abusing substances ( p = 0.02) and living independently ( p = 0.00). Conventionally treated patients were older than atypically treated patients. Conventionally treated patients suffered schizophrenia almost twice as long as atypically treated patients. Atypically treated patients enjoyed substantially better quality of life than conventionally treated patients on all measures. The effects of confounding variables, i.e. age, duration, accommodation, co-morbid substance misuse and time spent in hospital, were evaluated with the General Linear Model. This confirmed the status of drug treatment as the primary predictor of all aspects of QOL.

Conclusion: We conclude that quality of life is genuinely superior on atypical treatment even allowing for the confounding effects of differential prescribing habits: atypical treatment tends to be reserved for younger, less seriously ill patients. There is no scientific or clinical rationale to support this practice.
A Reply to Veli-Matti Kärkkäinen’s Response
Authors: Richie Tony
Published: March 2007

This reply to Veli-Matti Kärkkäinen further affirms the importance of work in the theology of religions for Pentecostals and Charismatics today that first prompted the author’s original inquiry into the views of a major early Pentecostal leader, Bishop J.H. King, concerning interfaith encounter and understanding. This dialogue with Kärkkäinen supports suggestions that an overall program of rediscovering, reclaiming, restoring, and revisioning our Pentecostal theology of religions heritage seems advisable. King’s obviously optimistic theology of religions, however, must be carefully distinguished from pluralism and set in the context of its Wesleyan roots and Evangelical emphases. Further development of what King provides in embryonic form is demanded. King represents an optimistic but still Christocentric strain shared by other Pentecostals within early stages of the movement. Not at all amounting to an uncritical approbation of world religions, this revolutionary discovery does decidedly enlarge understandings of Christ’s lordship beyond the pale of any particular religion. Careful terminology in order to avoid misunderstanding is called for and conceded. Pentecostal hypersensitivity regarding theology of religions highlights the need for constant clarification of contrariness to liberal religious pluralism. King’s legacy invalidates any assumption that earlier (older) Pentecostal resources on religions are exclusively pessimistic. Implications are immense for Christian mission and interreligious relations.
Why does Luke use Tongues as A Sign of the Spirit’s Empowerment?
Authors: Keener Craig
Published: March 2007

Luke does not present tongues as a sign of Spirit baptism merely arbitrarily, but because it is logically connected to the purpose of baptism in the Spirit. Luke emphasizes baptism in the Spirit as power to testify for Christ cross-culturally; what better sign to evidence this particular empowerment of the Spirit than inspiration to speak in the languages of other cultures?
A Response to James Shelton concerning Jesus and Healing: Yesterday and Today
Authors: Warrington Keith
Published: March 2007

This is a response to an article written by James Shelton (‘“Not Like It Used to Be?” Jesus, Miracles, and Today’, JPT 14.2 [April 2006], pp. 219-27) apparently in response to an article of mine, ‘Acts and the Healing Narratives: Why’, published in JPT 14.2 (April 2006), pp. 189-217. In it I sought to explore the purposes of Luke in selecting and presenting the healing miracles in the way that he did in the Acts of the Apostles whilst positing lessons for the readers then and now. This rejoinder to Professor Shelton relates to areas of debate concerning healing, only some of which are located in the original article.
Radically Orthodox, Reformed, and Pentecostal: Rethinking the Intersection of Post/Modernity and the Religions in Conversation with James K.A. Smith
Authors: Yong Amos
Published: March 2007

The Radical Orthodoxy [RO] movement has been gaining momentum in the theological academy. Its most recent spokesperson, James Smith, attempts to extend the RO vision in dialogue with the Dutch Reformed tradition. Clearly, the central features of ‘Reformed’ RO empower a kind of prophetic engagement with the various domains of late modern society. At another level, however, the globalizing features of our time mean that the dominant pagan deities are not just secularism, nihilism, or capitalism, but also those of other religions. At this level, even a ‘Reformed’ RO may be unable to sustain an engagement with the plurality of mythoi operative in the public square. Rather than undermining the Radically-Reformed project revisioned by Smith, I propose a ‘pneumatological assist’ and argue that a more robust pneumatological theology (suggested but undeveloped by Smith) enables the kind of engagement that is required in our religiously plural late modern world.
The Spirit, Religions, and the World as Sacrament: A Response to Amos Yong’s Pneumatological Assist
Authors: Smith James
Published: March 2007

This article responds to Amos Yong’s critique of the author’s Introducing Radical Orthodoxy by focusing on two themes: (1) his analysis of the tension between my creational, participatory or sacramental ontology and my more antithetical assertions regarding the Church as a unique polis; and (2) the question of apologetics, dialogue, and interreligious engagements. In response, I develop an intensity account of participation that applies to both ontology and theology of culture.
A salty tongue
Authors: Haut Mavis
Published: March 2007

Valerie Solanas deserves fresh assessment. An innovator whose aberrant humour has not been fully recognized, Solanas embarked on the male-dominated route of a type of satire that has most commonly been represented in the form of male stand-up comedy. She does not engage in the irony, absurdly overstated ‘femininity’ or parodic self-reference with which many women comedians have ridiculed male behaviour. Her Scum Manifesto (1968) declares war on the patriarchal establishment in all its multiple forms: government, capitalism, the economy, law, work, the family and male sexuality. She uses the term men to condemn all persons of either sex who perpetuate the supremacy of patriarchal institutions, which she believes in all seriousness to be a deadly threat to humanity. Solanas also denounces all forms of withdrawal, separatism and élitism, which, in her view, seriously compromise the wider political applications of SCUM. This paper interprets the notorious shooting of Andy Warhol, which, especially since the film made on this subject, is often uncritically regarded as proof of Solanas’s insanity, as an iconoclastic act of theatre in which Solanas abandoned clear-cut distinctions between life and art.
Hsp72 up-regulates Epstein-Barr virus EBNALP coactivation with EBNA2
Authors: Peng Chih-Wen , Zhao Bo , Chen Hong-Chi , Chou Min-Luen , Lai Chiou-Yan , Lin Shinn-Zong , Hsu Hsue-Yin , Kieff Elliott
Published: March 2007

The Epstein-Barr virus (EBV) transcriptional coactivator EBNALP specifically associates and colocalizes with Hsp72 in lymphoblastoid cell lines. We now find that overexpression of Hsp72 more than doubled EBNALP coactivation with EBNA2 of a transfected EBV LMP1 promoter in B lymphoblasts, did not affect EBNA2 or EBNALP protein levels, and strongly up-regulated EBNA2 and EBNALP coactivation of LMP1 protein expression from the endogenous EBV genome in latency I infected Akata cells. The Hsp72 ATP, protein binding, and the C-terminal regulatory domains were required for full activity. An EBNALP deletion mutant, EBNALPd45, which does not associate with Hsp72, coactivated with EBNA2, but was not affected by Hsp72 overexpression, despite Hsp72 up-regulation of wild-type EBNALP coactivation with EBNA2 at all levels of EBNALP expression, indicating the importance of Hsp72 association with EBNALP for Hsp72 up-regulation of coactivation. Of importance, a 90% RNAi knockdown of Hsp72 reduced EBNALP coactivation with EBNA2 of transfected EBV LMP1 and Cp promoters by approximately 50%. Overexpression of the Hsp72 C-terminal interacting and regulatory protein, CHIP, strongly down-regulated EBNALP coactivation, independently of CHIP ubiquitin ligase activity. CHIP effects were Hsp72 dependent, indicating a background downmodulating role for CHIP in Hsp72 augmentation of EBNA2 and EBNALP coactivation. Based on these and other cited data, we favor a model in which Hsp72 chaperones EBNALP shuttling of repressors from EBNA2-enhanced promoters.
Roles of RabGEF1/Rabex-5 domains in regulating FcϵRI surface expression and FcϵRI-dependent responses in mast cells
Authors: Kalesnikoff Janet , Rios Eon J. , Chen Ching-Cheng , Alejandro Barbieri M. , Tsai Mindy , Tam See-Ying , Galli Stephen J.
Published: March 2007

RabGEF1/Rabex-5, a guanine nucleotide exchange factor (GEF) for the endocytic pathway regulator, Rab5, contains a Vps9 domain, an A20-like zinc finger (ZnF) domain, and a coiled coil domain. To investigate the importance of these domains in regulating receptor internalization and cell activation, we lentivirally delivered RabGEF1 mutants into RabGEF1-deficient (−/−) mast cells and examined FcϵRI-dependent responses. Wild-type RabGEF1 expression corrected phenotypic abnormalities in −/− mast cells, including decreased basal FcϵRI expression, slowed FcϵRI internalization, elevated IgE + Ag–induced degranulation and IL-6 production, and the decreased ability of −/− cytosol to support endosome fusion. We showed that RabGEF1's ZnF domain has ubiquitin ligase activity. Moreover, the coiled coil domain of RabGEF1 is required for Rabaptin-5 binding and for maintaining basal levels of Rabaptin-5 and surface FcϵRI. However, mutants lacking either of these domains normalized phenotypic abnormalities in IgE + antigen–activated −/− mast cells. By contrast, correction of these −/− phenotypes required a functional Vps9 domain. Thus, FcϵRI-mediated mast cell functional activation is dependent on RabGEF1's GEF activity.
SBMLeditor: effective creation of models in the Systems Biology Markup Language (SBML)
Authors: Rodriguez Nicolas , Donizelli Marco , Le Novère Nicolas
Published: March 2007

Background

The need to build a tool to facilitate the quick creation and editing of models encoded in the Systems Biology Markup language (SBML) has been growing with the number of users and the increased complexity of the language. SBMLeditor tries to answer this need by providing a very simple, low level editor of SBML files. Users can create and remove all the necessary bits and pieces of SBML in a controlled way, that maintains the validity of the final SBML file.

Results

SBMLeditor is written in JAVA using JCompneur, a library providing interfaces to easily display an XML document as a tree. This decreases dramatically the development time for a new XML editor. The possibility to include custom dialogs for different tags allows a lot of freedom for the editing and validation of the document. In addition to Xerces, SBMLeditor uses libSBML to check the validity and consistency of SBML files. A graphical equation editor allows an easy manipulation of MathML. SBMLeditor can be used as a module of the Systems Biology Workbench.

Conclusion

SBMLeditor contains many improvements compared to a generic XML editor, and allow users to create an SBML model quickly and without syntactic errors.
ProCMD: a database and 3D web resource for protein C mutants
Authors: D'Ursi Pasqualina , Marino Francesca , Caprera Andrea , Milanesi Luciano , Faioni Elena M , Rovida Ermanna
Published: March 2007

Background

Activated Protein C (ProC) is an anticoagulant plasma serine protease which also plays an important role in controlling inflammation and cell proliferation. Several mutations of the gene are associated with phenotypic functional deficiency of protein C, and with the risk of developing venous thrombosis. Structure prediction and computational analysis of the mutants have proven to be a valuable aid in understanding the molecular aspects of clinical thrombophilia.

Results

We have built a specialized relational database and a search tool for natural mutants of protein C. It contains 195 entries that include 182 missense and 13 stop mutations. A menu driven search engine allows the user to retrieve stored information for each variant, that include genetic as well as structural data and a multiple alignment highlighting the substituted position. Molecular models of variants can be visualized with interactive tools; PDB coordinates of the models are also available for further analysis. Furthermore, an automatic modelling interface allows the user to generate multiple alignments and 3D models of new variants.

Conclusion

ProCMD is an up-to-date interactive mutant database that integrates phenotypical descriptions with functional and structural data obtained by computational approaches. It will be useful in the research and clinical fields to help elucidate the chain of events leading from a molecular defect to the related disease. It is available for academics at the URL http://www.itb.cnr.it/procmd/.
NF-κB mediates the transcription of mouse calsarcin-1 gene, but not calsarcin-2, in C2C12 cells
Authors: Wang Heng , Yang Shulin , Yang E , Zhu Zhengmao , Mu Yulian , Feng Shutang , Li Kui
Published: March 2007

Background

The calsarcins comprise a novel family of muscle-specific calcineurin-interaction proteins that play an important role in modulating both the function and substrate specificity of calcineurin in muscle cells. The expression of calsarcin-1 (CS-1) is restricted to slow-twitch skeletal muscle fibres, whereas that of both calsarcin-2 (CS-2) and calsarcin-3 (CS-3) is enriched in fast-twitch fibres. However, the transcriptional control of this selective expression has not been previously elucidated.

Results

Our real-time RT-PCR analyses suggest that the expression of CS-1 and CS-2 is increased during the myogenic differentiation of mouse C2C12 cells. Promoter deletion analysis further suggests that an NF-κB binding site within the CS-1 promoter is responsible for the up-regulation of CS-1 transcription, but no similar mechanism was evident for CS-2. These findings are further supported by the results of EMSA analysis, as well as by overexpression and inhibition experiments in which NF-κB function was blocked by treatment with its inhibitor, PDTC. In addition, the overexpression of NFATc4 induces both the CS-1 and CS-2 promoters, whereas MEF2C only activates CS-1.

Conclusion

Our present data suggest that NF-κB is required for the transcription of mouse CS-1 but not CS-2, and that the regulation of the calsarcins is mediated also by the NFAT and MEF2 transcription factors. These results provide new insights into the molecular mechanisms governing transcription in specific muscle fibre cells. The calsarcins may also serve as a valuable mechanistic tool to better understand the regulation of calcineurin signalling during muscle differentiation.
CTLA-4+49A/G and CT60 gene polymorphisms in primary Sjögren syndrome
Authors: Gottenberg Jacques-Eric , Loiseau Pascale , Azarian Mariam , Chen Chun , Cagnard Nicolas , Hachulla Eric , Puechal Xavier , Sibilia Jean , Charron Dominique , Mariette Xavier , Miceli-Richard Corinne
Published: March 2007

CTLA-4 encodes cytotoxic T lymphocyte-associated antigen-4, a cell-surface molecule providing a negative signal for T-cell activation. CTLA-4 gene polymorphisms have been widely studied in connection with genetic susceptibility to various autoimmune diseases, but studies have led to contradictory results in different populations. This case-control study sought to investigate whether CTLA-4 CT60 and/or +49A/G polymorphisms were involved in the genetic predisposition to primary Sjögren syndrome (pSS). We analysed CTLA-4 CT60 and +49A/G polymorphisms in a first cohort of 142 patients with pSS (cohort 1) and 241 controls, all of Caucasian origin. A replication study was performed on a second cohort of 139 patients with pSS (cohort 2). In cohort 1, the CTLA-4 +49A/G*A allele was found on 73% of chromosomes in patients with pSS, compared with 66% in controls (p = 0.036; odds ratio (OR) 1.41, 95% confidence interval (CI) 1.02 to 1.95). No difference in CTLA-4 CT60 allelic or genotypic distribution was observed between patients (n = 142) and controls (n = 241). In the replication cohort, the CTLA-4 +49A/G*A allele was found on 62% of chromosomes in patients with pSS, compared with 66% in controls (p = 0.30; OR 0.85, 95% CI 0.63 to 1.16). Thus, the CTLA-4 +49A/G*A allele excess among patients from cohort 1 was counterbalanced by its under-representation in cohort 2. When the results from the patients in both cohorts were pooled (n = 281), there was no difference in CTLA-4 +49A/G allelic or genotypic distribution in comparison with controls. Our results demonstrate a lack of association between CTLA-4 CT60 or +49A/G polymorphisms and pSS. Premature conclusions might have been made if a replication study had not been performed. These results illustrate the importance of case-control studies performed on a large number of patients. In fact, sampling bias may account for some contradictory results previously reported for CTLA-4 association studies in autoimmune diseases.