bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of HPV test versus conventional and automation‐assisted Pap screening as potential screening tools for preventing cervical cancer
Authors: Nieminen Pekka , Vuorma Sirkku , Viikki Merja , Hakama Matti , Anttila Ahti 
Published: July 2004

Objective  To evaluate new techniques in primary cervical cancer screening programmes.Design  Cross sectional pilot study.Setting  Department of Obstetrics and Gynaecology, Helsinki University Hospital.Population  Consecutive 2032 human papillomavirus (HPV) DNA and Pap smear samples were taken. Histological diagnoses were obtained from 460 patients.Methods  We compared the validity of the high risk (HR) HPV DNA detection test to automation‐assisted and conventional Pap smear screening.Main outcome measures  Specificity and sensitivity of screening methods.Results  Twenty‐three percent of women were HPV positive. Forty‐five of 46 had high grade lesions and cancers were HR HPV DNA positive, whereas 72/93 of low grade and more severe lesions were HR HPV DNA positive. When histologically verified high grade lesions were observed, the relative sensitivity of HR Hybrid Capture 2 (HR HC2) test was 98% compared with conventional Pap smear and Papnet tests, which performed 54%versus 58%, 83%versus 86% and 93%versus 98% relative sensitivity respectively, using cytological diagnoses HSIL (high grade squamous intraepithelial lesion), LSIL (low grade squamous intraepithelial lesion) or ASCUS (atypical squamous cells of undetermined significance) as the cutoff. The specificity of HC2 test (77–79%) was comparable with the ASCUS+ (ASCUS and more severe) cytology (68–79%), but lower when compared with LSIL+ (91–95%) or especially HSIL+ (97–99%) Pap smear results.Conclusion  Pap smear, as a screening test, is very different from HPV DNA detecting test HR HC 2. If cutoff LSIL or more severe lesions is used, primary Pap smear is clearly more specific than HR HC2, but markedly less sensitive. Due to high relative sensitivity of the HPV, only very few histologically confirmed high grade lesions would be detected among HPV negatives using simultaneous cytology. On the other hand, using HPV DNA test alone would lead to multifold amounts of referrals for colposcopy. A posterior Pap smear assessment among HPV positives might be helpful in increasing sensitivity and specificity of screening and defining those who need an immediate referral or treatment. We plan to incorporate primary HR HPV DNA test with posterior Pap smear reading of HPV positives into our ongoing randomised prospective multiarm trial evaluating new techniques in organised screening for cervical cancer in Finland.
The impact of guidelines on mild hypertension in pregnancy: time series analysis
Authors: Foy Robbie , Ramsay Craig R. , Grimshaw Jeremy M. , Penney Gillian C. , Vale Luke , Thomson Andrew , Greer Ian A. 
Published: July 2004

Objective  To determine the impact of a national strategy to promote implementation of a guideline on the management of mild, non‐proteinuric hypertension in pregnancy.Design  Simple, interrupted time series analysis.Setting  Four maternity units in Scotland.Population  Women delivering a live or stillborn baby.Methods  Dissemination of the guideline under the auspices of a national clinical effectiveness programme, supported by a national launch meeting and feedback from a survey of obstetricians highlighting aspects of care that could be improved.Main outcome measures  Appropriateness of initial investigation and subsequent clinical management, and costs of guideline development and implementation activities.Data collection  Twenty‐four months pre‐intervention and 12 months post‐intervention data were abstracted from a random sample of case notes.Results  Initial investigation was consistent with recommendations for 59.9% out of 1263 women and subsequent clinical management for 67.6% out of 1081 in whom a diagnosis could be made from available data. There were no significant changes in the appropriateness of initial investigation (10.6%; 95% confidence interval [CI] −0.1% to 19.3%; decreasing by 1.2% per month post‐implementation, 95% CI −2.5% to 0.1%) or clinical management (−0.3%; 95% CI −8.7% to 11.2%). Guideline development and implementation cost an estimated £2784 per maternity unit in Scotland.Conclusions  Clinical care of mild hypertension in pregnancy remains highly inconsistent. The lack of the intervention effect may be related to the complexity of the guideline recommendations and the nature of the implementation strategy.
Home‐based versus hospital‐based postnatal care: a randomised trial
Authors: Boulvain Michel , Perneger Thomas V. , Othenin‐Girard Véronique , Petrou Stavros , Berner Michel , Irion Olivier 
Published: July 2004

Objective  To compare a shortened hospital stay with midwife visits at home to usual hospital care after delivery.Design  Randomised controlled trial.Setting  Maternity unit of a Swiss teaching hospital.Population  Four hundred and fifty‐nine women with a single uncomplicated pregnancy at low risk of caesarean section.Methods  Women were randomised to either home‐based (n= 228) or hospital‐based postnatal care (n= 231). Home‐based postnatal care consisted of early discharge from hospital (24 to 48 hours after delivery) and home visits by a midwife; women in the hospital‐based care group were hospitalised for four to five days.Main outcome measures  Breastfeeding 28 days postpartum, women's views of their care and readmission to hospital.Results  Women in the home‐based care group had shorter hospital stays (65 vs 106 hours, P < 0.001) and more midwife visits (4.8 vs 1.7, P < 0.001) than women in the hospital‐based care group. Prevalence of breastfeeding at 28 days was similar between the groups (90%vs 87%, P= 0.30), but women in the home‐based care group reported fewer problems with breastfeeding and greater satisfaction with the help received. There were no differences in satisfaction with care, women's hospital readmissions, postnatal depression scores and health status scores. A higher percentage of neonates in the home‐based care group were readmitted to hospital during the first six months (12%vs 4.8%, P= 0.004).Conclusions  In low risk pregnancies, early discharge from hospital and midwife visits at home after delivery is an acceptable alternative to a longer duration of care in hospital. Mothers' preferences and economic considerations should be taken into account when choosing a policy of postnatal care.
Premature death among teenage mothers
Authors: Otterblad Olausson Petra , Haglund Bengt , Ringbäck Weitoft Gunilla , Cnattingius Sven 
Published: July 2004

Objective  Some data suggest an association between teenage childbearing and premature death. Whether this possible increase in risk is associated with social circumstances before or after childbirth is not known. We studied premature death in relation to age at first birth, social background and social situation after first birth.Design  Population‐based cohort study.Setting  Women born in Sweden registered in the 1985 Swedish Population Census.Population  Swedish women born 1950–1964 who had their first infant before the age of 30 years (N= 460,434).Methods  Information on the women's social background and social situation after first birth was obtained from Population Censuses. The women were followed up with regard to cause of death from December 1, 1990 to December 31, 1995. Mortality rate ratios and 95% confidence intervals (CI) were calculated.Main outcome measures  Mortality rates by cause of death.Results  Independent of socio‐economic background, teenage mothers faced an increased risk of premature death later in life compared with older mothers (rate ratio 1.6, 95% CI 1.4–1.9). The increased risk was most evident for deaths from cervical cancer, lung cancer, ischaemic heart disease, suicide, inflicted violence and alcohol‐related diseases. Some, but not all, of these increases in risk were associated with the poorer social position of teenagers mothers.Conclusions  Teenage mothers, independent of socio‐economic background, face an increased risk of premature death. Strategies to reduce teenage childbearing are likely to contribute to improved maternal and infant health.
Specific localization of the annexin II heterotetramer in brain lipid raft fractions and its changes in spatial learning
Authors: Zhao Wei‐Qin , Waisman David M. , Grimaldi Maurizio 
Published: July 2004

AbstractAnnexin‐II (AII) is a Ca2+‐dependent phospholipid‐binding protein that is present in both intracellular and extracellular compartments. In the present study AII immunoreactivity was found in a subpopulation of neurons in specific brain regions, including the cerebral cortex and the surface of hippocampal pyramidal neurons from adult rats. AII from synaptic membranes was detected by immunoblotting as multiple species containing the monomer (AII36) and heterotetramer (AIIt). AIIt was resistant to β‐mercaptoethanol and dithiothreitol in sodium dodecyl sulfate–polyacrylamide gel electrophoresis, but was completely reduced to monomers (36 kDa) by two‐dimensional electrophoresis. AIIt resided exclusively in the detergent‐resistant lipid rafts concentrated in neuronal dendrites, and its recruitment to those structures was enhanced by antibody cross‐link. AII abundantly distributed on the outer leaflet of neuronal membranes and between spaces of neurons appeared to be neuronal adhesive. The formation of AIIt required synthesis of sphingolipids and cholesterol, and its stability depended on Ca2+. Increases in neuronal activities such as depolarization and learning were shown to promote formation of AIIt. Our results suggest that, via a dynamic association with dendritic lipid rafts, AII may play a role in synaptic signal transduction and remodeling. This probably involves focal adhesion and interactions with actin that are associated with brain development and memory consolidation.
Molecular genetic responses to lysergic acid diethylamide include transcriptional activation of MAP kinase phosphatase‐1, C/EBP‐β and ILAD‐1, a novel gene with homology to arrestins
Authors: Nichols Charles D. , Sanders‐Bush Elaine 
Published: July 2004

AbstractWe recently demonstrated that the potent hallucinogenic drug lysergic acid diethylamide (LSD) dynamically influences the expression of a small collection of genes within the mammalian prefrontal cortex. Towards generating a greater understanding of the molecular genetic effects of hallucinogens and how they may relate to alterations in behavior, we have identified and characterized expression patterns of a new collection of three genes increased in expression by acute LSD administration. These genes were identified through additional screens of Affymetrix DNA microarrays and examined in experiments to assess dose–response, time course and the receptor mediating the expression changes. The first induced gene, C/EBP‐β, is a transcription factor. The second gene, MKP‐1, suggests that LSD activates the MAP (mitogen activated protein) kinase pathway. The third gene, ILAD‐1, demonstrates sequence similarity to the arrestins. The increase in expression of each gene was partially mediated through LSD interactions at 5‐HT2A (serotonin) receptors. There is evidence of alternative splicing at the ILAD‐1 locus. Furthermore, data suggests that various splice isoforms of ILAD‐1 respond differently at the transcriptional level to LSD. The genes thus far found to be responsive to LSD are beginning to give a more complete picture of the complex intracellular events initiated by hallucinogens.
Relationships between superoxide levels and delayed calcium deregulation in cultured cerebellar granule cells exposed continuously to glutamate
Authors: Vesce Sabino , Kirk Liana , Nicholls David G. 
Published: July 2004

AbstractThe relationship is investigated between superoxide levels in single cultured rat cerebellar granule neurons exposed continuously to glutamate in low KCl medium and the deregulation of cytoplasmic Ca2+. Cells that maintain a regulated cytoplasmic‐free Ca2+ and mitochondrial polarization in the presence of glutamate show no increase in superoxide levels until the onset of cytoplasmic Ca2+ deregulation. Oxidative stress of mitochondrial origin is readily detectable, as the inhibitors rotenone and antimycin A markedly increase superoxide levels with no effect on cytoplasmic‐free Ca2+. The potent cell‐permeant superoxide dismutase/catalase mimetic manganese tetrakis (N‐ethylpyridinium‐2yl) porphyrin, MnTE‐PyP, abolishes the deregulation‐related increase in superoxide but has no effect on deregulation itself. A combination of catalase with the free radical scavenger 4‐hydroxy‐TEMPO also fails to reduce deregulation. Following the loss of Ca2+ homeostasis nuclei undergo condensation; this morphological change is not inhibited by MnTE‐PyP and cannot account for the increased ethidium fluorescence. Phospholipase A2 inhibitors decrease the deregulation‐related increase in superoxide without protecting against deregulation. In conclusion, our study indicates that deregulation is not caused by NMDA receptor‐mediated oxidative stress as NMDA receptor activation does not increase superoxide levels until the onset of deregulation. Furthermore, the majority of superoxide is produced in the cytoplasm rather than in mitochondria.
Increased dopamine release in vivo by estradiol benzoate from the central amygdaloid nucleus of Parkinson's disease model rats
Authors: Liu Bin , Xie Junxia 
Published: July 2004

AbstractIn addition to the dopaminergic neurons in the nigrostriatal system, the properties of dopaminergic neurons in the mesolimbic system, such as the amygdala, are also of interest and importance because of their specific neuromodulatory effects in the pathophysiology of Parkinson's disease (PD). Using the fast cyclic voltammetry (FCV) technique, we present evidence to indicate that electrically‐evoked dopamine (DA) release from the amygdala, especially the central amygdaloid nucleus (CAN), of ovariectomized (OVX) female rats was significantly enhanced with increasing doses of estradiol benzoate (EB; 30, 50 and 100 µg/kg). Impaired DA release from the amygdala of an OVX rat PD model can also be increased by EB treatment (50 µg/kg) to a level similar to that of controls. The well established neuroprotective effects of estrogen may be beneficial for reducing the dysfunction of dopaminergic neurons in mesolimbic structures of rat PD models and PD patients.
Examination of the rate of peptide biosynthesis in neuroendocrine cell lines using a stable isotopic label and mass spectrometry
Authors: Che Fa‐Yun , Yuan Quan , Kalinina Elena , Fricker Lloyd D. 
Published: July 2004

AbstractThe biosynthesis of neuroendocrine peptides is typically examined by following the rate of appearance of a radioactive amino acid into mature forms of peptides. In the present study, we labeled cell lines with l‐leucine containing 10 deuterium residues (d10‐Leu) and used mass spectrometry to measure the biosynthetic rate of γ‐lipotropin in the AtT‐20 cell line and insulin in the INS‐1 cell line. After 3 h of labeling, both peptides show detectable levels of the d‐labeled form in the cells and media. The relative levels of the d‐labeled forms are greater in the media than in the cells, consistent with previous studies that found that newly synthesized peptides are secreted at a higher rate than older peptides under basal conditions. When AtT‐20 cells were stimulated with KCl or forskolin, the ratio of d‐ to H‐labeled γ‐lipotropin in the medium decreased, suggesting that the older peptide was in a compartment that could be released upon the appropriate stimulation. Overexpression of proSAAS in AtT‐20 cells reduced the ratio of d‐ to H‐labeled γ‐lipotropin, consistent with the proposed role of proSAAS as an endogenous inhibitor of prohormone convertase‐1. Labeling with d10‐Leu was also used to test whether altering the pH of the secretory pathway with chloroquine affected the rate of peptide biosynthesis. In AtT‐20 cells, 30 µm chloroquine for 3 or 6 h significantly reduced the rate of formation of γ‐lipotropin in both cells and media. Similarly, INS‐1 cells treated with 10, 30, or 60 µm chloroquine for 6 h showed a significant decrease in the rate of formation of insulin in both cells and media. These results are consistent with the acidic pH optima for peptide processing enzymes. Stable isotopic labeling with d10‐Leu provides a sensitive method to examine the rate of peptide formation in neuroendocrine cell lines.
The c‐Raf inhibitor GW5074 provides neuroprotection in vitro and in an animal model of neurodegeneration through a MEK‐ERK and Akt‐independent mechanism
Authors: Chin Paul C. , Liu Li , Morrison Bradley E. , Siddiq Ambreena , Ratan Rajiv R. , Bottiglieri Teodoro , D'Mello Santosh R. 
Published: July 2004

AbstractCerebellar granule neurons undergo apoptosis when switched from a medium containing high potassium (HK) to one that has low potassium (LK). LK‐induced cell death is blocked by GW5074 {5‐Iodo‐3‐[(3,5‐dibromo‐4‐hydroxyphenyl) methylene]‐2‐indolinone}, a synthetic drug that inhibits c‐Raf activity in vitro. GW5074 has no direct effect on the activities of several apoptosis‐associated kinases when assayed in vitro. In contrast to its effect in vitro, treatment of neurons with GW5074 causes c‐Raf activation (when measured in vitro in the absence of the drug) and stimulates the Raf‐MEK‐ERK pathway. Treatment of neurons with GW5074 also leads to an increase in the activity of B‐Raf, which is not inhibited by GW5074 in vitro at concentrations at which the drug exerts its neuroprotective effect. PD98059 and U0126, two distinct inhibitors of MEK, block the activation of ERK by GW5074 but have no effect on its ability to prevent cell death. Overexpression of a dominant‐negative form of Akt does not reduce the efficacy of GW5074, demonstrating an Akt‐independent mechanism of action. Neuroprotection is inhibited by SN‐50, a specific inhibitor of nuclear factor‐kappa B (NF‐κB) and by the Ras inhibitor S‐trans, trans‐farnesylthiosalicylic acid (FTS) implicating NF‐κB and Ras in the neuroprotective signaling pathway activated by GW5074. In addition to preventing LK‐induced apoptosis, treatment with GW5074 protects against the neurotoxic effects of MPP+ and methylmercury in cerebellar granule neurons, and glutathione depletion‐induced oxidative stress in cortical neurons. Furthermore, GW5074 prevents neurodegeneration and improves behavioral outcome in an animal model of Huntington's disease. Given its neuroprotective effect on distinct types of cultured neurons, in response to different neurotoxic stimuli, and in an animal model of neurodegeneration, GW5074 could have therapeutic value against neurodegenerative pathologies in humans.
The tyrosine kinase inhibitor AG126 restores receptor signaling and blocks release functions in activated microglia (brain macrophages) by preventing a chronic rise in the intracellular calcium level
Authors: Kann Oliver , Hoffmann Anja , Schumann Ralf R. , Weber Joerg R. , Kettenmann Helmut , Hanisch Uwe‐Karsten 
Published: July 2004

AbstractWe recently reported that lasting activation of mouse microglial cells with bacterial lipopolysaccharide (LPS) chronically elevated the basal intracellular calcium concentration ([Ca2+]i). This correlated to an attenuated calcium signaling of complement (C5a) and purinergic (UTP) receptors as well as to the capacity for effective production of cytokines–chemokines. Here, we demonstrate that these adjustments in the [Ca2+]i regulation require a critical protein tyrosine kinase (PTK) function – even in varying stimulation scenarios. Changes in basal [Ca2+]i and calcium signaling are not restricted to Gram‐negative bacterial confrontation. Pneumococcal cell wall (PCW) modelling Gram‐positive infection causes virtually the same effects. Moreover, decreases in calcium signaling efficacy are neither associated with altered receptor expression, nor mediated by autocrine loops. Administration of microglial release products, transfer of conditioned supernatant or presence of a radical scavenger during LPS or PCW treatments have no consequence. However, both the elevation in basal [Ca2+]i as well as the suppression of C5a‐ and UTP‐evoked calcium signals are selectively and dose‐dependently reversed by tyrphostin AG126, a PTK inhibitor that, moreover, blocks inducible nitric oxide and cytokine–chemokine release. The findings suggest that the AG126‐sensitive PTK critically controls both sensory and executive features of the microglial activation process via sustained up‐regulation of basal [Ca2+]i.
Arachidonic acid increases choline acetyltransferase activity in spinal cord neurons through a protein kinase C‐mediated mechanism
Authors: Chalimoniuk Malgorzata , King‐Pospisil Kelley , Pedersen Ward A. , Malecki Andrzej , Wylegala Edward , Mattson Mark P. , Hennig Bernhard , Toborek Michal 
Published: July 2004

AbstractArachidonic acid (AA) plays an important role as a signaling factor in the CNS. Therefore, exposure to AA may affect cholinergic neurons in the spinal cord. To test this hypothesis, mRNA expression and activity of choline acetyltransferase (ChAT) was measured in cultured spinal cord neurons treated with increasing concentrations (0.1–10 µm) of AA. Exposure to AA increased mRNA levels and activity of ChAT in dose‐ and time‐dependent manners. The most marked effect of AA on ChAT expression was observed in spinal cord neurons treated with 10 µm AA for 1 h. To study the mechanisms associated with these effects, ChAT mRNA levels and activity were measured in cultured spinal cord neurons exposed to AA and inhibitors of protein kinase C (PKC), such as 1‐(5‐isoquinolinesulfonyl)‐2‐methylpiperazine dichloride (H‐7) and chelerythrine. Inhibition of PKC completely prevented an AA‐induced increase in ChAT expression. In addition, exposure of spinal cord neurons to phorbol‐12‐myristate‐13‐acetate (PMA), an activator of PKC, mimicked AA‐induced stimulation of ChAT activity. The AA‐mediated increase in ChAT mRNA levels and activity was also prevented by treatments with EGTA, indicating the role of calcium metabolism in induction of this enzyme. In contrast, treatments with 7‐nitroindazole (7‐NI, a specific inhibitor of neuronal nitric oxide synthase), sodium vanadate (NaV, a non‐specific inhibitor of phosphatases), and N‐acetyl‐cysteine (NAC, an antioxidant) had no effect on AA‐induced changes in ChAT activity. The protein synthesis inhibitor cycloheximide completely blocked AA‐mediated increase in ChAT activity. These results indicate that the AA‐evoked increase in ChAT activity in spinal cord neurons is mediated by PKC, presumably at the transcriptional level.
Systemic serotonin sulfate in opisthobranch mollusks
Authors: Stuart Jeffrey N. , Ebaugh Jason D. , Copes Ashley L. , Hatcher Nathan G. , Gillette Rhanor , Sweedler Jonathan V. 
Published: July 2004

AbstractSerotonin (5‐hydroxytryptamine, 5‐HT) is a ubiquitous modulatory neurotransmitter with roles as a neurohormone and neurotransmitter. However, few studies have been performed characterizing this molecule and its related metabolites in circulating fluids. Here, we demonstrate native 5‐HT sulfate, but much lower levels of 5‐HT, in hemolymph of the marine mollusk Pleurobranchaea californica. The metabolite 5‐HT sulfate forms from 5‐HT uptake and metabolism in central ganglia of Aplysia californica and in the visceral nerve and eye of Pleurobranchaea, but not in hemolymph itself. In addition, 5‐hydroxyindole acetic acid (5‐HIAA), while not detected in hemolymph, forms in higher quantities than does 5‐HT sulfate in the eye and visceral nerve, and γ‐glu‐5‐HT is also observed in this area but never in hemolymph. As systemic 5‐HT sulfate appears not to originate from the optic region or from systemic 5‐HT, 5‐HT sulfate likely derives from the nervous system. Circulating 5‐HT sulfate is at least 10‐fold higher during the light portion of a 12 : 12‐h light/dark cycle than during the dark portion (p < 0.0007), but there is no obvious trend for free systemic tryptophan (Trp) (p > 0.3) in Pleurobranchaea. 5‐HT in mollusks is associated with general arousal state; thus, diurnal systemic changes in a 5‐HT catabolite may reflect a regulatory role for indole catabolism in behavioral rhythms.