bluuebunny/crossref_metadata_2025_split huggingface dataset:
The tension‐free vaginal tape in older women
Authors: Karantanis Emmanuel , Fynes Michelle M. , Stanton Stuart L. 
Published: July 2004

Objective  To evaluate peri‐operative morbidity, continence outcome and patient satisfaction in older women (≥65 years) compared with younger women undergoing tension‐free vaginal tape.Design  Case controlled study.Setting  Tertiary Urogynaecology Unit.Sample  Women undergoing tension‐free vaginal tape for urodynamic stress incontinence between July 1999 and July 2002 were included. Those with detrusor overactivity, voiding difficulty at urodynamics or requiring concomitant prolapse surgery were excluded.Methods  Older women were case matched to a younger cohort for BMI, parity, mode of anaesthesia and whether it was a primary or secondary continence procedure.Main outcome measures  Operative morbidity and continence outcome were assessed at six weeks. After a minimum six months follow up, patient satisfaction and continence outcome were assessed using the Genitourinary Treatment Satisfaction Score (GUTSS).Results  The median hospital stay was one day and overall urinary tract infection rate was similar in both groups. Post‐operative voiding difficulty rates were 3% in older versus 15% in younger women (P= 0.09). At six weeks, 65% of older versus 79% of younger women were dry (P= 0.2). At a median of 12 months, 15 (45%) of older versus 24 (73%) of younger women had no urinary symptoms (P= 0.05). Median GUTSS scores for satisfaction with continence outcome were lower for older 90% compared with 100% in younger women (P= 0.003).Conclusions  Tension‐free vaginal tape is an effective continence intervention in older women but has a lower continence satisfaction rate compared with younger women.
Transvaginal repair of anterior and posterior compartment prolapse with Atrium polypropylene mesh
Authors: Dwyer Peter L. , O'Reilly Barry A. 
Published: July 2004

Objective  To determine the efficacy and safety of a new technique using Atrium polypropylene mesh (Atrium, Hudson, New Hampshire, USA) as an overlay graft for repair of large or recurrent anterior and posterior compartment prolapse.Design  A retrospective review of women who had vaginal prolapse surgery with Atrium mesh reinforcement.Setting  Tertiary referral urogynaecology unit in Australia.Population  Forty‐seven women where mesh was placed under the bladder base with lateral extensions onto the pelvic sidewall, 33 women where a Y‐shaped mesh was placed from the sacrospinous ligaments to the perineal body and 17 women who had mesh placement in both compartments.Methods  Women were assessed by site‐specific vaginal examination pre‐operatively and post‐operatively at six weeks, six months and two years.Main outcome measures  All complications. Rate of recurrent prolapse assessed by the Baden–Walker halfway classification system.Results  Mean follow up was 29 months (range 6 to 52). Four of 64 women with anterior mesh placement (6%) developed a grade 2 asymptomatic cystocele. Five women (5%) required further surgery for recurrent prolapse at a non‐mesh site. Erosion occurred in nine women (9%). Three healed after intravaginal oestrogen cream, five after excision of exposed mesh and vaginal closure and one woman also had surgical closure of a rectovaginal fistula. The risk of mesh erosion decreased over the study period. Urinary, coital and bowel symptoms were significantly improved following surgery.Conclusions  This technique shows promise in correcting pelvic organ prolapse. Vaginal mesh erosion is the most common complication and is related to surgical experience.
Emergency contraceptive pills in Sweden: evaluation of an information campaign
Authors: Larsson Margareta , Eurenius Karin , Westerling Ragnar , Tydén Tanja 
Published: July 2004

Objective  To evaluate a community‐based intervention regarding emergency contraceptive pills, including a mass media campaign and information to women visiting family planning clinics.Design  Quasi‐experimental.Setting  Two counties in Sweden.Population  Eight hundred randomly selected women aged 16–30 years, 400 women in the intervention group and 400 in a comparison group.Methods  Postal questionnaires before (2002) and after (2003) the intervention.Main outcome measures  Exposure to the intervention, knowledge, attitudes, practices and intention to use emergency contraceptive pills.Results  Before the intervention, the response rate was 71% (n= 564); after the intervention, the corresponding figure was 83% (n= 467); overall response rate 58%. Two‐thirds (64%) of the targeted women had noticed the information campaign. One out of six who had visited a family planning clinic during the intervention year recalled being given information about emergency contraceptive pills. Specific knowledge and attitudes improved over time in both groups, but there was no difference in change between the groups. The proportion of women who had used emergency contraceptive pills increased from 27% to 31% over time. Intention to use emergency contraceptive pills in case of need was reported by 74% of the women and remained stable over time, but logistic regression showed that information during the previous year contributed to willingness to use the method in the intervention group.Conclusions  Knowledge, attitudes and practices about emergency contraceptive pills increased in both groups. Emergency contraceptive pills is gradually becoming a more widely known, accepted and used contraceptive method in Sweden, a trend that may have limited the impact of the intervention.
Is home‐based administration of prostaglandin safe and feasible for medical abortion? Results from a multisite study in Vietnam
Authors: Ngoc Nguyen Thi Nhu , Nhan Vu Quy , Blum Jennifer , Mai Tran Thi Phuong , Durocher Jill M. , Winikoff Beverly 
Published: July 2004

Objectives  To study the efficacy and acceptability of a simplified medical abortion regimen in Vietnam.Design  Open‐label study.Setting  One peri‐urban and three urban hospitals and four urban maternal–child health family planning clinics located in Northern, Central and Southern Vietnam.Sample  A total of 1601 women seeking abortion services from January 2001 to December 2001.Methods  Consenting women presenting for abortion services with gestations less than 56 days LMP who met the inclusion criteria were given 200 mg mifepristone and offered the choice of either home or clinic administration of 400 μg oral misoprostol two days later.Main outcome measure  Complete abortion rate of 89.2% (n= 1395), with 1.5% (n= 24) of the women lost to follow up. The majority of women (>90%) reported that their medical abortion experience was either ‘very satisfactory’ or ‘satisfactory’.Results  There was a strong preference for home administration of misoprostol, with more than four‐fifths of the study population selecting to administer the prostaglandin at home. Location of misoprostol administration did not affect efficacy rate. Regardless of location selected, women expressed a high degree of satisfaction with the medical abortion experience.Conclusions  Medical abortion with the option of home administration of misoprostol is safe and feasible for introduction into the Vietnamese healthcare system.
Molecular characterization of neurohybrid cell death induced by Alzheimer's amyloid‐β peptides via p75NTR/PLAIDD
Authors: Hashimoto Yuichi , Kaneko Yuka , Tsukamoto Emi , Frankowski Harald , Kouyama Keisuke , Kita Yoshiko , Niikura Takako , Aiso Sadakazu , Bredesen Dale E. , Matsuoka Masaaki , Nishimoto Ikuo 
Published: July 2004

AbstractOne of the most important pathological features of Alzheimer's disease (AD) is extracellular senile plaques, whose major component is amyloid‐β peptides (Aβ). Aβ binds to the extracellular domain of p75NTR (p75 neurotrophin receptor) and induces neuronal cell death. We investigated the molecular mechanism of Aβ‐induced neurotoxicity in detail from the standpoint of interaction between p75NTR and its recently identified relative, PLAIDD (p75‐like apoptosis‐inducing death domain). Using F11 neuronal hybrid cells, we demonstrate that there are two distinct pathways for Aβ‐induced toxicity mediated by p75NTR. One pathway that has been previously elucidated, is mediated by p75NTR, Go, JNK, NADPH oxidase and caspase3‐related caspases. We found that PLAIDD and Gi proteins, heterotrimeric G proteins, are involved in the alternative Aβ‐induced neurotoxicity mediated by p75NTR. The alternative pathway triggered by Aβ is thus mediated by p75NTR, PLAIDD, Gi, JNK, NADPH oxidase and caspase3‐related caspases. In addition, we found that HN, ADNF, IGF‐I, or bFGF inhibits both pathways of Aβ‐induced neurotoxicity mediated by p75NTR.
In vivo activation of insulin receptor tyrosine kinase by melatonin in the rat hypothalamus
Authors: Anhê Gabriel F. , Caperuto Luciana C. , Pereira‐Da‐Silva Marcio , Souza Lilian C. , Hirata A. Emiko , Velloso Lício A. , Cipolla‐Neto José , Carvalho Carla R. O. 
Published: July 2004

AbstractMelatonin is the pineal hormone that acts via a pertussis toxin‐sensitive G‐protein to inhibit adenylate cyclase. However, the intracellular signalling effects of melatonin are not completely understood. Melatonin receptors are mainly present in the suprachiasmatic nucleus (SCN) and pars tuberalis of both humans and rats. The SCN directly controls, amongst other mechanisms, the circadian rhythm of plasma glucose concentration. In this study, using immunoprecipitation and immunoblotting, we show that melatonin induces rapid tyrosine phosphorylation and activation of the insulin receptor β‐subunit tyrosine kinase (IR) in the rat hypothalamic suprachiasmatic region. Upon IR activation, tyrosine phosphorylation of IRS‐1 was detected. In addition, melatonin induced IRS‐1/PI(3)‐kinase and IRS‐1/SHP‐2 associations and downstream AKT serine phosphorylation and MAPK (mitogen‐activated protein kinase) phosphorylation, respectively. These results not only indicate a new signal transduction pathway for melatonin, but also a potential cross‐talk between melatonin and insulin.
Inhibition of the E2F‐1/p53/Bax pathway by tauroursodeoxycholic acid in amyloid β‐peptide‐induced apoptosis of PC12 Cells
Authors: Ramalho Rita M. , Ribeiro Paulo S. , Solá Susana , Castro Rui E. , Steer Clifford J. , Rodrigues Cecília M. P. 
Published: July 2004

AbstractAmyloid β‐peptide (Aβ)‐induced cell death may involve activation of the E2F‐1 transcription factor and other cell cycle‐related proteins. In previous studies, we have shown that tauroursodeoxycholic acid (TUDCA), an endogenous bile acid, modulates Aβ‐induced apoptosis by interfering with crucial events of the mitochondrial pathway. In this study, we examined the role of E2F and p53 activation in the induction of apoptosis by Aβ, and investigated novel molecular targets for TUDCA. The results showed that despite Bcl‐2 up‐regulation, PC12 neuronal cells underwent significant apoptosis after incubation with the active fragment Aβ (25–35), as assessed by DNA fragmentation, nuclear morphology and caspase‐3‐like activation. In addition, transcription through the E2F‐1 promoter was significantly induced and associated with loss of the retinoblastoma protein. In contrast, levels of E2F‐1, p53 and Bax proteins were markedly increased. Overexpression of E2F‐1 in PC12 cells was sufficient to induce p53 and Bax proteins, as well as nuclear fragmentation. Notably, TUDCA modulated Aβ‐induced apoptosis, E2F‐1 induction, p53 stabilization and Bax expression. Further, TUDCA protected PC12 cells against p53‐ and Bax‐dependent apoptosis induced by E2F‐1 and p53 overexpression, respectively. In conclusion, the results demonstrate that Aβ‐induced apoptosis of PC12 cells proceeds through an E2F‐1/p53/Bax pathway, which, in turn, can be specifically inhibited by TUDCA, thus underscoring its potential therapeutic use.
Metabotropic glutamate and dopamine receptors co‐regulate AMPA receptor activity through PKA in cultured chick retinal neurones: effect on GluR4 phosphorylation and surface expression
Authors: Gomes André R. , Cunha Paulo , Nuriya Mutsuo , Faro Carlos J. , Huganir Richard L. , Pires Euclides V. , Carvalho Ana Luísa , Duarte Carlos B. 
Published: July 2004

AbstractGlutamate receptor phosphorylation has been implicated in several forms of modulation of synaptic transmission. It has been reported that protein kinase A (PKA) can phosphorylate the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA) receptor subunit GluR4 on Ser842, both in vitro and in vivo. Here, we studied the regulation of GluR4 phosphorylation and intracellular trafficking by PKA and by metabotropic receptors coupled to adenylyl cyclase (AC), in cultured chick retinal amacrine‐like neurones, which are enriched in GluR4. The regulation of AMPA receptor activity by PKA and by metabotropic AC‐coupled receptors was also investigated by measuring the [Ca2+]i response to kainate in Na+‐free medium. Stimulation of AC with forskolin (FSK), or using the selective agonist of dopamine D1 receptors (±)‐1‐phenyl‐2,3,4,5‐tetrahydro‐(1H)‐3‐benzazepine‐7,8‐diol (SKF38393), increased the [Ca2+]i response to kainate, GluR4 phosphorylation at Ser842 and GluR4 surface expression. Pre‐incubation of the cells with (2S,2′R,3′R)‐2‐(2′,3′‐dicarboxycyclopropyl)glycine (DCG‐IV), an agonist of group II metabotropic glutamate receptors (mGluR), which are coupled to inhibition of AC, inhibited the effect of FSK and of SKF38393 on AMPA receptor activity, GluR4 phosphorylation and expression at the plasma membrane. These results indicate that there is a functional cross‐talk between dopamine D1 receptors and group II mGluR in the regulation of GluR4 phosphorylation and AMPA receptor activity. Our data show that GluR4 phosphorylation at Ser842 by PKA, and its recruitment to the plasma membrane upon phosphorylation, is regulated by metabotropic receptors.
Insulin receptor substrate of 53 kDa links postsynaptic shank to PSD‐95
Authors: Soltau Michaela , Berhörster Kerstin , Kindler Stefan , Buck Fritz , Richter Dietmar , Kreienkamp Hans‐Jürgen 
Published: July 2004

AbstractThe insulin receptor substrate of 53 kDa (IRSp53) is a target of the small GTPase cdc42 which is strongly enriched in the postsynaptic density of excitatory synapses. IRSp53 interacts with the postsynaptic shank1 scaffolding molecule in a cdc42 regulated manner. The functional significance of the cdc42/IRSp53 pathway in postsynaptic sites is however, unclear. Here we identify PSD‐95 as a second synaptic interaction partner of IRSp53. Interaction is mediated by a C‐terminal PDZ binding motif in IRSp53 and the second PDZ domain of PSD‐95. In HEK cells, overexpressed IRSp53 induces filopodia and targets PSD‐95 into these processes. Immunoprecipitation and immunocytochemistry experiments demonstrate that the interaction occurs at postsynaptic sites in the brain. By virtue of its PDZ‐binding and SH3 domains, IRSp53 is capable of inducing the formation of a triple complex (shank1/IRSp53/PSD‐95).
Neuronal expression of myeloperoxidase is increased in Alzheimer's disease
Authors: Green Pattie S. , Mendez Armando J. , Jacob Jason S. , Crowley Jan R. , Growdon Whit , Hyman Bradley T. , Heinecke Jay W. 
Published: July 2004

AbstractMyeloperoxidase, a heme protein expressed by professional phagocytic cells, generates an array of oxidants which are proposed to contribute to tissue damage during inflammation. We now report that enzymatically active myeloperoxidase and its characteristic amino acid oxidation products are present in human brain. Further, expression of myeloperoxidase is increased in brain tissue showing Alzheimer's neuropathology. Consistent with expression in phagocytic cells, myeloperoxidase immunoreactivity was present in some activated microglia in Alzheimer brains. However, the majority of immunoreactive material in brain localized with amyloid plaques and, surprisingly, neurons including granule and pyramidal neurons of the hippocampus. Confirming neuronal localization of the enzyme, several neuronal cell lines as well as primary neuronal cultures expressed myeloperoxidase protein. Myeloperoxidase mRNA was also detected in neuronal cell lines. These results reveal the unexpected presence of myeloperoxidase in neurons. The increase in neuronal myeloperoxidase expression we observed in Alzheimer disease brains raises the possibility that the enzyme contributes to the oxidative stress implicated in the pathogenesis of the neurodegenerative disorder.
Frame‐shifted amyloid precursor protein found in Alzheimer's disease and Down's syndrome increases levels of secreted amyloid β40
Authors: Van Dijk R. , Fischer D. F. , Sluijs J. A. , Sonnemans M. A. F. , Hobo B. , Mercken L. , Mann D. M. A. , Hol E. M. , Van Leeuwen F. W. 
Published: July 2004

AbstractFrame‐shifted amyloid precursor protein (APP+1), which has a truncated out‐of‐frame C‐terminus, accumulates in the neuropathological hallmarks of patients with Alzheimer's disease pathology. To study a possible involvement of APP+1 in the pathogenesis of Alzheimer's disease, we expressed APP695 and APP+1 in the HEK293 cell‐line and studied whether the processing of APP695 was affected. APP+1 is a secretory protein, but high expression of APP695 and APP+1 results in the formation of intracellular aggregate‐like structures containing both proteins and Fe65, an adaptor protein that interacts with APP695. APP+1 is shown to interact with APP695, suggesting that these structures consist of functional protein complexes. Such an interaction can also be anticipated in post‐mortem brains of young Down's syndrome patients without any sign of neuropathology. Here we observed APP+1 immunoreactivity in beaded fibres. Additional support for functional consequences on the processing of APP695 comes from a 1.4‐fold increase in levels of secreted amyloid β40 in cells co‐expressing APP695 and APP+1, although APP+1 itself does not contain the amyloid β sequence. Taken together, these data show that co‐expression of APP695 and APP+1 affects the processing of APP695 in a pro‐amyloidogenic way and this could gradually contribute to Alzheimer's disease pathology, as has been implicated in Down's syndrome patients.
Neuronal A1 receptors mediate increase in extracellular kynurenic acid after local intrastriatal adenosine infusion
Authors: Wu Hui‐Qiu , Fuxe Kjell , Schwarcz Robert 
Published: July 2004

AbstractThe naturally occurring purine nucleoside adenosine has pronounced anticonvulsant and neuroprotective properties and plays a neuromodulatory role in the CNS. Kynurenic acid (KYNA) is an astrocyte‐derived, endogenous neuroinhibitory compound, which shares several of adenosine's properties. In a first attempt to examine possible interactions between these two biologically active molecules, adenosine was focally applied into the striatum of freely moving rats by reverse microdialysis, and changes in extracellular KYNA were monitored over time. A 2‐h infusion of adenosine increased KYNA levels in a dose‐dependent manner, with 10 mm of adenosine causing a twofold elevation within 1 h. This effect was reversible and was effectively blocked by coinfusion of the specific A1 adenosine receptor antagonist 8‐cyclopentyltheophylline (100 µm). In contrast, coinfusion of adenosine with MSX‐3 (100 µm), an A2A receptor antagonist, did not affect the adenosine‐induced increase in KYNA levels. Local striatal perfusion with the A1 receptor agonist N6‐cyclopentyladenosine (100 µm) mimicked the effect of adenosine, whereas perfusion with the A2A receptor agonist CGS‐21680 (100 µm) was ineffective. Finally, we tested the effect of adenosine (10 mm) on extracellular KYNA in striata that had been injected with quinolinate (60 nmol/1 µL) 7 days earlier. In this neuron‐depleted tissue, perfusion with adenosine failed to affect extracellular KYNA levels. These data demonstrate that adenosine is capable of raising extracellular KYNA in the rat striatum by interacting with postsynaptic neuronal A1 receptors. This mechanism may result in a synergism between the neurobiological effects of adenosine and KYNA.
Oligomeric potential of the M2 muscarinic cholinergic receptor
Authors: Park Paul S.‐H. , Wells James W. 
Published: July 2004

AbstractG protein‐coupled receptors are known to exist as oligomers. Although such aggregates often are referred to as dimers, there is little direct evidence regarding their oligomeric size. In the present investigation, c‐Myc‐, FLAG‐, and influenza hemagglutinin (HA)‐tagged forms of the M2 muscarinic receptor have been coexpressed in Sf9 cells to probe for aggregates larger than a dimer. Immunochromatography, immunoprecipitation, and immunoblotting were carried out with various combinations of antibodies directed against the different epitopes to demonstrate that all three tagged forms of the receptor can be immunopurified within a single complex. Extracts of the M2 muscarinic receptor from Sf9 cells therefore contain aggregates that are at least trimeric, and the levels detected point to the existence of larger complexes. The data also suggest that the oligomers coexist with a sizeable population of monomers.
Functional expression of rat ABCG2 on the luminal side of brain capillaries and its enhancement by astrocyte‐derived soluble factor(s)
Authors: Hori Satoko , Ohtsuki Sumio , Tachikawa Masanori , Kimura Norihisa , Kondo Tetsu , Watanabe Masahiko , Nakashima Emi , Terasaki Tetsuya 
Published: July 2004

AbstractThe purpose of the present study was to clarify the expression, transport properties and regulation of ATP‐binding cassette G2 (ABCG2) transporter at the rat blood–brain barrier (BBB). The rat homologue of ABCG2 (rABCG2) was cloned from rat brain capillary fraction. In rABCG2‐transfected HEK293 cells, rABCG2 was detected as a glycoprotein complex bridged by disulfide bonds, possibly a homodimer. The protein transported mitoxantrone and BODIPY‐prazosin. In rat brain capillary fraction, rABCG2 protein was also detected as a glycosylated and disulfide‐linked complex. Immunohistochemical analysis revealed that rABCG2 was localized mainly on the luminal side of rat brain capillaries, suggesting that rABCG2 is involved in brain‐to‐blood efflux transport. For the regulation study, conditionally immortalized rat brain capillary endothelial (TR‐BBB13), astrocyte (TR‐AST4) and pericyte (TR‐PCT1) cell lines were used as an in vitro BBB model. Following treatment of TR‐BBB13 cells with conditioned medium of TR‐AST4 cells, the Ko143 (an ABCG2‐specific inhibitor)‐sensitive transport activity and rABCG2 mRNA level were significantly increased, whereas conditioned medium of TR‐PCT1 cells had no effect. These results suggest that rat brain capillaries express functional rABCG2 protein and that the transport activity of the protein is up‐regulated by astrocyte‐derived soluble factor(s) concomitantly with the induction of rABCG2 mRNA.