bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk factors in predicting a poor response to sildenafil citrate in elderly men with erectile dysfunction
Authors: Park Kwanjin , Ku Ja Hyun , Kim Soo Woong , Paick Jae‐Seung 
Published: January 2005

OBJECTIVETo assess the clinical efficacy of sildenafil and the potential predictors of poor response to sildenafil in elderly patients with erectile dysfunction (ED).PATIENTS AND METHODSThe study included 162 patients (aged ≥ 60 years) treated with sildenafil for at least 8 weeks; all patients were evaluated with a history, physical examination, measurement of total testosterone and a pharmacological erection test. Sexual function before and 8 weeks after treatment was assessed using the self‐administered International Index of Erectile Function (IIEF). Treatment was considered successful when the patient attained a higher grade on the erectile function (EF) domain score, and an affirmative response to the overall assessment question. Factors influencing treatment outcome were evaluated by univariate and multivariate statistical analysis.RESULTSThe overall efficacy with sildenafil was 47% (76/162). On univariate analysis, uncontrolled diabetes, current smoking, hypogonadism (<3 µg/L testosterone) and low pretreatment EF domain score (<17) were selected as predictors of a poor response. On multivariate logistic regression, a low pretreatment EF domain score was the strongest independent prognostic factor for a poor response (odds ratio 2.25, 95% confidence interval, 1.45–7.33), and this was followed by hypogonadism (1.89, 1.12–3.16) and current smoking (1.34, 1.04–3.52).CONCLUSIONIn a real clinical setting, sildenafil was effective for about half of the elderly men. The baseline EF domain score, hypogonadism and current smoking were significantly associated with failure of sildenafil. These results suggest that modifying reversible risk factors, e.g. stopping smoking and replacing testosterone, would be beneficial in augmenting the efficacy of sildenafil in elderly men.
Anti‐tumour activity of heat‐shock protein 60‐recognizing CD4+ T cells against syngeneic murine renal cell carcinoma
Authors: Eto Masatoshi , Harada Mamoru , Tatsugami Katsunori , Harano Masahiko , Koga Hirofumi , Matsuzaki Goro , Naito Seiji 
Published: January 2005

OBJECTIVESTo determine whether heat‐shock protein (HSP) 60‐recognizing CD4+ T cells show antitumour activity against renal carcinoma (RENCA) cells, as HSP is highly expressed by tumour cells and induced in cells by various stresses, including transformation.MATERIALS AND METHODSRENCA, a renal cortical adenocarcinoma cell line of BALB/c origin, was used. Expression of major histocompatibility complex (MHC) class I, class II and HSP‐60 on RENCA tumour cells was analysed by flow cytometry. BASL1.1, an autoreactive T‐helper type 1 type CD4+ T cell clone established by us, and that recognises HSP‐60, was also used for a tumour‐neutralising assay.RESULTSThe RENCA cells were negative for MHC class II, but expressed intracellular HSP‐60. In the tumour‐neutralising assay, BASL1.1 cells significantly suppressed the in vivo growth of RENCA cells. Three of five mice rejected RENCA cells when co‐inoculated with BASL1.1 cells.CONCLUSIONSThese results indicate that HSP‐60‐recognizing CD4+ T cells have the potential to eliminate renal cell carcinoma in vivo and that the eliciting of an anti‐self T cell response at the tumour site can lead to regression of renal cancer.
Ferulic acid ethyl ester protects neurons against amyloid β‐ peptide(1–42)‐induced oxidative stress and neurotoxicity: relationship to antioxidant activity
Authors: Sultana Rukhsana , Ravagna Agrippino , Mohmmad‐Abdul Hafiz , Calabrese Vittorio , Butterfield D. Allan 
Published: February 2005

AbstractAlzheimer's disease (AD) is neuropathologically characterized by depositions of extracellular amyloid and intracellular neurofibrillary tangles, associated with loss of neurons in the brain. Amyloid β‐peptide (Aβ) is the major component of senile plaques and is considered to have a causal role in the development and progress of AD. Several lines of evidence suggest that enhanced oxidative stress and inflammation play important roles in the pathogenesis or progression of AD. The present study aimed to investigate the protective effects of ethyl‐4‐hydroxy‐3‐methoxycinnamic acid (FAEE), a phenolic compound which shows antioxidant and anti‐inflammatory activity, on Aβ(1–42)‐induced oxidative stress and neurotoxicity. We hypothesized that the structure of FAEE would facilitate radical scavenging and may induce protective proteins. Aβ(1–42) decreases cell viability, which was correlated with increased free radical formation, protein oxidation (protein carbonyl, 3‐nitrotyrosine), lipid peroxidation (4‐hydroxy‐2‐trans‐nonenal) and inducible nitric oxide synthase. Pre‐treatment of primary hippocampal cultures with FAEE significantly attenuated Aβ(1–42)‐induced cytotoxicity, intracellular reactive oxygen species accumulation, protein oxidation, lipid peroxidation and induction of inducible nitric oxide synthase. Treatment of neurons with Aβ(1–42) increases levels of heme oxygenase‐1 and heat shock protein 72. Consistent with a cellular stress response to the Aβ(1–42)‐induced oxidative stress, FAEE treatment increases the levels of heme oxygenase‐1 and heat shock protein 72, which may be regulated by oxidative stresses in a coordinated manner and play a pivotal role in the cytoprotection of neuronal cells against Aβ(1–42)‐induced toxicity. These results suggest that FAEE exerts protective effects against Aβ(1–42) toxicity by modulating oxidative stress directly and by inducing protective genes. These findings suggest that FAEE could potentially be of importance for the treatment of AD and other oxidative stress‐related diseases.
Attenuated microglial activation mediates tolerance to the neurotoxic effects of methamphetamine
Authors: Thomas David M. , Kuhn Donald M. 
Published: February 2005

AbstractMethamphetamine causes persistent damage to dopamine nerve endings of the striatum. Repeated, intermittent treatment of mice with low doses of methamphetamine leads to the development of tolerance to its neurotoxic effects. The mechanisms underlying tolerance are not understood but clearly involve more than alterations in drug bioavailability or reductions in the hyperthermia caused by methamphetamine. Microglia have been implicated recently as mediators of methamphetamine‐induced neurotoxicity. The purpose of the present studies was to determine if a tolerance regimen of methamphetamine would attenuate the microglial response to a neurotoxic challenge. Mice treated with a low‐dose methamphetamine tolerance regimen showed minor reductions in striatal dopamine content and low levels of microglial activation. When the tolerance regimen preceded a neurotoxic challenge of methamphetamine, the depletion of dopamine normally seen was significantly attenuated. The microglial activation that occurs after a toxic methamphetamine challenge was blunted likewise. Despite the induction of tolerance against drug‐induced toxicity and microglial activation, a neurotoxic challenge with methamphetamine still caused hyperthermia. These results suggest that tolerance to methamphetamine neurotoxicity is associated with attenuated microglial activation and they further dissociate its neurotoxicity from drug‐induced hyperthermia.
The mesolimbic dopaminergic response to novel palatable food consumption increases dopamine‐D1 receptor‐mediated signalling with complex modifications of the DARPP‐32 phosphorylation pattern
Authors: Rauggi Riccardo , Scheggi Simona , Cassanelli Anna , De Montis Maria Graziella , Tagliamonte Alessandro , Gambarana Carla 
Published: February 2005

AbstractAcute cocaine administration increases extraneuronal dopamine and Thr34 phosphorylation of dopamine‐ and cAMP‐regulated phosphoprotein (Mr 32 kDa; DARPP‐32) in striatal and cortical areas. Novel palatable food consumption increases extraneuronal dopamine in the same areas. We examined the DARPP‐32 phosphorylation pattern in food non‐deprived rats at different times after vanilla sugar consumption. The phosphorylation state of DARPP‐32 and two cAMP‐dependent protein kinase (PKA) substrates, GluR1 and NR1, were detected by immunoblotting. Thirty to 45 min after vanilla sugar consumption, phospho‐Thr34 DARPP‐32, GluR1 and NR1 levels increased in the nucleus accumbens, and phospho‐Thr75 DARPP‐32 levels decreased. At 60 min, all parameters returned to baseline values. However, 2 and 3 h after vanilla sugar consumption, phospho‐Thr34 DARPP‐32 levels decreased, while phospho‐Thr75 DARPP‐32 levels increased. In contrast to the pattern observed in the NAcS, no delayed changes in DARPP‐32 phosphorylation were observed in the mPFC. Both early and delayed DARPP‐32, GluR1 and NR1 phosphorylation changes were prevented by a dopamine D1 receptor antagonist administration. The delayed modifications in nucleus accumbens DARPP‐32 phosphorylation were prevented by an mGluR5 antagonist administration. The mesolimbic dopaminergic response to an unfamiliar taste is correlated to a gustatory memory trace development, and the observed changes in DARPP‐32 phosphorylation may be part of this process.
Tech: a RhoA GEF selectively expressed in hippocampal and cortical neurons
Authors: Marx Ruth , Henderson Jennifer , Wang James , Baraban Jay M. 
Published: February 2005

AbstractRecent studies implicating the Rho family of small G proteins in the regulation of neuronal morphology have focused attention on identifying key components of Rho signaling pathways in neurons. To this end, we have conducted studies aimed at defining the localization and function of Tech, a Rho guanine nucleotide exchange factor (GEF) family member that is highly enriched in brain. We have found that Tech is selectively expressed in cortical and hippocampal neurons with prominent Tech immunostaining apparent in the cell bodies and dendrites of these cells. In vitro studies with prototypical members of the major Rho subfamilies, RhoA, Rac1 and Cdc42, indicate that Tech binds selectively to and activates RhoA. To assess whether Tech may be involved in the regulation of neuronal morphology, we examined the effects of Tech constructs on the morphology of cortical neurons grown in primary culture. We found that a constitutively active Tech construct, Tech 245ΔC, decreases the number of dendritic processes present on these neurons. This reduction appears to be mediated by activation of RhoA as it is blocked by insertion of a point mutation into the DH domain of Tech which blocks its ability to activate RhoA or coexpression of a dominant negative RhoA construct. As Tech protein levels increase during post‐natal development and remain at peak levels into adulthood, these results indicate that Tech regulates RhoA signaling pathways in developing and mature forebrain neurons.
Neurofilament‐light increases the cell surface expression of the N‐methyl‐d‐aspartate receptor and prevents its ubiquitination
Authors: Ratnam Joseline , Teichberg Vivian I. 
Published: February 2005

AbstractNMDA (N‐methyl‐d‐aspartate) subtype of glutamate receptors are core components of dendritic spine postsynaptic densities (PSDs), in which they are anchored via their carboxy‐terminal tails to cytoskeletal proteins. In this study, we examined the role of the neuronal intermediate filament protein, neurofilament‐light (NF‐L), also a component of the PSD, in the regulation of NMDA receptor (NMDAR) expression and function in a heterologous system. Coexpression of NF‐L with NR1 or NR2B subunits of the NMDAR in HEK293 (human embryonic kidney 293) cells did not result in surface expression as measured by surface biotinylation and cell ELISAs, whereas the combined expression of the three elements resulted in a 20% increase in the surface abundance of NR1, along with a concomitant increase in NMDAR‐mediated cytotoxicity. Investigating the origin of this increase, we found that the NR1 subunits are ubiquitinated in HEK293 cells, and that the coexpression of NF‐L antagonizes this process. These results suggest a possible means of stabilization of NR1 via its association with NF‐L.
Enhancement of glutamate uptake mediates the neuroprotection exerted by activating group II or III metabotropic glutamate receptors on astrocytes
Authors: Yao Hong‐Hong , Ding Jian‐Hua , Zhou Fang , Wang Fang , Hu Li‐Fang , Sun Tao , Hu Gang 
Published: February 2005

AbstractWe investigated whether the activation of astroglial group II and III metabotropic glutamate receptors (mGluRs) could exert neuroprotective effects and whether the neuroprotection was related to glutamate uptake. Our results showed that the activation of astroglial group II or III mGluRs exerted neuroprotection against 1‐methyl‐4‐phenylpyridinium (MPP+) astroglial conditioned medium‐induced neurotoxicity in midbrain neuron cultures. Furthermore, MPP+ decreased glutamate uptake of primary astrocytes and C6 glioma cells, which was recovered by activating group II or III mGluRs. Specific group II or III mGluRs antagonists completely abolished the neuroprotective effects and the enhancement of glutamate uptake of their respective agonists. Our results showed that the primary cultured rat astrocytes and C6 glioma cells expressed receptor proteins for group II mGluR2/3, group III mGluR4, mGluR6 and mGluR7. C6 glioma cells expressed mRNA for group II mGluR3, group III mGluR4, mGluR6, mGluR7 and mGluR8. In conclusion, we confirmed that the activation of astroglial mGluRs exerted neuroprotection, and demonstrated that the mechanism underlying this protective role was at least partially related to the enhancement of glutamate uptake.
Activation of c‐fos by lipopolysaccharide in glial cells via p38 mitogen‐activated protein kinase‐dependent activation of serum or cyclic AMP/calcium response element
Authors: Simi Anastasia , Edling Ylva , Ingelman‐Sundberg Magnus , Tindberg Niclas 
Published: February 2005

AbstractPathological conditions such as ischaemic stroke and inflammatory disorders cause c‐fos activation in the brain. This activation contributes to the initiation of the brain's inflammatory response, orchestrated by activated glial cells. The inflammatory signalling cascades leading to c‐fos activation in glial cells are not well characterized. Thus, we have attempted a detailed analysis of the cis‐acting elements, transcription factors and upstream kinase pathways involved in the activation of c‐fos by lipopolysaccharide (LPS) in primary rat cortical glial cells. We found that (1) LPS‐induced c‐fos mRNA levels were sensitive to p38 mitogen‐activated protein kinase (MAPK) inhibitors but not to mitogen‐activated/extracellular signal‐regulated kinase (ERK) or calcium–calmodulin‐dependent kinase inhibitors, (2) LPS activated both serum response element (SRE) and cyclic AMP/calcium response element (CRE)‐driven luciferase reporters in transient transfection assays, (3) LPS induced the phosphorylation of Elk1 CRE‐binding protein (CREB)/activated transcription factor‐1 (ATF‐1) and the activation of GAL4‐Elk1 and GAL4‐CREB chimeric proteins, and (4) mutation of both SRE and CRE elements was necessary and sufficient to completely abolish LPS induction of a rat c‐fos proximal promoter‐luciferase reporter. Thus, c‐fos activation by LPS in glial cells occurs via the SRE or CRE in an independent manner, and involves the Elk1 or CREB/ATF‐1 transcription factors. Elk1‐mediated transactivation was dependent on p38 MAPK, suggesting a crucial role of these factors in mediating inflammatory responses in the CNS.
Dolichol is the major lipid component of human substantia nigra neuromelanin
Authors: Fedorow Heidi , Pickford Russell , Hook James M. , Double Kay L. , Halliday Glenda M. , Gerlach Manfred , Riederer Peter , Garner Brett 
Published: February 2005

AbstractNeuromelanin is a dark brown pigment present at high concentrations in dopaminergic neurones of the human substantia nigra (SN). Early electron microscopic examinations of neuromelanin fine structure revealed a significant neutral lipid component; however, the identity of this lipid has remained unknown. Here we show that the lipid component of neuromelanin pigment derived from human SN is the polyisoprenoid dolichol. Established methods were used to isolate the pigment from the SN of 32 brains and the lipid fraction was recovered in high purity and yield. Using reversed‐phase HPLC, atmospheric pressure chemical ionization mass spectrometry, and 1H‐ and 13C‐NMR techniques, we showed that the neuromelanin dolichol contained 17–23 isoprenoid units. Dolichol accounted for 14% of the mass of neuromelanin pigment; low levels of other hydrophobic compounds were detected (e.g. ubiquinone‐10, α‐tocopherol and cholesterol together accounted for < 0.5% of the neuromelanin lipid mass). This is the first time that dolichol has been identified in such a physiological setting and significantly advances our understanding of neuromelanin pigment structure and biosynthetic pathways. Furthermore, these studies identify a potential novel role for the isoprenoid pathway in the regulation of neuromelanin function and neurodegeneration within the SN.
Increased leaf reflectance in tropical trees under elevated CO2
Authors: Thomas Sean C. 
Published: February 2005

AbstractGlobally increasing atmospheric CO2 concentrations are known to affect many aspects of plant physiology and development; however, little attention has been given to leaf and canopy optical properties. Three tropical trees in the Leguminosae, an important canopy tree family in many tropical forests, responded similarly to an experimental doubling of CO2 partial pressure with a 9–23% increase in spectral leaf reflectance to light in the visible (400–700 nm) waveband. Decreased leaf chlorophyll content under elevated CO2 may explain part of the observed increase in reflectance. However, analyses that statistically corrected for chlorophyll content effects on reflectance still indicated a significant CO2 effect. This results, in conjunction with the spectral pattern of the response, suggests that the primary mechanism is increased optical masking of chlorophyll under elevated CO2. The magnitude of the increase in leaf reflectance is sufficient to suggest that increased canopy reflectance of tropical forests (and possibly other terrestrial ecosystems) may be an important negative feedback in the response of global net radiative climate forcing to increasing atmospheric CO2.
Mutations in PA2491 (
mexS
) Promote MexT-Dependent
mexEF-oprN
Expression and Multidrug Resistance in a Clinical Strain of
Pseudomonas aeruginosa
Authors: Sobel Mara L. , Neshat Shadi , Poole Keith 
Published: February 2005

ABSTRACT

Disruption of the PA2491 gene in a mini-Tn
5
-
tet
insertion mutant of a clinical isolate of
Pseudomonas aeruginosa
increased expression of the
mexEF-oprN
multidrug efflux genes and decreased production of outer membrane protein OprD, concomitant with enhanced resistance to chloramphenicol, quinolones, and imipenem, which was reminiscent of previously described
nfxC
mutants. PA2491 encodes a probable oxidoreductase previously shown to be positively regulated by the MexT positive regulator of
mexEF-oprN
expression (T. Köhler, S. F. Epp, L. K. Curty, and J. C. Pechére, J. Bacteriol.
181:
6300-6305, 1999). Spontaneous multidrug-resistant mutants of the
P. aeruginosa
clinical isolate hyperexpressing
mexEF-oprN
and showing reduced production of OprD were readily selected in vitro, and all of them were shown to carry mutations in PA2491, highlighting the probable significance of such mutations as determinants of MexEF-OprN-mediated multidrug resistance in vivo.
Ectoine-Induced Proteins in
Sinorhizobium meliloti
Include an Ectoine ABC-Type Transporter Involved in Osmoprotection and Ectoine Catabolism
Authors: Jebbar Mohamed , Sohn-Bösser Linda , Bremer Erhard , Bernard Théophile , Blanco Carlos 
Published: February 2005

ABSTRACT

To understand the mechanisms of ectoine-induced osmoprotection in
Sinorhizobium meliloti
, a proteomic examination of
S. meliloti
cells grown in minimal medium supplemented with ectoine was undertaken. This revealed the induction of 10 proteins. The protein products of eight genes were identified by using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. Five of these genes, with four other genes whose products were not detected on two-dimensional gels, belong to the same gene cluster, which is localized on the pSymB megaplasmid. Four of the nine genes encode the characteristic components of an ATP-binding cassette transporter that was named
ehu
, for ectoine/hydroxyectoine uptake. This transporter was encoded by four genes (
ehuA
,
ehuB
,
ehuC
, and
ehuD
) that formed an operon with another gene cluster that contains five genes, named
eutABCDE
for ectoine utilization. On the basis of sequence homologies,
eutABCDE
encode enzymes with putative and hypothetical functions in ectoine catabolism. Analysis of the properties of
ehuA
and
eutA
mutants suggests that
S. meliloti
possesses at least one additional ectoine catabolic pathway as well as a lower-affinity transport system for ectoine and hydroxyectoine. The expression of
ehuB
, as determined by measurements of UidA activity, was shown to be induced by ectoine and hydroxyectoine but not by glycine betaine or by high osmolality.
Putative Coiled-Coil Structural Elements of the BBA68 Protein of Lyme Disease Spirochetes Are Required for Formation of Its Factor H Binding Site
Authors: McDowell John V. , Harlin Matthew E. , Rogers Elizabeth A. , Marconi Richard T. 
Published: February 2005

ABSTRACT
Factor H and factor H like-protein 1 (FHL-1) are complement regulatory proteins that serve as cofactors for the factor I-mediated cleavage of C3b. Some Lyme disease and relapsing fever spirochete species bind factor H to their surface to facilitate immune evasion. The Lyme disease spirochetes produce several factor H binding proteins (FHBPs) that form two distinct classes. Class I FHBPs (OspE orthologs and paralogs) bind only factor H, while class II FHBPs (BBA68) bind both factor H and FHL-1. BBA68 belongs to a large paralogous protein family, and of these paralogs, BBA69 is the member most closely related to BBA68. To determine if BBA69 can also bind factor H, recombinant protein was generated and tested for factor H binding. BBA69 did not exhibit factor H binding ability, suggesting that among family 54 paralogs, factor H binding is unique to BBA68. To identify the determinants of BBA68 that are involved in factor H binding, truncation and site-directed mutational analyses were performed. These analyses revealed that the factor H binding site is discontinuous and provide strong evidence that coiled-coil structural elements are involved in the formation of the binding site.