bluuebunny/crossref_metadata_2025_split huggingface dataset:
Furo[2,3‐d]pyrimidines and Oxazolo[5,4‐d]pyrimidines as Inhibitors of Receptor Tyrosine Kinases (RTK)
Authors: Martin‐Kohler Andreas , Widmer Jörg , Bold Guido , Meyer Thomas , Séquin Urs , Traxler Peter 
Published: April 2004

AbstractReceptor tyrosine kinases such as VEGFR2 (vascular endothelial growth factor receptor 2, KDR) or EGFR (epidermal growth factor receptor) play crucial roles in a variety of diseases, such as cancer. Recently, some pyrrolopyrimidines were shown to be potent EGFR inhibitors. Therefore, new types of oxazolo[5,4‐d]pyrimidines and furo[2,3‐d]pyrimidines were synthesized (Schemes 1 and 2). Appropriately substituted derivatives of these classes of compounds inhibited VEGFR2 and EGFR with IC50 values in the low nanomolar range (see Table). Generally, the furopyrimidines were somewhat more active than the oxazolopyrimidines. The best inhibitors, 20m, 20p, and 20r, had an IC50 of 3 nM towards EGFR and showed a good selectivity, being distinctly less active towards VEGFR2.
Five New Sesquiterpenoids from Parasenecio petasitoides
Authors: Zhang Hua , Liao Zhi‐Xin , Yue Jian‐Min 
Published: April 2004

AbstractFrom the whole plants of Parasenecio petasitoides, five new sesquiterpenoids were isolated, (E,E)‐3α,9β‐dihydroxy‐6βH,11βH‐13‐norgermacra‐1(10),4‐dien‐11,6‐carbolactone (2), (E,E)‐2α,9β‐dihydroxy‐6βH,11βH‐13‐norgermacra‐1(10),4‐dien‐11,6‐carbolactone (3), (E,E)‐2α,9β‐dihydroxy‐6βH,11αH‐13‐norgermacra‐1(10),4‐dien‐11,6‐carbolactone (4), (E)‐15‐hydroxy‐2‐oxo‐6βH,11αH‐13‐norguaia‐3‐ene‐11,6‐carbolactone (7), and (E)‐11β,15‐dihydroxy‐2‐oxo‐6βH‐13‐norguaia‐3‐ene‐11,6‐carbolactone (8), together with three known compounds, deacetyl herbolide A (1), jacquilenin (5), and (E)‐15‐hydroxy‐2‐oxo‐6βH,11βH‐13‐norguaia‐3‐ene‐11,6‐carbolactone (6). The structures of these natural products were elucidated spectroscopically, especially by 1D‐ and 2D‐NMR techniques, in combination with high‐resolution mass spectroscopy.
Putting error bars on the Ab Initio theoretical estimates of the magnetic coupling constants: The parent compounds of superconducting cuprates as a case study
Authors: Muñoz D. , De Graaf C. , Illas F. 
Published: April 2004

AbstractThe influence of the basis set size and computational method in the calculation of the magnetic coupling constant J is evaluated using a series of cuprate superconductor parent compounds as a case study. The variational DDCI method and an iterative modification, the IDDCI method, are tested, as well as the perturbative CASPT2 method, with two different reference wave functions. Results show that the DDCI magnetic coupling constant is in rather good agreement with the experiment, although it shows a moderate basis set dependency. The IDDCI results are less dependent on the size of the basis set, but slightly overestimate the magnetic coupling constant. CASPT2 results are nearly independent of the chosen basis set. With a minimal active space values are obtained that are about 20% smaller than the DDCI results. The experimental coupling constant can be reproduced when an extended reference wave function is used. © 2004 Wiley Periodicals, Inc. J Comput Chem 10: 1234–1241, 2004
Human FGF‐1 gene transfer promotes the formation of collateral vessels and arterioles in ischemic muscles of hypercholesterolemic hamsters
Authors: Caron Alexis , Michelet Sandrine , Caron Anne , Sordello Sylvie , Ivanov Marie‐Agnès , Delaère Pia , Branellec Didier , Schwartz Bertrand , Emmanuel Florence 
Published: April 2004

AbstractBackgroundAcidic fibroblast growth factor (FGF‐1) has been identified as a potent mitogen for vascular cells, inducing formation of mature blood vessels in vitro and in vivo and represents one of the most promising approaches for the treatment of ischemic cardiovascular diseases by gene therapy. Nevertheless, and most probably due to the few experimental models able to address the issue, no study has described the therapeutic effects of FGF‐1 gene transfer in subjects with peripheral arterial disease (PAD) exhibiting a clinically relevant cardiovascular pathology.MethodsIn order to assess the potency of FGF‐1 gene transfer for therapeutic angiogenesis in ischemic skeletal muscles displaying decreased gene expression levels and sustained impaired formation of collateral vessels and arterioles, we developed a model of PAD in hamsters with a background of hypercholesterolemia. Hamsters fed a cholesterol‐rich diet and subjected to hindlimb ischemia exhibit a sustained impaired angiogenic response, as evidenced by decreased angiographic score and histological quantification of arterioles in the ischemic muscles.ResultsIn this model, we demonstrate that NV1FGF (a human FGF‐1 expression plasmid), given intramuscularly 14 days after induction of hindlimb ischemia, promoted the formation of both collateral vessels and arterioles 14 days after treatment (i.e. 28 days post‐ischemia).ConclusionsOur data provide evidence that NV1FGF can reverse the cholesterol‐induced impairment of revascularization in a hamster model of hindlimb ischemia by promoting the growth of both collateral vessels and arterioles in ischemic muscles exhibiting significantly decreased levels of gene expression compared with control muscles. Therefore, this study underscores the relevance of NV1FGF gene therapy to overcome perfusion defects in patients with PAD. Copyright © 2004 John Wiley & Sons, Ltd.
Commuters and marauders: an examination of the spatial behaviour of serial criminals
Authors: Meaney Rebecca 
Published: April 2004

AbstractThe demographic characteristics of serial offenders that distinguish between the commuter and the marauder offence styles were examined. Proposed by Canter and Larkin (1993) these two styles represent competing models of criminal spatial behaviour under which the home base plays a role in offence site selection. Data on serial burglars, arsonists and sex offenders were extracted from the criminal records maintained by the NSW Police Service. The offence style of each offender's crime series was identified in order to relate the offence style to the demographic variables, and to examine the offender's first and last offences in a series. A commuter offence style was more likely to be adopted by burglars and generally by adult males. A marauding offence style was apparent in sex offenders and metropolitan based offenders. There was a progression in the distance travelled to offend across all crime types, as the last offence was located further from the home base by comparison with the first. These findings serve to validate the conceptual distinction between commuter and marauder offence styles. Several implications for further research are addressed. Copyright © 2004 John Wiley & Sons, Ltd.
Hepatitis B infection of the liver in chronic hepatitis C without detectable hepatitis B virus DNA in serum
Authors: Mariscal Luisa Fernanda , Rodríguez‐Iñigo Elena , Bartolomé Javier , Castillo Inmaculada , Ortiz‐Movilla Nuria , Navacerrada Cristina , Pardo Margarita , Pérez‐Mota Arturo , Graus Javier , Carreño Vicente 
Published: April 2004

AbstractHepatitis B virus (HBV) DNA may persist in the liver in the absence of serum HBV–DNA after a self‐limited acute hepatitis B. This may also occur in patients with chronic hepatitis C virus (HCV) infection but its prevalence and its impact on liver histology is unknown. HBV–DNA was tested by polymerase chain reaction (PCR) and by in situ hybridisation in liver biopsies from 98 patients with chronic hepatitis C who were hepatitis B surface antigen negative and serum HBV–DNA negative by PCR. HBV–DNA resulted positive in the liver of 37/98 (37.7%) patients without serum HBV–DNA. To test whether these patients had serum HBV–DNA levels under the detection limit of the PCR assay used in this study (50 copies/ml), PCR products in which HBV–DNA was undetectable after visualization of agarose gels were analysed by dot‐blot hybridisation. With this method, HBV–DNA was positive in serum of 12/37 patients with liver HBV–DNA. Thus, 25/98 (25.5%) patients have HBV–DNA detectable only in liver. This was confirmed by in situ hybridisation, the percentage of infected hepatocytes ranging from 0.1% to 12%. In patients in whom the HCV infection was shorter than 20 years, HBV infected patients had higher (P = 0.01) fibrosis score (1.64 ± 1.21) than HBV negative cases (0.53 ± 0.66). In conclusion, a significant proportion of patients with chronic HCV infection have HBV–DNA in the liver in the absence of viral DNA in serum. The impact of this finding on liver histology deserves further research. J. Med. Virol. 73:177–186, 2004. © 2004 Wiley‐Liss, Inc.
Prevalence and clinical implications of occult hepatitis B viral infection in hemophilia patients in Japan
Authors: Toyoda Hidenori , Hayashi Kazuhiko , Murakami Yoshiki , Honda Takashi , Katano Yoshiaki , Nakano Isao , Goto Hidemi , Kumada Takashi , Takamatsu Junki 
Published: April 2004

AbstractThe prevalence and clinical implications of occult hepatitis B virus (HBV) infection were investigated in the Japanese patients with hemophilia in whom a high prevalence of infection with transfusion‐transmissible viruses has been reported. HBV DNA was detected in the sera of 22 of 43 (51.2%) patients with hemophilia who were negative for HBV surface antigen (HBs), indicating that these patients had occult HBV infection. No factor, including age, type or severity of hemophilia, presence of HBs or HBV core (HBc) antibody, or coinfection with hepatitis C virus (HCV) or human immunodeficiency virus (HIV) was associated with occult HBV infection, except for high anti‐HBc titer and/or coinfection with HCV genotype 1 (1a or 1b). In general, occult HBV infection did not appear to have significant clinical implications. However, in patients in whom HBV was detected by PCR specific for the surface (S)–region, higher alanine aminotransferase levels were observed. The genotype of the occult HBV in the present study was exclusively the domestic type indigenous to Japan (genotype C), suggesting a different route of transmission for HBV in comparison to HCV and HIV in this population. J. Med. Virol. 73:195–199, 2004. © 2004 Wiley‐Liss, Inc.
Molecular and serological evaluation of surface antigen negative hepatitis B virus infection in blood donors from Venezuela
Authors: Gutiérrez Cristina , Devesa Marisol , Loureiro Carmen Luisa , León Graciela , Liprandi Ferdinando , Pujol Flor Helene 
Published: April 2004

AbstractSurface antigen negative hepatitis B virus (HBV) infection was evaluated in Venezuela, by molecular characterization of blood samples positive for antibodies to core antigen (anti‐HBc) and negative for surface antigen (HBsAg) in blood donors (residual infections). HBV DNA was found in 11/258 samples (4.3%), and was significantly associated with high levels of anti‐HBc antibodies (>25 UI/ml, P < 0.05), while no correlation was found between the presence of HBV DNA and the levels of anti‐HBs. Synonymous and non‐synonymous mutations were found in the HBV surface region (but not vaccine escape mutants) and in the precore/core region (precore mutants in 2/7 samples and 33–45 bp deletions near the N‐terminal core region in 4/19 samples). While HBV genotype F prevails among HBsAg positive samples from blood donors in Venezuela, residual infection isolates were mainly genotypes A and D. Phylogenetic analysis of viral surface and core region revealed discrepancies in genotype designation in 6/9 samples, suggesting the presence of mixed infection or recombination. In conclusion, HBV residual infection in Venezuela does not seem to be frequently observed in HBV genotype F. This type of infection is frequently associated with variants exhibiting mutations in the surface gene that might be affecting the correct recognition by commercial tests, with precore mutants and with core internal deletions. These variants do not seem to cause severe liver disease, and on the contrary, were found circulating at low viremia. J. Med. Virol. 73:200–207, 2004. © 2004 Wiley‐Liss, Inc.
IL‐10 levels in Dengue patients: Some findings from the exceptional epidemiological conditions in Cuba
Authors: Pérez Ana B. , García Gissel , Sierra Beatriz , Alvarez Mayling , Vázquez Susana , Cabrera María V. , Rodríguez Rosmary , Rosario Delfina , Martínez Eric , Denny Thomas , Guzmán María G. 
Published: April 2004

AbstractThe pathogenesis associated with Dengue haemorrhagic fever, has yet to be fully elucidated, with no definitive in vivo evidence. The exceptional epidemiological circumstances in Cuba allow the evaluation of different mediators in a well‐defined situation. In the present study, we describe the determination of levels of IL‐12, IL‐10 and RANTES in the sera of Cuban patients hospitalised with Dengue fever or Dengue haemorrhagic fever. The results showed that levels of serum IL‐10 were higher in patients than controls, and those patients with secondary infections had consistently higher levels. All the Dengue haemorrhagic fever patients had increased levels of IL‐10. In contrast, levels of IL‐12 did not differ between patients and controls. Finally, RANTES serum levels detected in patients were lower than those observed in the controls. The association of increased levels of IL‐10 in Dengue patients with a sequential infection suggests a possible role of this cytokine in the pathogenesis of Dengue disease. J. Med. Virol. 73:230–234, 2004. © 2004 Wiley‐Liss, Inc.
Early inhibition of nitric oxide production increases HSV‐1 intranasal infection
Authors: Gamba Gisela , Cavalieri Hernan , Courreges Maria C. , Massouh Ernesto J. , Benencia Fabian 
Published: April 2004

AbstractHere, we studied the role of nitric oxide (NO) production during the first steps of the respiratory infection of BALB/c mice with herpes simplex virus type 1 (HSV‐1), strain F. Nitric oxide synthase II (NOS‐II) mRNA and protein were detected by reverse transcription (RT)‐PCR and dot blot, respectively in samples of lungs and turbinates early post‐infection (p.i.). Immunohistochemical analysis revealed pulmonar macrophages and PMN expressing NOS‐II in the lungs of infected animals. Animals intranasally treated with aminoguanidine (AG), a NOS inhibitor, during the first steps of infection, showed a dose‐dependent increase in pneumonitis compared to controls. Viral titres in turbinates, lungs, and brains were higher in AG treated mice. Finally, histopathology studies revealed a stronger inflammation in eyes, and lungs of these animals. Taken together, these results suggest a role of NO in controlling primary HSV intranasal infection. J. Med. Virol. 73:313–322, 2004. © 2004 Wiley‐Liss, Inc.
Cyclin‐dependent kinase 5 increases perikaryal neurofilament phosphorylation and inhibits neurofilament axonal transport in response to oxidative stress
Authors: Shea Thomas B. , Zheng Ya‐Li , Ortiz Daniela , Pant Harish C. 
Published: April 2004

AbstractCyclin‐dependent kinase 5 (cdk5) phosphorylates the high molecular weight neurofilament (NF) protein. Overexpression of cdk5 inhibits NF axonal transport and induces perikaryal accumulation of disordered phospho‐NF cables. Experimental and clinical motor neuron disease is characterized by oxidative stress, increased cdk5 activity, and accumulation of phospho‐NFs within perikarya or proximal axons. Because oxidative stress increases cdk5 activity in experimental motor neuron disease, we examined whether oxidative stress induced cdk5‐mediated NF phosphorylation. Treatment of cultured neuronal cells with hydrogen peroxide inhibited axonal transport of green fluorescent protein‐tagged NF subunits and induced perikaryal accumulation of NF phosphoepitopes normally confined to axons. These effects were prevented by treatment with the cdk5 inhibitor roscovitine or transfection with a construct expressing the endogenous cdk5 inhibitor peptide. These findings indicate that oxidative stress can compromise NF dynamics via hyperactivation of cdk5 and suggest that antioxidants may alleviate multiple aspects of neuropathology in motor neuron disease. © 2004 Wiley‐Liss, Inc.
Functional analysis of mouse 3‐phosphoglycerate dehydrogenase (Phgdh) gene promoter in developing brain
Authors: Shimizu Motohiro , Furuya Shigeki , Shinoda Yoko , Mitoma Junya , Okamura Tadashi , Miyoshi Ichiro , Kasai Noriyuki , Hirabayashi Yoshio , Suzuki Yasuo 
Published: April 2004

AbstractD‐3‐Phosphoglycerate dehydrogenase (Phgdh; EC 1.1.1.95) is a necessary enzyme for de novo L‐serine biosynthesis via the phosphorylated pathway. Targeted disruption of the mouse Phgdh gene has been shown to result in embryonic lethality, accompanied by severe abnormalities in brain development. Phgdh is expressed exclusively by neuroepithelium and radial glia in developing brain and later mainly by astrocytes. To elucidate the molecular mechanism that regulates such cell‐type‐specific expression of Phgdh in developing brain, an upstream 3.5‐kilobase‐pair (kbp) region of the gene harboring the promoter was characterized in primary cultures and transgenic mice. Analysis of Phgdh 5′‐nested deletions in transfected cultures indicated that overall reporter luciferase levels were higher in glial cultures than those in neuronal cultures. Although basal promoter activity of the gene appeared to depend on an Sp1 binding sequence residing between –193 and –184 in both glial and neuronal cultures, an upstream 5′‐flanking region between –1,794 and –1,095 contributed to up‐regulation of Phgdh transcription in a glial‐cell‐specific manner. In the cerebral cortex of transgenic mouse embryos, the Phgdh promoter‐LacZ transgene DNA containing –1,794/+4 promoter sequences directed β‐galactosidase (β‐Gal) expression mainly to Phgdh‐positive neuroepithelium and radial glia. This glial preference diminished when β‐Gal expression was driven solely by the upstream 0.2‐kbp minimal promoter. However, glial preference of β‐Gal expression was restored by placing the 700‐base‐pair 5′‐DNA segment upstream of the minimal promoter. These observations suggest the presence of cis‐acting elements that confer the cell type specificity of Phgdh transcription in the distal promoter region. © 2004 Wiley‐Liss, Inc.
Diazoxide preconditioning protects against neuronal cell death by attenuation of oxidative stress upon glutamate stimulation
Authors: Nagy Krisztina , Kis Bela , Rajapakse Nishadi C. , Bari Ferenc , Busija David W. 
Published: April 2004

AbstractWe examined the effects of diazoxide, the putative mitochondrial adenosine triphosphate‐sensitive potassium (mitoKATP) channel opener, against glutamate excitotoxicity in primary cultures of rat cortical neurons. Cells were treated with diazoxide for 24 hr and then exposed to 200 μM glutamate. Cell viability was measured 24 hr after glutamate exposure. We found that treatment 24 hr before glutamate exposure with 250 and 500 μM diazoxide but not with another mitoKATP channel opener, nicorandil, increased neuronal viability from 54 ± 2% to 84 ± 2% and 92 ± 3%, respectively (n = 25–40). These effects were not inhibited by the putative mitoKATP channel blocker 5‐hydroxydecanoic acid. Diazoxide application increased production of reactive oxygen species (ROS) and coapplication of M40401, a superoxide dismutase mimetic, prevented delayed preconditioning. The 24 hr preconditioned neurons showed significantly reduced ROS production upon glutamate stimulation compared to that in untreated cells. These results suggest that diazoxide induces delayed preconditioning in cultured cortical neurons via increased ROS production and attenuation of oxidative stress upon glutamate stimulation. © 2004 Wiley‐Liss, Inc.
17β‐estradiol attenuates glutamate‐induced apoptosis and preserves electrophysiologic function in primary cortical neurons
Authors: Sribnick Eric Anthony , Ray Swapan Kumar , Nowak Mark Walter , Li Li , Banik Naren Lal 
Published: April 2004

AbstractGlutamate toxicity causes neuronal death in neurodegenerative diseases; hence, there is a need for therapeutic agents rendering functional neuroprotection. We tested the effects of 17β‐estradiol (estrogen) in rat primary cortical neurons after glutamate exposure. Wright staining and ApopTag assays indicated that 0.5 μM glutamate for 24 hr caused apoptosis. Glutamate‐induced apoptosis correlated with upregulation of calpain, a proapoptotic shift in the Bax:Bcl‐2 ratio, and increased activation of caspase‐3. Pretreatment with 10 nM estrogen prevented apoptosis, attenuated calpain upregulation, shifted the Bax:Bcl‐2 ratio toward survival, and decreased caspase‐3 activation. Single‐cell voltage‐clamp techniques were used to record whole‐cell currents associated with Na+ channels, N‐methyl‐D‐aspartate receptor channels, and kainate receptor channels. No significant differences were recorded in membrane capacitance at −70 mV in neurons treated with estrogen or estrogen plus glutamate, relative to controls. Notably, no changes in capacitance indicated that neurons treated with estrogen and glutamate did not experience apoptosis‐associated cell shrinkage. No membrane potential could be recorded in the neurons treated with glutamate due to apoptosis. All recorded currents were similar in amplitude and activation/inactivation kinetics in control neurons and neurons treated with estrogen plus glutamate. Estrogen thus preserved both neuronal viability and function in this in vitro glutamate toxicity model. © 2004 Wiley‐Liss, Inc.
Static and Dynamic Light Scattering of Polyelectrolyte/Surfactant Solutions: the Na‐Hyaluronate/(C10TAB) System
Authors: Villetti Marcos A. , Borsali Redouane , Crespo Janaina S. , Soldi Valdir , Fukada Kazuhiro 
Published: April 2004

AbstractSummary: This work discusses the interactions between the anionic polyelectrolyte sodium hyaluronate (Na‐Hy) and the cationic surfactant decyltrimethylammonium bromide (C10TAB). Static and dynamic light scattering experiments were carried out in the single homogenous phases (region I: [C10TAB] < 0.040 M and region III: [C10TAB] > 0.350 M) in “salt‐free” and at different added salt concentrations (NaCl) in order to gain more understanding on the chain conformation and on the dynamics of polyelectrolyte/surfactant systems. In region I, the Na‐Hy “salt‐free” system exhibits the expected polyelectrolyte properties, i.e. the scattering intensity increases with the addition of surfactant or salt. As a consequence of this screening of the electrostatic interactions, a decrease in both the radius of gyration Rg and the second virial coefficient A2 is observed. This decrease is found more pronounced in the presence of surfactant C10TAB than in the case of added salt (Na‐Hy/NaCl). Consequently, the calculated apparent persistence length Lt, assuming a worm‐like chain at high ionic strength, is found about 58 Å in the case of surfactant and Lt = 71 Å in the case of added salt. This result demonstrates clearly that the binding of the surfactant to Na‐Hy is stronger than in the case of added salt and is at the origin of the phase separation that occurs at the concentration of C10TAB > 0.040 M. As far as the dynamic properties are concerned, the autocorrelation functions in “salt‐free” solutions measured in region I are better described by two relaxation modes (intermediate and slow) and by three relaxation modes (fast, intermediate and slow) in region III. The three relaxation modes reflect respectively the dynamics of free micelles (fast mode), association‐dissociation equilibrium of micelle‐like clusters (intermediate mode) and polymer‐micelles adsorption (slow mode). At high ionic strength (added salt) in region III, the micelle diameter increases (fast mode), the intermediate mode disappears and the polymer‐micelles adsorption diffusion coefficient increases due to the screening of the electrostatic interactions.Phase diagram of Na‐Hy polyelectrolyte in C10TAB surfactant and NaCl salt.imagePhase diagram of Na‐Hy polyelectrolyte in C10TAB surfactant and NaCl salt.