bluuebunny/crossref_metadata_2025_split huggingface dataset:
NITROREDUCTASE: A PRODRUG‐ACTIVATING ENZYME FOR CANCER GENE THERAPY
Authors: Searle Peter F , Chen Ming‐Jen , Hu Longqin , Race Paul R , Lovering Andrew L , Grove Jane I , Guise Chris , Jaberipour Mansooreh , James Nicholas D , Mautner Vivien , Young Lawrence S , Kerr David J , Mountain Andrew , White Scott A , Hyde Eva I 
Published: November 2004

SUMMARY1. The prodrug CB1954 (5‐(aziridin‐1‐yl)‐2,4‐dinitrobenzamide) is activated by Escherichia coli nitroreductase (NTR) to a potent DNA‐crosslinking agent.2. Virus‐mediated expression of NTR in tumour cells sensitizes them to CB1954 in vitro and in vivo, providing the basis for a strategy of cancer gene therapy.3. A phase I trial of CB1954 in cancer patients has been completed, documenting the pharmacokinetics and establishing an acceptable dose. Subsequent trials of the replication‐defective adenovirus CTL102 in patients with resectable tumours have documented expression of NTR in injected colorectal liver metastases, hepatocellular carcinoma, head and neck cancer and prostate cancer. Trials combining CTL102 and CB1954 are underway.4. An oncolytic (replication‐competent) adenovirus vector allowed increased expression of NTR in vitro and in a mouse tumour model, resulting in a greater reduction in tumour growth when combined with CB1954 treatment.5. Alternative prodrugs may eventually prove superior to CB1954; a nitroaryl phosphoramide mustard prodrug activated by NTR shows a greater therapeutic index than CB1954 in a human ovarian carcinoma.6. The crystal structure of NTR provided the basis for site‐directed mutagenesis, which has identified a number of mutants with improved kinetics of CB1954 activation. These can provide improved cell sensitization to CB1954. Combinations of these are being tested.7. The basis for a positive selection for improved NTR variants has been demonstrated.
RANDOMIZED TRIAL OF A SINGLE, DOUBLE AND TRIPLE DOSE OF 10 MG/KG OF A HUMAN FORMULATION OF TRICLABENDAZOLE IN PATIENTS WITH FASCIOLIASIS
Authors: Talaie Haleh , Emami Habib , Yadegarinia Davood , Nava‐Ocampo Alejandro A , Massoud Jafar , Azmoudeh Mohammad , Mas‐Coma Santiago 
Published: November 2004

SUMMARY1. A study performed > 10 years ago and case reports published recently suggest that triclabendazole is effective for the treatment of patients with fascioliasis.2. To confirm the efficacy of a human formulation of triclabendazole, we enrolled 165 patients into the present study and divided the subjects into two groups: (i) those who had fascioliasis, as evidenced by the presence of ova in their stools; and (ii) patients with clinical and laboratory data suggesting fascioliasis.3. Patients were randomly allocated to receive 10 mg/kg, p.o., triclabendazole for 1, 2 or 3 days (single‐, double‐ and triple‐dose groups, respectively). Medical history and physical and laboratory examinations were performed at baseline and at 7, 14, 30 and 60 days after treatment. Results were based on 152 patients who completed the study.4. A sharp decrease in the proportion of clinical signs and symptoms was observed in all groups immediately after treatment. Ova disappeared from the stools of all patients in the single‐ and double‐dose groups. Thirty days after treatment, ova were identified in the stools of two patients in the triple‐dose group who received a second course of triclabendazole.5. All cases were cured on day 60. However, the cure rate was lower when the patients with suggestive fascioliasis were included in the analysis. The cure rate was not significantly different (P > 0.05) among the three dose groups. No cases of toxic hepatitis were observed.6. In conclusion, oral administration of 10 mg/kg of the human pharmaceutical preparation of triclabendazole for 1–3 days is safe and effective in the treatment of human fascioliasis.
Reversible cognitive deterioration after a single episode of severe hypoglycaemia: a case report
Authors: Kubiak T. , Kuhr B. , Inselmann D. , Hermanns N. , Kulzer B. , Haak T. 
Published: November 2004

AbstractA case of a male 34‐year‐old Type 1 diabetic patient who experienced a prolonged severe hypoglycaemic episode is presented. After the hypoglycaemic event, the patient suffered from moderate to severe neuropsychological impairments. On the basis of neuropsychological assessment results, diabetes therapy was modified (less complex insulin regimen, fixed insulin doses and fixed carbohydrate distribution). At a follow‐up examination (3 months), presumable complete recovery of cognitive function was observed. This case demonstrates the possible detrimental neuropsychological effects of severe hypoglycaemia, that, in this case, turned out to be reversible. It highlights the clinical implications of impaired cognitive function on self‐care and self‐management abilities and the usefulness of neuropsychological testing in clinical diabetes care.
Feasibility of a quality assurance programme of bedside blood glucose testing in a hospital setting: 7 years’ experience
Authors: Nobels F. , Beckers F. , Bailleul E. , De Schrijver P. , Sierens L. , Van Crombrugge P. 
Published: November 2004

AbstractAims  Description of the long‐term use of a quality assurance (QA) programme for bedside capillary blood glucose (CBG) testing in a general hospital.Methods  The main points of the programme were selection of instrumentation using a standardized testing procedure, design and implementation of a quality control (QC) procedure, and training and motivation of nurses. The QC procedures consisted of a daily aqueous control and a weekly split‐sample control (a measurement on a capillary blood sample using the glucose meter and on a simultaneously drawn venous sample with the laboratory analyser). When the result was out of range, a laboratory technician visited the ward to investigate the problem. All wards received a weekly report.Results  The programme was introduced in 1995 and followed up through 2002. The split‐sample control was more efficient in detecting clinically relevant errors than the aqueous control. Most errors (91–97%) were operator‐related rather than instrument‐related. The compliance with the split‐sample controls remained high, with 84–91% of weekly controls performed over 7 years. Respectively 91, 95 and 96% of the measurements remained within the range of ± 20% of the laboratory value in the years 2000, 2001 and 2002.Conclusion  A QA programme of bedside CBG testing can successfully be implemented. It is feasible to obtain a satisfying level of measurement accuracy and to maintain a high level of compliance with the programme over several years. Split‐sample controls are an essential part of the control procedure.
Electrodermal reactivity and its association to substance use disorders
Authors: Taylor Jeanette 
Published: November 2004

AbstractPoor electrodermal response modulation is associated with substance use disorders, but the specificity of the relationship has not been tested. To test this, 112 college students were assessed for psychiatric symptoms using structured interviews and for ability to modulate skin conductance responses to 2‐s 92‐ or 110‐dB white noise blasts that varied in temporal predictability. Twenty‐eight good and 28 poor modulators were compared on symptoms of alcohol and illicit drug use disorders, personality disorders (antisocial, borderline, histrionic, and narcissistic), social and specific phobia, and depression. As expected, poor modulators had significantly more symptoms of substance use disorders than good modulators. Groups did not differ in symptoms of anxiety disorder, depression, or personality disorders marked by disinhibition. Poor electrodermal response modulation may reflect a biological risk factor for substance use disorders in particular.
P300 amplitude in nonalcoholic adolescent twin pairs who become discordant for alcoholism as adults
Authors: Carlson Scott R. , Iacono William G. , McGue Matt 
Published: November 2004

AbstractPast reports suggest that reduced P300 amplitude is associated with risk for alcoholism. We examined whether visual P300 amplitude could identify familial risk for alcohol disorders in individuals not known to be at risk at the time P300 was recorded. These individuals were twins from pairs where neither twin had an alcohol disorder at age 17 but familial risk was established at age 20 when one twin developed an alcohol disorder whereas the other did not. Of special interest was the P300 of the unaffected twin recorded at age 17 when both twins were alcoholism free. We found reduced P300 in the unaffected twin compared to pairs where both members were continuously disorder free. Hence, P300 was reduced in alcohol disorder‐free individuals whose twin siblings subsequently developed alcoholism, further supporting reduced P300 amplitude as an endophenotype indexing familial risk for alcoholism.
The application of jackknife‐based onset detection of lateralized readiness potential in correlative approaches
Authors: Stahl Jutta , Gibbons Henning 
Published: November 2004

AbstractThe onset of the lateralized readiness potential (LRP) represents an interesting parameter within mental chronometry. According toMiller, Patterson, and Ulrich (1998), reliability increases when LRP onsets are detected in jackknifed LRP waveforms. Until now, jackknifed LRP onsets could be analyzed in factorial designs only. The aim of the present study was to extend the application of jackknifing to correlative approaches (e.g., in personality research). Using different onset scoring techniques, in several simulations run on realistic LRP data jackknifing and single‐subject procedures were compared regarding their estimates of a simulated true correlation. For all scoring techniques but regression, jackknifed coefficients were on average higher than the respective single‐subject coefficients, and statistical power was higher. Overall, combining jackknifing with a 50%‐relative onset criterion is recommended.
Hemodynamic effects of dietary caffeine, sleep restriction, and laboratory stress
Authors: James Jack E. , Gregg M. Elizabeth 
Published: November 2004

AbstractThis study examined the separate and interactive effects of caffeine, sleep restriction, and task‐induced laboratory stress in 96 healthy male and female volunteers. Participants alternated weekly between ingesting placebo and caffeine (1.75 mg/kg) three times daily for 4 consecutive weeks, while being either rested or sleep restricted. Finapres measurements of blood pressure, cardiac output, and total peripheral resistance showed that caffeine produced persistent blood pressure increases with a vascular hemodynamic profile. Sleep restriction produced a pronounced vascular response not associated with appreciable changes in blood pressure, whereas blood pressure increases induced by cognitive activity showed mixed cardiac and vascular responses. The findings suggest that life‐long dietary caffeine may contribute significantly to the development of cardiovascular disease.
Introducing a baroreflex model for studying cardiovascular effects of mental workload
Authors: Van Roon Arie M. , Mulder Lambertus J.M. , Althaus Monika , Mulder Gijsbertus 
Published: November 2004

AbstractA quantitative baroreflex control model is presented aimed at estimating differences in autonomic activation due to mental task performance. The model, which builds on earlier work of Wesseling and colleagues, is strongly supported by well‐established knowledge of physiological control processes. Spectral measures of heart rate and blood pressure variability provide the information to estimate autonomic gain and tone parameters. The article gives a detailed model description as well as an evaluation in terms of spectral variability distributions, respiratory sinus arrhythmia, and vagal control mechanisms. The estimation procedure is outlined while presenting two studies that describe the effects of mental workload and vagal blockade, respectively. It is concluded that, using the model approach, cardiovascular effects of mental task performance can be interpreted in terms of specific changes in autonomic state. The model is implemented in a Matlab/Simulink environment and is available for other researchers in the field.
In Vitro Activities of OPT-80 and Comparator Drugs against Intestinal Bacteria
Authors: Finegold Sydney M. , Molitoris Denise , Vaisanen Marja-Liisa , Song Yuli , Liu Chengxu , Bolaños Mauricio 
Published: November 2004

ABSTRACT

The activities of OPT-80 against 453 intestinal bacteria were compared with those of seven other drugs. OPT-80 showed good activity against most clostridia, staphylococci, and enterococci, but streptococci, aerobic and facultative gram-negative rods, anaerobic gram-negative rods, and
Clostridium ramosum
were resistant. Poor activity against anaerobic gram-negative rods may maintain colonization resistance.
Antimicrobial Susceptibility ofBordetella bronchisepticaIsolates from Porcine Respiratory Tract Infections
Authors: Kadlec Kristina , Kehrenberg Corinna , Wallmann Jürgen , Schwarz Stefan 
Published: November 2004

ABSTRACTMICs for 349Bordetella bronchisepticaisolates from respiratory tract infections of swine were determined by broth microdilution. The lowest MIC at which 90% of isolates tested are inhibited (MIC90) was that of tetracycline and enrofloxacin (0.5μ g/ml), whereas the highest MIC90s were those of tilmicosin and cephalothin (32 μg/ml) as well as streptomycin (256μ g/ml).
Members of the Genera
Paenibacillus
and
Rhodococcus
Harbor Genes Homologous to Enterococcal Glycopeptide Resistance Genes
vanA
and
vanB
Authors: Guardabassi L. , Christensen H. , Hasman H. , Dalsgaard A. 
Published: November 2004

ABSTRACT

Genes homologous to enterococcal glycopeptide resistance genes
vanA
and
vanB
were found in glycopeptide-resistant
Paenibacillus
and
Rhodococcus
strains from soil. The putative
d
-Ala:
d
-Lac ligase genes in
Paenibacillus thiaminolyticus
PT-2B1 and
Paenibacillus apiarius
PA-B2B were closely related to
vanA
(92 and 87%) and flanked by genes homologous to
vanH
and
vanX
in
vanA
operons.
Identification of a Naturally Processed Cytotoxic CD8 T-Cell Epitope of Coxsackievirus B4, Presented by HLA-A2.1 and Located in the PEVKEK Region of the P2C Nonstructural Protein
Authors: Varela-Calvino Ruben , Skowera Ania , Arif Sefina , Peakman Mark 
Published: November 2004

ABSTRACTThe adaptive immune system generates CD8 cytotoxic T lymphocytes (CTLs) as a major component of the protective response against viruses. Knowledge regarding the nature of the peptide sequences presented by HLA class I molecules and recognized by CTLs is thus important for understanding host-pathogen interactions. In this study, we focused on identification of a CTL epitope generated from coxsackievirus B4 (CVB4), a member of the enterovirus group responsible for several inflammatory diseases in humans and often implicated in the triggering and/or acceleration of the autoimmune disease type 1 diabetes. We identified a 9-mer peptide epitope that can be generated from the P2C nonstructural protein of CVB4 (P2C1137-1145) and from whole virus by antigen-presenting cells and presented by HLA-A2.1. This epitope is recognized by effector memory (gamma interferon [IFN-γ]-producing) CD8 T cells in the peripheral blood at a frequency of responders that suggests that it is a major focus of the anti-CVB4 response. Short-term CD8 T-cell lines generated against P2C1137-1145are cytotoxic against peptide-loaded target cells. Of particular interest, the epitope lies within a region of viral homology with the diabetes-related autoantigen, glutamic acid decarboxylase-65 (GAD65). However, P2C1137-1145-specific cytotoxic T lymphocyte (CTL) lines were not activated to produce IFN-γ by the GAD65peptide homologue and did not show cytotoxic activity in the presence of appropriately labeled targets. These results describe the first CD8 T-cell epitope of CVB4 that will prove useful in the study of CVB4-associated disease.
Surface Stability and Immunogenicity of the Human Immunodeficiency Virus Envelope Glycoprotein: Role of the Cytoplasmic Domain
Authors: Ye Ling , Bu Zhigao , Vzorov Andrei , Taylor Dahnide , Compans Richard W. , Yang Chinglai 
Published: November 2004

ABSTRACTThe effects of two functional domains, the membrane-proximal YXXΦ motif and the membrane-distal inhibitory sequence in the long cytoplasmic tail of the human immunodeficiency virus type 1 (HIV-1) envelope protein (Env), on immunogenicity of the envelope protein were investigated. Genes with codons optimized for mammalian expression were synthesized for the HIV 89.6 Env and a truncated Env with 50 amino acids in the cytoplasmic domain to delete the membrane distal inhibitory sequence for surface expression. Additional genes were generated in which the tyrosine residue in the YXXΦ motif was changed into a serine. Pulse-chase radioactive labeling and immunoprecipitation studies indicated that both domains can mediate endocytosis of the HIV Env, and removal of both domains is required to enhance HIV Env protein surface stability. Analysis of immune responses induced by DNA immunization of mice showed that the DNA construct for the mutant Env exhibiting enhanced surface stability induced significantly higher levels of antibody responses against the HIV Env protein. Our results suggest that the HIV Env cytoplasmic domain may play important roles in virus infection and pathogenesis by modulating its immunogenicity.
Efficient Replication by Herpes Simplex Virus Type 1 Involves Activation of the IκB Kinase-IκB-p65 Pathway
Authors: Gregory D. , Hargett D. , Holmes D. , Money E. , Bachenheimer S. L. 
Published: November 2004

ABSTRACT
Infection by herpes simplex virus type 1 (HSV-1) induces a persistent nuclear translocation of NFκB. To identify upstream effectors of NFκB and their effect on virus replication, we employed mouse embryo fibroblast (MEF)-derived cell lines with deletions of either IKK1 or IKK2, the catalytic subunits of the IκB kinase (IKK) complex. Infected MEFs were assayed for virus yield, loss of IκBα, nuclear translocation of p65, and NFκB DNA-binding activity. Absence of either IKK1 or IKK2 resulted in an 86 to 94% loss of virus yield compared to that of normal MEFs, little or no loss of IκBα, and greatly reduced NFκB nuclear translocation. Consistent with reduced virus yield, accumulation of the late proteins VP16 and gC was severely depressed. Infection of normal MEFs, Hep2, or A549 cells with an adenovirus vector expressing a dominant-negative (DN) IκBα, followed by superinfection with HSV, resulted in a 98% drop in virus yield. These results indicate that the IKK-IκB-p65 pathway activates NFκB after virus infection. Analysis of NFκB activation and virus replication in control and double-stranded RNA-activated protein kinase-null MEFs indicated that this kinase plays no role in the NFκB activation pathway. Finally, in cells where NFκB was blocked because of DNIκB expression, HSV failed to suppress two markers of apoptosis, cell surface Annexin V staining and PARP cleavage. These results support a model in which activation of NFκB promotes efficient replication by HSV, at least in part by suppressing a host innate response to virus infection.
Protein Transduction Domains Fused to Virus Receptors Improve Cellular Virus Uptake and Enhance Oncolysis by Tumor-Specific Replicating Vectors
Authors: Kühnel Florian , Schulte Bernd , Wirth Thomas , Woller Norman , Schäfers Sonja , Zender Lars , Manns Michael , Kubicka Stefan 
Published: November 2004

ABSTRACT

Expression of cellular receptors determines viral tropism and limits gene delivery by viral vectors. Protein transduction domains (PTDs) have been shown to deliver proteins, antisense oligonucleotides, liposomes, or plasmid DNA into cells. In our study, we investigated the role of several PTD motifs in adenoviral infection. When physiologically expressed, a PTD from human immunodeficiency virus transactivator of transcription (Tat) did not improve adenoviral infection. We therefore fused PTDs to the ectodomain of the coxsackievirus-adenovirus receptor (CAR
ex
) to attach PTDs to adenoviral fiber knobs. CAR
ex
-Tat and CAR
ex
-VP22 allowed efficient adenoviral infection in nonpermissive cells and significantly improved viral uptake rates in permissive cells. Dose-dependent competition of CAR
ex
-PTD-mediated infection using CAR
ex
and inhibition experiments with heparin showed that binding of CAR
ex
-PTD to both adenoviral fiber and cellular glycosaminoglycans is essential for the improvement of infection. CAR
ex
-PTD-treated adenoviruses retained their properties after density gradient ultracentrifugation, indicating stable binding of CAR
ex
-PTD to adenoviral particles. Consequently, the mechanism of CAR
ex
-PTD-mediated infection involves coating of the viral fiber knobs by CAR
ex
-PTD, rather than placement of CAR
ex
domains on cell surfaces. Expression of CAR
ex
-PTDs led to enhanced lysis of permissive and nonpermissive tumor cells by replicating adenoviruses, indicating that CAR
ex
-PTDs are valuable tools to improve the efficacy of oncolytic therapy. Together, our study shows that CAR
ex
-PTDs facilitate gene transfer in nonpermissive cells and improve viral uptake at reduced titers and infection times. The data suggest that PTDs fused to virus binding receptors may be a valuable tool to overcome natural tropism of vectors and could be of great interest for gene therapeutic approaches.
MUC4 is increased in high grade intraepithelial neoplasia in Barrett’s oesophagus and is associated with a proapoptotic Bax to Bcl-2 ratio
Authors: Bax D A , Haringsma J , Einerhand A W C , van Dekken H , Blok P , Siersema P D , Kuipers E J , Kusters J G 
Published: November 2004

Background:Patients with Barrett’s oesophagus (BO) are at risk of oesophageal adenocarcinoma. Because the pattern of mucosal mucins changes during neoplastic progression, it may serve as a marker of intraepithelial neoplasia.Aims:To determine the expression pattern of mucins in neoplastic BO epithelium (high grade dysplasia) and correlate it with the expression of apoptosis markers Bax and Bcl-2.Methods:Thirty seven patients with BO were studied: 16 without intraepithelial neoplasia, six with high grade intraepithelial neoplasia (HGN), and 15 with infiltrating adenocarcinoma. Biopsies were obtained from squamous epithelium, Barrett’s epithelium, and (when present) foci of suspected HGN or adenocarcinoma. MUC1–4, MUC5AC, MUC5B, MUC6, Bax, and Bcl-2 mRNA were determined by semiquantitative RT-PCR. MUC2, MUC5AC, and MUC6 protein was determined by immunoblotting.Results:Mucin expression varied between neoplastic progression stages in BO. Mucin mRNA levels were low in squamous epithelium, except for MUC4, and were at least four times higher in BO and HGN (p<0.001), but less so in adenocarcinoma. MUC4 expression was significantly lower in BO than in normal squamous epithelium, whereas in HGN and adenocarcinoma, levels were significantly higher than in BO (p = 0.037). The Bax:Bcl-2 ratio was increased in HGN compared with BO (p = 0.04). MUC2, MUC5AC, and MUC6 protein values correlated with mRNA data.Conclusions:Mucin expression varies during the development of oesophageal adenocarcinoma in BO. MUC4 could serve as a tumour marker in this process. In contrast to animal studies, upregulation of MUC4 in HGN is associated with increased apoptosis, suggesting that MUC4 plays a minor role in apoptosis regulation in BO.