bluuebunny/crossref_metadata_2025_split huggingface dataset:
Continuous normothermic hemihepatic vascular inflow occlusion over 60 min for hepatectomy in patients with cirrhosis caused by hepatitis B virus
Authors: Wen Tianfu , Chen Zheyu , Yan Lunan , Li Bo , Zeng Yong , Wu Guochang , Zheng Guangqi 
Published: April 2007

Aim:  To evaluate the safety of remnant liver in cirrhotic patients who had undergone irregular hepatectomy with continuous normothermic hemihepatic vascular inflow occlusion for over 60 min.Methods:  A group of 133 cirrhotic patients who had hepatitis B virus accompanied by hepatocellular carcinoma and had undergone irregular hepatectomy by hemihepatic vascular inflow occlusion was studied. According to the time of hemihepatic vascular inflow occlusion, patients were assigned either to the control group, treatment60 group, or treatment90 group. The quantity of blood loss and blood transfusion, routine liver biochemistry and postoperative complications were retrospectively analyzed.Results:  The data showed that there were no significant differences in postoperative complications between the three groups. Compared to the preoperative day, the levels of aspartate transaminase (AST), alanine transaminase (ALT), prothrombin time (PT) and serum bilirubin on postoperative days 1 and 3 were significantly increased in all three groups and the levels of albumin and platelet were significantly decreased on postoperative day 1. Duration of hospital stay and the levels of ALT and AST on postoperative days 1, 3 and 7 were higher in the treatment90 group than in the control group and treatment60 group (P < 0.05). However, no significant differences were displayed in the length of hospital stay and the levels of AST, ALT, PT, albumin, platelet count and serum bilirubin on postoperative days 1, 3 and 7 between the control group and the treatment60 group (P > 0.05).Conclusion:  Hemihepatic vascular inflow occlusion over 60 min is a possible method for irregular hepatectomy in patients with cirrhosis caused by the hepatitis B virus. However, caution must be exercised in utilizing this method where the time of vascular occlusion is over 90 min.
Sensitivity of Monkey B Virus (
Cercopithecine herpesvirus
1) to Antiviral Drugs: Role of Thymidine Kinase in Antiviral Activities of Substrate Analogs and Acyclonucleosides
Authors: Focher Federico , Lossani Andrea , Verri Annalisa , Spadari Silvio , Maioli Andrew , Gambino Joseph J. , Wright George E. , Eberle Richard , Black Darla H. , Medveczky Peter , Medveczky Maria , Shugar David 
Published: April 2007

ABSTRACT

Herpes B virus (B virus [BV]) is a macaque herpesvirus that is occasionally transmitted to humans where it can cause rapidly ascending encephalitis that is often fatal. To understand the low susceptibility of BV to the acyclonucleosides, we have cloned, expressed, and characterized the BV thymidine kinase (TK), an enzyme that is expected to “activate” nucleoside analogs. This enzyme is similar in sequence and properties to the TK of herpes simplex virus (HSV), i.e., it has a broad substrate range and low enantioselectivity and is sensitive to inhibitors of HSV TKs. The BV enzyme phosphorylates some modified nucleosides and acyclonucleosides and
l
enantiomers of thymidine and related antiherpetic analogs. However, the potent anti-HSV drugs acyclovir (ACV), ganciclovir (GCV), and 5-bromovinyldeoxyuridine were poorly or not phosphorylated by the BV enzyme under the experimental conditions. The antiviral activities of a number of marketed antiherpes drugs and experimental compounds were compared against BV strains and, for comparison, HSV type 1 (HSV-1) in Vero cell cultures. For most compounds tested, BV was found to be about as sensitive as HSV-1 was. However, BV was less sensitive to ACV and GCV than HSV-1 was. The abilities of thymidine analogs and acyclonucleosides to inhibit replication of BV in Vero cell culture were not always proportional to their substrate properties for BV TK. Our studies characterize BV TK for the first time and suggest new lead compounds, e.g., 5-ethyldeoxyuridine and pencyclovir, which may be superior to ACV or GCV as treatment for this emerging infectious disease.
Statistical Methods for Establishing Quality Control Ranges for Antibacterial Agents in Clinical and Laboratory Standards Institute Susceptibility Testing
Authors: Turnidge John , Bordash Gerry 
Published: April 2007

ABSTRACT
Quality control (QC) ranges for antimicrobial agents against QC strains for both dilution and disk diffusion testing are currently set by the Clinical and Laboratory Standards Institute (CLSI), using data gathered in predefined structured multilaboratory studies, so-called tier 2 studies. The ranges are finally selected by the relevant CLSI subcommittee, based largely on visual inspection and a few simple rules. We have developed statistical methods for analyzing the data from tier 2 studies and applied them to QC strain-antimicrobial agent combinations from 178 dilution testing data sets and 48 disk diffusion data sets, including a method for identifying possible outlier data from individual laboratories. The methods are based on the fact that dilution testing MIC data were log normally distributed and disk diffusion zone diameter data were normally distributed. For dilution testing, compared to QC ranges actually set by CLSI, calculated ranges were identical in 68% of cases, narrower in 7% of cases, and wider in 14% of cases. For disk diffusion testing, calculated ranges were identical to CLSI ranges in 33% of cases, narrower in 8% of cases, and 1 to 2 mm wider in 58% of cases. Possible outliers were detected in 8% of diffusion test data but none of the disk diffusion data. Application of statistical techniques to the analysis of QC tier 2 data and the setting of QC ranges is relatively simple to perform on spreadsheets, and the output enhances the current CLSI methods for setting of QC ranges.
Genome Sequence of a Clinical Isolate of
Campylobacter jejuni
from Thailand
Authors: Poly Frédéric , Read Timothy , Tribble David R. , Baqar Shahida , Lorenzo Maria , Guerry Patricia 
Published: April 2007

ABSTRACT

Campylobacter jejuni
CG8486, which belongs to the HS4 complex, was isolated from a patient with inflammatory diarrhea in Thailand. This strain caused a diarrheal disease in ferrets comparable to that caused by
C. jejuni
strain 81-176, but it was much less invasive for epithelial cells in vitro than 81-176. Complete genome sequencing of CG8486 revealed a 1.65-Mb genome that was very similar to the other two published genomes of clinical isolates of
C. jejuni
, the genomes of 81-176 and NCTC 11168, with a limited number of CG8486-specific genes mapping outside the hypervariable carbohydrate biosynthesis loci. These data suggest that the genes required for induction of inflammatory diarrhea are among the genes shared by CG8486 and 81-176 but that either major changes in the carbohydrate loci and/or more subtle changes in other genes may modulate virulence.
Assessment of the Kinetics ofTreponema pallidumDissemination into Blood and Tissues in Experimental Syphilis by Real-Time Quantitative PCR
Authors: Salazar Juan C. , Rathi Asha , Michael Nelson L. , Radolf Justin D. , Jagodzinski Linda L. 
Published: April 2007

ABSTRACTLittle is known about the size and kinetics of treponemal burdens in blood and tissues during acquired or experimental syphilitic infection. We used real-time quantitative PCR to measureTreponema pallidumDNA levels in rabbits infected intratesticularly with the prototype Nichols strain. At the outset, we performed a series of in vitro blood spiking experiments to determine the effect of blood processing procedures on the distribution of treponemes in various blood components.T. pallidumDNA levels in plasma and whole blood were approximately 10-fold higher than those in serum and more than 200-fold greater than those in peripheral blood mononuclear cells (PBMCs). Ten rabbits were inoculated intratesticularly with doses of treponemes ranging from 4 × 107to 2 × 108organisms. In five rabbits,T. pallidumDNA levels were measured sequentially in serum, plasma, whole blood, and PBMCs until sacrifice at peak orchitis, at which time brain, kidney, liver, spleen, and testicles were harvested; blood and organs were also harvested at orchitis from the other five rabbits.T. pallidumDNA was detected in plasma within 24 h postinfection. Treponeme levels in whole blood and blood components increased significantly with the development of peak orchitis. Overall, levels in serum and PBMCs were lower than those in plasma and whole blood; this disparity was particularly marked at early time points. Significantly greater numbers of spirochetes were found in the spleen than in liver, kidney, or brain tissue at the time of sacrifice. Our findings highlight the remarkable capacity ofT. pallidumto disseminate from the site of infection to blood and tissues, and they identify the spleen as a prime target for treponemal invasion.
Identification of a
Campylobacter jejuni
Protein That Cross-Reacts with Cholera Toxin
Authors: Albert M. John , Haridas Shilpa , Steer David , Dhaunsi Gursev S. , Smith A. Ian , Adler Ben 
Published: April 2007

ABSTRACT

The question of whether
Campylobacter jejuni
produces a cholera toxin-like toxin (CTLT) has been controversial. The objective of this study was to identify the factor that cross-reacts with CT from
C. jejuni
. Filtrates of
C. jejuni
grown in four different liquid media reported to promote CTLT production were tested by Chinese hamster ovary (CHO) cell elongation assay and for reactivity with CT antibody using GM1 ganglioside enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Protein sequence was determined by matrix-assisted laser desorption ionization-time of flight (MALDI TOF-TOF). Filtrates from seven reference strains reported to produce CTLT and from 80 clinical strains were negative in the CHO cell assay, but those from three reference strains and 16 clinical strains were positive by GM1 ELISA. All strains tested, including
C. jejuni
NCTC 11168, which does not contain a CT gene homologue, possessed a 53-kDa protein which reacted with CT antibody by immunoblotting. This band was identified as the major outer membrane protein, PorA, of
C. jejuni
. CT antibody reacted by immunoblotting with a recombinant PorA, but antibody to the recombinant PorA did not react with CT. Our results indicate that
C. jejuni
does not produce a functional CTLT, but the reactivity of PorA with CT antibody would lead to the erroneous conclusion that
C. jejuni
produces a functional CTLT.
Both Complement- and Fibrinogen-Dependent Mechanisms Contribute to Platelet Aggregation Mediated by
Staphylococcus aureus
Clumping Factor B
Authors: Miajlovic Helen , Loughman Anthony , Brennan Marian , Cox Dermot , Foster Timothy J. 
Published: April 2007

ABSTRACT

Staphylococcus aureus
can stimulate activation and aggregation of platelets, which are thought to be factors in the development of infective endocarditis. Previous studies have identified clumping factor A (ClfA) and fibronectin binding proteins A and B (FnBPA and FnBPB) as potent platelet aggregators. These proteins are able to stimulate rapid platelet aggregation by either a fibrinogen- or a fibronectin-dependent process which also requires antibodies specific to each protein. Slower aggregation has been seen in other systems where specific fibrinogen binding ligands are absent and platelet aggregation is mediated by complement and specific antibodies. Bacteria expressing ClfB aggregate platelets with a longer lag time than ClfA or FnBPA and FnBPB. In order to investigate whether ClfB causes platelet aggregation in a complement- or fibrinogen-dependent manner, a non-fibrinogen-binding mutant of ClfB (ClfB Q235A) was constructed.
Lactococcus lactis
expressing ClfB Q235A was able to stimulate platelet aggregation in platelet-rich plasma without a significant increase in lag time. The requirements for platelet aggregation were investigated using gel-filtered platelets. Fibrinogen and specific anti-ClfB antibodies were found to be sufficient to allow platelet aggregation mediated by the wild-type ClfB protein. It seems that ClfB causes platelet aggregation by a fibrinogen-dependent mechanism. The non-fibrinogen-binding ClfB mutant was unable to stimulate platelet aggregation under these conditions. However, bacteria expressing ClfB Q235A caused platelet aggregation in a complement-dependent manner which required specific anti-ClfB antibodies.
Virulence Potential of
Ehrlichia chaffeensis
Strains of Distinct Genome Sequences
Authors: Miura Koshiro , Rikihisa Yasuko 
Published: April 2007

ABSTRACT

Human monocytic ehrlichiosis, one of the most frequent life-threatening tick-borne zoonoses, is caused by
Ehrlichia chaffeensis
that lacks endotoxin and peptidoglycan. While sequence polymorphisms in several genes in
E. chaffeensis
strains have been reported, global genomic divergence and biological differences among strains are unknown. The objectives of the present study were to compare the genome sequences of strains of
E. chaffeensis
and to examine the virulence potentials of the strains with defined genome sequences. Genomic DNA was extracted from purified
E. chaffeensis
strains Wakulla and Liberty, and comparative genome hybridization was performed using a densely tiled microarray of 147,027 chromosome positions of the
E. chaffeensis
strain Arkansas genome. The results revealed that 4,663 and 5,325 positions in the chromosomes of strains Wakulla and Liberty, respectively, were different from those in the chromosome of strain Arkansas, including three common major polymorphic chromosomal regions. Of various functional categories, the differences were most concentrated in genes predicted to encode cell envelope proteins. Of all the open reading frames (ORFs), 21
omp-1
(p28 gene) paralogs, nine genes encoding hypothetical proteins, two genes encoding ankyrin repeat proteins, and
hemE
contained the most differences. Several highly polymorphic ORFs were confirmed by sequencing. When the
E. chaffeensis
strains were inoculated into severe combined immunodeficiency mice, the order of the severity of clinical signs and the bacterial burden detected in mice was Wakulla > Liberty > Arkansas. Severe diffuse inflammation and granulomatous inflammation were evident in the livers of mice infected with strains Wakulla and Arkansas, respectively, but not in the livers of mice infected with strain Liberty. These results revealed distinct virulence phenotypes of
E. chaffeensis
strains with defined genome sequences.
Overexpressed Cyclophilin A in Cancer Cells Renders Resistance to Hypoxia- and Cisplatin-Induced Cell Death
Authors: Choi Kyu Jin , Piao Yu Ji , Lim Min Jin , Kim Jin Hwan , Ha Joohun , Choe Wonchae , Kim Sung Soo 
Published: April 2007

Abstract
Cyclophilin A (CypA) has been reported to be overexpressed in cancer cells, especially in solid tumors. To determine the role of CypA in tumorigenesis, we investigated the induction of CypA as well as the role it plays in cancer cells. Here, we have shown that induction of CypA is associated with hypoxia in a variety of cells, including DU145 human prostate cancer cell line. Our analysis of the CypA promoter clearly showed that CypA up-regulation is mediated by hypoxia-inducible factor-1α transcription factor. Interestingly, overexpression of CypA prevented hypoxia- and cisplatin-induced apoptosis, and this was associated with the suppression of reactive oxygen species generation and depolarization of mitochondrial membrane potential, whereas small interfering RNA–based CypA knockdown aggravated these factors. These results suggest that CypA is important in tumorigenesis, especially in tumor apoptosis. [Cancer Res 2007;67(8):3654–62]
M3 Muscarinic Receptor Antagonists Inhibit Small Cell Lung Carcinoma Growth and Mitogen-Activated Protein Kinase Phosphorylation Induced by Acetylcholine Secretion
Authors: Song Pingfang , Sekhon Harmanjatinder S. , Lu Allison , Arredondo Juan , Sauer David , Gravett Courtney , Mark Gregory P. , Grando Sergei A. , Spindel Eliot R. 
Published: April 2007

Abstract
The importance of acetylcholine as a neurotransmitter in the nervous system is well established, but little is yet known about its recently described role as an autocrine and paracrine hormone in a wide variety of nonneuronal cells. Consistent with the expression of acetylcholine in normal lung, small cell lung carcinoma (SCLC) synthesize and secrete acetylcholine, which acts as an autocrine growth factor through both nicotinic and muscarinic cholinergic mechanisms. The purpose of this study was to determine if interruption of autocrine muscarinic cholinergic signaling has potential to inhibit SCLC growth. Muscarinic receptor (mAChR) agonists caused concentration-dependent increases in intracellular calcium and mitogen-activated protein kinase (MAPK) and Akt phosphorylation in SCLC cell lines. The inhibitory potency of mAChR subtype–selective antagonists and small interfering RNAs (siRNAs) on acetylcholine-increased intracellular calcium and MAPK and Akt phosphorylation was consistent with mediation by M3 mAChR (M3R). Consistent with autocrine acetylcholine secretion stimulating MAPK and Akt phosphorylation, M3R antagonists and M3R siRNAs alone also caused a decrease in basal levels of MAPK and Akt phosphorylation in SCLC cell lines. Treatment of SCLC cells with M3R antagonists inhibited cell growth both in vitro and in vivo and also decreased MAPK phosphorylation in tumors in nude mice in vivo. Immunohistochemical staining of SCLC and additional cancer types showed frequent coexpression of acetylcholine and M3R. These findings suggest that M3R antagonists may be useful adjuvants for treatment of SCLC and, potentially, other cancers. [Cancer Res 2007;67(8):3936–44]
Selective Down-Regulation of Glioma-Associated Oncogene 2 Inhibits the Proliferation of Hepatocellular Carcinoma Cells
Authors: Kim Youngsoo , Yoon Joon Won , Xiao Xiaokun , Dean Nicholas M. , Monia Brett P. , Marcusson Eric G. 
Published: April 2007

Abstract
The sonic hedgehog (Shh) pathway contributes to the initiation and progression of tumors with various origins when aberrantly activated. In this study, we investigated if the Shh pathway is important for the proliferation of hepatocellular carcinoma (HCC) cells and also began to identify which components of the pathway play a pivotal role in the biology of HCC. Expression levels of components in the pathway were measured, and glioma-associated oncogene (Gli) 2 levels were found to be considerably higher in human HCC lines compared with normal liver. Gli2 levels were also higher in tumor tissue from HCC patients compared with normal liver. Antisense oligonucleotides (ASO) were used to specifically down-regulate Gli2, and this led to decreased proliferation of various HCC cell lines. However, inhibition of Gli1 and Gli3 with ASOs did not decrease proliferation in most HCC cell lines and inhibitors targeting the upstream components of the pathway, including smoothened (Smo), displayed antiproliferative effects in only a subset of HCC cell lines. Moreover, in cancer cells harboring Smo mutations or unresponsive to the Smo inhibitor 3-keto-N-aminoethylaminoethylcaproyldihydrocinnamoyl cyclopamine, the Gli2 ASO was still able to inhibit proliferation. The importance of Gli2 in HCC proliferation was further confirmed by the changes in expression levels of genes, such as Bcl-2, c-Myc, and p27, following suppression of Gli2 expression. Taken together, these results suggest that, among the Gli transcription factors, Gli2 plays a predominant role in the proliferation of HCC cells and the suppression of Gli2 expression may provide a useful therapeutic option for the treatment of HCC. [Cancer Res 2007;67(8):3583–93]
Mechanism of Action of the Microtubule-Targeted Antimitotic Depsipeptide Tasidotin (Formerly ILX651) and Its Major Metabolite Tasidotin C-Carboxylate
Authors: Ray Anasuya , Okouneva Tatiana , Manna Tapas , Miller Herbert P. , Schmid Steven , Arthaud Larry , Luduena Richard , Jordan Mary Ann , Wilson Leslie 
Published: April 2007

Abstract
Tasidotin (ILX-651), an orally active synthetic microtubule-targeted derivative of the marine depsipeptide dolastatin-15, is currently undergoing clinical evaluation for cancer treatment. Tasidotin inhibited proliferation of MCF7/GFP breast cancer cells with an IC50 of 63 nmol/L and inhibited mitosis with an IC50 of 72 nmol/L in the absence of detectable effects on spindle microtubule polymer mass. Tasidotin inhibited the polymerization of purified tubulin into microtubules weakly (IC50 ∼ 30 μmol/L). However, it strongly suppressed the dynamic instability behavior of the microtubules at their plus ends at concentrations ∼5 to 10 times below those required to inhibit polymerization. Its major actions were to reduce the shortening rate, the switching frequency from growth to shortening (catastrophe frequency), and the fraction of time the microtubules grew. In contrast with all other microtubule-targeted drugs thus far examined that can inhibit polymerization, tasidotin did not inhibit the growth rate. In contrast to stabilizing plus ends, tasidotin enhanced microtubule dynamic instability at minus ends, increasing the shortening length, the fraction of time the microtubules shortened, and the catastrophe frequency and reducing the rescue frequency. Tasidotin C-carboxylate, the major intracellular metabolite of tasidotin, altered dynamic instability of purified microtubules in a qualitatively similar manner to tasidotin but was 10 to 30 times more potent. The results suggest that the principal mechanism by which tasidotin inhibits cell proliferation is by suppressing spindle microtubule dynamics. Tasidotin may be a relatively weak prodrug for the functionally active tasidotin C-carboxylate. [Cancer Res 2007;67(8):3767–76]
Therapeutic Effect of Rapamycin on Gallbladder Cancer in a Transgenic Mouse Model
Authors: Wu Qi , Kiguchi Kaoru , Kawamoto Toru , Ajiki Tetsuo , Traag Jeanine , Carbajal Steve , Ruffino Lynnsie , Thames Howard , Wistuba Ignacio , Thomas Melanie , Vasquez Karen M. , DiGiovanni John 
Published: April 2007

Abstract
The macrolide fungicide rapamycin has shown significant antiproliferative action toward a variety of tumor types. In this study, we used BK5.erbB2 transgenic mice as an animal model to examine the therapeutic effect of rapamycin as a potential treatment for gallbladder cancer. Homozygous BK5.erbB2 mice overexpressing the wild-type rat erbB2 gene in basal epithelial cells of the gallbladder have an ∼70% incidence of gallbladder adenocarcinoma by 2 to 3 months of age. Groups of mice (∼2–3 months of age) were treated with rapamycin by i.p. injection (once daily for 14 days) and then sacrificed 24 h after the last treatment. Rapamycin significantly reduced the incidence and severity of gallbladder carcinoma in BK5.erbB2 mice in a dose-dependent manner. Tumors responsive to treatment exhibited a higher number of apoptotic cells. Furthermore, rapamycin treatment led to decreased levels of phosphorylated p70 S6 kinase (Thr389) in gallbladder tissue as assessed by both Western blot and immunofluorescence analyses. Finally, immunofluorescence staining revealed elevated phosphorylated Akt (Ser473) and phosphorylated mammalian target of rapamycin (mTOR; Ser2448) in human gallbladder cancer compared with normal gallbladder tissue. Based on our results using a novel genetically engineered mouse model and the fact that the Akt/mTOR pathway is activated in human gallbladder cancer, rapamycin and related drugs may be effective therapeutic agents for the treatment of human gallbladder cancer. [Cancer Res 2007;67(8):3794–800]