bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytoprotection by bcl‐2 gene transfer against ischemic liver injuries together with repressed lipid peroxidation and increased ascorbic acid in livers and serum
Authors: Yanada Shinobu , Saitoh Yasukazu , Kaneda Yasufumi , Miwa Nobuhioko 
Published: September 2004

AbstractThe maximum gene exhibition was shown to be achieved at 48 h after transfection with human bcl‐2 (hbcl‐2) genes built in an SV40 early promoter‐based plasmid vector and HVJ‐liposome for cultured rat hepatocytes. The similar procedure of hbcl‐2 transfection was therefore conducted for livers in rats via the portal vein, and after 48 h followed by post‐ischemic reperfusion (I/R) operation for some hepatic lobes. The I/R‐induced hepatic injuries were in situ observed as both cell morphological degeneration and cellular DNA strand cleavages around capillary vessels of the ischemic liver lobes as detected by HE stain and TUNEL assay, and were biochemically observed as release of two hepatic marker enzymes AST and ALT into serum. All the I/R‐induced injuries examined were appreciably repressed for rats transfected with hbcl‐2; hbcl‐2 was expressed in hepatocytes around the capillaries of ischemic regions such as the median lobe and the left lobe, but scarcely around those of non‐ischemic regions. Thus cytoprotection against I/R‐induced injuries may be attributed to the I/R‐promoted expression of transferred hbcl‐2 genes. The possibility was examined firstly by methylphenylindole method, which showed that I/R‐enhanced lipid peroxidation in the reference vector‐transfected livers were markedly repressed in the hbcl‐2‐transfected livers. Contents of ascorbic acid (Asc) in serum and livers of hbcl‐2‐transfected rats were enriched, unexpectedly, versus those of non‐transfected rats, and were as abundant as 1.90‐fold and 1.95‐ to 2.60‐fold versus those in the pre‐ischemic state, respectively. After I/R, an immediate decline in serum Asc occurred in hbcl‐2‐transfectants, and was followed by prompt restoration up to the pre‐ischemic Asc levels in contrast to the unaltered lower Asc levels in non‐transfectants except a transient delayed increase. Hepatic Asc contents were also diminished appreciably at the initial stage after I/R in the ischemic lobes of hbcl‐2‐transfectants, which however retained more abundant Asc versus non‐transfectants especially at the initial I/R stage when scavenging of the oxidative stress should be most necessary for cytoprotection. The results showed a close correlation between cytoprotection by exogenously transferred hbcl‐2 and repressive effects on the lipid peroxidation associated with Asc consumption or redistribution. © 2004 Wiley‐Liss, Inc.
Tumor–host interactions
Authors: Tisdale M.J. 
Published: September 2004

AbstractA number of malignant tumors interact with the host to cause a syndrome of cachexia, characterized by extensive loss of adipose tissue and skeletal muscle mass, but with preservation of proteins in visceral tissues. Although anorexia is frequently present, the body composition changes in cancer cachexia cannot be explained by nutritional deprivation alone. Loss of skeletal muscle mass is a result of depression in protein synthesis and an increase in protein degradation. The main degradative pathway that has been found to have increased expression and activity in the skeletal muscle of cachectic patients is the ubiquitin‐proteasome proteolytic pathway. Cachexia‐inducing tumors produce catabolic factors such as proteolysis‐inducing factor (PIF), a 24 kDa sulfated glycoprotein, which inhibit protein synthesis and stimulate degradation of intracellular proteins in skeletal muscle by inducing an increased expression of regulatory components of the ubiquitin‐proteasome proteolytic pathway. While the oligosaccharide chains in PIF are required to initiate protein degradation the central polypeptide core may act as a growth and survival factor. Only cachexia‐inducing tumors are capable of elaborating fully glycosylated PIF, and the selectivity of production possibly rests with the acquisition of the necessary glycosylating enzymes, rather than expressing the gene for the polypeptide core. Loss of adipose tissue is probably the result of an increase in catabolism rather than a defect in anabolism. A lipid mobilizing factor (LMF), identical with the plasma protein Zn‐α2‐glycoprotein (ZAG) is found in the urine of cachectic cancer patients and is produced by tumors causing a decrease in carcass lipid. LMF causes triglyceride hydrolysis in adipose tissue through a cyclic AMP‐mediated process by interaction with a β3‐adrenoreceptor. Thus, by producing circulating factors certain malignant tumors are able to interfere with host metabolism even without metastasis to that particular site. © 2004 Wiley‐Liss, Inc.
A fragment of the hypophosphatemic factor, MEPE, requires inducible cyclooxygenase‐2 to exert potent anabolic effects on normal human marrow osteoblast precursors
Authors: Nagel D.E. , Khosla S. , Sanyal A. , Rosen D.M. , Kumagai Y. , Riggs B. Lawrence 
Published: September 2004

AbstractMEPE, 56.6 kDa protein isolated from tumors associated with hypophosphatemic osteomalacia, increases renal phosphate excretion and is expressed in normal human bone cells. AC‐100, a central 23‐amino acid fragment of MEPE, contains motifs that are important in regulating cellular activities in the bone microenvironment. Thus, we assessed in vitro effects of AC‐100 on multipotential normal human marrow stromal (hMS) cells that have the capacity to differentiate into mature osteoblasts. Proliferation was quantified by [H3]thymidine uptake and cell counting and differentiation by the levels of mRNA for the α2‐chain of type I procollagen (COL1A2), alkaline phosphatase (AP), and osteocalcin (OC) measured using real time reverse transcriptase PCR (RT‐PCR) and by the formation of mineralized nodules. AC‐100 increased proliferation by 257 ± 89% (P < 0.005), increased gene expression of COL1A2 by 339 ± 85% (P < 0.005), AP by 1,437 ± 40% (P < 0.001), and OC by 1,962 ± 337% (P < 0.001). In addition, it increased mineralized nodule formation by 81 ± 14% (P < 0.001) in a dose‐ and time‐dependent fashion. In equimolar dosages, the parent compound, MEPE, had the full activity of the AC‐100 fragment. AC‐100 elicited a comparable response to both IGF‐I and BMP‐2 with respect to proliferation and differentiation of hMS cells. Using gene expression microarray analysis, we demonstrated that AC‐100 increased (by ∼3‐fold) the mRNA for cyclooxgenase‐2 (COX‐2), an inducible enzyme required for prostaglandin synthesis. Moreover, NS‐398, a specific inhibitor of COX‐2 action completely blocked AC‐100‐induced increases in proliferation and differentiation. Thus, AC‐100 has potent anabolic activity on osteoblast precursor cells in vitro and these effects require the induction of COX‐2. © 2004 Wiley‐Liss, Inc.
Role of cell signalling involved in induction of apoptosis by benzo[a]pyrene and cyclopenta[c,d]pyrene in Hepa1c1c7 cells
Authors: Solhaug Anita , Refsnes Magne , Holme Jørn A. 
Published: September 2004

AbstractThe reactive metabolites of benzo[a]pyrene (B[a]P) and cyclopenta[c,d]pyrene (CPP) induced an accumulation/phosphorylation of p53 in Hepa1c1c7 cells, whereas inhibition of p53 reduced the apoptosis. Judged by the inhibiting effect of wortmannin, phosphatidyl‐inositol‐3 (PI‐3) kinases such as DNA‐dependent protein kinase (DNA‐PK), ATM (ataxia‐telangiectasia mutated), and/or ATR (ATM related kinase), appeared to be involved in the DNA damage recognition and the B[a]P‐/CPP‐induced accumulation of p53. B[a]P and CPP also induced phosphorylation of jun‐N‐terminal kinase (JNK) and p38 mitogen activated protein kinase (MAPK). While inhibition of JNK had no effects on the B[a]P‐/CPP‐induced apoptosis, inhibition of p38 MAPK activity reduced this effect. Interestingly, survival signals such as phosphorylation of Akt and Bad seemed to be induced by the B[a]P‐/CPP‐compounds. Furthermore, also extracellular signal‐regulated kinase (ERK)1/2 was activated and seemed to function as a survival signal in B[a]P‐/CPP‐induced apoptosis. © 2004 Wiley‐Liss, Inc.
A novel subfamily of zinc finger genes involved in embryonic development
Authors: Nakamura Mako , Runko Alexander P. , Sagerström Charles G. 
Published: September 2004

AbstractC2H2 zinc finger proteins make up one of the largest protein families in eukaryotic organisms. Recent study in several different systems has identified a set of novel zinc finger proteins that appear to form a distinct subfamily that we have named the NET family. Members of the NET family (Noc, Nlz, Elbow, and Tlp‐1) share two protein motifs—a buttonhead box and an Sp motif—with zinc finger proteins from the Sp family. However, the NET family is uniquely characterized by a single atypical C2H2 zinc finger, in contrast to the Sp family that contains three tandem C2H2 fingers. Here, we review current information about the biochemical function and in vivo role for members of this subfamily. In general, NET family proteins are required during embryonic development. They appear to act by regulating transcription, most likely as repressors, although they are unlikely to bind DNA directly. In the future, it will be important to directly test if NET family proteins control transcription of specific target genes, perhaps via interactions with DNA‐binding transcription factors, as well as to further explore their function in vivo. © 2004 Wiley‐Liss, Inc.
P2Y receptors play a critical role in epithelial cell communication and migration
Authors: Klepeis Veronica E. , Weinger Ilene , Kaczmarek Elzbieta , Trinkaus‐Randall Vickery 
Published: September 2004

AbstractCellular injury induces a complex series of events that involves Ca2+ signaling, cell communication, and migration. One of the first responses following mechanical injury is the propagation of a Ca2+ wave (Klepeis et al. [2001] J Cell Sci 114(Pt 23):4185–4195). The wave is generated by the extracellular release of ATP, which also induces phosphorylation of ERK (Yang et al. [2004] J Cell Biochem 91(5):938–950). ATP and other nucleotides, which bind to and activate specific purinergic receptors were used to mimic injury. Our goal was to determine which of the P2Y purinergic receptors are expressed and stimulated in corneal epithelial cells and which signaling pathways are activated leading to changes in cell migration, an event critical for wound closure. In this study, we demonstrated that the P2Y1, P2Y2, P2Y4, P2Y6, and P2Y11 receptors were present in corneal epithelial cells. A potency profile was determined by Ca2+ imaging for nucleotide agonists as follows: ATP ≥ UTP > ADP ≥ UDP. In contrast, negligible responses were seen for β,γ‐meATP, a general P2X receptor agonist and adenosine, a P1 receptor agonist. Homologous desensitization of the Ca2+ response was observed for the four nucleotides. However, P2Y receptor internalization and degradation was not detected following stimulation with ATP, which is in contrast to EGFR internalization observed in response to EGF. ATP induced cell migration was comparable to that of EGF and was maximal at 1 μM. Cells exposed to ATP, UTP, ADP, and UDP demonstrated a rapid twofold increase in phosphorylation of paxillin at Y31 and Y118, however, there was no activation elicited by β,γ‐meATP or adenosine. Additional studies demonstrated that wound closure was inhibited by reactive blue 2. These results indicate that P2Y receptors play a critical role in the injury repair process. © 2004 Wiley‐Liss, Inc.
A theoretical study of solvent effects on tautomerism and electronic absorption spectra of 3‐hydroxy‐2‐mercaptopyridine and 2,3‐dihydroxypyridine
Authors: Yan Weizhong , Xue Ying , Zhu Hua , Zeng Jun , Xie Daiqian 
Published: September 2004

AbstractThe tautomerization equilibria of 3‐hydroxy‐2‐mercaptopyridine (HMP) and 2,3‐dihydroxypyridine (DHP) in vacuo and in ethanol solution have been studied using the density functional theory (DFT) at B3LYP/6‐31G(d) level. The results indicate that the thione form of HMP and the keto form of DHP are the most stable tautomers in the equilibrium, and the energy barrier for the thiol–thione and enol–keto proton transfer decreases significantly when the tautomerism is mediated by a specific ethanol molecule in solution. The time‐dependent density functional theory—polarizable continuum model (TDDFT‐PCM) calculations on all tautomers of HMP and DHP in vacuo and in ethanol have assigned the lowest π → π* excitations of thione and keto tautomers to the observed absorption bands of HMP and DHP in solutions. The solvation is predicted to have relatively small effect on these π → π* excitations in ethanol. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1833–1839, 2004
Fast fragments: The development of a parallel effective fragment potential method
Authors: Netzloff Heather M. , Gordon Mark S. 
Published: September 2004

AbstractThe Effective Fragment Potential (EFP) method for solvation decreases the cost of a fully quantum mechanical calculation by dividing a chemical system into anab initioregion that contains the solute plus some number of solvent molecules, if desired, and an “effective fragment” region that contains the remaining solvent molecules. Interactions introduced with this fragment region (for example, Coulomb and polarization interactions) are added as one‐electron terms to the total system Hamiltonian. As larger systems and dynamics are just starting to be studied with the EFP method, more needs to be done to decrease the calculation time of the method. This article considers parallelization of both the EFP fragment‐fragment and mixed quantum mechanics (QM)‐EFP interaction energy and gradient computation within the GAMESS suite of programs. The iteratively self‐consistent polarization term is treated with a new algorithm that makes use of nonblocking communication to obtain better scalability. Results show that reasonable speedup is achieved with a variety of sizes of water clusters and number of processors. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1926–1935, 2004
Hypergravity decreases carbonic anhydrase‐reactivity in inner ear maculae of fish
Authors: Anken Ralf H. , Beier Marion , Rahmann Hinrich 
Published: September 2004

AbstractPrevious investigations revealed that fish inner ear otolith growth depends on the amplitude and the direction of gravity. Both otolith total size, otolith bilateral size‐asymmetry and the total and bilateral calcium‐incorporation are also affected by gravity. Hypergravity, e.g., slows down otolith growth and diminishes bilateral otolith asymmetry as compared to 1 g control specimens raised in parallel. Since the enzyme carbonic anhydrase (CA) plays a prominent role in otolithic calcification, the reactivity of inner ear CA during otolith growth under hypergravity was investigated. CA‐reactivity was demonstrated histochemically and densitometrically on sections of inner ear maculae of larval cichlid fish (Oreochromis mossambicus), that were kept for 6 hrs in a 3 g hypergravity centrifuge. The total unilateral macular CA‐reactivity and the bilateral difference in CA between the left and the right maculae were significantly lower in 3 g animals than in 1g controls. The result is in complete agreement with previous studies indicating that a regulatory mechanism, which adjusts otolith size and asymmetry towards the gravity vector, acts via activation/deactivation of macular CA. J. Exp. Zool. 301A:815–819, 2004. © 2004 Wiley‐Liss, Inc.
Anatomy of and patterns of water currents through the mantle cavities of pleurotomariid gastropods
Authors: Voltzow Janice , Morris Paul J. , Linsley Robert M. 
Published: September 2004

AbstractThe paired pallial organs of pleurotomariids (slit shells) are generally interpreted as representing the primitive gastropod condition. Relatively few individual pleurotomariids have been observed alive; most anatomical descriptions have been based on retracted, preserved material. In this study, live animals were observed in still and moving water, videotaped, photographed, and relaxed prior to anatomical description. The pleurotomariid Perotrochus maureri formed a siphon with its mantle at the posterior end of the slit in the shell. As expected, water was expelled from the mantle cavity through this siphon. Dye released along the aperture, the area traditionally considered to be the incurrent window, was never observed to enter the mantle cavity. Instead, water entered through the slit just anterior to the siphon. A similar pattern was observed in the deep‐slit pleurotomariid Entemnotrochus adansonianus. Thus the “anal” slit provided the sites for the incurrent as well as the excurrent windows. This surprising flow pattern is inconsistent with the traditional scenario of early gastropod evolution. J. Morphol. 262:659–666, 2004. © 2004 Wiley‐Liss, Inc.
Evaluation of [Gd(Bz‐TTDA)]2– as a potential contrast agent in MR imaging of the hepatobiliary system: An animal study
Authors: Hsu Jui‐Sheng , Jaw Twei‐Shiun , Liu Gin‐Chung , Wang Yun‐Ming , Chen Shih‐Hsien , Kuo Yu‐Ting , Jao Jo‐Chi , Li Chun‐Wei , Tsai Kun‐Bow 
Published: September 2004

AbstractPurposeTo evaluate the potential of a new lipophilic paramagnetic complex [Gd(Bz‐TTDA)]2– [(4s)‐4‐benzyl‐3,6,10‐tri(carboxymethyl)‐3,6,10‐triazadodecandioic acid]2– designed for use as a hepatobiliary MR contrast agent.Materials and MethodsMR imaging studies for normal and hepatocellular carcinoma (HCC) rat models were performed using a 1.5‐T scanner. Sequential multislice T1‐weighted turbo field echo (TFE) (TR/TE/flip angle: 15 msec/6.1 msec/25°) coronal images of normal rats were obtained before and after intravenous injections of 0.1 mmol/kg [Gd(Bz‐TTDA)]2– in study groups (N = 12) or 0.1 mmol/kg gadopentate dimeglumine (Gd‐DTPA)2– in control groups (N = 12). Similar protocols of MR imaging with additional T2‐weighted images were used for the rats with implanted HCC in both study and control groups (N = 12, in each group). MR images were analyzed to evaluate the time‐enhancement change (% increase of signal‐to‐noise ratio [SI/N]) in normal liver, renal cortex, renal medulla, and tumors. The liver‐lesion contrast‐to‐noise ratios (CNR) were also evaluated in study and control groups. The rats were killed immediately after the last MR scan to undergo autopsy and histopathologic observation. The acute toxicity test (medial lethal dose, LD50) in mice was also done.ResultsThe liver enhancement in normal rats reached a plateau 5–50 minutes after injection of [Gd(Bz‐TTDA)]2–, maintained for three hours, then gradually declined. Intensity of enhancement in liver, renal cortex, and medulla after injection of [Gd(Bz‐TTDA)]2– was significantly higher than with Gd‐DTPA. The efficacy of tumor characterization with injection of [Gd(Bz‐TTDA)]2– was similar to that of Gd‐DTPA at the early dynamic phase of the contrast study. However, the liver‐lesion CNRs were significantly higher in the study group in the later phase, when tumor enhancement decreased and liver enhancement persisted. The dose of LD50 in acute toxicity test of [Gd(Bz‐TTDA)]2– in mice was 7.5 mmol/kg.ConclusionThe preliminary results in this animal study indicated that [Gd(Bz‐TTDA)]2– has the potential of becoming a reliable liver MR contrast agent. J. Magn. Reson. Imaging 2004;20:632–639. © 2004 Wiley‐Liss, Inc.
Interleaved echo‐planar imaging for fast multiplanar magnetic resonance temperature imaging of ultrasound thermal ablation therapy
Authors: Stafford R. Jason , Price DVM Roger E. , Diederich Chris J. , Kangasniemi Marko , Olsson Lars E. , Hazle John D. 
Published: September 2004

AbstractPurposeTo develop a multiplanar magnetic resonance temperature imaging (MRTI) technique based on interleaved gradient‐echo echo‐planar imaging (EPI), verify in phantom, develop software tools to process and display data on a clinical scanner in near real‐time, and demonstrate feasibility to monitor ultrasound thermal ablation therapy in vivo.Materials and MethodsTemperature estimation used complex phase‐difference subtraction of the EPI MRTI data to indirectly measure the temperature‐dependent water proton‐resonance‐frequency shift. Software tools were developed to run on a clinical 1.5‐T MR scanner that processed and displayed relevant temperature and thermal dosimetry data during the course of thermal ablation treatments in canine brain and prostate in vivo.ResultsEPI MRTI provided multi‐planar acquisitions and increased temperature sensitivity and lipid suppression. Relative to a single‐plane fast gradient‐echo MRTI sequence at comparable spatial and temporal resolutions in phantom, EPI MRTI demonstrated a three‐fold increase in sensitivity and slice coverage per TR. In vivo monitoring of ultrasound thermal ablation therapy in canine brain and prostate demonstrated the usefulness of the temperature and thermal dose information.ConclusionMulti‐planar MRTI allowed progression of thermal damage to be monitored and treatment parameters adjusted in near real‐time (less than five second delay). EPI MRTI is an effective multi‐planar monitoring method during ultrasound thermal ablation procedures. J. Magn. Reson. Imaging 2004;20:706–714. © 2004 Wiley‐Liss, Inc.
Robust field map generation using a triple‐echo acquisition
Authors: Windischberger Christian , Robinson Simon , Rauscher Alexander , Barth Markus , Moser Ewald 
Published: September 2004

AbstractPurposeTo establish a fast and robust technique for generating magnetic field maps for the correction of geometric distortions in echo‐planar magnetic resonance (MR) images.Materials and MethodsMultislice gradient‐echo (GE) images were acquired at echo times of 6, 6.5, and 7.5 msec in order to cover a field shift range of ±666 Hz in the resulting B0 maps. To account for possible phase wrap scenarios, seven phase triples were calculated for each pixel. Linear regression of the phase vs. echo time was performed for each set. The slope of the set with the minimum fitting error was taken as the true magnetic field in the respective pixel.ResultsBased on the fitting error distribution, the technique is shown to be feasible and effective for assessing the field distribution in the brain at 3 T, especially in inferior brain areas (amygdalae, hippocampus). Examples of echo‐planar images distortion corrected using the calculated field maps are shown.ConclusionThe approach presented yields robust estimation of magnetic field maps and requires under a minute of additional acquisition time and only seconds of computational time. As such, it is easily possible to apply image distortion correction in routine functional MR imaging (fMRI) studies, enabling improved coregistration of brain activation maps with structures on anatomical images. J. Magn. Reson. Imaging 2004;20:730–734. © 2004 Wiley‐Liss, Inc.